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.

切除脑肿瘤的程度是与 脑癌患者长期生存。不幸的是，完成了完整的切除 术前定义的肿瘤区域仍然是重大的临床挑战。这是应得的 部分，缺乏可用的术中工具来帮助外科医生区分健康 对于神经功能和取消组织至关重要的组织。此外，没有现有 临床技术，术中或术前，能够鉴定浸润性脑癌 细胞。我们的R21应用的目的是推进一种新型的光学分子成像方法 - 刺激的拉曼散射光谱光学相干断层扫描（SRS-SOCT）和 证明它可以克服当前的临床限制来识别脑肿瘤和 他们的边缘。这种新颖的方法利用（1）空间和光谱多路复用功能 SOCT以高空间分辨率实现快速，体积的，分子成像； （2） 通过振动光谱法提供的丰富分子信息（通过SRS）明确区分 在取消组织和健康组织之间（即为疾病提供对比度）。这个小说的SRS-SOCT 技术克服了以前方法的重大局限性（包括OCT和SRS 单独），并启用快速，高度特异性的无标签分子成像，非常适合 识别脑肿瘤边缘。该提案的目的如下：AIM 1，任务1重点 在构建具有新型激光源的SRS-SOCT系统时，可提供高空间 - 以高信噪比的解析光谱信息。 AIM 1，任务2将推进现有 信号处理（计算）方法以提取复合物，空间分辨光谱 信息。 AIM 2将使用完善的散装和浸润性脑肿瘤动物模型 评估SRS-SOCT的能力以鉴定肿瘤组织。最后，对于目标3，我们将进一步 验证使用冻结切片的人类标本和 新鲜出色的脑肿瘤。因为SRS-SOCT检测到脂质的生化特征 蛋白质，该方法对于检测其他富含脂质的组织中的肿瘤，例如 胸部。成功完成这项工作将证明SRS-SOCT的潜力 识别散装和浸润的脑肿瘤，为一种新型的术中工具铺平了道路 有可能提高神经外科手术的成功率和延长患者的生存率 患有恶性脑肿瘤。