Stimulated Raman scattering spectroscopic optical coherence tomography (SRS-SOCT) for label-free molecular imaging of brain tumor pathology

脑肿瘤的切除范围是影响脑肿瘤预后的重要因素之一。 延长脑癌患者的生存期。不幸的是，实现完全切除 术前确定的肿瘤区域仍然是一个重要的临床挑战。这是由于，在 部分原因是缺乏术中工具来帮助外科医生区分健康的 对神经功能和癌组织至关重要的组织。此外，没有现有的 能够识别浸润性脑癌的术中或术前临床技术 细胞我们的R21应用的目标是推进一种新的光学分子成像方法- 受激拉曼散射光谱光学相干层析成像（SRS-SOCT）-和 证明它可以克服目前识别脑肿瘤的临床局限性， 他们的利润。这种新颖的方法利用（1）空间和频谱复用能力 的SOCT实现快速，体积，分子成像与高空间分辨率;和（2） 通过振动光谱（通过SRS）提供丰富的分子信息， 在癌组织和健康组织之间（即，为疾病提供对比）。这种新型SRS-SOCT 技术克服了先前方法（包括OCT和SRS）的显著局限性 单独），并能够实现快速，高度特异性，无标记的分子成像， 识别脑肿瘤边缘本建议的目标如下：目标1，任务1侧重于 建立一个具有新型激光光源的SRS-SOCT系统，该系统提供高空间- 具有高信噪比的分辨光谱信息。目标1，任务2将推进现有的 信号处理（计算）方法，以提取复杂的，空间分辨的光谱 信息. Aim 2将使用一个良好建立的大块和浸润性脑肿瘤动物模型， 评估SRS-SOCT识别肿瘤组织的能力。最后，对于目标3，我们将进一步 验证SRS-SOCT用于使用来自冷冻切片的人类标本识别脑肿瘤， 刚切除的脑瘤由于SRS-SOCT检测来自脂质和 蛋白质，该方法也可以用于检测其他富含脂质的组织中的肿瘤，例如 乳房这项工作的成功完成将证明SRS-SOCT的潜力， 识别大块和浸润性脑肿瘤，为新型术中工具铺平道路， 具有提高神经外科手术成功率和延长患者生存期的潜力 患有恶性脑肿瘤。

The extent of resection of brain tumors is one of the most important factors associated with prolonged survival for patients with brain cancer. Unfortunately, achieving complete resection of the preoperatively-defined tumor region remains a significant clinical challenge. This is due, in part, to the lack of intraoperative tools available to help surgeons differentiate between healthy tissue that is crucial for neurological function and cancerous tissue. Further, there is no existing clinical technology, intraoperative or preoperative, that is able to identify infiltrative brain cancer cells. The goal of our R21 application is to advance a novel optical molecular imaging method— stimulated Raman scattering spectroscopic optical coherence tomography (SRS-SOCT)—and demonstrate that it can overcome current clinical limitations for identifying brain tumors and their margins. This novel approach leverages (1) the spatial and spectral multiplexing capabilities of SOCT to achieve fast, volumetric, molecular imaging with high spatial resolution; and (2) the rich molecular information provided by vibrational spectroscopy (via SRS) to clearly differentiate between cancerous and healthy tissues (i.e., provide contrast for disease). This novel SRS-SOCT technology overcomes significant limitations of previous methods (including OCT and SRS alone), and enables fast, highly-specific, label-free molecular imaging that is uniquely suited for identifying brain tumor margins. The aims for this proposal are as follows: Aim 1, task 1 focuses on building an SRS-SOCT system with a novel laser light source that provides high spatially- resolved spectral information with high signal-to-noise ratio. Aim 1, task 2 will advance existing signal processing (computational) methods to extract the complex, spatially-resolved spectral information. Aim 2 will use a well-established bulk and infiltrative brain tumor animal model to evaluate the capabilities SRS-SOCT to identify tumor tissue. Finally, for Aim 3, we will further validate SRS-SOCT for identifying brain tumors using human specimens from frozen sections and freshly excised brain tumors. Because SRS-SOCT detects biochemical signatures from lipids and proteins, the method can also be of value for detecting tumors in other lipid rich tissues, such as breast. Successful completion of this work will demonstrate the potential of SRS-SOCT for identifying bulk and infiltrating brain tumors, paving the way for a novel intraoperative tool that has the potential to increase the success rate of neurosurgery and prolong survival for patients with malignant brain tumors.