Importance The positron emission tomography (PET) tracer [¹⁸F]flortaucipir allows in vivo quantification of paired helical filament tau, a core neuropathological feature of Alzheimer disease (AD), but its diagnostic utility is unclear. Objective To examine the discriminative accuracy of [¹⁸F]flortaucipir for AD vs non-AD neurodegenerative disorders. Design, Setting, and Participants In this cross-sectional study, 719 participants were recruited from 3 dementia centers in South Korea, Sweden, and the United States between June 2014 and November 2017 (160 cognitively normal controls, 126 patients with mild cognitive impairment [MCI], of whom 65.9% were amyloid-β [Aβ] positive [ie, MCI due to AD], 179 patients with AD dementia, and 254 patients with various non-AD neurodegenerative disorders). Exposures The index test was the [¹⁸F]flortaucipir PET standardized uptake value ratio (SUVR) in 5 predefined regions of interest (ROIs). Cut points for tau positivity were determined using the mean +2 SDs observed in controls and Youden Index for the contrast AD dementia vs controls. Main Outcomes and Measures The reference standard was the clinical diagnosis determined at the specialized memory centers. In the primary analysis, the discriminative accuracy (ie, sensitivity and specificity) of [¹⁸F]flortaucipir was examined for AD dementia vs all non-AD neurodegenerative disorders. In secondary analyses, the area under the curve (AUC) of [¹⁸F]flortaucipir SUVR was compared with 3 established magnetic resonance imaging measures (hippocampal volumes and AD signature and whole-brain cortical thickness), and sensitivity and specificity of [¹⁸F]flortaucipir in MCI due to AD vs non-AD neurodegenerative disorders were determined. Results Among 719 participants, the overall mean (SD) age was 68.8 (9.2) years and 48.4% were male. The proportions of patients who were amyloid-β positive were 26.3%, 65.9%, 100%, and 23.8% among cognitively normal controls, patients with MCI, patients with AD dementia, and patients with non-AD neurodegenerative disorders, respectively. [¹⁸F]flortaucipir uptake in the medial-basal and lateral temporal cortex showed 89.9% (95% CI, 84.6%-93.9%) sensitivity and 90.6% (95% CI, 86.3%-93.9%) specificity using the threshold based on controls (SUVR, 1.34), and 96.8% (95% CI, 92.0%-99.1%) sensitivity and 87.9% (95% CI, 81.9%-92.4%) specificity using the Youden Index–derived cutoff (SUVR, 1.27) for distinguishing AD dementia from all non-AD neurodegenerative disorders. The AUCs for all 5 [¹⁸F]flortaucipir ROIs were higher (AUC range, 0.92-0.95) compared with the 3 volumetric MRI measures (AUC range, 0.63-0.75; all ROIsP < .001). Diagnostic performance of the 5 [¹⁸F]flortaucipir ROIs were lower in MCI due to AD (AUC range, 0.75-0.84). Conclusions and Relevance Among patients with established diagnoses at a memory disorder clinic, [¹⁸F]flortaucipir PET was able to discriminate AD from other neurodegenerative diseases. The accuracy and potential utility of this test in patient care require further research in clinically more representative populations.

OBJECTIVE. The aim of our study was to evaluate the usefulness of the reversed halo sign on high-resolution CT in the diagnosis of cryptogenic organizing pneumonia.MATERIALS AND METHODS. Between 1996 and 2001, we saw 31 patients with biopsy-proven cryptogenic organizing pneumonia. During the same period, we also saw 30 patients with non-cryptogenic organizing pneumonia diseases, from which cryptogenic organizing pneumonia should be differentiated: Wegener's granulomatosis (n = 14), diffuse bronchioloalveolar carcinoma (n = 10), chronic eosinophilic pneumonia (n = 5), and Churg-Strauss syndrome (n = 1). Two independent observers analyzed CT findings and recorded how frequently the so-called reversed halo sign (central ground-glass opacity and surrounding air-space consolidation of crescentic and ring shape) was seen on high-resolution CT.RESULTS. The most common patterns of parenchymal abnormalities of cryptogenic organizing pneumonia were ground-glass opacity (28/31 patients, 90%) and consolidation (27/31...

Objective: To investigate the topographical distribution of tau pathology and its effect on functional and structural changes in patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) by using ¹⁸F-AV-1451 PET. Methods: We included 20 patients with AD, 15 patients with MCI, and 20 healthy controls, and performed neuropsychological function tests, MRI, as well as ¹⁸F-florbetaben (for amyloid) and ¹⁸F-AV-1451 (for tau) PET scans. By using the regional volume-of-interest masks extracted from MRIs, regional binding values of standardized uptake value ratios and volumes were measured. We compared regional binding values among 3 diagnostic groups and identified correlations among the regional binding values, performance in each cognitive function test, and regional atrophy. Results: ¹⁸F-AV-1451 binding was increased only in the entorhinal cortex in patients with MCI, while patients with AD exhibited greater binding in most cortical regions. In the 35 patients with MCI and AD, ¹⁸F-AV-1451 binding in most of the neocortex increased with a worsening of global cognitive function. The visual and verbal memory functions were associated with the extent of ¹⁸F-AV-1451 binding, especially in the medial temporal regions. The ¹⁸F-AV-1451 binding also correlated with the severity of regional atrophy of the cerebral cortex. Conclusions: Tau PET imaging with ¹⁸F-AV-1451 could serve as an in vivo biomarker for the evaluation of AD-related tau pathology and monitoring disease progression. The accumulation of pathologic tau is more closely related to functional and structural deterioration in the AD spectrum than β-amyloid.

¹¹C-PBR28 ([methyl-¹¹C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine) is a recently developed radioligand to image peripheral benzodiazepine receptors (PBRs) in brain. The aim of this study was to estimate the human radiation doses of ¹¹C-PBR28 based on biodistribution data in monkeys and humans. In addition, we scanned 1 human subject who fortuitously behaved as if he lacked the PBR binding protein. Methods: Whole-body PBR images were acquired after intravenous bolus administration of ¹¹C-PBR28 in 7 healthy humans (651 ± 111 MBq) and 2 rhesus monkeys (370 ± 59.9 MBq). One monkey was scanned after receptor blockade with PK 11195 (10.7 mg/kg intravenously). Results: For typical subjects (subjects 1–6), the 3 organs with highest exposure were those with the high PBR densities (kidneys, spleen, and lungs), and the effective dose was 6.6 μSv/MBq. The unusual subject (subject 7) had 60%–90% less uptake in these 3 organs, resulting in 28% lower effective dose. The activity in the baseline monkey scans was greater than that in humans for organs with high PBR densities. For this reason, the human effective dose was overestimated by 60% with monkey biodistribution data. The monkey with receptor blockade had an overall distribution qualitatively similar to that of the unusual human subject (subject 7), with decreased exposure to lungs, kidney, and spleen. Conclusion: The effective dose of ¹¹C-PBR28 was modest and was similar to that of several other ¹¹C-radioligands. Lack of receptor binding in the unusual human subject and in the monkey with receptor blockade decreased exposure to organs with high PBR densities and enhanced uptake in excretory and metabolic pathways.