Matthieu Pelletier-Galarneau

New SPECT and PET radiopharmaceuticals for imaging cardiovascular disease

Nuclear cardiology has experienced exponential growth within the past four decades with converging capacity to diagnose and influence management of a variety of cardiovascular diseases. Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) with technetium-99m radiotracers or thallium-201 has dominated the field; however new hardware and software designs that optimize image quality with reduced radiation exposure are fuelling a resurgence of interest at the preclinical and clinical levels to expand beyond MPI. Other imaging modalities including positron emission tomography (PET) and magnetic resonance imaging (MRI) continue to emerge as powerful players with an expanded capacity to diagnose a variety of cardiac conditions. At the forefront of this resurgence is the development of novel target vectors based on an enhanced understanding of the underlying pathophysiological process in the subcellular domain. Molecular imaging with novel radiopharmaceuticals engineered to target a specific subcellular process has the capacity to improve diagnostic accuracy and deliver enhanced prognostic information to alter management. This paper, while not comprehensive, will review the recent advancements in radiotracer development for SPECT and PET MPI, autonomic dysfunction, apoptosis, atherosclerotic plaques, metabolism, and viability. The relevant radiochemistry and preclinical and clinical development in addition to molecular imaging with emerging modalities such as cardiac MRI and PET-MR will be discussed.

Pulmonary Scintigraphy for the Diagnosis of Acute Pulmonary Embolism: A Survey of Current Practices in Australia, Canada, and France

There are currently no data published regarding the proportion of nuclear medicine centers using SPECT or SPECT/CT rather than planar ventilation/perfusion (V/Q) imaging in patients with suspected acute pulmonary embolism (PE). Furthermore, the reporting criteria used for interpretation of both planar and SPECT V/Q scans are variable and data are lacking regarding which criteria are commonly used in various centers. The aim of this study was to assess current practices regarding the performance and interpretation of lung scintigraphy across 3 different countries. Methods: A short online survey composed of simple multiple-choice questions was distributed to nuclear medicine departments in Australia, Canada, and France during the period April to December 2014. The survey covered image acquisition, interpretation criteria for SPECT and planar images, and use of pseudoplanar images and radiopharmaceuticals. Information was initially solicited by 2 sets of e-mails, which pointed to the survey internet link. Departments were subsequently contacted by telephone. A single response per department was consolidated. Results: Three hundred thirty-one responses were collected (Australia, 74; Canada, 48; and France, 209). Twenty-eight percent of centers indicated use of V/Q planar imaging alone whereas 72% of centers included some form of SPECT in their acquisition protocol for evaluation of PE, specifically V/Q SPECT in 36%, V/Q SPECT/CT in 29%, Q SPECT/CT in 2%, and both V/Q planar and SPECT in 5%, with a strong variability among countries. The most commonly used criteria for SPECT interpretation were the those of the European Association of Nuclear Medicine (60%). Criteria used for planar interpretation were heterogeneous (European Association of Nuclear Medicine criteria, 35%; Prospective Investigation of Pulmonary Embolism Diagnosis study, 29%; no standardized criteria, 21%). Sixty-three percent of departments used pseudoplanar images in addition to SPECT images. Conclusion: In the 3 countries surveyed, SPECT has largely replaced planar imaging for evaluation of PE, with almost half of the SPECT studies incorporating a CT acquisition. Criteria used for interpretation are inconsistent, especially for planar imaging.

Incremental Prognostic Value of Quantified Vulnerable Plaque by Cardiac Computed Tomography: A Pilot Study.

Background: Coronary computed tomography (CT) angiography (CCTA) has the ability to detect, characterize, and quantify atherosclerotic plaques. The aim of our study was to evaluate the prognostic power of CCTA-quantified plaque subtypes. Materials and Methods: A total of 36 patients with adverse events and 36 Morise score–matched patients who remained event free on follow-up were identified. Using CCTA images, plaque subtype volumes in the major epicardial arteries were analyzed using predetermined attenuation ranges in Hounsfield units (HU): 1 to 30 HU (low attenuating), 31 to 70 HU (intermediate attenuating), 71 to 150 HU (high attenuating), and mean coronary lumen+2 SD to 1000 HU (calcified). Each epicardial artery was divided into proximal, mid, and distal segments, and plaque volumes were normalized for arterial segment length. Results: The baseline characteristics of the 2 cohorts were similar. Low-attenuation and intermediate-attenuation plaque volumes were greater in the proximal segments as well as in the entire length in the adverse event compared with the event-free group. High-attenuation plaque volume was increased only in the proximal segments in the adverse event group. There was no difference in the volume of calcified plaque between the 2 groups. The log rank test using a cutoff of 3.99 mm3/mm for combined intermediate and low plaque volume showed more adverse events in patients with a plaque volume of ≥3.99 mm3/mm. Conclusions: Adverse events appear to be associated with greater volumes of low-attenuation and intermediate-attenuation plaques that reflect lipid and fibrous atherosclerosis. The difference between the 2 groups is most apparent in the proximal epicardial arteries.

Metastatic ovarian carcinoma showing surprisingly widespread subcutaneous 99mTc-MDP soft-tissue uptake.

Cutaneous involvement is generally unusual for metastases in a variety of primary malignancies including patients diagnosed with ovarian cancer. We report the rare observance of subcutaneous lesions from an aggressive ovarian primary carcinoma with unusual uptake of 99mTc-MDP on a tomographic whole-body bone scan without osseous metastatic lesions or uptake. The findings were correlated with cross-sectional imaging in addition to histological analysis.

Effects of Hypercapnia on Myocardial Blood Flow in Healthy Human Subjects

Elevation of the end-tidal partial pressure of CO2 (PETco2) increases cerebral and myocardial blood flow (MBF), suggesting that it may be a suitable alternative to pharmacologic stress or exercise for myocardial perfusion imaging. The purpose of this study was to document the pharmacodynamics of CO2 for MBF using prospective end-tidal targeting to precisely control arterial Pco2 and PET to measure the outcome variable, MBF. Methods: Ten healthy men underwent serial 82Rb PET/CT imaging. Imaging was performed at rest and during 6-min hypercapnic plateaus (baseline; PETco2 at 50, 55, and 60 mm Hg; repeat of PETco2 at 60 mm Hg; and repeat of baseline). MBF was measured using 82Rb injected 3 min after the beginning of hypercapnia and a 1-tissue-compartment model with flow-dependent extraction correction. Results were compared with those obtained during an adenosine stress test (140 μg/kg/min). Results: Baseline PETco2 was 38.9 ± 0.8 (mean ± SD) mm Hg (range, 35–43 mm Hg). All PETco2 targets were sustained, with SDs of less than 1.5 mm Hg. Heart rate, systolic blood pressure, rate × pressure product, and respiratory frequency increased with progressive hypercapnia. MBF increased significantly at each level of hypercapnia to 1.92-fold over baseline (0.86 ± 0.24 vs. 0.45 ± 0.08 mL/min/g; P = 0.002) at a PETco2 of 60 mm Hg. MBF after the administration of adenosine was significantly greater than that with the maximal hypercapnic stimulus (2.00 vs. 0.86 mL/min/g; P < 0.0001). Conclusion: To our knowledge, this study is the first to assess the response of MBF to different levels of hypercapnia in healthy humans with PET. MBF increased with increasing levels of hypercapnia; MBF at a PETco2 of 60 mm Hg was double that at baseline.

The role of bone scintigraphy with single-photon emission computed tomography-computed tomography in the diagnosis and evaluation of calciphylaxis

Calciphylaxis, also known as calcific uremic arteriolopathy, is an uncommon disease, typically found in patients with the end-stage renal disease. Pathophysiological features include small vessel vasculopathy with mural calcification, fibrosis, and thrombosis. The clinical presentation varies but often consists of the necrosis of skin and subcutaneous tissues, with or without visceral organ involvement due to small vessel vasculopathy. This condition has a significant morbidity and mortality, making accurate diagnosis imperative. We present a case of calciphylaxis investigated using planar bone scintigraphy and single-photon emission computed tomography-computed tomography (SPECT-CT). This case stresses the value of SPECT-CT to accurately localize the abnormal uptake in subcutaneous soft tissue microcalcifications and confirms the exact location and extent of pathology.

Role of PET/CT in Assessing Cardiac Sarcoidosis

Sarcoidosis is a multisystem disease of unknown origin, predominantly affecting young adults, and characterized by compact noncaseating epithelioid cell granulomas. The term sarkoid was first introduced in 1899 by Caesar Boeck, a Norwegian dermatologist, to describe benign cutaneous lesions that resembled sarcoma on histopathological examination. With the development and progress of new imaging modalities including positron emission tomography (PET) and magnetic resonance imaging (MRI), there has been a recent increase in interest from clinicians and researchers regarding the diagnosis and treatment of cardiac sarcoidosis.

Incidental mammary fibromyoblastoma on 82Rb myocardial perfusion imaging.

82Rb is frequently used in PET myocardial perfusion imaging to detect ischemia. We present the case of a 64-year-old man referred for PET myocardial perfusion imaging to rule out ischemia. On PET images, an abnormal focus of uptake was present in the subcutaneous soft tissue overlying the right chest, which corresponded to a soft-tissue nodule on CT. This lesion was biopsied and proved to be a mammary fibromyoblastoma, an extremely rare and benign lesion. This case is presented to emphasize the importance of reviewing extracardiac structures on PET/CT myocardial perfusion studies.

Molecular Imaging of Cardiac Sarcoidosis

Purpose of ReviewCardiac involvement is increasingly being recognized as a cause of significant morbidity and mortality in patients with sarcoidosis. Unfortunately, imaging cardiac sarcoidosis (CS) remains a challenge and often relies on advanced imaging modalities. The aim of this review is to provide an up-to-date overview of the role of molecular imaging for the diagnosis of cardiac sarcoidosis, with particular emphasis on the use of FDG and non-FDG PET.Recent FindingsIn the last few years, FDG-PET has established itself as an accurate imaging study for the assessment of CS. New diagnostic criteria have recently appeared which incorporate FDG-PET findings in the diagnostic workup for CS. In addition, a joint SNMMI-ASNC Expert Consensus document has appeared on the role of FDG-PET in CS. Recent advances in the field have focused on the role of PET for diagnosis, assessment of therapy, and use of non-FDG tracers to image myocardial inflammation.SummaryThe role of PET is rapidly evolving but is now firmly established as an important component in the imaging assessment of CS.

Randomized Trial Comparing the Effects of Ticagrelor Versus Clopidogrel on Myocardial Perfusion in Patients With Coronary Artery Disease

Background Ticagrelor is a P2Y12 receptor inhibitor used in acute coronary syndromes to reduce platelet activity and to decrease thrombus formation. Ticagrelor is associated with a reduction in mortality incremental to that observed with clopidogrel, potentially related to its non–antiplatelet effects. Evidence from animal models indicates that ticagrelor potentiates adenosine‐induced myocardial blood flow (MBF) increases. We investigated MBF at rest and during adenosine‐induced hyperemia in patients with stable coronary artery disease treated with ticagrelor versus clopidogrel. Methods and Results This randomized double‐blinded crossover study included 22 patients who received therapeutic interventions of ticagrelor 90 mg orally twice a day for 10 days and clopidogrel 75 mg orally once a day for 10 days, with a washout period of at least 10 days between the treatments. Global and regional MBF and myocardial flow reserve were measured using rubidium 82 positron emission tomography/computed tomography at baseline and during intermediate‐ and high‐dose adenosine. Global MBF was significantly greater with ticagrelor versus clopidogrel (1.28±0.55 versus 1.13±0.47 mL/min per gram, P=0.002) at intermediate‐dose adenosine and not different at baseline (0.65±0.19 versus 0.60±0.15 mL/min per gram, P=0.084) and at high‐dose adenosine (1.64±0.40 versus 1.61±0.19 mL/min per gram, P=0.53). In regions with impaired myocardial flow reserve (<2.5), MBF was greater with ticagrelor compared with clopidogrel during intermediate and high doses of adenosine (P<0.0001), whereas the differences were not significant at baseline. Conclusions Ticagrelor potentiates global and regional adenosine‐induced MBF increases in patients with stable coronary artery disease. This effect may contribute to the incremental mortality benefit compared with clopidogrel. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01894789.