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A major challenge in neuroscience is visualizing the structure of the human brain at different scales. Traditional histology reveals micro- and meso-scale brain features but suffers from staining variability, tissue damage, and distortion, which impedes accurate 3D reconstructions. The emerging label-free serial sectioning optical coherence tomography (S-OCT) technique offers uniform 3D imaging capability across samples but has poor histological interpretability despite its sensitivity to cortical features. Here, we present a novel 3D imaging framework that combines S-OCT with a deep-learning digital staining (DS) model. This enhanced imaging modality integrates high-throughput 3D imaging, low sample variability and high interpretability, making it suitable for 3D histology studies. We develop a novel semi-supervised learning technique to facilitate DS model training on weakly paired images for translating S-OCT to Gallyas silver staining. We demonstrate DS on various human cerebral cortex samples, achieving consistent staining quality and enhancing contrast across cortical layer boundaries. Additionally, we show that DS preserves geometry in 3D on cubic-centimeter tissue blocks, allowing for visualization of meso-scale vessel networks in the white matter. We believe that our technique has the potential for high-throughput, multiscale imaging of brain tissues and may facilitate studies of brain structures. Enhanced 3D brain imaging modality by integrating serial-sectioning OCT with semi-supervised digital staining.

The study of aging and neurodegenerative processes in the human brain requires a comprehensive understanding of cytoarchitectonic, myeloarchitectonic, and vascular structures. Recent computational advances have enabled volumetric reconstruction of the human brain using thousands of stained slices, however, tissue distortions and loss resulting from standard histological processing have hindered deformation‐free reconstruction. Here, the authors describe an integrated serial sectioning polarization‐sensitive optical coherence tomography (PSOCT) and two photon microscopy (2PM) system to provide label‐free multi‐contrast imaging of intact brain structures, including scattering, birefringence, and autofluorescence of human brain tissue. The authors demonstrate high‐throughput reconstruction of 4 × 4 × 2cm3 sample blocks and simple registration between PSOCT and 2PM images that enable comprehensive analysis of myelin content, vascular structure, and cellular information. The high‐resolution 2PM images provide microscopic validation and enrichment of the cellular information provided by the PSOCT optical properties on the same sample, revealing the densely packed fibers, capillaries, and lipofuscin‐filled cell bodies in the cortex and white matter. It is  shown that the imaging system enables quantitative characterization of various pathological features in aging process, including myelin degradation, lipofuscin accumulation, and microvascular changes, which opens up numerous opportunities in the study of neurodegenerative diseases in the future. The integrated serial sectioning polarization sensitive optical coherence tomography (PSOCT) and two‐photon microscopy (2PM) system provides label‐free imaging of birefringence (|ne − no|), scattering (µs), and autofluorescence of human brain tissue that allows for quantitative measurement of myelin content, vascular structure, and cellular information that can be applied in the study of brain aging and neurodegeneration.

This article explores issues connected with the circuit design of a device for optical diffusion tomography, which we are currently designing. We plan to use the device in experimental studies for the development of a faster method of brain hematoma detection. We reviewed currently existing methods for emergency diagnosis of hematomas, primarily the Infrascanner model 2000, for which we identified weaknesses, and outlined suggestions for improvements. This article describes the method of scanning tissues based on a triangulated arrangement of sources and receivers of optical radiation, and it discusses the optoelectronic system that implements that principle.

INTRODUCTION Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE) are tauopathies with gray matter (GM) myelin changes that are challenging to assess with standard imaging. New methods are needed to quantify myelin integrity in autopsy brain tissues. METHODS We used polarization‐sensitive optical coherence tomography (PS‐OCT) to measure bulk tissue relative retardance and birefringence microscopy for high‐resolution imaging of myelin degradation. Samples included five AD, five CTE, and four age‐matched normal controls. RESULTS When controlling for age and postmortem interval, no statistically significant differences in white matter retardance or GM myelin defect density were observed between groups. The age difference between controls (64 ± 4.7 years, mean ± SD) and disease groups (80.3 ± 7 years) emerged as an important confounding factor. Amyloid beta and tau staining showed weak correlations with myelin defects. DISCUSSION Our label‐free approach enables large‐volume imaging of brain tissue, a valuable tool for studying myelin changes in neurodegenerative diseases. Highlights Multi‐modal assessment of myelin integrity using polarization‐sensitive optical coherence tomography (PS‐OCT) and high‐resolution birefringence microscopy. Age emerged as a critical confounding factor; no significant disease differences were found. Weak correlation between myelin defects and deposition of amyloid beta/tau was found in prefrontal gray matter. Label‐free optical methods enable high‐resolution, large‐volume imaging of myelin.

INTRODUCTION Cerebrovascular alterations are associated with the pathology of Alzheimer's disease (AD). Yet, the role of these alterations is not fully understood, partly due to a paucity of data from mesoscopic vasculature (24–240 µm diameter). METHODS We used label‐free, serial‐sectioning optical coherence tomography to reconstruct mesoscopic cerebrovasculature of the dorsolateral prefrontal cortex (DLPFC) samples from AD and control subjects. We quantified three‐dimensional alterations to the vascular networks and measured the correlations between vascular alterations and deposits of amyloid β protein (Aβ) and phosphorylated tau protein (p‐tau). RESULTS The AD group had significantly reduced volume fraction, vessel length density, and branch density. There were negative trends between a subset of the vascular metrics and the density of Aβ and p‐tau. DISCUSSION AD samples in DLPFC present with significant mesoscopic cerebrovasculature alterations. This insight helps close the knowledge gap between micro‐ and macroscopic cerebrovascular pathologies. Highlights Volumetric imaging of mesoscopic cerebrovasculature with serial‐sectioning optical coherence tomography (OCT). Vascular metrics: volume fraction, length density, branch density, and tortuosity. Human ex vivo samples from dorsolateral prefrontal cortex (Alxzheimer's disease [AD] and controls). Compared to controls, AD had reduced vascularity. Serial‐sectioning OCT provides novel insights into mesoscopic cerebrovasculature.

The study of neurodegenerative processes in the human brain requires a comprehensive understanding of cytoarchitectonic, myeloarchitectonic, and vascular structures. Recent computational advances have enabled volumetric reconstruction of the human brain using thousands of stained slices, however, tissue distortions and loss resulting from standard histological processing have hindered deformation-free reconstruction of the human brain. The development of a multi-scale and volumetric human brain imaging technique that can measure intact brain structure would be a major technical advance. Here, we describe the development of integrated serial sectioning Polarization Sensitive Optical Coherence Tomography (PSOCT) and Two Photon Microscopy (2PM) to provide label-free multi-contrast imaging, including scattering, birefringence and autofluorescence of human brain tissue. We demonstrate that high-throughput reconstruction of 4×4×2cm sample blocks and simple registration of PSOCT and 2PM images enable comprehensive analysis of myelin content, vascular structure, and cellular information. We show that 2 in-plane resolution 2PM images provide microscopic validation and enrichment of the cellular information provided by the PSOCT optical property maps on the same sample, revealing the sophisticated capillary networks and lipofuscin filled cell bodies across the cortical layers. Our method is applicable to the study of a variety of pathological processes, including demyelination, cell loss, and microvascular changes in neurodegenerative diseases such as Alzheimer's disease (AD) and Chronic Traumatic Encephalopathy (CTE).