MRI Based Brain-Specific 3D-Printed Model Aligned to Stereotactic Space for Registering Histology to MRI

Studies that seek to predict the brain microstructure based on MRI require precise alignment of processed brain histology slices to the corresponding 3D MRI data. However, achieving such alignment is a challenging problem, due to tissue distortions and the different contrasts seen in MRI and the processed tissue. Here we present a pipeline for aligning a histology volume to the MRI data of the tissue and to a stereotaxic brain atlas. To this end, we segment the volume of the brain from ex-vivo MRI data, align the MRI data obtained in the native space to an MRI stereotaxic template and create a 3D printed model (a mold or cradle) that precisely fits the brain. The pipeline then makes it possible to create grooves in the 3D model, for guiding blades for cutting slabs of tissue. Placing the brain in the brain-specific 3D printed model aligns the tissue to the MRI data by default. Aligning the MRI data to an MRI stereotaxic template makes it possible to section histology slices parallel to the standard stereotaxic axes of the atlas. This facilitates comparisons to other MRI contrasts and to images of processed tissue aligned to the standard space, while maintaining the high-resolution of the tissue images along the standard stereotaxic plane. Guiding the positioning of the grooves according to species-specific anatomical information from the co-registered atlas facilitates region-specific histology. The pipeline we introduce can be used to create brain-specific sectioning models for a variety of species, including humans, primates, and rodents. To demonstrate the generalizability of the pipeline across species, we show models generated for macaques and rats.