7 Tesla MRI Followed by Histological 3D Reconstructions in Whole-Brain Specimens

Post mortemmagnetic resonance imaging (MRI) studies on the human brain are of great interest for the validation ofin vivoMRI. It facilitates a link between functional and anatomical information available from MRIin vivoand neuroanatomical knowledge available from histology/immunocytochemistry. However, linkingin vivoandpost mortemMRI to microscopy techniques poses substantial challenges. Fixation artifacts and tissue deformation of extracted brains, as well as co registration of 2D histology to 3D MRI volumes complicate direct comparison between modalities. Moreover,post mortembrain tissue does not have the same physical properties asin vivotissue, and therefore MRI approaches need to be adjusted accordingly. Here, we present a pipeline in which whole-brain humanpost mortem in situMRI is combined with subsequent tissue processing of the whole human brain, providing a 3-dimensional reconstruction via blockface imaging. To this end, we adapted tissue processing procedures to allow bothpost mortemMRI and subsequent histological and immunocytochemical processing. For MRI, tissue was packed in a susceptibility matched solution, tailored to fit the dimensions of the MRI coil. Additionally, MRI sequence parameters were adjusted to accommodate T1 and T2*shortening, and scan time was extended, thereby benefiting the signal-to-noise-ratio that can be achieved using extensive averaging without motion artifacts. After MRI, the brain was extracted from the skull and subsequently cut while performing optimized blockface imaging, thereby allowing three-dimensional reconstructions. Tissues were processed for Nissl and silver staining, and co-registered with the blockface images. The combination of these techniques allows direct comparisons across modalities.