Reflectance confocal microscopy-optical coherence tomography (RCM-OCT) imaging of oral lesions: Toward an affordable device and approach for developing countries

口腔癌的高发病率和盛行率发生在15-20岁的中低收入人群 亚洲和非洲国家(LMIC)。诊断标准是先进行目视检查，然后进行活检。 鼻部口腔损伤。但是16%-100%的视觉检查的低和可变的特异性导致活组织检查 估计有37%-51%的不确定病变(仅在印度就有140万-210万个病变)和良性到恶性病变- NANT活检率为2-24。在LMIC环境中，患者对活检和后续护理的依从性较低(35%-63%) 由于痛苦、恐惧、时间和成本。我们的新解决方案是具有低成本手持反射的非侵入性成像- 共焦显微镜(RCM)-光学相干层析(OCT)设备。血吸虫病的诊断和分级 口腔异型增生的基础是上皮细胞的异型性和潜在的结构变化。RCM图像- ING显示了整个上皮的细胞形态，深达300微米。OCT成像显示上皮层- 肌层和下层固有层至更深1毫米处。RCM-OCT联合成像与单次去噪 VICE将使细胞异型性和共置视野中的结构变化同时成像 指导诊断、对异型增生分级、监测恶变进展和评估侵袭性。分层，使用 一种定量的RCM-OCT评分算法，将引导口腔病变分流到低度异型增生，这可以 接受监测或立即使用非手术治疗，而不是高级别，后者可能立即 活组织检查与癌的对比，后者将通过手术切除。诊断可以与治疗相结合，所有 集成在一次患者探视中--“一站式”患者护理模式。我们是一个学术行业 纪念斯隆·凯特琳癌症中心(纽约，NY)，物理科学公司(马萨诸塞州安多弗)，加州- BER成像和诊断(纽约州罗切斯特)和我们在塔塔纪念医院(TMH)的LMIC合作者 孟买)。对于FOAPAR-21-166，创新被定义为“交付新能力以结束--的可能性” 用户。“创新将是提供带有用于口腔内成像的新探头的RCM-OCT设备，以及 设计了一种定量诊断评分算法，以指导床上实时诊断和治疗- 边上。该设备将交付给TMH，当扩大规模并在本地进行维护时，最终成本将为25,000美元 在LMIC制造，这将支持RCM-OCT作为一种新的、负担得起的成像能力在 LMIC。在初步研究中，RCM-OCT成像检测口腔病变和癌症的灵敏度为100% 特异度为80%。我们的具体目标是(1)设计一种手持式RCM-OCT设备，用于在 口腔；(2)对4422例患者进行前瞻性检查，以进行诊断、异常增生分级和评估 口腔病变和体内癌的侵袭。测试将在LMIC环境中进行，在孟买的TMH和他们的 瓦拉纳西的地区诊所。LMIC的可负担性、提供护理：我们设备的投资回报 在癌症中心可以在6-9个月内完成，而值得治疗的患者的护理成本可以低至零到 成像费是50美分。我们在印度取得的初步成功将为全球在LMIC方面的努力提供种子。

High rates of incidence and prevalence of oral cancers occur in 15-20 developing low-and-middle income countries (LMICs) in Asia and Africa. Visual clinical examination followed by biopsy is the standard for diag- nosing oral lesions. But the low and variable specificity of 16-100% of visual examinations results in biopsies of an estimated 37-51% indeterminate lesions (1.4-2.1 million lesions in India, alone) and in benign-to-malig- nant biopsy ratios of 2-24. Patient compliance for biopsy and follow-up care is low (35-63%) in LMIC settings due to pain, fear, time and cost. Our novel solution is noninvasive imaging with a low-cost handheld reflec- tance confocal microscopy (RCM) - optical coherence tomography (OCT) device. Diagnosis and grading of oral dysplasia are based on cellular atypia in the epithelium and underlying architectural changes. RCM imag- ing shows cellular morphology in the entire epithelium to depth of 300 µm. OCT imaging shows epithelial lay- ers and underlying lamina propria to deeper depth of 1 mm. Combined RCM-OCT imaging with a single de- vice will enable simultaneous imaging of cellular atypia and architectural changes in co-located fields of view to guide diagnosis, grade dysplasia, monitor progression to malignancy and assess invasion. Stratification, with a quantitative RCM-OCT scoring algorithm, will guide triage of oral lesions into low-grade dysplasia, which can be monitored or immediately treated with non-surgical therapies, versus high-grade, which may be immediately biopsied, versus carcinoma, which will be surgically excised. Diagnosis may be combined with treatment, all integrated in a single patient visit - a “one stop shop” patient care paradigm. We are an academic-industry team at Memorial Sloan Kettering Cancer Center (New York, NY), Physical Sciences Inc. (Andover, MA), Cali- ber Imaging and Diagnostics (Rochester, NY) and our LMIC collaborators at Tata Memorial Hospital (TMH, Mumbai). For FOA PAR-21-166, innovation is defined to be “likelihood of delivering a new capability to end- users.” Innovations will be in delivering an RCM-OCT device with a new probe for intra-oral imaging and in designing a quantitative diagnostic scoring algorithm to guide diagnosis and treatment, in real-time, at the bed- side. The device will be delivered to TMH and will ultimately cost $25,000, when scaled up and locally manu- factured in LMICs, which will support dissemination of RCM-OCT as a new and affordable imaging capability in LMICs. In preliminary studies, RCM-OCT imaging detected oral lesions and cancers with sensitivity of 100% and specificity of 80%. Our specific aims are (1) to design a handheld RCM-OCT device for imaging in the oral cavity; (2) to prospectively test on 4,422 patients for diagnosis, grading of dysplasia and assessment of invasion in oral lesions and cancers in vivo. Testing will be in LMIC settings, at TMH in Mumbai and in their regional clinic in Varanasi. Affordability, delivery of care in LMICs: the return-on-investment on our device can be in 6-9 months at cancer centers, while the cost of care to deserving patients can be as little as zero to 50 cents for the imaging procedure. Our initial success in India will seed global effort in LMICs.