Stable extent of recurrently active cardiac and cutaneous sarcoidosis

Background: Recurrent or persistently active sarcoidosis is a risk factor for permanent organ damage. Whether this damage is due to accumulated focal injuries or progressive disease extent is not known, as the natural history of chronic inflammation in sarcoidosis is poorly characterized. The objective of this study is to determine the pattern of disease in recurrently active sarcoidosis. Methods: We identified patients with recurrent cardiac sarcoidosis (N = 21) retrospectively from an imaging database, and with recurrent cutaneous sarcoidosis (N = 17) from a prospective registry. The longitudinal patterns of cardiac sarcoidosis were established by findings on cardiac positron emission tomography scans, and of cutaneous sarcoidosis by the validated Cutaneous Sarcoidosis Activity and Morphology Instrument clinical scoring system. Patterns of recurrent disease were compared to baseline findings. Results: Recurrent sarcoidosis occurred in a nearly identical pattern and distribution as baseline disease, and spread of disease was rarely observed for both cardiac and cutaneous sarcoidosis: 97% of heart segments positive on recurrence scans were positive on baseline scans, and only one new region of facial disease was observed. In some cases, recurrence followed years of apparent remission. Discussion: Across phenotypes, and across a long period of follow-up, the extent of sarcoidosis was stable in spite of fluctuations in disease activity. For patients with a demonstrated history of recurrent disease affecting critical organs, our findings support the need for long-term follow-up

Diagnostic Performance of the Visual Reading of 123I-Ioflupane SPECT Images With or Without Quantification in Patients With Movement Disorders or Dementia

Visual interpretation of 123I-ioflupane SPECT images has high diagnostic accuracy for differentiating parkinsonian syndromes (PS), from essential tremor and probable dementia with Lewy bodies (DLB) from Alzheimer disease. In this study, we investigated the impact on accuracy and reader confidence offered by the addition of image quantification in comparison with visual interpretation alone. Methods: We collected 304 123I-ioflupane images from 3 trials that included subjects with a clinical diagnosis of PS, non-PS (mainly essential tremor), probable DLB, and non-DLB (mainly Alzheimer disease). Images were reconstructed with standardized parameters before striatal binding ratios were quantified against a normal database. Images were assessed by 5 nuclear medicine physicians who had limited prior experience with 123I-ioflupane interpretation. In 2 readings at least 1 mo apart, readers performed either a visual interpretation alone or a combined reading (i.e., visual plus quantitative data were available). Readers were asked to rate their confidence of image interpretation and judge scans as easy or difficult to read. Diagnostic accuracy was assessed by comparing image results with the standard of truth (i.e., diagnosis at follow-up) by measuring the positive percentage of agreement (equivalent to sensitivity) and the negative percentage of agreement (equivalent to specificity). The hypothesis that the results of the combined reading were not inferior to the results of the visual reading analysis was tested. Results: A comparison of the combined reading and the visual reading revealed a small, insignificant increase in the mean negative percentage of agreement (89.9% vs. 87.9%) and equivalent positive percentages of agreement (80.2% vs. 80.1%). Readers who initially performed a combined analysis had significantly greater accuracy (85.8% vs. 79.2%; P = 0.018), and their accuracy was close to that of the expert readers in the original studies (range, 83.3%-87.2%). Mean reader confidence in the interpretation of images showed a significant improvement when combined analysis was used (P < 0.0001). Conclusion: The addition of quantification allowed readers with limited experience in the interpretation of 123I-ioflupane SPECT scans to have diagnostic accuracy equivalent to that of the experienced readers in the initial studies. Also, the results of the combined reading were not inferior to the results of the visual reading analysis and offered an increase in reader confidenc

[¹⁸F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson’s Disease

Neuroinflammation is implicated as a key pathologic mechanism in many neurodegenerative diseases and is thought to be mediated in large part by microglia, native phagocytic immune cells of the CNS. Abnormal aggregation of the protein α-synuclein after phagocytosis by microglia is one possible neuropathophysiological mechanism driving Parkinson’s disease (PD). We conducted a human pilot study to evaluate the feasibility of targeting the inducible isoform of nitric oxide synthase using the [18F]NOS radiotracer to measure neuroinflammation in idiopathic PD. Ten adults consisting of 6 PD patients and 4 healthy controls (HC) underwent one hour of dynamic [18F]NOS positron emission tomography (PET) brain imaging with arterial blood sampling. We observed increased [18F]NOS whole brain distribution volume (VT) in PD patients compared to age-matched healthy controls (p p = 0.72). These findings suggest elevated oxidative stress, a surrogate marker of inflammation, is present in early-stage idiopathic PD and indicate that [18F]NOS PET imaging is a promising, non-invasive method to measure neuroinflammation

The role of resting myocardial blood flow and myocardial blood flow reserve as a predictor of major adverse cardiovascular outcomes.

Cardiac perfusion PET is increasingly used to assess ischemia and cardiovascular risk and can also provide quantitative myocardial blood flow (MBF) and flow reserve (MBFR) values. These have been shown to be prognostic biomarkers of adverse outcomes, yet MBF and MBFR quantification remains underutilized in clinical settings. We compare MBFR to traditional cardiovascular risk factors in a large and diverse clinical population (60% African-American, 35.3% Caucasian) to rank its relative contribution to cardiovascular outcomes. Major adverse cardiovascular events (MACE), including unstable angina, non-ST and ST-elevation myocardial infarction, stroke, and death, were assessed for consecutive patients who underwent rest-dipyridamole stress 82Rb PET cardiac imaging from 2012-2015 at the Hospital of the University of Pennsylvania (n = 1283, mean follow-up 2.3 years). Resting MBF (1.1 ± 0.4 ml/min/g) was associated with adverse cardiovascular outcomes. MBFR (2.1 ± 0.8) was independently and inversely associated with MACE. Furthermore, MBFR was more strongly associated with MACE than both traditional cardiovascular risk factors and the presence of perfusion defects in regression analysis. Decision tree analysis identified MBFR as superior to established cardiovascular risk factors in predicting outcomes. Incorporating resting MBF and MBFR in CAD assessment may improve clinical decision making

Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism.

UnlabelledThe nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine binds directly to nicotinic acetylcholine receptors (nAChRs) to exert its psychoactive effects. This study examined the relationship between NMR and nAChR (α4β2* subtype) availability using PET imaging of the radiotracer 2-(18)F-fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-(18)F-FA-85380, or 2-(18)F-FA).MethodsTwenty-four smokers-12 slow metabolizers (NMR &lt; 0.26) and 12 normal metabolizers (NMR ≥ 0.26)-underwent 2-(18)F-FA-PET brain imaging after overnight nicotine abstinence (18 h before scanning), using a validated bolus-plus-infusion protocol. Availability of nAChRs was compared between NMR groups in a priori volumes of interest, with total distribution volume (VT/fP) being the measure of nAChR availability. Cravings to smoke were assessed before and after the scans.ResultsThalamic nAChR α4β2* availability was significantly reduced in slow nicotine metabolizers (P = 0.04). Slow metabolizers exhibited greater reductions in cravings after scanning than normal metabolizers; however, craving was unrelated to nAChR availability.ConclusionThe rate of nicotine metabolism is associated with thalamic nAChR availability. Additional studies could examine whether altered nAChR availability underlies the differences in treatment response between slow and normal metabolizers of nicotine