Cells are not uniformly distributed in the human cerebral cortex. Rather, they are arranged in a regional and laminar fashion that span a range of scales. Here we demonstrate an innovative imaging and analysis pipeline to construct a reliable cell census across the human cerebral cortex. Magnetic resonance imaging (MRI) is used to establish a macroscopic reference coordinate system of laminar and cytoarchitectural boundaries. Cell counting is obtained with both traditional immunohistochemistry, to provide a stereological gold-standard, and with a custom-made inverted confocal light-sheet fluorescence microscope (LSFM) for 3D imaging at cellular resolution. Finally, mesoscale optical coherence tomography (OCT) enables the registration of the distorted histological cell typing obtained with LSFM to the MRI-based atlas coordinate system.
In fetal-brain MRI, head-pose changes between prescription and acquisition present a challenge to obtaining the standard sagittal, coronal and axial views essential to clinical assessment. As motion limits acquisitions to thick slices that preclude retrospective resampling, technologists repeat~55-second stackof-slices scans (HASTE) with incrementally reoriented field of view numerous times, deducing the head pose from previous stacks. To address this inefficient workflow, we propose a robust head-pose detection algorithm using full-uterus scout scans (EPI) which take~5 seconds to acquire. Our~2-second procedure automatically locates the fetal brain and eyes, which we derive from maximally stable extremal regions (MSERs). The success rate of the method exceeds 94% in the third trimester, outperforming a trained technologist by up to 20%.The pipeline may be used to automatically orient the anatomical sequence, removing the need to estimate the head pose from 2D views and reducing delays during which motion can occur.
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