Speaker
Description
Background: Postmortem MRI has opened-up avenues to study brain structure at sub-millimeter ultra high-resolution revealing details not possible to observe with in vivo MRI. Here, we present a novel package (purple-mri) which performs segmentation, parcellation and registration of postmortem MRI. Additionally, we provide a framework to perform one-of-its-kind vertex-wise group-level studies linking morphometry/histopathology in common coordinate system for postmortem MRI.
Method: We developed a combined voxel- and surface-based pipeline combining deep learning with classical techniques for topology correction, cortical modeling, inflation, registration for accurate parcellation of postmortem cerebral hemispheres (Fig.1 Khandelwal et al. 2024). Moreover, using the GM/WM segmentations derived from postmortem hemisphere and FreeSurfer-processed antemortem MRI, we perform deformable image registration between the two modalities for each brain specimen. Vertex-wise thickness analysis was performed to assess tau and neuronal loss distribution in corresponding specimens of postmortem (7T at 0.3mm3; N=75) and antemortem (3T at 0.8mm3; N=49) MRI (Table 1) with AD continuum diagnosis. The semi-quantitative average tau and neuronal loss ratings were derived from histopathological examination across the brain. All analyses include age, sex, and postmortem (or antemortem) interval as covariates.
Result: Our method parcellates postmortem brain hemisphere using a variety of brain atlases even in areas with low contrast (anterior/posterior regions), profound imaging artifacts and severe atrophied brains (Fig. 1). Our registration pipeline provides one-to-one correspondence between the two modalities. For thickness/pathology associations, small sparse significant clusters in superior temporal and precuneus in antemortem MRI (N=49) were observed. However, postmortem MRI showed much stronger associations across large clusters in the temporal, entorhinal cortex, and cingulate for both the matched cases (N=49) and the full cohort (N=75), regions implicated in ADRD.
Conclusion: Purple-mri paves the way for large-scale postmortem image analysis. Stronger associations between thickness and average tau burden/neuronal loss than antemortem MRI shows that our pipeline (purple-mri) could inform the development of more precise and sensitive invivo biomarkers by mapping information from postmortem to antemortem MRI in a common reference coordinate framework just as is the norm for antemortem studies.
