Wisse, Laura E. M.
Automated deep learning segmentation of high-resolution 7 T postmortem MRI for quantitative analysis of structure-pathology correlations in neurodegenerative diseases
Khandelwal, Pulkit, Duong, Michael Tran, Sadaghiani, Shokufeh, Lim, Sydney, Denning, Amanda, Chung, Eunice, Ravikumar, Sadhana, Arezoumandan, Sanaz, Peterson, Claire, Bedard, Madigan, Capp, Noah, Ittyerah, Ranjit, Migdal, Elyse, Choi, Grace, Kopp, Emily, Loja, Bridget, Hasan, Eusha, Li, Jiacheng, Bahena, Alejandra, Prabhakaran, Karthik, Mizsei, Gabor, Gabrielyan, Marianna, Schuck, Theresa, Trotman, Winifred, Robinson, John, Ohm, Daniel, Lee, Edward B., Trojanowski, John Q., McMillan, Corey, Grossman, Murray, Irwin, David J., Detre, John, Tisdall, M. Dylan, Das, Sandhitsu R., Wisse, Laura E. M., Wolk, David A., Yushkevich, Paul A.
Postmortem MRI allows brain anatomy to be examined at high resolution and to link pathology measures with morphometric measurements. However, automated segmentation methods for brain mapping in postmortem MRI are not well developed, primarily due to limited availability of labeled datasets, and heterogeneity in scanner hardware and acquisition protocols. In this work, we present a high resolution of 135 postmortem human brain tissue specimens imaged at 0.3 mm$^{3}$ isotropic using a T2w sequence on a 7T whole-body MRI scanner. We developed a deep learning pipeline to segment the cortical mantle by benchmarking the performance of nine deep neural architectures, followed by post-hoc topological correction. We then segment four subcortical structures (caudate, putamen, globus pallidus, and thalamus), white matter hyperintensities, and the normal appearing white matter. We show generalizing capabilities across whole brain hemispheres in different specimens, and also on unseen images acquired at 0.28 mm^3 and 0.16 mm^3 isotropic T2*w FLASH sequence at 7T. We then compute localized cortical thickness and volumetric measurements across key regions, and link them with semi-quantitative neuropathological ratings. Our code, Jupyter notebooks, and the containerized executables are publicly available at: https://pulkit-khandelwal.github.io/exvivo-brain-upenn
Regional Deep Atrophy: a Self-Supervised Learning Method to Automatically Identify Regions Associated With Alzheimer's Disease Progression From Longitudinal MRI
Dong, Mengjin, Xie, Long, Das, Sandhitsu R., Wang, Jiancong, Wisse, Laura E. M., deFlores, Robin, Wolk, David A., Yushkevich, Paul A.
Longitudinal assessment of brain atrophy, particularly in the hippocampus, is a well-studied biomarker for neurodegenerative diseases, such as Alzheimer's disease (AD). In clinical trials, estimation of brain progressive rates can be applied to track therapeutic efficacy of disease modifying treatments. However, most state-of-the-art measurements calculate changes directly by segmentation and/or deformable registration of MRI images, and may misreport head motion or MRI artifacts as neurodegeneration, impacting their accuracy. In our previous study, we developed a deep learning method DeepAtrophy that uses a convolutional neural network to quantify differences between longitudinal MRI scan pairs that are associated with time. DeepAtrophy has high accuracy in inferring temporal information from longitudinal MRI scans, such as temporal order or relative inter-scan interval. DeepAtrophy also provides an overall atrophy score that was shown to perform well as a potential biomarker of disease progression and treatment efficacy. However, DeepAtrophy is not interpretable, and it is unclear what changes in the MRI contribute to progression measurements. In this paper, we propose Regional Deep Atrophy (RDA), which combines the temporal inference approach from DeepAtrophy with a deformable registration neural network and attention mechanism that highlights regions in the MRI image where longitudinal changes are contributing to temporal inference. RDA has similar prediction accuracy as DeepAtrophy, but its additional interpretability makes it more acceptable for use in clinical settings, and may lead to more sensitive biomarkers for disease monitoring in clinical trials of early AD.