Carmela Nappi

First experience of simultaneous PET/MRI for the early detection of cardiac involvement in patients with Anderson-Fabry disease

PurposeAnderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder associated with severe multiorgan dysfunction and premature death. Early diagnosis and treatment strategies play a key role in patient outcome. We investigated the potential role of hybrid PET/MR imaging in the assessment of early cardiac involvement in AFD patients.MethodsThirteen AFD patients without cardiac symptoms and with normal left ventricular function underwent simultaneous cardiac PET/MR imaging after administration of 18F-FDG. Cardiac FDG uptake was quantified by measuring the standardized uptake value in 17 myocardial segments in each subject. The coefficient of variation (COV, i.e. the standard deviation divided by the average) of the uptake of the 17 segments was calculated as an index of heterogeneity in the heart.ResultsSix patients exhibited focal late gadolinium enhancement (LGE) indicating intramyocardial fibrosis, and four of these also had positive short inversion time inversion recovery (STIR) sequences. All patients with LGE and positive STIR MR images showed focal FDG uptake in the corresponding myocardial segments indicating inflammation. Of the seven patients with negative LGE and STIR images, five showed homogeneous FDG cardiac uptake and two showed heterogeneous FDG uptake. The COV was significantly greater in patients with focal FDG uptake (0.25 ± 0.02) than in those without (0.14 ± 0.07, p < 0.01).ConclusionPET/MR imaging is clinically feasible for the early detection of cardiac involvement in patients with AFD. Further studies evaluating the role of hybrid PET/MR imaging in management of the disease in larger patient populations are warranted.

Biparametric 3T Magentic Resonance Imaging for prostatic cancer detection in a biopsy-naïve patient population: a further improvement of PI-RADS v2?

OBJECTIVES To prospectively determine the diagnostic accuracy of a biparametric 3T magnetic resonance imaging protocol (BP-MRI) for prostatic cancer detection, compared to a multiparametric MRI protocol (MP-MRI), in a biopsy naïve patient population. METHODS Eighty-two untreated patients (mean age 65±7.6years) with clinical suspicion of prostate cancer and/or altered prostate-specific antigen (PSA) levels underwent a MP-MRI, including T2-weighted imaging, diffusion-weighted imaging (with the correspondent apparent diffusion coefficient maps) and dynamic contrast enhanced sequence, followed by prostate biopsy. Two radiologists reviewed both the BP-MRI and the MP-MRI protocols to establish a radiological diagnosis. Receiver operating characteristics curves were obtained to determine the diagnostic performance of the two protocols. RESULTS The mean PSA level was 8.8±8.1ng/ml. A total of 34 prostatic tumors were identified, with a Gleason score that ranged from 3+3 to 5+4. Of these 34 tumors, 29 were located within the peripheral zone and 5 in the transitional zone. BP-MRI and MP-MRI showed a similar performance in terms of overall diagnostic accuracy, with an area under the curve of 0.91 and 0.93, respectively (p=n.s.). CONCLUSIONS BP-MRI prostate protocol is feasible for prostatic cancer detection compared to a standard MP-MRI protocol, requiring a shorter acquisition and interpretation time, with comparable diagnostic accuracy to the conventional protocol, without the administration of gadolinium-based contrast agent.

PET/MR in Children

The rapid increase in incidence of diagnosed malignant diseases in children over the last decades, combined with innovations in molecular oncology, neuroimaging, and hybrid imaging, has encouraged researchers and physicians to make a special effort in optimizing technological resources to approach pediatric patients using high-resolution imaging devices with concern about radiation exposure. In this context, a truly hybrid imaging tool, such as simultaneous positron emission tomography/magnetic resonance (PET/MR), presents the appealing advantage to combine serial image technology (MR) and a volumetric (PET) method, at the same time under the same conditions, to define and to assess a pathophysiological pattern for each disease in every single patient aiming to customize therapeutic strategy, therefore improving survival rate. Furthermore, a simultaneous approach enables to overcome some of the limitations of current PET/computed tomography (CT) scan, such as misregistration of attenuation (CT) and emission (PET) images due to spatial and temporal mismatch between CT and PET acquisitions, thus reducing artifactual false-positive result percentage. In addition, the possibility of matching two powerful modalities such as MR and PET opens the way for new challenging clinical applications for disease characterization that are currently under investigation, e.g., multiorgan disorders. In this chapter we will focus on the potential clinical role of PET/MR in pediatric diseases.

State of the Art in Cardiac Hybrid Technology: PET/MR

Simultaneous PET/MRI is an emerging technique combining two powerful imaging modalities in a single device. The wide variety of available tracers for perfusion and metabolic studies and the high sensitivity of positron emission tomography (PET) combined with the high spatial resolution and soft tissue contrast of magnetic resonance imaging (MRI) in depicting cardiac morphology and function as well as MRI’s absence of ionizing radiation makes PET/MRI very attractive to radiologists and clinicians. Nevertheless, PET/MR scientific and clinical promise is to be considered in the context of numerous technical challenges that hinder its use in the clinical setting. For example, in order for a PET system to work correctly within an MR field, major changes are required to the photon detection chain such as the elimination of photomultiplier tubes, etc. Another significant limitation of PET/MRI is the lack of an electron density map (as is the case with PET-CT) that can be readily obtained from MRI (the latter measures proton not electron density) and used to correct PET data for attenuation. Moreover, as with PET-CT, cardiac and respiratory motions cause image degradations that affect image quality and accuracy both in static and dynamic PET imaging. As a result, overcoming these (and other) technical limitations is a very active area of research both in academic institutions as well as industry. In this paper, we review recent literature on cardiac PET/MRI, present the state-of-the-art of this technology, and explore promising preclinical and clinical cardiac applications where PET/MRI could play a substantial role.

Beyond ultrasound: advances in multimodality cardiac imaging

The rapid technological evolution accomplished in noninvasive cardiac imaging techniques over the past few decades has provided physicians with a large armamentarium for the evaluation of patients with known or suspected coronary heart disease. Noninvasive assessment of coronary artery calcium or noninvasive coronary angiography may be performed using computed tomography or magnetic resonance imaging. These techniques evaluate the presence of atherosclerosis rather than ischemia. Conversely, nuclear cardiology is the most widely used noninvasive approach for the assessment of myocardial perfusion and function. These techniques coupled with the development of dedicated image fusion software packages to merge data sets from different modalities have paved the way for hybrid imaging. This article provides a description of the available noninvasive imaging techniques in the assessment of coronary anatomy, myocardial perfusion, and cardiac function in patients with known or suspected coronary heart disease.

Effect of time-of-flight and point spread function modeling on detectability of myocardial defects in PET.

PURPOSE A study was designed to investigate the impact of time-of-flight (TOF) and point spread function (PSF) modeling on the detectability of myocardial defects. METHODS Clinical FDG-PET data were used to generate populations of defect-present and defect-absent images. Defects were incorporated at three contrast levels, and images were reconstructed by ordered subset expectation maximization (OSEM) iterative methods including ordinary Poisson, alone and with PSF, TOF, and PSF+TOF. Channelized Hotelling observer signal-to-noise ratio (SNR) was the surrogate for human observer performance. RESULTS For three iterations, 12 subsets, and no postreconstruction smoothing, TOF improved overall defect detection SNR by 8.6% as compared to its non-TOF counterpart for all the defect contrasts. Due to the slow convergence of PSF reconstruction, PSF yielded 4.4% less SNR than non-PSF. For reconstruction parameters (iteration number and postreconstruction smoothing kernel size) optimizing observer SNR, PSF showed larger improvement for faint defects. The combination of TOF and PSF improved mean detection SNR as compared to non-TOF and non-PSF counterparts by 3.0% and 3.2%, respectively. CONCLUSIONS For typical reconstruction protocol used in clinical practice, i.e., less than five iterations, TOF improved defect detectability. In contrast, PSF generally yielded less detectability. For large number of iterations, TOF+PSF yields the best observer performance.

Long-Term Survival Benefit of Coronary Revascularization in Patients Undergoing Stress Myocardial Perfusion Imaging

BACKGROUND We assessed the relationship between clinical outcome and coronary revascularization according to stress-gated myocardial perfusion single-photon emission computed tomography (MPS) in an observational series of patients with suspected or known coronary artery disease (CAD), on long-term follow-up. METHODSANDRESULTS The study group consisted of 2,059 patients. During a median follow-up of 61 months, 184 events occurred (126 cardiac deaths and 58 non-fatal MI). The impact of revascularization during follow-up on event-free survival was evaluated using an extended Cox regression model, adjusting for potential clinical and MPS confounders. Revascularization was treated as a binary non-reversible time-dependent covariate. Predefined interactions tested were: (1) revascularization and summed difference score (SDS); (2) revascularization and post-stress left ventricular (LV) ejection fraction (EF); and (3) SDS and post-stress LVEF. Revascularization had a significant effect on event-free survival (adjusted HR, 0.19; P<0.001). Significant interactions were found between revascularization and SDS (P=0.045), and between LVEF and SDS (P=0.015). The protective effect of revascularization increased as SDS increased. For SDS <6 the reduction in HR was detectable only for reduced LVEF. CONCLUSIONS Both the degree of stress-induced ischemia and LVEF predict the effect of revascularization on outcome in patients with suspected or known CAD. The protective effect of revascularization appears to be greater in patients with severe ischemia and preserved LVEF.

Early Cardiac Involvement Affects Left Ventricular Longitudinal Function in Females Carrying α-Galactosidase A Mutation: Role of Hybrid Positron Emission Tomography and Magnetic Resonance Imaging and Speckle-Tracking Echocardiography

Background: Hybrid 18F-fluorodeoxyglucose (FDG) positron emission tomography and magnetic resonance imaging may differentiate mature fibrosis or scar from fibrosis associated to active inflammation in patients with Anderson-Fabry disease, even in nonhypertrophic stage. This study was designed to compare the results of positron emission tomography and magnetic resonance cardiac imaging with those of speckle-tracking echocardiography in heterozygous Anderson-Fabry disease females. Methods and Results: Twenty-four heterozygous females carrying &agr;-galactosidase A mutation and without left ventricular hypertrophy underwent cardiac positron emission tomography and magnetic resonance using 18F-FDG for glucose uptake and 2-dimensional strain echocardiography. 18F-FDG myocardial uptake was quantified by measuring the coefficient of variation (COV) of the standardized uptake value using a 17-segment model. Focal 18F-FDG uptake with COV >0.17 was detected in 13 patients, including 2 patients with late gadolinium enhancement at magnetic resonance. COV was 0.30±0.14 in patients with focal 18F-FDG uptake and 0.12±0.03 in those without (P<0.001). Strain echocardiography revealed worse global longitudinal systolic strain in patients with COV >0.17 compared with those with COV ⩽0.17 (−18.5±2.7% versus −22.2±1.8%; P=0.024). For predicting COV >0.17, a global longitudinal strain >−19.8% had 77% sensitivity and 91% specificity and a value >2 dysfunctional segments 92% sensitivity and 100% specificity. Conclusions: In females carrying &agr;-galactosidase A mutation, focal 18F-FDG uptake represents an early sign of disease-related myocardial damage and is associated with impaired left ventricular longitudinal function. These findings support the hypothesis that inflammation plays an important role in glycosphingolipids storage disorders.

Coronary atherosclerotic burden vs. coronary vascular function in diabetic and nondiabetic patients with normal myocardial perfusion: a propensity score analysis

PurposeTo assess the relationship between coronary atherosclerotic burden and vascular function in diabetic and nondiabetic patients after balancing for coronary risk factors.MethodsWe studied 672 patients without overt coronary artery disease and normal myocardial perfusion on stress 82Rb PET/CT imaging. To account for differences in baseline characteristics between diabetic patients and nondiabetic patients, we created a propensity score-matched cohort considering clinical variables and coronary risk factors.ResultsBefore matching, diabetic patients had higher coronary artery calcium (CAC) scores (p < 0.001) and lower coronary flow reserve (CFR; p < 0.001) than nondiabetic patients. After matching, CAC scores were comparable between diabetic and nondiabetic patients, but diabetic patients still had lower hyperaemic myocardial blood flow (p < 0.001) and CFR (p < 0.05). Patients were categorized by ln(CAC score) quartiles. There was a decrease in CFR with increasing CAC score quartile in both diabetic patients (p for trend < 0.01) and nondiabetic patients (p for trend < 0.005). Diabetes was associated with lower CFR across quartile categories (p < 0.002). In a multivariable linear regression analysis, CAC score was inversely related to CFR in both diabetic patients (p < 0.05) and nondiabetic patients (p < 0.001).ConclusionDiabetic patients had higher CAC scores than nondiabetic patients, but the difference disappeared when clinical characteristics were taken into account. Of note, diabetic patients also had lower CFR regardless of CAC score than nondiabetic patients after matching. Thus, coronary atherosclerotic burden and vascular function have to be seen as two different entities.

Reclassification of cardiovascular risk by myocardial perfusion imaging in diabetic patients with abnormal resting electrocardiogram

BACKGROUND AND AIMS Despite an extensive use of stress myocardial perfusion single-photon emission computed tomography (MPS), no study addressed the role of perfusion imaging in diabetic patients with abnormal resting electrocardiogram (ECG). We compared analytical approaches to assess the added value of stress MPS variables in estimating coronary heart disease outcomes in diabetic patients with abnormal resting ECG. METHODS AND RESULTS A total of 416 patients with diabetes and abnormal resting ECG who underwent stress MPS were prospectively followed up after the index study. The end point was the occurrence of a major cardiac event, including cardiac death and nonfatal myocardial infarction. At the end of follow-up (median 58 months), 42 patients experienced events. MPS data increased the predictive value of a model including traditional cardiovascular risk factors and left ventricular (LV) ejection fraction (likelihood ratio χ² from 17.54 to 24.15, p < 0.05, with a C statistic of 0.72, 95% confidence interval: 0.65-0.79). The addition of MPS data resulted in reclassification of 25% of the sample with a net reclassification improvement of 0.20 (95% confidence interval: 0.05-0.36). Overall, 63 patients were reclassified to a lower risk category, with a 5-year event rate of 3.5%, and 40 patients were reclassified to a higher risk category, with a 5-year event rate of 20%. CONCLUSION The addition of MPS findings to a model based on traditional cardiovascular risk factors and LV ejection fraction improves risk classification for incident cardiac events in diabetic patients with abnormal resting ECG.