MR Microscopy for 3D Identification of Cortical Tubers, White Matter “Microtubers” and Radial Migration Lines in Ex Vivo Pediatric TSC with Epilepsy

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We compared 7T MRI to optical microscopy for the detection of abnormalities in two pediatric TSC + AED-refractory resection specimens. 3D reconstruction of microscopy slides is challenging because there are non-uniform shrinkage artifacts and deformations. Nevertheless, 2D optical microscopy of stained blocks enables visualization of sub-cellular structures (<10 um). At 100 um resolution, 3D MRI enables visualization of cellular layers. Thus the 2D stained blocks provide a 'ground truth' for validating the features detected via 7T protocols designed to produce optimal T1w-, T2w-, and diffusion-weighted imaging contrast. After MR acquisition, the resection en bloc specimens were sectioned and stained with/for H&E, LFB, NFP, Smi31, and GFAP. The 7T images were reconstructed into a 3D volume and manually matched to the 2D histology slides. We show that (1) both 7T MRI and optical microscopy are sufficient to visualize cortical tubers and aberrant features in the white matter, (2) a “microtuber” in 2D stained slices is coincident with radial migration lines (RMLs) in 7T imaging and (3) diffuse abnormalities persist beyond the tuber in TSC. This preliminary study demonstrates the feasibility of MR microscopy for 3D characterization of abnormalities in two pediatric TSC cases. Hence, MRI may help identify treatment response biomarkers in TSC with epilepsy. Additionally, via histology we discovered a “microtuber” in the white matter of the optic radiation, which is coincident with RMLs in MRI. Next, we will pursue 3D reconstruction of microscopy slides and higher spatial resolution MRI via limited field-of-view or super-resolution reconstruction.