Faculty Bibliography

PURPOSE/OBJECTIVE:To assess the diagnostic performance of FDG-PET/MRI for the preoperative diagnosis and staging of peritoneal carcinomatosis (PC) using surgical Sugarbaker's PC index (PCI) as the reference in a multireader pilot study. METHODS:Fourteen adult patients (M/F: 3/11, mean age: 57 ± 12 year) with PC were prospectively included in this single-center study. Patients underwent FDG-PET/MRI prior to surgery (mean delay: 14 d, range: 1-63 d). Images were reviewed independently by 2 abdominal radiologists and 2 nuclear medicine physicians. The radiologists assessed contrast-enhanced abdominal MR images, while the nuclear medicine physicians assessed PET images fused with T2-weighted images. The abdomen was divided in 13 regions, scored from 0 to 3. A hybrid FDG-PET/MRI radiological PCI was created by combining the study data. Radiological PCI was compared to the surgical PCI on a per-patient and per-region basis. Inter-reader agreement was evaluated. RESULTS:Mean surgical PCI was 10 ± 8 (range: 0-24). Inter-reader agreement was almost perfect for all sets for radiologic PCI (Kappa: 0.81-0.98). PCI scores for all reading sets significantly correlated with the surgical PCI score (r range: 0.57-0.74, p range: < 0.001-0.003). Pooled per-patient sensitivity, specificity, and accuracy were 75%/50%/71.4% for MRI, 66.7%/50%/64.3% for FDG-PET, and 91.7%/50%/85.7% for FDG-PET/MRI, without significant difference (p value range 0.13-1). FDG-PET/MRI achieved 100% sensitivity and 100% specificity for a cutoff PCI of 20. Per-region sensitivity and accuracy were lower: 37%/61.8% for MRI, 17.8%/64.3% for FDG-PET, and 52.7%/60.4% for FDG-PET/MRI, with significantly higher sensitivity for FDG-PET/MRI. Per-region specificity was higher for FDG-PET (95%) compared to MRI (78.4%) and FDG-PET/MRI (66.5%). CONCLUSION/CONCLUSIONS:FDG-PET/MRI achieved an excellent diagnostic accuracy per-patient and weaker performance per-region for detection of PC. The added value of PET/MRI compared to MRI and FDG-PET remains to be determined.

PURPOSE OF REVIEW/OBJECTIVE:Myocardial viability is an important pathophysiologic concept which may have significant clinical impact in patients with left ventricular dysfunction due to ischemic heart disease. Understanding the imaging modalities used to assess viability, and the clinical implication of their findings, is critical for clinical decision-making in this population. RECENT FINDINGS/RESULTS:The ability of dobutamine echocardiography, single-photon emission computed tomography, positron emission tomography, and cardiac magnetic resonance imaging to predict functional recovery following revascularization is well-established. Despite different advantages and disadvantages for each imaging modality, each modality has demonstrated reasonable performance characteristics in identifying viable myocardium. Recent data, however, has called into question whether this functional recovery leads to improved clinical outcomes. Although the assessment of viability can be used to aid in clinical decision-making prior to revascularization, its broad application to all patients is limited by a lack of data confirming improvement in clinical outcomes. Thus, viability assessments may be best applied to select patients (such as those with increased surgical risk) and integrated with clinical, laboratory, and imaging data to guide clinical care. Future research efforts should be aimed at establishing the impact of viability on clinical outcomes.

Introduction: Pheochromocytomas (PCC) and paragangliomas (PGL) are neuroendocrine tumors arising from pluripotent neural crest stem cells and are associated with neurons of the autonomic nervous system. PCCs/PGLs are often hereditary and multifocal, and their biologic behavior and metabolic activity vary, making imaging of these tumors challenging. (1) The imaging gold standard has been 123I MIBG complemented by CT or MRI. PGLs being neuroendocrine tumors express somatostatin receptors enabling imaging with 68Ga-68 DOTA-coupled peptides such as DOTATATE. Most PGLs and PCCs are benign and slow growing, metastasis or malignant degeneration can occur. Sympathetic PGLs may hyper secrete catecholamines while parasympathetic PGLs are mostly non-secretory. Somatostatin cell surface receptor (SSR) overexpression is common in neuroendocrine tumors including PGL and PCCs. SSR type2 is the most commonly over expressed. (1) Sympathetic paragangliomas present with features of catecholamine-excess, such as headaches, palpitations, diaphoresis and hypertension. Whereas, parasympathetic paragangliomas present more commonly with mass-effect such as cranial nerve palsies, a neck mass or tinnitus.(1) Molecular genetic research to date has so far identified multiple susceptible genes for tumors of the paraganglia system, which can be classified into two groups. The pseudo hypoxic cluster is characterized by constitutive activation of hypoxia inducible factors leading to inhibition of oxidative phosphorylation and activation of glycolytic pathway via the Warburg effect -includes the succinate dehydrogenase (SDH) subunit B, C, D, complex assembly factor 2 (AF2, also called SDH5) and A, Von Hippel-Lindau disease (VHL), Hypoxia Inducible Factor (HIF) Type 2 and fumarate hydratase (FH) genes. The kinase signaling subgroup, includes characteristic mutations in RE arranged during Transfection (RET) in Multiple Endocrine Neoplasia type 2 (MEN2), Neurofibromatosis type 1 (NF1), transmembrane protein127 (TMEM127), MYC associated factor X(MAX), EGLN1 (PHD2), KIF1 and IDH1.(1) Educational Objectives: Paraganganglioma pathology. Clinical presentation of paragangliomas Morphologic and Functional imaging of paragangliomas. Case Examples: depicting paragangliomas in GA-68 DOTATATE PET/CT imaging.
Summary: Pheochromocytomas present diverse group of cancers with a varying different clinical features and presentation. Timely and correct diagnosis is of utmost importance for their management. Morphologic imaging as well as functional imaging plays important role in, the correct interpretation and localization of these tumors. Ga 68 ODTATE PET/CT can play a pivotal role for diagnosis of these tumors and can help and guide subsequent therapeutic decisions.(2)

Background: Immune checkpoint inhibitors (ICI) used in the oncologic practice of advanced hematologic and solid malignancies have reshaped the landscape of treating these illnesses, as they provide a survival benefit. ICI modulate the immune system by augmenting an antitumor lymphocytic response, which can also cause imbalances in immunologic tolerance affecting healthy tissues and manifesting in numerous immunerelated adverse events (irAEs). irAEs commonly involve the endocrine system. These complications can be life-threatening and require rapid recognition for proper management, including treatment interruption or systemic glucocorticoids. Understanding the pattern of FDG uptake from ICI-induced endocrinopathies is essential for identifying these AEs and possibly predicting who is at risk for developing AEs. The purpose of this study was to retrospectively identify the PET/CT manifestations of patients with clinically apparent irAEs.
Method(s): A retrospective review of 435 patients treated with ICI at our institution from 2011 to 2017 was performed. Clinical records were reviewed for demographics, type of cancer, ICI, duration of treatment, biochemical data, and the onset of endocrine irAEs. We reviewed FDG PET/CT scans of patients who received ICI who had a baseline scan at treatment initiation, and a follow-up scan within at least four months of documentation of endocrine irAEs.
Result(s): A total of 55 cases of endocrine adverse events were documented in 54 patients that included thyroid disorders, hypophysitis, adrenal insufficiency, and worsening hyperglycemia. Of the 54 patients, 37 were excluded because they did not have a baseline or follow PET/CT scans. Of the remaining 17 patients, four did not have any abnormalities in endocrine glands and were deemed negative. 13 patients that had adequately performed FDG PET/CT scan were found to have manifestations potentially explained by endocrine irAEs. More than one endocrine gland could be affected in each patient. PET/CT abnormalities included diffuse increased uptake in 12 patients in which 11 was clinically documented. Interval increased in the pituitary gland was found in 5 patients; however, there was no documentation of hypophysitis in those. One patient had increased adrenal uptake with documented adrenal insufficiency.
Conclusion(s): Of the 435 patients that received ICI, 54 (12.4%) patients developed endocrine irAEs. Seventeen patients had adequate PET/CT, and 13 (76.5%) had imaging manifestations that were evident by PET/CT. This preliminary data suggest that whole-body FDG PET/CT can be a useful noninvasive tool for assessing irAEs, including endocrinopathies. Adequate PET/CT acquisition should include the skull base in the field of view so that irAEs involving the pituitary gland are not missed. A baseline scan is necessary to differentiate from physiologic organ uptake from a different benign process and those related to irAEs. Association of irAEs and clinical response to ICI has been noted, and more in this regard should be evaluated not only with metabolic imaging but also with upcoming immune checkpoint expression molecular imaging that could predict treatment response and possible adverse events. More extensive data need to be analyzed to corroborate the above findings further

Purpose of Review: As medical knowledge and innovation reaches new heights, there is a growing gap in medical advancements between low- and middle-income countries (LMICs) and high-income countries (HICs). The former has lack of basic health care and preventive or diagnostic services for early cancer while the latter has access to novel diagnostic and therapeutic modalities. Recent Findings: Key to overcoming this disparity is finding ways to bridge this divide across distances and continental divides through innovative technology and sharing of knowledge by committed individuals and through public private partnerships. Many initiatives that include onsite and online training programs for regional healthcare providers have shown that the gap in medical training between HICs and LMICs can be narrowed. Summary: The following article shines a light on this disparity and provides exemplary case studies of ways in which this gap between LMICs and HICs can be bridged.

Existing surveys of radiopharmaceutical doses for U.S. nuclear medicine laboratories are of limited scope and size. Dose data are important because they can be used to benchmark individual laboratories, understand geographic variations in practice, and provide source data for societal guidelines and appropriateness criteria. Diagnostic reference levels (DRLs) and achievable administered activities (AAAs) for 13 noncardiac adult gamma camera and PET/CT examinations were derived retrospectively from American College of Radiology accreditation data (January 1, 2015, to December 31, 2017). The calculated DRL and AAA are consistent with previously published surveys. The distributions of radiopharmaceutical doses across facilities are in general consistent but show variation within a particular examination. Analysis of dose distribution suggests this variation results from differences in clinical protocols, educational gaps, and/or equipment factors. The AAA for the surveyed facilities exceeds dose ranges proposed in societal practice guidelines for several common nuclear medicine studies. Compared with similar surveys from Europe and Japan, geographic variation is observed, with some doses greater and others lower than used in the United States. Overall, radiopharmaceutical dose variation within the United States and internationally, and deviation from societal guidelines, imply that these dose-related benchmarks may be used to further standardize and improve clinical practice.

Significant advances continue in the development of cancer-specific molecular imaging agents and modalities for diagnosing, staging, and treating various cancer types. For these advances to successfully translate to widespread clinical use, both regulatory approval by the U.S. Food and Drug Administration (FDA), and completion of the reimbursement approval process with the Centers for Medicare & Medicaid Services (CMS), must be achieved. To this end, methods for expediting these processes are being addressed by both agencies. This report summarizes a one-day meeting held May 15, 2017 with officials from the National Cancer Institute (NCI), FDA, and CMS; members of the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the World Molecular Imaging Society (WMIS), the American College of Radiology (ACR), the Radiological Society of North America (RSNA), the International Society for Strategic Studies in Radiology (IS3R), the Medical Imaging and Technology Alliance (MITA), molecular imaging scientists from some major hospitals/institutions and industry representatives, who joined together to learn about the pathways of approval, coverage, and payment decisions. The meeting's focus was three-part: i) to broaden the conversation to other agents/modalities and address both the reimbursement and regulatory components; ii) to present a current view of FDA regulatory innovations in cancer imaging development, a past and present view of PET/MI agent approval processes, and a current view of CMS reimbursement protocols; and iii) to discuss scientific issues involved in orchestrating agency-required Phase III clinical trials as presented through three case examples: a PET probe targeting the prostate specific membrane antigen (PSMA) for imaging prostate cancer, an optical antibody probe for image-guided head and neck cancer surgery targeting epidermal growth factor receptor (EGFR), and ultrasonography with targeted microbubbles against a neovasculature target, kinase insert domain receptor (KDR), for ovarian cancer. Additionally, the meeting served to provide more clarity to researchers on trial design, to delineate more uniformly required steps investigators should take to successfully translate their innovations. Reported here are the meeting's discussion items and recommendations for continued honing of the approval and reimbursement processes investigators must navigate.

Aim: Determine if MR-guided FDG-PET reconstruction improves diagnostic accuracy and epileptogenic lesion localization for patients with focal epilepsy. Introduction: Abnormalities detected on MRI or FDG PET alter clinical management and prognosis in patients with focal epilepsy considering surgery (1). Concordant MRI findings are not always present, whereas -80% of adult patients with chronic seizures have FDG PET abnormalities. State-of-art FDG PET, however, remains limited by partial volume effects (PVEs) that reduce sensitivity particularly for extra-temporal epilepsy (2). MR-guided (MRG) PET reconstruction reduces PVEs (3). We tested the hypothesis that MRG PET reconstruction increases correct localization of epileptogenic lesions across readers with different levels of clinical experience.
Method(s): After IRB approval, a neuroradiologist with 1000+ brain PET interpretations identified 26 epilepsy subjects that underwent simultaneous FDG PET-MRI (Siemens Biograph mMR, Siemens Healthcare, Erlangen, Germany) with final adjudicated diagnosis either as normal (N=10) or cortical dysplasia (N=16). PET emission images were reconstructed using conventional OSEM and MRG PET reconstructions (asymmetric Bowsher prior with 3D MPRAGE as anatomical prior image). Then, 3 blinded readers (with 12, 6 & 18 years of experience; respectively) evaluated cases containing either OSEM or MRG PET in the sagittal, axial and coronal planes for each case (MRI data was not provided). Readers determined if there were focal FDG abnormalities consistent with an epileptogenic zone, then assigned ordinal values to image quality (0-3; where 3 was "excellent") and diagnostic confidence (1-3; where 3 = "definite" abnormality or normal study).
Result(s): The figure below shows coronal OSEM and MRG PET reconstructions (A & B respectively) with co-registered MRI (C) - MRG PET better demonstrated the focal FDG abnormality associated with right frontal cortical dysplasia. All 3 readers rated MRG PET images higher in overall quality (2.6 +/- 0.7 vs 2.0 +/- 0.5, Mann-Whitney test, P<0.00001). Reconstruction method did not affect diagnostic confidence (2.6 +/- 0.7 vs 2.9 +/- 0.4, Mann-Whitney test, P=0.555). Readers 2 & 3 (with less experience reading brain FDG PET), improved their localization of the seizure focus using MRG PET images from 42.9 to 75%, and 50 to 75% correct respectively. Reader 1, with the most experience, demonstrated no change in correct localization (85.7 vs 83.3%), but reported more confidence in the diagnosis (P=0.033). Global percentage correct for all 3 raters increased from 59.5% to 77.8% (chi-squared test, P=0.086). MRG PET images increased interpretation sensitivity from 69% to 75%, specificity from 70% to 83% and accuracy from 70% to 78%, but these changes did not reach statistical significance.
Conclusion(s): These initial results demonstrate that MRG PET reconstruction of FDG data can increase correct seizure localization for PET readers with less experience. Study limitations include that clinical history, anatomical correlation and non-attenuation corrected FDG PET images were not available to blinded readers. Future work will increase the number of subjects evaluated by the 3 readers to increase statistical power