生体数学モデルを用いたアミロイドおよびタウトレーサーのスクリーニング

Tohoku University渡部浩司課

Multi-Modality Imaging of Atheromatous Plaques in Peripheral Arterial Disease: Integrating Molecular and Imaging Markers

Peripheral artery disease (PAD) is a common and debilitating condition characterized by the narrowing of the limb arteries, primarily due to atherosclerosis. Non-invasive multi-modality imaging approaches using computed tomography (CT), magnetic resonance imaging (MRI), and nuclear imaging have emerged as valuable tools for assessing PAD atheromatous plaques and vessel walls. This review provides an overview of these different imaging techniques, their advantages, limitations, and recent advancements. In addition, this review highlights the importance of molecular markers, including those related to inflammation, endothelial dysfunction, and oxidative stress, in PAD pathophysiology. The potential of integrating molecular and imaging markers for an improved understanding of PAD is also discussed. Despite the promise of this integrative approach, there remain several challenges, including technical limitations in imaging modalities and the need for novel molecular marker discovery and validation. Addressing these challenges and embracing future directions in the field will be essential for maximizing the potential of molecular and imaging markers for improving PAD patient outcomes

Evaluation of the Feasibility of Screening Tau Radiotracers Using an Amyloid Biomathematical Screening Methodology

The purpose of this study is to evaluate the feasibility of extending a previously developed amyloid biomathematical screening methodology to support the screening of tau radiotracers during compound development. 22 tau-related PET radiotracers were investigated. For each radiotracer, in silico MLogP, Vx, and in vitro KD were input into the model to predict the in vivo K1, k2, and BPND under healthy control (HC), mild cognitive impaired (MCI), and Alzheimer’s disease (AD) conditions. These kinetic parameters were used to simulate the time activity curves (TACs) in the target regions of HC, MCI, and AD and a reference region. Standardized uptake value ratios (SUVR) were determined from the integrated area under the TACs of the target region over the reference region within a default time window of 90–110 min. The predicted K1, k2, and BPND values were compared with the clinically observed values. The TACs and SUVR distributions were also simulated with population variations and noise. Finally, the clinical usefulness index (CUI) ranking was compared with clinical comparison results. The TACs and SUVR distributions differed for tau radiotracers with lower tau selectivity. The CUI values ranged from 0.0 to 16.2, with 6 out of 9 clinically applied tau radiotracers having CUI values higher than the recommend CUI value of 3.0. The differences between the clinically observed TACs and SUVR results showed that the evaluation of the clinical usefulness of tau radiotracer based on single target binding could not fully reflect in vivo tau binding. The screening methodology requires further study to improve the accuracy of screening tau radiotracers. However, the higher CUI rankings of clinically applied tau radiotracers with higher signal-to-noise ratio supported the use of the screening methodology in radiotracer development by allowing comparison of candidate radiotracers with clinically applied radiotracers based on SUVR, with respect to binding to a single target

Biomathematical screening of amyloid radiotracers with clinical usefulness index

Introduction: To facilitate radiotracers’ development, a screening methodology using a biomathematicalmodel and clinical usefulness index (CUI) was proposed to evaluate radiotracers’ diagnosticcapabilities.Methods: A total of 31 amyloid positron emission tomography radiotracers were evaluated. A previouslydeveloped biomathematical model was used to simulate 1000 standardized uptake valueratios with population and noise simulations, which were used to determine the integrated receiveroperating characteristics curve (Az), effect size (Es), and standardized uptake value ratio (Sr) ofconditions-pairs of healthy control–mild cognitive impaired and mild cognitive impaired–Alzheimer’s disease. CUI was obtained from the product of averaged AzðAzÞ, EsðEsÞ, and SrðSrÞ.Results: The relationships of Az, Es, and Sr with CUI were different, suggesting that they assesseddifferent radiotracer properties. The combination of Az, Es, and Sr complemented each other and resultedin CUI of 0.10 to 5.72, with clinically applied amyloid positron emission tomography radiotracershaving CUI greater than 3.0.Discussion: The CUI rankings of clinically applied radiotracers were close to their reported clinicalresults, attesting to the applicability of the screening methodology

Comparison of metrics for the evaluation of medical segmentations using prostate MRI dataset

10.1016/j.compbiomed.2021.104497Computers in Biology and Medicine13410449

Improved amyloid burden quantification with nonspecific estimates using deep learning

10.1007/s00259-020-05131-zEUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING4861842-185