A novel method for tracking the progression of WMHs through the alignment of premortem in‐vivo to postmortem ex‐vivo MRI and histopathology

Abstract

Background White matter hyperintensities (WMHs) are neuroimaging features associated with Alzheimer’s disease (AD). Ex‐vivo studies may enable better characterization of WMHs pathological substrates. In this work, we present a novel method that leverages in‐vivo and ex‐vivo MRIs and histopathology to analyze the progression of WMHs in AD. Method A single subject’s in‐vivo MRI scans at four different time points were analyzed. Ex‐vivo scans of the brain left hemisphere were done using 16‐Tx and 32‐Rx TicTacToe coil3 and a 3‐D printed enclosure with integrated cutting guides1 (Fig. 1). The WMHs were segmented on the T2‐weighted FLAIR in‐vivo MRI 2, and registered onto the final time point via SPM’s normalized mutual information‐based algorithm. All four WMH segmentations were warped to the ex‐vivo MRI’s space by applying the deformation field from the ITK in‐vivo to ex‐vivo registration. Result The 3D printed enclosure achieved an accurate alignment between gross pathology, ex‐vivo and in‐vivo MRI (Fig. 1). Then, we computed the WMHs’ growth over time warped onto the ex‐vivo MRI (Fig. 2). This growth was quantified as the total number of voxels in each segmentation longitudinally with a quadratic fit with an R2 =0.99 (Fig. 2). Lastly, we found a significant change in the distribution of WMH segmentations over time as evident by their normalized histograms (Fig. 3). Conclusion We present a novel method to track the progression of WMHs in‐vivo to ex‐vivo MRI and gross pathology. Future studies will perform a voxel‐wise analysis on the WMHs in MRI scans, both in‐vivo and ex‐vivo, along with its histological correlates to gain insight into the underlying cellular mechanisms during the biomarker’s development. References: 1. Nadim Farhat et al. “Reusable 3D printed enclosure with integrated cutting guides for the alignment of high resolution ex‐vivo MRI with ex‐vivo gross brain photographs.” 2021 ISMRM Meeting (Under revision). 2. Wu, M. et al (2006). “A fully automated method for quantifying and localizing white matter hyperintensities on MR images.” Psychiatry Research: Neuroimaging, 148(2‐3), 133‐142. 3. T. Santini et al., “In‐vivo and numerical analysis of the eigenmodes produced by a multi‐level Tic‐Tac‐Toe head transmit array for 7 Tesla MRI,” PLoS One, vol. 13, no. 11, p. e0206127, Nov. 2018.