Fluorescence microscopy for evaluation of Mohs surgical margins

摘要 莫氏手术是一种广泛使用的治疗非黑色素瘤皮肤癌的技术，这种皮肤癌的发病率极低。 通过对从体内取出的组织进行成像来提高复发率，以确保完全切除。然而，莫斯速度很慢，而且 劳动密集度极高，因为它依赖于冰冻切片处理来产生组织学图像。成本和 与冷冻切片处理相关的吞吐量减少限制了患者对其的可用性，同时也导致了 医疗保健费用。我的研究开发了荧光成像技术、快速组织标记和图像处理 能够在处理过程中减少数量级的皮肤组织病理的实时评估技术 与冻结切片相比的时间。 这项提案将为莫氏手术开发先进的外科成像技术，这一应用程序成本太高- 对现有技术如双光子荧光显微镜敏感。第一个目标将评估以下各项的准确性 莫氏手术切缘的荧光诊断：废弃莫氏标本用紫外线显微镜成像 表面激发(MUSE)是一种既便宜又有前途的Mohs手术方法。第二 AIM将开发两种基于MUSE的新成像系统。这些技术将实现数量级的减少 与最先进的双光子或冰冻切片相比，在成本和成像时间方面，使新的应用能够在 皮肤病理学。MUSE成像对比度和分辨率的显著提高将使用NOVICE 照明策略和高速图像传感器。最终目标是对这些技术进行成像研究 在Mohs外科实践中开发的先前目标，展示了相对于冷冻的敏感性和特异性 同时减少治疗病人的时间。这些研究将证明，新的成像技术可以减少 与Mohs手术相关的时间，使更多人能够获得图像引导手术，并降低医疗成本。 这项建议将建立在我的光学和软件工程经验的基础上，同时为我提供重要的新 皮肤病理学、数字病理学、皮肤癌外科治疗和临床研究设计方面的培训。 这项未经指导的提案将在贝弗利·福克纳-琼斯博士和詹姆斯·康诺利博士的指导下进行 他们是临床医生--病理学领域的科学家和专家。此外，我将与一家新的临床医生密切合作 合作者，莫氏外科医生杜大雄。这种多学科、协作的环境将提供一个极好的 独立于我在麻省理工学院的博士后导师和临床研究培训的职业成长机会 使我能够在外科成像和数字病理学方面建立一个独立的研究计划。

Abstract Mohs surgery is a widely used technique for the treatment of nonmelanoma skin cancer that obtains extremely low recurrence rates by imaging tissue as it is removed from the body to ensure complete resection. However, Mohs is slow and extremely labor intensive because it depends on frozen sections processing to produce histological images. The cost and reduced throughput associated with frozen section processing limits its availability to patients while contributing to rising health care costs. My research has developed fluorescent imaging technologies, rapid tissue labeling, and image processing technologies enabling real-time evaluation of pathology in skin tissue with an order of magnitude reduction in processing time as compared to frozen sections. This proposal will develop advanced surgical imaging technology for Mohs surgery, an application that is too cost- sensitive for existing technologies such as two photon fluorescence microscopy. The first aim will assess the accuracy of fluorescent diagnosis of Mohs surgical margins by imaging discarded Mohs specimens using microscopy with ultraviolet surface excitation (MUSE), a method demonstrated to be both inexpensive and promising for Mohs surgery. The second aim will develop two new imaging systems based on MUSE. These techniques will enable an order of magnitude reduction in cost and imaging time compared to state of the art two photon or frozen sections, enabling new applications in dermatopathology. Dramatic improvements in MUSE imaging contrast and resolution will be realized using novel illumination strategies and high speed image sensors. The final aim will perform an imaging study of the technologies developed in the previous aims in a Mohs surgical practice, demonstrating sensitivity and specificity relative to frozen sections while reducing the time to treat patients. These studies will demonstrate that new imaging technology can reduce the time associated with Mohs surgery, enabling greater access to image-guided surgery and reducing healthcare costs. This proposal will build upon my optical and software engineering experience while providing me with important new training in dermatopathology, digital pathology, the surgical treatment of skin cancer, and the design of clinical studies. This unmentored proposal will be conducted under the guidance of Dr. Beverly Faulkner-Jones and Dr. James Connolly and who are clinician-scientists and experts in the fields of pathology. In addition, I will work closely with a new clinical collaborator, Dr. Daihung Do, a Mohs surgeon. This multi-disciplinary, collaborative environment will provide an excellent opportunity for professional growth independent of my postdoctoral advisor at MIT and training in clinical research while enabling me to establish an independent research program in surgical imaging and digital pathology.