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（由申请人提供）：本项目目的是将台式线扫描共聚焦显微镜转化为莫氏手术术中成像的临床仪器，并测试在患者基底细胞癌（BCC）和鳞状细胞癌（SCC）边缘检测的可行性，使用氯化铝作为造影剂对核形态进行反射染色。达到临床预期的灵敏度和特异性将是验证和展示Mohs手术在皮肤和其他潜在的多种术中成像应用的技术平台的定量里程碑。其动机是创造一种相对简单，小型和低成本的共聚焦显微镜，用于实时成像的反射率，以指导手术在不同的设置。建议立即应用于术中bcc和SCCs的定位，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、头颈部、乳房、膀胱、肝脏和其他组织的手术。bcc和SCCs的发病率最高，估计每年仅在美国就有130万新发病例和大约100万例手术。手术是由冷冻病理指导的，这是劳动密集型和耗时的。共聚焦显微镜成像体内的核细节，因此可以实现术中直接对患者进行实时映射。可对手术暴露的原位组织进行癌缘快速检查，以指导准确和完整的切除，同时保留周围的正常组织。成像可作为病理指导手术的辅助手段，同时节省人工和成本。患者可能受益于更有效的手术，更少的麻醉和更少的手术室时间。初步结果表明，在手术暴露的患者原位剃须活检伤口中，局部应用氯化铝增强癌组织与正常组织的对比，检测bcc的可行性。此外，实验室台式线扫描共聚焦显微镜显示了活体人体皮肤核和细胞细节的出色成像。光学切片1.7¿m，横向分辨率0.8¿m，与病理相当。台式显微镜的硬件成本不到1.5万美元。我们的假设是，台式线扫描仪器可能转化为一个紧凑的共聚焦显微镜在床边使用。用氯化铝快速、安全地对核形态进行染色，可以在术中通过反射对比对bcc和SCCs进行定位，从而指导手术。具体目的是(1)建立一种紧凑的线扫描共聚焦显微镜，用于术中成像的反射对比，(b)在60例患者的试点临床研究中，测试显微镜和基于氯化铝的造影剂在Mohs手术中术中原位检测手术伤口BCC和SCC边缘的效果。灵敏度和特异性将根据莫氏冷冻病理学的黄金标准来确定，以验证该技术的可行性。