Intra-operative confocal imaging to guide Mohs surgery

术中共聚焦成像指导莫氏手术

基本信息

批准号：
8323371
负责人：
MILIND RAJADHYAKSHA
金额：
$ 80.46万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-30 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8323371
关键词：
Aluminum Anesthesia procedures Area Atlas of Cancer Mortality in the United States Basal cell carcinoma Biopsy Bladder Breast Cellular Morphology Cervical Chloride Ion Chlorides Clinical Clinical Research Confocal Microscopy Contrast Media Dermatology Detection Development Diagnosis Epidermis Excision Face Freezing Funding Funding Opportunities Future Goals Gold Head and neck structure Healthcare 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 Pain Pathology Patients Preparation Procedures Resolution Scanning Screening procedure Sensitivity and Specificity Shave Biopsy Skin Skin Cancer Squamous cell carcinoma Staining method Stains Surgical wound Technology Testing Time Tissues Topical application Translating base cancer type cost image guided intervention in vivo instrument instrumentation interest intervention program melanoma public health relevance response

项目摘要

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）：该项目的目标是将台式线扫描共聚焦显微镜转化为用于莫氏手术期间术中成像的临床仪器，并测试检测基底细胞癌（BCC）和使用氯化铝作为对比剂对患者的鳞状细胞癌 (SCC) 边缘进行反射染色核形态，达到临床预期的灵敏度和特异性将是验证和演示技术的定量里程碑。该平台用于皮肤莫氏手术和其他潜在的多样化术中成像应用，其动机是创建一种相对简单、小型且低成本的共聚焦显微镜，用于反射实时成像，以指导不同环境下的手术。该应用是在术中绘制 BCC 和 SCC 来指导莫氏手术，未来的应用可能包括绘制癌症图，以指导口腔、头颈、乳房、膀胱、肝脏和其他组织中发生的 BCC 和 SCC 的手术。最高费率据估计，仅在美国每年就有 130 万例新病例被诊断出来，并且估计进行了 100 万例手术，手术是在冷冻病理学的指导下进行的，这既费力又耗时。可以在术中直接对患者进行实时快速检查手术暴露的组织，以指导准确和完整的切除，同时保留周围的正常组织。病理学指导手术，同时节省劳动力和成本，患者可能会受益于更有效的手术、更少的麻醉和更少的手术室时间。初步结果证明了通过局部应用氯化铝来增强癌症与正常组织的对比度来检测基底细胞癌的可行性。此外，实验室台式线扫描共聚焦显微镜在体内对人体皮肤的核和细胞细节进行了出色的成像，光学切片为 1.7。 ¿米，横向分辨率为 0.8 ¿ m，与病理学的硬件成本相当，我们的假设是台式线扫描仪器可以转化为用于现场使用的紧凑型共聚焦显微镜。用氯化铝对核形态进行快速、安全的染色可以在术中对 BCC 和 SCC 进行反射对比，以指导手术。在一项关于 60 的初步临床研究中，使用共聚焦显微镜进行术中反射对比成像，以及 (b) 测试显微镜和基于氯化铝的对比剂，以在莫氏手术期间原位手术伤口中检测 BCC 和 SCC 边缘。将根据莫氏冷冻病理学的金标准确定敏感性和特异性，以验证该技术的可行性。公共健康相关性：共聚焦显微镜可以直接、实时地对患者进行皮肤癌的筛查和诊断，例如黑色素瘤、基底细胞癌和鳞状细胞癌，或者可以指导此类癌症的手术。指导可能是非侵入性的，只需最少的活检、最小的疼痛和最少的费用，仅在皮肤病学方面，共焦显微镜检查也可能每年节省 20 亿美元。用于无创诊断和治疗许多其他类型的癌症，如口腔癌、头颈癌、乳腺癌和宫颈癌。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Confocal imaging of carbon dioxide laser-ablated basal cell carcinomas: An ex-vivo study on the uptake of contrast agent and ablation parameters.

二氧化碳激光消融基底细胞癌的共焦成像：关于造影剂摄取和消融参数的离体研究。

DOI：
发表时间：
2016-02
期刊：
影响因子：
2.4
作者：
Sierra, Heidy;Damanpour, Shadi;Hibler, Brian;Nehal, Kishwer;Rossi, Anthony;Rajadhyaksha, Milind
通讯作者：
Rajadhyaksha, Milind

Detection of skin cancer margins in Mohs excisions with high-speed strip mosaicing confocal microscopy: a feasibility study.

用高速条带镶嵌共聚焦显微镜检测莫氏切除中的皮肤癌边缘：可行性研究。

DOI：
发表时间：
2013-10
期刊：
影响因子：
0
作者：
Larson, B;Abeytunge, S;Seltzer, E;Rajadhyaksha, M;Nehal, K
通讯作者：
Nehal, K

Patterns of the use of reflectance confocal microscopy at a tertiary referral dermatology clinic.

三级转诊皮肤科诊所使用反射共焦显微镜的模式。

DOI：
发表时间：
2022-10
期刊：
影响因子：
13.8
作者：
Mehta, Paras P;Oh, Yuna;Cordova, Miguel;Chen, Chih;Halpern, Allan;Harris, Ucalene;Kentley, Jonathan;Kurtansky, Nicholas R;Kose, Kivanc;Lee, Erica H;Marchetti, Michael A;Marghoob, Ashfaq;Markova, Alina;Navarrete;Nehal
通讯作者：
Nehal

Optimal detection pinhole for lowering speckle noise while maintaining adequate optical sectioning in confocal reflectance microscopes.

最佳检测针孔可降低散斑噪声，同时在共焦反射显微镜中保持足够的光学切片。