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

项目摘要/摘要 目前皮肤癌诊断的标准是活检，具有侵入性，速度慢，成本高。皮肤 癌症是美国最常见的癌症。可疑皮肤病变的活组织检查是 皮肤癌诊断。在美国，每年有1500万到2000万例皮肤活检。一旦活检的组织是 从患者身上取出活组织标本，将其运送到异地实验室进行处理和 染色。最后，病理学家通过在显微镜下分析标本来做出诊断。这一过程 对医疗系统来说是侵入性的、缓慢的和负担沉重的成本。一次诊断可能需要2-4次 这会延误后续就诊时的治疗，增加医生的利用率和病人的等待时间。 此外，大多数活组织检查被确定为良性的，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的诊断，而不需要活组织检查。 但它的影响仅限于美国63家三级医院和教学医院。RCM是唯一一家通过FDA批准的 一种可以非侵入性地检查细胞细节的成像方法。2017年，RCM获得CPT 报销代码，这是激励医疗保健提供者在他们的做法中采用RCM。然而， 尚未广泛采用主要是由于以下弱点：设备成本较高(约100,000美元)， 非便携性(基于购物车)和低成像速度(6-9帧/秒(Fps)，可延长RCM 成像时间缩短至15分钟，并中断了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，并使非侵入性、 皮肤癌快速诊断可在大多数临床环境中使用。在之前的R21项目中，康博士(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。我们演示了PRCM 乌干达和亚利桑那州皮肤癌的成像。2019年，ArgoMD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。我们的计划 商用PRCM设备将提供当前RCM的三个独特优势：低设备成本(2,000美元)， 便携性(钢笔大小)和快速成像(203 Fps)。这些优势将使prcm渗透到更广泛的领域。 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，速度要快20倍 成像速度比目前的RCM设备更快。我们将通过以下具体目标实现这一目标： 目的1：研制一种高速pRCM装置。我们将显著提高PRCM成像速度 研制一种新型散斑调制照明光学元件。 目的2：通过对皮损的活体成像，评价高速准分子激光原位角膜磨镶术。20处皮肤癌可疑病变 将与pRCM设备和当前的RCM设备进行成像，以评估图像质量。

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.