A key challenge in medical imaging is determining a precise correspondence between image properties and tissue microstructure. This comparison is hindered by disparate scales and resolutions between medical imaging and histology. We present a new technique, 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND), for registering medical images with 3D histology to overcome these limitations. Ex vivo 120 × 120 × 200 μm resolution diffusion-MRI (dMRI) data was acquired at 7 T from adult C57Bl/6 mouse hippocampus. Tissue was then optically cleared using CLARITY and stained with cellular markers and confocal microscopy used to produce high-resolution images of the 3D-tissue microstructure. For each sample, a dense array of hippocampal landmarks was used to drive registration between upsampled dMRI data and the corresponding confocal images. The cell population in each MRI voxel was determined within hippocampal subregions and compared to MRI-derived metrics. 3D-BOND provided robust voxel-wise, cellular correlates of dMRI data. CA1 pyramidal and dentate gyrus granular layers had significantly different mean diffusivity (p > 0.001), which was related to microstructural features. Overall, mean and radial diffusivity correlated with cell and axon density and fractional anisotropy with astrocyte density, while apparent fibre density correlated negatively with axon density. Astrocytes, axons and blood vessels correlated to tensor orientation.

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Macrophages in the diaphragm of fetal, growing and adult rats were investigated using electron microscopy. In addition, frozen sections of the diaphragm, muscles of the anterior abdominal wall and muscles of the calf were stained for acid phosphatase activity and examined with the light microscope. Macrophages were frequently observed in the muscles at 20 days of gestation and until the animals were 2 weeks old. They were less frequently found in the 4-week-old rats and very rarely found in the 8-week-old and adult rats. They were found in intimate contact with, sometimes apparently surrounding, certain muscle fibres which were very electron dense and considered to be degenerating. In addition, myofibrils were found as phagosomes within the macrophage cytoplasm. There was evidence to support the theory that macrophages develop from mesenchymal cells in embryonic tissue. Cells considered to be early macrophages and containing small lysosomes were found in the muscles at 16 and 18 days of gestation. In all other respects these cells resembled mesenchymal cells. It is proposed that cell death may be a normal developmental event in skeletal muscle, in which macrophages play an important role in the removal of the dead fibres.