Identifying Mild Alzheimer's Disease With First 30-Min 11C-PiB PET Scan

Abstract

Introduction11C-labeled Pittsburgh compound B (11C-PiB) PET imaging can provide information for the diagnosis of Alzheimer's disease (AD) by quantifying the binding of PiB to β-amyloid deposition in the brain. Quantification index, such as standardized uptake value ratio (SUVR) and distribution volume ratio (DVR), has been exploited to effectively distinguish between healthy and subjects with AD. However, these measures require a long wait/scan time, as well as the selection of an optimal reference region. In this study, we propose an alternate measure named amyloid quantification index (AQI), which can be obtained with the first 30-min scan without the selection of the reference region.Methods11C-labeled Pittsburgh compound B PET scan data were obtained from the public dataset “OASIS-3”. A total of 60 mild subjects with AD and 60 healthy controls were included, with 50 used for training and 10 used for testing in each group. The proposed measure AQI combines information of clearance rate and mid-phase PIB retention in featured brain regions from the first 30-min scan. For each subject in the training set, AQI, SUVR, and DVR were calculated and used for classification by the logistic regression classifier. The receiver operating characteristic (ROC) analysis was performed to evaluate the performance of these measures. Accuracy, sensitivity, and specificity were reported. The Kruskal–Wallis test and effect size were also performed and evaluated for all measures. Then, the performance of three measures was further validated on the testing set using the same method. The correlations between these measures and clinical MMSE and CDR-SOB scores were analyzed.ResultsThe Kruskal–Wallis test suggested that AQI, SUVR, and DVR can all differentiate between the healthy and subjects with mild AD (p < 0.001). For the training set, ROC analysis showed that AQI achieved the best classification performance with an accuracy rate of 0.93, higher than 0.88 for SUVR and 0.89 for DVR. The effect size of AQI, SUVR, and DVR were 2.35, 2.12, and 2.06, respectively, indicating that AQI was the most effective among these measures. For the testing set, all three measures achieved less superior performance, while AQI still performed the best with the highest accuracy of 0.85. Some false-negative cases with below-threshold SUVR and DVR values were correctly identified using AQI. All three measures showed significant and comparable correlations with clinical scores (p < 0.01).ConclusionAmyloid quantification index combines early-phase kinetic information and a certain degree of β-amyloid deposition, and can provide a better differentiating performance using the data from the first 30-min dynamic scan. Moreover, it was shown that clinically indistinguishable AD cases regarding PiB retention potentially can be correctly identified.

New Insights into Brain Imaging Methods for Rehabilitation of Brain Diseases

“…Neurosci. 70, 1244-1254 Zhang, S., Zhu, T., Tian, Y., Jiang, W., Li, D., and Wang, D. (2022). Early screening model for mild cognitive impairment based on resting-state functional connectivity: a functional near-infrared spectroscopy study.…”

Advances in diagnosing mild cognitive impairment and Alzheimer’s disease using 11C-PIB- PET/CT and common neuropsychological tests

“…AQI was calculated linearly by combining AQI_roi of the featured brain regions, and its coefficients were determined by linear regression. AQI measured the difference between PiB retention and brain tracer clearance with higher accuracy and sensitivity than SUVR and DVR ( Shen et al, 2022 ). A combination of AQI with magnetic resonance imaging (MRI) can be used to predict the progression of MCI with higher accuracy than that with AQI alone ( Patel et al, 2020 ).…”

Friends and Foes in Alzheimer’s Disease

“…The so-called Pittsburgh-B agent, radiolabeled with C-11 (PiB) is an FDA-approved agent that has been used in clinical practice as an amyloid-seeking radiotracer [ 81 ]. PET studies by Shen et al [ 82 ] suggest that PiB tests at 30 min after application detect “mild” AD, but its accumulation pattern in the white matter of aging individuals may interfere with appropriate interpretation in healthy individuals is poorly understood [ 83 ]. On the other hand, PiB localization has been identified before clinical evidence is present, but this appeared to be a nonspecific phenomenon for AD [ 84 ].…”