Stanford University Department of Structural Biology, Stanford, CA, 94304, USA.
Stanford University Department of Neurosurgery, Stanford, CA, 94304, USA.
Sci Rep. 2019 Jul 17;9(1):10388. doi: 10.1038/s41598-019-45902-9.
Current in vivo neuroimaging techniques provide limited field of view or spatial resolution and often require exogenous contrast. These limitations prohibit detailed structural imaging across wide fields of view and hinder intraoperative tumor margin detection. Here we present a novel neuroimaging technique, speckle-modulating optical coherence tomography (SM-OCT), which allows us to image the brains of live mice and ex vivo human samples with unprecedented resolution and wide field of view using only endogenous contrast. The increased visibility provided by speckle elimination reveals white matter fascicles and cortical layer architecture in brains of live mice. To our knowledge, the data reported herein represents the highest resolution imaging of murine white matter structure achieved in vivo across a wide field of view of several millimeters. When applied to an orthotopic murine glioblastoma xenograft model, SM-OCT readily identifies brain tumor margins with resolution of approximately 10 μm. SM-OCT of ex vivo human temporal lobe tissue reveals fine structures including cortical layers and myelinated axons. Finally, when applied to an ex vivo sample of a low-grade glioma resection margin, SM-OCT is able to resolve the brain tumor margin. Based on these findings, SM-OCT represents a novel approach for intraoperative tumor margin detection and in vivo neuroimaging.
目前的活体神经影像学技术提供的视野或空间分辨率有限，并且通常需要外源性对比。这些限制阻碍了在宽视场范围内进行详细的结构成像，并阻碍了术中肿瘤边界的检测。在这里，我们提出了一种新的神经影像学技术，即散斑调制光学相干断层扫描（SM-OCT），它仅使用内源性对比，就可以以前所未有的分辨率和宽视场对活鼠和离体人样本进行成像。散斑消除提供的更高可见度揭示了活鼠大脑中的白质束和皮质层结构。据我们所知，本文报告的数据代表了在活体中在几毫米的宽视场范围内实现的最高分辨率的鼠类白质结构成像。当应用于原位鼠胶质母细胞瘤异种移植模型时，SM-OCT 可以轻松识别分辨率约为 10μm 的脑肿瘤边界。离体人颞叶组织的 SM-OCT 显示出精细的结构，包括皮质层和有髓轴突。最后，当应用于低级别胶质瘤切除边界的离体样本时，SM-OCT 能够分辨出脑肿瘤边界。基于这些发现，SM-OCT 代表了一种用于术中肿瘤边界检测和活体神经影像学的新方法。
