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

口腔病变的反射共焦显微镜-光学相干断层扫描 (RCM-OCT) 成像：为发展中国家提供负担得起的设备和方法

• 批准号: 10735695
• 负责人: Pankaj Chaturvedi
• 金额: $ 72.87万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10735695
• 关键词: Adoption; Adult; Africa; Africa South of the Sahara; Algorithms; Architecture; Asia; Atypia; Benign; Biopsy; Caliber; Cancer Center; Carcinoma; Caring; Cellular Morphology; Central Asia; Cessation of life; Clinic; Clinical; Code; Confocal Microscopy; Connective Tissue; Detection; Developing Countries; Devices; Diagnosis; Diagnostic; Dysplasia; Engineering; Epithelial Attachment; Epithelium; Erythroplasia; Fibrosis; Fright; Future; Guidelines; Head and Neck Surgery; Head and neck structure; Healthcare; Hospitals; Image; Imaging Device; Imaging Techniques; Incidence; India; Industry; Invaded; Investments; Lamina Propria; Lesion; Leukoplakia; Malignant - descriptor; Malignant Neoplasms; Memorial Sloan-Kettering Cancer Center; Monitor; New York; Operative Surgical Procedures; Optical Coherence Tomography; Oral; Oral Diagnosis; Oral Medicine; Oral cavity; Pain; Pathology; Patient Care; Patients; Population; Prevalence; Protein Structure Initiative; Public Health; Reporting; Severities; Skin Cancer; Specificity; Stratification; Testing; Time; Triage; Underserved Population; Validation; Visit; Visual; World Health Organization; cancer care; cancer diagnosis; care costs; care delivery; cellular imaging; clinical examination; compliance behavior; cost; design; design,build,test; diagnosis standard; follow-up; image guided; imaging approach; imaging capabilities; imaging detection; in vivo; innovation; intraoral probe; keratinization; laptop; low and middle-income countries; malignant mouth neoplasm; manufacture; meter; microscopic imaging; non-invasive imaging; novel; optical imaging; oral dysplasia; oral lesion; outreach clinics; physical science; portability; prospective test; reflectance confocal microscopy; research clinical testing; scale up; socioeconomics; success; timeline

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.

口腔癌的发病率和患病率高发生在15-20发展中国家的低收入和中等收入人群中， 亚洲和非洲的低收入国家。临床肉眼检查后进行活检是诊断的标准， 鼻状口腔病变。但是，16-100%的视觉检查的低特异性和可变特异性导致活检 估计有37-51%的不确定病变（仅在印度就有140 - 210万处病变）和良性至恶性病变， Nant活组织检查比率为2-24。在LMIC环境中，患者对活检和随访护理的依从性较低（35-63%） 因为痛苦恐惧时间和成本我们的新解决方案是使用低成本手持式反射镜进行无创成像， 透射共焦显微镜（RCM）-光学相干断层扫描（OCT）装置。诊断和分级 口腔发育不良是基于上皮细胞的增生和潜在的结构变化。RCM图像- 扫描显示整个上皮细胞的细胞形态，深度为300 µm。OCT成像显示上皮层- 将RCM-OCT成像与单次去甲肾上腺素联合应用， vice将能够在同一位置的视野中同时成像细胞的细胞结构和结构变化， 指导诊断、异型增生分级、监测恶性进展和评估侵袭。分层， 定量RCM-OCT评分算法将指导口腔病变分类为低度异型增生， 与可能立即接受非手术治疗的高级别相比， 活组织检查与手术切除的癌相比。诊断可能与治疗相结合，所有 集成在单个患者访问中-“一站式”患者护理范例。我们是一个学术产业 Memorial Sloan Kettering Cancer Center（纽约，NY）的团队，Physical Sciences Inc.（Andover，MA），卡利- ber成像和诊断（罗切斯特，纽约）和我们在塔塔纪念医院（TMH， 孟买）。对于FOA PAR-21-166，创新被定义为“提供新能力的可能性， 用户”。创新将在于提供带有用于口腔内成像的新探头的RCM-OCT设备，并在 - 设计定量诊断评分算法，以在病床上实时指导诊断和治疗， 的方面想该设备将交付给TMH，最终成本为25，000美元，当规模扩大并在当地制造时， 在中低收入国家制作，这将支持RCM-OCT作为一种新的、负担得起的成像能力在 中低收入国家。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% 特异性为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4，422例患者进行前瞻性测试，以进行诊断，异型增生分级和评估， 口腔病变和体内癌症的侵袭。测试将在LMIC设置，在孟买的TMH和他们的 瓦拉纳西的一家地区诊所中低收入国家的医疗服务价格和交付：我们设备的投资回报率 可以在6-9个月内在癌症中心，而护理的成本，值得患者可以低至零， 成像程序50美分。我们在印度的初步成功将为全球在中低收入国家的努力奠定基础。