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

受激拉曼散射光谱光学相干断层扫描 (SRS-SOCT) 用于脑肿瘤病理学无标记分子成像

• 批准号: 9443282
• 负责人: Francisco E Robles
• 金额: $ 18.91万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-01 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9443282
• 关键词: Address; Adipose tissue; Animal Model; Archives; Area; Autacoids; Biochemical; Brain Neoplasms; Brain Pathology; Breast; Cancerous; Clinical; Cognitive; Collaborations; Complex; Computational algorithm; Computing Methodologies; Consult; Crude Extracts; Custom; Diagnostic; Disease; Emerging Technologies; Equilibrium; Excision; Exhibits; Feedback; Fiber; Foundations; Frequencies; Frozen Sections; Generations; Glioma; Goals; Histopathology; Human; Image; Image Analysis; Impairment; Individual; Institutes; Label; Laboratories; Language; Lasers; Light; Lipids; Malignant Neoplasms; Malignant neoplasm of brain; Methods; Modeling; Molecular; Morphology; Motor; Nervous System Physiology; Neurosurgeon; Noise; Normal tissue morphology; Operative Surgical Procedures; Optical Coherence Tomography; Optics; Patients; Performance; Proteins; Protocols documentation; Rattus; Resolution; Scanning; Sensory; Services; Signal Transduction; Source; Specimen; Spectrum Analysis; Speed; Surgeon; System; Techniques; Technology; Testing; Time; Tissue Procurements; Tissues; Tumor Pathology; Tumor Tissue; Universities; Visual; Work; attenuation; base; brain tissue; brain tumor resection; cancer cell; cost effective; design; experimental study; gliosarcoma; human model; human tissue; imaging modality; improved; malignant breast neoplasm; molecular imaging; neuro-oncology; neurosurgery; new technology; novel; novel strategies; optical imaging; response; signal processing; success; tomography; tool; tumor; vibration

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.

脑肿瘤的切除范围是与脑肿瘤相关的最重要因素之一 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大的临床挑战。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者和健康者。 对神经功能和癌组织至关重要的组织。此外，目前还没有 术中或术前能够识别浸润性脑癌的临床技术 细胞。我们 R21 应用的目标是推进一种新颖的光学分子成像方法—— 受激拉曼散射光谱光学相干断层扫描 (SRS-SOCT) — 以及 证明它可以克服当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了 (1) 空间和光谱复用功能 SOCT 实现具有高空间分辨率的快速体积分子成像；和（2） 振动光谱（通过 SRS）提供丰富的分子信息，可清晰区分 癌组织和健康组织之间的对比（即提供疾病对比）。这本小说SRS-SOCT 技术克服了以前方法（包括 OCT 和 SRS 单独），并实现快速、高度特异性、无标记的分子成像，特别适合 识别脑肿瘤边缘。该提案的目标如下： 目标 1、任务 1 重点 建立具有新型激光光源的 SRS-SOCT 系统，可提供高空间- 以高信噪比解析光谱信息。目标 1、任务 2 将推进现有的 提取复杂的空间分辨光谱的信号处理（计算）方法 信息。目标 2 将使用成熟的散装和浸润性脑肿瘤动物模型来 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 使用来自冷冻切片的人体标本验证 SRS-SOCT 识别脑肿瘤的能力 刚切除的脑肿瘤。因为 SRS-SOCT 检测脂质和 蛋白质，该方法对于检测其他富含脂质的组织中的肿瘤也有价值，例如 胸部。这项工作的成功完成将展示 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了道路 有潜力提高神经外科手术的成功率并延长患者的生存期 患有恶性脑肿瘤。