High-speed, portable reflectance confocal microscope (pRCM) for imaging skin cancer

项目总结/摘要 目前皮肤癌诊断的标准护理，活检，是侵入性的，缓慢的，成本负担。皮肤 癌症是美国最常诊断的癌症。可疑皮肤病变活检是治疗的关键步骤 皮肤癌诊断美国每年进行1500万至2000万次皮肤活检。一旦活检组织 从患者体内取出后，将活检样本运送到场外实验室进行处理， 染色最后，病理学家通过在显微镜下分析标本来做出诊断。这个过程 是侵入性的，缓慢的，并且对医疗保健系统的成本是负担的。诊断可能需要多达2-4 这会延迟后续就诊时的治疗，增加医生的利用率和患者的等待时间。 此外，大多数活检被确定为良性，导致不必要的成本和发病率。 反射共聚焦显微镜（RCM）已被证明可以提高皮肤癌诊断而无需活检， 但其影响仅限于美国约63家三级和教学医院。RCM是唯一一个FDA批准的 成像方法，可以非侵入性地检查细胞的细节。2017年，RCM获得CPT认证 报销代码，这是激励医疗保健提供者在其实践中采用RCM。然而，在这方面， 主要由于以下缺点而没有广泛采用：高设备成本（~ 100，000美元）， 非便携性（基于推车）和成像速度慢（6-9帧/秒（fps），这可能会延长RCM 成像时间缩短至15分钟，并破坏现有的临床工作流程）。 我们的首要目标是开发一种低成本、便携式RCM（pRCM）设备， 快速皮肤癌诊断在大多数临床环境中可用。在之前的R21项目中，Kang博士（PI， 亚利桑那大学）发明了世界上第一个基于智能手机的pRCM设备。我们证明了pRCM 乌干达和亚利桑那州的皮肤癌成像。2019年，ArgosMD成立，将pRCM商业化 技术，并与亚利桑那大学签署了独家许可协议。我们预计的 商业pRCM设备将提供三个独特的优势，超过目前的RCM：低设备成本（2,000美元）， 便携性（笔大小）和快速成像（203 fps）。这些优势将使pRCM渗透到广泛的领域 临床环境（例如，皮肤科、初级保健、农村和零售诊所），并实现非侵入性、实时 在这些环境中诊断皮肤癌。 在这个STTR第一阶段项目中，我们的目标是开发一种新的和改进的pRCM设备，速度快20倍， 成像速度比目前的RCM设备。我们将通过以下具体目标实现这一目标： 目标1：开发高速pRCM设备。我们将显著提高pRCM成像速度， 开发了一种新型的散斑调制照明光学系统。 目的2：通过体内皮肤病变成像评估高速pRCM。20处疑似皮肤癌的病变 将使用pRCM器械和当前RCM器械进行成像，以评价图像质量。

Project Summary/Abstract The current standard of care for skin cancer diagnosis, biopsy, is invasive, slow, and burdensome in cost. Skin cancer is the most commonly diagnosed cancer in the US. Biopsy of suspicious skin lesion is the key step of skin cancer diagnosis. 15-20 million skin biopsies are performed in the US annually. Once biopsied tissue is removed from a patient, the biopsy specimen is transported to an off-site laboratory for processing and staining. Finally, a pathologist renders a diagnosis by analyzing the specimen under microscopy. This process is invasive, slow, and burdensome in cost for the healthcare system. A diagnosis can take as many as 2-4 weeks, which delays treatment upon a subsequent visit, increasing physician utilization and patient wait times. Additionally, the majority of the biopsies are determined to be benign, causing unnecessary cost and morbidity. Reflectance confocal microscopy (RCM) has been shown to improve skin cancer diagnosis without a biopsy, but its impact has been confined to ~63 tertiary and teaching hospitals in the US. RCM is the only FDA-cleared imaging method that can non-invasively examine cellular details. In 2017, RCM was granted CPT reimbursement codes, which is incentivizing healthcare providers to adopt RCM in their practices. However, widespread adoption has not occurred mainly due to the following weaknesses: high device cost (~$100,000), non-portability (cart-based), and slow imaging speed (6-9 frames/sec (fps), which can prolong the RCM imaging to 15 minutes and disrupt the existing clinical workflow). Our overarching goal is to develop a low-cost, portable RCM (pRCM) device and make non-invasive, rapid skin cancer diagnostics accessible in most clinical settings. In a previous R21 project, Dr. Kang (PI, University of Arizona) invented the world’s first smartphone-based, pRCM device. We demonstrated pRCM imaging of skin cancers in Uganda and Arizona. In 2019, ArgosMD was formed to commercialize the pRCM technology, and signed an exclusive licensing agreement with the University of Arizona. Our projected commercial pRCM device will provide three unique strengths over the current RCM: low device cost ($2,000), portability (pen-sized), and fast imaging (203 fps). These strengths will enable pRCM penetrate a wide range of clinical settings (e.g., dermatology, primary care, rural and retail clinics) and enable non-invasive, real-time diagnosis of skin cancers in these settings. In this STTR Phase I project, we aim to develop a new and improved pRCM device with 20 times faster imaging speed than current RCM devices. We will achieve this goal through following specific aims: Aim 1: Develop a high-speed pRCM device. We will significantly increase the pRCM imaging speed by developing a novel speckle-modulated illumination optics. Aim 2: Evaluate high-speed pRCM by imaging skin lesions in vivo. Twenty lesions suspicious for skin cancer will be imaged with the pRCM device and current RCM device to evaluate the image quality.