While these techniques are important advances in bridging micrometric microscopy and whole brain imaging, they also include limitations. For example, micro-optical sectioning tomography 11 was introduced to automatically image entire mouse brains at a resolution of ( 0.33 × 0.33 × 1 ) μ m 3.
Lefebvre et al human brain mapping manual#
Recent developments of automatic tools combined with microscopy allowed to overcome the need for manual operations, thus drastically reducing acquisition time.
However, this was a labor-intensive work, where each slice was manually placed on glass plates and corrected for cutting defects. This need was demonstrated with the Big Brain initiative, 10 where 7400 histological slides of a single human brain were cut, digitized, and stitched back together to yield an entire brain resolved at 20 μ m and totaling 1 Tb of data.
Lefebvre et al human brain mapping serial#
5 – 9 Serial histology to obtain large tissue section datasets is becoming essential to help bridge spatial scales among imaging at the cellular level and morphology at the millimeter scale. There is an increasing consensus among brain scientists toward the importance of neuronal pathways among brain regions to understand neurodegenerative diseases and brain injury. While histology has had tremendous impact on our understanding of the brain anatomy and function, observation under a microscope of a thin slice of tissue gives a very poor representation of the whole organ.
To this day, microscopic imaging of cellular tissue, commonly termed histology, remains the gold standard for histopathologists. Over the past decades, advances in this field gave rise to new imaging techniques, 1 – 4 generating new contrast information at the cellular level. Light microscopy remains the main tool used to investigate cellular structure. The high correspondence between the OCT template brain and its in vivo counterpart demonstrates the potential of whole brain histology to validate in vivo imaging. Brain labeling using the Allen brain framework showed little variation in regional brain volume among imaging modalities with no statistical differences. The OCT brain template yielded a highly detailed map of the brain structure, with a high contrast in white matter fiber bundles and was highly resemblant to the in vivo MRI template. To assess deformation caused by tissue sectioning, reconstruction algorithms, and fixation, OCT datasets were compared to both in vivo and ex vivo magnetic resonance imaging (MRI) imaging. The datasets resulted in thousands of volumetric tiles resolved at a voxel size of (4.9×4.9×6.5) μm3 stitched back together to give a three-dimensional map of the brain from which a template OCT brain was obtained. Abstract An automated serial histology setup combining optical coherence tomography (OCT) imaging with vibratome sectioning was used to image eight wild type mouse brains.
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