Co- registration of MRI- defined White Matter Lesions with Ex- Vivo Histopathology

ABSTRACT
In older adults hyperintense signal is often found in the cerebral white matter on T2-weighted magnetic resonance imaging. These white matter lesions are found to be clinically associated with a cognitive, mood, and functional disturbances. These lesions are believed to have heterogenous origin, including both inflammatory and ischemic components. However, histopathologic correlations are limited since the WMLs are only seen on in-vivo scans and not on the postmortem ex-vivo MRI. Thus, alignment from in-vivo to ex-vivo MRIs is essential for improved understanding of the histopathology of WMLs. In the current study we address this challenge by developing an automated alignment method to register the in-vivo MRI to ex-vivo histopathology. Further WMH histological characterization is a long term goal that this method would facilitate. We scanned subjects (N=3, age during in-vivo scan= 87 (SD 1), age at death = 91(SD 1)) in-vivo and at postmortem (left hemisphere (LH)) to obtain T1-weighted, T2-weighted fluid attenuated inversion recovery (FLAIR) 7T MRIs. The ex-vivo tissues were cut into slabs of 1cm thickness and photographs were obtained. The ex-vivo MRI LH was reoriented into the same orientation as the in-vivo LH using FSL linear affine registration (flirt). The ex-vivo LH was mirrored to also create a full-brain ex-vivo image. Both ex-vivo and in-vivo whole brains were run through the SPM segmentation feature to acquire their forward and inverse deformation fields into MNI template. Spatial normalization within SPM12 was then used to apply the deformation fields to the original images. The forward deformation fields were applied to their corresponding MRIs to normalize them to the MNI template, while the ex-vivo inverse deformation field was applied to both the in-vivo and ex-vivo MRI. This method was applied to both the FLAIR MRI and the corresponding white matter segmentations. This produced a registration across the in-vivo, ex-vivo, FLAIR and white matter hyper intensities. The alignment allows us to view the WMLs on both the ex-vivo MRI and the postmortem histology.