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（由适用提供）：该项目的目的是将台式线扫描的共聚焦显微镜转化为临床仪器，用于在MOHS手术过程中进行术中成像，并测试可行性，用于对患者的核型塑料型核苷的核能来检测基本的细胞癌（BCC）和鳞状细胞癌（SCC）的核癌（Skamous）细胞癌（SCC）。达到临床预期的灵敏度和特异性将是验证和展示皮肤中MOHS手术的技术平台的定量里程碑，以及其他潜在的不同术中成像应用。动机是创建一个相对简单，小和低成本的共聚焦显微镜，以在反射率中进行实时成像，以指导潜水员环境中的手术。拟议的即时应用是对BCC和SCC的术中映射，以指导MOHS手术。未来的应用可能包括映射癌症以指导口腔，头颈，乳房，膀胱，肝脏和其他组织的手术。 BCC和SCC的发生率最高，估计有130万例新病例，仅在美国，估计每年就进行了100万次手术。手术以劳动密集型且耗时的冷冻病理为指导。共聚焦显微镜图像体内核细节，因此可以实时直接对患者进行术中映射。可以在原位进行手术暴露的组织对癌症边缘的快速检查，以指导准确而完全的惊喜，同时保留周围正常组织。该成像可以作为指导手术的病理学的辅助，同时节省劳动和成本。患者可以通过更有效的手术，减少麻醉和减少手术室的时间受益。初步结果证明了检测BCC的可行性，局部应用氯化铝来增强癌症至正常的组织对比度，在手术暴露于患者的手术剃须期伤口中。此外，实验室基准线扫描共聚焦显微镜显示体内人类皮肤中核和细胞细节的出色成像。光学截面为1.7€，横向分辨率为0.8？m，与病理相媲美。台式显微镜的硬件成本不到$ 15,000。我们的假设是，可以将台式线扫描仪器转换为紧凑的共聚焦显微镜，以便在床边使用。用氯化铝对核形态的快速染色可以使BCC和SCC的反射率对比度术内映射，以指导手术。（1）的具体目的是在反射率对比中建立紧凑的扫描共聚焦显微镜，以测试基于术中BCC和SCC边缘伤口的MOHS手术期间，在MOHS手术期间，在60次临床研究中，测试了基于术中BCC和SCC边缘伤口的术中基于氯化铝的对比。敏感性和特异性将根据MOHS冷冻病理的黄金标准确定，以验证该技术的可行性。公共卫生相关性：共聚焦显微镜可以筛查和诊断黑色素瘤，基本瘤和鳞状细胞癌等皮肤癌，或者可以直接和实时对患者进行此类癌症的手术。筛查，诊断或手术指导可能是无创的，对活检，最小疼痛和最小费用的需求最少。仅在皮肤病学中，美国医疗保健可能每年可能节省20亿美元。共聚焦显微镜也可能被证明可用于非侵袭性诊断和治疗许多其他类型的癌症，例如口服，头颈，乳房和颈椎。

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：
10.1002/lsm.22415
发表时间：
2016
期刊：
Lasers in surgery and medicine
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

Confocal microscopy-guided laser ablation for superficial and early nodular Basal cell carcinoma: a promising surgical alternative for superficial skin cancers.

DOI：
10.1001/jamadermatol.2013.10225
发表时间：
2014-09
期刊：
JAMA DERMATOLOGY
影响因子：
10.9
作者：
Chen, Chih-Shan Jason;Sierra, Heidy;Cordova, Miguel;Rajadhyaksha, Milind
通讯作者：
Rajadhyaksha, Milind

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

DOI：
10.1016/j.jaad.2021.11.054
发表时间：
2022-10
期刊：
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
影响因子：
13.8
作者：
Mehta, Paras P.;Oh, Yuna;Cordova, Miguel;Chen, Chih-Shan;Halpern, Allan;Harris, Ucalene;Kentley, Jonathan;Kurtansky, Nicholas R.;Kose, Kivanc;Lee, Erica H.;Marchetti, Michael A.;Marghoob, Ashfaq;Markova, Alina;Navarrete-Dechent, Cristian;Nehal, Kishwer;Rajadhyaksha, Milind;Rossi, Anthony;Sahu, Aditi;Sun, Mary;Jain, Manu;Rotemberg, Veronica
通讯作者：
Rotemberg, Veronica

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