Real-time histopathology for intra-operative tumor margin delineation

术中肿瘤边缘勾画的实时组织病理学

• 批准号: 9268434
• 负责人: Christian Freudiger
• 金额: $ 28.09万
• 依托单位: INVENIO IMAGING INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9268434
• 关键词: Area; Biological; Biopsy; Biopsy Specimen; Brain; Brain Neoplasms; Characteristics; Clinical; Collaborations; Color; Custom; Data; Development; Devices; Diagnosis; Disease; Dyes; Effectiveness; Engineering; Excision; Eye; Feedback; Fiber; Glioma; Goals; Gold; Grant; Histologic; Histology; Histopathology; Image; Imaging Device; Infiltration; Investigation; Label; Laboratories; Lasers; Medical; Medical Device; Metastatic malignant neoplasm to brain; Microscope; Microscopic; Microscopy; Molecular; Mosaicism; Navigation System; Neurologic Deficit; Operative Surgical Procedures; Outcome; Patients; Phase; Preparation; Primary Brain Neoplasms; Prognostic Factor; Quality of life; Recurrence; Regulation; Resectable; Resolution; Safety; Sampling; Scheme; Science; Sensitivity and Specificity; Side; Silicon; Slide; Specimen; Spectrum Analysis; Speed; Staining method; Stains; Sterility; Suction; Surgeon; Surgically-Created Resection Cavity; System; Techniques; Testing; Time; Tissue imaging; Tissues; Translational Research; Validation; Work; base; biomaterial compatibility; blind; brain surgery; brain tissue; clinical imaging; clinical translation; design; diagnostic accuracy; ex vivo imaging; experience; graphical user interface; imaging system; improved; innovation; instrument; microscopic imaging; new technology; novel; prototype; public health relevance; translational medicine; tumor; vibration

 DESCRIPTION (provided by applicant): Surgical resection is the cornerstone treatment for the majority of the 20,000 primary brain tumors and 250,000 brain metastases diagnosed each year in the US. Extent of resection is an important prognostic factor, as most tumor recurrence is in or near the resection cavity. Unfortunately, safely maximizing the extent of resection remains a challenge, in part due to the difficulty of differentiating tumor from normal brain tissue. Consequently, suboptimal surgical outcomes are common for brain tumor patients. A recent study showed that among patients with safely resectable tumors, complete resection was achieved in only 23.5% of patients. Stimulated Raman Scattering (SRS) microscopy, co-developed by the technical Co-PI Dr. Freudiger, allows label- free imaging of biological tissues based on the intrinsic vibrational spectroscopy of their molecular components (Science 322, 1857 (2008)). In collaboration with clinical Co-PI Dr. Orringer we recently demonstrated SRS microscopy enables rapid histology with image quality and diagnostic accuracy comparable to gold-standard H&E staining but without the time delay caused by tissue sectioning and dye staining (Science Translational Medicine 5, 201 (2013)). Compared to other techniques under investigation, SRS produces the best image quality, and, consequently the highest sensitivity and specificity for detecting tumor infiltration. The overall goal for this Phase 2 grant is to develop the first FDA cleared clinical SRS instrument, based on the validated prototype incorporating our custom fiber-laser. This innovation will lead to the introduction of a novel technology to improve the safety and accuracy of brain tumor surgery. Specifically, we will establish quality systems for design and assembly according to federal regulations (21CRF820). We will then design the clinical SRS instrument to overcome the limitations of the prototype, i.e. improve the imaging speed for multi-color mosaic imaging, automate the sample loading scheme, modify the form factor, include design controls for compliance with electrical and laser safety standards, develop a simple graphical user interface, and develop a sterile consumable. We will work with an independent test laboratory to demonstrate safety according to the IEC60601 standard for medical devices and the IEC60825 standard for laser products. The clinical Co-PI will validate the effectiveness by performing a blind-read study comparing SRS imaging to the gold- standard H&E histopathology. Biocompatibility of the consumable will be demonstrated by compliance with ISO10993. As the final goal, we will work with an experienced regulatory consultant to obtain FDA clearance for the product.

 描述（由申请人提供）：手术切除是美国每年诊断的20，000例原发性脑肿瘤和250，000例脑转移瘤中大多数的基础治疗。切除范围是一个重要的预后因素，因为大多数肿瘤复发是在或附近的切除腔。不幸的是，安全地最大化切除范围仍然是一个挑战，部分原因是难以区分肿瘤和正常脑组织。因此，次优手术结局对于脑肿瘤患者是常见的。最近的一项研究表明，在可安全切除肿瘤的患者中，仅23.5%的患者实现了完全切除。受激拉曼散射（SRS）显微术由技术合作者Dr. Freudiger共同开发，允许基于生物组织分子组分的固有振动光谱对生物组织进行无标记成像（Science 322，1857（2008））。Orringer博士最近与临床合作PI合作，证明SRS显微镜能够快速组织学，图像质量和诊断准确性与金标准H&E染色相当，但没有组织切片和染料染色引起的时间延迟（Science Translational Medicine 5，201（2013））。与其他正在研究的技术相比，SRS产生最好的图像质量，因此检测肿瘤浸润的灵敏度和特异性最高。第二阶段拨款的总体目标是开发第一个FDA批准的临床SRS仪器，基于经过验证的原型，并结合我们的定制光纤激光器。这一创新将导致引入一种新技术，以提高脑肿瘤手术的安全性和准确性。具体而言，我们将根据联邦法规（21 CRF 820）建立设计和组装质量体系。然后，我们将设计临床SRS仪器，以克服原型的局限性，即提高多色马赛克成像的成像速度，自动化样品加载方案，修改形状因子，包括符合电气和激光安全标准的设计控制，开发简单的图形用户界面，并开发无菌耗材。我们将与独立的测试实验室合作，根据IEC 60601医疗器械标准和IEC 60825激光产品标准证明安全性。临床Co-PI将通过进行盲读研究，将SRS成像与金标准H&E组织病理学进行比较，确认有效性。耗材的生物相容性将通过符合ISO 10993来证明。作为最终目标，我们将与经验丰富的监管顾问合作，以获得FDA对该产品的批准。