Dentatorubrothalamic tract localization with postmortem MR diffusion tractography compared to histological 3D reconstruction

Diffusion-weighted imaging (DWI) tractography is a technique with great potential to characterize the in vivo anatomical position and integrity of white matter tracts. Tractography, however, remains an estimation of white matter tracts, and false-positive and false-negative rates are not available. The goal of the present study was to compare postmortem tractography of the dentatorubrothalamic tract (DRTT) by its 3D histological reconstruction, to estimate the reliability of the tractography algorithm in this specific tract. Recent studies have shown that the cerebellum is involved in cognitive, language and emotional functions besides its role in motor control. However, the exact working mechanism of the cerebellum is still to be elucidated. As the DRTT is the main output tract it is of special interest for the neuroscience and clinical community. A postmortem human brain specimen was scanned on a 7T MRI scanner using a diffusion-weighted steady-state free precession sequence. Tractography was performed with PROBTRACKX. The specimen was subsequently serially sectioned and stained for myelin using a modified Heidenhain-Woelke staining. Image registration permitted the 3D reconstruction of the histological sections and comparison with MRI. The spatial concordance between the two modalities was evaluated using ROC analysis and a similarity index (SI). ROC curves showed a high sensitivity and specificity in general. Highest measures were observed in the superior cerebellar peduncle with an SI of 0.72. Less overlap was found in the decussation of the DRTT at the level of the mesencephalon. The study demonstrates high spatial accuracy of postmortem probabilistic tractography of the DRTT when compared to a 3D histological reconstruction. This gives hopeful prospect for studying structure-function correlations in patients with cerebellar disorders using tractography of the DRTT.