Faculty Bibliography

Dual imaging with both contrast enhanced CT scan and PET-CT is recommended for evaluation of lymphoma. We compared the performance in identification and size measurements of involved lymph nodes in FDG-avid lymphomas on the low dose non-contrast enhanced CT of a PET-CT scan with those on a diagnostic contrast enhanced CT scan. The size of FDG-avid lymph nodes was measured in both the short and long axis on both the low dose non-contrast CT of the PET-CT and the contrast enhanced CT by two independent readers. A total of 307 FGD avid lymph nodes were identified in 52 patients. There was no statistically significant differences in the measured size of the nodes on the non-contrast and contrast enhanced scans (p=0.21). Baseline staging and restaging of FDG-avid lymphomas can be performed with one test, PET-CT, without an accompanying contrast enhanced CT scan, with no effect on the measured nodal size.

PURPOSE/OBJECTIVE:Positron emission tomography (PET) imaging of yttrium-90 in the liver post radioembolization has been shown useful for personalized dosimetry calculations and evaluation of extrahepatic deposition. The purpose of this study was to quantify the benefits of several MR-based data correction approaches offered by using a combined PET/MR system to improve Y-90 PET imaging. In particular, the feasibility of motion and partial volume corrections were investigated in a controlled phantom study. METHODS:The ACR phantom was filled with an initial concentration of 8 GBq of Y-90 solution resulting in a contrast of 10:1 between the hot cylinders and the background. Y-90 PET motion correction through motion estimates from MR navigators was evaluated by using a custom-built motion stage that simulated realistic amplitudes of respiration-induced liver motion. Finally, the feasibility of an MR-based partial volume correction method was evaluated using a wavelet decomposition approach. RESULTS:Motion resulted in a large (∼40%) loss of contrast recovery for the 8 mm cylinder in the phantom, but was corrected for after MR-based motion correction was applied. Partial volume correction improved contrast recovery by 13% for the 8 mm cylinder. CONCLUSIONS:MR-based data correction improves Y-90 PET imaging on simultaneous PET/MR systems. Assessment of these methods must be studied further in the clinical setting.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder most commonly associated with repetitive traumatic brain injury (TBI) and characterized by the presence of neurofibrillary tangles of tau protein, known as a tauopathy. Currently, the diagnosis of CTE can only be definitively established postmortem. However, a new positron emission tomography (PET) ligand, [18F]T807/AV1451, may provide the antemortem detection of tau aggregates, and thus various tauopathies, including CTE. Our goal was to examine [18F]T807/AV1451 retention in athletes with neuropsychiatric symptoms associated with a history of multiple concussions. Here we report a 39-year-old retired National Football League player who suffered 22 concussions and manifested progressive neuropsychiatric symptoms. Emotional lability and irritability were the chief complaints. Serial neuropsychological exams revealed a decline in executive functioning, processing speed and fine motor skills. Naming was below average but other cognitive functions were preserved. Structural analysis of longitudinally acquired magenetic resonance imaging scans revealed cortical thinning in the left frontal and lateral temporal areas, as well as volume loss in the basal ganglia. PET with [18F]florbetapir was negative for amyloidosis. The [18F]T807/AV1451 PET showed multifocal areas of retention at the cortical gray matter-white matter junction, a distribution considered pathognomonic for CTE. [18F]T807/AV1451 standard uptake value (SUV) analysis showed increased uptake (SUVr⩾1.1) in bilateral cingulate, occipital, and orbitofrontal cortices, and several temporal areas. Although definitive identification of the neuropathological underpinnings basis for [18F]T807/AV1451 retention requires postmortem correlation, our data suggest that [18F]T807/AV1451 tauopathy imaging may be a promising tool to detect and diagnose CTE-related tauopathy in living subjects.

Objectives Widespread adoption of new imaging technologies requires that diagnostic performance is maintained as technology migrates from expert sites into general use. This Blinded Independent Evaluation (BIE) study was designed to demonstrate that naive readers could be trained to interpret fluciclovine F18 (aka 18F FACBC) images with acceptable diagnostic performance and reproducibility. Methods A reader training program using standardised interpretation methodology was established following an expert consensus meeting facilitated by the SNMMI Clinical Trial Network. The BIE was conducted at the American College of Radiology Clinical Research Centre. 3 independent board-certified radiologists or nuclear medicine physicians were trained and their proficiency assessed, using training and proficiency image sets distinct from those used in the blinded read itself. Fluciclovine F18 PET-CT images (n=121) and corresponding standard of truth data (SoT), from 110 subjects with biochemical relapse of prostate cancer, were collected from Emory University, Atlanta, USA. The images were from a single time-point acquisition undertaken from the symphysis pubis to above the diaphragm starting 5 min post-injection of ~10mCi fluciclovine F18 and were acquired on a GE DLS (2D) or GE D690 (3D). The readers evaluated the images in a random sequence blinded to clinical data. Primary objectives were: i) the diagnostic performance of individual readers and overall interpretation (2/3 reader concordance) compared to SoT (histopathology and/or clinical follow-up); ii) inter-reader reproducibility. Analyses were conducted at Lesion, Region (Prostate {including bed} or Extra-Prostatic) and Subject level. Secondary objectives included comparison to the expert reader at Emory and assessment of intra-reader reproducibility. Results Table 1 shows the diagnostic performance results by reader and overall interpretation on a regional basis, using the composite SoT (histopathology and clinical follow up). The lower specificity in the Prostate region is due to the overall low number of patients with true negative disease in this region. Inter-reader agreement amongst the three readers was 94.7% , 74.4%, 70.3% for the Lesion, Prostate and Extra-Prostatic regions, respectively, with associated Fleiss' Kappa values of 0.54, 0.50 and 0.57. Intra-reader agreement was 97.8%, 96.9%, 99.1% at the Lesion level, 100%, 100%, 91.7% for the Prostate region and 83.3%, 75.0%, 83.3% for the Extra-Prostatic region. The degree of agreement between the blinded read and the on-site read of the fluciclovine F18 scans was 95.4%, 95.4% , 94.2% at the Lesion level, 90.9%, 90.1%, 76.9% for the Prostate region, 81.8%, 82.6%, 76.9% for the Extra-Prostatic region. Conclusions Use of standardised interpretation methodology and a specific training program for the assessment of fluciclovine F18 PET-CT images enables naive readers to achieve good diagnostic performance and reproducibility when staging recurrent prostate cancer patients. These finding support the wider dissemination of this technology in the future. (Table Presented)

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder resulting from repetitive mild brain trauma. Currently, the definite diagnosis of CTE is established postmortem, and diagnosis in life is complicated by symptom overlap with Alzheimer's disease (AD) and the increased risk of developing AD after repeated head injuries. We aim to determine whether neuropsychological testing and neuroimaging can provide biomarkers for diagnosing CTE in vivo. Methods: This is the clinical case of a 39-year-old retired National Football League player with a history of 22 concussions and cognitive complaints. Evaluation included neurologic and neuropsychological assessment, structural MRI, [18F]florbetapir amyloid positron emission tomography (PET) imaging, and experimental tau PET imaging with [18F]T807. Additional neuropsychological data from 2010 and a structural MRI from 2011 enabled longitudinal analysis of neuropsychological performance, cortical thickness, and subcortical volumes. Results: Cognitive performance declined from 2010-2015, especially in the domains of executive functioning, verbal fluency, and fine motor skills. Performance was below average on a naming task but was average or higher in other memory and language tests. In longitudinal structural analysis, left Broca's area and medial orbitofrontal cortex, left lateral temporal areas, and the left basal ganglia showed greatest volume losses (more than 2%), with apparent sparing of medial temporal lobe structures. PET imaging was negative for amyloid but revealed possible multifocal [18F]T807 retention, consistent with postmortem patterns of tau deposition in CTE at the junction of cortical grey matter and white matter. Conclusions: Although the definitive identification of the neuropathological retention of [18F]T807 requires postmortem correlation, our data suggest that [18F]T807 may inform future diagnostic criteria for CTE in living patients and help develop predictive biomarkers for specifying CTE from AD

We evaluated the predictive value of interim positon emission tomography (I-PET) after one course of chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients with DLBCL were enrolled. All patients had PET/computed tomography (CT) scans performed after one course of chemotherapy (PET-1). I-PET scans were categorized according to International Harmonization Project criteria (IHP), Deauville 5-point scale (D 5PS) with scores 1-3 considered negative (D 5PS > 3) and D 5PS with scores 1-4 considered negative (D 5PS = 5). Ratios of tumor maximum standardized uptake value (SUVmax) to liver SUVmax were also analyzed. We found no difference in progression-free survival (PFS) between PET-negative and PET-positive patients according to IHP and D 5PS > 3. The 2-year PFS using D 5PS = 5 was 50.9% in the PET-positive group and 84.8% in the PET-negative group (p = 0.002). A tumor/liver SUVmax cut-off of 3.1 to distinguish D 5PS scores of 4 and 5 provided the best prognostic value. PET after one course of chemotherapy was not able to safely discriminate PET-positive and PET-negative patients in different prognostic groups.

UNLABELLED:Our objective was to determine whether early change in standardized uptake values (SUVs) of 3'deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) using PET with CT could predict pathologic complete response (pCR) of primary breast cancer to neoadjuvant chemotherapy (NAC). The key secondary objective was to correlate SUV with the proliferation marker Ki-67 at baseline and after NAC. METHODS:This prospective, multicenter phase II study did not specify the therapeutic regimen, thus, NAC varied among centers. All evaluable patients underwent (18)F-FLT PET/CT at baseline (FLT1) and after 1 cycle of NAC (FLT2); 43 patients were imaged at FLT1, FLT2, and after NAC completion (FLT3). The percentage change in maximum SUV (%ΔSUVmax) between FLT1 and FLT2 and FLT3 was calculated for the primary tumors. The predictive value of ΔSUVmax for pCR was determined using receiver-operating-characteristic curve analysis. The correlation between SUVmax and Ki-67 was also assessed. RESULTS:Fifty-one of 90 recruited patients (median age, 54 y; stage IIA-IIIC) met the eligibility criteria for the primary objective analysis, with an additional 22 patients totaling 73 patients for secondary analyses. A pCR in the primary breast cancer was achieved in 9 of 51 patients. NAC resulted in a significant reduction in %SUVmax (mean Δ, 39%; 95% confidence interval, 31-46). There was a marginal difference in %ΔSUVmax_FLT1-FLT2 between pCR and no-pCR patient groups (Wilcoxon 1-sided P = 0.050). The area under the curve for ΔSUVmax in the prediction of pCR was 0.68 (90% confidence interval, 0.50-0.83; Delong 1-sided P = 0.05), with slightly better predictive value for percentage mean SUV (P = 0.02) and similar prediction for peak SUV (P = 0.04). There was a weak correlation with pretherapy SUVmax and Ki-67 (r = 0.29, P = 0.04), but the correlation between SUVmax and Ki-67 after completion of NAC was stronger (r = 0.68, P < 0.0001). CONCLUSION/CONCLUSIONS:(18)F-FLT PET imaging of breast cancer after 1 cycle of NAC weakly predicted pCR in the setting of variable NAC regimens. Posttherapy (18)F-FLT uptake correlated with Ki-67 on surgical specimens. These results suggest some efficacy of (18)F-FLT as an indicator of early therapeutic response of breast cancer to NAC and support future multicenter studies to test (18)F-FLT PET in a more uniformly treated patient population.

OBJECTIVE:Pheochromocytomas are complex tumors that require a comprehensive and systematic management plan orchestrated by a multidisciplinary team. METHODS:To achieve these ends, The Mount Sinai Adrenal Center hosted an interdisciplinary retreat where experts in adrenal disorders assembled with the aim of developing a clinical pathway for the management of pheochromocytomas. RESULTS:The result was a consensus for the diagnosis, perioperative management, and postoperative management of pheochromocytomas, with specific recommendations from our team of adrenal experts, as well as a review of the current literature. CONCLUSION/CONCLUSIONS:Our clinical pathway can be applied by other institutions directly or may serve as a guide for institution-specific management.