Smartphone confocal microscopy for diagnosing Kaposi’s sarcoma

 描述（由申请人提供）：艾滋病相关卡波西肉瘤（KS）是撒哈拉以南非洲最常见的艾滋病相关癌症。即使在现代抗逆转录病毒疗法（ART）时代，在撒哈拉以南非洲地区诊断为KS后的生存率也很差，一些国家的三年生存率仅为30%。在低收入和中等收入国家，由于缺乏及时和准确诊断KS所需的资源，及时治疗受到阻碍。在这个项目中，我们提出了一种新的诊断方法，使用智能手机共聚焦显微镜，以提供及时诊断KS。该设备的便携性意味着它可以被带到现场，而不需要农村地区的患者长途跋涉进行KS诊断。在我们的方法中，KS疑似皮肤病变在体内用智能手机共聚焦显微镜在短的手术时间内成像（预期成像时间< 10分钟）。共焦图像可以通过蜂窝网络立即发送到专家共焦图像读取器以进行图像阅读，或者可以使用在智能手机中实现的自动图像分析应用程序来进行诊断。因此，及时地将诊断传递给患者，并且在患者仍在当地诊所时开始治疗。在目标1中，我们将开发智能手机共聚焦显微镜。我们将使用一种反射共焦显微镜技术，狭缝光谱编码共焦显微镜（Slit-SECM），它可以通过使用廉价的光源和智能手机中的成像传感器来获取二维图像。我们将优化设计智能手机共聚焦显微镜，制造它，并测试它的成像性能。在目标2中，我们将评估智能手机共聚焦显微镜在乌干达诊断KS的临床实用性。疑似KS的皮肤病变将使用智能手机共聚焦显微镜进行成像，并将共聚焦图像与相应的组织学图像进行比较，这是目前的金标准。在病例对照研究中，将测试诊断灵敏度和特异性。虽然该项目的重点是诊断低收入国家的KS，但在未来，这种相同的方法可以适用于资源贫乏和资源丰富环境中的其他疾病的诊断。例如，在黑色素瘤的诊断和治疗过程中，智能手机共聚焦显微镜可以适用于对黑色素瘤病变进行非侵入性成像，以指导活检和手术治疗。结合内窥镜成像光学器件，智能手机共聚焦显微镜可用于筛查早期宫颈癌。我们坚信，智能手机共聚焦显微镜将大大改善一系列疾病的早期诊断，最终目标是帮助减少地球仪的健康差距。

 DESCRIPTION (provided by applicant): AIDS-related Kaposi sarcoma (KS) is the most common HIV-associated cancer in sub-Saharan Africa. Even in the modern antiretroviral therapy (ART) era, survival after a diagnosis with KS in sub-Saharan Africa is poor, with a three year survival rate in some countries of only 30%. Timely treatment has been hampered in low- and middle- income countries (LMICs) due to lack of resources that are needed for prompt and accurate KS diagnosis. In this project, we propose a new diagnostic approach that uses a smartphone confocal microscope to provide timely diagnosis of KS. The portable nature of the device means that it can be brought into the field, rather than requiring patients in rural areas t travel long distances for KS diagnosis. In our approach, KS- suspected skin lesions are imaged in vivo with a smartphone confocal microscope in a short procedural time (expected imaging time < 10 minutes). Confocal images can be immediately sent to an expert confocal image reader over the cellular network for image reading, or an automated image analysis application implemented in the smartphone can be used to render a diagnosis. As a result, the diagnosis is delivered to the patient in a timely manner and the treatment is initiated while the patient is stil at the local clinic. In Aim 1, we will develop a smartphone confocal microscope. We will use a reflectance confocal microscopy technique, slit spectrally encoded confocal microscopy (Slit-SECM), which can acquire two-dimensional images by using inexpensive light source and the imaging sensor in the smartphone. We will optimally design the smartphone confocal microscope, fabricate it, and test it for imaging performance. In Aim 2, we will evaluate clinical utility of the smartphone confocal microscope to diagnose KS in Uganda. Skin lesions suspected to be KS will be imaged with the smartphone confocal microscope, and confocal images will be compared with corresponding histologic images, which is the current gold standard. In a case control study, diagnostic sensitivity and specificity will be tested. While thi project focuses on diagnosing KS in LMICs, in future this same approach can be adapted for diagnosis of other diseases in both resource poor and resource rich settings. For example, during melanoma diagnosis and treatment, the smartphone confocal microscope could be adapted to image melanoma lesions non-invasively to guide biopsy and surgical treatment. In conjunction with an endoscopic imaging optics, the smartphone confocal microscope can be used for screening of early-stage cervical cancers. We strongly believe that the smartphone confocal microscopy will greatly improve the early diagnosis of a range of conditions, with the ultimate goal of helping to reduce health disparity around the globe.