Mehrbod S. Javadi

Cardiac positron emission tomography.

Positron emission tomography (PET) is a powerful, quantitative imaging modality that has been used for decades to noninvasively investigate cardiovascular biology and physiology. Due to limited availability, methodologic complexity, and high costs, it has long been seen as a research tool and as a reference method for validation of other diagnostic approaches. This perception, fortunately, has changed significantly within recent years. Increasing diversity of therapeutic options for coronary artery disease, and increasing specificity of novel therapies for certain biologic pathways, has resulted in a clinical need for more accurate and specific diagnostic techniques. At the same time, the number of PET centers continues to grow, stimulated by PETs success in oncology. Methodologic advances as well as improved radiotracer availability have further contributed to more widespread use. Evidence for diagnostic and prognostic usefulness of myocardial perfusion and viability assessment by PET is increasing. Some studies suggest overall cost-effectiveness of the technique despite higher costs of a single study, because unnecessary follow-up procedures can be avoided. The advent of hybrid PET-computed tomography (CT), which enables integration of PET-derived biologic information with multislice CT-derived morphologic information, and the key role of PET in the development and translation of novel molecular-targeted imaging compounds, have further contributed to more widespread acceptance. Today, PET promises to play a leading diagnostic role on the pathway toward a future of high-powered, comprehensive, personalized, cardiovascular medicine. This review summarizes the state-of-the-art in current imaging methodology and clinical application, and outlines novel developments and future directions.

Prediction of Short-Term Cardiovascular Events Using Quantification of Global Myocardial Flow Reserve in Patients Referred for Clinical 82Rb PET Perfusion Imaging

Current noninvasive tests for coronary artery disease detect atherosclerosis or regional ischemia. Global myocardial flow reserve is not routinely identified, although it may be an additional marker of disease development and progression. Methods: For the clinical work-up of suspected or known stable coronary artery disease, 275 individuals had undergone rest–dipyridamole 82Rb myocardial perfusion imaging using PET. In addition to clinical measures of regional perfusion and function, an experimentally validated approach to quantify global myocardial flow reserve was used. Follow-up was obtained for 362 ± 277 d. Results: Myocardial blood flow and flow reserve showed significant correlation to systemic and cardiac hemodynamics and a weak association with risk factors such as age and history of hyperlipidemia. Flow reserve was expectedly lower in subjects with regional ischemia (1.70 ± 0.65 vs. 2.31 ± 0.97 in those without; P < 0.0001), but a wide range was observed in those without regional perfusion abnormalities. We used a composite endpoint of hard and soft events to determine that flow reserve below the median was predictive of adverse outcome in the overall population (P = 0.001) and in subjects with normal regional perfusion (n = 178; P = 0.036), whereas stress flow was predictive only in the overall population (P = 0.001). Age-adjusted multivariate analysis confirmed regional perfusion defects (relative hazard, 2.51; 95% confidence interval, 1.24–5.10; P = 0.009) and low global flow reserve (relative hazard, 2.93; 95% confidence interval, 1.30–6.65; P = 0.011) as independent predictors of cardiac events. Conclusion: In clinical cardiac 82Rb PET, globally impaired flow reserve is a relevant marker for predicting short-term cardiovascular events. It may be used for integration with currently established functional and morphologic test results and for guidance of preventive measures, especially in the absence of regional flow–limiting disease.

Definition of Vascular Territories on Myocardial Perfusion Images by Integration with True Coronary Anatomy: A Hybrid PET/CT Analysis

For interpretation of myocardial perfusion studies, tissue segments are usually assigned to coronary vascular territories based on general assumptions about the most frequent vascular distribution pattern. These assumptions may be inaccurate because of interindividual variability of coronary anatomy. This limitation may be overcome by hybrid imaging through the individual integration of coronary anatomy with myocardial tissue regions. Methods: We studied 71 consecutive patients who underwent 82Rb perfusion PET/CT, including CT angiography, for work-up of coronary artery disease on a 64-slice PET/CT scanner. Coronary vessels as defined by CT were assigned to each of 17 myocardial segments for PET analysis using fusion images. Reassigned segmental maps were compared with standard assignment as proposed by the American Heart Association model, without knowledge of individual anatomy. The validity of segmental assignment was tested in 6 dogs by comparison of PET/CT with ex vivo dye staining of coronary territories. Results: Dog studies showed excellent agreement between PET/CT-defined segments and ex vivo–stained territories (κ, 0.80). In patients, 72% (51/71) demonstrated differences from the standard assignment in at least 1 myocardial segment; 112 of 1,207 segments were reassigned to nonstandard vascular territories. Most frequently, standard right coronary segments were reassigned to the left circumflex territory (39% of reassigned segments), standard circumflex segments were reassigned to the left anterior descending territory (30%), and standard left anterior descending segments were reassigned to either circumflex or right coronary (12% and 11%, respectively). In 27 studies with a myocardial perfusion defect, relative uptake in the vascular territory with the defect was significantly lower after CT-based reassignment and was higher in remote territories, resulting in better separation (ratio of defect to remote, 0.75 ± 0.13 vs. 0.81 ± 0.12 before reassignment; P = 0.0014). Conclusion: Standard assumptions about vascular territory distribution in myocardial perfusion analysis are frequently inaccurate because of morphologic variability of the coronary tree. If hybrid imaging has been used to study coronary anatomy and myocardial tissue perfusion, then localization of perfusion abnormalities should be based on CT-derived anatomy. This may bring about more accurate assignment to culprit vessels and thus improved guidance and monitoring of targeted therapy.

124I PET-Based 3D-RD Dosimetry for a Pediatric Thyroid Cancer Patient: Real-Time Treatment Planning and Methodologic Comparison

Patient-specific 3-dimensional radiobiologic dosimetry (3D-RD) was used for 131I treatment planning for an 11-y-old girl with differentiated papillary thyroid cancer, heavy lung involvement, and cerebral metastases. 124I PET was used for pharmacokinetics. Calculation of the recommended administered activity, based on lung toxicity constraints, was performed in real time (i.e., during the data-acquisition interval). The results were available to the physician in time to influence treatment; these estimates were compared with conventional dosimetry methodologies. In subsequent, retrospective analyses, the 3D-RD calculations were expanded to include additional tumor dose estimates, and the conventional methodologies were reexamined to reveal the causes of the differences observed. A higher recommended administered activity than by an S-value–based method with a favorable clinical outcome was obtained. This approach permitted more aggressive treatment while adhering to patient-specific lung toxicity constraints. A retrospective analysis of the conventional methodologies with appropriate corrections yielded absorbed dose estimates consistent with 3D-RD.

Integration of Infarct Size, Tissue Perfusion and Metabolism by Hybrid Cardiac PET–CT–Evaluation in a Porcine Model of Myocardial Infarction

Background—Hybrid positron emission tomography/computed tomography (PET-CT) allows for combination of PET perfusion/metabolism imaging with infarct detection by CT delayed contrast enhancement. We used this technique to obtain biomorphological insights into the interrelation between tissue damage, inflammation, and microvascular obstruction early after myocardial infarction. Methods and Results—A porcine model of left anterior descending coronary artery occlusion/reperfusion was studied. Seven animals underwent PET-CT within 3 days of infarction, and a control group of 3 animals was scanned at >4 weeks. Perfusion and glucose uptake were assessed by [13N]-ammonia/[18F]-deoxyglucose (FDG), and 64-slice CT delayed contrast enhancement was measured. In the acute infarct model, CT revealed a no-reflow phenomenon suggesting microvascular obstruction in 80% of all infarct segments. PET showed increased FDG uptake in 68% of the CT-defined infarct segments. Ex vivo staining and histology showed active inflammation in the acute infarct area as an explanation for increased glucose uptake. In chronic infarction, CT showed no microvascular obstruction and agreed well with matched perfusion/metabolism defects on PET. Conclusions—Perfusion/metabolism PET and delayed enhancement CT can be combined within a single hybrid PET-CT session. Increased regional FDG uptake in the acute infarct area is frequently observed. In contrast to the chronic infarct setting, this indicates tissue inflammation that is commonly associated with microvascular obstruction as identified by no reflow on CT. The consequences of these pathophysiological findings for subsequent ventricular remodeling should be explored in further studies.

Prospective Evaluation of 99mTc-sestamibi SPECT/CT for the Diagnosis of Renal Oncocytomas and Hybrid Oncocytic/Chromophobe Tumors

UNLABELLED Nuclear imaging offers a potential noninvasive means of determining the histology of renal tumors. The aim of this study was to evaluate the accuracy of technetium-99m ((99m)Tc)-sestamibi single-photon emission computed tomography/x-ray computed tomography (SPECT/CT) for the differentiation of oncocytomas and hybrid oncocytic/chromophobe tumors (HOCTs) from other renal tumor histologies. In total, 50 patients with a solid clinical T1 renal mass were imaged with (99m)Tc-sestamibi SPECT/CT prior to surgical resection. Preoperative SPECT/CT scans were reviewed by two blinded readers, and their results were compared with centrally reviewed surgical pathology data. Following surgery, 6 (12%) tumors were classified as renal oncocytomas and 2 (4%) as HOCTs. With the exception of 1 (2%) angiomyolipoma, all other tumors were renal cell carcinomas (82%). (99m)Tc-sestamibi SPECT/CT correctly identified 5 of 6 (83.3%) oncocytomas and 2 of 2 (100%) HOCTs, resulting in an overall sensitivity of 87.5% (95% confidence interval [CI], 47.4-99.7%). Only two tumors were falsely positive on SPECT/CT, resulting in a specificity of 95.2% (95% CI, 83.8-99.4%). In summary, (99m)Tc-sestamibi SPECT/CT is a promising imaging test for the noninvasive diagnosis of renal oncocytomas and HOCTs. PATIENT SUMMARY We found that the imaging test (99m)Tc-sestamibi SPECT/CT can be used to accurately diagnose two types of benign kidney tumors. This test may be eventually used to help better evaluate patients diagnosed with a renal tumor.

White Paper Report of the RAD-AID Conference on International Radiology for Developing Countries: Identifying Challenges, Opportunities, and Strategies for Imaging Services in the Developing World

The RAD-AID Conference on International Radiology for Developing Countries was an assembly of individuals and organizations interested in improving access to medical imaging services in developing countries where the availability of radiology has been inadequate for both patient care and public health programs. The purpose of the meeting was to discuss data, experiences, and models pertaining to radiology in the developing world and to evaluate potential opportunities for future collaboration. Conference participants included radiologists, technologists, faculty members of academic medical institutions, and leadership of nongovernmental organizations involved in international health care and social entrepreneurship. Four main themes from the conference are presented in this white paper as important factors for the implementation and optimization of radiology in the developing world: (1) ensuring the economic sustainability of radiologic services through financial and administrative training support of health care personnel; (2) designing, testing, and deploying clinical strategies adapted for regions with limited resources; (3) structuring and improving the role of American radiology residents interested in global health service projects; and (4) implementing information technology models to support digital imaging in the developing world.

Advances in PET myocardial perfusion imaging: F-18 labeled tracers.

Coronary artery disease and its related cardiac disorders represent the most common cause of death in the USA and Western world. Despite advancements in treatment and accompanying improvements in outcome with current diagnostic and therapeutic modalities, it is the correct assignment of these diagnostic techniques and treatment options which are crucial. From a diagnostic standpoint, SPECT myocardial perfusion imaging (MPI) using traditional radiotracers like thallium-201 chloride, Tc-99m sestamibi or Tc-99m tetrofosmin is the most utilized imaging technique. However, PET MPI using N-13 ammonia, rubidium-82 chloride or O-15 water is increasing in availability and usage as a result of the growing number of medical centers with new-generation PET/CT systems taking advantage of the superior imaging properties of PET over SPECT. The routine clinical use of PET MPI is still limited, in part because of the short half-life of conventional PET MPI tracers. The disadvantages of these conventional PET tracers include expensive onsite production and inconvenient on-scanner tracer administration making them unsuitable for physical exercise stress imaging. Recently, two F-18 labeled radiotracers with longer radioactive half-lives than conventional PET imaging agents have been introduced. These are flurpiridaz F 18 (formerly known as F-18 BMS747158-02) and F-18 fluorobenzyltriphenylphosphonium. These longer half-life F-18 labeled perfusion tracers can overcome the production and protocol limitations of currently used radiotracers for PET MPI.

Stable Delineation of the Ischemic Area by the PET Perfusion Tracer 18F-Fluorobenzyl Triphenyl Phosphonium After Transient Coronary Occlusion

18F-fluorobenzyl triphenyl phosphonium (FBnTP) has recently been introduced as a myocardial perfusion PET agent. We used a rat model of transient coronary occlusion to determine the stability of the perfusion defect size over time and the magnitude of redistribution. Methods: Wistar rats (n = 15) underwent thoracotomy and 2-min occlusion of the left coronary artery (LCA), followed by reperfusion. During occlusion, 18F-FBnTP (92.5 MBq) and 201Tl-thallium chloride (0.74 MBq) were injected intravenously. One minute before the animals were sacrificed at 5, 45, and 120 min after reperfusion, the LCA was occluded again and 2% Evans blue was injected intravenously to determine the ischemic territory. The hearts were excised, frozen, and sliced for serial dual-tracer autoradiography and histology. Dynamic in vivo 18F-FBnTP PET was performed on a subgroup of animals (n = 4). Results: 18F-FBnTP showed stable ischemic defects at all time points after tracer injection and reperfusion. The defects matched the blue dye defect (y = 0.97x+1.5, R2 = 0.94, y = blue-dye defect, x = 18F-FBnTP defect). Count density analysis showed no defect fill-in at 45 min but slightly increased activity at 120 min (LCA/remote uptake ratio = 0.19 ± 0.02, 0.19 ± 0.05, and 0.34 ± 0.06 at 5, 45, and 120 min, respectively, P < 0.05). For comparison, 201Tl showed complete redistribution at 120 min (LCA/remote = 0.42 ± 0.04, 0.72 ± 0.03, and 0.97 ± 0.05 at 5, 45, and 120 min, respectively, P < 0.001). Persistence of the 18F-FBnTP defect over time was confirmed by in vivo dynamic small-animal PET. Conclusion: In a transient coronary occlusion model, perfusion defect size using the new PET agent 18F-FBnTP remained stable for at least 45 min and matched the histologically defined ischemic area. This lack of significant redistribution suggests a sufficient time window for future clinical protocols with tracer injection remote from the scanner, such as in a stress testing laboratory or chest pain unit.

Lowering radiation dose for integrated assessment of coronary morphology and physiology: First experience with step-and-shoot CT angiography in a rubidium 82 PET-CT protocol

AbstractBackground. Reduction of radiation exposure from computed tomography coronary angiography (CTA) will be a key factor for more liberal use in cardiac hybrid positron emission tomography (PET)-computed tomography (CT). We report our initial experience with a new algorithm for low-dose CTA based on a prospectively gated step-and-shoot technique. This limits acquisition to the diastolic phase and minimizes exposure time versus the previous standard of retrospectively gated helical acquisitions. Methods and Results. In 15 consecutive patients referred for integrated functional and morphologic workup by rubidium 82 perfusion PET-CTA, step-and-shoot CTA (SnapShot Pulse; GE Medical Systems) (120 kV, 600–800 mA) was acquired on a 64-slice GE Discovery Rx VCT PET-CT scanner and compared with a group of patients with conventional helical CTA (120 kV, with modulation of the milliampere level) who were matched with regard to clinical variables. Effective dose was estimated from dose-length product. The American Heart Association 15-segment coronary tree model was used to determine study interpretability. Potential for fusion with Rb-82 perfusion PET was tested by use of commercial software. In addition, direct dose measurements were conducted by use of an anthropomorphic phantom for more accurate dosimetry. The dose-length product-derived effective patient dose for step-and-shoot and helical CTA was 5.5±0.1 mSv versus 20.5±3.5 mSv (P<.0001). The mean number of evaluable segments per patient for the best phase of helical CTA was 12.5±2.8 (83.3%±18.7%) versus 13.3±2.2 (88.7%±14.7%) (P=not significant vs helical) for step-and-shoot CTA. Review of multiple phases increased the number for helical CTA to 13.7±1.7 (91.3%±11.3%;P=not significant vs step-and-shoot CTA, for which this was not an option). Semiautomated fusion with corresponding PET was feasible for all studies. Phantom data confirm effective doses of 5.4 mSv for step-and-shoot CTA and 19.6 mSv for helical acquisition. Conclusions. Low-dose prospectively gated CTA reduces radiation exposure by nearly 70% versus the previous standard of helical acquisition, without significant loss in interpretability and integrative potential with Rb-82 perfusion PET. This represents a step toward a broader, routine integration of CTA and perfusion PET for assessment of coronary morphology and physiology by cardiac PET-CT.