# A Practical Guide for Pediatric Nuclear Medicine

Zvi Bar-Sever Francesco Giammarile Ora Israel Helen Nadel *Editors* 

A Practical Guide for Pediatric Nuclear Medicine

Zvi Bar-Sever • Francesco Giammarile Ora Israel • Helen Nadel Editors

## A Practical Guide for Pediatric Nuclear Medicine

*Editors* Zvi Bar-Sever Nuclear Medicine Schneider Children's Medical Center Petah-Tikva, Israel

Ora Israel Rappaport School of Medicine Technion – Israel Institute of Technol Haifa, Israel

Francesco Giammarile Nuclear Medicine and Diagnostic Imaging International Atomic Energy Agency Vienna, Austria

Helen Nadel Pediatric Nuclear Medicine Lucile Packard Children's Hospital Palo Alto, CA, USA

#### ISBN 978-3-662-67630-1 ISBN 978-3-662-67631-8 (eBook) https://doi.org/10.1007/978-3-662-67631-8

Open Access provided by a grant from the International Atomic Energy Agency.

International Atomic Energy Agency

#### © IAEA: International Atomic Energy Agency 2023

The opinions expressed in this publication are those of the authors/editors and do not necessarily refect the views of the IAEA: International Atomic Energy Agency, its Board of Directors, or the countries they represent.

**Open Access** This book is licensed under the terms of the Creative Commons Attribution 3.0 IGO license (http://creativecommons.org/licenses/by/3.0/igo/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the IAEA: International Atomic Energy Agency, provide a link to the Creative Commons license and indicate if changes were made.

Any dispute related to the use of the works of the IAEA: International Atomic Energy Agency that cannot be settled amicably shall be submitted to arbitration pursuant to the UNCITRAL rules. The use of the IAEA: International Atomic Energy Agency's name for any purpose other than for attribution, and the use of the IAEA: International Atomic Energy Agency's logo, shall be subject to a separate written license agreement between the IAEA: International Atomic Energy Agency and the user and is not authorized as part of this CC-IGO license. Note that the link provided above includes additional terms and conditions of the license.

The images or other third party material in this book are included in the book's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the book's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifc statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.

The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affliations.

This Springer imprint is published by the registered company Springer-Verlag GmbH, DE, part of Springer Nature.

The registered company address is: Heidelberger Platz 3, 14197 Berlin, Germany

*This book is dedicated to the pioneers of this very special feld, to our patients and their families, and to our hard-working, loyal teams and colleagues.*

### **Foreword**

In the past few decades, Pediatric Nuclear Medicine and Molecular Imaging has become a rapidly growing area that includes diagnostic imaging, research, as well as therapeutic applications.

This publication highlights important aspects of the Nuclear Medicine practice in children as well as the differences with the approaches in adult patients.

Obtaining images of high diagnostic quality in infants and small children can be technically and medically challenging and often require special attention. It has been often stated that "Children are not small adults" and this is quite applicable to the practice of Nuclear Medicine in these small patients.

In children, administered activities are often signifcantly lower than in adults, requiring prolonged imaging acquisition times. Techniques for keeping the child still, sometimes for extended acquisition periods will be discussed. Such techniques include immobilization, sedation and exceptionally, general anesthesia.

Correct interpretation of pediatric images requires an awareness of the effects of normal growth and development on tracer pharmacokinetics and biodistribution as well as familiarity with pediatric diseases.

The introduction of technologies such as hybrid imaging, and new radiopharmaceuticals, are described in detail, underscoring the fact that these developments are aimed at improving diagnostic, structural and functional assessment of pediatric diseases.

This book provides a practical approach to the successful routine use of Nuclear Medicine procedures in children. It is based on the extensive expertise of dedicated pediatric nuclear medicine facilities and clinicians worldwide.

The IAEA has signifcantly enhanced the capabilities of many Member States in the feld of Nuclear Medicine, highlighting functional and metabolic imaging as indispensable tools for the diagnosis, treatment planning, and management of diseases. In this project, Nuclear Medicine and Molecular Imaging are driven one step forward, advancing towards the challenging but also very rewarding work with pediatric patients.

I hope that referring physicians, pediatricians, clinicians, and other specialists involved in the care of children will fnd in this a valuable, detailed, and practical resource of Pediatric Nuclear Medicine as well as "tips and tricks" that should be of value in the management of their clinical practice.

I also hope that medical professionals throughout the world will beneft from this publication, that readers of this book will achieve further familiarization with the many unique characteristics of Pediatric Nuclear Medicine and Molecular Imaging and that it will inspire deeper learning as well as innovation in this wonderful feld of medicine.

Radiology Ted Treves Harvard Medical School Boston, MA, USA, Divisions of Nuclear Medicine and Molecular Imaging, Boston Children's and Brigham and Women's Hospitals Boston, MA, USA

### **Preface**

This publication on clinical Nuclear Medicine dedicated to pediatric patients is directed at Nuclear Medicine physicians, radiologists, oncologists, and clinicians in various specialties, medical physicists, medical technologists, radiopharmacists, laboratory medicine scientists, and researchers.

New technologies and radiotracers have been developed and introduced into the clinical Nuclear Medicine arena over the last decades, in some parts of the world more rapidly than in others. This publication describes Nuclear Medicine imaging modalities in the specifc context of the management of pediatric patients. It provides a comprehensive overview of the current stateof-the-art in pediatric Nuclear Medicine, in addition to readdressing known tests, their protocols, clinical indications, and performance indices.

Training in using an accurate imaging methodology, in understanding and interpreting complex studies with potentially different tracer biodistribution, pitfalls and clinical relevance when used in children, are imperative for a successful implementation of present-day diagnostic and therapeutic capabilities. This publication aims to provide an answer to the need created for such training. It includes theoretical and practical aspects, as well as case-based presentations for each of the main indications for pediatric Nuclear Medicine tests that will ensure their use in an accurate and valuable clinical practice.

The authors are members of an international group of experts at the forefront of this feld and their contributions represent a culmination of their professional efforts defning a global perspective on the subject. The authors have provided representative teaching cases in addition to their own clinical expertise and to an in-depth review of the literature. The reader is provided with age-dependent, commonly encountered clinical cases. The publication contains 12 chapters, takes a systems approach, and provides reference-based practical information that will be useful in the routine clinical setting. Chapters are organized in a similar structure starting with an overview as to the clinical value of a specifc study and the most relevant clinical indications, methods to correctly request the study and prepare the patient. This is followed by description of the steps required to perform the study according to the most appropriate imaging protocol, based on those used by the expert authors in their home centers and presented in a "fash-card" format. The main normal biodistribution imaging patterns are presented, as well as useful calculations and settings when appropriate. Correlative imaging, review of variants, and possible drawbacks are detailed when deemed necessary. Each chapter discusses the Nuclear Medicine procedures that can and should be used in the specifc clinical pediatric arena. The length of the chapters varies according to the clinical signifcance of a particular test, the complexity of the methodology, and the number of cases included. Some longer chapters dedicated to the most common tests refect the more extensive use of a procedure in the pediatric population presenting more cases and extensive overviews.

In addition to the 11 chapters presenting specifc systems and/or diseases, the frst chapter provides general information detailing the advantages and limitations for performing Nuclear Medicine tests in children, as well as suggestions on how to approach, analyze, and provide relevant data to the patients, and to their parents or caregivers. Doses of radiopharmaceuticals follow, whenever possible, the most recent version of the EANM pediatric dosage card calculator and/or the North American consensus guidelines for administered radiopharmaceutical activities in children and adolescents. Minimizing a child's exposure to ionizing radiation is an important consideration, thoroughly discussed in this section which addresses the appropriateness of pediatric nuclear imaging. Well-known and widely accepted acronyms such as PET/CT, SPECT/CT, SPECT, CT, MRI as well as activity units (e.g., mCi, MBq) have always been used as abbreviations with the intent not to burden the reader.

The design and content of this publication will hopefully promote essential debates and feedback with the goal of having Nuclear Medicine as a useful tool in the process of diagnosing and treating diseases in children and provides a good setting for an evidence-based collaboration between Nuclear Medicine physicians and pediatricians working in various felds. It is also intended to assist professionals as well as institutions in making decisions regarding the frameworks for effective management of pediatric patients.

The authors gratefully acknowledge the IAEA for technical support. A special thanks to M. Felipe Mendez for continuous assistance in preparing the manuscript.

Petah-Tikva, Israel Zvi Bar-Sever Vienna, Austria Francesco Giammarile Haifa, Israel Ora Israel Palo Alto, CA, USA Helen Nadel

### **Contents**


### **List of Contributors**

**Zvi Bar-Sever** Schneider Children's Medical Center, Tel Aviv University, Petah Tiqva, Israel

Institute of Nuclear Medicine, Schneider Children's Medical Center, Tel Aviv University, Petah Tiqva, Israel

**Lorenzo Biassoni** Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

**Anita Brink** Nuclear Medicine Service, Division of Pediatric Medicine, University of Cape Town, Cape Town, South Africa

Nuclear Medicine and Diagnostic Imaging Section, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria

**Diego De Palma** Nuclear Medicine Unit, ASST Settelaghi, Varese, Italy

**Enrique Estrada-Lobato** Nuclear Medicine and Diagnostic Imaging Section, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria

**Francesco Giammarile** Nuclear Medicine and Diagnostic Imaging Section, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria

**Gopinath Gnanasegaran** Nuclear Medicine department, Royal Free London NHS Foundation Trust, London, UK

**Robert Howman-Giles** Nuclear Medicine Department, Children's Hospital at Westmead, University of Sydney, Sydney, NSW, Australia

**Ora Israel** Rappaport Faculty of Medicine, Technion, Haifa, Israel

**Kevin London** Nuclear Medicine Department, Children's Hospital at Westmead, University of Sydney, Sydney, NSW, Australia

**Helen Nadel** Lucile Packard Children's Hospital Stanford University, Palo Alto, CA, USA

**Diana Paez** Nuclear Medicine and Diagnostic Imaging Section, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria

**Thomas Neil Pascual** Department of Science and Technology, Manila, Philippines

**Barry Shulkin** Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN, USA

**Sharjeel Usmani** Department of Radiology and Nuclear Medicine, Sultan Qaboos Comprehensive Cancer CARE and Research Centre (SQCCCRC), Muscat, Oman

**Pietro Zucchetta** Nuclear Medicine Unit, Department of Medicine, Padova University Hospital, Padova, Italy

### **Abbreviations**





### **General Principles in Pediatric Nuclear Medicine 1**

Helen Nadel, Diana Paez, Zvi Bar-Sever, Ora Israel, and Francesco Giammarile

#### **1.1 General Information for Referring Physician, Parents, and NM Team [1–5]**

#### **Multidisciplinary Care Team**


H. Nadel (\*)

Lucile Packard Children's Hospital Stanford University, Palo Alto, CA, USA

D. Paez · F. Giammarile Nuclear Medicine and Diagnostic Imaging Section, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria

Z. Bar-Sever Schneider Children's Medical Center, Tel Aviv University, Petah Tiqva, Israel

O. Israel

B&R Rappaport Faculty of Medicine, Technion, Haifa, Israel

#### **Departmental Workfow—Scheduling the Study**


#### **Information to Be Requested at Booking the Study**

	- Allergies.
	- Renal function.
	- History of previous contrast reaction.

<sup>©</sup> The Author(s) 2023 Z. Bar-Sever et al. (eds.), *A Practical Guide for Pediatric Nuclear Medicine*, https://doi.org/10.1007/978-3-662-67631-8\_1

#### **Information to Be Provided to Parent/ Caregiver**

	- If this is planned, up to an hour is required for it to work so the patient should arrive an hour before the booking time of the study.
	- As an alternative, the parent/caregiver can put it on beforehand, outside of the department.

#### **Prior to the Study**


it is important to consider pregnancy and breastfeeding.


#### **On the Day of the Study**

On arrival explain to the parent/caregiver and child what is going to happen during the study. Knowing what to expect, reduces anxiety and improves cooperation. This translates to higherquality diagnostic images


#### **Radiation Risks [6–9]**


#### **Communicating Radiation Risks [10, 11]**


the exposure individuals receive from natural background radiation in 1 year.

• The image gently website (https://www. imagegently.org/Procedures/Nuclear-Medicine) has more information on explaining radiation risk from imaging procedures.

#### **Calculating the Administered Activity**


#### **Sedation [14–16]**

#### **Suggestions for Avoiding Sedation**




**Fig. 1.1** The EANM calculator screen shot. Reproduced with permission from https://www.eanm.org/contenteanm/uploads/2017/01/EANM\_Dosage\_Card\_040214. pdf. "This card summarises the views of the Paediatrics and Dosimetry Committees of the EANM and refects recommendations for which the EANM cannot be held



responsible. The dosage recommendations should be taken in the context of "good practice" of nuclear medicine and do not substitute for national and international legal or regulatory provisions." It is based upon work published in references [12, 30, 31]

the patient sit on their lap during an esophageal transit study or milk scan is less intimidating than sitting on the technologist's lap.

• When necessary parents/caregivers can assist the technologists in preventing motion during


**Fig. 1.2** North American Consensus Guidelines for Pediatric Administered Radiopharmaceutical Activities 2016. Reproduced with permission of imagegently.org


**Fig. 1.3** Dose calculator snapshot. (based Reproduced with permission from https://www.eanm.org/initiatives/ dosage-calculator/)

acquisition, for example, by gently securing the child's head when under the camera.


#### **Options for Distracting and Entertaining the Patient**


#### **Assessing the Need for Sedation**


#### **Principles and Protocols for Sedation/ General Anesthesia**

	- It can be indicated in young children beyond swaddling age and under 5 years of age or non-cooperative older children.
	- The need for sedation also depends on the study type, and should be considered in particular when performing SPECT/CT and PET/CT or PET/MRI.

#### **1.2 Performing and Reporting the Study**

#### **Preparing and Administration of Radiopharmaceutical**


#### **Setting up the Imaging Device**


#### **Positioning the Patient**


#### **Fig. 1.4** Firmly secured child using Velcro straps

**Fig. 1.5** Immobilized legs to reduce motion and better visualization of pelvic and shin bones

#### **Performing the Study**


#### **Reporting the Study**

• Check the tracer biodistribution and quality of images before reporting the study.

#### *The report should include:*


#### **1.3 Hybrid Imaging [17, 18]**

	- Attenuation correction and image optimization.
	- Study for anatomical localization.
	- Diagnostic CT with or without oral and/or IV contrast administration.
	- Low-dose CT for anatomical localization, mainly if the patient had a diagnostic standalone CT within a short time interval prior to the hybrid imaging study.
	- Optimized study for diagnostic evaluation.

#### **SPECT/CT [19]**

• Gamma camera imaging with single photon emitting radiotracers represents the majority of procedures in a routine pediatric nuclear medicine practice.

	- Precise localization of areas of abnormal and/or physiological SPECT tracer uptake.
	- Improving the sensitivity and specifcity of nuclear medicine procedures.
	- Allowing for quantitation.
	- Optimized guide for interventional diagnostic procedures.

#### **PET/CT [21–24]**


#### **PET/MRI [25, 26]**

	- Superior soft tissue contrast resolution.
	- It provides functional data, mainly for neurological cases.
	- Lack of ionizing radiation is highly appealing, particularly in pediatric, young adult, or pregnant patients.
	- With the development of full digital and total-body PET/CT and PET/MRI scanners, the administered activity can be signifcantly reduced.
	- Most children under 8 years of age will require sedation or general anesthesia for PET/MRI.
	- Non-sedated children may experience claustrophobia.
	- The technique and its evaluation are complex, the equipment is very costly and has limited availability in some countries.
	- PET/MRI has inferior performance (compared to CT) in detecting lung and cortical bone pathology.
	- There are more frequent artifacts on the attenuation correction maps.
	- A PET/MRI procedure can be of longer duration as compared to PET/CT, due to the prolonged MRI acquisition in cases of multiparametric sequences.

#### **Adverse Reactions to Contrast Media [27]**


important to recognize and manage the small but real risks inherent in the use of contrast media.


#### **1.4 Correlative Imaging [27–29]**


clinical scenarios, in particular, in suspected oncologic diseases and cancer predisposition syndromes, acute osteomyelitis, and infection and infammation in the brain and spine.


**Acknowledgment** The authors acknowledge the valuable contribution of John A. Kennedy, PhD, from the Rambam HealthCare Campus in Haifa, Israel.

#### **References**


IAEA-Coordinated Research Project. J Nucl Med. 2021;62(4):570–6.


The opinions expressed in this chapter are those of the author(s) and do not necessarily refect the views of the IAEA: International Atomic Energy Agency, its Board of Directors, or the countries they represent.

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 3.0 IGO license (http:// creativecommons.org/licenses/by/3.0/igo/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the IAEA: International Atomic Energy Agency, provide a link to the Creative Commons license and indicate if changes were made.

Any dispute related to the use of the works of the IAEA: International Atomic Energy Agency that cannot be settled amicably shall be submitted to arbitration pursuant to the UNCITRAL rules. The use of the IAEA: International Atomic Energy Agency's name for any purpose other than for attribution, and the use of the IAEA: International Atomic Energy Agency's logo, shall be subject to a separate written license agreement between the IAEA: International Atomic Energy Agency and the user and is not authorized as part of this CC-IGO license. Note that the link provided above includes additional terms and conditions of the license.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

### **Central Nervous System: The Brain and Cerebro-Spinal Fluid 2**

Lorenzo Biassoni, Helen Nadel, and Zvi Bar-Sever

#### **2.1 Brain Death Study**

#### **Clinical Indications**

• Confrmation of brain death.

#### **Pre-exam Information**


L. Biassoni (\*)

Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK e-mail: Lorenzo.Biassoni@gosh.nhs.uk

#### H. Nadel Lucile Packard Children's Hospital Stanford University, Palo Alto, CA, USA

Z. Bar-Sever Schneider Children's Medical Center, Tel Aviv University, Petah Tiqva, Israel

#### **Study Protocol for Brain Death Imaging [ 1, 2] Patient Preparation**

• In some institutions, when a nonspecifc radiopharmaceutical is used, a tourniquet is placed that encircles the head just above the eyebrows, ears, and around the posterior prominence of the skull. This reduces blood fow to the scalp and helps distinguish between cerebral and scalp activities.

#### **Radiopharmaceutical, Administered Activity and Mode of Delivery**

*Radiopharmaceutical:*


#### *Activity:*

• Weight based, 370–740 MBq (10– 20 mCi) or 18 MBq/Kg (0.5 mCi/kg).

Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and Society of Nuclear Medicine and Molecular Imaging (SNMMI) and image gently web sites.

Note the slight discrepancy: for HMPAO and ECD, the EANM dosage card indicates a minimum dose of 100 MBq.

Reference to national regulation guidelines, if available, should be considered.

#### **Acquisition Protocol**


#### *Using a brain-specifc perfusion tracer*


#### *Using a non-specifc cerebral perfusion tracer*


#### **Study Interpretation [3]**

	- Cerebral perfusion on dynamic images.
	- Filling of the cerebral sinuses on planar images.
	- Uptake of the tracer in cerebral structures on SPECT.

#### **In cases of brain death:**


#### **Correlative Imaging**


#### **Red Flags**


may be diffcult to interpret due to soft tissue accumulation of Pertechnetate. Using a brainspecifc perfusion tracer and SPECT/CT will improve diagnostic certainty.

• Even the slightest tracer activity on SPECT in any part of the brain precludes the diagnosis of brain death. If noted, a repeat brain death scan should be performed within a few days. Most repeat scans will show disappearance of the residual tracer activity.

#### **Take Home Messages**


#### **Representative Case Examples**

**Case 2.1. Brain Death (Fig. 2.1)**

**Fig. 2.1** History: A 9-month-old boy admitted to the hospital with hypovolemic shock due to gastroenteritis had a cardiopulmonary arrest 2 days before the study was requested. The brain death study was performed using Pertechnetate. Study report: There is no perfusion to the cerebrum on the dynamic images (**a**). There is no flling of the cerebral sinuses on the static images (**b**). Impression: The study shows a lack of perfusion to the entire brain confrming the clinical diagnosis of brain death

**Fig. 2.2** History: A 14-year-old boy with congenital heart disease underwent cardiac surgery and had a sudden postoperative cardiovascular collapse. His pupils were dilated. He lost all brain stem refexes. Brain CT demonstrated massive infarction of the entire left hemisphere and the right frontal lobe. His clinical status suggested brain death. A brain scan was performed following administration of ECD. Study report: Anterior radionuclide angiography (**a**) showed tracer distribution in the carotid arteries up to the base of the skull but no arterial blush in

the brain. Increased tracer uptake in the facial soft tissues was noted especially in the nasal area ("hot nose sign"). Early static images (**b**) showed no tracer localization in the brain parenchyma, but the posterior and lateral views showed uptake in the cerebellum, further confrmed on SPECT (**c**). Impression: Brain death could not be confrmed because of the residual perfusion visualized in the cerebellum. The patient's neurological status did not change, and a repeat study was obtained 5 days later

**Fig. 2.3** History: Repeat brain scan in a 14-year-old boy with suspected brain death and an equivocal study performed 5 days before. Study report: Anterior dynamic study (**a**) showed no cerebral perfusion. SPECT (**b**)

showed no uptake in the cerebrum or cerebellum. Impression: The study confrms the clinical diagnosis of brain death

#### **2.2 Drug-Resistant Epilepsy— Ictal and Interictal Brain Perfusion Spect**

#### **Clinical Indications**

	- There must be a good pre-test likelihood of unifocal seizures (or at least a dominant seizure).
	- The seizure should last long enough to be captured by the tracer injection (seizures lasting less than 20 s are unlikely to be captured

with an ictal SPECT, although the epileptogenic focus can still show prominent tracer uptake for some time after seizure ends).

#### **Pre-exam Information**


#### **Study Protocol for Brain Perfusion Imaging in Epilepsy [4–7]**

#### **Patient Preparation**


#### **Radiopharmaceuticals, Administered Activity, and Mode of Delivery**

#### *Radiopharmaceuticals*


#### *Activity*

• ECD and HMPAO: 7.4–11.1 MBq/kg (0.2–0.3 mCi/Kg), minimum 111– 185 MBq (3–5 mCi).

	- The North American consensus recommends 11.1 MBq (0.3 mCi/Kg), minimum dose of 185 MBq (5 mCi), and maximum of 740 MBq (20 mCi).
	- The EANM recommends a minimum dose of 100 MBq (2.7 mCi).

Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

#### *Mode of Delivery*

*For the ictal SPECT study*


#### *For the interictal SPECT study*


#### **Acquisition Protocol**

*Patient positioning:*


#### *Acquisition parameters for SPECT:*

	- For triple head camera: 120 steps, 40 steps/ head, 20–25 secs/step.
	- For dual-head camera: 120 steps, 60 steps/head, 30 secs/step.
	- Acquisition mode: step-and-shoot is more frequently used. Continuous mode acquisition may provide shorter scan times and improve patient comfort.
	- Matrix 128 × 128.
	- Zoom: the acquisition pixel size should be one-third to one-half of the expected resolution.

#### **Study Interpretation**

	- The exact time of EEG and clinical onset of the seizure.
	- The exact time of the tracer injection: start of the injection, end of the injection, end of fushing of the tracer with saline.
	- The exact time the seizure ends.
	- At least the time between fushing of tracer and seizure end (should be >15 secs).
	- EEG features at the time of seizure onset and immediately afterward.

#### **Correlative Imaging [8–12]**


#### **Red Flags**


hood of identifying the epileptogenic focus as an area of predominant hyperperfusion.

	- The time between the end of fushing and end of seizure: if this is shorter than 15 s the ictal SPECT may fail to capture the focus.
	- If the seizure lasts less than 15–20 s, it may be diffcult to capture with an ictal SPECT injection, since it takes about 15 s for the tracer to reach the brain after fushing with saline.
	- If the EEG fndings during/immediately after the seizure can lateralize and localize the seizure focus, identify the origin of the seizure and whether it generalized shortly after onset.

the hand of an accompanying person may enable them to perform the study without risk of head movement during the scan.

#### **Take Home Messages**


#### **Representative Case Examples**

**Case 2.3. Right Epileptogenic Focus (Fig. 2.4)**

**Fig. 2.4** History: A 1-year-old developmentally delayed boy, with asymmetric infantile spasms and focal seizures refractory to anti-epileptic medications, had a negative MRI. EEG showed continuous abnormalities in the right hemisphere, possibly the right anterior quadrant. For the ictal SPECT, ECD was administered during a typical cluster of spasms, with EEG changes lasting approximately 6 min. The injection was given 2:39 min after clinical seizure onset. The seizures continued for 79 s after fushing of the tracer. The EEG at the time of injection showed an extensive area of abnormality suggestive of seizures from the right hemisphere, possibly right anterior quadrant. Study report: On the ictal study (upper row) there is increased tracer uptake in the right anterior frontal region. In the interictal study (lower row) performed 2 days later there is slightly reduced tracer uptake in the right anterior frontal region. Subtraction of interictal from ictal SPECT images (blue area upper row) shows a signifcant difference in radioactive counts in the anterior region of the right hemisphere, which correlates with EEG fndings and clinical semiology. Impression: The fndings suggest the presence of an epileptogenic focus in the anterior quadrant of the right hemisphere in the right frontal region. The patient was referred for invasive monitoring for further consideration of a possible right frontal resection

#### **Case 2.4. Residual Right Epileptogenic Focus (Fig. 2.5)**

**Fig. 2.5** History: A child who had a right posterior parietal resection for focal cortical dysplasia continued to present with seizures after surgery. Study report: An ictal ECD SPECT (**a**) shows highly increased tracer uptake in the right parietal region, adjacent to the resection margin. This same area shows reduced uptake in the interictal

study (**b**). Impression: The fndings suggest a residual epileptogenic focus after surgical resection. Review of MRI with specifc sequences for epilepsy in this area showed changes compatible with residual focal cortical dysplasia. The child was referred for further surgery

#### **Case 2.5. Right Focal Cortical Dysplasia (Fig. 2.6)**

T1 RT Ictal 99mTcECD SPECT Interictal FDG PET

**Fig. 2.6** History: An 11-year-old boy had refractory partial and complex partial seizures, localized on EEG to the left frontal lobe. Study report: MRI showed a possible area of focal cortical dysplasia in the left frontal lobe (crosshairs MRI, left column). Ictal SPECT co-registered with MRI (center column) following injection of ECD shows focally increased tracer uptake in the left frontal area. This was confrmed in the interictal co-registered FDG PET/MRI study (right column). Impression: The study confrms an epileptogenic focus originating from the left focal frontal cortical dysplasia. Surgical resection was performed, and the patient is seizure-free at a 2-year follow-up

#### **2.3 Cerebro-Spinal Shunt Patency Studies**

#### **Clinical Indications**

• Patients with hydrocephalus with a CSF shunt who have clinical symptoms such as headache and vomiting, or an imaging suspicion of a malfunctioning shunt.

#### **Study Protocol for CSF Shunt Patency Imaging [13–15]**

#### **Patient Preparation**


#### **Radiopharmaceutical, Administered Activity and Mode of Delivery**

*Radiopharmaceutical:*


tive EANM and SNMMI and image gently web sites. Reference to national regulation guidelines, if available, should be considered. *Mode of delivery:*

• Injected intrathecal or into the reservoir.

#### **Acquisition Protocol**


#### **Study Interpretation**


#### **Correlative Imaging**


#### **Red Flags**


#### **Take Home Messages**


#### **Representative Case Examples**

#### **Case 2.6. Patent Shunt (Fig. 2.7)**

**Fig. 2.7** History: A 4-year-old boy with a ventriculoperitoneal CSF diversion shunt for congenital hydrocephalus presents with a recent headache and vomiting. MR showed mild dilatation of the ventricles with no change from the previous study. A Rickham reservoir was initially accessed aseptically, and CSF fuid was withdrawn for culture. Study report: The tracer was injected into the

Rickham reservoir (**a**, arrow) and passed rapidly from the ventricle into the shunt tube in the immediate postinjection images in posterior (**a**) and lateral (**b**) views. At 40 min post-injection (**c**) the tracer has distributed diffusely into the peritoneum. Impression: Patent ventriculoperitoneal shunt

#### **Case 2.7. Blocked Shunt (Fig. 2.8)**

**Fig. 2.8** History: A 7-year-old boy with a history of hydrocephalus secondary to a brain tumor, which had been successfully removed followed by insertion of a ventriculo-peritoneal shunt, developed lethargy and headache with occasional vomiting. MRI showed moderate dilatation of the ventricles. Study report: The tracer was injected via a Hakim reservoir (**a**, red arrow). The CSF appeared under increased pressure. On the immediate post-injection image in lateral projection, the tracer fows back into the ventricle (**a**, blue arrow) indicating a patent proximal end. On images of the chest and abdomen performed 1 h post-injection (**b**) the tracer is shown to have passed slowly down the shunt tube and does not distribute into the peritoneal cavity. Mild renal excretion is seen. Impression: The fndings indicate a blocked distal end of the ventriculo-peritoneal shunt

#### **References**


The opinions expressed in this chapter are those of the author(s) and do not necessarily refect the views of the IAEA: International Atomic Energy Agency, its Board of Directors, or the countries they represent.

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 3.0 IGO license (http:// creativecommons.org/licenses/by/3.0/igo/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the IAEA: International Atomic Energy Agency, provide a link to the Creative Commons license and indicate if changes were made.

Any dispute related to the use of the works of the IAEA: International Atomic Energy Agency that cannot be settled amicably shall be submitted to arbitration pursuant to the UNCITRAL rules. The use of the IAEA: International Atomic Energy Agency's name for any purpose other than for attribution, and the use of the IAEA: International Atomic Energy Agency's logo, shall be subject to a separate written license agreement between the IAEA: International Atomic Energy Agency and the user and is not authorized as part of this CC-IGO license. Note that the link provided above includes additional terms and conditions of the license.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

## **Cardiovascular System 3**

Pietro Zucchetta and Ora Israel

#### **3.1 First Pass Study**

#### **Clinical Indications [1, 2]**

	- Atrial septal defect
	- Ventricular septal defect
	- Truncus arteriosus
	- Patent ductus arteriosus
	- Complete atrio-ventricular canal
	- Aorto-pulmonary collaterals

P. Zucchetta (\*)

Nuclear Medicine Unit, Department of Medicine, Padova University Hospital, Padova, Italy e-mail: pietro.zuchetta@unipd.it

O. Israel

Rappaport Faculty of Medicine, Technion, Haifa, Israel

#### **Study Protocol for First Pass Studies [3] Radiopharmaceutical, Activity and Mode of Delivery**

*Radiopharmaceuticals:* One of the following can be used:


#### *Activity:*

• Weight-based; 9.6 MBq/kg (0.26 mCi/ kg), range 80 MBq (2.16 mCi)— 490 MBq (13.24 mCi).

Refer to the EANM paediatric dosage card and to the North American consensus guidelines on radiopharmaceutical

administration in children in the respective European Association of Nuclear Medicine (EANM) and Society of Nuclear Medicine and Molecular Imaging (SNMMI) and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

*Delivery:*

Injection technique:


#### **Acquisition Protocol**

	- Dynamic study and anterior supine position.
	- Has to be gated if equilibrium LVEF measurements are performed in addition to evaluation of the shunt.
	- Should start a few seconds before injection, to avoid missing the frst frames.
	- It is critical to center precisely the cardiac region in the feld-of-view (FOV) before injecting the bolus.

FOV should extend from the suprasternal notch to just below the xiphoid and include most lung parenchyma.


#### **Study Interpretation**

#### **Assessment of adequacy of bolus (Fig. 3.1)**


#### **Left-to-right shunt calculation (Fig. 3.1)**


**Fig. 3.1** Assessment of bolus adequacy and left-to-right shunt calculation. The square ROI depicts the SVC. The solid line represents the TAC obtained from counts measured in a ROI drawn over the lungs taking care to avoid the heart and large vessels. The broken line represents the area under the gamma-variate lung ftted curve. No addi-


tional curve is seen early after the lung curve to suggest premature recirculation related to a left-to-right shunt. The calculated Qp/Qs is 1.59. There is no evidence for a physiologically signifcant left-to-right shunt


#### **Correlative Imaging**


#### **Red Flags**


initial activity. This applies only to studies performed with DTPA and Pertechnetate. If both injections fail, the study should be postponed to another day.

• The ROI drawn over the lungs should avoid the heart and large vessels.

#### **Take Home Messages**


#### **Representative Case Examples**

**Case 3.1. Normal First Pass Study, Exclusion of Left-to-Right Shunt (Fig. 3.2)**

**Fig. 3.2** History: The study was requested to exclude a left-to-right cardiac shunt. Study report: Dynamic images demonstrate sequential arrival of activity into the superior vena cava, the right side of heart, pulmonary arteries, lungs, pulmonary veins and the left side of heart. Impression: Normal study. No left-to-right shunt was detected

#### **Case 3.2. Left-to-Right Shunt (Fig. 3.3)**

**Fig. 3.3** History: A child with a heart murmur was detected on routine stethoscope auscultation. Study report: Dynamic images show a sharp bolus travelling via the superior vena cava into the RV and the lungs. There is persisting tracer activity within the lungs due to premature recirculation through the left-to-right shunt, as well as in the LV and systemic circulation. Impression: Left-to-right shunt

#### **3.2 Myocardial Perfusion Scintigraphy**

#### **Clinical Indications [4]**


**Study Protocol for Myocardial Perfusion Studies [5, 6] Patient Preparation**

	- Vasodilators for 24 h.
	- Calcium antagonists for 2 days.
	- Beta-blockers for 3 days.
	- Theophylline for 24 days (particularly for adenosine test).

#### **Stress Testing** [7]


and/or parents/caregivers cannot offer the necessary compliance.


#### **Radiopharmaceutical, Administration Activity, Mode of Delivery**

*Radiopharmaceuticals*:


*Activity:*


Refer to the EANM paediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective European Association of Nuclear Medicine (EANM) and Society of Nuclear Medicine and Molecular Imaging (SNMMI) and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

#### **Acquisition Protocol**


#### **Study Interpretation**

	- Extent/size: small, medium, large.
	- Severity: mild, moderate, severe.
	- Presence and extent of reversibility: reversible or irreversible.
	- Location: based on segment model [9, 10].

#### **Red Flags**


#### **Take Home Messages**


usually without the need for the antidote (theophylline).

#### **Representative Case Examples**

**Case 3.3. Normal Myocardial Perfusion Study (Fig. 3.4)**

**Fig. 3.4** History: Patient with Takayasu's arteritis. Study report: An exercise gated myocardial perfusion stress test was performed. Overall study quality is excellent. There is normal myocardial perfusion at stress and rest. The LVEF is 89%. Conclusion: Normal myocardial perfusion scintigraphy

**Fig. 3.5** History: A 11-year-old boy after arterial switch operation for transposition of the great arteries with left coronary malformation complained of mild chest discomfort during exercise. Exercise ischemia is suspected. Stress/rest test (ergometer) followed by MIBI injection was performed. Study report: There is decreased perfusion in the anterior wall (apical and mid-planes, white arrows) improving at rest. Impression: Reversible hypoperfusion of the anterior wall

#### **Case 3.5. Partially Reversible Perfusion Defects (Fig. 3.6)**

**Fig. 3.6** History: A 14-year-old boy after arterial switch operation for transposition of the great arteries and anomalous origin of the coronary arteries. Stress/rest test (ergometer) followed by MIBI injection was performed. Study report: On the stress study (upper row) there is mild hypoperfusion of the antero-lateral wall (white arrows) and the septum (green arrows) with partial improvement on the rest study (lower row). Impression: Partially reversible hypoperfusion in antero-lateral wall and septum

#### **3.3 Blood Pool Scintigraphy of Vascular Structures**

#### **Clinical Indications [11, 12]**


#### **Pre-Exam Information**


#### **Study Protocol for RBC Scintigraphy [13]**

**Radiopharmaceutical, Activity and Mode of delivery.**

*Radiopharmaceutical:* [ 99mTc]RBCs (RBC) [14].

	- 1–3 ml of the patient's blood are drawn anticoagulated with heparin or acid citrate dextrose (ACD).
	- RBCs are labelled with a commercially available preparation according to the manufacturer's instructions.
	- General blood manipulation/handling precautions should be implemented. The labelled blood should be slowly re-injected to the patient from whom it was drawn.
	- +2Sn pyrophosphate is injected in appropriate, weight-based amount obtained from the package insert of the commercial cold kit.
	- Administration of [99m Tc] Pertechnetate follows 20 minutes later.

*Activity* (Pertechnetate):

• 74 MBq/Kg (2 mCi/kg), a minimum dose of 74 MBq (2 mCi).

Refer to the EANM paediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective European Association of Nuclear Medicine (EANM) and Society of Nuclear Medicine and Molecular Imaging (SNMMI) and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

#### **Acquisition Protocol**


#### **Study Interpretation**


#### **Correlative Imaging**


#### **Red Flags**


#### **Take Home Messages**


#### **Representative Case Examples**

**Case 3.6. Facial Hemangioma (Fig. 3.7)**

**Fig. 3.7** History: A 17-year-old girl presented with a 15-mm pulsatile mass in left face, suspected to be of vascular origin. Study report: Dynamic study of the head (**a**) following the injection of Tc-RBC does not show areas of increased blood fow. Early planar anterior view of the head (**b**) shows a slightly increased blood pool in the lateral aspect of the left face. Transaxial slices of SPECT/CT performed at 2 h after radiotracer administration (**c**) demonstrate an area of increased blood pool corresponding to swelling of soft tissues in the left temporal-zygomatic area. Impression: The fndings are consistent with a vascular lesion with venous blood supply in the left face. US-guided fne needle aspiration confrmed the diagnosis of hemangioma

#### **References**


ing arterial switch operation utilizing Regadenoson. Pediatr Cardiol. 2018;39(6):1249–57.


The opinions expressed in this chapter are those of the author(s) and do not necessarily refect the views of the IAEA: International Atomic Energy Agency, its Board of Directors, or the countries they represent.

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 3.0 IGO license (http:// creativecommons.org/licenses/by/3.0/igo/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the IAEA: International Atomic Energy Agency, provide a link to the Creative Commons license and indicate if changes were made.

Any dispute related to the use of the works of the IAEA: International Atomic Energy Agency that cannot be settled amicably shall be submitted to arbitration pursuant to the UNCITRAL rules. The use of the IAEA: International Atomic Energy Agency's name for any purpose other than for attribution, and the use of the IAEA: International Atomic Energy Agency's logo, shall be subject to a separate written license agreement between the IAEA: International Atomic Energy Agency and the user and is not authorized as part of this CC-IGO license. Note that the link provided above includes additional terms and conditions of the license.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

## **Pulmonary System 4**

Zvi Bar-Sever and Pietro Zucchetta

#### **4.1 Clinical Indications [1–4]**

	- Before and after lung transplantation.
	- In congenital lung malformations (e.g. lobar emphysema, cystic adenomatoid malformation and pulmonary sequestration).

P. Zucchetta

© The Author(s) 2023


#### **4.2 Pre-Exam Information**


**Study Protocol for Perfusion Lung Scan [2, 5, 6]**

#### **Radiopharmaceuticals, Activity and Mode of Delivery.**

*Radiopharmaceutical:*

• [ 99mTc]macroaggregated albumin (MAA), typically 10–40 microns in size.

Z. Bar-Sever et al. (eds.), *A Practical Guide for Pediatric Nuclear Medicine*, https://doi.org/10.1007/978-3-662-67631-8\_4

Z. Bar-Sever (\*)

Institute of Nuclear Medicine, Schneider Children's Medical Center, Tel Aviv University, Petah Tiqva, Israel

Nuclear Medicine Unit, Department of Medicine, Padova University Hospital, Padova, Italy

#### *Activity:*

	- If no ventilation scan is performed: 1.11 MBq/kg (0.03 mCi/kg), minimum activity: 14.8 MBq (0.4 mCi).
	- If perfusion scan is performed immediately after ventilation scan: 2.6 MBq/kg (0.07 mCi/kg).
	- The typical number of MAA particles should not exceed 50,000 in newborns and 165,000 in 1-year-old infants. In cases of right-to-left shunt, of pulmonary hypertension or of a single functioning lung, the number of particles should be 10,000.

Refer to the EANM paediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites. Reference to national regulation guidelines, if available, should be considered.

#### *Mode of delivery:*

• The tracer should be injected with the patient supine.

#### **Acquisition protocol**


#### **Study Protocol for Ventilation Lung Scan [2, 4, 7]**

#### **Radiopharmaceuticals, Activity and Mode of Delivery.**

*Radiopharmaceutical*


#### *Radioactive gases:*


#### *Activity:*


Refer to the EANM paediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

Note that 133Xe and 81mKr do not appear on the EANM dosage card.

#### *Mode of delivery:*


#### **Acquisition protocol**


#### **4.3 Perfusion and Ventilation Study Interpretation**

Visual patterns of perfusion and ventilation lung scans should be interpreted according to the requested clinical indication:

#### **Congenital heart disease: [9, 10]**


#### **Hepato-pulmonary syndrome [11]:**

• The shunt is intrapulmonary leading to the visualization of activity in the systemic circulation.

#### **Congenital and acquired airway disease [4]:**

• Global and regional distribution of pulmonary ventilation and perfusion are reported.

#### **Pulmonary embolism [12, 13]:**

• The hallmark of PE remains demonstrating a mismatch between absent or reduced perfusion in lung segments and preserved ventilation.

Specifcally, dynamic [133Xe] studies should be interpreted as follows:

• Initial images after a single breath refect regional lung ventilation.


#### **4.4 Perfusion and Ventilation Diferential Lung Function Analysis**

	- Differential lung perfusion and/or ventilation is calculated by comparing left and right lung counts obtained from whole lung regions-of-interest (ROIs) and is expressed in percentages.
	- ROIs can be placed on the posterior view only or both the posterior and anterior view to obtain conjugate counts for calculating the geometric mean.
	- ROIs can be split into upper middle and lower zones for each lung for a crude assessment of regional lung perfusion and ventilation. Modern processing software allows determination of these values according to lung lobes and segments and should be preferred when available.

R-L shunt (%) = [(total body counts−lung counts)/total body counts] × 100 [1].

	- Background corrected brain counts/background corrected lung counts x 100 (Normal value 0.42 ± 0.30) [14].

#### **4.5 Correlative Imaging**


#### **Red Flags**

	- Should not exceed 50,000 in newborns and 165,000 in 1-year-old infants.
	- Should be around 10,000 cases of right-toleft shunt, of pulmonary hypertension or of a single functioning lung.

seen in the thyroid, the gastric mucosa and renal collecting systems. In case of shunts the tracer will be seen in the brain.


#### **4.6 Take Home Messages**


calculated and is important for planning and monitoring therapeutic decisions, and for long-term follow-up.

	- The anatomy of the malformations and the corrective surgery that was performed.
	- If tracer was injected in the upper or lower extremity veins.

laries. It returns from the peripheral circulation to the lungs and is exhaled. Equilibrium is reached rapidly with a constant concentration in the lungs allowing static images.

• 81mKr ventilation requires little cooperation, has a very low radiation burden due to the short halflife of 81 mKr of 13 seconds and can be applied in studies of infants and young children.

#### **4.7 Representative Case Examples**

**Case 4.1. Assessment of Pulmonary Artery Stenosis (Fig. 4.1)**

**Fig. 4.1** History: A 4-year-old boy underwent perfusion lung scintigraphy to assess the impact of an isolated left pulmonary artery stenosis on the differential pulmonary perfusion. Anterior and posterior images (**a**) show a marked global reduction of the perfusion of the left lung. The differential perfusion was 90% and 10% to the right and left lungs, respectively. Based on these results he underwent cardiac catheterization with balloon dilatation of the left main pulmonary artery. A follow-up lung scan performed 6 months later (**b**) demonstrates improved perfusion to the left lung. The differential perfusion to the left lung increased from 10% to 36%. Impression: Marked improvement in left lung perfusion due to the successful intervention. NB: This case demonstrates how a perfusion lung scan guides decisions on the need for therapeutic interventions and evaluates their success

#### **Case 4.2. Right-to-Left Shunt (Fig. 4.2 )**

**Fig. 4.2** History: A 10-month-old boy with complex congenital cardiac anomalies including situs inversus, corrected transposition of the great arteries and pulmonary atresia, underwent a left-sided modifed Blalock Taussig shunt at the age of 1 month. Perfusion lung scan was performed to assess a stenosis of the right pulmonary artery. Study report: There is a reduction in the pulmonary perfusion of the right lung. In addition, there is diffuse tracer activity in the brain, in the parenchyma of both kidneys and in the spleen located in the right upper quadrant due to situs inversus (arrows). Impression: The fndings suggest the presence of a shunt from the pulmonary to the systemic circulation, a right-to-left shunt 4 Pulmonary System

**RPO LPO**

#### **Case 4.3. Congenital Cystic Adenomatoid Malformation (Fig. 4.3)**

**Fig. 4.3** History: A 4-month-old girl with a large congenital cystic adenomatoid malformation of the right lung as seen on chest CT (**a**). Study report: Baseline perfusion lung scintigraphy (**b**) shows a large perfusion defect in the right lung corresponding to the malformation. The differential perfusion was: right lung 28%, left lung 72%. Impression: Decreased perfusion to right lung corresponding to the structural malformation seen on CT. Subsequently, the infant underwent surgery to resect the malformation and to reconstruct the right pulmonary artery

#### **Case 4.4. Hypoplastic Left Lung (Fig. 4.4)**

**Fig. 4.4** History: A 7-month-old preterm infant with a hypoplastic left lung caused by congenital paralysis of the left hemi-diaphragm had lung perfusion scintigraphy to assess the differential pulmonary perfusion. Study report: Anterior and posterior perfusion images (**a**) and coronal

SPECT slices (**b**) show a small left lung with a marked reduction in pulmonary perfusion contributing only 12% to the total pulmonary perfusion. Impression: Hypoplastic left lung with a marked decrease in relative perfusion

#### **References**


The opinions expressed in this chapter are those of the author(s) and do not necessarily refect the views of the IAEA: International Atomic Energy Agency, its Board of Directors, or the countries they represent.

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 3.0 IGO license (http:// creativecommons.org/licenses/by/3.0/igo/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the IAEA: International Atomic Energy Agency, provide a link to the Creative Commons license and indicate if changes were made.

Any dispute related to the use of the works of the IAEA: International Atomic Energy Agency that cannot be settled amicably shall be submitted to arbitration pursuant to the UNCITRAL rules. The use of the IAEA: International Atomic Energy Agency's name for any purpose other than for attribution, and the use of the IAEA: International Atomic Energy Agency's logo, shall be subject to a separate written license agreement between the IAEA: International Atomic Energy Agency and the user and is not authorized as part of this CC-IGO license. Note that the link provided above includes additional terms and conditions of the license.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

57

## **Thyroid 5**

#### Barry Shulkin and Thomas Neil Pascual

#### **5.1 Thyroid Scintigraphy in Congenital Hypothyroidism**

#### **Clinical Indications [1–4]**


#### **Pre-Exam Information**


• History of exposure of the newborn to iodinecontaining antiseptics used in maternal (C-section) or newborn surgery or contrast media in radiologic procedures.

#### **Study Protocol for Thyroid Scintigraphy in Neonates [5, 6]**

#### **Patient Preparation**


#### **Radiopharmaceutical, Activity, and Mode of Delivery.**

*Radiopharmaceutical:*


https://doi.org/10.1007/978-3-662-67631-8\_5

B. Shulkin (\*)

Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN, USA e-mail: Barry.Shulkin@stjude.org

T. N. Pascual Department of Science and Technology, Manila, Philippines

#### *Activity:*


Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

#### *Delivery:*

• IV tracers are administered through a cannula, which should be adequately fushed with normal saline before and after the injection.

#### **Acquisition Protocol.**

*Pertechnetate:*


If a pinhole collimator is not available use general purpose, high or ultrahigh resolution collimator.

	- The infant is secured to the camera bed, with the arms by the side of the body.

eral view of the neck indicated in cases of ectopy, is obtained with the infant lying on his side.

	- Duration: 5–10 min/view. Alternatively: 250 Kcounts; for images with markers 50 Kcounts. Pinhole: 100–200 Kcounts. Zoom of 1.5–2 (typical), matrix 128 × 128 or 256 × 256.

*123I*


#### **Study Interpretation**

	- Symmetrical tracer uptake in both thyroid lobes, resembling a butterfy shape.
	- The gland is positioned at the base of the neck, the normal thyroid bed.
	- Faint uptake is seen in the salivary glands and the gastric mucosa.
	- Agenesis.
	- Maternal antithyroid antibodies in the newborn's blood (preventing tracer uptake).
	- In the upper neck midline, the region of the oropharynx, suggests a "lingual thyroid."
	- One or, occasionally, two foci in the lower neck, above the normal thyroid bed, located along the thyroglossal duct.
	- Maternal antibodies.

#### **Perchlorate Discharge Test [7]**


#### **Perchlorate Test Protocol**


#### **Correlative Imaging**


#### **Red Flags**


#### **Take Home Messages**


visualization and can be due to a number of causes, as described above.


#### **Representative Case Examples**

**Case 5.1. Non-visualization of Thyroid Gland (Fig. 5.1)**

**Fig. 5.1** History: Neonate with congenital hypothyroidism. Study report: In the left lateral view (right, with, and left, without markers), there is no evidence of functioning

thyroid tissue in the neck or elsewhere. Impression: The fndings are compatible with thyroid agenesis or a severely dysplastic thyroid

#### **Case 5.2. Sublingual Thyroid (Fig. 5.2)**

**Fig. 5.2** History: Neonate with congenital hypothyroidism. Study report: On left lateral views (left without markers, center with markers) there is a focal area of Pertechnetate uptake in the sublingual position. In the anterior view (right) the focus appears round-shaped and not in the typical butterfy shape of the normal thyroid gland. Impression: The fndings are compatible with a sublingual thyroid. This child is likely to need thyroxine for life

#### **Case 5.3. Ectopic Thyroid Tissue (Fig. 5.3)**

**Fig. 5.3** History: Neonate with congenital hypothyroidism. Study report: Following administration of Pertechnetate, on the left lateral view (left, without markers) there are two foci of tracer uptake behind the tongue. No tracer uptake is seen in the physiologic thyroid loca-

tion in the neck (right, with markers). Impression: The fndings are compatible with foci of functioning ectopic sublingual thyroid tissue. This child is likely to need thyroxine for life

#### **Case 5.4. Dyshormonogenesis (Fig. 5.4)**

**Fig. 5.4** History: Neonate with congenital hypothyroidism. Study report: There is high Pertechnetate uptake of 13.6% (normal range: 0.45–4%) in a normally located thyroid gland (left-lateral, right-anterior view) showing the usual butterfy shape. Impression: The fndings are compatible with dyshormonogenesis

#### **5.2 Thyroid Scintigraphy in Acquired Benign Thyroid Disease**

#### **Clinical Indications [8]**


#### **Pre-Exam Information**


#### **Study Protocol for Thyroid Scintigraphy**

#### **Patient Preparation**

	- Discontinue iodine-containing drugs, diet, and supplements.

Iodine-rich foods and supplements (e.g., seaweed, kelp, and sushi): 1 week.

Lugol's solution, Saturated Solution of Potassium Iodide (SSKI), KI tablets, vitamin/minerals: 1–3 weeks.

Cough medications and skin cleansers containing iodine: 2–4 weeks.

IV iodinated contrast: 4–6 weeks. Amiodarone: 3–6 months.

– Discontinue drugs that interfere with RAI uptake.

Methimazole, PTU: 3 days.

Lithium carbonate: 1 year (rarely used in children).

• In cases of oral RAI administration: fast for 1–2 hours prior to and 30 minutes after the administration to ensure adequate absorption.

#### **Radiopharmaceutical, Activity, and Mode of Delivery.**

*Radiopharmaceuticals:*


*Activity and mode of delivery:*

	- Administered orally: 3.7–7.4 MBq (0.1–0.2 mCi) after a fast of 1 h.
	- Administered IV: 0.28 MBq/kg (0.0075 mCi/kg) minimum 1 MBq (0.027 mCi), maximum 11 MBq (0.3 mCi).
	- Administered orally for RAIU measurements after a fast of 1–2 h.

#### **Acquisition Protocol**

• Collimator: general purpose, high- or ultrahigh resolution.

Pinhole collimator is recommended when available.

	- Pertechnetate: 20 min after administration.
	- 123I: 2–6 hours after oral and 1 hour after IV administration.
	- Pertechnetate: 100–200 Kcounts/ view.
	- 123I: 50–100 Kcounts/view or 5–20 min.

#### **RAIU Test**


#### **Study Interpretation (for Thyroid Scan and RAIU) [9–14]**

• The maximal length of each thyroid lobe should be measured serving as a tool to assess the size of the gland.

#### **Suspected hyperthyroidism**


#### **Hypothyroidism**


#### **Correlative Imaging [15–17]**

• Thyroid US should be correlated for assessment of gland appearance, presence of nodules, calcifcation, and vascularity.

#### **Red Flags [18, 19]**


medications/supplements, to IV administered contrast agents, to antithyroid drugs and hormonal replacement therapy.

• Certain processing software can calculate the percent tracer uptake in the gland from the injected dose. This requires measuring the full and empty syringe counts, and placing thyroid and background regions of interest. The percent uptake from injected dose can aid visual assessment of the intensity of tracer uptake but has not been formally validated and cannot routinely replace RAIU with a dedicated probe.

#### **Take Home Message**


patient for a 24-hour measurement the next day.

	- Medical history, thyroid function tests, medications, dietary supplements, other

factors that could affect the scan and RAIU results.


#### **Representative Case Examples**

**Case 5.5. Graves' Disease (Fig. 5.5)**

**Fig. 5.5** History: A 13-year-old girl presented with heat intolerance, excessive perspiration, tachycardia, palpitations, increased appetite, and weight loss. Thyroid function tests showed a barely measurable plasma TSH of 0.008 mIU/L (normal range 0.51–4.0 mIU/L), highly elevated levels of FT4 70 pmol/L (normal range 10.7– 18 pmol/L) and T3 > 30 pmol/L (normal levels 3.5–6.5 pmol/L). Physical examination revealed a large goiter. A Pertechnetate thyroid scan was requested to determine the cause of her overt hyperthyroidism. Study report: Anterior, LAO and RAO pinhole views (top row) and anterior parallel-hole collimator "bird's eye" view with size measurements (bottom row) show a markedly enlarged thyroid gland, right lobe larger than left, with intense, homogenous tracer activity. The percent tracer uptake from the injected dose of Pertechnetate is markedly elevated, 30%. Impression: The fndings are consistent with Graves' disease. The girl was treated with beta adrenergic antagonists and methimazole with gradual clinical and biochemical improvement

#### **Case 5.6. Autonomous Adenoma (Fig. 5.6)**

**Fig. 5.6** History: A 16-year-old girl complained of fatigue, weakness and headaches for several months. Her lab results showed low TSH levels, normal FT4 and mildly elevated T3. Physical examination revealed a nodule in the right thyroid lobe. Neck US demonstrated a 2.7 × 1.5 cm solid nodule in the lower pole of the right thyroid lobe. Study report: A Pertechnetate thyroid scan, anterior view with a parallel-hole collimator (left) and anterior pinhole image (right) show intense tracer uptake

in the lower part of the right thyroid lobe, at the location of the known nodule. The remainder of the right lobe and the entire left lobe show only very faint tracer activity. Impression: The fndings are consistent with an autonomous thyroid adenoma suppressing tracer uptake in the normal gland. FNA showed colloid, groups of follicular cells and scattered follicular and microfollicular structures with minor atypia. The patient underwent surgical resection of her right thyroid lobe

#### **5.3 Thyroid Cancer Imaging**

#### **Clinical Indications [20–25]**

	- To determine the presence and extent of residual functioning thyroid tissue.
	- To determine the need and dose of RAI for ablation of remnant thyroid tissue.
	- To determine the need and dose of RAI for treatment of metastatic or recurrent disease.
	- Surveillance.
	- To detect the presence and location of residual cancer, recurrence and/or metastases.

#### **Pre-Exam Information [26, 27]**

	- Iodine-rich foods and supplements (e.g., seaweed, kelp, and sushi): 1 week.
	- Lugol's solution, SSKI, KI tablets, vitamin/minerals: 1–3 weeks.
	- Cough medications and skin cleansers containing iodine: 2–4 weeks.
	- IV iodinated contrast: 4–6 weeks.
	- Amiodarone: 3–6 months.
	- Lithium carbonate: 1 year (rarely used in children).

• Confrm adequate TSH levels: 30 mIU/L or higher (measured 1–3 days before RAI administration).

#### **Study Protocol for Imaging Pediatric Thyroid Cancer [25, 27, 28]**

#### **Patient Preparation.**

*Methods to reach these TSH levels:*

	- Levothyroxine (l-T4) deprivation for 4 weeks.
	- Alternative: change to triiodothyronine (T3) for 4 weeks, followed by T3 discontinuation for 2 weeks before RAI scintigraphy.
	- No need to stop thyroid hormone treatment.
	- Day 1 and 2: intramuscular injection of 0.9 mg rhTSH.
	- Day 3: administration of RAI.
	- Day 4: imaging with 123I.

*On the day of the examination:*


#### **Radiopharmaceutical, Activity, and Mode of Delivery**

*Radiopharmaceuticals:*


#### *Activity:*


There is no consensus regarding weight-based administration of these tracers in children.

Reference to national regulation guidelines, if available, should be considered.

#### **Acquisition Protocol**

*Diagnostic scan:* 123I


131I


*Post-therapy scan.* 131I

• Time of imaging: 4–7 days post RAI therapy.

Acquisition parameters:

	- FOV: skull base-to-upper abdomen to evaluate for cervical, upper mediastinal, and pulmonary metastatic disease.
	- 20 sec/step, 64 projections, matrix 128 × 128; iterative reconstruction.

#### **Study Interpretation [29]**


#### **Correlative Imaging**


#### **Red Flags**


#### **Take Home Messages**

• Performing two post-therapy scans can be diffcult. The decision for a repeat scan should be made after the initial scan, in cases it is negative, and the patient's Tg is "positive," or if there is clinical or other imaging evidence of metastases. The delayed scan should attempt to identify the site of the elevated Tg or to defne whether the structural abnormality is RAI-avid.


#### **Representative Case Examples**

**Case 5.7. Post-Therapy 131I Study (Fig. 5.7)**

**Case 5.8. Papillary Thyroid Cancer, Lung Metastasis (Fig. 5.8)**

**Fig. 5.7** History: A 9-year-old girl had a right thyroid lobe resection followed by complete thyroidectomy for follicular thyroid cancer. Study report: on the post-surgery 123I thyroid scan (**a**) there are RAI-avid foci with 3% residual tracer uptake in the neck, more in the left lobe of the thyroid. Repeat surgery was performed only on the left side neck because of a signifcant amount of scar tissue on the right side. The patient then received a 1110 MBq

(30 mCi) ablative dose of 131I and was referred for a posttherapy whole-body scan (**b**). This study shows a focus of increased tracer uptake in the right neck, corresponding to the known remnant thyroid tissue in the right lobe. No additional lesions are seen. Note also physiologic RAI activity in the GIT, mainly the stomach and bowel, and the urinary bladder, and salivary glands. Impression: No evidence of metastatic thyroid cancer

**Fig. 5.8** History: A 6-year-old girl presented with a rightsided neck mass and underwent thyroidectomy. A 4-cm papillary carcinoma with extrathyroidal extension and lymph node involvement was found. Study report: The 123I post-thyroidectomy scan (**a**, whole-body anterior and posterior views, **b**, pinhole images of the neck) revealed several foci of remnant thyroid tissue in the neck as well as a focal area of tracer uptake in a left lung nodule as demonstrated on SPECT/CT (**c**), consistent with a RAI-avid left lung metastasis. The patient received a therapeutic dose of

3663 MBq (99 mCi) 131I . Post-therapy 131I whole-body (**d**) and pinhole images of the neck (**e**) show the same fndings seen on the pretreatment scan. Note also the large amount of physiological RAI excreted into the urinary bladder. A surveillance 123I follow-up study including a whole-body (**f**) and pinhole neck scan (**g**) performed 1 year after RAI treatment shows resolution of the previously seen foci of increased RAI activity in the neck and in the left lung metastasis. There are no new areas of abnormal RAI uptake. Impression: No evidence of thyroid cancer

**Fig. 5.9** History: A 14-year-old girl presented with a right thyroid nodule. US-guided FNA diagnosed papillary thyroid cancer. The patient underwent thyroidectomy and lymph node dissection. Right cervical lymph node metastases were found. Study report: A 123I whole-body scan performed after surgery was negative (**a**). The patient received RAI treatment with 3440 MBq (93 mCi) 131I. No sites of disease were found on a post-therapy scan (not shown). Six months later, the patient presented with rising Tg levels and suspicious cervical nodes on US. Because of known non-RAI-avid disease, the patient was referred to FDG-PET/CT (**b**) which shows a focal area of tracer uptake in the right upper cervical region. Impression: The fndings are consistent with right cervical lymph node metastasis, further confrmed following lymph node dissection

#### **References**


The opinions expressed in this chapter are those of the author(s) and do not necessarily refect the views of the IAEA: International Atomic Energy Agency, its Board of Directors, or the countries they represent.

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 3.0 IGO license (http:// creativecommons.org/licenses/by/3.0/igo/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the IAEA: International Atomic Energy Agency, provide a link to the Creative Commons license and indicate if changes were made.

Any dispute related to the use of the works of the IAEA: International Atomic Energy Agency that cannot be settled amicably shall be submitted to arbitration pursuant to the UNCITRAL rules. The use of the IAEA: International Atomic Energy Agency's name for any purpose other than for attribution, and the use of the IAEA: International Atomic Energy Agency's logo, shall be subject to a separate written license agreement between the IAEA: International Atomic Energy Agency and the user and is not authorized as part of this CC-IGO license. Note that the link provided above includes additional terms and conditions of the license.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

## **Digestive Tract 6**

Anita Brink, Lorenzo Biassoni, and Zvi Bar-Sever

#### **6.1 Gastroesophageal Refux Scintigraphy ("MILK SCAN")**

#### **Clinical Indications [1, 2]**

GER scintigraphy, is a sensitive, noninvasive, physiologic, direct technique indicated to detect GER and possible pulmonary aspiration in children with:


A. Brink (\*)

Nuclear Medicine and Diagnostic Imaging Section, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria

#### L. Biassoni

Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK e-mail: Lorenzo.Biassoni@gosh.nhs.uk

Z. Bar-Sever

Schneider Children's Medical Center, Tel Aviv University, Petah Tiqva, Israel

#### **Pre-Exam Information**


#### **Study Protocol for GER Test ("Milk Scan") [3]**

#### **Patient Preparation:**


#### **Radiopharmaceutical, Administered Activity, Mode of Delivery**

*Radiopharmaceutical:*


Nuclear Medicine Department, Division of Radiation Medicine, University of Cape Town, Cape Town, South Africa

#### *Activity:*


Reference to national regulation guidelines, if available, should be considered.

#### *Mode of Delivery—Feeding the Child:*


#### **Acquisition Protocol:**

	- Posterior dynamic images for 60 mins, 10–30 s/frame, matrix 128 × 128.
	- 1-h static anterior and posterior views of the chest, immediately after dynamic study, for an acquisition time of 3–5 mins, matrix 256 × 256.
	- 2–4 h static anterior and posterior views of the chest, after completion of the meal, for an acquisition time of 3–5 mins, matrix 256 × 256.
	- 24-h static images can be obtained as well.
	- Markers placed over suprasternal notch and xiphoid and/or 57Co transmission image of the thorax can be used to improve orientation and help determine the refux level and to adequately localize ectopic activity over the chest.

#### **Study Interpretation**

	- Number of episodes.
	- Level of refux: proximal or distal esophagus, oropharynx.
	- Intensity of refux: mild, moderate, severe.
	- Volume of refux: can be calculated by drawing a region-of-interest (ROI) over the activity in the esophagus and over the activity in the esophagus and stomach.

#### **Correlative Tests and Imaging**

	- Requires placement of a transnasal pH catheter into the esophagus to measure the pH over 24 h.
	- Extended monitoring provides an accurate estimation of the residence time of gastric content in the esophagus.
	- A drop in esophageal pH below 4 is suggestive of an acid refux episode.
	- Limitations: invasive nature; inability to detect episodes of nonacidic refux which have been associated with several pulmonary manifestations of GERD.
	- Intraluminal esophageal electrical impedance electrodes placed on a NG tube detect both acidic and nonacidic retrograde fow in the esophagus and are often coupled with esophageal pH monitoring thus increasing the sensitivity of the study.
	- It is less sensitive in detecting refux episodes and pulmonary aspiration.
	- It can show anatomical conditions that produce symptoms similar to GERD (pyloric stenosis, malrotation, etc.).
	- It can assess GER complications such as esophagitis and esophageal strictures.

#### **Red Flags**

• Extra care should be taken to avoid external contamination due to spillage of labelled milk during feeding or due to vomiting or regurgitation.


#### **Take Home Messages**


#### **Representative Case Examples**

**Case 6.1. Severe Gastroesophageal Refux Disease (Fig. 6.1)**

**Fig. 6.1** History: An 8-year-old child with Trisomy 21 and Moya-Moya disease. Aspiration was noted on a recently modifed barium swallow test. A milk scan was performed to assess for GER after administration of 18 MBq [Tc]Sn colloid in a volume of feed of 230 ml given through a nasogastric tube which was removed before the refux search. Study report (only the frames

recorded from 14 to 18 mins are shown): Refux reaching the proximal esophagus is seen on most of the 360 frames recorded during the observation period. The longest refux lasts 170 s. The refuxes contain up to 9 and 11% of total activity. Impression: The fndings are consistent with very severe GER

#### **Case 6.2. Pulmonary Aspiration (Fig. 6.2)**

**Fig. 6.2** History: A 12-year-old boy with spastic cerebral palsy and failure to thrive presented with swallowing diffculties. A GER study was performed to assess if GERD was the cause for his failure to thrive. The tracer and a milk-based meal were given orally. Study report: Multiple refuxes were observed during the GER study that fre-

quently reach buccal level (not shown). Posterior static images recorded at the end of the refux search (left) and at 2 h after tracer administration (right), demonstrate a large amount of tracer activity in the bronchial tree (arrows), more on the right. Impression: The fndings are consistent with pulmonary aspiration

#### **6.2 Gastric Emptying**

#### **Clinical Indications [4]**

	- Solid GE is considered more reliable and is the preferred study in older children and adolescents.
	- Liquid GE (better referred to as a semisolid meal), mostly milk based, is the only study that can be performed in infants and young children.

#### **Pre-Exam Information**


#### **Study Protocol for Liquid Gastric Emptying Test [1, 4, 5]**

#### **Patient Preparation:**

	- Plan the study to replace scheduled feeding (assuming the infant is fed every 3–4 h).
	- Bring the child's regular meal (cow milk, human milk, milk-based formula) in his/her regular feeding bottle and an additional empty bottle.

#### **Radiopharmaceutical, Administered Activity, Mode of Delivery**

*Radiopharmaceutical:*


#### *Activity:*


Reference to national regulation guidelines, if available, should be considered.

#### *Mode of Delivery:*


#### **Acquisition Protocol:**

*Liquid gastric emptying*—GE with milk or formula is often performed simultaneously with evaluation of GER.

#### **Acquisition Parameters:**


#### **Study Processing and Interpretation [6–8]**


#### **Study Protocol for Solid Gastric Emptying Test [1, 4, 5]**

#### **Patient Preparation:**


#### **Radiopharmaceutical, Administered Activity, Mode of Delivery**

*Radiopharmaceutical:*


#### *Activity:*

• A fxed dose of 9.25 MBq (0.25 mCi) for SC is recommended by the SNMMI. The EANM pediatric dose card uses patient weight to calculate the dose.

Refer to the pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

#### *Mode of Delivery:*

	- 120 grams of egg white
	- 2 toasted slices of white bread
	- 30 grams of strawberry jam
	- 120 ml of water

#### **Acquisition Protocol:**


#### **Study Processing and Interpretation [6–8]**

	- 37–90% at 1 h
	- 30–60% at 2 h
	- Less than 30% at 3 h.
	- Less than 10% at 4 h.

#### **Correlative Imaging**


#### **Red Flags**


#### **Take Home Messages**


• "Pseudo" normal reference values for liquid gastric emptying in children younger than 5 years were recently established, derived retrospectively from a selected group of over 2000 children without risk factors for gastric dysmotility who underwent GER scintigraphy.

#### **Representative Case Examples**

**Case 6.3. Delayed Gastric Emptying (Fig. 6.3)**

**Fig. 6.3** History: A 22-month-old girl with repeat episodes of regurgitation and vomiting was referred for evaluation. The patient was fed orally with 230 cc of milk formula labelled with Tc-sulfur colloid. Study report: Posterior view dynamic images obtained for 60 mins (**a**) demonstrate marked retention of tracer in the stomach.

Static images obtained at 1 h (**b**) and 4 h (**c**) after completion of feeding show signifcant gastric residual activity. The gastric residue from the initial gastric activity was 86% at 60 mins and 44% at 4 h. Impression: These fndings suggest delayed gastric emptying

#### **6.3 Esophageal Transit Studies**

#### **Clinical Indications**

Visual detection and quantitative evaluation of esophageal transit abnormalities.

#### **Study Protocol for Esophageal Transit Studies [1]**

#### **Patient Preparation:**


#### **Radiopharmaceutical, Administered Activity, Mode of Delivery**

#### *Radiopharmaceutical:*

• [ 99mTc]Sn-colloid or [99mTc]sulfur colloid.

#### *Activity:*

• A fxed dose of 9.25 MBq (0.25 mCi) for SC is recommended by the SNMMI. The EANM pediatric dose card uses patient weight to calculate the dose.

Refer to the pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

#### *Delivery:*

• A small volume (2.5–5 ml) of the feed is labelled and given to the patient with a syringe.

#### **Acquisition Protocol:**


#### **Study Interpretation**


#### **Normal Transit Study**


#### **Common Pathological Patterns**


**Fig. 6.4** Condensed image in a study with normal esophageal transit. Image (**a**) illustrates how the raw data of a single image of the dynamic series are compressed into a single column of the condensed image. Image (**b**) illustrates how the summed columns of each of the dynamic

image frames are arranged sequentially to form the condensed image. The condensed image makes it easier to assess the transit of activity through the esophagus from the mouth to the stomach


#### **Correlative Imaging**

• Modifed Barium swallow if available may provide useful additional information on the different phases of swallowing.

#### **Red Flags**


study. Placing paper towels under the child's chin allows the technologist to quickly remove contamination during study acquisition.


#### **Take Home Message**


#### **Representative Case Examples**

**Case 6.4. Normal Esophageal Transit Study (Fig. 6.5)**

**Fig. 6.5** History: A 9-month-old baby was repeatedly admitted to the hospital with recurrent chest infections and pneumonia over the last 5 months. The transit study was performed as a precursor to the GER study. Study report: There is rapid progression of tracer activity from the mouth to the stomach with all observed swallows (**a**). In condensed image (**b**), the black horizontal line at the top of the image represents the mouth and bottle, which both clear of activity after the frst few frames. The horizontal line at the bottom of the image represents activity in the stomach and only appears after a few frames. The vertical lines between the two horizontal lines are the swallows, each line corresponding to a single swallow. These lines are nearly vertical as you would expect in a patient with rapid transit of activity through the esophagus. The angle of the near vertical lines is infuenced by the position of the child and the frame rate. The angle between the vertical line and the line showing the passage of activity down the esophagus is wider if the child is supine or the frame rate is increased. Impression: Normal pattern of esophageal transit

**Case 6.5. Impaired Initiation of Swallowing (Fig. 6.6)**

**Fig. 6.6** History: A 16-month-old boy presented with feeding diffculties and symptoms of GER following an intraventricular bleed. Study report: There is a hold-up in the proximal third of the esophagus in several swallows (**a**). During the 1-min transit study 10 swallows were observed. In condensed image (**b**), the swallows have a repeat pattern of occurring in pairs, with the frst swallow of each pair showing prolonged hold-up in the proximal third of the esophagus. The hold-up persists at this level until the second swallow reaches this level, the activity then moves as a bolus to the distal esophagus. Impresison: This pattern suggests impaired initiation of swallowing seen in patients with neurological abnormalities

#### **6.4 Salivagram**

#### **Clinical Indications**

	- Children with neurological impairment, recurrent lung infections, and suspected pulmonary aspiration.
	- Children with normal neurological development presenting with recurrent lung infections or unexplained chronic lung disease.

#### **Study Protocol for Radionuclide Salivagram [9, 10]**

#### **Patient Preparation:**

There is no special patient preparation for this test. Ideally, the test should be done between feeds.

#### **Radiopharmaceutical, Administered Activity, Mode of Delivery**

#### *Radiopharmaceutical:*

• [ 99mTc]Sn-colloid or [99mTc]sulfur colloid.

#### *Activity:*

• 10–15 MBq (0.25–0.4 mCi) in small, approx. 0.1 ml, volume.

Refer to the pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

#### *Delivery:*

• The radiotracer is placed under the patient's tongue.

#### **Study Protocol:**

	- On dual head camera: optional simultaneous posterior and lateral acquisitions (detectors in "L" shape).

– If the patient is neurologically impaired with ongoing salivation it is useful to place linen savers under the head and over the chest. They can be replaced during the study if contamination occurs.

#### **Acquisition Parameters:**


#### **Study Interpretation [11]**

• Tracer visualizing the tracheobronchial tree or in the lung should be interpreted as aspiration.

#### **Correlative Imaging**


#### **Red Flags**


• If there is no clearance of buccal activity after 15 mins a small amount of water (about 0.25 ml) can be placed under the tongue.

#### **Take Home Messages**


#### **Representative Case Examples**

**Case 6.6. Normal Salivagram (Fig. 6.7)**

**Case 6.7. Tracheobronchial Aspiration (Fig. 6.8)**

**Fig. 6.7** History: A 6-month-old girl born prematurely developed nosocomial infections early during hospitalization. She had been admitted to the intensive care unit on four occasions with pneumonia and developed cystic lung disease. Study report: Early posterior images summed for

display at 10 s/frame (**a**) demonstrate prompt clearance of activity from the mouth to the stomach. No aspiration is detected. Planar images obtained after 1 h (**b**) show no evidence of tracer activity in the lungs. Impression: Normal salivagram. No evidence of pulmonary aspiration

**Fig. 6.8** History: A 13-year-old spastic quadriplegic patient with cerebral palsy presented with recurrent pneumonias. Study report: Early posterior images summed at 30 s/frame for display (**a**) show tracer activity entering the

trachea and stomach. Planar images obtained after 1 h (**b**) show tracer activity in the bronchi, bilaterally. Impression: Tracheobronchial aspiration

#### **6.5 Gastrointestinal Bleeding**

#### **Ectopic Gastric Mucosa (Meckel's Diverticulum Scan)**

#### **Clinical Indications [12, 13]**


tis, or, less common, due to recurrent intussusception.

• Unexplained anemia.

#### **Pre-Exam Information**


#### **Study Protocol for Meckel's Scan [13, 14]**

#### **Patient Preparation:**

	- Histamine H2 receptor antagonists reduce tracer release from the gastric mucosal cells. These drugs are most commonly used due to their availability, low cost, and infrequent side effects.
	- Cimetidine.

Orally (PO) for 1–3 days: 20 mg/ kg/day. In neonates 10–20 mg/kg/ day.

Intravenous (IV) 1 h before the scanning procedure: 300 mg in 100 mL of 5% dextrose over 20 min.

	- PO: 0.5 mg/kg/day.

IV 1 h before the scanning procedure: 0.25 mg/kg.

– Recently, proton pump inhibitors have been used to control acid secretion in children and some institutions may use this drug as a premedication. Currently, there are no fxed recommendations for the dose or the duration of this premedication.

#### **Radiopharmaceutical, Administered Activity, Mode of Delivery**

*Radiopharmaceutical:*

• [ 99mTc]pertechnetate (Pertechnetate).

#### *Activity:*

• 1.85 MBq/Kg (0.05 mCi/Kg), minimum dose 9.25 MBq (0.25 mCi).

Refer to the pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

#### **Acquisition Protocol [**15**]:**


#### *Acquisition Parameters:*

	- Post-void images are mandatory when there is signifcant bladder activity that can obscure focal uptake from an adjacent diverticulum.
	- Posterior and lateral views can help delineate renal uptake.
	- Standing/sitting views may be needed to differentiate normal tracer transit in the duodenum from uptake in ectopic gastric mucosa.
	- Additional views after diuretic administration may also be required.

#### **Study Interpretation [16]**

#### **Interpretation criteria for ectopic gastric mucosa:**

	- Other abdominal locations are occasionally seen.
	- The location of the focus may change during the study due to peristalsis.

#### **False positives: physiologic abdominal tracer biodistribution.**

• Focal tracer activity in the urinary tract:

Renal or extra-renal pelvis, dilated ureter, bladder diverticulum, vesicoureteral refux (VUR), ectopic kidney. Urinary tract activity is occasionally seen but it clears during the dynamic acquisition, unlike focal uptake in a Meckel's diverticulum.

	- Diffuse, usually in the left upper quadrant, or focal, commonly in the duodenal bulb.
	- Appears later in the study than uptake in ectopic gastric mucosa.
	- Cinematic display can identify normal tracer movement from the stomach to the duodenum and small bowel loops.

#### **False negatives:**


#### **Correlative Imaging**


#### **Red Flags**

	- Very small lesions that may frst appear a bit later than the stomach.
	- Uptake suspected to be in the excretory system. In doubtful cases, upright, postvoid, or repeat images after administration of furosemide may clear the urinary tract activity.
	- In patients who have acute GI bleeding with a signifcant drop in hemoglobin, the study may be falsely negative due to failure to deliver the tracer to the ectopic mucosa. This may necessitate a repeat scan 10–14 days later.
	- Active bleeding during imaging can dilute and shift tracer activity away from the diverticulum.

employed in vivo labelling of red blood cells (RBCs). Small amounts of persisting circulating Sn-pyrophosphate from the prior study, will cause Pertechnetate, injected for the Meckel's scan, to label RBCs and thus no uptake will be found in the gastric mucosa. This is not the case if in vitro labelling of the RBCs; then a Meckel's scan can be performed without interference.

#### **Take Home Messages**


lum. When adequately performed, it is reported to have a sensitivity of 94%, and a specifcity of 97%.

	- In small diverticula with low uptake.
	- For precise preoperative localization.
	- To identify ectopic gastric mucosa foci obscured by the bladder.

#### **Representative Case Examples**

**Case 6.8. Meckel's Diverticulum (Fig. 6.9)**

**Fig. 6.9** History: A 12-year-old boy presented with signifcant painless melena and a drop in hemoglobin. Study report: Following oral premedication with H2 blocker 6 h previously, Pertechnetate was injected, and dynamic fow images were obtained over 2 mins (not shown), followed by 15 mins of dynamic imaging of the abdomen and pelvis (**a**) Subsequently, static images were obtained at 20 mins (**b**). There is some activity in right and left kidney areas seen on the initial dynamic and static imaging that drained after the administration of 20 mg furosemide IV. There is a focal area of increased activity in the lower abdomen. SPECT of the abdomen and pelvis (**c**) identifes a focus of activity in the lower mid-abdomen (arrows). Impression: The fndings are consistent with an area of ectopic gastric mucosa in a Meckel's diverticulum

#### **Case 6.9. Meckel's Diverticulum (Fig. 6.10)**

**Fig. 6.10** History: An 11-year-old boy presented with recurrent abdominal pain and anemia. The study was requested in search of a possible Meckel's diverticulum with ectopic gastric mucosa as a cause of diverticulitis and was performed after premedication with ranitidine. Study report: Dynamic images obtained for 30 mins after administration of Pertechnetate show a focal uptake (arrow) in the lower pelvis, above the urinary bladder. This focus appeared simultaneously with the physiological uptake in the gastric mucosa and increased in intensity over time. Impression: The fndings are consistent with the diagnosis

of ectopic gastric mucosa. On surgery an infamed Meckel's diverticulum located proximal to the ileo-caecal valve was resected. Typically, a Meckel's diverticulum manifests as painless rectal bleeding in a young child, in most cases under 2 years of age. This case illustrates that occasionally less common presentations may be encountered, especially in older children, like in the present case in whom the child suffered from "Meckel's diverticulitis" with recurrent abdominal pain and chronic blood loss

#### **Blood Pool Scintigraphy**

#### **Clinical Indications**

• Detection of GIB.

#### **Pre-Exam Information**


#### **Study Protocol for GI Bleeding Scan [14, 17]**

#### **Patient Preparation:**

• No preparation is required.

#### **Radiopharmaceutical, Administered Activity, Mode of Delivery**

*Radiopharmaceutical:*

	- +2Sn pyrophosphate is injected in appropriate, weight-based amounts obtained from the package insert of the commercial cold kit.
	- Administration of Pertechnetate follows 20 mins later.

#### *Activity (Pertechnetate):*

• 74 MBq/Kg (2 mCi/Kg), minimum dose 74 MBq (2 mCi).

Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective European Association of Nuclear Medicine (EANM) and Society of Nuclear Medicine and Molecular Imaging (SNMMI) and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

#### *Delivery:*

• For in vitro labelled RBCs: the labelled blood should be slowly reinjected IV into the patient from whom it was drawn.

#### **Acquisition Protocol:**


#### *Acquisition Parameters:*


#### **Study Interpretation**


#### **Correlative Imaging**

• Angiography can be used both for detection of the GIB as well as for therapeutic purposes but requires larger bleeding volumes than scintigraphy.

#### **Red Flags**


#### **Take Home Messages**


**Fig. 6.11** History: A 3-year-old girl undergoing chemotherapy for leukemia experienced repeat episodes of melena and bright red blood rectal bleeding. Angiography failed to detect the bleeding source. Study report: Following reinjection of autologous Tc-labelled RBCs dynamic images of the abdomen acquired in the anterior

#### **Representative Case Examples Case 6.10. Left Upper Quadrant Gastrointestinal Bleeding (Fig. 6.11)**

#### **References**


view show abnormal tracer accumulation in the upper left quadrant (arrow). The uptake increases in intensity and changes in shape and location over time. Impression: These fndings suggest active gastrointestinal bleeding, most probably from the small intestines in the left upper quadrant


The opinions expressed in this chapter are those of the author(s) and do not necessarily refect the views of the IAEA: International Atomic Energy Agency, its Board of Directors, or the countries they represent.

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 3.0 IGO license (http:// creativecommons.org/licenses/by/3.0/igo/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the IAEA: International Atomic Energy Agency, provide a link to the Creative Commons license and indicate if changes were made.

Any dispute related to the use of the works of the IAEA: International Atomic Energy Agency that cannot be settled amicably shall be submitted to arbitration pursuant to the UNCITRAL rules. The use of the IAEA: International Atomic Energy Agency's name for any purpose other than for attribution, and the use of the IAEA: International Atomic Energy Agency's logo, shall be subject to a separate written license agreement between the IAEA: International Atomic Energy Agency and the user and is not authorized as part of this CC-IGO license. Note that the link provided above includes additional terms and conditions of the license.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

## **Liver and Spleen 7**

Anita Brink, Zvi Bar-Sever, and Lorenzo Biassoni

#### **7.1 Hepatobiliary Scintigraphy**

#### **Clinical Indications [1, 2]**


#### A. Brink (\*)

Nuclear Medicine and Diagnostic Imaging Section, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria

#### Z. Bar-Sever

Schneider Children's Medical Center, Tel Aviv University, Petah Tiqva, Israel

#### L. Biassoni

Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

#### **Pre-Exam Information**


#### **Study Protocol, Hepatobiliary Scintigraphy [3–5]**

#### **Patient Preparation:**

Fast: 4–6 h when the study is performed to investigate gallbladder pathology.

	- Preferred: ursodeoxycholic acid (UDCA), administered orally (PO) 20 mg/Kg every 12 h for 2–3 days prior to the study.
	- Alternative: Phenobarbital 5 mg/kg/ day, administered orally in two equal doses for 5 days prior to the study.

Nuclear Medicine Department, Division of Radiation Medicine, University of Cape Town, Cape Town, South Africa

<sup>©</sup> The Author(s) 2023 Z. Bar-Sever et al. (eds.), *A Practical Guide for Pediatric Nuclear Medicine*, https://doi.org/10.1007/978-3-662-67631-8\_7

#### **Radiopharmaceutical, Administered Activity, Mode of Delivery**

*Radiopharmaceutical:*


#### *Activity:*

	- Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.
	- Reference to national regulation guidelines, if available, should be considered.

#### **Acquisition Protocol:**


*Acquisition protocol* depends on the study indication; can be customized according to interim fndings.


*Suspected biliary atresia:*

• The study can be discontinued at earlier time points if there is clear evidence of tracer accumulation in the bowel.

*Suspected acalculous cholecystitis* includes a pharmacological intervention to stimulate gallbladder contraction:

	- Dose: 0.02 microgram/Kg diluted with saline to 30 ml.
	- Delivery: infusion pump at a rate of 1 ml/min for 30 mins.

#### **Study Processing:**


#### **Study Interpretation**

#### **Suspicion of Biliary Atresia [2, 6, 7]**

	- Severe neonatal hepatitis.
	- Other entities: bile plug syndrome in patients with cystic fbrosis, Alagille syndrome, dehydration, sepsis, and occasionally total parenteral nutrition may produce similar scintigraphic fndings.

#### **Acalculous Cholecystitis:**


#### **Choledochal Cysts:**


#### **Liver Transplant:[8–10]**

	- Contained bile leaks may be seen as ectopic sites of tracer accumulation usually close to the liver margins.
	- Free bile leaks typically manifest as ectopic tracer localization in the gutters or pelvic foor.

#### **Correlative Imaging [11–13]**


#### **Red Flags [9]**


#### **Take Home Messages**

	- Allows direct correlation between sites of tracer accumulation and anatomic fndings

such as fuid collections and abdominal cysts.


#### **Representative Case Examples**

#### **Case 7.1. Biliary Atresia (Fig. 7.1)**

**Fig. 7.1** History*:* A 6-week-old infant with prolonged direct hyperbilirubinemia. Biliary atresia was suspected. A hepatobiliary scan with Tc-Disofenin was performed. Study report: Dynamic images (**a**) obtained for 60 mins and static images obtained at 4 h (**b**) and 24 h after tracer administration (**c**) show tracer retention in the liver. There is no activity seen in the bowel. The 24-h images show faint tracer activity in the kidneys. The liver uptake is homogenous and there is no signifcant background activity. Impression: These fndings suggest that biliary atresia cannot be ruled out. The diagnosis was further confrmed by intraoperative transhepatic cholangiography

**Fig. 7.2** History: An 11-month-old girl presented with a large cyst in the region of the common bile duct as shown by US (**a**) and MRI (**b**, **c**) suspected to be a choledochal cyst. Scintigraphy was performed to assess the relationship of the cyst to the hepatobiliary system, which could not otherwise be established. Study report: Early dynamic scintigraphy (**d**) shows normal liver uptake and excretion,

with gradual tracer accumulation just below the inferior liver margin, most likely in the known cyst. Tracer activity was clearly noted in bowel loops with no evidence of obstruction. Late, 4- (**e**) and 24-h (**f**) images demonstrate continuing tracer pooling in the cyst (arrows). Impression: The fndings are consistent with a choledochal cyst, part of the biliary system

**Case 7.3. Acalculous Cholecystitis (Fig. 7.3)**

**Fig. 7.3** History: A 16-year-old boy experienced repeated episodes of upper abdominal colicky pain during and after meals. Cholecystitis was suspected. The US did not show stones in the gallbladder or bile ducts. Study report: Dynamic images acquired for 60 mins following tracer injection (**a**) show normal uptake in and excretion from the liver. There is tracer accumulation in the gallbladder. A fatty meal was given to stimulate gallbladder emptying, followed by only slight emptying on dynamic images acquired for additional 30 mins after ingestion of the meal (**b**). Gallbladder EF, calculated from static images obtained before and 30 mins after the fatty meal challenge (**c**) was 22% (normal values >35%). Impression: The fndings suggest acalculous cholecystitis with abnormal gallbladder contraction

#### **Case 7.4. Suspected Biliary Leak after Liver Transplant (Fig. 7.4)**

**Fig. 7.4** History: An 11-year-old girl underwent liver transplantation 3 weeks prior to the current examination. During her postoperative course, she developed septicemia and ascites and a bile leak was clinically suspected. Study report: Dynamic images acquired for 60 mins after tracer injection (**a**) show homogenous uptake in the transplanted liver with some accumulation at the site of the anastomosis, just below the inferior margin of the liver. There is prominent tracer activity in the tubing of the surgical drain positioned at the site of the anastomosis. No tracer transit into the bowel is noted. Static images at 1 h after tracer injection (**b**) show more tracer accumulation at the site of the anastomosis and a small amount in the bowel loops. At 4 h after tracer injection, anterior and posterior static images and a SPECT volume rendered image (MIP) (**c**) show cholestasis and tracer activity in the bowel loops. Impression: No evidence of bile leak

#### **7.2 Liver and Spleen Reticuloendothelial System Scintigraphy**

#### **Clinical Indications [14]**

At present, this study is performed quite rarely for relatively uncommon indications:


#### **Study Protocol for Liver-Spleen Scintigraphy [15]**

#### **Patient Preparation:**


#### **Radiopharmaceutical, Administered Activity, Mode of Delivery**

#### *Radiopharmaceutical:*

• [ 99mTc]sulfur colloid (SC).

#### *Activity:*

• 1.85 MBq/Kg (0.05 mCi/Kg), minimum dose 15 MBq (0.4 mCi).

Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

#### **Acquisition Protocol:**


#### **Study Interpretation (Fig. 7.5)**


**Case(s) 7.5 Patterns of liver and spleen SC uptake (Fig 7.5)**

**Fig. 7.5** Patterns of liver and spleen SC uptake. (**a**) Normal tracer uptake in liver and spleen in a 7-year-old girl with no evidence of immune defciency. (**b**) Reduced uptake in an anatomically normal spleen in a 4-month-old infant evaluated for functional hyposplenism following pneumococcal meningitis and pneumonia. (**c**) Transiently reduced uptake in the spleen in a 5-year-old girl following two episodes of pneumococcal meningitis who was suspected of functional hyposplenism. Reduced SC activity in the spleen supports the clinical suspicion (top row). The patient was treated with antibiotic prophylaxis. A repeat study 30 months later (bottom row) shows normalization of the tracer uptake by the spleen. Prophylaxis was discontinued

#### **Correlative Imaging**


#### **Red Flags**


• Occasionally there is a signifcant superposition of the left liver lobe and the spleen. Planar images may suggest asplenia and a transverselying liver. SPECT or SPECT/CT is essential to determine if there is, in fact, a superimposed functioning spleen.

#### **Take Home Messages**


#### **Representative Case Examples**

**Case 7.6. Asplenia (Fig. 7.6)**

**Fig. 7.6** History: A 4-month-old infant with heterotaxy syndrome that included ventricular and atrial septal defects and a right-sided stomach was evaluated for possible asplenia or polysplenia. Study report: Selected planar images (**a**) show a transverse lying liver and no splenic uptake, confrmed on selected SPECT slices (**b**). Impression: No evidence of functioning spleen tissue

#### **Case 7.7. Splenic Infarct (Fig. 7.7)**

**Fig. 7.7** History: This 12-year-old boy with previous biliary atresia and a functioning Kasai developed portal hypertension. He complained of recurrent sharp pain in the region of his enlarged spleen. There were concerns regarding a possible splenic infarct. Study report: The SPECT/CT study (selected SPECT and fused coronal, sagittal and transaxial slices, left, and MIP, right) shows a wedge-shaped defect in the lower pole of the spleen. Impression: The fndings are consistent with a splenic infarct in the lower pole of the spleen

#### **7.3 Spleen Scintigraphy with Denatured (Heat Damaged) Red Blood Cells**

#### **Clinical Indications [16]**


#### **Study Protocol for DRBC Spleen Scintigraphy [17, 18]**

#### **Patient Preparation:**


#### **Radiopharmaceutical, Administered Activity, Mode of Delivery**

#### *Radiopharmaceutical—Preparation:*

	- 1–3 ml of blood is drawn into a syringe containing heparin or acid citrate dextrose (ACD) solution for anticoagulation.
	- [ 99mTc] in vitro labelling of RBCs is performed.
	- Labelled RBCs are denatured by incubating the tube with the blood

in a warm water bath with a constant temperature of 49.5 °C for 15 mins.

– Allow the tube with the labelled blood to cool prior to reinjection.

#### *Activity:*

• 20–40 MBq (0.5–1 mCi).

Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

#### *Delivery:*

• Slow IV reinjection.

#### **Acquisition Protocol:**


#### **Study Interpretation**


#### **Correlative Imaging**

• US and cross-sectional imaging with CT and or MRI may confrm the presence, position, and appearance of splenic tissue.

#### **Red Flags**


• Scheduling no more than one RBC scan per session is a good practice to reduce the chance of labelled blood misadministration.

#### **Take Home Messages**


**Fig. 7.8** History: A newborn baby with heterotaxy syndrome and cardiac malformations that included patent ductus arteriosus, patent foramen ovale, and interrupted inferior vena cava was evaluated. Study report: Anterior and posterior planar images (**a**) and volume-rendered SPECT projections (**b**) show accumulation of DRBCs in three small adjacent spleens, ectopically located in the right upper abdomen (arrows). Impression: The fndings are consistent with polysplenia associated with left heterotaxy isomerism

#### **Representative Case Examples**

**Fig. 7.9** History: An 18-year-old girl with ITP underwent elective splenectomy because of life-threatening thrombocytopenia. The thrombocytopenia persisted despite the surgical removal of the spleen. Explorative laparotomy did not reveal any residual or ectopic splenic tissue. Study report: Planar views of the abdomen and lower chest (**a**) show a number of foci of DRBC uptake in the posterior upper abdomen, adjacent to the left posterior lower ribs (arrows). SPECT/CT (**b**) was performed to better localize the sites prior to re-exploration and showed intense uptake in one of the splenic nodules adjacent to the upper left posterior abdominal wall. Impression: Evidence for residual splenic tissue that was either not removed at previous surgery or represents splenosis due to auto-implantation of splenic tissue that occurred during operation

**Case 7.8. Polysplenia (Fig. 7.8)**

**Case 7.9. Residual splenic tissue (Fig. 7.9)**

#### **7.4 Liver Blood Pool Scintigraphy**

#### **Clinical Indications [19]**

• Detection and evaluation of hemangiomas.

#### **Study Protocol for RBC Scintigraphy [20]**

#### **Radiopharmaceutical, Administered Activity, Mode of Delivery**

#### *Radiopharmaceutical:*

	- In vitro labelling is the method of choice and should be employed when an adequate facility and proper radiopharmacy practices are available 1–3 ml of the patient's blood is drawn anticoagulated with heparin or acid citrate dextrose (ACD).
	- RBCs are labelled with a commercially available preparation according to the manufacturer's instructions.

#### *Activity:*

• Minimum dose 74 MBq (2 mCi), maximum dose 740 MBq (20 mCi).

Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

#### **Acquisition Protocol [**18**,** 22**]:**


*Acquisition Parameters:*


#### **Study Interpretation**


#### **Correlative Imaging**


#### **Red Flags**


#### **Take Home Messages**


#### **Representative Case Examples**

**Case 7.10. Liver Hemangioma (Fig. 7.10)**

**Fig. 7.10** History: A newborn in whom prenatal US detected a large mass in the left lobe of the liver confrmed on postnatal US was referred for RBCs scan since a hepatic hemangioma was included in the differential diagnosis. Study report: Late anterior and posterior planar images (**a**) show high physiologic activity in the splenic blood pool. A previously performed contrast-enhanced (ce) CT (**b**, left image) shows an enhancing mass (arrow) in the left hepatic lobe displacing the spleen posteriorly. SPECT (**b**, middle image) and co-registered SPECT-ceCT

#### **References**

1. Kianifar HR, et al. Accuracy of hepatobiliary scintigraphy for differentiation of neonatal hepatitis from biliary atresia: systematic review and meta-analysis of the literature. Pediatr Radiol. 2013;43(8):905–19.

(**b**, right image) show high blood pool with a central photopenic region in the mass (arrow). Uptake in the posterior portion of the mass is contiguous with the physiologic blood pool activity of the spleen. Impression: The fndings are consistent with a large liver hemangioma. Note that planar images could not identify the hemangioma because of the superposition of blood pool activities in the liver lesion and the spleen, which could be interpreted as normal spleen activity only


cholangiography, endoscopic retrograde cholangiopancreatography, percutaneous liver biopsy, risk scores and decisional fowchart. Pediatr Radiol. 2021;51(8):1545–54.


The opinions expressed in this chapter are those of the author(s) and do not necessarily refect the views of the IAEA: International Atomic Energy Agency, its Board of Directors, or the countries they represent.

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## **Genitourinary Tract 8**

Diego De Palma and Thomas Neil Pascual

#### **8.1 Dynamic Renal Scintigraphy**

#### **Clinical Indications [1]**


#### **Pre-Exam Information**


#### **Study Protocol for Dynamic Renography [2]**

#### **Patient Preparation**


D. De Palma (\*) Nuclear Medicine Unit, ASST Settelaghi, Varese, Italy

T. N. Pascual Department of Science and Technology, Manila, Philippines

<sup>©</sup> The Author(s) 2023 Z. Bar-Sever et al. (eds.), *A Practical Guide for Pediatric Nuclear Medicine*, https://doi.org/10.1007/978-3-662-67631-8\_8

### **Radiopharmaceutical, Administered Activity, Mode of Delivery**

*Radiopharmaceutical:*


#### *Activity:*

	- Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

#### **Acquisition Protocol**

*Patient Positioning*

	- If there is a history of an ectopic kidney, ensure that it is in the FOV and acquire, whenever possible, anterior view images contemporary and in addition to posterior views and calculate the differential renal function

(DRF) from the geometric mean of anterior and posterior renal counts.

– Patients with renal transplants will be acquired in the anterior view.

#### *Acquisition parameters*

Two acquisition protocols based on the timing of furosemide (F) administration can be used:

	- The pre- and post-furosemide dynamic images can be obtained as a single continuous acquisition or two separate acquisitions. In this second case, placing the child vertically for 5–10′ may allow the kidney to empty enough, at physician's judgement, to avoid furosemide administration and shorten the scan time.
	- Whenever the pelvis is not full after 20 or 30 mins furosemide administration should be delayed until the pelvis is flling up.

age is inadequate at the end of the post-furosemide dynamic sequence.


#### **Dynamic Renogram Study Processing and Interpretation [3, 5]**

#### **Study Processing**

	- Integral method using the area-under-thecurve (AUC) is preferred because it is less sensitive to patient's motion.
	- the Rutland Patlak method.
	- Draw renal regions-of-interest (ROIs) around the visible renal parenchyma being careful not to "cut" the kidney and not to include the collecting system. Large ROIs containing the yet unflled pelvis are not acceptable for the DRF calculation.
	- For MAG3 studies, the ROI is constructed on the 60–120 s summed image.
	- For DTPA, the ROI is constructed on the 120–180 s summed image.

**Fig. 8.1** Example of kidneys (red line for the left and pink for the right kidney) and background (purple on the left and blue on the right) ROIs


#### **Renogram Processing Quality Control**

It is advised to perform the following quality assurance steps, mainly in infants and children with impaired renal function: Process the renogram more than once to check for reproducible values. (i.e., within 4%), modifying size and location of the background ROIs or the time interval selected for the calculation.

#### **Processing the Diuretic Response**

	- Should be positioned on the summed images showing the maximal dilatation of the collecting system.
	- This ratio normalizes the residual activity to the parenchymal function of the kidney.
	- Typical time points for NORA calculation include the end of the post-furosemide dynamic sequence and, most importantly, the late, post-micturition, post-gravityassisted image.

#### **Study Interpretation**

	- The tracer uptake in each kidney at 1–2 mins after the beginning of the study and the appearance of the kidneys on these images.
	- With MAG3, which is a cortical agent, assesses for the presence of cortical defects, for signs of duplications of the excretory

system (see Sect. 8.2) and if there are abnormal renal positions or shapes.


#### **Correlative Imaging**


#### **Red Flags [6, 7]**

• If the F + 0 protocol is planned and the child has an adequate oral fuid intake, a venipuncture with a 25-gauge needle and a three-way stopcock for saline fushing can be used when only very thin veins seem available.

	- Renal immaturity in neonates makes it essential to use tubular agents such as MAG3.
	- In the presence of excessive movement during the frst 1–3 mins of the study, if available, utilize a dynamic motion correction program.
	- Looking at DRF values, check the correct drawing of background ROIs in case of apparent discrepancy between values and images. This is especially important in young infants with physiologic renal immaturity and in cases of impaired renal function. It may be also diffcult in some infants with huge hydronephrotic kidneys abutting the abdominal wall.
	- Acute UTI can cause a transient drop in DRF. In children presenting with signs or symptoms of UTI or fever, it may be useful to do a urinary dipstick on the day of the study to ensure that there is no ongoing infection at the time of the investigation.

#### **Take Home Messages**


acquire, whenever possible, anterior view images contemporary and in addition to posterior views using a dual-head camera to improve the accuracy of the DRF.


#### **Representative Case Examples**

#### **Case 8.1. Normal Renogram (Fig. 8.2)**

**Fig. 8.2** History: A 6-year-old boy with recurrent UTIs and possible VUR performed a renogram following administration of MAG3 as a precursor for the indirect cystogram. Study report: There is good symmetrical uptake in both kidneys. No cortical defects are seen. The calyces, pelvises, and bladder are visualized 3 mins after tracer injection. There is good clearance of activity from

the kidneys to the bladder, as shown on the summed 1 min images of the renogram. The DRF is normally balanced, left kidney 49%, right kidney 51%, and the perfusion and clearance curves are normal on the 1–2.5 min clearance image with drawn ROIs. Impression: This is a normal renogram

#### **Case 8.2. Dilated Right Excretory System with no Evidence of Obstruction (Fig. 8.3)**

**Fig. 8.3** History: A 6-month-old boy with mild-tomoderate dilatation of the right excretory system, seen on serial US examinations, performed a diuretic renal scan to exclude obstruction. The patient was orally pre-hydrated and the study was performed with the F+0 protocol, furosemide administered at a dose of 1 mg/kg. Study report: The dynamic phase over 25 mins shows mild-to-moderate dilatation of the right excretory system, with constant

visualization of the ureter that appears minimally convoluted. DRF is 52% on the left and 48% on the right. During the study acquisition there is good clearance of the tracer from both kidneys. The clearance curves confrm bilateral normal clearance, with tracer that has already cleared from the left side. Impression: There is no evidence of obstruction

#### **Case 8.3. Hydronephrotic Kidney, Follow-Up after Pyeloplasty for UPJ (Fig. 8.4)**

**Fig. 8.4** History: A 1-month-old girl presented with severe right hydronephrosis, frst detected on prenatal US, antero-posterior pelvic diameter (APD) 33 mm, further confrmed on postnatal US which showed an APD 23 mm and severe right renal parenchymal thinning. Study report: A MAG3 scan with the F+0 protocol was obtained (**a**), including a late post-void, gravity-assisted image at 45 mins. The right kidney is enlarged and hydronephrotic. Cortical uptake is reduced, especially in the lower pole, DRF 39%. There is prolonged CTT to the large, hydronephrotic right renal pelvis with no drainage. The left kidney shows normal parenchymal uptake, DRF 61%. The diuretic renogram curve is rising. The left kidney shows good although slow drainage. There is a signifcant residual activity in the right pelvis and a small residual amount in the left renal pelvis. The 45-min NORA value of the right kidney is elevated, 1.8. The fndings are consistent with right hydronephrosis with reduced parenchymal function and markedly impaired drainage. The left kidney shows a normal function with tracer pooling in the pelvis but no evidence of a signifcant obstruction. The patient underwent a right pyeloplasty to relieve the UPJ obstruction. Follow-up US studies showed a gradual reduction in the size of the right pelvis. A follow-up scan using the same study protocol was obtained 1 year later (**b**). The right kidney is normal in size with only a moderate pelvic impression. Cortical uptake has improved, DRF 43%. There is normal tracer accumulation in the right pelvis with good drainage. The left kidney shows normal parenchymal uptake, DRF 57%. The diuretic renogram curve is near normal, with good drainage. There is a small, nonsignifcant residual activity in the right pelvis and the 45-min NORA value of the right kidney is now normal, 0.4. Impression: Following the fndings of obstructive UPJ in the preoperative scan (**a**) and surgery to relieve the obstruction, a follow-up diuretic renogram (**b**) shows improved function and drainage of the right kidney with no evidence of residual obstruction. Normal left kidney with improved drainage as compared to the frst study

#### **Case 8.4. Hydronephrotic Kidney, Spontaneous Improvement (Fig. 8.5)**

**Fig. 8.5** History: A 1-month-old infant presented with right hydronephrosis, frst detected on prenatal US, confrmed on postnatal examination with an APD of 20 mm, a dilated calyceal system, parenchymal thinning (4 mm) and a renal longitudinal length of 64 mm versus 49 mm of the left kidney. Study report: A MAG3 scan with the F+0 protocol was obtained, including late post-void, gravityassisted image at 45 mins (**a**). During the frst 3 mins of the study, the right kidney appears enlarged and hydronephrotic, with a good cortical uptake, DRF 43%. There is slow CTT to a large, hydronephrotic right pelvis. The left kidney shows normal parenchymal uptake, DRF 57%. The diuretic renogram curve is rising with progressive accumulation of tracer in a huge right renal pelvis with no drainage. In the "post-void image" (diaper was changed), there is a signifcant residual activity in the right renal pelvis and a small residual amount in the left renal pelvis. The 45-min NORA value of the right kidney is markedly elevated (>3). These fndings suggest right hydronephrosis with preserved parenchymal function and markedly impaired drainage, worrisome for UPJ obstruction. The left kidney shows fast and complete drainage. Following these fndings, the infant entered a strict follow-up protocol. US performed at 3 months of age showed a decrease in the size of the right renal pelvis. The two kidneys had about the same longitudinal length, 56 vs 54 mm. A follow-up diuretic renogram using the same study protocol was obtained at the age of 4 months (**b**). During the frst 3 mins of the study, there is improvement in the appearance of the right kidney showing a smaller renal pelvic enlargement and good cortical uptake, with an unchanged DRF of 46%. CTT to a less dilated renal pelvis is still longer than for the left kidney which shows normal parenchymal uptake, DRF 54%. The renogram curve shows progressive tracer accumulation in the right renal pelvis with partial drainage. The left kidney shows fast and complete drainage. In the "postvoid image," there is a reduced but signifcant residual activity in the right renal pelvis. NORA of the right kidney has decreased to 1.9 but is still abnormal. Impression: Right hydronephrotic kidney with preserved parenchymal function and markedly impaired drainage, worrisome for UPJ obstruction which improves on the follow-up study performed 3 months later. Normal functioning left kidney with no evidence for signifcant obstruction

**Case 8.5. Duplicated Left Excretory System with Obstruction of the Upper Pole (Fig. 8.6)**

**Fig. 8.6** History: A 1-month-old girl presented with US fndings of complete duplication of the left excretory system and left intravesical ureterocele with dilatation of the upper pole excretory system. Diuretic renal study was requested to quantify the function of the upper pole. The patient was orally pre-hydrated. Study report: The study was performed with the F + 0 protocol, with a dose of Furosemide of 1 mg/kg. The diuretic renogram (**a**) shows dilatation of the upper pole of the left kidney. DRF was 56% on the left and 44% on the right. After about 8 mins there is a visualization of the left upper pole ureter that appears minimally convoluted. There is good clearance of

the tracer from the right and the lower half of the left kidney, confrmed on the clearance curves. Note an artifact due to superimposition of the very full bladder to the background ROI. A repeat second analysis was performed (**b**) drawing separate ROIs around the two left kidney moieties. Relative DRF was 55% for the lower and 45% for the upper pole. There is good clearance of the tracer from the lower half while the upper one does not satisfactorily empty. Impression: The fndings suggest obstruction of the upper pole of the left kidney due to ureterocele, with preservation of the regional function. Ureterocoele incision was then performed

#### **8.2 Renal Cortical Scintigraphy**

#### **Clinical Indications [11–13]**

	- DRF (one kidney relative to the other).
	- Upper vs. lower pole in cases of renal duplication.

#### **Pre-Exam Information**


#### **Study Protocol for Renal Cortical Scintigraphy [14, 15]**

#### **Patient Preparation**

• No patient preparation is required.

#### **Radiopharmaceutical, Administered Activity, Mode of Delivery**

*Radiopharmaceutical:*

• [ 99mTc]dimercaptosuccinic acid (DMSA) is the agent of choice.

*Activity:*

• 1.85 MBq/Kg (0.05 mCi/Kg), minimum dose 18.5 MBq (0.5 mCi).

Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to National Regulation Guidelines, if Available, Should Be Considered.

#### **Acquisition Protocol**


#### **Study Interpretation [7, 16]**

• Always based on at least a complete set of planar images (posterior, left and right posterior oblique, anterior whenever acquired) in black

**Fig. 8.7** Quality control of planar DMSA scan. Good quality images must show sharp renal outline and corticomedullary differentiation

and white, white background, with DRF clearly indicated, rounded up to the unit.


#### **Normal variants:**


**Fig. 8.8** DRF measurements in patients with renal ectopy. Calculations are based on the geometrical mean of counts measured in both anterior and posterior images

#### **Abnormal patterns:**


#### **Correlative Imaging [17, 18]**


#### **Red Flags**


• For diagnosis of scars, the DMSA study should be performed at least 6 months after the last documented infection to determine if the cortex has healed or was permanently damaged. Scans performed earlier than 6 months since the last UTI may be too early to identify true scarring.

#### **Take Home Message**


#### **Representative Case Examples**

**Case 8.6. Small Left Kidney with Scars (Fig. 8.9)**

**Fig. 8.9** History: A 5-year-old girl with a history of recurrent UTIs and a renal US reported as normal was referred for DMSA scintigraphy to assess for the presence of parenchymal scarring. Study report: Anterior and posterior planar images (**a**) show a small left kidney with an

irregular contour. There are multiple peripheral defects in the cortical outline accompanying volume loss of the left kidney, best depicted on the coronal SPECT slices (**b**). Impression: Small left kidney with multiple scars

#### **Case 8.7. UTI with Progression of Bilateral Renal Scars (Fig. 8.10)**

**Fig. 8.10** History: A 4-year-old girl with recurrent UTIs and VUR had been lost to follow-up and returned to the clinic after 4 years with an ongoing history of infections. Study reports: the frst DMSA study, anterior and posterior planar images (**a**) and coronal SPECT slices (**b**) show a small cortical defect in the lower pole of the right kidney (arrow) consistent with a small renal scar. The left kidney appears normal. The DRF of the right kidney is 43% and on the left 57%. On a follow-up DMSA study performed

4 years later planar images (**c**) and coronal SPECT slices (**d**) show decreased, inhomogeneous tracer uptake in the right kidney with multiple peripheral cortical defects (arrows). An additional cortical peripheral defect is noted in the lateral aspect of the upper pole of the left kidney (arrow). The DRF of the right kidney has dropped to 14%. Impression: Signifcant scarring has occurred in both kidneys in the 4-year time interval from the baseline study

**Case 8.8. Acute Pyelonephritis (Fig. 8.11) Case 8.9. Non-functioning Left Lower Renal Pole (Fig. 8.12)**

**Fig. 8.11** History: A 4-year-old girl was referred for scintigraphy due to recurrent UTIs. The frst DMSA scan was performed more than 6 months after the last infection. Seven months later she was hospitalized with high fever most probably due to a new UTI. An "acute" DMSA scan was performed during her hospitalization and compared to the previous study. Study reports: the frst DMSA study

planar posterior view (**a**) demonstrates a normal DMSA uptake pattern. The second study, the "acute" DMSA scan, planar posterior view (**b**) shows new areas of decreased uptake (arrows) in the right kidney with preserved renal contour. The right kidney DRF has decreased from 45% to 37%. Impression: The fndings on the second DMSA study are consistent with acute pyelonephritis

**Fig. 8.12** History: A 2-year-old boy presented with left duplex collecting system. The lower collecting system was severely hydronephrotic. A DMSA scan was obtained to assess the parenchymal function of the lower pole. Study report: Anterior and posterior planar images (**a**) and coronal SPECT slices (**b**) show a sharp demarcation between the upper and lower poles of the left kidney. The upper pole has normal cortical uptake, whereas the lower pole shows no uptake and function. Impression: Nonfunctioning lower pole of left kidney

#### **8.3 Glomerular Filtration Rate Radionuclide Measurement**

#### **Clinical Indications**


#### **General Principles for Glomerular Filtration Rate (GFR) Measurements [21]**

	- Is freely fltered in the glomerulus.
	- Does not bind to plasma proteins.
	- Is not secreted or reabsorbed by the renal tubules.
	- The "slope-intercept method": requires two blood samples at 2 and 4 h after tracer injection.
	- The "distribution volume" method: requires a single blood sample 110– 130 mins after tracer injection. This method is more practical in young children, avoiding repeated venipunctures. It is considered less accurate than the two-sample methods when GFR is expected to be <30 ml/ min/1.73m2 .

#### **Study Protocol for GFR Measurements** Considered. **[21–23]**

#### **Patient Preparation**

	- A scientifc scale
	- Volumetric fasks
	- A centrifuge
	- A well-counter

#### **Radiopharmaceutical, Administered Activity, Mode of Delivery**

*Radiopharmaceuticals:*


#### *Activity:*

	- For simple GFR estimate: 30 MBq (0.8 mCi, adult dose) × (patient BSA/1.73 m2 ).
	- For simultaneous GFR and DTPA dynamic renal scan: 120 MBq (3.2 mCi, adult dose) × (patient BSA/1.73 m2 ).

Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to National Regulation Guidelines, if Available, Should Be

#### **GFR Step-by-Step: The Single Blood Sample Using the "Weight" Method***"*


#### **GFR Single Blood Sample Processing**

• Centrifuge the blood samples at 3000 rotations/min for 5 mins to separate the plasma and blood cells.

	- 1 ml of your standard solution × 2.
	- 1 ml of the plasma sample × 2.

#### **GFR Calculation**


#### Counts injected counts ( ) / min

Counts of the plasma sample coun ( ) ts / min .


**Fig. 8.13** Excel sheet including all measured parameters and calculations made with the creatinine-based method


#### **GFR Quality Control**


#### *Normal Values [*25*]:*

Normal GFR values are 104 ± 20 ml/ min/1.73 m2 body surface area (BSA), in the age range 2–15 years.

Below 2 years of age:


#### **Red Flags**

	- 4.1% in patients with a GFR > 30 ml/min.
	- 11.5% in patients with a GFR < 30 ml/ min2 .

#### **Take Home Message**

• A detailed protocol of the two methods is available in the EANM guidelines for glomerular fltration rate determination in children [26].


#### **8.4 Direct Radionuclide Cystography (DRC)**

#### **Clinical Indications [28, 29]**


#### **Pre-Exam Information**


#### **Study Protocol for Direct Radionuclide Cystography [28, 30]**

#### **Patient Preparation**

*Preparation prior to bladder catheterization*

	- Infants <1 year: Capacity (ml) = (2.5 × age [months]) + 38.
	- Older children >1 year: Capacity (ml) = (2 + age [years]) × 30.

*Catheterization Technique*


#### **Radiopharmaceutical, Administered Activity, Mode of Delivery**

*Radiopharmaceutical:*

• [ 99mTc]DTPA.

*Activity:*

• 20 MBq (0.5 mCi) followed by 100– 500 ml saline according to bladder estimate volume.

Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.


#### **Acquisition Protocol**


#### **Study Processing**


#### **Study Interpretation**

	- Mild refux: in the ureter.
	- Moderate refux: in the non-dilated collecting system and ureter.
	- Severe refux: in dilated collecting system and ureter.

#### **Correlative Imaging**

• Fluoroscopic voiding cystourethrography (VCUG) has been the standard for detection and classifcation of VUR utilizing a 5-point scale. It is the best method to visualize the urethra in males and especially for detection of posterior urethral valves. It does require direct bladder catheterization and utilizes fuoroscopy to view bladder flling and presence of refux. The bladder can be flled more than once but because of use of fuoroscopy there is potential for a signifcantly increased radiation exposure to the child [32, 33].

• More recently the use of US contrast-enhanced voiding cysto-sonourethrography has been proposed as a replacement for previous techniques. It employs US without radiation exposure but still requires direct bladder catheterization. The posterior urethra can be adequately visualized when multiple cycles of bladder flling can occur. Like many US techniques, it is highly operator-dependent, and the learning curve and scanning time are longer in comparison to both X-ray and radionuclide methods [34].

#### **Red Flags**


tance should not be forced because, although very rarely, the catheter can enter a very dilated, the so-called "golf-hole," ureteral meatus.

• Sometimes, older non-toilet-trained children may feel such subjective pain during the frst attempt to void with the catheter in situ that they will subsequently refuse to void for many hours. In this case, it is up to the caring physician to decide when to stop the scan (normally, do not wait for more than 1 h).

#### **Take Home Message**


#### **Representative Case Examples**

#### **Case 8.10. Bilateral VUR (Fig. 8.14)**

**Fig. 8.14** History: A 4-year-old girl with recurrent UTI. Study report: During the flling phase (**a**, volume 250 ml) VUR is detected, more evident on the left side, persisting during the voiding phase (**b**), also seen on the post-void image (**c**). Impression: Bilateral moderate VUR

**Fig. 8.15** History: 1-year-old girl had a DRC performed one month after a febrile UTI. US had been reported as normal. Study report: After clean catheterization, the radiopharmaceutical was injected through the bladder catheter, followed by warm saline. A series of 5 s sequential frames was acquired, starting at the time of tracer administration. Selected frames show during the late flling phase, a left-side VUR which increases (arrow) during the voiding phase. The refux activity returns to the bladder after the end of the voiding, although incomplete. A second voiding phase without a new increase of the residual intra-pelviureteric activity is visible in the last three images. Impression: Unilateral active and passive severe VUR

#### **Case 8.12 Intermittent unilateral VUR (Fig. 8.16)**

**Fig. 8.16** History: Four-year-old girl. The frst episode of febrile UTI 3 months prior to current study, had an early relapse after the end of the 2-weeks course of antibiotic therapy. Study description: After clean catheterization, the radiopharmaceutical was injected through the bladder catheter, followed by warm saline. A series of 5-s sequential frames were acquired, starting together with the

administration. Grouped 10-sec images are shown. In the early flling phase, a left-side VUR is detected, randomly increasing and decreasing during the bladder flling. No active refux is visible during the voiding phase (blue box). Impression: Unilateral intermittent, passive, moderate VUR

#### **8.5 Indirect Radionuclide Cystogram (IRC)**

#### **Clinical Indications (***in Toilet-Trained Children!***) [36–38]**


#### **Study Protocol for Indirect Radionuclide Cystography [29, 36]**

#### **Patient Preparation**


#### **Radiopharmaceutical, Administered Activity, Mode of Delivery**

*Radiopharmaceutical:*

• [ 99mTc]MAG3.

*Activity:*

• 3.7–5.55 MBq/kg (0.10–0.15 mCi/kg). Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to National Regulation Guidelines, if Available, Should Be Considered.

#### **Acquisition Protocol**

	- Girls: Put a bedpan on the seat of a backless chair. A parent/caregiver can help stabilize the patient on the bedpan.
	- Boys: The patient stands and holds the urine bottle or his parent/caregiver does it for him.

To improve privacy, only one or two technologists, preferably of the same sex as the patient, are in the room with the parents and patient.

*Acquisition Parameters*


#### **Study Processing**

*Methods for accurate assessment of VUR, eliminating errors that may lead to false positives*:


#### Example:


#### **Study Interpretation**


#### **Correlative Imaging [1]**


#### **Red Flags [1, 38]**

• The technologist usually starts the acquisition once the patient is comfortably seated and positioned. In case of poorly cooperative chil-

**Fig. 8.17** Makeshift gender-adapted toilet in front of the camera. For girls (left) there is a bedpan on the seat of a backless chair. For boys, the patient stands and holds the urine bottle (right)

dren, it may be necessary to start during patient positioning.


#### **Take Home Messages**


#### **Representative Case Examples**

**Case 8.13. Normal Indirect Radionuclide Cystography (Fig. 8.18)**

**Fig. 8.18** History: A 5-year-old boy with recurrent UTIs and a family history of VUR. Study report: The posterior IRC images acquired for 1 s/frame show no evidence of refux and complete bladder emptying. Impression: Normal study

#### **Case 8.14. Positive Indirect Radionuclide Cystography (Fig. 8.19)**

**Fig. 8.19** History: An 11-year-old with bilateral VUR grade 3–4 diagnosed at 1 year of age. On US his left kidney was smaller than the right one. He was followed conservatively and remained asymptomatic for 10 years. Following a doubtful febrile UTI a renogram followed by an indirect cystogram was performed Study report: Parenchymal phase posterior images of the renogram (**a**) showed a small left kidney with a DRF of 32%, and a normal right kidney with a DRF of 68%. On IRC (**b**) refux into the left kidney is seen when the child starts to void (arrows). Bladder emptying is complete. Impression: Small left kidney with moderate refux during micturition

#### **Case 8.15. Non-functioning Left Kidney with Refux (Fig. 8.20)**

**Fig. 8.20** History: A 7-year-old girl with recurrent UTIs. On US her left kidney is small and hydronephrotic. A renogram followed by an indirect cystogram was performed. Study report: On posterior images of the renogram (**a**) acquired for 2 s/frame, perfusion and uptake to the right kidney is normal. There is prompt drainage of activity from the kidney to the bladder. There is no functioning tissue in the expected position of the left kidney. A

small amount of activity is seen entering the left kidney after the bladder starts to fll. On IRC (**b**), repeated episodes of refux into the left kidney are seen before the child starts to void and during voiding. This activity persists in the left kidney until the end of the study. Impression: Non-functioning left kidney with refux during bladder flling and micturition. Bladder emptying is incomplete. Normal functioning right kidney

#### **Case 8.16. Two-Voids IRC (Fig. 8.21)**

**Fig. 8.21** History: A 5-year-old boy with previous resection of posterior urethral valves and residual, bilateral, high-grade VUR. A renogram followed by an IRC was performed for evaluating DRF, drainage, and persistence of VUR. Study report: At the frst void (**a**) bladder emptying is complete but there is residual activity in the upper tract and the presence of VUR cannot be correctly assessed. At a second void after bladder reflling by the residual activity (**b**), bilateral VUR is clearly visible. Impression: Persistent bilateral VUR

#### **References**


tration of the ultrasound contrast agent Optison™ for vesicoureteral refux detection in children: a prospective clinical trial. Pediatr Radiol. 2018;48(2):216–26.


The opinions expressed in this chapter are those of the author(s) and do not necessarily refect the views of the IAEA: International Atomic Energy Agency, its Board of Directors, or the countries they represent.

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 3.0 IGO license (http:// creativecommons.org/licenses/by/3.0/igo/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the IAEA: International Atomic Energy Agency, provide a link to the Creative Commons license and indicate if changes were made.

Any dispute related to the use of the works of the IAEA: International Atomic Energy Agency that cannot be settled amicably shall be submitted to arbitration pursuant to the UNCITRAL rules. The use of the IAEA: International Atomic Energy Agency's name for any purpose other than for attribution, and the use of the IAEA: International Atomic Energy Agency's logo, shall be subject to a separate written license agreement between the IAEA: International Atomic Energy Agency and the user and is not authorized as part of this CC-IGO license. Note that the link provided above includes additional terms and conditions of the license.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

## **Lymphoscintigraphy 9**

Thomas Neil Pascual, Pietro Zucchetta, Kevin London, and Robert Howman-Giles

#### **9.1 Clinical Indications [1, 2]**

• Sentinel lymph node (SLN) localization in malignancies, more common in children with diagnosis of melanoma and soft tissue sarcoma

Assessment of lymphedema.

#### **9.2 Pre-exam Information**

	- Type and location of the malignancy.
	- History or planning of the surgical resection of the tumor.
	- Site of extremity edema.
	- History of surgery or trauma that could affect lymphatic drainage.
	- Suspected chyloascites or chylothorax.

T. N. Pascual (\*) Department of Science and Technology, Manila, Philippines

P. Zucchetta

Nuclear Medicine Unit, Department of Medicine, Padova University Hospital, Padova, Italy

K. London · R. Howman-Giles Nuclear Medicine Department, Children's Hospital at Westmead, University of Sydney, Camperdown, NSW, Australia

– Suspected developmental anomalies of the lymphatic system such as abdominal or thoracic lymphangiectasia.

#### **Study Protocol for Lymphoscintigraphy [3]**

#### **Patient preparation**


Study scheduling:

	- Number and type of injections depend on tumor type and whether it has been excised.
	- Coordination of lymphoscintigraphy and surgical excision of SLN is required.

© The Author(s) 2023

Z. Bar-Sever et al. (eds.), *A Practical Guide for Pediatric Nuclear Medicine*, https://doi.org/10.1007/978-3-662-67631-8\_9


#### **Radiopharmaceutical, Administrated activity, Mode of delivery**

*Radiopharmaceutical*

• [ 99mTc] labelled colloidal nanoparticles.

#### *Activity*

• 18.5–37 MBq (0.5–1.0 mCi) total dose for all ages.

#### *Delivery*


#### *For SLN mapping and biopsy*


• For cutaneous tumors of the head, neck, torso, and upper thighs, 2–4 injections around the tumor or site of surgical resection are essential because lymphatic drainage from these locations is unpredictable.

#### *For lymphedema or lymphatic malformation*


#### **Acquisition protocol**

*For SLN mapping and biopsy* [4, 5]:

	- For tumors in the limbs and head and neck, the FOV should include the adjacent torso.

– For tumors located in the torso, the entire torso should be imaged.


*For lymphedema or lymphatic malformations* [6–9]:


#### **9.3 Study Interpretation**

*For SLN mapping and biopsy* [4, 5, 10, 11]:


*For lymphedema or lymphatic malformations* [7, 8, 12, 13]:

	- Inguinal LNs within 45 min after foot injections.
	- Axillary LNs within 30 min after hand injections.
	- Liver within 4 h post-injection.
	- There is a delayed appearance of LNs
	- Lymphatic channels appear dilated.
	- Collateral lymphatic channels have been identifed.
	- Diffuse tracer activity is seen in the superfcial soft tissues (dermal backfow).
	- There is a paucity of tracer localization in inguinal and pelvic LNs.
	- Chylous pleural effusion and/or chylous ascites.
	- Intestinal lymphangiectasia or pulmonary lymphangiomatosis.
	- Tracer injection in the feet or left arm will show tracer accumulation in the pleural cavity.
	- Tracer injection in the right arm will show normal transit into the systemic circulation and normal liver accumulation.

#### **9.4 Correlative Imaging [9, 14]**


#### **9.5 Red Flags [15–17]**

	- Particle size differs among various commercial preparations. This can affect the velocity of tracer transit and the time required to detect the SLN.
	- In cases with tumors of the torso transit from the injection site is less predictable and could include more than one drainage basin.
	- External radionuclide markers to outline the body surface or a superimposed 57Co food source transmission image helps localize the sites of tracer activity.
	- Care should be taken not to miss a SLN if it may be located adjacent to the injection site and therefore masked by the high tracer activity. In these cases, use SPECT/CT whenever possible.
	- The study provides functional information on lymph transit. However, it may be limited in discerning the etiology of the abnormality and associated morphological fndings.
	- The injections into each limb should be performed in rapid succession to ensure

that differences in the rate of tracer transit in the limbs are not related to a delay in the timing of the second injection.


#### **9.6 Take Home Messages**


• Dermal backfow refers to a phenomenon in which lymphatic fuid leaks and accumulates in the skin and soft tissues by regurgitating the lymphatic fow because of increased pressure caused by occluded lymphatic vessels.

#### **9.7 Representative Case Examples**

**Case 9.1 Normal Lymphatic Transit (Fig. 9.1)**

**Fig. 9.1** History: An 8-year-old boy with a history of prematurity, short bowel syndrome due to necrotizing enterocolitis, and multi-organ transplantation of bowel, liver, and pancreas presented with lower limb edema. Study report: Anterior whole-body sweeps were obtained at various time points following intradermal injections of Tc-fltered sulfur colloid in the interdigital web space between the frst and second digits in both feet. Rapid ascent of tracer from the injection sites is noted. At 10 min post-injection, (**a**) tracer is seen in the major lymphatic

channels of the lower extremities as well as initial accumulation in the inguinal nodes. At 50 min post-injection (**b**) there is symmetrical tracer accumulation in inguinal and iliac nodes. Faint activity is noted in the liver suggesting initial drainage of lymphatic fuid into the systemic circulation. At 100 min (**c**) liver uptake is more obvious. Impression: Normal symmetric tracer transit through the lymphatic system with no evidence of obstruction or abnormal development of lymphatic channels

**Fig. 9.2** History: A 6-year-old boy presented with lymphedema of the left thigh and buttock that developed 6 months after surgery for a left inguinal hernia. Lymphoscintigraphy was performed following two intradermal injections of Tc-fltered sulfur colloid administered in the interdigital web space between the frst and second digits of the feet. Study report: Selected anterior whole-body sweeps starting at 75 min after tracer administration (**a**) show a symmetrical ascent of tracer from the injection sites through the major lymphatic channels of the lower extremities up to the groin levels. Activity is

also noted in the liver, indicating physiologic lymphatic drainage into the systemic circulation. Images obtained at 115 (**b**) and 180 min (**c**) post-injection show a relative paucity of tracer accumulation in left inguinal lymph nodes and a lack of tracer accumulation in the left iliac nodes. Diffuse tracer activity is noted in the superfcial soft tissues in the lateral (arrows) and medial aspects of the proximal left thigh, suggesting "dermal backfow." Impression: The fndings suggest lymphatic obstruction at the level of the left groin

#### **Case 9.3 Gastrointestinal Tract Lymphangiectasia (Fig. 9.3)**

**Fig. 9.3** History: An 8-year-old boy was investigated for protein-losing enteropathy with hypoalbuminemia and lymphocytopenia. Lymphoscintigraphy was performed following two dorsal pedal intradermal injections of Tc-antimony sulfde colloid. Study report: The initial dynamic images (**a**, **b**) show normal lymphatic collectors in the legs and activity in femoral and inguinal lymph nodes bilaterally. Delayed images at 1 h (**c**) show a diffuse increase in tracer activity in the left mid-abdomen and

only faint accumulation of tracer in the liver. Abdominopelvic SPECT MIP (**d**) and SPECT/CT (**e**, upper-transaxial, lower–coronal slices) demonstrate tracer activity in the gastrointestinal tract, specifcally in a bowel loop located in the left lower abdominal quadrant. Impression: The study suggests diffuse gastrointestinal lymphangiectasia, predominantly involving the small bowel, further confrmed by capsule endoscopy

#### **Case 9.4 Sentinel Lymph Node in a Patient with Melanoma (Fig. 9.4 )**

**Fig. 9.4** History: A 5-year-old boy with melanoma in the left leg was evaluated prior to surgery. Study report: Planar scintigraphy of the abdominopelvic region and thighs superimposed on a 57Co food source transmission image ( **a**) shows a focal area of uptake in the left inguinal region localized to a lymph node on SPECT and SPECT/CT coronal slices ( **b**). Impression: The focus of uptake represents the sentinel lymph node located in the left inguinal region. At surgery, this lymph node was resected and found negative for melanoma

**Case 9.5 Left Leg Swelling and Increasing Bilateral Leg Edema and Pleural Effusion (Fig. 9.5)**

**Fig. 9.5** History: A 9-year-old boy presented with left leg swelling, increasing bilateral leg edema, and pleural effusion. He had been previously treated for acute myeloblastic leukemia with total body external beam radiotherapy. Study report: Selected anterior whole-body sweeps starting at 75 min after tracer administration (**a**–**d**) show signifcant dermal backfow in the lower limbs, more pronounced on the left side (**a**–**c**) with adequate visualiza-

tion of bilateral inguinal lymph nodes. There is a visualization of the liver with signifcant abdominal dermal backfow (**d**). SPECT/CT shows axillary and mediastinal lymph nodes with a chylous leak into the left hemithorax (**e**). Impression: Collateral aberrant lymphatic drainage with abdominal wall dermal backfow, axillary and mediastinal lymph nodes, and chylous leak into the left hemithorax

#### **References**


The opinions expressed in this chapter are those of the author(s) and do not necessarily refect the views of the IAEA: International Atomic Energy Agency, its Board of Directors, or the countries they represent.

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 3.0 IGO license (http:// creativecommons.org/licenses/by/3.0/igo/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the IAEA: International Atomic Energy Agency, provide a link to the Creative Commons license and indicate if changes were made.

Any dispute related to the use of the works of the IAEA: International Atomic Energy Agency that cannot be settled amicably shall be submitted to arbitration pursuant to the UNCITRAL rules. The use of the IAEA: International Atomic Energy Agency's name for any purpose other than for attribution, and the use of the IAEA: International Atomic Energy Agency's logo, shall be subject to a separate written license agreement between the IAEA: International Atomic Energy Agency and the user and is not authorized as part of this CC-IGO license. Note that the link provided above includes additional terms and conditions of the license.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

### **Musculoskeletal System (Non-Oncologic Indications) 10**

Gopinath Gnanasegaran, Sharjeel Usmani, and Helen Nadel

#### **10.1 Clinical Indications**


#### **10.2 Pre-exam Information**


Lucile Packard Children's Hospital Stanford University, Palo Alto, CA, USA


#### **10.3 Bone Scintigraphy**

#### **Study Protocol for 99mTc-MDP Bone Scintigraphy [1, 2] Patient preparation**


#### **Radiopharmaceutical, administered activity, mode of delivery**

*Radiopharmaceutical:*

• [99mTc]methylene diphosphonate (MDP) or similar diphosphonates.

G. Gnanasegaran (\*)

Nuclear Medicine department, Royal Free London NHS Foundation Trust, London, UK e-mail: gopinath.gnanasegaran@nhs.net

S. Usmani

Department of Radiology and Nuclear Medicine, Sultan Qaboos Comprehensive Cancer CARE and Research Centre (SQCCCRC), Muscat, Oman

H. Nadel

#### *Activity:*

• 9.3 MBq/kg (0.25 mCi/Kg), minimum dose 40 MBq (1.1 mCi).

Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

#### *Delivery:*

• Select intravenous (IV) injection site to avoid possible sites of pathology. For example, upper extremity lesions will require a foot injection.

**Acquisition protocol:** Two- or threephase bone scan is recommended, fourphase protocol can be performed.

	- Dynamic blood fow study.
	- Blood pool (regional or whole body), immediately after the completion of the dynamic study.
	- Image total body vertex to toes in anterior and posterior projection
	- SPECT should be included in the third step in selected scenarios:
	- To areas of localized symptoms.
	- If an abnormality is detected on planar imaging.

SPECT/CT, if available should replace SPECT

	- In cases of uncertain fndings on routine 3-h scintigraphy.
	- When residual bladder activity overlies the pelvis and the child refuses to urinate or when bladder emptying is incomplete.
	- High or ultrahigh low-energy collimator.
	- Pinhole collimator, if available, can improve detection of lesions in the hip joint of distal extremities.
	- 2–5 s/frame for a total of 60 s, matrix 128 × 128, size-appropriate zoom
	- Recommended counts: Torso 300 Kcounts, extremities 150–200 Kcounts.
	- For lower extremity lesions the entire lower limbs pelvis and lumbar spine should be in the FOV.
	- 8 cm/min for ages 4–8 years
	- 10 cm/min for ages 8–12 years
	- 12 cm/min for ages 12–16 years
	- 15 cm/min above 16 years of age

terior projections, start with the pelvis when the bladder is empty.

	- Reduce the CT feld to include only the fndings on the SPECT component.
	- Tube settings depend on manufacturer and the applied protocol: low-dose or fully diagnostic CT (accordingly the settings can range between 80 and110 kVp).
	- CT slice thickness 2–2.5 mm with overlapping cuts.

#### **10.4 Study Interpretation [3, 4]**

	- Reduced or absent activity due to physiologic delayed ossifcation of certain bones (e.g., navicular bone of the foot, femoral head) must be differentiated from pathologic photopenic lesion.
	- Increased activity in the orbits on the anterior view of the skull is normal in the frst months of life.

– Focal activity in the ischio-pubic synchondrosis is normal in most cases and refects asymmetric closure of bone centers.

Focally increased tracer activity:


Focal reduced/photopenic tracer activity:


Diffuse decreased tracer activity:


Diffuse increased tracer uptake:


**Bone Scintigraphy Protocol Adjustments in Suspected Non-Accidental Injury [6, 7]**


#### **10.5 Correlative Imaging [8]**


• Check if the child has not performed a recent CT or MRI or if one is already planned before deciding on SPECT/CT.

#### **10.6 Red Flags [4, 6]**


• Suspected fractures or ischemia in weightbearing bones should be promptly reported to the referring physician to initiate preventive measures to avoid complications.

#### **10.7 Take Home Message**


Regional bone scans should not be performed.


#### **10.8 Representative Case Examples**

**Case 10.1 Osteomyelitis (Fig. 10.1)**

**Fig. 10.1** History: An 11-year-old boy presented with a painful left hip 2 weeks after playing soccer. X-rays and US were normal. Study report: In the early blood pool study (**a**) there is increased tracer uptake in the left anterior inferior iliac spine (arrow). The late planar anterior (**b**) and posterior (**c**) scans show focal increased osteoblastic activity in the same area (arrow). SPECT/CT, axial, coronal, and sagittal low-dose CT slices (**d**) show no bone erosion around marked focal osteoblastic reaction

seen in the left iliac bone on fused images (**e**). Impression: The pathological uptake on bone scintigraphy, in association with the lack of abnormalities on the CT part of the SPECT/CT most likely exclude tumor. SPECT/CT cannot exclude subtle lesions such as stress fractures or enthesopathy. Acute osteomyelitis was the suggested diagnosis despite the lack of systemic fever, further confrmed by blood cultures positive for *S. aureus*

**Fig. 10.2** History: A 4-month-old girl presented with a swollen left arm. X-ray showed a left humeral fracture. Study report: On early blood pool images (not shown), there is an increased blood pool in the distal left humerus and mid-left tibia. Late planar scans show foci of increased

tracer uptake in the mid-to-distal left humerus and midleft tibia. Impression: The pattern of focal increased tracer uptake in the left humerus and left tibia are highly suggestive of non-accidental injury despite normal X-ray of the tibia

#### **Case 10.3 Spondylolysis (Fig. 10.3)**

**Fig. 10.3** History: An 11-year-old boy presented with a month-long low back pain after playing football. X-rays showed mild scoliosis, convex to the left, but was otherwise normal. Study report: Bone scintigraphy shows a normal blood pool (**a**) but mildly increased tracer uptake on the right side of the lower lumbar spine in the late planar scans (**b**). SPECT, transaxial (**c**) and coronal (**d**) slices,

shows focal increased uptake in the right pars interarticularis of L4 vertebra. SPECT/CT (**e**), transaxial, coronal and sagittal CT (left) and fused (right) images, demonstrate bilateral sclerosis, more pronounced at the site of the focal increased tracer uptake in the right pars interarticularis of L4 vertebra. Impression: The fndings are consistent with an L4 spondylolytic fracture

**Fig. 10.4** History: An 8-year-old boy presented with complaints of right hip pain and right-sided limping for 2 weeks, without a history of fever or trauma. Study report: The early phase images (not shown) were unremarkable. Anterior and posterior late whole-body images (**a**, **b**) show reduced tracer uptake in the right femoral head

(arrows). SPECT anterior projection MIP (**c**) and coronal, sagittal, and transaxial slices (**d**–**f**) show a photopenic area in the right proximal femoral epiphysis (arrows) confrming the fndings on the whole body sweeps. Impression: The fndings suggest avascular necrosis of the right femoral head (Legg-Calve-Perthes disease)

#### **10.9 18F-Sodium Fluoride (NAF) Bone PET/CT**

#### **Study Protocol for NaF Bone PET/CT [1, 9–11]**

#### **Patient preparation**


#### **Radiopharmaceutical, administered activity and mode of delivery**

*Radiopharmaceutical:*


Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

#### *Delivery:*

• Select the injection site to avoid possible sites of pathology.

#### **Acquisition protocol**


#### **10.10 Study Interpretation**


#### **10.11 Correlative Imaging**

• Correlation with radiographs is required when assessing skeleton.

#### **10.12 Red Flags [12, 13]**

• Interpreting NaF studies in children requires a learning curve. The study has a high sensitivity and there is therefore a need to identify patterns of physiologic variants and differentiate them from pathological uptake foci.

#### **10.13 Take Home Messages [14, 15]**


#### **10.14 Representative Case Examples**

**Case 10.5 Normal NaF PET Study (Fig. 10.5)**

**Fig. 10.5** History: A 7-year-old boy was referred to NaF PET/CT for further evaluation of low back pain. Study report: Whole-body PET, anterior (left) and lateral (right) MIP, show increased symmetric tracer uptake in the epiphyseal plates of the long bones in the upper and lower limbs and the anterior end of the ribs, bilaterally, consistent with areas of physiologic activity in growing plates. Impression: No evidence of abnormal osteoblastic lesions in the spine

**Fig. 10.6** History: A 9-year-old boy was referred to NaF PET/CT following 1-month long complaints of pain in the left leg. Study report: Whole-body MIP (left) shows a focal area of increased tracer uptake at the medial aspect of the upper shaft of left tibia. Coronal and sagittal (right) and transaxial (center) PET, CT, and fused PET/CT slices

at the level of the proximal tibia show an eccentric, welldefned lytic lesion with a rim of sclerosis, with corresponding increased tracer uptake at the posteromedial part of the left upper tibia. Impression: The fndings are consistent with a fbrous cortical defect

#### **Case 10.7 Bilateral Ischio-Pubic Synchondrosis (Fig. 10.7)**

**Fig. 10.7** History: A 7-year-old boy with right orbital rhabdomyosarcoma was evaluated as part of a metastatic survey. Study report: Anterior (**a**) and lateral MIP (**b**), as well as transaxial PET, CT, and fused NaF PET/CT slices at the level of the symphysis pubis (**c**) show physiological symmetric increase uptake at the growing ends of the bone, including costochondral junctions, and the epiphyseal plates of the upper and lower limbs. There is increased tracer uptake in both distal rami of the pubis (arrows). Impression: The fndings demonstrate focal increased tracer uptake in sites of bilateral ischio-pubic synchondrosis. This is a normal variant and should not be interpreted as fractures. No evidence of bone metastases

#### **Case 10.8 Patellar Tendon Insertion Enthesopathy (Fig. 10.8)**

**Fig. 10.8** History: A 13-year-old boy is complaining of right knee pain for 3 months. Plain X-rays were unremarkable. Study report: NaF PET/CT, anterior (**a**) and oblique MIP (**b**), as well as sagittal (**c**) and transaxial (**d**) PET, CT, and fused slices at the level of the proximal tib-

iae show focal increased tracer uptake at the cortical surface of right tibial tuberosity (arrow). Impression: The fndings are consistent with patellar tendon insertion enthesopathy

#### **Case 10.9 Sickle Cell Anemia (Fig. 10.9)**

**Fig. 10.9** History: A 16-year-old boy with known sickle cell anemia presented with subacute bone pain. Study report: NaF PET MIP (**a**), transaxial (**b**) and coronal (**c**) PET, CT and fused images show multiple areas of

increased tracer uptake at right clavicle, bilateral ribs, the left humeral shaft, and the right trochanteric region. Impression: The osteoblastic lesions represent active bone remodeling at multiple bone infarcts

#### **References**


The opinions expressed in this chapter are those of the author(s) and do not necessarily refect the views of the IAEA: International Atomic Energy Agency, its Board of Directors, or the countries they represent.

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 3.0 IGO license (http:// creativecommons.org/licenses/by/3.0/igo/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the IAEA: International Atomic Energy Agency, provide a link to the Creative Commons license and indicate if changes were made.

Any dispute related to the use of the works of the IAEA: International Atomic Energy Agency that cannot be settled amicably shall be submitted to arbitration pursuant to the UNCITRAL rules. The use of the IAEA: International Atomic Energy Agency's name for any purpose other than for attribution, and the use of the IAEA: International Atomic Energy Agency's logo, shall be subject to a separate written license agreement between the IAEA: International Atomic Energy Agency and the user and is not authorized as part of this CC-IGO license. Note that the link provided above includes additional terms and conditions of the license.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

## **Infection and Infammation Imaging 11**

Ora Israel, Enrique Estrada-Lobato, and Thomas Neil Pascual

#### **11.1 Clinical Indications**

*Commonly evaluated pediatric infectious processes* [1–3]:

	- Osteomyelitis (diagnosis, differential diagnosis, single vs. multifocal disease)
	- Discitis
	- Arthritis
	- Immune-compromised children [4–6].
	- Febrile neutropenia (absolute neutrophil count below 500/mm3 ) in immunesuppressed and/or cancer patients [7].

O. Israel (\*)

B&R Rappaport Faculty of Medicine, Technion, Haifa, Israel

E. Estrada-Lobato

Nuclear Medicine and Diagnostic Imaging Section, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria

T. N. Pascual Department of Science and Technology, Manila, Philippines

*Additional indications in children* [8]

	- Vasculitis
	- Chronic granulomatous diseases (e.g., sarcoidosis)

#### **11.2 Pre-exam Information**

	- Measure and record the patient height and weight.
	- Current symptoms, pertinent physical fndings, duration of signs and symptoms.
	- Pre-existing conditions.
	- Previously or currently received therapy such as antibiotics, corticosteroids, chemotherapy, radiation therapy, and diphosphonates.
	- Prior orthopedic or non-orthopedic surgery, presence of orthopedic hardware.

*For the activity of all radiotracers to be administered:*

Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

#### **Study Protocol for Bone Scintigraphy [2, 10]**

#### **Patient preparation:**


#### **Radiopharmaceutical, activity, mode of delivery**

*Radiopharmaceuticals:*

• [ 99mTc]-MDP (MDP)

*Activity:*

• 9.3 MBq/kg (0.25 mCi/Kg), minimum dose 40 MBq (1.1 mCi).

**Acquisition protocol** (**Figs. 11.1, 11.2, and 11.3)**

	- 8 cm/min for children aged 4–8 years.
	- 10 cm/min for ages 8–12 years
	- 12 cm/min for ages 12–16 years
	- 15 cm/min over 16 years of age.
	- Multiple spot views (alternatively) to cover the entire skeleton in anterior and posterior projections: matrix 256 × 256, counts: torso 500 Kcounts, skull 300 Kcounts, knees 100–200 Kcounts, hands and feet 50–100 Kcounts. 2nd variant: the time to obtain 500 Kcounts for the torso should be recorded and used to time the acquisition of the other body parts.
	- CT component using pediatric settings with dose modulation.
	- CT feld of view to the fnding on SPECT, tube setting depending on whether the CT is intended to be acquired as low dose or fully diagnostic CT (range: between 80 and 110 kVp); CT slice thickness 2–2.5 mm with overlapping cuts.

#### **11.3 Study Interpretation of Bone Scintigraphy [12]**

• Osteomyelitis is based on increased local blood fow and bone turnover. The scintigraphic pattern is characterized by increased blood fow and blood pool (tissue hyperemia) and focal increased uptake in the skeletal phase (Fig. 11.1).

	- Cellulitis presents with diffuse increased blood fow and blood pool in soft tissue adjacent to bony structures and mild diffuse increased tracer activity in the same area on the skeletal phase.
	- Arthritis presents with diffuse uptake in all bony structures of a joint, with or without accompanying fndings in the blood fow and blood pool phases.
	- Discitis typically presents as increased uptake in two adjacent vertebral bodies above and below the infamed disc.

**Study Protocol for Tc-WBC Scan [8, 13] Patient preparation:**


amounts of blood (considering the specifc pediatric population).

#### **Radiopharmaceutical, activity, mode of delivery**

*Radiopharmaceutical*

• [ 99mTc]-WBC

*Activity*

• 3.7–7.4 MBq/kg (0.1–0.2 mCi/Kg), minimum dose 40 MBq (1.1 mCi)

For detailed instructions regarding the WBC labelling technique, see appropriate guidelines. The blood volume required for WBC labelling has to be adjusted and reduced as much as possible in young infants [14].

#### **Acquisition protocol** (Fig 11.4)

	- Early images, 30 min post-injection, including of the chest and upper abdomen as well as images for in vivo quality control of WBC labelling.
	- Delayed images: 3–4 h post-injection.
	- Late images: 20–24 h post-injection.
	- Size appropriate zoom, matrix 256 × 256.
	- Acquisition options:

Time corrected for isotope decay: early images are acquired with a set number of counts or time, followed by delayed and late images corrected for the 99mTc 6-h halflife. Different images can be compared with the same intensity scale avoiding operator-dependent changes in the image display.

Fixed time/image: 5–10 min/projection. Diffcult to interpret because of interfering data from other organs.

	- SPECT parameters if performed after delayed step: 20–30 sec/step (depending on the injected activity).
	- SPECT can be also added to the late step (20–24 h post-injection) with following parameters:

30–50 sec/step (depending on the injected activity and FOV to be imaged, longer for peripheral parts, shorter for abdomen).

Indicated if there are new sites of pathological uptake not seen on earlier scans.

• Modifed parameters for IBD: Images acquisition at 30 min and 2–3 h postinjection only (Fig. 11.5).

#### **11.4 Study Interpretation of Tc-WBC Scan [13]**

Diagnosis of infection is made by comparing delayed and late images:

	- Similar/slightly decreasing uptake over time.
	- Slight increase in size and/or intensity over time.

Physiologic biodistribution, pitfalls, and positivity criteria:

	- Location: earlier in cardio-vascular vs. bone and CNS infection.
	- Virulence: higher in active vs. chronic processes.
	- Pathogen: lower in fungal vs. bacterial infection.
	- Antibiotic or steroid therapy may decrease Tc-WBC uptake.

#### **Study Protocol for [18F] -FDG [2, 6, 15, 16]**

#### **Patient preparation:**


**Radiopharmaceutical, activity, mode of delivery**

*Radiopharmaceuticals:*

• [ 18F] -FDG (FDG)

*Activity*

• 3.7–5.2 MBq/kg (0.1–0.14 mCi/kg) minimum 26 MBq (0.7 mCi).

#### **Acquisition protocol**


#### **11.5 Study Interpretation of FDG**


#### **11.6 Correlative Imaging [18]**


specifcity and accuracy of nuclear medicine tests.

• MRI advantages stem from its lack of ionizing radiation. It also has higher soft tissue contrast than CT.

#### **11.7 Red Flags [2]**

#### *Tc-MDP*


#### *WBC*


#### *FDG*


#### **Matching of Radiotracers Used for Specifc Pediatric Infectious and Infammatory Processes**

	- Osteomyelitis: Tc-MDP, WBC, FDG
	- Discitis: Tc-MDP, FDG
	- Arthritis: Tc-MDP, FDG
	- Vasculitis: FDG (Fig. 11.10)
	- Chronic granulomatous diseases: FDG

#### **11.8 Take Home Messages**

	- In low pre-test probability of infection and suspected chronic or non-bacterial processes, FDG imaging is preferred.
	- In case of high WBC counts, ESR or CRP values: Tc-WBC scan can be the frst test.
	- WBC accumulation is generally more specifc for infection than increased FDG uptake.
	- Images from different time points have to be displayed at the same intensity scale (Figs. 11.4 and 11.5).
	- Any adjustment of the image intensity scale must be applied to all images together to avoid operator bias.
	- Patients receiving antibiotic treatment should not be excluded from performing Tc-WBC scans.
	- Hyperglycemia and antibiotic treatment most probably do not affect signifcantly the diagnostic potential of the study in suspected infection [19, 20].

– A specifc dietary regimen has to be applied in patients evaluated for the suspicion or monitoring of a cardiac infectious process.

#### *MSK infectio*n [21]:

	- In the axial skeleton, including cases with suspected spinal fusion hardware infection (superior to WBC).
	- FDG imaging can also detects extraosseous lesions.

#### *FUO* [6, 16, 23, 24]


#### **11.9 Representative Case Examples**

**Case 11.1 Osteomyelitis, Tc-MDP (Fig. 11.1)**

**Fig. 11.1** History: A 6-year-old boy presented with a painful left knee. Radiographs were normal, and blood CRP and ESR were elevated. A whole-body bone scan was performed after injection of Tc-MDP. Study report: The dynamic (**a**) and blood pool (**b**) images show increased perfusion and hyperemia to the upper part of the left knee. Delayed planar scintigraphy of the region of the knees (anterior view, **c**, and posterior view, **d**) shows focal increased tracer uptake in the left distal femoral metaphysis. The remainder of the whole-body scan was normal (not shown). Impression: The fndings are suggestive of acute osteomyelitis. Blood cultures grew *Staphylococcus aureus*

#### **Case 11.2 Osteomyelitis, Tc-MDP (Fig. 11.2)**

**Fig. 11.2** History: A 10-year-old boy had surgery for septic arthritis of the right knee and ankle, with no signifcant clinical improvement. Bone scintigraphy was performed after injection of Tc-MDP for the suspicion of additional sites of infection. Study report: Early wholebody blood pool scintigraphy, anterior view (**a**, right) shows a rim of increased hyperemia surrounding an area of decreased activity in the right tibia. Increased blood pool activity is also seen in the region of the right knee

and foot. Delayed whole-body scintigraphy (**b**) shows a "cold" area of absent radiotracer uptake in the proximal two-thirds of the right tibia and decreased activity in the proximal tibial growth plate. There is also increased tracer uptake in the right knee joint and foot. Impression: The fndings of a "cold bone" in this setting suggest a bony abscess or bone necrosis. The child had surgery and a large volume of pus was drained from the tibia, confrming the diagnosis of osteomyelitis

#### **Case 11.3 Osteomyelitis in Complicated Bone, Tc-MDP (Fig. 11.3)**

**Fig. 11.3** History: An 18-year-old boy with posttraumatic right femoral amputation 18 months prior to this examination presented with a draining fstula from the right femoral stump. Osteomyelitis was suspected and a bone scan was performed after administration of Tc-MDP. Study report: Blood pool images (**a**, upper right quadrant) demonstrate hyperemia at the margin of the right femoral stump. On delayed planar bone scintigraphy

(**a** left) there is focal increased tracer activity in the right femoral stump. There is also diffuse increased uptake along the bones of the left calf and foot due to limping. SPECT/CT (**b**) indicates that the area of focal radiotracer uptake in the right femoral stump corresponds to signs of chronic osteomyelitis on the CT component. Impression: The fndings suggest chronic osteomyelitis at the right femoral stump

#### **Case 11.4 Infected Hematoma of the Skull, Tc-WBC (Fig. 11.4)**

**Fig. 11.4** History: A 9-year-old girl presented one day after falling and hitting the right side of her head. She subsequently developed a hematoma and periorbital swelling. She had a 1-year background history of weight loss and proptosis compatible with thyrotoxicosis and developed a thyroid storm after the initial contrast brain CT. Due to ongoing temperature spikes, a blood culture was performed and was positive for *Streptococcus constellatus*, a bacteria known to cause abscess formation. The patient did not respond to appropriate treatment and a Tc-WBC was requested. Study report: On the 3-h whole-body scan (**a**) there is an abnormal accumulation of Tc-WBC in the right-sided skull hematoma, increasing in intensity on the 24-h study (**b**). Impression: The fndings are suggestive of an infected hematoma on the right side of the skull. The patient was taken to surgery immediately after the scan and approximately 300 mL of pus was drained from the scalp lesion

**Fig. 11.5** History: An 18-year-old girl presenting with recurrent abdominal pain, fecal blood, and watery stool was evaluated with a Tc-WBC study for the clinical suspicion of infammatory bowel disease. Study report: Planar scans at 15 and 45 min after tracer injection (**a**) show an area of abnormal tracer uptake in the right abdomen. Transaxial SPECT (**b**) and SPECT/CT (**c**) slices at the

level of the lower abdomen localize this focus of uptake to the terminal ileum. A delayed planar scan (**a**, bottom row) performed at 90 min post-injection shows the progression of the tracer activity into the ascending colon. Impression: The fndings suggest terminal ileitis, further confrmed at endoscopy

#### **Case 11.6 Chronic Recurrent Multifocal Osteomyelitis, FDG (Fig. 11.6)**

**Fig. 11.6** History: A 7-year-old girl presented with joint pain, fever, and abnormal lab tests (elevated ESR, CRP, ASLO). Bone scintigraphy and abdominal US were normal and she was referred to PET/CT with FDG for further evaluation. Study report: Whole body maximum intensity projection (MIP) of the PET component (**a**) shows focally increased tracer uptake in both knees, involving the femoral and tibial metaphyses, also seen on transaxial PET/CT slices (**b**, **c**), as well as in both ankles, with no corresponding CT abnormalities. Impression: The fndings suggest multifocal osteomyelitis, but a different etiology involving the bony structures cannot be excluded. Further evaluation with MRI was suggested. MRI of the left knee (not shown) demonstrated bone marrow edema, mild periostitis, and joint effusion. The differential diagnosis included chronic recurrent multifocal osteomyelitis, leukemia infltration, and eosinophilic granuloma. Tissue sampling was recommended. CT-guided biopsy of the left distal femur demonstrated the presence of marked fbrosis, reactive trabecular changes, and focal neutrophil infltration, with no evidence of leukemic infltrates. The patient was diagnosed with chronic recurrent osteomyelitis and subsequently showed a good response to treatment with methotrexate and steroids

#### **Case 11.7 Fever of Unknown Origin (FUO), Aspergillosis, FDG (Fig. 11.7)**

**Fig. 11.7** History: A 2-year-old girl with leukemia developed pancreatitis secondary to chemotherapy followed by a persistent fever that did not respond to antibiotics. CT showed mild infammatory changes in the lungs. A wholebody FDG PET/CT was performed to look for occult infective or infammatory sites. Study report: FDG PET MIP image (**a**) and selected axial PET/CT slices at the level of the upper abdomen and chest (**b**, **c**) show multiple foci of abnormal tracer uptake throughout the subcutaneous and soft tissues, the lungs, pancreas, and spleen (yellow arrows), with a specifc focal site of uptake in the heart (**c**, yellow arrow). Impression: The fndings are suggestive of possible mycotic deposits. Biopsy and culture of a skin lesion revealed *Aspergillus*. Following a change of treatment to more specifc antifungal agents, the patient's clinical status improved. On a repeat PET/CT study performed 2 months later (not shown), there is marked improvement with the disappearance of most tracer avid foci

#### **Case 11.8 FUO, Septic Emboli, FDG (Fig. 11.8)**

**Fig. 11.8** History: A 7-year-old girl presented with fever, 39 °C, for 3 weeks. She had been previously diagnosed and treated for a urinary tract infection. She had positive blood cultures and echocardiography demonstrated the presence of endocarditis. FDG PET/CT was performed for further evaluation of potential extracardiac foci of infection. Study report: Coronal PET slices (**a**) show foci of increased tracer uptake in both lungs. Selected trans-

axial PET/CT (**b**) and CT (**c**) of the chest localize these sites of increased uptake to nodules and ground-glass opacities in both upper lung lobes and in a right lower lobe consolidation. Note also increased FDG uptake in an enlarged spleen. Impression: The fndings are consistent with septic pulmonary emboli. Hypermetabolic splenomegaly is considered to be reactive to the infectious process

**Case 11.9 FUO, Pericarditis, FDG (Fig. 11.9)**

**Fig. 11.9** History: An 8-year-old girl previously treated for pneumonia complained of fever (39.4 C) for three weeks. C-reactive protein was elevated. Abdominal US was normal. A whole-body FDG PET/CT was performed in search of a focal etiology that could explain the high, prolonged fever. Study report: Selected coronal, sagittal, and transaxial PET slices (**a**) show increased linear tracer uptake located in thickened pericardium and mild pericar-

dial effusion surrounding the heart as demonstrated on transaxial PET/CT slices of the thorax (**b**). In addition, note physiologic tracer uptake in the thymus. Impression: The fndings suggest the presence of pericarditis. Cardiac echography showed a new pericardial effusion. The patient was diagnosed with acute pericarditis and idiopathic juvenile arthritis and showed an excellent response to treatment with NSAIDS

#### **Case 11.10 Vasculitis, FDG—PET/MRI (Fig. 11.10)**

**Fig. 11.10** History: A 12-year-old girl presented with persistent thoracic level back pain, intermittent fever, and elevated ESR. Cross-sectional imaging showed thickening of her aortic arch and bilateral great vessels. Takayasu's arteritis was diagnosed, and the patient was referred to FDG PET/MRI. Study report: The PET/MRI study (left PET-MIP, center column selected transaxial thoracic PET, MRI, and PET/MRI slices, right selected coronal cervical PET and MRI slices) shows increased FDG uptake in wall thickening of the left common carotid artery, extending from the origin to the bifurcation, and, to a lesser extent, along the caudal aspect of the right common carotid artery near the origin (arrows). In the chest, there is increased uptake in mild wall thickening of the thoracic aorta, involving the ascending and descending parts and the aortic arch (arrows). There is also mildly increased radiotracer uptake in the walls of the abdominal aorta, extending to the proximal iliac arteries. There is no abnormal metabolic activity or wall thickening involving the abdominal great branching arteries including the celiac axis, and the superior mesenteric and inferior mesenteric arteries. Impression: Multifocal mild wall thickening and increased metabolic activity of the left more than right common carotid arteries, thoracic and abdominal aorta, and proximal common iliac arteries. The increased metabolic activity suggests the presence of active arteritis

#### **References**


for investigation of fever in immunocompromised children. J Paediatr Child Health. 2018;54(5):487–92.


The opinions expressed in this chapter are those of the author(s) and do not necessarily refect the views of the IAEA: International Atomic Energy Agency, its Board of Directors, or the countries they represent

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 3.0 IGO license (http:// creativecommons.org/licenses/by/3.0/igo/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the IAEA: International Atomic Energy Agency, provide a link to the Creative Commons license and indicate if changes were made.

Any dispute related to the use of the works of the IAEA: International Atomic Energy Agency that cannot be settled amicably shall be submitted to arbitration pursuant to the UNCITRAL rules. The use of the IAEA: International Atomic Energy Agency's name for any purpose other than for attribution, and the use of the IAEA: International Atomic Energy Agency's logo, shall be subject to a separate written license agreement between the IAEA: International Atomic Energy Agency and the user and is not authorized as part of this CC-IGO license. Note that the link provided above includes additional terms and conditions of the license.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

## **Pediatric Malignancies 12**

Helen Nadel, Barry Shulkin, Zvi Bar-Sever, and Francesco Giammarile

#### **12.1 General Tracer-Related Parameters**

#### **Radiopharmaceutical and Administered Activity**

The EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites should be followed [1, 2].

Reference to national regulation guidelines, if available, should be considered.

H. Nadel (\*)

Lucile Packard Children's Hospital Stanford University, Palo Alto, CA, USA

#### B. Shulkin

Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN, USA

#### Z. Bar-Sever

Schneider Children's Medical Center of Israel, Tel Aviv University, Petah Tiqva, Israel

#### F. Giammarile

Nuclear Medicine and Diagnostic Imaging Section, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria

#### **Box 12.1 FDG Imaging Protocol [3–6]**

#### **Patient Preparation**

	- Early arrival (30–45 min prior to planned radiotracer injection time) to settle patient, establish IV line, and warm the patient in a temperaturecontrolled room with the addition of warm regular or electric blankets.

<sup>©</sup> The Author(s) 2023

Z. Bar-Sever et al. (eds.), *A Practical Guide for Pediatric Nuclear Medicine*, https://doi.org/10.1007/978-3-662-67631-8\_12


#### **Radioisotope:**

• [ 18F]-Fluorodeoxyglucose (FDG)

#### **Activity:**

• 3.7–5.2 MBq/kg (0.10–0.14 mCi/kg), minimum dose 26 MBq (0.7 mCi).

Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

• FDG activity can be reduced when using modern PET technology, to 0.06–0.08 mCi/ kg 2.46–2.96 MBq/kg [7].

#### **Acquisition Protocol**


#### **Study Interpretation for FDG Imaging [8–10]**

• Standardized elements to include in the PET/ CT report can be found at the SNMMI website http://interactive.snm.org/docs/PET\_PROS/ ElementsofPETCTReporting.pdf

	- Intensity: mild, moderate, or severe, or compared to the blood pool and liver activity.
	- Pattern: focal, diffuse, linear.
	- Localization: based on CT or MRI.
	- Infant mouth with feeding or sucking during the uptake phase.
	- Thymus: uptake decreases with age but may increase after chemotherapy, thymic rebound.
	- Brown fat: usually bilateral in the neck, supraclavicular regions, axillae, mediastinum, paravertebral regions, and perinephric areas. Infradiaphragmatic activity considered to be brown fat is seen, as a rule, in conjunction with supradiaphragmatic brown fat.
	- Diffuse uptake in bone marrow following hematopoietic stimulating drugs such as G-CSF.
	- Increased uptake in infectious and infammatory processes, and in other benign entities.
	- Uptake in post-surgical scars.
	- Uptake in growth plate.
	- Hyperinsulinemia and hyperglycemia.
	- Small lesions, with limited tracer avidity.
	- Low metabolic tumors are rare in children but may occur with differentiated thyroid cancer and well-differentiated NETs.
	- Tumor necrosis.
	- Recent radiation or chemotherapy.
	- Recent treatments such as high-dose corticosteroid therapy and anti-retroviral medication.

#### **Box 12.2 Radioiodinated Meta-Iodobenzylguanidine (MIBG) Imaging Protocol [11, 12]**

#### **Patient Preparation**

	- Starting 2 days prior to and continued for 3 days after injection.
	- Dose: 0.6 mL of 5 % solution/day, single dose or split into 2 × 0.3 mL doses.
	- Delivery: diluted in any drink such as milk or juice as may cause a burn in the throat if undiluted.
	- Starting 30–60 min prior to tracer administration, on day 0 and continued for a week.
	- Dose: <1 month—one drop orally/ day; 1 month—3 years: 2 drops orally/twice a day; 3–18 years of age: 3 drops orally/three times a day; ≥70 kg—adult: 6 drops orally (2 drops/3 times a day).
	- Starting 1 h prior to tracer injection, up to 5 times within the next 36 h.
	- Dose: 10 mg/kg, maximum 500 mg, minimum 50 mg.
	- Delivery: 200 mg tablet can be crushed, dissolved in 2 mL of sterile water, and administered by syringe or placed on a sugar lump.

#### **Radiopharmaceuticals**


#### **Activity**


#### **Acquisition Protocols** *123I-MIBG:*

	- In older children: whole-body anterior and posterior projections, 5 cm/ min, minimum 30 min, matrix 1024 × 512 or 1024 × 256.
	- In young children: multiple spot views of the entire body are preferred, matrix 256 × 256, trunk: 10 min/500 Kcounts. Limbs and skull 100 Kcounts, skull (anterior, posterior, left and right lateral views).
	- SPECT: 120 projections, 25–35 s/ step, matrix 128 × 128, iterative reconstruction.

*131I-MIBG:*

• Time of scan: 48 h post-injection, possible supplements at 72 h.


#### **Study Interpretation for MIBG Imaging [11, 13, 14]**

	- Adrenal glands: symmetric, mild (≤to the liver), normal size on CT.
	- Brown fat.
	- Thyroid (uptake of free iodine in case of poor blockade).
	- Lung atelectasis, pneumonia.
	- Heterogeneous liver uptake (including focal uptake in the left lobe).
	- Kidneys and/or dilated ureters.
	- Rare-vascular malformations, accessory spleen, ectopic kidneys, foregut duplication, hemorrhagic cysts, ovarian torsion, and hernia.
	- MIBG-negative neuroblastoma (10% of cases)
	- MIBG-negative metastases
	- Small lesions, below the camera resolution

#### **Box 12.3 [18F] Fluoro-Dihydroxyphenylalanine (FDOPA) Imaging Protocol [11, 15]**

#### **Patient Preparation**


#### **Activity**

• 3 MBq/Kg (0.08 mCi/Kg), minimum dose is 26 MBq (0.7 mCi).

#### **Acquisition Protocol**


#### **Study Interpretation for FDOPA Imaging [16, 17]**

	- High: basal ganglia, liver, adrenals, pancreas (variable).
	- Moderate: myocardium, skeletal muscles, growth plate.
	- Faint: breasts, oral cavity, esophagus, bowel.
	- Excretion: biliary (gallbladder and biliary tract) and urinary (kidneys, ureters, urinary bladder).
	- Physiologically intense, variable uptake in uncinate process of pancreas.
	- Stasis in small intrahepatic bile ducts and/ or in the urinary system.
	- Growth plate fractures.
	- Lesions adjacent to sites with high physiologic uptake.
	- Small lesions.
	- Lesions with low tracer avidity.

#### **Box 12.4 [68Ga]-Peptides Imaging Protocol [15]**

#### **Patient Preparation**


#### **Radiopharmaceuticals**

• 68Ga-DOTA-TATE, -TOC, -NOC.

#### **Activity**

• 2 MBq/kg (0.054 mCi/kg), minimum dose is 14 MBq (0.3 mCi).

#### **Acquisition Protocol**


#### **Study Interpretation for 68Ga-Peptide Imaging [18, 19]**

	- High uptake: pancreas (uncinate process), spleen, kidneys, pituitary gland.
	- Moderate uptake: liver, salivary glands, thyroid, bowel.
	- Faint uptake: adrenals, prostate, breast.
	- Physiologic uptake in uncinate process, accessory spleens, splenosis, epiphyseal growth plates.
	- Meningiomas.
	- Skeletal lesions such as fractures, vertebral hemangioma, fbrous dysplasia.
	- Infammatory processes such as reactive

lymph nodes, post-radiation therapy changes.

	- Small lesions.
	- Lesions adjacent to sites with high physiologic uptake.
	- Tumors with low or variable SSTR expression.
	- Lesion dedifferentiation.

#### **Box 12.5 Bone Imaging Protocols [20–24]**

#### **Patient Preparation**


#### **Radiopharmaceuticals**


#### **Activity**


Refer to the EANM pediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective EANM and SNMMI and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

**Acquisition Protocols** *Bone scintigraphy*

	- 8 cm/min for ages 4–8 years.
	- 10 cm/min for ages 8–12 years.
	- 12 cm/min for ages 12–16 years.
	- 15 cm/min over 16 years of age.
	- To areas of localized symptoms.
	- If an abnormality is detected on planar imaging.
	- For the CT component of SPECT/ CT—tube setting will depend on whether the CT is intended to be low dose or fully diagnostic.
	- In cases of uncertain fndings on routine 3-h scintigraphy.
	- When residual bladder activity overlies the pelvis and the child refuses to urinate or when bladder emptying is incomplete.

#### *Bone NaF PET/CT:*


#### **Study Interpretation for Bone Imaging**

	- Homogeneous throughout the entire skeleton.
	- Visualization of kidneys, ureters, bladder.
	- Increased uptake in metaphyses of children and adolescents.
	- Intensity higher or lower than in adjacent or in corresponding contralateral bone.
	- Pattern: focal or diffuse.
	- Location and number of foci.
	- Patterns of ST uptake:
		- Diffuse decreased: due to increased heterogeneous uptake in bone. Diffuse increased: renal failure, short uptake time, of signifcant tracer extrav
			- asation at the injection site.

Focal increased: infection/infammation, trauma, (calcifed) ST metastasis.

	- Urinary contamination or diversion reservoirs
	- Injection artifacts
	- Patient motion
	- Faulty energy window for image acquisition

#### **12.2 Lymphoma and Sarcoma**

#### **Clinical Indications—Imaging with FDG (see also Box 12.1) [22, 26–29]**


#### **Specifc Study Interpretation Criteria**

*Lymphoma* [30]

	- Score 1: No uptake above the background.
	- Score 2: Uptake ≤ mediastinum.
	- Score 3: Uptake > mediastinum but ≤ liver.
	- Score 4: Uptake moderately increased compared to the liver at any site.
	- Score 5: Uptake markedly increased compared to the liver at any site.
	- Score X: New areas of uptake unlikely to be related to lymphoma.

#### *Sarcoma* [31–33]

• Reduction in standard uptake values (SUV) max from baseline of greater than 50% has been associated with overall improved progression-free survival.

#### **Correlative Imaging [34]**


#### **Red Flags**


#### **Take Home Messages**


diseases can often occur distal to elbows and knees.

#### **Representative Case Examples**

#### **Case 12.1 Diffuse Large B-cell Non-Hodgkin's Lymphoma (NHL), Staging (Fig. 12.1)**

**Fig. 12.1** History: An 18-year-old boy with diffuse large B-cell NHL was referred for staging. Study report: FDG-PET MIP (**a**) and selected PET, CT, and PET/CT transaxial slices at the level of the upper chest (**b**) show an area of intense, inhomogeneous, abnormal tracer uptake in a 9 × 9 cm mass in the anterior mediastinum, involving the ST and bone, specifcally the left 1–4 ribs and sternum, with suspected involvement of the left lung. Note physiological cervical and axillary uptake in brown fat. There are no other sites of nodal hypermetabolism in the neck and chest, and no pulmonary nodules. There is no nodal hypermetabolism in the retroperitoneal or pelvic lymphatic chains. The spleen is normal in size and tracer avidity. There is focal increased physiological tracer uptake in paraspinal and right suprarenal brown fat. There are no areas of abnormal uptake in the appendicular and axial skeleton. Impression: The fndings are consistent with lymphoma of the mediastinum involving bony structures and possibly the left lung. The patient received four courses of chemotherapy and a repeat FDG-PET/CT study (not shown) demonstrated a complete metabolic response

**Fig. 12.2** History: A 9-year-old boy with newly diagnosed Burkitt's NHL following biopsy of the nasopharynx was referred for staging. Study report: FDG-PET MIP (**a**) and selected transaxial slices PET, CT, and PET/CT of the head (**b**) show intense pathological tracer uptake in a mass involving the nasopharynx, the oropharynx, and the base of the skull. Low-to-medium intensity uptake (SUVmax 2.24–5.51) is noted in 8 mm cervical lymph nodes, more prominent on the left. There is no nodal hypermetabolism in the chest and no pulmonary nodules. There is no nodal hypermetabolism in abdominal, retroperitoneal, or pelvic

lymphatic chains. The spleen is normal in size, with homogenous, mildly increased tracer avidity. There are no areas of abnormal uptake in the appendicular and axial skeleton. Impression: The fndings are consistent with lymphoma involving the nasopharynx and possibly cervical nodes, mainly on the left side of the neck. Lowintensity activity in additional cervical lymph nodes can be related to an infammatory reaction. Diffuse, homogenous tracer activity in the spleen, most probably due to increased hematopoiesis or an infammatory reaction

**Case 12.3 Hodgkin Lymphoma (HL), Staging, Monitoring Treatment Response and Follow-Up (Fig. 12.3)**

**Fig. 12.3** History: A 7-year-old boy with newly diagnosed HL. Study report: At staging (**a**) FDG-PET MIP and selected transaxial PET, CT, and PET/CT slices at the level of the upper neck show intense abnormal tracer uptake in a nodal mass involving the neck and supra- and infra-clavicular regions on the right. Note also mild increased physiologic activity in bilateral infraclavicular sites of brown fat and in the thymus in the anterior mediastinum. There is no nodal hypermetabolism in the chest and no pulmonary nodules. There is no nodal hypermetabolism in the abdominal, retroperitoneal, or pelvic lymphatic chains. The spleen is normal in size and tracer avidity. There are no areas of abnormal uptake in the appendicular and axial skeleton. Impression: Supradiaphragmatic sites of nodal HL. The patient received treatment according to protocol and achieved a complete response. At the end of treatment (**b**): MIP and selected PET, CT, and transaxial PET/CT slices at the level of the upper mediastinum show that the supradiaphragmatic abnormal uptake foci in sites of HL have disappeared. There is mild-to-moderate tracer activity in an enlarged hyperplastic thymus and in sites of physiologic brown fat above the diaphragm. There is no nodal hypermetabolism in the neck and chest and in the abdominal, retroperitoneal, or pelvic lymphatic chains. There are no pulmonary nodules. The spleen is normal in size and tracer avidity. There are no areas of abnormal uptake in the appendicular and axial skeleton. Impression: No evidence of active HL. Increased uptake in the thymus, consistent with post-treatment hyperplasia. The patient was followed up and re-evaluated 2 years later for suspicion of recurrence. At restaging (**c**): MIP (left), selected coronal PET slices (center) and transaxial PET, CT (with bone windows), and PET/CT slices at the level of the lower thorax (right) show new, intensely abnormal tracer uptake in signifcant lymphadenopathy in the left cervical, supraand infra-clavicular regions. Note mild physiologic uptake in a hyperplastic thymus. There is no nodal hypermetabolism in the chest and in abdominal, retroperitoneal, or pelvic lymphatic chains. There is a new focal site of increased tracer uptake in the T9 vertebral body, with no corresponding lesion seen on CT. In addition, there is diffuse homogeneous increased activity throughout the skeleton. Impression: The fndings are consistent with sites of nodal and skeletal recurrence of HL. Diffuse increased tracer activity in the skeleton, most probably reactive to increased hematopoiesis

**Case 12.4 Post-transplant Lymphoproliferative Disorder (PTLD), Transformation to Non-Hodgkin's Lymphoma (NHL)–PET/MRI (Fig. 12.4)**

**Fig. 12.4** History: A 7-year-old boy with known heterotaxy. Status after heart transplant in 2013, presented with a left neck mass. At clinical examination, he was found to have diffuse lymphadenopathy, small bowel intussusception, and kidney masses. The patient was referred with a suspicion of PTLD. PET/MRI was performed after administration of FDG and contrast for the MRI component. Study report: MIP images of FDG-PET and MRI demonstrate tracer activity in both maxillary sinuses, in a right costo-phrenic lymph node and in bilateral avid pulmonary nodules, mainly in a left apical pleural-based lesion. There is focal uptake in bowel in the right upper quadrant, due to small bowel-small bowel intussusception seen on prior CT. There is abnormal uptake in a conglomerate of left renal masses. There is no nodal hypermetabolism in the abdominal, retroperitoneal, or pelvic lymphatic chains. The spleen is absent, consistent with the history of heterotaxy. There are multiple abnormal foci of tracer uptake in the skeleton. A soft tissue mass encompasses the left mandibular ramus. Additional foci of increased activity are seen in the mandible and maxilla bilaterally, the occiput, the left glenoid, the pelvic bones, the right femoral shaft, and the left femoral neck. Diffuse bony involvement includes multilevel vertebral bodies, some with soft tissue and epidural extension. There is increased uptake and enhancement along multiple nerve roots, such as the sacral nerves and left L2 nerve root. Impression: The fndings are consistent with diffuse FDG-avid disease including bony involvement of the axial and appendicular skeleton, bilateral renal masses, lymphadenopathy above the diaphragm, bowel involvement, and lung lesions, suggesting PTLD with transformation to NHL, further confrmed by subsequent biopsy. Status after known heterotaxy and orthotopic heart transplant

#### **Case 12.5 Osteosarcoma, Metastatic to Bone, Staging (Fig. 12.5)**

**Fig. 12.5** History: A 14-year-old girl presented for evaluation of a destructive lesion in the right distal femur suggestive of a primary bone tumor. Study report: There is no nodal hypermetabolism in the head and neck. Note physiological cervical and axillary uptake in brown fat. There is no nodal hypermetabolism in the chest and no pulmonary nodules. There is no nodal hypermetabolism in abdominal, retroperitoneal, or pelvic lymphatic chains. The spleen is normal in size and tracer avidity. There is intense tracer uptake in the known lesion in the distal right femur seen on the FDG-PET MIP image (**a**). Additional foci of moderately increased tracer uptake are seen in mixed, lytic-blastic bone lesions in the right proximal humerus (**b**, arrow) and L2 vertebral body (**c**, arrow). Impression: The fndings are consistent with right femur osteosarcoma with skeletal metastases

#### **Case 12.6 Metastatic Rhabdomyosarcoma (Fig. 12.6)**

**Fig. 12.6** History: A 14-year-old boy presented with a left testicular mass. FDG-PET/CT was performed for staging evaluation. Study report: MIP (left), transaxial (center) and coronal (right) CT, PET, and fused slices at the level of retroperitoneal lymphadenopathy demonstrate focal increased tracer activity in the left testicular mass (thin arrow), hypermetabolic left retroperitoneal paraaortic lymphadenopathy, extending from the level of the left kidney (thick arrow and arrowhead) to just above the bladder. Impression: The fndings are consistent with left testicular neoplasm with left retroperitoneal extensive metastatic lymphadenopathy. Biopsy diagnosed rhabdomyosarcoma

#### **12.3 Neuroblastoma**

#### **Clinical Indications [11]**


#### **Correlative Imaging [37, 38]**


imaging modality when epidural or intracranial disease is suspected.

MIBG *Scintigraphy of Neuroblastoma*

#### **Specifc Study Interpretation Criteria (***See also* **Box 12.2—***Imaging with MIBG***)**

• Pathological tracer uptake is found in the primary tumor and in metastases in lymph nodes, liver, bone, bone marrow, and rarely, skin, lungs, and brain.

#### *MIBG Scoring Systems* [39]

	- The Curie Score (Children's Oncology Group—COG) divides the skeleton into 9 compartments and a 10th compartment for the soft tissues. The uptake score for each compartment ranges from 0 to 3 [40].
	- The SIOPEN score (International Society of Paediatric Oncology Europe Neuroblastoma), only scores skeletal disease. The skeleton is divided into 12 segments. The uptake score for each segment refects the disease extent in that segment and ranges from 0 to 6 [41].

#### **Red Flags [14]**

• Careful drug history should be obtained before imaging. Numerous drugs interfere with the uptake or retention of MIBG and should be discontinued for approximately 4 biological half-lives. A detailed list of interfering drugs, most of them rarely used in children, can be found in Appendix 1 of the EANM guidelines [11]. The main drugs to be withdrawn in children are those used for symptomatic treatment of asthma and of upper respiratory tract infections (decongestants), and occasional antihypertensive drugs.


#### **Take Home Messages [14]**


test. It is the current standard due to appropriate physical characteristics for the best image quality and dosimetry.

	- Biological heterogeneity in populations of tumor cells can alter their MIBG avidity.
	- Changes occur during the course of the disease course.
	- MIBG avidity of relapsed disease might differ from the initial disease.
	- After treatment, uptake in residual tumor deposits may persist due to differentiation of the tumor to mature MIBG-avid ganglioneuroma.
	- MIBG imaging plays a theranostic role in the assessment of neuroblastoma.
	- Alternative imaging of neuroblastoma with PET tracers can be considered.

PET *Imaging of Neuroblastoma* (*see also* Box 12.1, Box 12.3, and Box 12.4)

#### **Clinical Indications [42, 43]**


FDOPA [44–46] (*See also* Box 12.3)

• FDOPA uptake is relatively specifc for NETs including neuroblastoma. When available, it is considered the preferred PET alternative to 123I-MIBG.

#### **Red Flags**


#### **Take Home Messages [47]**


#### FDG [5] (*see also* Box 12.1)

	- Uptake is proportional to the degree of malignancy.
	- Lack of specifcity, mainly for assessing the presence of bone marrow involvement, a very common location for neuroblastoma metastases and also a site of physiologic FDG uptake.
	- Cranial vault lesions may be diffcult to detect on FDG imaging due to the adjacent high brain activity.

68GA-PEPTIDES [15, 48, 49] (*see also* Box 12.4)

#### **Clinical Indication**


#### **Red Flags**


#### **Take Home Messages**


• They have rapid clearance from the blood and renal excretion. Maximum tumor activity is reached at 70 ± 20 min.

#### **Relevant Case Examples**

**Case 12.7 Metastatic Neuroblastoma—MIBG Scintigraphy (Fig. 12.7)**

**Fig. 12.7** History: A 16-month-old boy presented with multiple soft tissue masses over the right eye and the right thigh, and an additional palpable mass in the abdomen. Biopsy of the right thigh mass and of the bone marrow diagnosed neuroblastoma. Study report: MIBG scintigraphy, anterior and posterior planar spot views of the whole body, demonstrate foci of abnormally increased tracer uptake involving the known soft tissue masses in the roof of the right orbit, in the right upper abdomen (with a cold, photopenic, central area, most probably necrosis) and the upper right thigh. There are also multiple foci of increased tracer uptake in the skeleton, in the left mandible, ribs, and vertebrae. Impression: The fndings are consistent with metastatic neuroblastoma

#### **Case 12.8 Metastatic Neuroblastoma, Response to Treatment—MIBG Scintigraphy (Figs. 12.8 and 12.9)**

**Fig. 12.8** History: An 18-month-old infant girl presented with a large abdominal mass suspected of neuroblastoma. A baseline MIBG scan was obtained for initial staging. Study report: Planar spot images of the whole body (**a**) show intense tracer uptake in the abdominal mass, as well as in multiple skeletal metastases in the skull, upper limbs, pelvis, and lower limbs. SPECT, low dose CT and SPECT/

CT transaxial, sagittal, and coronal slices (**b**–**d**) show a left paravertebral, metastatic mediastinal mass (cross hair) that was not evident on planar images. Impression: The fndings suggest metastatic neuroblastoma, further confrmed by biopsy of the abdominal mass. The patient started induction chemotherapy

**Fig. 12.9** A follow-up 123I-MIBG scan was obtained 2 months after the start of treatment according to the therapy protocol. Study report: MIBG scintigraphy, anterior, and posterior planar spot views of the whole body, (**a**) show normal tracer distribution with a resolution of the uptake in the abdominal tumor and in the metastatic sites.

Transaxial, sagittal, and coronal SPECT, CT, and SPECT/ CT slices (**b**–**d**) demonstrate that the size of the abdominal tumor has signifcantly decreased. The crosshair is positioned over a calcifed portion of the residual tumor and shows no tracer uptake. Impression: The fndings indicate a complete metabolic response

#### **Case 12.9 Metastatic Neuroblastoma, Heterogeneous Uptake on MIBG Scintigraphy (Fig. 12.10 )**

**Fig. 12.10** History: A 2-month-old girl presented with a large right-sided abdominal neuroblastoma and massive enlargement of the liver. MIBG SPECT/CT was obtained for initial staging. Study report: scintigraphy, anterior and posterior spot views of the whole body ( **a**) shows intense tracer uptake in a huge liver occupying both sides of the abdomen. Tracer activity in the rest of the body is faint. Using manipulation of the image gray scale ( **b**) physiological tracer localization is identifed in the orbits, skull base (arrows), and lower limbs. Transaxial and sagittal SPECT ( **c**) and fused SPECT/CT slices ( **d**) show intense tracer uptake in an enlarged liver occupying both sides of the abdomen. There is no appreciable MIBG uptake in the primary tumor in the right upper abdomen (crosshair). SPECT co-registered to an external diagnostic, contrastenhanced CT to better delineate the primary tumor ( **e** – **g**) shows no MIBG uptake in a large abdominal tumor. Impression: The fndings are consistent with a non-MIBG-avid abdominal neuroblastoma with MIBG-avid metastases to liver and bone marrow. The difference in MIBG avidity between the primary tumor and the distant metastases refects the biological heterogeneity of neuroblastoma cell populations

**Fig. 12.11** History: A 5-year-old boy presenting with a thoracoabdominal mass was referred with the suspicion of neuroblastoma. Study report: At diagnosis MIP (**a**) and selected transaxial PET, CT, and PET/CT slices at the level of the lower thorax/upper abdomen (**b**) show an area of inhomogeneous abnormal tracer uptake (SUVmax up to 6.4) in a heterogeneous mass, 7 × 10 × 10 cm in size, located right paravertebral to the lower thoracic spine, most probably involving the right foramina of T10. There is no increased activity in lymph nodes in the neck and chest and in the abdominal, retroperitoneal, or pelvic lymphatic chains. There are no pulmonary nodules. The spleen is normal in size and tracer avidity. There are no areas of abnormal uptake in the appendicular and axial skeleton. Impression: The fndings suggest the diagnosis

of neuroblastoma with suspected involvement of the right foramina of T10. The diagnosis of intermediate-risk neuroblastoma was confrmed by pathology. Laminectomy of T7–T10 with partial surgical removal of the tumor was performed and protocol treatment was started. At 2 months post-surgery a 2nd FDOPA PET/CT study was performed prior to the institution of a new treatment line. MIP (**c**) and selected coronal PET slices (**d**) demonstrate intense abnormal tracer uptake in new right supraclavicular lymphadenopathy, in a conglomerate of pleural nodules in the right hemithorax that involve the mid- and lower mediastinum and the chest wall muscles and in right para-aortic lymph nodes (arrow). Impression: The fndings demonstrate signifcant tumor progression

#### **Case 12.11 Metastatic Neuroblastoma, PET/ CT with 68Ga-DOTATATE PET/CT (Fig. 12.12 )**

**Fig. 12.12** History: An 8-year-old girl with refractory stage 4 neuroblastoma was referred to PET/CT to determine suitability for 177Lu-DOTATATE therapy. Study report: PET MIP, anterior, and posterior views, show multiple areas of abnormal tracer uptake in the primary tumor in the upper abdomen and in skeletal metastases involving vertebrae, the pelvis, and proximal femuri. Impression: The fndings are consistent with metastatic neuroblastoma with SSTRs, a suitable candidate to PRRT

#### **12.4 Other Neuroendocrine Tumors**

68GA-PEPTIDE IMAGING OF NETS (see also Box 12.4—Imaging with 68Ga-peptides)

#### **Clinical Indications [15]**


#### **Red Flags [50]**

• Brown fat visualization is not a common problem in 68Ga-peptide imaging in NETs.

#### **Take Home Message**


FDOPA IMAGING OF NETS (*See also* Box 12.3*—Imaging with FDOPA*)

#### **Clinical Indications [51, 52]**


#### **Red Flags**


#### **Take Home Message**

	- Earlier and shorter acquisition time
	- Improved patient comfort
	- Improved spatial resolution
	- Less radiation exposure

#### **Representative Case Examples**

#### **Case 12.12 Paraganglioma (PGL), 68Ga-DOTATE PET/CT (Fig. 12.13)**

**Fig. 12.13** History: A 9-year-old girl presented with hypertension and headaches and was diagnosed with a right lumbar paravertebral PGL with a SDH gene line mutation. The tumor was resected and hypertension and symptoms improved. Four years later, at the age of 13 years, the patient presented again with hypertension. MRI showed recurrence of the mass in the right paravertebral region. PET/CT was performed for restaging of the recurrence. Study report: MIP (left) and selected transaxial (right top) and coronal (right bottom) PET/CT slices at the level of the mid-abdomen show increased focal tracer uptake in the right paravertebral mass (yellow arrow) as well as in a metastatic focus in the left 6th rib (blue arrow). There is no increased activity in lymph nodes in the neck and chest and no pulmonary nodules. There are no additional areas of abnormal uptake in the appendicular and axial skeleton. Impression: The fndings are consistent with recurrent PGL metastatic to bone. Both sites were resected, however, a follow-up scan performed 6 months later showed tumor progression with multiple bone metastases. The patient was treated with 177Lu- DOTATATE and remained stable for 2 years

#### **Case 12.13 Pheochromocytoma—FDG-PET/ CT (Fig. 12.14)**

**Fig. 12.14** History: An 11-year-old boy presented with hypertension. CT scan showed a left adrenal mass. 123I-MIBG was negative (not shown). Study report: FDG-PET/CT shows abnormal uptake in the left adrenal mass (arrow) on transaxial, sagittal, and coronal PET (top right) and CT (bottom right) slices and coronal CT image of torso. There is no nodal hypermetabolism. There is no nodal hypermetabolism in the neck and chest and in the

abdominal, retroperitoneal, or pelvic lymphatic chains. There are no pulmonary nodules. The spleen is normal in size and tracer avidity. There are no areas of abnormal uptake in the appendicular and axial skeleton. Impression: The fndings are suggestive of malignancy with no evidence of metastatic disease. Biopsy diagnosed pheochromocytoma

#### **12.5 Musculo-Skeletal Malignancies (see also Box 12.5)**

#### **Clinical Indications [21, 23, 54–56]**


#### **Correlative Imaging**

• In the presence of specifc symptoms, plain radiographs are followed as a rule by MRI, the frst choice investigation in most children with bone tumors.

#### **Red Flags**


region of the abnormality seen on SPECT to reduce radiation exposure.

• The CT component of a bone SPECT/CT can be acquired as a pediatric low-dose CT for localization and attenuation correction or as a diagnostic CT. Many skeletal lesions are adequately evaluated even with low-dose CT parameters.

#### **Take Home Messages**


#### **Representative Case Examples**

**Case 12.14 Metastatic Neuroblastoma, Bone Scintigraphy**

**Fig. 12.15** History: A 5-year-old boy presented with right-sided limp. Clinical examination was normal. Plain radiographs of his pelvis and lower limbs were normal. Lab tests including ESR and CRP were mildly elevated. Study report: Bone scintigraphy, anterior and posterior planar spot views of the whole body, demonstrate multiple focal areas of increased tracer uptake in the skull, right proximal humerus, both scapulae, upper and lower thoracic and lumbar vertebrae, right acetabulum and distal femora (right more than left). Note asymmetrical metaphyseal activity specifcally in the distal femora. Impression: The fndings are consistent with neuroblastoma metastatic to bone. Abdominal US revealed a mass in the right adrenal. Tissue sampling diagnosis was stage IV neuroblastoma. Total body MIBG scintigraphy showed tracer uptake in the primary tumor and metastatic bone lesions

#### **Case 12.15 Ewing Sarcoma, Staging, Bone Scintigraphy (Fig. 12.16)**

**Fig. 12.16** History: An 8-year-old boy presented with a large pelvic mass. Histopathology diagnosed Ewing's sarcoma. Bone scintigraphy was performed for staging. Study report: Anterior and posterior whole body (**a**) and lateral spot views of the skull (**b**) show marked displacement of the urinary bladder to the left upper pelvis due to the known large tumor. Activity is noted in a urinary catheter to the left side of the body. Skeletal lesions are noted in the parietal and occipital skull, left orbit (arrow), L1, acetabulum, the right pelvis involving the superior pubic ramus, ischium, and ilium, as well as in the proximal and distal (arrow) left femur. Coronal (**d**) and sagittal (**e**) SPECT slices show the L1 lesion (crosshairs). Transaxial (**f**) and coronal (**g**) slices show a lesion in the internal pelvic rim. MIP image (**c**) provides an overview of the pelvic and lumbar lesions (arrows). Impression: The fndings suggest stage 4 pelvic Ewing's sarcoma with multiple skeletal metastases

#### **Case 12.16 Metastatic Osteosarcoma, Bone Scintigraphy (Fig. 12.17)**

**Fig. 12.17** History: An 8-year-old girl with left femoral osteosarcoma underwent bone scintigraphy for staging. Study report: Anterior and posterior whole body (**a**) and spot views (**b**) of the thighs show intense tracer uptake in the known primary tumor in the left mid-thigh. A "skip" lesion is seen in the distal left femur, better appreciated on the spot views (**b**). MIP (**c**) and transaxial slices (**d**, **e**)

from the SPECT of the thorax show several lesions in the left chest, localized to the posterior mediastinum and lung parenchyma. Impression: The fndings are consistent with metastatic stage 4 osteosarcoma of the left femur with a skip lesion in the distal left femur and additional boneforming metastases in the ST of the left hemithorax

#### **Case 12.17 Osteosarcoma, NaF PET/CT (Fig. 12.18)**

**Fig. 12.18** History: An 8-year-old girl with chondroblastic osteosarcoma of the right femur performed NaF PET/ CT for staging. Study report: Anterior (**a**) and lateral (**b**) MIP projections and sagittal PET, CT, and PET/CT slices at the level of the thigh (**c**) show inhomogeneous increase

tracer uptake in a destructive lesion in the mid-shaft of the right femur. No other skeletal lesions are seen. Impression: The fndings demonstrate the primary osteosarcoma in the right femur with no evidence of metastatic spread

**Fig. 12.19** History: A 11-year-old girl complains of right hip pain for 2 months and was referred to NaF PET/CT for further evaluation. Study report: Anterior MIP (**a**) and selected transaxial PET, CT, and PET/CT slices at the level of the mid-thorax (**b**) and lower pelvis (**c**) show two foci of inhomogeneous increased tracer activity localized

at the distal one-third of the right humeral shaft and the trochanteric region of the right femur, with corresponding lytic lesions on CT images (arrows). Impression: The fndings are consistent with aggressive osteoblastic bone lesions in the right humerus and proximal right femur. Biopsy diagnosed Langerhans cell histiocytosis

#### **References**


dren affected by neuroblastoma in comparison with (123)I-mIBG scan: the frst prospective study. J Nucl Med. 2020;61(3):367–74.


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