Marcelo F. Di Carli Maurizio Dondi Ra aele Giubbini Diana Paez *Editors* 

# IAEA Atlas of Cardiac PET/CT

A Case-Study Approach

IAEA Atlas of Cardiac PET/CT

Marcelo F. Di Carli • Maurizio Dondi Rafaele Giubbini • Diana Paez Editors

# IAEA Atlas of Cardiac PET/CT

A Case-Study Approach

*Editors* Marcelo F. Di Carli Brigham and Women's Hospital Boston, MA USA

Raffaele Giubbini Department of Nuclear Medicine University of Brescia Brescia, Italy

Maurizio Dondi Division of Human Health International Atomic Energy Agency Vienna, Austria

Diana Paez Division of Human Health International Atomic Energy Agency Vienna, Austria

This book is an open access publication with a grant from the International Atomic Energy Agency. ISBN 978-3-662-64498-0 ISBN 978-3-662-64499-7 (eBook) https://doi.org/10.1007/978-3-662-64499-7

© IAEA: International Atomic Energy Agency 2022

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## **Preface**

Noncommunicable diseases (NCDs) are responsible for 71% of deaths globally and, among them, cardiovascular diseases (CVDs) are the leading cause of death, accounting for almost 44%, followed by cancer with 22%, respiratory diseases with 9%, and diabetes with 4% (World Health Organization n.d.-a). According to the World Health Organization (WHO) 15 million people, aged between 30 and 69 years, die annually from an NCD. More than 85% of these "premature" deaths occur in low- and middle-income countries. Cardiovascular diseases account for the majority of NCD-related deaths. When distributed by region, the South-East Asia Region has the highest probability (25%) of dying young due to NCDs, followed by Africa with 22%: deaths which are greatly preventable (World Health Organization n.d.-b).

Among CVDs, ischemic heart disease (IHD) plays an important role and, according to the Institute for Health Metrics and Evaluation, an independent global health research center at the University of Washington, IHD was responsible for 15.96% of deaths worldwide in 2017. Considering the WHO regions, the highest incidence, 24.51%, was registered in the European Region, followed by the Eastern Mediterranean Region with 20.76%, the Americas with 16.12%, the Western Pacifc Region with 15.94%, the South-East Asia Region with 14.91%, and fnally Africa with only 5.49% of global deaths associated with IHD. It is also pertinent to note that between 2000 and 2017, the global number of IHD deaths increased by 0.26% per year (The Institute for Health Metrics and Evaluation n.d.).

In 2015, the United Nations established the Sustainable Development Goals (SDGs), a set of 17 specifc goals aimed at transforming our world by 2030 and achieving a better and more sustainable future for all. Goal 3 focuses on ensuring healthy lives and promoting well-being for all at all ages, and target 3.4 addresses the challenges of reducing premature NCD mortality by 30% by 2030.

As a member of the United Nations family, the International Atomic Energy Agency (IAEA) is committed to supporting its member states in achieving the SDGs. Within the IAEA's Division of Human Health, the Nuclear Medicine and Diagnostic Imaging Section aims at supporting the attainment of target 3.4 by means of establishing and strengthening the practice of medical imaging. Special emphasis has been placed on supporting the development of nuclear cardiology within a framework of appropriate use and quality of clinical practice (International Atomic Energy Agency 2012; Vitola et al. 2009).

Several noninvasive imaging tools help to diagnose, stratify risk, and guide management of cardiac patients. They include nuclear cardiology techniques, using either single photon emission computed tomography (SPECT) or positron emission tomography coupled with computer tomography (PET/CT). While myocardial imaging with SPECT has been fully embraced by the cardiology community and is widely available worldwide, PET/CT introduction has been slower due not only to its higher costs but also to the limited availability of PET/CT scanners. According to the IAEA Medical imAGIng and Nuclear Medicine global resources database (IMAGINE) (IAEA n.d.), there are more than 5000 PET/CT scanners installed worldwide, used primarily for oncology applications. Therefore, it is important to help colleagues make better use of the resources available to them and to expand PET/CT applications to cardiology.

This Atlas aims at presenting a wide portfolio of examples of PET/CT studies in different cardiac conditions and at providing a rationale for the implementation of this technology in an array of clinical conditions.

The publication is divided into fve chapters, beginning with technical considerations on radiopharmaceuticals utilized for cardiac PET/CT; acquisition protocols; and recognition of artifacts. The spectrum of current clinical indications is then covered, including a fnal section giving an overview of emerging applications. Each case is structured in a simple way containing the following information: (1) clinical indication for the PET/CT study, (2) brief clinical history, (3) main relevant PET/CT fndings, (4) teaching points.

The objective of this publication is to lay out a case-based presentation of the main indications for PET/CT in cardiology to provide nuclear cardiology practitioners, in both developed and developing world, with a tool to understand the value in the appropriate clinical conditions. This should facilitate the introduction of PET/CT procedures and ensure that, in clinical practice, those studies are accurate and helpful.

Vienna, Austria Diana Paez

#### **References**

World Health Organization. (n.d.-a). Noncommunicable diseases. http://www.who.int/news-room/fact-sheets/ detail/noncommunicable-diseases. Accessed August 1st, 2021.

World Health Organization. (n.d.-b). Cardiovascular diseases https://www.who.int/news-room/fact-sheets/ detail/cardiovascular-diseases-(cvds) Accessed August 1st, 2021.

The Institute for Health Metrics and Evaluation. (n.d.). https://vizhub.healthdata.org/gbd-compare/ Accessed August 1st, 2021.

Nuclear Cardiology: Guidance and Recommendations for Implementation in Developing Countries. IAEA Human Health Series 23. International Atomic Energy Agency, Vienna, 2012.

Vitola JV, Shaw LJ, Allam AH, Orellana P, Peix A, Ellmann A, et al. Assessing the need for nuclear cardiology and other advanced cardiac imaging modalities in the developing world. J Nucl Cradiol 2009; 16:956–61.

IAEA Medical imaging and nuclear medicine global resources database (IMAGINE). (n.d.). https://humanhealth.iaea.org/HHW/DBStatistics/IMAGINEMaps.html Accessed August 1st, 2021.

## **Contents**


## **Contributors**

**D. Albano** Department of Nuclear Medicine, University of Brescia, Brescia, Italy **E. Alexanderson** Instituto Nacional De Cardiologia Ignacio Chavez, Mexico City, Mexico **M. Bertoli** Department of Nuclear Medicine, Spedai Civili Brescia, Brescia, Italy **L. Camoni** Department of Nuclear Medicine, University of Brescia, Brescia, Italy **I. Carvajal** Instituto Nacional De Cardiologia Ignacio Chavez, Mexico City, Mexico **S. Cuddy** Brigham and Women's Hospital, Boston, MA, USA **Marcelo F. Di Carli** Brigham and Women's Hospital, Boston, MA, USA **S. Divakaran** Brigham and Women's Hospital, Boston, MA, USA **Maurizio Dondi** Division of Human Health, International Atomic Energy Agency, Vienna, Austria **S. Dorbala** Brigham and Women's Hospital, Boston, MA, USA **R. Endozo** Institute of Nuclear Medicine, University College London Hospital, London, UK **Raffaele Giubbini** Department of Nuclear Medicine, University of Brescia, Brescia, Italy **E. Milan** Nuclear Cardiology Lab and PET Centre, Treviso Hospital, Treviso, Italy **Diana Paez** Division of Human Health, International Atomic Energy Agency, Vienna, Austria **P. Raggi** Division of Cardiology, University of Alberta, Edmonton, AB, Canada **C. Rodella** Department of Medical Physics, Spedali Civili Brescia, Brescia, Italy **V. Singh** Midwest Heart and Vascular Specialists, HCA Midwest Health, Kansas City, MO, USA **A. Thornton** Institute of Nuclear Medicine, University College London Hospital, London, UK **M. Williams** The University of Edinburgh, Edinburgh, UK

# **Technical Considerations for Cardiac PET/CT**

Marcelo F. Di Carli, Rafaele Giubbini, D. Albano, E. Milan, I. Carvajal, E. Alexanderson, Diana Paez, and Maurizio Dondi

Positron emission tomography (PET) is a non-invasive imaging technique that employs positron-emitting radionuclides labelled to biological molecules. Unlike other imaging techniques, such as computer tomography (CT) and magnetic resonance imaging (MRI) that provide anatomical or structural information, PET allows obtaining unique quantitative information of important biologic processes in vivo (e.g. myocardial perfusion and metabolism, infammation, innervation, receptor density).

Although there is expanded use of PET for oncology, cardiac PET is emerging as an important modality for the detection of physiologically signifcant coronary artery disease (CAD), evaluation of infltrative diseases (e.g. sarcoidosis, amyloidosis), assessment of myocardial viability, and for infective endocarditis. Modern PET systems are combined with CT, which provides additional information about the burden of atherosclerosis and plaque morphology.

A unique advantage of PET is its ability to enable absolute quantifcation of myocardial blood fow in mL/min/g of myocardial tissue. As reviewed in this Atlas, the quantitative blood fow information enhances the diagnostic value of

M. F. Di Carli

R. Giubbini · D. Albano Department of Nuclear Medicine, University of Brescia, Brescia, Italy

e-mail: raffaele.giubbini@unibs.it; domenico.albano@unibs.it E. Milan

Nuclear Cardiology Lab and PET Centre, Treviso Hospital, Treviso, Italy e-mail: elisa.milan@aulss2.veneto.it

I. Carvajal · E. Alexanderson Instituto Nacional De Cardiologia Ignacio Chavez, Mexico City, Mexico

D. Paez · M. Dondi (\*) Division of Human Health, International Atomic Energy Agency, Vienna, Austria e-mail: d.paez@iaea.org

PET myocardial perfusion imaging, improves risk stratifcation and helps guide patient management.

#### **1.1 General Description of PET Radiopharmaceuticals**

#### **PET Radiotracers for Myocardial Perfusion Imaging**

*Rubidium-82 (Rb-82)*: It is a monovalent cationic analogue of potassium and is produced in a commercially available generator by decay from strontium-82 attached to an elution column. It is the most commonly used radiopharmaceutical for myocardial perfusion imaging with PET, particularly in the USA. The strontium-82 has a half-life of 25.5 days and decays to rubidium-82 by electron capture. The physical half-life of Rb-82 is 76 seconds. Rb-82 is eluted with normal saline by a computer-controlled elution pump, directly connected by intravenous tubing to the patient. The generator can be eluted approximately every 10 min, which allows for very rapid serial rest and stress imaging. Given its ultrashort half-life, exercise is not possible with Rb-82. Rb-82 is extracted from plasma with high effciency by myocardial cells via the Na+/K+ ATPase pump. Myocardial extraction of Rb-82 is superior to that of Tc99m-labelled perfusion tracers but lower than that of N-13 ammonia at high fow rates. The energy of positrons emitted from the decay of Rb-82 is much higher than that of N-13 or F-18. Consequently, the distance between the decay site and the annihilation site (so-called positron range) is higher for Rb-82, which negatively affects the spatial resolution of PET images.

*N-13 Ammonia*: It has a high frst pass extraction at high myocardial blood fow, which makes it ideal for myocardial perfusion imaging. The main limitation is that its 9.96-min half-life requires an on-site cyclotron and radiochemistry synthesis capability. Novel 'bench top' cyclotrons have recently become commercially available potentially allowing more widespread clinical use of N-13 ammonia. This commercially available mini-cyclotron with automated synthesis allows on-site production of N-13 ammonia without

**1**

Brigham and Women's Hospital, Boston, MA, USA e-mail: mdicarli@bwh.harvard.edu

the need of a larger production facility. Following IV injection, it undergoes rapid blood pool clearance with diffusion across cell membranes and trapping inside the cardiomyocyte following irreversible enzymatic conversion to glutamic acid. Myocardial retention of N-13 ammonia may be heterogeneous in some patients with apparent defects in the lateral left ventricular wall. N-13 ammonia images also may be degraded by occasional intense liver activity, which can interfere with the evaluation of the inferior wall. Although the sequestration of N-13 ammonia in the lungs is usually minimal, it may be increased in patients with depressed left ventricular systolic function or chronic pulmonary disease and, occasionally, in smokers and interfere with the evaluation of the lateral wall. Its relatively long half-life also allows to be combined with exercise.

*O-15 Water*: It is a cyclotron product and has a physical half-life of 2.07 min. O-15 water is a freely diffusible agent with very high myocardial extraction across a wide range of myocardial blood fows. The degree of extraction is independent of fow which makes it an ideal agent for quantifcation of myocardial blood fow. However, because it is a freely diffusible tracer, imaging is challenging due to its high concentration in the blood pool. Parametric fow images can be used to delineate the presence and extent of regional perfusion defects, but they are of relatively lower quality compared to Rb-82 and N-13 ammonia. Generation of gated images for calculation of LV volumes and ejection fraction is challenging and not performed routinely.

*F-18 Flurpiridaz*: It is an investigational perfusion tracer currently under evaluation in phase III clinical trials ( 18F-BMS747158-02, NCT03354273). It has higher frst pass myocardial extraction than Rb-82 and N-13 ammonia. The use of F-18 with a 108-min half-life makes it ideal for unit dose distribution, thereby facilitating broader access to cardiac PET imaging without the need of an on-site cyclotron or a 82St/82Rb generator.

#### **Myocardial Metabolism**

*F-18 Fluorodeoxyglucose (FDG)*: It is an analogue of glucose produced in a cyclotron with associated specialized radiochemistry modules. The relatively long half-life of F-18 allows for off-site production and commercial unit dose distribution. Like regular glucose, FDG is transported into the myocardium by specifc glucose transporters (GLUT-1 and GLUT-4) via facilitated diffusion. Inside the cardiomyocyte, FDG undergoes phosphorylation and trapping and is a marker of glucose metabolism. FDG is currently used for myocardial viability assessment and for delineation of myocardial infammation/infection.

#### **1.2 PET Acquisition Protocols**

Figure 1.1 below provides a schematic representation of the common protocols used for imaging myocardial perfusion with PET/CT. Please see specifc protocols for myocardial viability in Sect. 2.7 and infammation/infection imaging in Sect. 4.1.

*CT Scan*: Patient positioning is performed with a CT scout image or topogram, which is followed by a low-dose CT transmission scan used for correction of attenuation by soft tissues. The acquisition parameters for the CT transmission scan varies with the confguration of the CT scanner (e.g. 8, 16, 64 multidetector CT). However, the general scan settings include a slow rotation speed, relatively high pitch, variable tube potential (e.g. 80–140 kVp depending on patient size) and a low tube current. The CT transmission scan is non-gated and acquired during shallow free breathing. In patients without known CAD, it is common to also include a separate gated CT scan for quantifcation of coronary artery calcifcations. In the absence of a non-contrast gated CT scan, coronary artery calcifcations can also be assessed semi-quantitatively from the CT transmission scan obtained for attenuation correction. In selected patients, it is also possible to obtain a coronary CT angiogram (CCTA) immediately following the assessment of myocardial perfusion, but this necessitates at least a 64-slice multidetector CT scanner.

*Emission Scans*: The radiotracer dose should be adjusted based on the patient size, equipment and acquisition protocol (i.e. 2D vs 3D mode), and imaging protocol (e.g. same dose vs low-high dose protocols for N-13 ammonia). There are several ways in which the emission perfusion images can be acquired including:


**Fig. 1.1** Schematic outline of myocardial perfusion imaging protocols with PET. *Rega* regadenoson, *Adeno* adenosine, *Dipy* dipyridamole

• *List-mode imaging*: This is the ideal and most common approach when using modern PET cameras. In a listmode acquisition, each coincidence event is recorded with detection time and position information, as well as ECG information that allows to determine the time the event occurred during the cardiac cycle. The detection time information is used to retrospectively format the data into multiple time frames after completion of the acquisition. List-mode data can be then reformatted in many different ways including static or summed images, gated images and multi-frame or dynamic images.

*Stress Testing*: It is usually performed with pharmacologic means, most commonly vasodilators (e.g. adenosine, dipyridamole, or regadenoson) or alternatively inotropes (i.e. dobutamine). As briefy mentioned in Sect. 1.2, exercise can be performed with N-13 ammonia and in the future it will also be possible with F-18 furpiridaz. Exercise cannot be performed with rubidium-82 or O-15 water. It is important to keep in mind that exercise protocols do not currently allow to quantify myocardial blood fow, which as described above necessitates the acquisition of the initial arterial phase data to generate an arterial input function.

#### **Myocardial Perfusion Imaging Sequence**


• *Stress-only*. Please see limitations above. Perhaps this protocol is ideally suited for patients undergoing exercise stress PET myocardial perfusion imaging.

#### **Further Reading**

Murthy, V. L., Bateman, T. M., Beanlands, R. S., Berman, D. S., Borges-Neto, S., Chareonthaitawee, P. Corbett, J. R. (2017). Clinical Quantifcation of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC. Journal of Nuclear Cardiology, 25(1), 269–297.

Dilsizian, V., Bacharach, S.L., Beanlands, R.S. et al. ASNC imaging guidelines/SNMMI procedure standard for positron emission tomography (PET) nuclear cardiology procedures. Journal of Nuclear Cardiology (2016); 23: 1187–1226.

#### **1.3 Examples of Studies with 13N-Ammonia; 82Rubidium and 15O-Water**

**Case 1: PET MPI Using 13N-Ammonia**

#### **History**

• A 59-year-old male with hypertension, dyslipidaemia, diabetes mellitus and obesity without known coronary artery disease (CAD) was referred for a rest/stress 13N-ammonia myocardial perfusion PET/CT to evaluate for atypical angina and dyspnoea (Figs. 1.2 and 1.3).

#### **PET/CT Images**

**Fig. 1.2** Rest and Regadenoson-stress myocardial perfusion images obtained with 13N-ammonia as the perfusion tracer. Images are displayed in short axis (top), horizontal long axis (middle) and vertical long axis (bottom) of the heart with the stress images on the top of each

pair. The images demonstrate normal regional myocardial perfusion. The isolated small defect on the infero-apical segment is often seen, refects a partial volume effect and does not represent a pathological fnding

**Fig. 1.3** TOP panel: Time-activity curves for the arterial input function (dark and light green curves) and myocardial tissue (yellow and red curves) for the stress and rest myocardial perfusion images. BOTTOM panel: Myocardial blood fow (MBF) measurements (in mL/min/g) at rest and during Regadenoson-stress for each coronary artery territory and for the entire left ventricle. The myocardial fow reserve (stress over rest MBF) is also shown. The results show normal maximal MBF (>1.8 mL/min/g) and fow reserve (>2) in all coronary territories and for the entire left ventricle

#### **Findings**


#### **Differential Diagnosis**


#### **Correlative Imaging**

• None

#### **Management**

• Reassurance and risk factor management

#### **Teaching Points**

• A visually normal myocardial perfusion PET study with normal stress myocardial blood fow and fow reserve has very high sensitivity and negative predictive value for excluding fow limiting CAD.

• The normal myocardial fow reserve excludes the possibility of obstructive CAD and coronary microvascular dysfunction.


#### **Case 2: PET MPI Using 82Rubidium**

#### **History**


#### **Findings**


Myocardial blood fow (MBF) measurements (in mL/ min/g) at rest and during Regadenoson-stress for each coronary artery territory and for the entire left ventricle are shown in Fig. 1.3. The myocardial fow reserve (stress over rest MBF) is also shown.

**Fig. 1.4** Rest and Regadenoson-stress myocardial perfusion images obtained with 82Rubidium as the perfusion tracer. Images are displayed in short axis (top), horizontal long axis (middle) and vertical long axis (bottom) of the heart with the stress images on the top of each pair. The images demonstrate normal and homogeneous distribution of the radiotracer throughout the LV without regional perfusion defects

#### **Differential Diagnosis**

• None

#### **Correlative Imaging**

• None

#### **Management**

• Reassurance and risk factor management

#### **Teaching Points**


#### **Further Reading**

Mc Ardle B, Dowsley T, deKemp R, Wells G, Beanlands R. Does Rubidium-82 PET Have Superior Accuracy to SPECT Perfusion Imaging for the Diagnosis of Obstructive Coronary Disease?. Journal of the American College of Cardiology. 2012;60:1828–1837.


**Acknowledgement** 82Rubidium images are courtesy of Dr. Mouaz Al-Mallah, Methodist Hospital, Houston, Texas.

#### **Case 3: PET MPI Using 15O-Water**

#### **History**

• A 59-year-old female with a history of hyperlipidaemia, hypertension, obesity and hyperthyroidism was referred for a rest/stress 15O-water myocardial perfusion PET/ CT to evaluate for atypical angina and fatigue (Figs. 1.6 and 1.7).

#### **PET/CT Images**

**Fig. 1.6** Rest and Regadenoson-stress myocardial perfusion images obtained with 15O-water as the perfusion tracer. Images are displayed in short axis (top), horizontal long axis (middle) and vertical long axis (bottom) of the heart with the stress images on the top of each pair. The images demonstrate normal and homogeneous distribution of the radiotracer throughout the LV without regional perfusion defects

**Fig. 1.7** TOP panel: parametric polar maps depicting segmental MBF values for the vasodilator-stress and rest 15O-water myocardial perfusion images. The colour in the polar maps is scaled to the corresponding

MBF value. The polar map on the far right depicts the corresponding myocardial fow reserve. BOTTOM panel: shows the corresponding rest and stress MBF values, and the fow reserve


#### **Differential Diagnosis**


#### **Correlative Imaging**

• None

#### **Management**

• Reassurance and risk factor management

#### **Teaching Points**

• A visually normal myocardial perfusion PET study with normal stress myocardial blood fow and fow reserve has very high sensitivity and negative predictive value for excluding fow limiting CAD. Indeed, a recent comparative effectiveness trial demonstrated that quantitative 15O-water myocardial perfusion PET had the highest accuracy for diagnosing and ruling out obstructive CAD compared to CT coronary angiography with or without FFRCT and SPECT myocardial perfusion imaging (see suggested reading).

• The normal myocardial fow reserve also excludes the possibility of coronary microvascular dysfunction.

#### **Further Reading**


**Acknowledgement** 15O-water images are courtesy of Drs. Henrich Harms and Jens Sorensen, Uppsala University, Sweden.

#### **1.4 Recognizing and Troubleshooting Artefacts**

#### **1.4.1 Misregistration**

**Case 4**

#### **History**

• A 57-year-old male without a history of coronary artery disease (CAD) was referred for a rest/stress myocardial perfusion PET/CT to evaluate for atypical angina (Figs. 1.8 and 1.9).

#### **PET/CT Images**

**Fig. 1.8** LEFT panel: Rest and Regadenoson-stress myocardial perfusion PET/CT images obtained with 13N-ammonia. The display is as in case # 1. The images demonstrate a medium sized perfusion defect of severe intensity involving the mid and basal anterolateral and inferolateral LV segments (arrows), showing complete reversibility. RIGHT panel: The fused perfusion/CT transmission images demonstrate misregistration of the lateral and anterolateral walls on the stress images, which are overlapping the left lung feld on the CT (arrows). This misalignment leads to an attenuation correction artefact, resulting in an apparent perfusion defect

**Fig. 1.9** Rest and Regadenoson-stress myocardial perfusion PET/CT images after correction of the misregistration between the perfusion and CT transmission images. The images now demonstrate normal myocardial perfusion and a normal scan


#### **Differential Diagnosis**

• Obstructive CAD with single vessel myocardial ischaemia

#### **Correlative Imaging**

• None

#### **Management**

• Reassurance and risk factor management

#### **Teaching Points**

• Careful inspection of the emission/CT transmission alignment is a critical quality control step in the assessment of cardiac PET/CT images.



#### **1.4.2 Cardiac Motion Artefacts**

#### **Case 5**

#### **History**


#### **PET/CT Images** (Figs. 1.10 and 1.11)

A quality check for LV motion during acquisition shows a downshift of the LV during the LV cavity flling at rest and an upshift of myocardial wall in the stress study (Fig. 1.11).

After correction for patient movements, both MBF and MFR values normalize (Table 1.1).

**Fig. 1.10** MPI shows a mild reversible perfusion defect of the apical region. The quantitative values (see Table 1.1; non-motion corrected data (NMC data) show an abnormal (too high) MBF at rest in the RCA territory resulting in an impairment of the MFR in the same territory

**Fig. 1.11** Downshift of the LV during the LV cavity flling at rest (upper left panel; lower row; red boxes) and an upshift of myocardial wall in the stress study (lower left panel; upper row; red boxes). The upper right and lower right panels show the Motion Corrected studies

**Table 1.1** MBF and MFR values before and after motion correction. Quantitative values show an abnormal (too high) MBF at rest in the RCA territory and impairment of the MFR in the same territory due to an abnormally high MBF at rest. MBF normalizes (3.21) after MC


*MBF* myocardial blood fow, *MFR* myocardial fow reserve, *NMC* no motion correction, *MC* motion correction


#### **Correlative Imaging**

• Coronary angiography showing normal coronary anatomy (Fig. 1.12)

**Fig. 1.12** Selective view of the right and left coronary arteries show normal coronary anatomy of both RCA (left panel) and left coronary system (right panel)

#### **Differential Diagnosis**

• Obstructive CAD with single vessel myocardial ischaemia

#### **Teaching Points**


#### **Management**

• Reassurance and risk factor management


#### **Case 6**

#### **History**

• A 62-year-old female with obesity and HIV infection was referred for a rest/stress myocardial perfusion PET/CT to evaluate for atypical angina and dyspnoea (Figs. 1.13 and 1.14).

#### **PET/CT Images**

**Fig. 1.13** Summed rest and Regadenoson-stress myocardial perfusion PET/CT images obtained with 13N-ammonia. The display is as in case # 1. The images demonstrate blurring of the mid and basal anterolateral and inferolateral walls, resulting in a perfusion defect of moderate intensity in these LV segments (arrows), showing complete reversibility

**Fig. 1.14** Motion-free end-diastolic rest and Regadenoson-stress myocardial perfusion PET/CT images. These images demonstrate normal myocardial perfusion and a normal scan


#### **Differential Diagnosis**

• Obstructive CAD

#### **Correlative Imaging**

• None

#### **Management**

• Reassurance and risk factor management

#### **Teaching Points**


#### **Further Reading**

Di Carli M, Dorbala S, Meserve J, El Fakhri G, Sitek A, Moore S. Clinical Myocardial Perfusion PET/CT. Journal of Nuclear Medicine. 2007;48:783–793.

#### **1.4.3 Ammonia Lateral Defect**

#### **Case 7**

#### **History**


**PET/CT Images** (Fig. 1.15)

**Fig. 1.15** Summed rest and Regadenoson-stress myocardial perfusion PET/CT images obtained with 13 N-ammonia. Fixed perfusion defect in the lateral wall (arrows). Normal left ventricular systolic function and normal MFR


#### **Differential Diagnosis**

• Ischaemic disease in the left circumfex territory

#### **Correlative Image**

• Coronary Computed Tomography (Fig. 1.16)

**Fig. 1.16** Normal coronary computed tomography angiography, without evidence of obstructive lesions

#### **Management**

• None

#### **Teaching Points**



#### **1.4.4 Non-Responder to Coronary Vasodilators**

#### **Case 8**

#### **History**


#### **PET/CT Images**

• A frst study showed normal perfusion both at stress and rest, but low MFR values (Fig. 1.17).

**Fig. 1.17** The initial MPI shows a normal perfusion but MFR values below normal for all coronary territories

Enquired after completion of the imaging procedure the patient admitted that he had a cup of coffee 30 min before the stress test, despite detailed instructions given at registration. The study was repeated with repeated instructions to the patient to avoid caffeine (Fig. 1.18).


**Fig. 1.18** The repeated study shows a severe, reversible perfusion defect in the LCX territory and postero-septal segment after dipyridamole infusion, together with TID. MFR calculation shows reduced values for all coronary arteries, more prominent for the LCX


#### **Management**

• Repetition of the study after instructions to the patient to avoid caffeine

#### **Teaching Points**


• Personnel should enquire at reception if instructions have been complied with.

#### **Further Reading**


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## **Evaluation of Ischemic Heart Disease**

Marcelo F. Di Carli, Rafaele Giubbini, P. Raggi, V. Singh, D. Albano, L. Camoni, M. Bertoli, C. Rodella, Maurizio Dondi, R. Endozo, A. Thornton, and Diana Paez

The use of PET/CT hybrid imaging in ischemic heart disease, integrating information from PET and CT, has grown in the last decade, particularly because of its capacity of quantifying myocardial perfusion, allowing the assessment of myocardial blood fow (MBF) and myocardial fow reserve (MFR). This feature makes PET/CT the technique best suited to detect multivessel coronary artery disease which might not be identifed with SPECT due to its inherent limitation in cases of balanced ischemia. Additionally, the CT component of these hybrid imaging systems allows calculation of coronary artery calcium score (ChACS) and the visualization of the epicardial coronary arteries with coronary CT angiography (CCTA). PET/CT has therefore a great potential in the diagnosis and management of CAD. This chapter will cover several clinical cases, illustrating many different clinical applications in ischemic heart disease.

#### **2.1 Multi-Parametric Evaluation of Ischemic Heart Disease**

As discussed in Sect. 1.3, all modern PET tomographs are now combined with CT scanner into a hybrid PET/CT camera. Each component of the integrated system provides

M. F. Di Carli

Brigham and Women's Hospital, Boston, MA, USA e-mail: mdicarli@bwh.harvard.edu

R. Giubbini · D. Albano · L. Camoni Department of Nuclear Medicine, University of Brescia, Brescia, Italy e-mail: raffaele.giubbini@unibs.it; domenico.albano@unibs.it; luca.camoni@unibs.it

P. Raggi Division of Cardiology, University of Alberta, Edmonton, AB, Canada

V. Singh

Midwest Heart and Vascular Specialists, HCA Midwest Health, Kansas City, MO, USA e-mail: vasvi.singh@hcahealthcare.com

unique and comprehensive quantitative information for the evaluation of patients with known or suspected CAD (Fig. 2.1a–d).

The **extent and severity of regional perfusion defects** on the summed myocardial perfusion images allow delineation of the extent and severity of **focal coronary artery disease** (Fig. 2.1a). Regional myocardial perfusion is usually assessed by semi-quantitative visual analysis of the rest and stress images. The segmental scores are then summed into global scores that refect the total burden of regional and global ischemia and/or scar. Objective quantitative image analysis is a helpful tool for a more accurate and reproducible estimation of total defect size and severity and is generally used in combination with the semi-quantitative visual analysis. The semi-quantitative (visual) and quantitative scores of ischemia and scar are linearly related to the risk of adverse CV events and are useful in guiding patient management, especially the need for revascularization, and for assessing response to medical therapy.

The acquisition of ECG-gated myocardial perfusion images allows quantifcation of regional and global systolic function, and LV volumes (Fig. 2.1b). ECG-gated images with PET are typically collected at rest and during peak stress. A **drop in LVEF during stress** testing is always an

M. Bertoli Department of Nuclear Medicine, Spedai Civili Brescia, Brescia, Italy e-mail: mattia.bertoli@asst-spedalicivili.it C. Rodella Department of Medical Physics, Spedali Civili Brescia, Brescia, Italy e-mail: carlo.rodella@asst-spedalicivili.it M. Dondi (\*) · D. Paez Division of Human Health, International Atomic Energy Agency, Vienna, Austria e-mail: d.paez@iaea.org R. Endozo · A. Thornton Institute of Nuclear Medicine, University College London Hospital, London, UK e-mail: raymond.endozo@nhs.net; andrew.thornton11@nhs.net

**2**

abnormal response and can be helpful to identify **high-risk patients with multivessel CAD**.

ECG-gated CT scanning for coronary artery calcium offers a reproducible, easy-to-perform method to reliably determine whether coronary calcifcation is present or absent, without the need of intravenous contrast administration (Fig. 2.1c). The **extent and severity of coronary calcifcation** can be quantifed by validated scoring techniques (e.g., Agatston score). The non-gated CT transmission scan used for attenuation correction of the PET data may also be used to assess the extent of coronary calcifcations using semi-quantitative visual analysis. Given the apparent clinical relevance of atherosclerotic burden assessment in guiding intensifcation of preventive therapies, a formal CAC score or at least a semiquantitative assessment of CAC should be assessed and reported in all patients without known CAD undergoing myocardial perfusion PET/CT imaging.

The **quantifcation of myocardial blood fow (in mL/ min/g of myocardium) and myocardial fow reserve** (defned as the ratio between maximal stress and rest myocardial blood fow) are important physiologic parameters that refect the extent and severity of **diffuse atherosclerosis (obstructive and nonobstructive) and microvascular dysfunction**, and can be measured by routine post-processing of myocardial perfusion PET images (Fig. 2.1d). As discussed in the section of Evaluation of Ischemic Heart Disease, these measurements of fow and fow reserve have important diagnostic and prognostic implications in the evaluation and management of the patients with known or suspected CAD.

**a b**


**c d**


**Fig. 2.1** Comprehensive qualitative and quantitative information for the evaluation of patients with known or suspected CAD using PET/CT. (**a**) Focal disease. (**b**) LV function and volumes. (**c**) Atherosclerosis burden. (**d**) Diffuse disease + CMD

#### **Further Reading**


tron emission tomography myocardial perfusion imaging identifes patients with a survival beneft from early revascularization. European Heart Journal. 2019;41:751–759.

Einstein AJ, Johnson LL, Bokhari S, Son J, Thompson RC, Bateman TM et al. Agreement of visual estimation of coronary artery calcium from low-dose CT attenuation correction scans in hybrid PET/CT and SPECT/ CT with standard Agatston score. J Am Coll Cardiol. 2010 Nov 30;56(23):1914–21. https://doi.org/10.1016/j. jacc.2010.05.057.

#### **2.2 Asymptomatic Patient**

#### **2.2.1 Intermediate-High Clinical Risk: High CACS**

**Case 9**

#### **History**


Myocardial blood fow (MBF) and myocardial fow reserve (MFR) were also calculated (Table 2.1).

CCTA and PET studies were used, confrming the substantially normal perfusion in the LAD territory (Fig. 2.4).

**Fig. 2.2** Coronary computed tomography angiography showing 30% occlusion of LM and proximal LAD and 50–70% stenosis after origin of D1

**Fig. 2.3** Summed rest and Regadenoson-stress myocardial perfusion PET/CT images obtained with 13N-ammonia showing normal perfusion

**Table 2.1** Normal MBF and MFR after Regadenoson in all three coronary vascular territories


**Fig. 2.4** CCTA/MPI fusion image showing a very mild and limited in size tracer uptake reduction on the distal LAD

#### **Findings**


#### **Teaching Points**


#### **Management**

• High-risk patient with indication to OMT, no ICA was performed.


#### **2.2.2 Intermediate-High Clinical Risk: Abnormal Prior Test**

#### **Case 10**

#### **History**

• A 75-year-old asymptomatic male with hypertension after a prior abnormal myocardial perfusion SPECT (Fig. 2.5) was referred for a rest/stress myocardial perfusion PET/ CT (Fig. 2.6) to evaluate before thoracic surgery.

#### **SPECT Images**

**Fig. 2.5** Rest and adenosine-stress 99mTc-Sestamibi myocardial perfusion SPECT images demonstrate a medium sized perfusion defect of moderate intensity involving the mid and basal inferior and basal inferoseptal walls (arrows), showing mild reversibility

#### **PET/CT Images**

**Fig. 2.6** Summed rest and adenosine-stress myocardial perfusion PET images obtained with 82Rubidium demonstrate normal myocardial perfusion


#### **Differential Diagnosis**

• Obstructive CAD with ischemia in the RCA territory

#### **Correlative Imaging**

• None

#### **Management**

• Reassurance and risk factor management

#### **Teaching Points**

• While females often show artifactual uptake reduction on the anterolateral wall due to breast tissue attenuation, males may show the same artifact in the inferior wall, due to the diaphragm.



#### **2.3 Patient with Ischemic Equivalent (Angina and/or Dyspnea)**

#### **2.3.1 Single Vessel MPI and Normal LVEF, with Single Vessel Abnormal MFR**

#### **Case 11**

#### **History**


• Referred to PET/CT for assessment of ischemic burden (Fig. 2.8) and quantifcation of MFR (Table 2.2) and functionality (Table 2.3)

**Fig. 2.7** Selective view of the right (**a**, **b**) and left (**c**, **d**) coronary arteries demonstrating an 80% RCA stenosis (yellow arrows), mild irregularities in the LAD without stenoses and LCX without stenoses

#### **PET/CT Images**

**Fig. 2.8** Summed rest and adenosine-stress myocardial perfusion PET images obtained with 13N ammonia demonstrate severe perfusion defect involving the inferior wall with complete reversibility

**Table 2.2** Summary of the quantitative blood fow data demonstrating reduced MFR in the RCA territory, but preserved in the LAD and LCX territories


#### **Table 2.3** Left ventricular function



#### **Differential Diagnosis**

• None

#### **Teaching Points**


#### **Correlative Imaging**

• Coronary angiography

#### **Management**



#### **Case 12**

#### **History**


#### **PET/CT Images**

This patient also underwent CCTA fused with PET image (Fig. 2.10a, b)

**Fig. 2.9** Summed rest and vasodilator-stress myocardial perfusion PET images obtained Rubidium-82 show a medium sized perfusion defect of severe intensity involving the mid anteroseptal wall, the apical LV segments, and the LV apex with complete reversibility

**Table 2.4** Summary of the quantitative blood fow data demonstrating high MBF at rest, with good augmentation during stress albeit lower in the LAD territory. The MFR is reduced in the LAD territory but preserved in the LCX and RCA territories


**Fig. 2.10** The fused myocardial perfusion PET/CCTA demonstrate severe stenosis of the mid LAD coronary artery (panels **a** and **b**) involving the proximal frst diagonal branch (arrows). 3D rendering of PET study (**b**) shows hypoperfusion involving the antero-septal wall


#### **Differential Diagnosis**

• Obstructive CAD

#### **Correlative Imaging**

• Invasive coronary angiography (Fig. 2.11)

**Fig. 2.11** Selective views from coronary angiography demonstrating a complex critical stenosis of the mid LAD and diagonal coronary arteries (red arrow)

#### **Management**

• The patient underwent successful PCI of the LAD/diagonal arteries.

#### **Teaching Points**

• This case example illustrates the complementary value of quantitative stress MBF and fow reserve information in diagnosis and management. In this example, the normal stress MBF and MFR in the LCX and RCA territories helped exclude the presence of multivessel CAD.

#### **Further Reading**

Johnson N, Gould K, Di Carli M, Taqueti V. Invasive FFR and Noninvasive CFR in the Evaluation of Ischemia: What is the Future?. Journal of the American College of Cardiology. 2016;67:2772–2788.


#### **2.3.2 Single Vessel MPI and Normal LVEF, with MultiVessel Abnormality on MFR**

#### **Case 13**

#### **History**


#### **PET/CT Images**

Coronary angiography showed multivessel disease (Fig. 2.13).

**Fig. 2.12** Summed rest and Regadenoson-stress myocardial perfusion PET images obtained 13N ammonia demonstrate a perfusion defect involving the anterior wall and the apex with complete reversibility at rest.

**Table 2.5** Stress MBF is diffusely abnormal in all coronary vascular territories with no gradient of fow from base to apex in the RCA territory. MFR is regionally reduced in the LAD and LCX territories


#### **Table 2.6** LVEF and LV volumes at rest and at peak stress


**Fig. 2.13** Selective views of the left coronary system (left panel) demonstrating a 70% LAD stenosis (red arrow), 90% LCX stenosis (yellow arrow) and diffuse atherosclerosis of the RCA (right panel)


#### **Differential Diagnosis**

• Multivessel obstructive CAD

#### **Teaching Points**


• Global hypoperfusion with reduction of both max MBF and MFR in all vascular territories due to severe stenoses (LAD and LCX) and microvascular dysfunction (RCA).

#### **Correlative Imaging**

• Coronary angiography

#### **Management**



#### **2.3.3 Single Vessel MPI and Normal LVEF, with MultiVessel Abnormal MFR**

#### **Case 14**

#### **History**

• A 65-year-old male with a history of renal transplant and new onset LV dysfunction and heart failure, was referred for a Regadenoson myocardial perfusion PET study to evaluate for CAD (Fig. 2.14), MBF quantifcation (Table 2.7), and CCTA (Fig. 2.15).

#### **PET/CT Images**

**Fig. 2.14** Rest and Regadenoson-stress 13N-ammonia myocardial perfusion PET/CT images demonstrate severely dilated LV, moderate lung uptake, and a small perfusion defect of severe intensity involving the mid and basal inferolateral wall, which is fxed (arrows)

**Table 2.7** Summary of the quantitative blood fow data demonstrating severe reduction in stress myocardial blood fow in all coronary artery territories and globally (normal value >1.8 mL/min/g), resulting in moderate reduction in myocardial fow reserve (normal value >2.0)


**Fig. 2.15** Cross-sectional ECG-gated non-contrast cardiac CT image demonstrating severe coronary calcifcations in the proximal LAD (purple) and LCX (orange) coronary arteries. The Agatston score was 2905


#### **Differential Diagnosis**


#### **Correlative Imaging**

• Invasive coronary angiography demonstrates: (1) minimal irregularities in the left anterior descending (LAD) artery, (2) diffuse disease in the frst, second, and third diagonal branches, (3) minimal irregularities in the left circumfex (LCX) artery, and 30% stenosis in the proximal right coronary artery (RCA) (Fig. 2.16).

**Fig. 2.16** Selected coronary angiographic views demonstrating minimal irregularities in the LAD artery; diffuse disease in the frst, second, and third diagonal branches; minimal irregularities in the LCX artery, and 30% stenosis in the proximal RCA

#### **Management**

• Medical therapy for heart failure and myocardial ischemia and aggressive risk factor management

#### **Teaching Points**



#### **Case 15**

#### **History**

• A 52-year-old male with hypercholesterolemia, HIV, hepatitis B, previous Burkitt's lymphoma, and typical angina was referred for myocardial perfusion PET (Fig. 2.17) with quantitation of MBF (Table 2.8).

#### **PET Images**

**Fig. 2.17** Stress and rest 82Rb myocardial perfusion PET demonstrate a medium sized perfusion defect of severe intensity throughout the inferior wall with complete reversibility

**Table 2.8** Summary of the quantitative blood fow data demonstrating severe reduction in stress myocardial blood fow in all coronary artery territories and globally (normal value >1.8 mL/min/g). Myocardial fow reserve is only impaired in the RCA territory (normal value >2.0)


**Fig. 2.18** Fused myocardial perfusion PET/coronary CT angiography (PET/CCTA). The coronary CTA images demonstrate a total occlusion of the proximal dominant RCA (panels **a** and **b**). There is also evidence of diffuse coronary artery calcifcations on the LAD and LCX arteries. 3D rendering of PET study (**b**) shows hypoperfusion involving the inferior wall


#### **Differential Diagnosis**


#### **Correlative Imaging**

• Invasive coronary angiography confrmed the presence of a totally occluded RCA (Fig. 2.19).

**Fig. 2.19** Selective angiographic views of the coronary arteries demonstrate obstructive CAD in the RCA and no lesions on the left system

#### **Management**

• The patient underwent recanalization of the total RCA occlusion.

#### **Teaching Points**


LAD and LCX arteries explain in part the reduction in stress MBF.


#### **2.3.4 High-Risk Scan (Multivessel Defects, TID, Drop in EF, Abnormal MFR)**

#### **Case 16**

#### **History**


#### **PET/CT Images**

**Table 2.9** Summary of the quantitative blood fow data demonstrating MBF and MFR impairment during Regadenoson in LAD and RCA territories and globally (normal value >1.8 mL/min/g). Myocardial fow reserve is impaired in the RCA and LAD territories (normal value >2.0)


**Fig. 2.20** Rest and Regadenoson-stress 13N-ammonia myocardial perfusion PET/CT images demonstrate dilated LV and a large and severe perfusion defect throughout the mid and distal anterior and anteroseptal walls, LV apical segments, and the LV apex, showing complete reversibility


#### **Differential Diagnosis**

• Single vessel vs. multivessel disease

#### **Correlative Imaging**

• Coronary angiography (Fig. 2.21)

**Fig. 2.21** Selective angiographic views of the coronary arteries showed a severe stenosis of the proximal LAD with post-stenotic aneurysm and >90 stenosis of the frst diagonal branch (**a**, **b**). A long **LAD**

wraps around the **apex** and supplies the mid to distal inferior wall of the left ventricle (**b**, **d**). The LCX and RCA show luminal irregularities without focal stenosis (**c**, **d**)

#### **Management**

• The patient underwent by-pass grafting of the LAD.

#### **Teaching Points**


#### **Further Reading**

Kobayashi N, Maehara A, Brener S, Généreux P, Witzenbichler B, Guagliumi G, et al. Usefulness of the Left Anterior Descending Coronary Artery Wrapping Around the Left Ventricular Apex to Predict Adverse Clinical Outcomes in Patients With Anterior Wall ST-Segment Elevation Myocardial Infarction (from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction Trial). The American Journal of Cardiology. 2015;116:1658–1665.


#### **Case 17**

#### **History**

• A 78-year-old female with history of dyslipidemia, hypertension, diabetes mellitus type 2, and Chron's disease was referred for vasodilator PET/CT with 82Rb, after suffering a prolonged episode of chest pain (Fig. 2.22 and Table 2.10).

# **PET Images**

**Table 2.10** Summary of the quantitative blood fow data demonstrating severe reduction in stress myocardial blood fow in all coronary artery territories and globally (normal value >1.8 mL/min/g). MFR is impaired in the RCA and LAD territories (normal value >2.0)


**Fig. 2.22** Stress and rest 82Rb myocardial perfusion PET images. There is transient ischemic dilatation of the left ventricle during stress. Also, there is increased tracer uptake of the free wall of the right ventricle, more pronounced during stress. There is a large, severe, and reversible perfusion defect involving the mid anteroseptal wall, apical LV segments and LV apex, showing complete reversibility. In addition, there is a medium sized perfusion defect of moderate severity throughout the inferolateral wall, also showing complete reversibility


#### **Differential Diagnosis**

• Severe multivessel obstructive CAD

#### **Correlative Imaging**

• Invasive coronary angiography (Fig. 2.23)

**Fig. 2.23** Selective angiographic views of the coronary arteries: RAO cranial projection showing a high-degree stenosis of the mid LAD (left panel: yellow circle) and proximal obtuse marginal coronary artery (red circle). Right panel: LAO view showing a high-degree stenosis of the proximal to mid RCA (red circle)

#### **Management**

• This patient was deemed at high risk and—in line with the best current evidence for treatment of multivessel disease in patients with diabetes mellitus—was referred for coronary artery by-pass surgery.

#### **Teaching Points**



**Table 2.11** Summary of the quantitative blood fow data demonstrating severe reduction in stress myocardial blood fow in all coronary artery territories and globally (normal value >1.8 mL/min/g), with relatively normal myocardial fow reserve (normal value >2.0)


#### **Case 18**

#### **History**


#### **PET/CT Images**

**Fig. 2.24** Stress-rest 13N-ammonia PET images demonstrate TID at peak stress and a large and severe defect, completely reversible at rest, involving the mid anterior and anteroseptal walls, the apical LV segments and the LV apex


#### **Differential Diagnosis**

• Severe multivessel obstructive CAD.

#### **Correlative Imaging**

• Coronary angiography (Fig. 2.25).

**Fig. 2.25** Selective view of the left coronary system demonstrating a 70% left main stenosis and 70% ostial LAD stenosis and 70% stenosis of the mid RCA

• The patient underwent high-risk CABG.

#### **Teaching Points**



#### 2 Evaluation of Ischemic Heart Disease

#### **Case 19**

#### **History**


**Fig. 2.26** Coronary angiography showing occlusion of the RCA before primary PCI (**a**) and patent vessel (**b**) after PCI. Additional disease is present on LCX and LAD (**c**). LCX is treated with staged PCI (**d**, **e**)

**Fig. 2.27** Stress-rest 13N-ammonia PET images demonstrate a reversible perfusion defect involving the apical LV segments and the LV apex

**Table 2.12** Summary of the quantitative blood fow data demonstrating reduced MBF in all vascular territories with MFR reduction only in the LAD and LCX territories


#### **Findings**


#### **Management**

• This patient was referred for ICA (Fig. 2.28).

**Fig. 2.28** The new ICA documented a tight stenosis of the distal RCA (panel **a**—before, panel **b** after PCI) with a wrap-around distribution to the apical LV segments and LV apex, which explains the distribution of

the perfusion abnormality and MFR data. ICA of left coronary system demonstrated a persistent good result of previous PCI (panel **c**)

#### **Teaching Points**


#### **Further Reading**

Shibutani H, Akita Y, Yutaka K, Yamamoto S, Matsui Y, Yoshinaga M, et al. Acute myocardial infarction with "wrap around" right coronary artery mimicking Takotsubo cardiomyopathy: a case report. BMC Cardiovascular Disorders. 2016;16:16–71.


#### **2.4.1 Normal MPI, TID, and Globally Reduced MFR**

#### **Case 20**

#### **History**

• A 79-year-old asymptomatic male with a history of dyslipidemia and hypertension referred to PET/CT (Fig. 2.29 and Table 2.13) for evaluation of new onset LV dysfunction by echocardiography (not shown).

#### **PET/CT Images**

**Table 2.13** Summary of rest and stress MBF and myocardial fow reserve showing a global severe reduction in stress MBF and MFR.


**Fig. 2.29** Stress-rest 13N-ammonia PET images showing a medium sized perfusion defect of severe intensity throughout the inferior and basal inferoseptal wall


#### **Correlative Imaging**

• Invasive coronary angiography (Fig. 2.30):

#### **Management**

• The patient underwent CABG.

#### **Teaching Points**

• The quantitative fow information helps ascertain the extent and severity of obstructive CAD.

#### **Further Reading**


**Fig. 2.30** Selective coronary angiographic views demonstrate severe three vessel obstructive CAD including a long and severe stenosis in the mid LAD, a severe stenosis in the proximal LCX artery, and a total occlusion of a dominant RCA

#### **Case 21**

#### **History**


#### **PET/CT Images**

**Table 2.14** Summary of rest and stress MBF and myocardial fow reserve showing diffuse reduction of stress MBF without base to apical gradients and of MFR


**Fig. 2.31** Stress-rest 13N-ammonia PET images demonstrate transient mild LV dilatation during stress (TID ratio = 1.27) without evidence of regional perfusion defects


#### **Differential Diagnosis**

• Obstructive CAD vs microvascular disease.

#### **Teaching Points**


#### **Management**



#### **Case 22**

• He was referred to PET/CT (Fig. 2.33 and Table 2.15) for evaluation of exertional dyspnea and chest pain.

#### **History**

• A 68-year-old male with a history of hypertension. He underwent recent coronary CT angiography (Fig. 2.32), which demonstrated extensive coronary atherosclerosis.

**Fig. 2.32** Coronary CT angiography showing extensive coronary atherosclerosis involving LAD and LCX (arrows)

#### **PET/CT Images** (Figs. 2.33 and 2.34)

**Fig. 2.33** Stress-rest 13N-ammonia PET images demonstrate normal myocardial perfusion

**Table 2.15** Summary of the quantitative blood fow data demonstrating a moderate reduction in stress myocardial blood fow (normal value >1.8 mL/min/g) with preserved myocardial fow reserve (normal value >2.0) in all coronary artery territories and globally


**Fig. 2.34** Segmental MBF showing no gradients


#### **Differential Diagnosis**

• None

#### **Correlative Imaging**

• None

#### **Management**

• Aggressive risk factor management

#### **Teaching Points**

• The presence of extensive atherosclerosis on the CCTA without regional perfusion abnormalities on the PET myocardial perfusion images, associated with moderate reduction in stress myocardial blood fow and preserved fow reserve is consistent with nonobstructive atherosclerosis.

• The presence of reduced stress myocardial blood fow with normal myocardial fow reserve by quantitative PET imaging associates with low clinical risk (<1% cardiac death rate/year). However, he has severe nonobstructive atherosclerosis that increases the risk for myocardial infarction and requires aggressive lipid lowering therapy and management of his hypertension.


#### **Case 23**

#### **History**

• A 52-year-old obese female (BMI: 35) with a history of hypertension referred for evaluation for atypical angina and dyspnea. She underwent a rest and Regadenosonstress 13N-ammonia myocardial perfusion PET/CT study (Fig. 2.35 and Table 2.16) and CACS assessment (Fig. 2.36).

#### **PET/CT Images**

**Fig. 2.35** Rest and Regadenoson-stress 13N-ammonia myocardial perfusion PET/CT images demonstrate normal myocardial perfusion both at rest and during stress

**Table 2.16** Summary of the quantitative blood fow data demonstrating preserved stress myocardial blood fow (normal value >1.8 mL/ min/g) but reduced myocardial fow reserve (normal value >2.0) in all coronary artery territories and globally


**Fig. 2.36** Cross-sectional transaxial chest CT image demonstrating no evidence of coronary artery calcifcations


#### **Differential Diagnosis**


#### **Correlative Imaging**

• None

#### **Management**

• Management of hypertension and weight reduction

#### **Teaching Points**

• The normal myocardial perfusion PET images associated with the absence of coronary calcifcations and normal stress myocardial blood fow are consistent with a low likelihood of fow-limiting CAD or nonobstructive atherosclerosis.

• However, the presence of increased rest myocardial blood fow and mild reduction in myocardial fow reserve places her at an intermediate clinical risk (1–3% cardiac death rate/year). This phenotype is common among women who typically have a low prevalence of obstructive atherosclerosis and has been linked to microvascular disease, which may be the source of her symptoms.


#### **2.4.2 Abnormal PET with Abnormal FFR**

#### **Case 24**

#### **History**

• 62-year-old male with a history of hypertension, hypercholesterolemia and diabetes, and known CAD with prior PCI of the left anterior descending (LAD) and left circumfex (LCX) arteries, referred for evaluation of atypical chest pain. He underwent rest/stress myocardial perfusion PET imaging using 15O-water (Fig. 2.37).

#### **PET/CT Images**

**Fig. 2.37** Rest/stress MPI shows severe defect involving the anterior wall, septum, and apex, with normal LV size. Complete reversibility at rest.


#### **Differential Diagnosis**

• Obstructive CAD

#### **Correlative Imaging**

• Invasive coronary angiography (Fig. 2.38)

**Fig. 2.38** Invasive coronary angiography showing an angiographic severe luminal stenosis in the proximal LAD (\*) and diffuse distal atherosclerosis. The LCX and small right coronary artery (RCA) did not

show any signifcant stenosis. Corresponding fractional fow reserve (FFR) measurement of the LAD stenosis was abnormal of 0.52 (normal value ≥0.80)

#### 2 Evaluation of Ischemic Heart Disease

#### **Management**

• The LAD lesion was successfully treated with a PCI and 2 drug eluting stents.

#### **Teaching Points**


#### **Further Reading**

Driessen R, Danad I, Stuijfzand W, Raijmakers P, Schumacher S, van Diemen P, et al. Comparison of Coronary Computed Tomography Angiography, Fractional Flow


**Acknowledgement** PET and angiographic images are courtesy of Drs. Roel Driessen, Ibrahim Danad, and Paul Knaapen, VU University Medical Center, Amsterdam, the Netherlands.

#### **2.5 Patient with Suspected Coronary Microvascular Dysfunction**

**2.5.1 Without Atherosclerosis**

#### **2.5.1.1 Hypertensive Heart Disease**

**Case 25**

#### **History**


#### **PET/CT Images**

**Table 2.17** Summary of the quantitative blood fow data demonstrating severe and diffuse abnormalities of MBF and MFR


**Fig. 2.39** Rest and vasodilator-stress 13N-ammonia showing normal rest and stress myocardial perfusion images. The mild and fxed reduction in tracer uptake in the inferolateral wall represents a normal variant for 13N-ammonia

#### 2 Evaluation of Ischemic Heart Disease

#### **Findings**


#### **Differential Diagnosis**

• Multivessel obstructive CAD with balanced ischemia vs microvascular dysfunction

#### **Correlative Imaging**

• CCTA (Fig. 2.40)

#### **Teaching Points**


ography to exclude the possibility of multivessel obstructive CAD. In this case, CCTA shows angiographically normal coronary arteries.

#### **Management**

• Optimized medical treatment


**Fig. 2.40** Coronary CT angiography shows no evidence of coronary atherosclerosis

#### **2.5.1.2 Nonischemic CM**

#### **Case 26**

#### **History**

• A 78-year-old female with a history of hypertension and diabetes presenting with new onset heart failure, reduced LV systolic function, and ventricular arrhythmias was referred to PET/CT (Fig. 2.41 and Table 2.18). Her ECG shows a left bundle branch block (Fig. 2.42).

#### **PET/CT Images**

**Table 2.18** Summary of the quantitative blood fow data demonstrating a moderate reduction in stress myocardial blood fow (normal value >1.8 mL/min/g) and myocardial fow reserve (normal value >2.0) in all coronary artery territories and globally


**Fig. 2.41** Rest and adenosine-stress 13N-ammonia myocardial perfusion PET/CT images. There is severe LV dilatation and moderately increased RV tracer uptake on both the stress and rest images. There is mildly reduced tracer uptake in the septum on both stress and rest imag-

ing, which is consistent with her LBBB. The fxed defect involving the LV apex is consistent with apical thinning and resulting partial volume effect

**Fig. 2.42** Rest ECG demonstrating a LBBB


#### **Differential Diagnosis**


#### **Correlative Imaging**

• Rest ECG

#### **Teaching Points**


endocardial ischemia and increased myocardial stress, subclinical myocardial injury and diffuse interstitial fbrosis, worsening systolic and diastolic function, heart failure, arrhythmias, and adverse cardiovascular events.

#### **Management**


#### **Further Reading**

Majmudar M, Murthy V, Shah R, Kolli S, Mousavi N, Foster C, et al. Quantifcation of coronary fow reserve in patients with ischaemic and non-ischaemic cardiomyopathy and its association with clinical outcomes. European Heart Journal – Cardiovascular Imaging. 2015;16:900–909.


#### **2.5.1.3 Fabry's Disease**

#### **Case 27**

#### **History**


**Table 2.19** Summary of the quantitative blood fow data demonstrating diffuse reduction in stress MBF regionally and globally, as well as of MFR


**Fig. 2.43** Rest and Regadenoson-stress 13N-ammonia showing severe transient LV dilatation during stress with increased RV tracer uptake. There are no regional perfusion abnormalities. At rest, there is evidence of LV hypertrophy


#### **Differential Diagnosis**

• Obstructive CAD vs microvascular dysfunction from Fabry's disease.

#### **Correlative Imaging**

• Cardiac MR (Figs. 2.44 and 2.45)

**Fig. 2.44** Cardiac MR images demonstrating severe LV hypertrophy

**Fig. 2.45** Cardiac MR images with T1-mapping demonstrating abnormally short T1 velocity (<800 ms), consistent with glycosphingolipid accumulation, associated with edema on T2-weighted imaging

#### **Management**


#### **Teaching Points**


#### **Further Reading**


**Acknowledgement** Cardiac MR images courtesy of Prof Davide Farina and Dr. Emanuele Gavazzi, Institute of Radiology, University of Brescia.

#### **Case 28**

#### **History**


RCA Left coronary system

**Fig. 2.46** Selective views of invasive coronary angiography showing normal coronary tree

Short axis

**Fig. 2.47** Rest and Regadenoson-stress 13N-ammonia showing mild LV dilatation at stress without regional perfusion abnormalities



80

**Fig. 2.48** ECG at rest (panel on the left) and 2′ after Regadenoson infusion (panel on the right), showing ischemic modifcations during vasodilator stress


#### **Differential Diagnosis**


#### **Correlative Imaging**

• Cardiac MRI (Figs. 2.49 and 2.50)

**Fig. 2.49** Cardiac MRI showing LV hypertrophy

#### **Management**


#### **Teaching Points**

• Coronary microvascular dysfunction is common in Fabry's disease and develops early in the natural history the disease.

#### **Further Reading**

Tomberli B, Cecchi F, Sciagrà R, Berti V, Lisi F, Torricelli F, et al. Coronary microvascular dysfunction is an early feature of cardiac involvement in patients with Anderson-Fabry disease. European Journal of Heart Failure. 2013;15:1363–1373.

**Acknowledgement** Cardiac MR images courtesy of Prof Davide Farina and Dr. Emanuele Gavazzi, Institute of Radiology, University of Brescia.

#### **2.5.1.4 Amyloidosis**

#### **Case 29**

#### **History**


**Table 2.21** Summary of the quantitative blood fow data demonstrating a severe reduction in stress myocardial blood fow (normal value >1.8 mL/min/g) and myocardial fow reserve (normal value >2.0) in all coronary artery territories and globally


#### **PET/CT Imaging**

**Fig. 2.51** Rest and adenosine-stress 13N-ammonia myocardial perfusion PET/CT images. There is marked transient ischemic dilatation (TID ratio: 1.43, normal: 1.05) of the LV cavity during stress. The stress myocardial perfusion images demonstrate a large perfusion defect of

severe intensity throughout the mid and basal LV segments, showing complete reversibility. The combined extent and severity of ischemia during stress involved 45% of the LV mass


#### **Differential Diagnosis**

• Multivessel obstructive CAD vs coronary microvascular dysfunction

#### **Correlative Imaging**


**Fig. 2.52** Selective views of the coronary angiography demonstrate no evidence of coronary artery disease

**Fig. 2.53** Short axis view of the cardiac MRI showing diffuse subendocardial late gadolinium enhancement in the base of the left ventricle

#### **Management**


#### **Teaching Points**



#### **2.5.1.5 Hypertrophic Cardiomyopathy**

#### **Case 30**

#### **History**


**Table 2.22** Summary of the quantitative blood fow data demonstrating a diffuse and severe reduction in stress myocardial blood fow (normal value >1.8 mL/min/g) and myocardial fow reserve (normal value >2.0) in all coronary artery territories and globally


**PET/CT Imaging**

**Fig. 2.54** Rest and adenosine-stress 13N-ammonia myocardial perfusion PET/CT images. There is moderate TID of the LV cavity during stress. The stress myocardial perfusion images demonstrate a medium sized perfusion defect of moderate intensity involving the apical LV

segments and the LV apex, showing complete reversibility. The combined extent and severity of ischemia during stress involves 10% of the LV mass. There is evidence of asymmetric septal hypertrophy


#### **Differential Diagnosis**

• Multivessel obstructive coronary artery disease vs microvascular disease.

#### **Correlative Imaging**


**Fig. 2.55** Invasive coronary angiography demonstrates no evidence of obstructive coronary artery disease

**Fig. 2.56** Four and two chamber contrast-enhanced cardiac MRI images show severe left ventricular hypertrophy, with more pronounced septal hypertrophy. There is a large amount of patchy mesocardial late gado-

linium enhancement in multiple myocardial segments but is more pronounced in the severely hypertrophied segments. Overall, fndings are consistent with asymmetric obstructive hypertrophic cardiomyopathy

#### **Management**

• Coronary angiography is an important consideration in the context of the PET fndings and anginal symptoms, which in this case helped exclude epicardial coronary artery disease.

#### **Teaching Points**


• Like in other forms of cardiomyopathy, the severity of CMD in patients with HCM identifes those at higher risk of adverse cardiovascular events.


#### **2.5.1.6 Stress Cardiomyopathy**

#### **Case 31**

#### **History**


#### **SPECT Imaging**

**Fig. 2.57** Stress/rest 99mTc-sestamibi SPECT myocardial perfusion images demonstrate aneurysmal dilatation of the LV associated with a large perfusion defect of severe intensity throughout the mid anteroseptal wall, apical LV segments and the LV apex, which was essentially fxed.


#### **FDG PET/CT Imaging**

**Fig. 2.58** Rest 99mTc-sestamibi SPECT myocardial perfusion (rest perfusion rows) and 18F-FDG PET images (FDG rows) demonstrating signifcant FDG uptake throughout all hypoperfused LV segments

(perfusion-FDG mismatch), consistent with the presence of combined nonviable and viable but hibernating myocardium throughout the mid LAD territory involving approximately 38% of the LV mass

• There is signifcant FDG uptake throughout all hypoperfused LV segments (perfusion-FDG mismatch), consistent with the presence of combined nonviable and viable but hibernating myocardium throughout the mid LAD territory involving approximately 38% of the LV mass.

#### **Differential Diagnosis**

• Subacute anterior myocardial infarction with signifcant residual viable but hibernating myocardium due to obstructive CAD

#### **Correlative Imaging**

• Invasive coronary angiography demonstrated minimal luminal irregularities without obstructive CAD (Fig. 2.59).

**Fig. 2.59** Invasive coronary angiography demonstrates no evidence of obstructive coronary artery disease

#### **Management**


#### **Teaching Points**


tion is the underlying pathophysiology for the extensive area of hibernating myocardium in the LAD territory and, likely, for the acute presentation with cardiac arrest. The clinical presentation and imaging fndings are consistent with stress cardiomyopathy.

• The absence of revascularizable disease poses a management challenge as there is residual ischemic myocardium.

#### **Further Reading**

Pelliccia F, Kaski J, Crea F, Camici P. Pathophysiology of Takotsubo Syndrome. Circulation. 2017;135:2426–2441.

Templin C, Ghadri J, Diekmann J, Napp L, Bataiosu D, Jaguszewski M, et al. Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy. New England Journal of Medicine. 2015;373:929–938.

#### **2.5.2 Nonobstructive Atherosclerosis**

#### **2.5.2.1 Diabetes**

**Case 32**

#### **History**


#### **PET/CT Images**

**Fig. 2.60** Adenosine-stress and rest 13N-ammonia myocardial perfusion PET/CT images demonstrate normal LV size. There is mild RV dilatation with moderate increase tracer uptake during stress. There are no regional perfusion defects on the stress and rest images

**Fig. 2.61** Segmental stress myocardial blood fow demonstrates no signifcant base to apical gradients

**Table 2.23** Summary of the quantitative blood fow data demonstrating severe reduction in stress MBF (normal value >1.8 mL/min/g) and MFR (normal value >2.0) in all coronary artery territories and globally



#### **Differential Diagnosis**


#### **Correlative Imaging**

• Invasive coronary angiography (Fig. 2.62)

**Fig. 2.62** Selective coronary angiographic views demonstrate nonobstructive stenosis. The moderate stenosis in the proximal LAD (arrows) was associated with an FFR of 0.87

#### **Management**

• Management of ischemic heart disease, coronary risk factors, and glycemic control.

#### **Teaching Points**



#### **2.5.2.2 Obese**

#### **Case 33**

#### **History**


**Table 2.24** Summary of the quantitative blood fow data demonstrating a diffuse and severe reduction in stress myocardial blood fow (normal value >1.8 mL/min/g) with moderate reduction in myocardial fow reserve (normal value >2.0) in all coronary artery territories and globally


#### **PET/CT Images**

**Fig. 2.63** Stress/rest 13N-ammonia PET myocardial perfusion images. There is normal regional myocardial perfusion on both the stress and rest images


#### **Differential Diagnosis**

• None

#### **Teaching Points**


#### **Correlative Imaging**

• None

#### **Management**

• Counselling on lifestyle modifcations and weight loss


#### **2.5.2.3 Heart Failure with Preserved Ejection Fraction**

#### **Case 34**

#### **History**


**Table 2.25** Summary of the quantitative blood fow data demonstrating a diffuse and severe reduction in stress myocardial blood fow (normal value >1.8 mL/min/g) with moderate reduction in myocardial fow reserve (normal value >2.0) in all coronary artery territories and globally


**Fig. 2.64** Stress/rest 13N-ammonia PET myocardial perfusion images. The images demonstrate transient ischemic dilatation (TID). There is a medium sized perfusion defect of moderate intensity involving the LV apex, apical LV segments, the mid and basal anterior wall, showing

complete reversibility. In addition, there is medium sized perfusion defect of moderate severity throughout the inferoseptal wall, also showing complete reversibility

#### **PET/CT Imaging**


• The stress myocardial blood fow and fow reserve are markedly reduced both regionally and globally.

#### **Differential Diagnosis**


#### **Correlative Imaging**

• Given the PET scan fndings, the patient was referred to invasive coronary angiography, which showed a patent LAD stent with diffuse nonobstructive CAD and a long 70% stenosis in the mid RCA with an FFR of 0.78 (Fig. 2.65).

**Fig. 2.65** Selective invasive coronary angiographic views demonstrating a patent LAD stent with diffuse nonobstructive CAD and a long 70% stenosis in the mid RCA (blue arrow) with an associated FFR of 0.78

#### **Management**

• Medical management of myocardial ischemia and heart failure

#### **Teaching Points**


tion, chronic circulating levels of high-sensitivity troponins are common in patients with LV hypertrophy, diabetes, and chronic kidney disease and are associated with increased incidence of cardiovascular death and heart failure.


#### **2.5.3 Obstructive CAD**

#### **2.5.3.1 Normal PI + Single Vessel Reduced MFR**

**Case 35**

#### **History**


#### **PET/CT Imaging**

**Table 2.26** Summary of the quantitative blood fow data demonstrating a severe reduction in stress myocardial blood fow (normal value >1.8 mL/min/g) in the LAD territory with normal stress fow in fow reserve in the LCX and RCA territories (normal value >2.0)


**Fig. 2.66** Stress/rest 13N-ammonia PET myocardial perfusion images. There is evidence of apical thinning but overall the images demonstrate normal myocardial perfusion without defnitive regional defects. The

ECG-gated images demonstrated an LVEF of 64% at rest that increased to 67% at stress, with normal LV volumes


#### **Differential Diagnosis**

• Obstructive CAD in the LAD coronary artery

#### **Correlative Imaging**

• Given the PET scan fndings, the patient was referred to invasive coronary angiography, which showed an 85% stenosis in the proximal LAD with mild diffuse nonobstructive cardiac allograft vasculopathy in the LCX and RCA (Fig. 2.67).

**Fig. 2.67** Selective invasive coronary angiographic views demonstrating a severe stenosis in the proximal LAD coronary artery (arrow). There is mild diffuse allograft vasculopathy in the LCX and RCA arteries

#### **Management**

• The patient was referred to invasive coronary angiography which confrmed a severe stenosis in the proximal LAD coronary artery, which was subsequently stented.

#### **Teaching Points**



#### **2.6 Patient with Known CAD**

#### **2.6.1 Prior PCI**

**Case 36**

#### **History**


#### **PET/CT Images**

**Table 2.27** There is mildly reduced stress MBF in the RCA territory. MFR is preserved in all coronary territories and globally


**Fig. 2.68** Stress-rest 13N ammonia PET MPI demonstrating a small and severe perfusion defect in the mid and basal inferolateral wall, which is fxed.


#### **Differential Diagnosis**

• Non-cardiac chest pain

#### **Correlative Imaging**

• Coronary CT angiography (Fig. 2.69)

**Fig. 2.69** Selective multiplanar reformatted CT angiographic images demonstrating scattered calcifcations of all three coronary arteries without obstructive stenosis. Stent on LCX is patent

#### **Management**

• Optimized medical treatment

#### **Teaching Points**



#### **2.6.2 Prior CABG**

#### **Case 37**

#### **History**


**Table 2.28** Summary of quantitative fow data demonstrating moderate diffuse reduction in stress myocardial blood fow in all territories, more severe in the proximal LAD territory. MFR regionally reduced in the area of the myocardial perfusion defect


#### **PET/CT Imaging**

**Fig. 2.70** Stress/rest 13N-ammonia PET myocardial perfusion images demonstrate a medium sized perfusion defect of severe intensity involving the mid and basal anterior and anteroseptal walls (arrows), showing complete reversibility. The apical LV segments and the LV apex have

relatively preserved myocardial perfusion during stress. In addition, there is a small and severe perfusion defect involving the basal inferolateral wall (arrows), which is fxed.


#### **Differential Diagnosis**

• Obstructive CAD

#### **Correlative Imaging**

Follow-up invasive coronary angiography demonstrated:


#### **Management**

• The area of moderate ischemia in the proximal LAD territory with preservation of perfusion in the distal part of the territory is caused by progression of disease in the native LAD proximal to the touchdown of the LIMA graft. The small fxed defect in the LCX/obtuse marginal territory corresponds to a totally occluded LCX. She was continued on dual anti-platelet therapy and anti-anginal therapy was intensifed. On a follow-up offce visit, she remains angina free.

#### **Teaching Points**


#### **Further Reading**

Murthy V, Bateman T, Beanlands R, Berman D, Borges-Neto S, Chareonthaitawee P, et al. Clinical Quantifcation of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC. Journal of Nuclear Cardiology. 2017;25:269–297.

#### **2.6.3 Prior MI (Single Territory MI + Globally Reduced MFR and Multi VD on Cath)**

#### **Case 38**

#### **History**


**Table 2.29** Summary of the quantitative blood fow data demonstrating marked reduction in stress myocardial blood fow and moderate reduction in fow reserve in all coronary artery territories


**Fig. 2.71** Stress/rest 13N-ammonia PET myocardial perfusion images. There is mild transient ischemic dilation of the LV cavity during stress. There is a medium sized perfusion defect of severe intensity throughout the inferior wall, showing only mild reversibility (arrows). In addition, there is a small perfusion defect of severe intensity involving the LV apex, which shows complete reversibility (arrow)

#### **PET/CT Imaging**


ate reduction in flow reserve in all coronary artery territories.

#### **Differential Diagnosis**


#### **Correlative Imaging**

• Follow-up invasive coronary angiography demonstrated a total occlusion of the mid RCA with moderate right-toright collaterals. The left main and LAD arteries had mild irregularities. The LCX has a moderate stenosis (Fig. 2.72).

**Fig. 2.72** Selective invasive coronary angiographic views demonstrating a total occlusion of the RCA (arrow) with right-to-tight collaterals and moderate diffuse nonobstructive atherosclerosis of the LCX and LAD coronary arteries (arrows)

#### **Management**

• The patient underwent PCI of the total mid RCA occlusion and intensifcation of medical therapy of myocardial ischemia.

#### **Teaching Points**


opment of obstructive stenosis. In patients with stable CAD, reductions in microcirculatory reserve exacerbate the functional signifcance of upstream coronary stenosis and may magnify the severity of inducible myocardial ischemia.

• From a clinical perspective, the presence of CMD in patients with stable obstructive CAD has several important diagnostic, prognostic, and management implications.


#### **2.6.3.1 Infarct with Peri-infarct Ischemia**

#### **Case 39**

#### **History**


#### **PET/CT Images**

**Table 2.30** Summary of the quantitative blood fow data demonstrating reduction in fow reserve in RCA and LCX artery territories


**Fig. 2.73** Stress/rest 13N-ammonia PET myocardial perfusion images. There is no tracer uptake on the infero-basal segment and mild reduction on the remaining inferior wall. Gated study shows an LVEF of 50% at rest that decreased to 46% on stress

#### This patient also underwent CCTA (Fig. 2.74)

**Fig. 2.74** CCTA shows a permeable RCA stent (without restenosis); LAD and LCX without signifcant occlusion. The reduced MFR may be explained due to microvascular dysfunction


#### **Differential Diagnosis**

• Stent dysfunction or progression of coronary obstructive disease in non-treated coronaries

#### **Teaching Points**

• Myocardial perfusion imaging with PET is good to detect new areas of ischemia in patients treated previously with a stent.

• Revascularization guided by ischemia optimizes the treatment of the patients.

#### **Management**

• New cath to evaluate the presence of intrastent stenosis or new signifcant obstructive lesions


#### **2.6.3.2 Evaluation of Patients with Total Coronary Occlusions**

#### **Case 40**

#### **History**


**Fig. 2.75** Selective invasive coronary angiographic views demonstrating a total occlusion of the RCA (arrow) with right-to-tight collaterals and moderate diffuse nonobstructive atherosclerosis of the LCX and LAD coronary arteries (arrows)

#### **PET/CT Imaging**

**Fig. 2.76** Stress/rest 13N-ammonia PET myocardial perfusion images. There is a large and severe perfusion defect throughout the inferior, inferoseptal, and inferolateral walls (arrows), showing moderate inferolateral reversibility

**Table 2.31** Summary of the quantitative blood fow data demonstrates markedly reduced stress myocardial blood fow in the infarct-related territory of the RCA, which is expected. Stress myocardial blood fow and fow reserve are preserved in the LAD and LCX territories



#### **Differential Diagnosis**

• None

#### **Correlative imaging**

• None

#### **Management**

• He was managed medically by intensifying his antianginal regimen with good symptomatic response.

#### **Teaching Point**

• The combination of semi-quantitative and quantitative myocardial perfusion imaging makes PET an effective noninvasive modality to help manage symptomatic patients with complex CAD and known chronic total occlusions.



#### **2.6.3.3 Evaluation of Ischemia in Patients with Staged PCI**

#### **Case 41**

#### **History**


**PET/CT Images**

**Table 2.32** Summary of the quantitative blood fow data demonstrates a reduction of stress MBF in all coronary territories with preserved MFR



#### **Differential Diagnosis**

• None

#### **Correlative Imaging**

• Coronary angiography (Fig. 2.78).

**Fig. 2.78** Selective angiographic images demonstrating severe left main stenosis before and after stent placement (red arrows). Additionally, there is diffuse atherosclerosis of the RCA, distal LAD, and LCX coronary arteries

#### **Management**

• The patient was managed by optimization of anti-ischemic therapy.

#### **Teaching Points**



#### **2.7 Patient with Ischemic Cardiomyopathy**

#### **2.7.1 Patient Preparation for Viability Evaluation**

The PET viability protocol includes an assessment of myocardial perfusion at rest and stress, when clinically appropriate, followed by a metabolic assessment with F-18 fuorodeoxyglucose (FDG). In the glucose-loaded state and in ischemia (regardless of glucose loading), glucose is the preferred substrate for myocardial energy metabolism. Under these circumstances, FDG uptake and retention refects the rate of exogenous glucose utilization and is a marker of myocardial viability.

#### **Patient Preparation for FDG Imaging**

Because utilization of energy-producing substrates by the myocardium is largely a function of their concentration in plasma and hormone levels (especially plasma insulin, insulin/glucagon ratio, growth hormone, and catecholamines) and of oxygen availability for oxidative metabolism, careful patient preparation is necessary to obtain diagnostic FDG images. For a detailed step-by-step description of the available methods for patient preparation before FDG imaging, the reader should review the Guidelines for PET Imaging published by the American Society of Nuclear Cardiology and the Society of Nuclear Medicine. Briefy, the available approaches to patient preparation include:

*Fasting*: This is the simplest method because it does not require any substrate manipulation. With this approach, ischemic but viable tissue shows as a "hot spot" due to the preferential FFA utilization by normal (nonischemic) myocardium. While imaging interpretation would seem straightforward, the lack of tracer uptake in normal (reference) myocardium may occasionally lead to an overestimation of the amount of residual viability within a dysfunctional territory.

*Oral or intravenous glucose loading*: This is the recommended approach to FDG imaging. The goal of glucose loading is to stimulate the release of endogenous insulin in order to decrease the plasma levels of FFA and facilitate the transport of FDG into cardiomyocytes. Patients are usually fasted for at least 6 h and then receive an oral or intravenous glucose load. Most patients require the administration of IV insulin to maximize myocardial FDG uptake.

*Hyperinsulinemic-euglycemic clamp*: This approach is technically demanding and time-consuming. It consists of a constant infusion of insulin IV with adjustments in glucose infusion to avoid hypoglycemia until the body reaches steady state between glucose infusion and disposal. At this point, no further adjustments are necessary and FDG can be administered. Because it is technically demanding, most laboratories reserve this approach for challenging conditions (e.g., diabetes and severe congestive heart failure).

*Free fatty acid inhibition*: Acipimox (not available in the United States) and niacin are both nicotinic acid derivatives that inhibit peripheral lipolysis, thereby reducing plasma FFA levels and, indirectly, forcing a switch to preferential myocardial glucose utilization. These drugs are usually given 60 to 90 minutes prior to FDG administration.

#### **2.7.2 Mismatch**

#### **Case 42**

#### **History**


Coronary angiography

**Fig. 2.79** Selective angiographic views of the left coronary system demonstrating a chronic LCX occlusion before (yellow arrow in left panel) and after successful PCI (right panel)

#### **SPECT and PET/CT Images**

**Fig. 2.80** Rest 99mTc Tetrosfosmin myocardial perfusion SPECT and FDG PET study showing a dilated LV with a large and severe perfusion defect involving the mid and apical anterior and anteroseptal, and lat-

eral walls, the apical LV segments and the LV apex with moderate FDG uptake especially in the lateral wall.

• Rest 99mTc Tetrosfosmin myocardial perfusion SPECT and FDG PET study show a dilated LV with a large and severe perfusion defect involving the mid and apical anterior and anteroseptal, and lateral walls, the apical LV segments and the LV apex with moderate FDG uptake especially in the lateral wall. Mismatch of severe perfusion defect and residual FDG uptake shows persistent viability in chronically hypoperfused myocardial segments.

#### **Differential Diagnosis**

• Myocardial scar vs hibernating myocardium

#### **Management**

• The patient underwent revascularization of the LCX coronary artery.

#### **Teaching Points**


perfusion-FDG matched defect implies nonviable myocardium.

• A perfusion-FDG mismatched defect predicts improvement in regional/global LV dysfunction after revascularization.


#### 2 Evaluation of Ischemic Heart Disease

#### **2.7.3 Match**

#### **Case 43**

#### **History**

• 69-year-old male with ischemic cardiomyopathy and prior CABG was referred for a PET scan to assess for myocardial viability (Fig. 2.81). His cardiac risk factors include hypertension, dyslipidemia, and a family history of ischemic heart disease.

#### **PET/CT Imaging**

**Fig. 2.81** Rest 13N-ammonia myocardial perfusion and 18F-deoxyglucose (FDG) PET images. The images demonstrate a severely dilated LV and normal tracer uptake in the lungs. They also demonstrate a mildly dilated RV with normal RV tracer uptake at rest. The rest perfusion images show a large and severe perfusion defect throughout the inferior and inferolateral walls with concordantly reduced FDG uptake (perfu-

sion-FDG matched defect), consistent with nonviable myocardium in the LCX/obtuse marginal territory (arrows). Rest myocardial perfusion and FDG uptake are normal in the LAD and RCA territories. The blackout myocardial perfusion (left), FDG (middle), and comparison viability (right) polar maps confrm the extent of nonviable myocardium in the LCX/OM territory


#### **Differential Diagnosis**

• None

#### **Correlative Imaging**

• None

#### **Management**

• This patient was continued to be managed medically.

#### **Teaching Points**



#### **2.7.4 Match + Stress-Induced Ischemia**

#### **Case 44**

#### **History**


There is a large perfusion defect of severe intensity involving the mid anterior, anterolateral and anteroseptal walls, the apical LV segments and the LV apex, showing near complete reversibility. FDG uptake in this area is normal, except in the anteroseptal wall, which is reduced compared to perfusion (so-called reversed perfusion-FDG mismatched defect).

#### **PET/CT Imaging**

**Fig. 2.82** Stress-rest 13N-ammonia myocardial perfusion and rest 18F-deoxyglucose (FDG) PET images. There is severe LV dilatation and increased lung uptake on both the rest and stress images


#### **Differential Diagnosis**

• None

#### **Management**

	- Left main: LMCA has a focal 80% stenosis.
	- The proximal LAD has a focal 90% stenosis.
	- The frst obtuse marginal branch has a focal 100% stenosis.
	- The mid RCA is totally occluded.
	- The LIMA graft to mid LAD is patent.

• Given the results of the PET scan and his ventricular arrhythmias and worsening heart failure, the patient underwent PCI of his native LAD coronary artery.

#### **Correlative Imaging**

• None

#### **Teaching Points**



#### **2.8 Evaluation of Medical Therapy**

#### **Case 45**

#### **History**


**Fig. 2.83** Selective coronary angiographic views demonstrating total occlusion of RCA (left panel) and LCX (middle panel), and successful recanalization of the LCX total occlusion (right panel)

**Fig. 2.84** Stress-rest 13N-ammonia PET images demonstrating a medium sized perfusion defect of moderate severity in the inferior wall showing complete reversibility

**Table 2.33** Quantitative analysis shows relatively preserved stress MBF and normal MFR in the LAD and LCX territories. Stress MBF and MFR are both reduced in the RCA territory


#### **Findings**

• The myocardial perfusion PET scan demonstrated a moderate amount of stress-induced ischemia with complete viability in the territory of the occluded RCA, with relatively preserved stress MBF and MFR in the LAD and LCX territories.

#### **Management**


**Fig. 2.85** Stress-rest 13N-ammonia PET images demonstrating near complete resolution of the inferior perfusion defect seen on the index PET scan

**Table 2.34** Summary of quantitative blood fow data showing normal stress and MFR in the LAD and LCX territories, with mild reduction of stress MBF with normal MFR in the RCA territory


#### **Findings**

• The follow-up PET myocardial perfusion scan a year after optimization of medical therapy demonstrates signifcant interval improvement in myocardial perfusion in all vascular territories including near complete resolution of the area of ischemic in the territory of the occluded RCA.

#### **Management**

• Given the results of the follow-up PET scan, consideration for PCI of the RCA was deferred.

#### **Differential Diagnosis**

• None

#### **Teaching Points**


#### **Further Reading**

Ohira H, Dowsley T, Dwivedi G, deKemp R, Chow B, Ruddy T, et al. Quantifcation of myocardial blood fow using PET to improve the management of patients with stable ischemic coronary artery disease. Future Cardiology. 2014;10:611–631.

#### **2.9 Evaluation of CAV After Heart Transplantation**

Cardiac allograft vasculopathy (CAV) remains a troublesome long-term complication of heart transplantation. It is manifested by a unique and unusually accelerated form of coronary disease affecting both intramural and epicardial coronary arteries and veins. CAV is characterized by vascular injury induced by a variety of noxious stimuli, including the immune system response to the allograft, ischemia-reperfusion injury, viral infection, immunosuppressive drugs, and classic risk factors such as hyperlipidemia, insulin resistance, and hypertension. The obstructive vascular lesions are thought to progress through repetitive endothelial injury followed by repair response. The role of major histocompatibility complex donor-recipient differences in the pathogenesis of CAV has not yet been completely elucidated. Intracoronary ultrasound studies reveal a dual morphology with donortransmitted or de novo focal, noncircumferential plaques in proximal segments and/or a diffuse, concentric pattern observed in distal segments. A lack of correlation between microvascular and epicardial vessel disease suggests discordant manifestations and progression of CAV.

**Keywords** CAV, 82Rb myocardial perfusion PET images

#### **2.9.1 Severe CAV**

#### **Case 47**

#### **History**


#### **PET/CT**

**Fig. 2.86** Stress and rest 82Rb myocardial perfusion PET images. There is transient ischemic dilatation of the left ventricle during stress. There is increased tracer uptake of the free wall of the right ventricle on both stress and rest images. The stress images show a large perfusion

**Table 2.35** Summary of quantitative fow data showing severely reduced stress fows in the LCX and LAD territories. MFR is reduced in the LAD. The relatively preserved MFR in the LCX territory is related to the presence of a prior nontransmural scar in this area. Stress MBF and MFR were normal in the RCA territory


defect of severe intensity involving the mid and apical anterolateral and anterior walls, and the LV apex, showing complete reversibility. In addition, there is a small perfusion defect of moderate intensity in the mid lateral wall with minimal reversibility


#### **Differential Diagnosis**

• Grade 3 cardiac allograft vasculopathy

#### **Correlative Imaging**

• Coronary angiography (Fig. 2.87)

**Fig. 2.87** Selective view from coronary angiography showing complete occlusion of the mid LAD (yellow circle) and proximal frst obtuse marginal coronary artery (red circle)

#### **Management**

• Patient was referred for revascularization of the LAD and LCX coronary arteries.

#### **Teaching Points**


#### **Further Reading**


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**Evaluation of Infiltrative Cardiomyopathies**

Marcelo F. Di Carli, V. Singh, S. Divakaran, S. Cuddy, S. Dorbala, Rafaele Giubbini, and Maurizio Dondi

Infltrative cardiomyopathies are a group of disorders characterized by the abnormal deposition of proteins and/or infammatory cells leading to cardiac dysfunction and electrical disorders. This chapter will illustrate the role of PET/CT in cardiac sarcoidosis and amyloidosis, and the complementary role of PET/MR and 99mTc PYP SPECT.

#### **3.1 Cardiac Sarcoidosis**

#### **3.1.1 Background**

Sarcoidosis is a multisystem disorder that is characterized histologically by non-caseating, non-necrotic granulomas. Although it most commonly manifests in the lungs or with lymphadenopathy, it can affect any organ. Only 40–50% of patients with cardiac sarcoidosis (CS) diagnosed at autopsy had the diagnosis made during their lifetime.

Areas of active cardiac infammation demonstrated increased glucose metabolism and therefore increased FDG uptake on PET. On the contrary MPI (by SPECT or PET with perfusion tracers) can show areawes of hypoperfusion due to infammation and vascular compression due to edema or myocardial fbrosis and scar. Depending on the degree

M. F. Di Carli · S. Divakaran · S. Cuddy · S. Dorbala

Midwest Heart and Vascular Specialists, HCA Midwest Health,

V. Singh

Kansas City, MO, USA

e-mail: vasvi.singh@hcahealthcare.com

of active infammation on FDG-PET and resting perfusion defects on MPI, the disease can be staged as no evidence of activity (no infammation or scar), early stage (active infammation with mild or no scar), progressive disease (active infammation with moderate scar), or fbrous disease (minimal or no infammation with severe scar).

The evaluation of myocardial uptake of 18F-FDG PET in cardiac sarcoidosis is not simple as the metabolic utilization of glucose can be physiological, and ischemia may affect myocardial uptake. Therefore, adequate patient preparation aimed to suppress myocardial utilization is mandatory.

The presence of obstructive coronary disease and myocardial ischemia should be excluded by stress imaging, CT angiography or, when needed, invasive coronary angiography.

Evaluation of myocardial uptake requires an accurate quality control to exclude attenuation artifacts due to misalignment between PET and CT or presence of attenuators (devices, prosthetic valves, coronary calcifcation). Both attenuation corrected, and uncorrected images should be considered. Semiquantitative measurements can be helpful in serial follow-up after appropriate treatment, as it is in other non-cardiac localizations. Integrated PET/MR or PET/ CT and MR fusion imaging could be useful to increasing specifcity of MR fndings and for follow-up.

Brigham and Women's Hospital, Boston, MA, USA e-mail: mdicarli@bwh.harvard.edu; sdivakaran@bwh.harvard.edu; Scuddy1@bwh.harvard.edu; sdorbala@bwh.harvard.edu R. Giubbini Department of Nuclear Medicine, University of Brescia, Brescia, Italy e-mail: raffaele.giubbini@unibs.it

> M. Dondi (\*) Division of Human Health, International Atomic Energy Agency, Vienna, Austria

<sup>©</sup> The Author(s) 2022 137 M. F. Di Carli et al. (eds.), *IAEA Atlas of Cardiac PET/CT*, https://doi.org/10.1007/978-3-662-64499-7\_3

#### **3.1.2 DIAGNOSIS: Examples Illustrating Diagnostic Certainty (Unlikely, Possible, Probable, Highly Probable)**

#### **Case 48**

#### **History**

• 61-year-old female with a remote history of biopsyproven pulmonary sarcoidosis was referred for FDG cardiac PET due to a new left bundle branch block (Figs. 3.1 and 3.2).

#### **PET/CT Images**

**Fig. 3.1** Rest 99mTc-sestamibi SPECT myocardial perfusion and rest 18F-deoxyglucose (FDG) PET/CT images. There is no evidence of regional perfusion defects. There is adequate suppression of FDG uptake in the normal myocardium. The FDG images demonstrate no evidence of focal glucose uptake in the heart

**Fig. 3.2** Limited whole-body FDG PET/CT images demonstrate no evidence of metabolically active extracardiac sarcoidosis


#### **Differential Diagnosis**

• None

#### **Correlative Imaging**


**Fig. 3.3** Selective short axis views of her contrast-enhanced cardiac magnetic resonance imaging (MRI) demonstrate patchy subepicardial late gadolinium enhancement (LGE) in the basal anteroseptum (arrows)

#### **Management**


#### **Teaching Points**



#### **Case 49**

#### **History**

• 69-year-old male without obstructive coronary artery disease by angiography was referred for a cardiac PET to evaluate for cardiac sarcoidosis due to recurrent ventricular tachycardia (Figs. 3.4 and 3.5).

#### **PET/CT Images**

**Fig. 3.4** Rest 99mTc-sestamibi SPECT myocardial perfusion and 18F-deoxyglucose (FDG) PET/CT images. There is no evidence of regional perfusion defects. There is inadequate suppression of FDG

uptake in the normal myocardium. The FDG images demonstrate mildmoderate diffuse glucose uptake in the heart

**Fig. 3.5** Limited whole-body FDG PET/CT images demonstrate no evidence of metabolically active extracardiac sarcoidosis


#### **Differential Diagnosis**


#### **Correlative Imaging**

• None

#### **Management**

• The patient underwent an electrophysiology study where three ventricular tachycardia morphologies were identifed. Two were ablated, and one was not due to proximity to the conduction system. His ventricular tachycardia has remained controlled since then on antiarrhythmic drug therapy.

#### **Teaching Points**

• FDG PET likelihood of cardiac sarcoidosis is possible (10–50%) when there is a single perfusion defect without associated FDG uptake OR no perfusion defects but non-specifc FDG uptake (diffuse FDG uptake of the left ventricular myocardium or focal FDG uptake with signal intensity that is only mildly increased when compared with background/blood pool uptake), like in this case.



#### **Case 50**

#### **History**


Coronary angiography

**Fig. 3.6** Selective coronary angiographic views demonstrating normal coronary arteries

#### **PET/CT Images**

**Fig. 3.7** Rest 82Rubidium myocardial perfusion and 18F-deoxyglucose (FDG) PET/CT images. The cardiac FDG images demonstrate adequate suppression of glucose uptake. There is predominantly matched reduction in perfusion and FDG uptake except for the mid and basal anteroseptal wall that shows increased glucose uptake (perfusion-FDG mismatched defect) (arrows)

**Fig. 3.8** Limited whole-body FDG PET/CT images demonstrate no evidence of metabolically active extracardiac sarcoidosis


#### **Differential Diagnosis**


#### **Management**

• The patient was treated with prednisone for immunosuppression, but without improvement in his heart failure. He eventually underwent successful heart transplantation. Explant histology confrmed the presence of cardiac sarcoidosis.

#### **Teaching Points**



#### **Case 51**

#### **History**


#### **SPECT and PET/CT Images**

**Fig. 3.10** Limited whole-body PET/CT imaging shows multiple FDG-avid bilateral mediastinal, hilar, and upper abdominal lymph nodes (arrows)


#### **Differential Diagnosis**

#### **Correlative Imaging** (Fig. 3.11)


• None

**Fig. 3.11** RIGHT panel: Gross photograph of a 4-chamber view of the explanted heart shows diffuse involvement of the myocardium by sarcoidosis (arrows). The right ventricle is extensively involved, as is the interventricular septum, with more patchy involvement of the left ventricle. LEFT panel: Photomicrograph of hematoxylin and eosin

(H&E) stained section showing myocardium with a non-necrotizing granuloma containing abundant giant cells. There is fbrosis and a lymphocytic infltrate at the periphery of the granuloma (200× original magnifcation)

#### **Management**

• The patient eventually underwent left ventricular assist device placement and subsequent successful cardiac transplantation for end-stage sarcoid cardiomyopathy.

#### **Teaching Points**

• FDG PET likelihood of cardiac sarcoidosis is highly probable (>90%) when there are multiple, noncontiguous perfusion defects with associated FDG uptake or multiple areas of focal FDG uptake and extracardiac FDG uptake is present.

#### **Further Reading**

Vita T, Okada D, Veillet-Chowdhury M, Bravo P, Mullins E, Hulten E, et al. Complementary Value of Cardiac Magnetic Resonance Imaging and Positron Emission Tomography/Computed Tomography in the Assessment of Cardiac Sarcoidosis. Circulation: Cardiovascular Imaging. 2018;11.


#### **3.1.3 Complementary Value of FDG PET and MRI**

#### **Case 52**

#### **History**


#### **MR Imaging**

**Fig. 3.12** Selected mid short axis slice of the patient's contrast-enhanced cardiac MRI. There is dense subepicardial late gadolinium enhancement involving the basal and mid inferoseptal and to a lesser extent the anterior and anteroseptal walls (arrows). There is additional subepicardial late gadolinium enhancement in the apical inferoseptal segment at the inferior RV insertion site (not shown) 3 Evaluation of Infltrative Cardiomyopathies

#### **PET/CT Imaging**

**Fig. 3.13** Rest 99mTc-sestamibi SPECT myocardial perfusion and 18F-deoxyglucose (FDG) PET/CT images. The rest perfusion images showed a small and severe perfusion defect involving the mid and basal inferoseptal and basal anteroseptal LV segments. The FDG images

demonstrate adequate suppression of glucose uptake by normal myocardium. There is intense focal FDG uptake in the mid and basal inferoseptal wall and mild uptake in the basal anteroseptal wall (perfusion-FDG mismatched defects, arrows)

**Fig. 3.14** Limited whole PET/CT images demonstrating increased FDG uptake in upper mediastinal and hilar nodes, consistent with active extracardiac sarcoidosis (arrows)

MR Imaging


PET/CT Imaging


#### **Differential Diagnosis**

• Myocarditis: Given clinical presentation and absence of troponin elevation, this diagnosis was considered less likely.

#### **Management**

• Given the absence of recurrent ventricular arrhythmias and after detailed discussion with the patient regarding potential beneft vs risk of immunosuppressive therapy, it was decided to perform watchful waiting and eventually repeat the FDG PET scan during follow-up to look for signs of disease progression.

#### **Teaching Points**



#### **3.1.4 Diferential Diagnosis**

#### **Case 53**

#### **History**


**Fig. 3.15** PET/CT images showing a medium-sized perfusion defect in the apical LV segments and apex on rest 82Rubidium myocardial perfusion study. There is intense 18F-deoxyglucose (FDG) uptake in the apical lateral and the mid and basal anterolateral walls

**Fig. 3.16** Limited whole-body PET/CT images demonstrating no evidence of abnormal extracardiac FDG uptake

PET/CT Images


#### **Differential Diagnosis**


#### **Management**

• The patient underwent genetic testing which revealed a disease-causing mutation in the phospholamban gene (c.40\_42delAGA) consistent with the diagnosis of arrhythmogenic cardiomyopathy. His heart failure progressed and required left ventricular assist device placement and he eventually underwent successful cardiac transplantation.

#### **Correlative Imaging** (Fig. 3.17)


**Fig. 3.17** LEFT panel: Gross photograph of four chamber view of the explanted heart showing fatty replacement of the right ventricular free wall characteristic of AC. An AICD lead is seen in the right heart along with evidence of an apically placed left ventricular assist device. RIGHT

panel: Photomicrograph of hematoxylin and eosin (H&E) stained section demonstrating transmural fbrofatty infltration of the right ventricular free wall without other signifcant pathology. Occasional islands of viable myocardium remain. (40× original magnifcation)

#### **Teaching Points**

• The pattern of perfusion abnormalities and non-matching focal FDG uptake makes this case "probable" for cardiac sarcoidosis. FDG PET cardiac sarcoidosis likelihood is probable (50–90%) when there are multiple, noncontiguous perfusion defects without associated FDG uptake OR a single perfusion defect with associated focal or focal on diffuse FDG uptake OR there are no perfusion defects, but focal or focal on diffuse FDG uptake.

#### **Further Reading**

Divakaran S, Stewart G, Lakdawala N, Padera R, Zhou W, Desai A, et al. Diagnostic Accuracy Of Advanced Imaging In Cardiac Sarcoidosis: An Imaging-Histologic Correlation Study In Patients Undergoing Cardiac Transplantation. Journal of the American College of Cardiology. 2019;73:934.


#### **Case 54**

#### **History**

• 47-year-old female with a history of lymphocytic myocarditis with restrictive cardiomyopathy and chronotropic incompetence requiring dual chamber pacemaker placement was referred for FDG PET for the evaluation of cardiac sarcoidosis and rest 99mTc-sestamibi SPECT myocardial perfusion (Figs. 3.18 and 3.19).

#### **PET/CT Images**


#### **Differential Diagnosis**


#### **Correlative Imaging**

• None

#### **Management**

• The patient eventually underwent biventricular assist device placement and subsequent successful cardiac transplantation for end-stage restrictive cardiomyopathy. Histology of the explanted heart revealed restrictive cardiomyopathy with biventricular hypertrophy and active myocarditis.

#### **Teaching Points**



#### **3.1.5 Risk Stratifcation by FDG PET**

#### **Case 55**

#### **History**

• 43-year-old male with history of ventricular tachycardia status post ICD implantation was referred for FDG PET to evaluate for possible cardiac sarcoidosis (Figs. 3.20 and 3.21).

#### **SPECT and PET/CT Images**

**Fig. 3.20** Rest 99mTc-sestamibi SPECT MPI and 18F-FDG PET scan

**Fig. 3.21** Limited whole-body PET/CT images showing no evidence of metabolically active extracardiac sarcoidosis


#### **Differential Diagnosis**


#### **Management**

• Initiation of immunosuppressive therapy for the patient was deferred as the patient did not have defnitive evidence of active infammation.

#### **Correlative Imaging**

• None

#### **Teaching Points**


#### **Further Reading**

Blankstein R, Osborne M, Naya M, Waller A, Kim C, Murthy V, et al. Cardiac Positron Emission Tomography Enhances Prognostic Assessments of Patients With Suspected Cardiac Sarcoidosis. Journal of the American College of Cardiology. 2014;63:329–336.

#### **Case 56**

#### **History**

• 75-year-old female with known pulmonary sarcoidosis presented with ventricular tachycardia/cardiac arrest. She received a secondary prevention ICD and was subsequently referred for an FDG PET/CT to evaluate for cardiac sarcoidosis (Fig. 3.22).

#### **SPECT and PET/CT Images**


**Fig. 3.22** Rest 99mTc-sestamibi SPECT myocardial perfusion and 18F-deoxyglucose (FDG) PET/CT images


#### **Differential Diagnosis**

• None

#### **Correlative Imaging**

• None

#### **Management**

• The patient was started on anti-infammatory therapy including corticosteroids.

#### **Teaching Points**

• FDG PET likelihood of cardiac sarcoidosis is highly probable (>90%) when there are multiple, noncontiguous perfusion defects with associated FDG uptake or multiple areas of focal FDG uptake and extracardiac FDG uptake present.

• The presence of a perfusion-FDG mismatched defect associated with focal FDG uptake in the RV free wall identifes patients at high risk for ventricular arrhythmias and death.


#### **3.1.6 Evaluation of Response to Therapy**

#### **Case 57**

#### **History**


#### **SPECT and PET/CT Images**

**Fig. 3.23** Baseline study. Rest 99mTc-sestamibi myocardial perfusion and 18F-deoxyglucose (FDG) PET/CT


Baseline study (Fig. 3.23):


Follow-up study (7 months after baseline) (Fig. 3.24):


Quantitative analysis of the intensity and extent of FDG uptake shows a decrease of both SUVmax and volume of FDG uptake (Table 3.1).

#### **Correlative Imaging**

• None

#### **Table 3.1** Quantitative analysis


#### **Management**

• After the baseline scan, the patient was started on prednisone (20 mg/day) and methotrexate (20 mg/week). Following the results of the second scan, the patient began tapering immunosuppressive therapy.

#### **Differential Diagnosis**

• None

#### **Teaching Points**



#### **Case 58**

#### **History**


#### **SPECT and PET/CT Images**

**Fig. 3.25** Baseline study. Rest 99mTc-sestamibi myocardial perfusion SPECT and 18F-deoxyglucose (FDG) PET/CT

**Fig. 3.26** Follow-up study. Rest 99mTc-sestamibi myocardial perfusion SPECT and 18F-deoxyglucose (FDG) PET/CT

Baseline study (Fig. 3.25)


Follow-up study (6 months after baseline scan) (Fig. 3.26)


Quantitative analysis of the intensity and extent of FDG uptake (Table 3.2).

#### **Table 3.2** Quantitative analysis


• None

#### **Correlative Imaging**

• None

#### **Management**

• After the baseline scan, the patient was started on prednisone (20 mg/day) and methotrexate (15 mg/week). Following the results of the second scan, the patient underwent intensifcation of immunosuppressive therapy.

#### **Teaching Points**



#### **3.2 Cardiac Amyloidosis**

#### **3.2.1 Background**

Nuclear imaging is particularly useful in characterizing cardiac amyloidosis. Amyloidosis is characterized by loss of natural structure of protein precursors and subsequent aggregation of insoluble fbrillar compound. Fibrils are sustained by a secondary antiparallel β-foils structure. Amyloid deposits are found in the extracellular tissue of many organs and deposits can be either focal or systemic. Cardiac involvement is a leading cause of morbidity and mortality due to systemic amyloidosis. Myocardium, conduction system, and vascular structures can be affected. Typically, it shows characteristics of restrictive cardiomyopathy but both diastolic and systolic function are compromised.

The most frequent types of systemic amyloidosis with cardiac involvement are:

1. acquired monoclonal immunoglobulin light chain amyloidosis (AL) due to plasma cells proliferation producing light chain gamma globulins. Treatment of AL cardiac amyloidosis requires treatment of the underlying plasma 165

cell dyscrasia with chemotherapy and treatment for heart failure.


In all three forms, myocardial involvement is frequent and carries major clinical consequences.

Diagnosis of cardiac amyloidosis is based on (a) biopsy positive Congo red/Thiofavin + polarized light microscopy, (b) genetic analysis/mass spectrometry to identify the protein precursor, (c) contrast MR with gadolinium, showing delayed enhancement of the myocardium in a nonsubendocardial distribution.

#### **3.2.2 Targeted Amyloid Imaging in ATTR and AL Amyloidosis**

#### **Case 59**

#### **History**

• 72-year-old male with worsening dyspnea on exertion, lower leg swelling and fatigue, and an abnormal echocardiogram was referred for a 99mTc pyrophosphate (PYP) scan to evaluate for cardiac amyloidosis (Fig. 3.27) and 18F-Florbetapir PET/CT imaging (Fig. 3.28).


**Fig. 3.27** Whole-body study using 99mTc PYP

**Fig. 3.28** 18F-Florbetapir PET/CT imaging


#### **Differential Diagnosis**


#### **Teaching Points**

• Bone scintigraphy 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), hydroxymethylene diphosphonate (HMDP), or PYP has high sensitivity and specifcity for cardiac transthyretin (ATTR) amyloidosis; and can be used to diagnose cardiac ATTR amyloidosis when a monoclonal gammopathy is excluded.


#### **Correlative Imaging**

• Echocardiography (Fig. 3.29)

**Fig. 3.29** 2-D echocardiography images and systolic strain map. The apical 4-chamber view (left panel) on echocardiography demonstrates thickened left ventricular walls and bi-atrial enlargement. There is also an increased echogenicity of the myocardium. A 17-segment polar map

#### **Management**

• The patient's heart failure medications were optimized. He was started on a recently approved TTR stabilizer, tafamidis, to slow the progression of the disease.

#### **Further Reading**

Chareonthaitawee P, Beanlands R, Chen W, Dorbala S, Miller E, Murthy V, et al. Joint SNMMI–ASNC Expert Consensus Document on the Role of 18F-FDG PET/CT in

(right panel) of global longitudinal strain (GLS) values demonstrates the typical appearance of cardiac amyloidosis with reduced global GLS (−10.2%; normal < −16%), and reduced GLS at the mid and base, and preserved apical GLS

Cardiac Sarcoid Detection and Therapy Monitoring. Journal of Nuclear Medicine. 2017;58:1341–1353.

Dorbala S, Ando Y, Bokhari S, Dispenzieri A, Falk R, Ferrari V, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/ SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 1 of 2—evidence base and standardized methods of imaging. Journal of Nuclear Cardiology. 2019;26:2065–2123.

#### **Case 60**

#### **History**


**Fig. 3.30** 99mTechnetium pyrophosphate (PYP): chest planar views demonstrate mildly increased uptake of the radiotracer in the cardiac region

**Fig. 3.31** Selected SPECT/CT transaxial section of fused PYP images showing minimal or no radiotracer uptake in the myocardium

This patient also underwent 18F-Florbetapir PET/CT imaging as part of a research protocol (Fig. 3.32).

**Fig. 3.32** 18F-Florbetapir PET/CT imaging showing intense cardiac uptake of the radiotracer


#### **Differential Diagnosis**

• Light chain (AL) cardiac amyloidosis

#### **Correlative Imaging** (Fig. 3.33)


**Fig. 3.33** LEFT panel: 2-D echocardiography demonstrates mildly thickened left ventricular walls. There is also a small pericardial effusion seen best along the right ventricular free wall. RIGHT side:

Contrast-enhanced MRI images show a typical appearance of diffuse transmural late gadolinium enhancement of the left ventricle and of the right ventricle

#### **Management**


#### **Teaching Points**


this does not exclude ATTR amyloidosis, it makes it less likely.


#### **Further Reading**


The opinions expressed in this chapter are those of the author(s) and do not necessarily refect the views of the [NameOfOrganization], 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 [NameOfOrganization], 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 [NameOfOrganization] that cannot be settled amicably shall be submitted to arbitration pursuant to the UNCITRAL rules. The use of the [NameOfOrganization]'s name for any purpose other than for attribution, and the use of the [NameOfOrganization]'s logo, shall be subject to a separate written license agreement between the [NameOfOrganization] 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.

#### © The Author(s) 2022 173 M. F. Di Carli et al. (eds.), *IAEA Atlas of Cardiac PET/CT*, https://doi.org/10.1007/978-3-662-64499-7\_4

# **Evaluation of CV Inflammation and Infection**

Rafaele Giubbini, E. Milan, V. Singh, Marcelo F. Di Carli, Maurizio Dondi, I. Carvajal, E. Alexanderson, C. Rodella, and Diana Paez

Early diagnosis of endocarditis has an important prognostic value because a delay in antibiotic therapy and cardiac surgery may adversely affect clinical outcome. However, its diagnosis remains a challenging one.

Clinical diagnosis of infective endocarditis (IE) is based on the modifed Duke criteria, which are mainly related to the results of blood cultures; echocardiography, either transthoracic or transesophageal, and clinical fndings. According to these criteria the probability of IE is classifed as defnite, possible, or rejected. However, in clinical practice, the modifed Duke criteria show a low diwagnostic accuracy for early diagnosis of IE, especially in presence of device-related IE (prosthetic valve and implantable pacemaker/defbrillator devices), for which

R. Giubbini

Department for Nuclear Medicine, University of Brescia, Brescia, Italy

e-mail: raffaele.giubbini@unibs.it

E. Milan

Nuclear Cardiology Lab and PET Centre, Treviso Hospital, Treviso, Italy e-mail: elisa.milan@aulss2.veneto.it

V. Singh Midwest Heart and Vascular Specialists, HCA Midwest Health, Kansas City, MO, USA e-mail: vasvi.singh@hcahealthcare.com

M. F. Di Carli Brigham and Women's Hospital, Boston, MA, USA e-mail: mdicarli@bwh.harvard.edu

M. Dondi (\*) · D. Paez Division of Human Health, International Atomic Energy Agency, Vienna, Austria e-mail: d.paez@iaea.org

I. Carvajal · E. Alexanderson Instituto Nacional De Cardiologia Ignacio Chavez, Mexico City, Mexico

C. Rodella Department of Medical Physics, Spedali Civili Brescia, Brescia, Italy e-mail: carlo.rodella@asst-spedalicivili.it

echocardiography is quite frequently normal or inconclusive. Moreover, when IE is suspected, the use of a wholebody modality of imaging is recommended to identify the presence of a possible extra-cardiac primary infection focus, as well as to assess the spread of infection (infective embolism).

Recently, the European Society of Cardiology incorporated 18F-FDG PET/CT fndings in its guidelines as major criteria in the diagnostic algorithm of patients with suspected device-related IE in order to reduce the rate of misdiagnosed IE, classifed in the "Possible IE" category.

The rationale behind the use of PET/CT is related to the increased 18F-FDG uptake in presence of elevated glucose metabolism (infected cells, activated leucocytes, monocytes, macrophages, CD4+ T-lymphocytes).

In order to optimize 18F-FDG PET/CT fndings, some aspects need to be pointed out:


**4**


#### **Further Reading**


#### **4.1 Patient Preparation for Assessing Infammation/Infection**

The role of FDG PET/CT for diagnosing infammation involving implanted structures such as intracardiac devices (ICD) and prosthetic valves, or other conditions such as infammatory cardiomyopathies or cardiac sarcoidosis, has been already recognized.

However, due to the physiologic myocardial FDG uptake, the diffculty is to identify areas of pathological uptake at cardiac level. To this purpose, specifc patient preparation is requested to ideally suppress cardiac glucose metabolism while enhancing contrast to infammatory FDG deposits and identify areas of active infammation and/or granulomatous disease.

One strategy is to instruct patients to undergo a preparation rich in fat and low in carbohydrates, eating one fatty meal prior to the exam and fast the day of the procedure.


#### **4.2 Suspected Prosthetic Valve Endocarditis (PVE)**

#### **4.2.1 False Positive (with and w/o AC)**

#### **Case 61**

#### **History**


#### **PET/CT Images**

**Fig. 4.1** Coronal FDG PET image demonstrating intense glucose uptake around the left hip

**Fig. 4.2** PET/CT images demonstrating intense focal FDG uptake around the pacemaker lead (arrow, Top Panel), which persists in the nonattenuation corrected images (arrow, Lower Panel)

**Fig. 4.3** PET/CT images showing intense FDG accumulation in the area corresponding to intense mitral annular calcifcation (arrow, Top Panel), which appears non-signifcant in the non-attenuation corrected images (arrow, Lower Panel)


#### **Differential Diagnosis**


#### **Management**


#### **Teaching Points**



#### **4.2.2 Focal Abscess Before and After Antibiotic Therapy**

#### **Case 62**

#### **History**


#### **18F-FDG PET/CT**

**Fig. 4.4** Baseline FDG PET/CT study showing intense uptake at the level of the bioprosthetic valve

**Fig. 4.5** FDG PET images with and without attenuation correction

**Fig. 4.6** Follow-up FDG PET/CT study, after antibiotic therapy, showing substantial decrease of the intensity of the focal uptake area

**Fig. 4.7** Follow-up FDG PET images with and without attenuation correction

#### Baseline study

	- There is substantial decrease in the intensity and extent of FDG uptake along the bioprosthetic aortic valve, which is minimal on the non-attenuation corrected images. The SUVmax was 4.1.

#### **Differential Diagnosis**

• None

#### **Correlative Imaging**

• None

#### **Management**


#### **Teaching Points**



#### **4.3 Device Infection**

#### **4.3.1 Generator Pocket and Lead Infection**

#### **Case 63**

#### **History**

• 74-year-old male with previous pacemaker/ICD implant admitted with fever underwent FDG PET/CT for suspected infective endocarditis (Fig. 4.8).

#### **PET/CT Images**

**Fig. 4.8** Coronal, sagittal, and axial FDG PET/CT images (left and middle panels), non-attenuation corrected axial (right upper panel) and MIP PET image (right lower panel), showing a focus of intense FDG uptake in the pacemaker generator pocket


#### **Differential Diagnosis**


#### **Management**

• The focality and intensity of the FDG uptake was considered indicative of an infection focus in the pacemaker generator pocket. The patient started antibiotic therapy and a pocket surgical revision was considered.

#### **Teaching Points**

• FDG PET is the most useful technique to evaluate pacemaker infection, especially within the pacemaker generator pocket.



#### **4.3.2 Device Infection in Patient with Amyloidosis**

#### **Case 64**

#### **History**


**Fig. 4.9** Planar and SPECT 99mTc-DPD imaging. The planar images demonstrate intense tracer uptake in the left and right ventricles which is greater than ribs (Perugini grade 3). The SPECT images show that uptake is predominantly in the mid to basal segments

**Fig. 4.10** PET/CT images demonstrating intense focal FDG uptake associated with the section of the pacemaker lead in the right ventricle. No FDG uptake is noted in the pacemaker generator pocket

**Fig. 4.11** PET images without attenuation correction which demonstrate persistence of intense focal FDG uptake associated with the pacemaker lead in the right ventricle


#### **Management**


#### **Teaching Points**



#### **4.4 Vasculitis**

#### **4.4.1 Diagnosis and Response to Therapy**

#### **Case 65**

#### **History**


#### **PET/CT Images**

**Fig. 4.12** Whole-body PET/CT images during the index admission showing multiple foci of intense FDG uptake in the mediastinum and hilar regions (arrows) and in the abdominal aorta and iliac arteries (arrows)

**Fig. 4.13** Follow-up whole-body PET/CT images obtained 9 and 18 months after the initial scan demonstrate complete resolution of FDG uptake in the thorax and markedly reduced but still active infammation in the abdominal aorta and proximal iliac arteries


#### **Management**

• The patient was initiated on immunosuppressive therapy with corticosteroids. Tocilizumab was added after the 9-month FDG PET/CT study.

#### **Correlative Imaging** (Fig. 4.14)

• Whole-body contrast CT angiography was performed during initial hospital admission. It showed dilation of the abdominal aorta with aneurysm of the right iliac artery and several ulcerations.

**Fig. 4.14** Contrast CT angiography showing dilation of the abdominal aorta with aneurysm of the right iliac artery and several ulcerations

#### **Differential Diagnosis**


#### **Teaching Points**

• FDG PET/CT is a very effective tool for monitoring treatment response in infammatory diseases including sarcoidosis and vasculitis.

#### **Further Reading**

Piekarski E, Benali K, Rouzet F. Nuclear Imaging in Sarcoidosis. Seminars in Nuclear Medicine. 2018;48:246–260.

Versari A, Pipitone N, Casali M, Jamar F, Pazzola G. Use of imaging techniques in large vessel vasculitis and related conditions. The Quarterly Journal of Nuclear Medicine and Molecular Imaging. 2018;62:34–39.

#### **4.4.2 Large Vessel Vasculitis**

#### **Case 66**

#### **History**


**Fig. 4.15** FDG PET (top), CT angiography (middle), and fused limited whole-body PET/CT images


#### **Differential Diagnosis**


#### **Management**

• The patient was started on immunosuppression with good clinical response. No follow-up imaging was available.

#### **Teaching Points**

• FDG PET/CT is useful to assess the presence and extent of arterial infammation and provides important information that can inform initiation and monitoring of treatment as discussed in Case 64.

#### **Further Reading**


The opinions expressed in this chapter are those of the author(s) and do not necessarily refect the views of the [NameOfOrganization], 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 [NameOfOrganization], 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 [NameOfOrganization] that cannot be settled amicably shall be submitted to arbitration pursuant to the UNCITRAL rules. The use of the [NameOfOrganization]'s name for any purpose other than for attribution, and the use of the [NameOfOrganization]'s logo, shall be subject to a separate written license agreement between the [NameOfOrganization] 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.

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# **Emerging Applications**

**5**

Marcelo F. Di Carli, Rafaele Giubbini, M. Williams, M. Bertoli, Maurizio Dondi, Diana Paez, and E. Milan

Cardiovascular imaging has recently expanded to the search for unstable plaques at high risk of rupturing and causing acute coronary events. A vulnerable plaque has been described histologically as a plaque with a large lipid core, a thin fbrous cap, and infammation at the margins of the plaque. One of the most interesting recent fndings is the discovery that plaques exhibiting high-risk characteristics may be associated with inducible myocardial ischemia even in the absence of luminal obstruction. Currently, anatomical and functional imaging of coronary atherosclerosis can be performed with computed tomography angiography and positron emission tomography, as briefy reviewed in this chapter.

Molecular imaging with positron emission tomography (PET) allows investigators to image some of the components of a high-risk plaque. The PET tracers most used are 18F-fuoro-deoxy-glucose (FDG) and sodium fuoride (18F-NaF). Of these, 18F-fuoro-deoxy-glucose (FDG) is a glucose analogue actively taken up by cells with a high metabolic rate but has the inherent limitation of its preferential uptake by the myocardium that clouds the uptake by the much smaller coronary vessels. 18F-NaF has been in use for a long time to image bone metastases, but it was only recently discovered as a tracer to image atherosclerosis. 18F-NaF accumulates in plaques accruing calcium apatite and all nascent plaques accrue microcalcifcations that may evolve into larger deposits. The initial proof that 18F-NaF could identify patients with vulnerable plaques was provided in a study that involved patients in the acute setting. In a study performed with 18F-NaF imaging has been employed in patients with either acute coronary syndromes, or stable angina and/or undergoing carotid endarterectomy. 18F-NaF uptake localized in culprit arteries of patients with acute coronary syndromes, and carotid arteries with ruptured plaques in patients with cerebrovascular events. A similar carotid artery fnding was reported in a second publication of patients with stroke or transient ischemic attacks.

M. F. Di Carli Brigham and Women's Hospital, Boston, MA, USA e-mail: mdicarli@bwh.harvard.edu

R. Giubbini Department of Nuclear Medicine, University of Brescia, Brescia, Italy e-mail: raffaele.giubbini@unibs.it

M. Williams The University of Edinburgh, Edinburgh, UK e-mail: michelle.williams@ed.ac.uk

M. Bertoli Department of Nuclear Medicine, Spedai Civili Brescia, Brescia, Italy e-mail: mattia.bertoli@asst-spedalicivili.it

M. Dondi (\*) · D. Paez Division of Human Health, International Atomic Energy Agency, Vienna, Austria e-mail: d.paez@iaea.org

E. Milan Nuclear Cardiology Lab and PET Centre, Treviso Hospital, Treviso, Italy e-mail: elisa.milan@aulss2.veneto.it

#### **5.1 Plaque Imaging**

#### **Case 67**

#### **History**


#### **Coronary Angiography**

**Fig. 5.1** Invasive coronary angiography at the time of the ST elevation myocardial infarction showed mild disease in the mid RCA and an occluded LAD

#### **PET/MR Images**

**Fig. 5.2** 18F-sodium fuoride PET-MR showed radiotracer uptake in the proximal LAD (arrow)

• 18F-sodium fuoride PET-MRI showed radiotracer uptake in the proximal LAD (arrow) at the site of the recent plaque rupture.

#### **Differential Diagnosis**

• ST elevation myocardial infarction caused by plaque rupture and treated with a drug eluting stent.

#### **Correlative Imaging**

This patient underwent CCTA (Fig. 5.3).

**Fig. 5.3** Computed tomography coronary angiography showed two patent stents in the left anterior descending coronary artery with some minor mixed plaque in the proximal LAD

#### **Management**

• The patient recovered well from his invasive coronary angiography and will be seen in the cardiology clinic.

#### **Teaching Points**



#### **5.2 Cardiac Toxicity After Chemo/ Radiation**

#### **5.2.1 Cardiac Involvement at Oncological PET**

#### **Case 68**

#### **History**


#### **PET/CT Imaging**

**Fig. 5.4** Limited whole body FDG PET/CT images at baseline and following chemotherapy. In the last follow-up scan, there is complete remission of metabolic activity both in the neck and in the upper abdomen. The images also show progressive increase of myocardial FDG uptake

#### 5 Emerging Applications

#### **Findings**


#### **Differential Diagnosis**


**Fig. 5.5** Stress-rest 99mTc Tetrofosmin


#### **Management and Teaching Points**



#### **5.2.2 Pericarditis After Chemotherapy**

#### **Case 69**

#### **History**

• A 66-year-old female with Hodgkin's Lymphoma (HL) undergoing interim PET/CT (Fig. 5.6) to monitor treatment response after two cycles ABVD (doxorubicin + bleomycin + vinblastine + dacarbazine).

**Fig. 5.6** Limited whole body FDG PET/CT demonstrating a small pericardial effusion with moderate tracer uptake in the pericardium

This patient was then submitted to TTE (Fig. 5.7).

**Fig. 5.7** Transthoracic echocardiogram confrming the presence of a moderate pericardial effusion


#### **Management**

• The patient received anti-infammatory therapy.

#### **Teaching Points**


#### **Further Reading**


The opinions expressed in this chapter are those of the author(s) and do not necessarily refect the views of the [NameOfOrganization], 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 [NameOfOrganization], 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 [NameOfOrganization] that cannot be settled amicably shall be submitted to arbitration pursuant to the UNCITRAL rules. The use of the [NameOfOrganization]'s name for any purpose other than for attribution, and the use of the [NameOfOrganization]'s logo, shall be subject to a separate written license agreement between the [NameOfOrganization] 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.