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（由适用提供）：该项目的目的是开发和测试一种围围次术共焦成像引导的方法，用于激光消融基本细胞癌（BCCS）。 BCC是世界上最常见的恶性肿瘤之一，估计每年在美国诊断出250万例新病例，欧洲和澳大利亚有70万例。由冷冻病理指导的MOHS手术是标准治疗方法。但是，该程序是劳动密集型且昂贵的，在美国，治疗费用约为20亿美元。因此，越来越多地采用侵入性和较便宜的非手术替代疗法。激光消融对于微创侵入性去除浅表和早期结节类型的BCC（每年约60万例，在欧洲和澳大利亚的200,000例）特别有效。可以以受控的方式以µm薄层擦拭皮肤。然而，组织的蒸发使得无需立即进行病理评估肿瘤的存在或清除。 （有人可能会说，患者还剩下“大量的组织”，这可以用于病理学，但这将违反一种侵入性较低的方法的目的。）缺乏病理反馈会导致可变效率和有限的治疗率。高分辨率的核水平光学成像方法这种共聚焦显微镜可以直接检测出残留BCC的存在或清除患者，并提供直接的病理样反馈。然而，消融会产生热凝血和剩余的基础组织中的生存力丧失（伤口），随后可能阻碍了对比剂的摄取，用于标记核形态和残留肿瘤的成像。我们的假设是，可以通过最佳的消融参数（脉冲持续时间，通量，脉冲数，波长）控制热凝血来保留足够的组织生存能力。这可能随后允许摄取造影剂并在体内检测残留的BCC肿瘤。这种成像引导的方法可以提高浅表和早期结节BCC的消融效率和治愈速率。每年约有80万名患者（全球）受益于侵入性手术。关于优秀人类皮肤标本的初步研究证实了我们的假设。对五个BCC在体内进行测试证明了直接对患者进行围手术成像的潜力，以引导消融。具体目的是（1）研究基础伤口中组织的热凝结和生存能力与两个消融参数（脉冲，脉冲数），并确定保持足够可行性的最佳参数； （2）确定在优秀人类皮肤标本中的对比剂（乙酸）与最佳消融参数的摄取，并具有针对病理学的定量验证； （3）通过测试可行性，以检测出出色的人类皮肤标本上的BCC的可行性，并对病理进行定量验证，以模拟对体内患者的实施； （4）测试围手术成像引导消融对患者的可行性，对病理和临床随访的定量验证。