Diffusion tensor MRI with tract-based spatial statistics and histology reveals undiscovered lesioned areas in kainate...

In this study, we used tract-based spatial statistics (TBSS) to analyze diffusion tensor MR imaging (DTI) data acquired from the rat brain, ex vivo, for the first time. The aim was to highlight potential changes in the whole brain anatomy in the kainic acid model of epilepsy, and further characterize the changes with histology. Increased FA was observed in dorsal endopiriform nucleus, external capsule, corpus callosum, dentate gyrus, thalamus, and optic tract. A decrease in FA was seen in the horizontal limb of the diagonal band, stria medullaris, habenula, entorhinal cortex, and superior colliculus. Some of the areas have been described in kainic acid model before. However, we also found regions that to our knowledge have not been previously reported to undergo structural changes, in this model, including stria medullaris, nucleus of diagonal band, habenula, superior colliculus, external capsule, corpus callosum, and optic tract. Four of the areas highlighted in TBSS (dentate gyrus, entorhinal cortex, thalamus and stria medullaris) were analyzed in more detail with Nissl, Timm, and myelin-stained histological sections, and with polarized light microscopy. TBSS together with targeted histology confirmed that DTI changes were associated with altered myelination, neurodegeneration, and/or calcification of the tissue. Our data demonstrate that DTI in combination with TBSS has a great potential to facilitate the discovery of previously undetected anatomical changes in animal models of brain diseases.