Intra-operative confocal imaging-guided Mohs surgery

术中共聚焦成像引导莫氏手术

• 批准号: 6801944
• 负责人: MILIND RAJADHYAKSHA
• 金额: $ 30.72万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-20 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6801944
• 关键词: adolescence (12-20); adult human (21+); aluminum; basal cell carcinoma; bioengineering /biomedical engineering; bioimaging /biomedical imaging; biomedical equipment development; chloride ion; clinical research; human subject; image guided surgery /therapy; imaging /visualization /scanning; microscopy

DESCRIPTION (provided by applicant): The goal of this proposal is to develop and clinically test a real-time optical imaging modality based on confocal reflectance microscopy, with enhancement of nuclear-to-dermal contrast using acetic acid and crossed polarization, to intra-operatively examine basal cell cancers to guide Mohs micrographic surgery. Basal cell cancers (BCCs) are among the fastest growing cancers (>1.2 million new USA cases/year); because they occur most frequently on older people and in high risk anatomical sites (near or on the eyes, mouth, nose, ears), precise microsurgery is necessary with minimum damage to the surrounding normal tissue. Mohs surgery is time-consuming (one to several hours) and tedious because several (2-20) excisions must be made, and frozen histology sections carefully prepared and examined for each. Realtime confocal reflectance imaging may make Mohs surgery significantly more efficient by enabling direct intraoperative examination for cancer nests and cancer-to-normal tissue margins on the patient; this will reduce the number of excisions and avoid frozen histology. Both the patient and surgeon will save several hours per procedure in the operating room. Although proposed for Mohs surgery of BCCs, this real-time intra-operative imaging modality may, in fact, prove useful in a variety of other microsurgical settings. The research will be a collaboration between Northeastern University (Boston) and Memorial Sloan-Kettering Cancer Center (New York). This project will be implemented in two phases: (1) an ex vivo study using freshly excised skin specimens from Mohs surgeries, to (a) design a confocal microscope that mimics the Mohs surgeon's examination of frozen histology: rapid low-resolution examination of BCC nests in wide fields-of-view followed by high-resolution inspection of nuclear morphology in small fields-of-view, and develop (b) optimum contrast enhancement methods using topical acetic acid (induces condensation of chromatin that increases light backscatter from nuclei) and optical crossed polarization (suppresses light backscatter from the surrounding normal dermis), (c) optimum hemostasis methods using either topical aluminum chloride or electrocautery, (d) image understanding by detailed correlation of images to histology; and (2) an intraoperative study, involving (a) design of a specialized confocal articulated telescope, to enable (b) imaging of BCCs on patients during surgery, to evaluate the optimum contrast enhancement and hemostasis methods, correlate confocal images to histology and quantitatively determine diagnostic/screening accuracy. The overall goal is to develop an optical (confocal) intra-operative imaging instrument for Mohs and other modes of microsurgery.

描述（由申请人提供）： 该提案的目标是开发并临床测试一种基于共焦反射显微镜的实时光学成像方式，使用乙酸和交叉偏振增强核与真皮对比度，以在术中检查基底细胞癌以指导莫氏显微手术。基底细胞癌 (BCC) 是增长最快的癌症之一（美国每年新增病例超过 120 万例）；由于它们最常发生在老年人和高危解剖部位（眼睛、嘴巴、鼻子、耳朵附近或上面），因此需要进行精确的显微手术，以尽量减少对周围正常组织的损害。莫氏手术非常耗时（一到几个小时）且乏味，因为必须进行多次（2-20）次切除，并且每个切除都要仔细准备和检查冷冻组织学切片。实时共焦反射成像可以在术中直接检查患者的癌巢和癌与正常组织的边缘，从而显着提高莫氏手术的效率；这将减少切除次数并避免组织学冷冻。每次手术患者和外科医生都可以在手术室中节省几个小时。尽管提议用于基底细胞癌的莫氏手术，但事实上，这种实时术中成像方式可能在各种其他显微外科环境中有用。该研究将由东北大学（波士顿）和纪念斯隆-凯特琳癌症中心（纽约）合作进行。该项目将分两个阶段实施：(1) 使用莫氏手术新鲜切除的皮肤标本进行离体研究，(a) 设计模拟莫氏外科医生冷冻组织学检查的共聚焦显微镜：快速低分辨率基底细胞癌检查在宽视场中筑巢，然后在小视场中对核形态进行高分辨率检查，并开发 (b) 使用局部乙酸的最佳对比度增强方法（诱导染色质凝结，从而增加来自细胞核的光反向散射）和光学交叉偏振（抑制来自周围正常真皮的光反向散射），（c）使用局部氯化铝或电灼的最佳止血方法，（d）通过图像与组织学的详细关联来理解图像； (2) 术中研究，包括 (a) 设计专门的共焦铰接式望远镜，以便 (b) 在手术期间对患者的基底细胞癌进行成像，评估最佳的对比增强和止血方法，将共焦图像与组织学和定量相关联确定诊断/筛查的准确性。总体目标是开发一种用于莫氏和其他显微手术模式的光学（共焦）术中成像仪器。