Smartphone Confocal Endoscopy for Detecting Cervical Precancer

项目概要/摘要 宫颈癌仍然是低收入和中等收入国家的一个重大健康问题。超过 每年530，000例宫颈癌病例和270，000例宫颈癌相关死亡中的80%发生在 中低收入国家。在中低收入国家缺乏开展有组织的筛查和治疗服务的资源， 宫颈恶性肿瘤分期诊断由于这种资源短缺，宫颈癌相关 东非国家的死亡率为每10万人中有27.6人死亡，与2.3人相比，这一比例高得令人无法接受。 在美国每10万人。醋酸目视检查（VIA）和HPV检测是两种低成本的筛查方法 在中低收入国家通常采用的方法。多项研究表明，宫颈癌的发病率可 通过HPV和VIA检测筛查并相应治疗患者，然而，主要缺点是， VIA和HPV检测的特异性较低，因为大多数筛查结果为阳性的女性（80%至90%） 具有值得治疗的显著宫颈恶性肿瘤（即，宫颈癌前病变或癌症）。所得 过度治疗使低风险妇女遭受不必要的疾病，并对资源造成压力。共焦 在检测宫颈癌前病变方面，显微镜检查提供了高灵敏度（93-100%）和特异性（93- 100 但是由于高的设备成本（>$50，000），其在LMIC中的实用性受到限制。我们提出了一个新的 用低成本（<3，000美元）智能手机共聚焦准确诊断宫颈癌前病变的方法 内窥镜检查，并在一次就诊中提供充分的治疗。在这种方法中，可疑的宫颈病变是 用智能手机共焦内窥镜在体内成像。在共聚焦图像中可视化的细胞形态 进行定量分析，以诊断宫颈癌前病变，并在治疗期间进行适当的治疗。 同样的访问。我们的方法将在两个方面改善患者护理：i）具有高特异性的共聚焦显微镜， 我们将可减少不必要的过度治疗;及ii）由于仪器成本低廉，我们将可加强单一- 访问，在农村诊所采用“筛查和治疗”的方法。在这个R21项目中，我们将开发智能手机共焦 内窥镜和进行试点研究成像宫颈在乌干达的体内。我们以前开发了一个低- 成本智能手机共聚焦显微镜，并已在乌干达展示了体内共聚焦皮肤成像。在这 项目，我们正在翻译的智能手机共聚焦显微镜技术的宫颈成像，通过开发 微型内窥镜导管。在Aim 1中，我们将开发用于成像的智能手机共焦内窥镜 子宫颈我们将优化设计i）一个低成本的智能手机共焦模块，与ii）一个微型 内窥镜导管并测试成像性能。在目标2中，我们将展示体内共焦成像 在乌干达的病人身上。将分析共聚焦图像，并与相应的组织学检查结果进行比较。 并对诊断准确性进行初步分析。我们坚信我们的低- 成本，智能手机共聚焦显微镜技术将大大提高一系列的早期诊断， 我们的目标是帮助减少地球仪各地的健康差距。

Project Summary/Abstracts Cervical cancer remains a significant health problem in low- and middle- income countries (LMICs). More than 80% of the 530,000 annual cervical cancer cases and 270,000 annual cervical cancer-related deaths occur in LMICs. Lack of resources for conducting organized screening and treatment services in LMICs leads to late stage diagnosis of cervical malignancy. As a result of this resource shortage, cervical cancer associated mortality rate in east African countries is 27.6 per 100,000, which is unacceptably high when compared to 2.3 per 100,000 in the US. Visual inspection with acetic acid (VIA) and HPV tests are the two low-cost screening approaches commonly utilized in LMICs. Several studies showed that cervical cancer incidence rate can be reduced by screening with HPV and VIA tests and treating the patient accordingly. However, main drawback of the VIA and HPV tests is low specificity, as most women with a positive screening result (80% to 90%) will not have significant cervical malignancy that warrants treatment (i.e., cervical precancer or cancer). The resulting overtreatment exposes low-risk women to unnecessary morbidity and poses a strain on resources. Confocal microscopy provides both high sensitivity (93-100%) and specificity (93-100%) in detecting cervical precancer but its utility in LMICs has been limited due to the high device cost (>$50,000). We are proposing a new approach of accurately diagnosing cervical precancer with a low-cost (<$3,000) smartphone confocal endoscope and providing adequate treatment in a single visit. In this approach, suspected cervical lesions are imaged in vivo with the smartphone confocal endoscope. Cellular morphologies visualized in confocal images are quantitatively analyzed to diagnose cervical precancer and adequate treatment is performed during the same visit. Our approach will improve patient care in two areas: i) with high specificity of confocal microscopy, we will be able to reduce unnecessary overtreatment; and ii) with the low device cost, we will enhance a single- visit, “screen-and-treat” method in rural clinics. In this R21 project, we will develop the smartphone confocal endoscope and conduct a pilot study of imaging cervix in vivo in Uganda. We have previously developed a low- cost smartphone confocal microscope and have demonstrated in vivo confocal skin imaging in Uganda. In this project, we are translating the smartphone confocal microscopy technology for cervical imaging by developing a miniature endoscopic catheter. In Aim 1, we will develop a smartphone confocal endoscope for imaging cervix. We will optimally design i) a low-cost smartphone confocal module that connects with ii) a miniature endoscopic catheter and test the imaging performance. In Aim 2, we will demonstrate in vivo confocal imaging of cervix in patients in Uganda. Confocal images will be analyzed in comparison with corresponding histologic images and preliminary analysis will be conducted on diagnostic accuracy. We strongly believe that our low- cost, smartphone confocal microscopy technology will greatly improve the early diagnosis of a range of conditions, with the ultimate goal of helping to reduce health disparity around the globe.