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.

在体内，小鼠大脑深层皮层和皮层下区域的微创显微镜一直具有挑战性。为了应对这一挑战，我们提出了一种体内高数值孔径光学相干显微镜 (OCM) 方法，该方法充分利用了 1700 nm 附近的吸水窗口，其中大脑中的弹道衰减最小化。分析和优化了关键问题，包括检测器噪声、过量光源噪声、色散和分辨率-散斑权衡。通过保留颅内空间的减薄头骨制剂进行成像，我们展示了小鼠新皮质和一些皮层下区域整个深度的细胞结构和骨髓结构的体积成像。在阿尔茨海默病模型中，我们报告了浅层和深层皮质层的发现不同，突出了深度光学活检的重要性。与其他显微技术相比，我们的 1700 nm OCM 方法实现了内在对比度、微创性和深部脑成像高分辨率的独特组合。