Peri-operative confocal imaging-guided laser ablation of basal cell carcinomas

基底细胞癌围术期共焦成像引导激光消融术

• 批准号: 9143766
• 负责人: MILIND RAJADHYAKSHA
• 金额: $ 53万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-11 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9143766
• 关键词: Ablation; Acetic Acids; Address; Adopted; Alternative Therapies; Area; Australia; Basal cell carcinoma; Biopsy; Clinical; Clinical Pathology; Coagulation Process; Confocal Microscopy; Contrast Media; Cornea; Curettage procedure; Cutaneous Melanoma; Detection; Diagnosis; Europe; Evaluation; Excision; Face; Feedback; Freezing; Goals; Head and neck structure; Health; Human; Image; Imaging technology; Imiquimod; Incidence; Label; Lasers; Length; Low-Level Laser Therapy; Malignant Neoplasms; Microscopy; Mohs Surgery; Morphology; Nuclear; Operative Surgical Procedures; Outcome; Pathology; Patients; Physiologic pulse; Predictive Value; Procedures; Process; Radio; Residual Tumors; Residual state; Resolution; Sensitivity and Specificity; Skin; Skin Cancer; Skin Carcinoma; Specificity; Specimen; Testing; Tissue Viability; Tissues; Treatment Cost; Validation; cancer diagnosis; cost; follow-up; image guided; improved; in vivo; microscopic imaging; minimally invasive; optical imaging; standard care; tumor; uptake; wound

 DESCRIPTION (provided by applicant): The goal of this project is to develop and test a peri-operative confocal imaging-guided approach for laser ablation of basal cell carcinomas (BCCs). BCCs are among the most common malignancies in the world, with an estimated 2.5 million new cases diagnosed every year in the USA and 700,000 in Europe and Australia. Mohs surgery, guided by frozen pathology, is the standard treatment. However, the procedure is labor- intensive and expensive, with treatment costs of about $2 billion every year in the USA. Consequently, less invasive and less expensive non-surgical alternative therapies are being increasingly adopted. Laser ablation is particularly effective for minimally invasive removal of superficial and early nodular types of BCCs (about 600,000 cases per year in the USA and 200,000 in Europe and Australia). Skin can be ablated in µm-thin layers in a controlled manner. However, tissue is vaporized such that there is none available for immediate pathological evaluation for the presence or clearance of tumor. (One may say that there's "plenty of tissue" remaining on the patient that can be taken for pathology, but this would defeat the very purpose of a less invasive approach.) The lack of pathological feedback results in variable efficacy and limited cure rate. A high-resolution nuclear-level optical imaging approach such confocal microscopy may detect the presence or clearance of residual BCCs directly on the patient, and provide immediate pathology-like feedback. However, ablation produces thermal coagulation and loss of viability in the remaining underlying tissue (wound), which may subsequently impede the uptake of a contrast agent for labeling nuclear morphology and imaging of residual tumor. Our hypothesis is that adequate tissue viability may be preserved by controlling the thermal coagulation with optimal choice of ablation parameters (pulse duration, fluence, number of pulses, wave- length). This may subsequently allow uptake of contrast agent and detection of residual BCC tumor in vivo. Such an imaging-guided approach may improve the efficacy and cure rate of ablation for superficial and early nodular BCCs. About 800,000 patients (worldwide) may benefit, per year, with a less invasive procedure. Preliminary studies on excised human skin specimens confirms our hypothesis. Testing on five BCCs in vivo demonstrates the potential for peri-operative imaging directly on patients to guide ablation. The specific aims are to (1) investigate depth of thermal coagulation and viability of tissue in the underlying wound versus two ablation parameters (fluence, number of pulses), and determine optimal parameters for preserving adequate viability; (2) determine the uptake of contrast agent (acetic acid) versus optimal ablation parameters in excised human skin specimens, with quantitative validation against pathology; (3) simulate implementation on patients in vivo, by testing feasibility for detecting clearance of BCCs on excised human skin specimens versus optimal ablation parameters, with quantitative validation against pathology; (4) test feasibility of peri-operative imaging- guided ablation on patients, with quantitative validation against pathology and clinical follow-up.

 描述（由申请人提供）：该项目的目标是开发和测试一种围手术期共聚焦成像引导的基底细胞癌（BCC）激光消融方法。 BCC 是世界上最常见的恶性肿瘤之一，美国每年估计诊断出 250 万例新病例，欧洲和澳大利亚诊断出 70 万例。以冷冻病理学为指导的莫氏手术是标准治疗方法。然而，该手术是劳动密集型且昂贵的，在美国每年的治疗费用约为 20 亿美元。因此，越来越多地采用侵入性较小且成本较低的非手术替代疗法。激光消融对于浅表和早期结节型基底细胞癌的微创切除特别有效（美国每年约 600,000 例，欧洲和澳大利亚每年约 200,000 例）。皮肤可以以可控的方式被消融成微米薄层。然而，组织被蒸发，因此无法立即对肿瘤的存在或清除进行病理学评估。 （有人可能会说患者身上残留有“大量组织”可以进行病理学检查，但这将违背微创方法的初衷。）缺乏病理反馈会导致疗效参差不齐，治愈率有限。高分辨率核级光学成像方法（例如共焦显微镜）可以直接检测患者身上残留 BCC 的存在或清除，并提供即时的病理样反馈。然而，消融会在剩余的底层组织（伤口）中产生热凝固和活力丧失，这可能随后阻碍用于标记核形态和残留肿瘤成像的造影剂的摄取。我们的假设是，通过选择最佳消融参数（脉冲持续时间、能量密度、脉冲数、波长）来控制热凝固，可以保留足够的组织活力。这可能随后允许摄取造影剂并检测体内残留的 BCC 肿瘤。这种影像引导的方法可以提高浅表和早期结节性 BCC 消融的疗效和治愈率。每年（全球）约 800,000 名患者可能受益于微创手术。对切​​除的人体皮肤标本的初步研究证实了我们的假设。对五个 BCC 的体内测试表明，直接对患者进行围手术期成像以指导消融的潜力。具体目标是（1）研究热凝固深度和下面伤口组织的活力与两个消融参数（注量、脉冲数）的关系，并确定保持足够活力的最佳参数； (2) 确定切除的人体皮肤标本中造影剂（乙酸）的摄取与最佳消融参数的关系，并根据病理学进行定量验证； (3) 通过测试在切除的人体皮肤标本上检测 BCC 清除率与最佳消融参数的可行性，并根据病理学进行定量验证，模拟在患者体内的实施； （4）测试围手术期影像引导消融对患者的可行性，并根据病理学和临床随访进行定量验证。