Dataset Information

Visualization of ischemic stroke-related changes on 18F-THK-5351 positron emission tomography.

ABSTRACT: The 18F-THK-5351 radiotracer has been used to detect the in vivo tau protein distribution in patients with tauopathy, such as Alzheimer's disease and corticobasal syndrome. In addition, 18F-THK-5351 can also monitor neuroinflammatory process due to high affinity to astrogliosis. We aimed to explore 18F-THK-5351 distribution patterns and characteristics in patients with recent ischemic stroke.Fifteen patients received 18F-THK-5351 positron emission tomography (PET) and diffusion tensor imaging (DTI) approximately 3 months after ischemic stroke. A region of interest (ROI) was placed in the peri-ischemic area and was mirrored on the contralateral side as the control, and a proportional value was derived from the ratio of the peri-ischemic ROI value over the mirrored ROI value. Increased 18F-THK-5351 retention was observed in the areas around and remote from the stroke location. The proportional 18F-THK-5351 values were negatively correlated with the proportional fractional anisotropy values (r?=?-?0.39, P?=?0.04).18F-THK-5351 PET imaging provides a potential tool for in vivo visualization of the widespread ischemia-related changes associated with a microstructural disruption in recent ischemic stroke patients.

SUBMITTER: Huang KL

PROVIDER: S-EPMC6047954 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Visualization of ischemic stroke-related changes on <sup>18</sup>F-THK-5351 positron emission tomography.

Huang Kuo-Lun KL Hsu Jung-Lung JL Lin Kun-Ju KJ Chang Chien-Hung CH Wu Yi-Ming YM Chang Ting-Yu TY Chang Yeu-Jhy YJ Liu Chi-Hung CH Ho Meng-Yang MY Wey Shiaw-Pyng SP Yen Tzu-Chen TC Okamura Nobuyuki N Hsiao Ing-Tsung IT Lee Tsong-Hai TH

EJNMMI research 20180716 1

<h4>Background</h4>The <sup>18</sup>F-THK-5351 radiotracer has been used to detect the in vivo tau protein distribution in patients with tauopathy, such as Alzheimer's disease and corticobasal syndrome. In addition, <sup>18</sup>F-THK-5351 can also monitor neuroinflammatory process due to high affinity to astrogliosis. We aimed to explore <sup>18</sup>F-THK-5351 distribution patterns and characteristics in patients with recent ischemic stroke.<h4>Results</h4>Fifteen patients received <sup>18</su ...[more]

PMID: 30014313

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Project description:ImportancePositron emission tomography (PET) may increase the diagnostic accuracy and confirm the underlying neuropathologic changes of Alzheimer disease (AD).ObjectiveTo determine the accuracy of antemortem [18F]flortaucipir PET images for predicting the presence of AD-type tau pathology at autopsy.Design, setting, and participantsThis diagnostic study (A16 primary cohort) was conducted from October 2015 to June 2018 at 28 study sites (27 in US sites and 1 in Australia). Individuals with a terminal illness who were older than 50 years and had a projected life expectancy of less than 6 months were enrolled. All participants underwent [18F]flortaucipir PET imaging, and scans were interpreted by 5 independent nuclear medicine physicians or radiologists. Supplemental autopsy [18F]flortaucipir images and pathological samples were also collected from 16 historically collected cases. A second study (FR01 validation study) was conducted from March 26 to April 26, 2019, in which 5 new readers assessed the original PET images for comparison to autopsy.Main outcomes and measures[18F]flortaucipir PET images were visually assessed and compared with immunohistochemical tau pathology. An AD tau pattern of flortaucipir retention was assessed for correspondence with a postmortem B3-level (Braak stage V or VI) pathological pattern of tau accumulation and to the presence of amyloid-β plaques sufficient to meet the criteria for high levels of AD neuropathological change. Success was defined as having at least 3 of the 5 readers above the lower bounds of the 95% CI for both sensitivity and specificity of 50% or greater.ResultsA total of 156 patients were enrolled in the A16 study and underwent [18F]flortaucipir PET imaging. Of these, 73 died during the study, and valid autopsies were performed for 67 of these patients. Three autopsies were evaluated as test cases and removed from the primary cohort (n = 64). Of the 64 primary cohort patients, 34 (53%) were women and 62 (97%) were white; mean (SD) age was 82.5 (9.6) years; and 49 (77%) had dementia, 1 (2%) had mild cognitive impairment, and 14 (22%) had normal cognition. Prespecified success criteria were met for the A16 primary cohort. The flortaucipir PET scans predicted a B3 level of tau pathology, with sensitivity ranging from 92.3% (95% CI, 79.7%-97.3%) to 100.0% (95% CI, 91.0%-100.0%) and specificity ranging from 52.0% (95% CI, 33.5%-70.0%) to 92.0% (95% CI, 75.0%-97.8%). A high level of AD neuropathological change was predicted with sensitivity of 94.7% (95% CI, 82.7%-98.5%) to 100.0% (95% CI, 90.8%-100.0%) and specificity of 50.0% (95% CI, 32.1%-67.9%) to 92.3% (95% CI, 75.9%-97.9%). The FR01 validation study also met prespecified success criteria. Addition of the supplemental autopsy data set and 3 test cases, which comprised a total of 82 patients and autopsies for both the A16 and FR01 studies, resulted in improved specificity and comparable overall accuracy. Among the 156 enrolled participants, 14 (9%) experienced at least 1 treatment-emergent adverse event.Conclusions and relevanceThis study's findings suggest that PET imaging with [18F]flortaucipir could be used to identify the density and distribution of AD-type tau pathology and the presence of high levels of AD neuropathological change, supporting a neuropathological diagnosis of AD.

Dataset Information

Visualization of ischemic stroke-related changes on 18F-THK-5351 positron emission tomography.

Publications

Visualization of ischemic stroke-related changes on <sup>18</sup>F-THK-5351 positron emission tomography.

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