Intra-operative confocal imaging to guide Mohs surgery

术中共聚焦成像指导莫氏手术

• 批准号: 8015350
• 负责人: MILIND RAJADHYAKSHA
• 金额: $ 68.12万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8015350
• 关键词: Aluminum; Anesthesia procedures; Area; Atlas of Cancer Mortality in the United States; Basal cell carcinoma; Bladder; Breast; Cellular Morphology; Chloride Ion; Chlorides; Clinical; Clinical Research; Confocal Microscopy; Contrast Media; Detection; Development; Diagnosis; Epidermis; Excision; Face; Freezing; Funding; Funding Opportunities; Future; Goals; Gold; Head and neck structure; Human; Image; In Situ; Incidence; Laboratories; Lateral; Left; Liver; Malignant Neoplasms; Maps; Microscope; Mohs Surgery; Morphology; Motivation; National Institute of Biomedical Imaging and Bioengineering; Normal tissue morphology; Nuclear; Operating Rooms; Operative Surgical Procedures; Optics; Oral; Pathology; Patients; Preparation; Procedures; Resolution; Scanning; Sensitivity and Specificity; Shave Biopsy; Skin; Squamous cell carcinoma; Staining method; Stains; Technology; Testing; Time; Tissues; Topical application; Translating; base; cost; image guided intervention; in vivo; instrument; instrumentation; interest; intervention program; response

DESCRIPTION (provided by applicant): The goal of this project is to translate a bench-top line-scanning confocal microscope into a clinical instrument for intra-operative imaging during Mohs surgery, and to test feasibility for detecting basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) margins on patients, using aluminum chloride as a contrast agent for staining nuclear morphology in reflectance. Reaching clinically expected sensitivity and specificity will be the quantitative milestones to validate and demonstrate a technology platform for Mohs surgery in skin and other potentially diverse intra-operative imaging applications. The motivation is to create a relatively simple, small and low-cost confocal microscope for real-time imaging in reflectance, to guide surgery in diverse settings. The proposed immediate application is intra-operative mapping of BCCs and SCCs to guide Mohs surgery. Future applications may include mapping of cancers to guide surgery in oral, head-and-neck, breast, bladder, liver and other tissues. BCCs and SCCs occur with among the highest rates of incidence, with an estimated 1.3 million new cases diagnosed and an estimated 1 million surgeries performed every year in the USA alone. Surgery is guided by frozen pathology which is labor-intensive and time-consuming. Confocal microscopy images nuclear detail in vivo and thus may enable intra-operative mapping directly on the patient in real-time. Rapid examination of cancer margins may be performed on surgically exposed tissue in situ, to guide accurate and complete excision, while preserving surrounding normal tissue. The imaging may serve as an adjunct to pathology for guiding surgery, while saving labor and cost. Patients may benefit with more efficient procedures, less anesthesia and less time in the operating room. Preliminary results demonstrate the feasibility of detecting BCCs, with topically applied aluminum chloride to enhance cancer-to-normal tissue contrast, in surgically-exposed shave-biopsy wounds in situ on patients. Furthermore, a laboratory bench-top line-scanning confocal microscope demonstrates excellent imaging of nuclear and cellular detail in human skin in vivo. The optical sectioning is 1.7 ¿m and lateral resolution is 0.8 ¿m, which is comparable to that of pathology. The hardware cost of the bench-top microscope is less than $15,000. Our hypothesis is that the bench-top line-scanning instrumentation may be translated toward a compact confocal microscope for use at-the-bedside. Rapid and safe staining of nuclear morphology with aluminum chloride may enable intra-operative mapping, in reflectance contrast, of BCCs and SCCs to guide surgery. The specific aims are (1) to build a compact line-scanning confocal microscope for intra-operative imaging in reflectance contrast, and (b) to test the microscope and aluminum chloride-based contrast for intra operative detection of BCC and SCC margins in surgical wounds in situ during Mohs surgery, in a pilot clinical study on 60 patients. Sensitivity and specificity will be determined, against the gold standard of Mohs frozen pathology, to validate the feasibility of the technology. PUBLIC HEALTH RELEVANCE: Confocal microscopy may enable screening and diagnosis of skin cancers such as melanomas and basal- and squamous-cell carcinomas, or may guide surgery of such cancers, directly and in real-time on the patient. The screening, diagnosis or surgical guidance may be noninvasive, with minimal need for biopsy, minimal pain and minimal expense. In dermatology alone, US healthcare may potentially save $2 billion every year. Confocal microscopy may also prove useful for noninvasively diagnosing and treating many other types of cancers such as oral, head-and-neck, breast and cervical.

描述(申请人提供)：该项目的目标是将台式线扫描共聚焦显微镜转化为临床仪器，用于在Mohs手术中进行术中成像，并测试使用氯化铝作为造影剂在反射率中染色核形态的可行性，以检测患者基底细胞癌(BCC)和鳞状细胞癌(SCC)边缘的可行性。达到临床预期的灵敏度和特异度将是验证和展示皮肤Mohs手术和其他可能多样化的术中成像应用的技术平台的量化里程碑。其目的是创造一种相对简单、小巧和低成本的实时反射成像共焦显微镜，以指导不同环境下的手术。建议的直接应用是术中标测BCC和SCC，以指导MoHs手术。未来的应用可能包括绘制癌症地图，以指导口腔、头颈、乳房、膀胱、肝脏和其他组织的手术。基底细胞癌和鳞状细胞癌的发病率最高，仅在美国每年就估计有130万新确诊病例和约100万例手术。手术以冰冻病理为指导，劳动强度大，耗时长。共聚焦显微镜成像在体内的核细节，因此可以实现术中直接在患者身上实时标测。可以对手术暴露的原位组织进行癌边缘的快速检查，以指导准确和完整的切除，同时保留周围的正常组织。影像可作为病理学的辅助手段，指导手术，同时节省人力和成本。患者可能会受益于更有效的手术程序，更少的麻醉和更少的手术室时间。初步结果表明，在患者手术暴露的原位剃须活检伤口中，使用局部应用氯化铝来增强癌与正常组织的对比度，检测基底细胞癌是可行的。此外，实验室台式行扫描共聚焦显微镜在活体人体皮肤中展示了出色的核和细胞细节成像。光切面为1.7？m，横向分辨率为0.8？m，与病理结果相当。台式显微镜的硬件成本不到15,000美元。我们的假设是，台式线扫描仪器可以转化为紧凑的共焦显微镜，用于床边使用。用氯化铝快速、安全地对细胞核形态进行染色，可以在术中以反射对比的方式标测基底细胞和鳞状细胞，以指导手术。具体目的是(1)建立一个紧凑的线扫描共聚焦显微镜，用于术中反射率对比成像，以及(B)在60例患者的初步临床研究中，测试显微镜和基于氯化铝的对比剂，用于在Mohs手术中原位检测手术伤口的BCC和SCC边缘。将根据莫氏冷冻病理学的黄金标准来确定灵敏度和特异度，以验证该技术的可行性。 公共卫生相关性：共聚焦显微镜可以对黑色素瘤、基底细胞癌和鳞状细胞癌等皮肤癌进行筛查和诊断，也可以直接和实时地指导此类癌症的手术。筛查、诊断或手术指导可能是非侵入性的，需要最小的活检，最小的痛苦和最小的费用。仅在皮肤病方面，美国的医疗保健每年就可能节省20亿美元。共聚焦显微镜还可以用于非侵入性诊断和治疗许多其他类型的癌症，如口腔癌、头颈部癌、乳腺癌和宫颈癌。