Zhu Jun, Freitas Hercules Rezende, Maezawa Izumi, Jin Lee-Way, Srinivasan Vivek J
Department of Biomedical Engineering, University of California Davis, Davis, CA, 95616, USA.
Department of Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, CA, 95817, USA.
Light Sci Appl. 2021 Jul 14;10(1):145. doi: 10.1038/s41377-021-00586-7.
In vivo, minimally invasive microscopy in deep cortical and sub-cortical regions of the mouse brain has been challenging. To address this challenge, we present an in vivo high numerical aperture optical coherence microscopy (OCM) approach that fully utilizes the water absorption window around 1700 nm, where ballistic attenuation in the brain is minimized. Key issues, including detector noise, excess light source noise, chromatic dispersion, and the resolution-speckle tradeoff, are analyzed and optimized. Imaging through a thinned-skull preparation that preserves intracranial space, we present volumetric imaging of cytoarchitecture and myeloarchitecture across the entire depth of the mouse neocortex, and some sub-cortical regions. In an Alzheimer's disease model, we report that findings in superficial and deep cortical layers diverge, highlighting the importance of deep optical biopsy. Compared to other microscopic techniques, our 1700 nm OCM approach achieves a unique combination of intrinsic contrast, minimal invasiveness, and high resolution for deep brain imaging.
在活体小鼠大脑的深层皮质和皮质下区域进行微创显微镜检查一直具有挑战性。为应对这一挑战，我们提出了一种活体高数值孔径光学相干显微镜（OCM）方法，该方法充分利用了1700nm左右的水吸收窗口，在此窗口下大脑中的弹道衰减最小。对包括探测器噪声、过量光源噪声、色散以及分辨率与散斑权衡等关键问题进行了分析和优化。通过保留颅内空间的薄颅骨制备进行成像，我们展示了小鼠新皮层及一些皮质下区域整个深度的细胞结构和髓鞘结构的体积成像。在阿尔茨海默病模型中，我们报告了浅层和深层皮质层的研究结果存在差异，突出了深部光学活检的重要性。与其他显微技术相比，我们的1700nm OCM方法实现了固有对比度、最小侵入性和高分辨率用于深部脑成像的独特组合。
