Simultaneous coaxial widefield imaging and reflectance confocal microscopy for improved diagnosis of skin cancers in vivo

同时同轴宽场成像和反射共焦显微镜可改善皮肤癌的体内诊断

• 批准号: 10372929
• 负责人: Octavia Irma Camps
• 金额: $ 63.79万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-15 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10372929
• 关键词: Address; Adoption; Affordable Care Act; Aging; Algorithmic Software; Algorithms; Benign; Biopsy; Caliber; Cancer Center; Categories; Cellular Morphology; Clinic; Clinical; Code; Collaborations; Computer Vision Systems; Computer software; Current Procedural Terminology; Dermatologist; Dermatology; Dermis; Dermoscopy; Devices; Diagnosis; Diagnostic; Drops; Effectiveness; Endoscopes; Engineering; Epidermis; Grant; Head and neck structure; Image; Imaging Techniques; Lesion; Lesion by Morphology; Letters; Location; Machine Learning; Malignant - descriptor; Malignant Neoplasms; Medicaid services; Medicare/Medicaid; Memorial Sloan-Kettering Cancer Center; Microscope; Microscopic; Montana; Morphology; Optics; Oral; Outcome; Pathology; Patient Care; Patients; Performance; Predictive Value; Procedures; Public Health; Publishing; Research; Research Personnel; Resolution; Sensitivity and Specificity; Site; Skin; Skin Cancer; Specificity; Surface; Technology; Testing; Time; United States Centers for Medicare and Medicaid Services; Universities; Visual; base; blind; cancer diagnosis; clinical examination; clinical practice; cost; design; design and construction; diagnostic accuracy; diagnostic strategy; gastrointestinal; image guided; image processing; image registration; improved; in vivo; innovation; instrument; instrumentation; interest; lens; medical specialties; microscopic imaging; miniaturize; novel; novel diagnostics; optical imaging; prospective test; reflectance confocal microscopy; response; routine practice; skin lesion; volunteer

1 Dermatologists rely on visual (clinical widefield) and dermoscopic examination of skin lesions to guide the need 2 for biopsy. With this approach, sensitivity is high, but specificity tends to be quite variable and lower, resulting 3 in millions of biopsies of benign lesions every year. To improve specificity, several optical technologies are 4 being developed to noninvasively detect skin cancer. Of these, reflectance confocal microscopy (RCM) is the 5 furthest advanced in clinical utility, proven for diagnosing skin cancers with high sensitivity and specificity. 6 RCM imaging, guided by dermoscopy, detects skin cancers with 2 times superior specificity, and reduces the 7 benign-to-malignant biopsy rate by 2 times, compared to that with dermoscopy alone. In 2016, the Centers for 8 Medicare and Medicaid Services granted current procedural terminology (CPT) reimbursement codes for RCM 9 imaging of skin. RCM imaging combined with dermoscopy is now advancing into clinical practice, sparing pa- 10 tients from unnecessary biopsies of benign lesions. However, toward widespread acceptance and adoption, a 11 key challenge is that clinical widefield examination, dermoscopy and RCM imaging are currently performed as 12 three separate procedures with separate devices. Clinicians do not precisely know the location of RCM imag- 13 es relative to the surrounding contextual lesion morphology that is seen with clinical widefield examination and 14 dermoscopy, resulting in lower and more variable diagnostic accuracy (particularly, sensitivity, positive and 15 negative predictive values). We propose a novel solution: (i) a new objective lens with an integrated micro- 16 camera, to deliver a concurrent widefield image of the skin surface surrounding the location of RCM imaging; 17 (ii) a new software algorithm for widefield image-based tracking of the location of RCM images within a dermoscopic 18 field of view; (iii) a new diagnostic approach that will proactively use widefield imaging to locate RCM images in 19 dermoscopic images. We intend to deliver this integrated widefield clinical, dermoscopic and RCM imaging ap- 20 proach into the clinic, toward a new standard for more accurate, consistent and faster RCM imaging to guide 21 patient care. Preliminary studies with a “mock” objective lens and micro-camera on a bench-top set-up 22 demonstrated excellent optical sectioning (~2 µm) and resolution (~1 µm) for RCM imaging, and accurate and 23 repeatable location of RCM fields-of-view within the widefield image. RCM images showed excellent cellular 24 and morphologic detail in vivo. Our specific aims are (1) to develop a handheld reflectance confocal micro- 25 scope with integrated widefield camera; (2) to develop image processing algorithms for real-time widefield im- 26 aging-guided tracking of RCM image locations within dermoscopic fields; (3) to test and validate performance 27 on 100 patients. Although our proposition is for skin lesions, the research will surely have wider impact for 28 imaging in other settings, particularly, with miniaturized confocal microscopes and endoscopes, which have 29 very small fields-of-view. We are a highly synergistic team from Montana State University, Memorial Sloan 30 Kettering Cancer Center, Northeastern University and Caliber Imaging and Diagnostics (formerly, Lucid Inc.).

1 皮肤科医生依靠对皮肤病变的视觉（临床宽视野）和皮肤镜检查来指导需要 2 用于活检。使用这种方法，灵敏度很高，但特异性往往变化很大且较低，因此 每年对良性病变进行数百万次活检。为了提高特异性，采用了多种光学技术 4 正在开发用于无创检测皮肤癌。其中，反射共焦显微镜 (RCM) 是最 5 临床实用性最先进，已被证明能够以高灵敏度和特异性诊断皮肤癌。 6 RCM 成像在皮肤镜检查的指导下，以 2 倍的优越特异性检测皮肤癌，并减少 7 良恶性活检率比单纯皮肤镜检查提高2倍。 2016 年，该中心 8 医疗保险和医疗补助服务授予 RCM 现行程序术语 (CPT) 报销代码 9 皮肤成像。 RCM 成像与皮肤镜检查相结合现已进入临床实践， 10 名患者免受不必要的良性病变活检。然而，为了得到广泛接受和采用， 11 主要挑战是目前临床广视野检查、皮肤镜检查和 RCM 成像 12 三个独立的程序具有独立的设备。临床医生并不确切知道 RCM 影像的位置 13 es 相对于通过临床宽视野检查观察到的周围病变形态 14 皮肤镜检查，导致诊断准确性较低且变化更大（特别是敏感性、阳性和 15 个阴性预测值）。我们提出了一种新颖的解决方案：（i）带有集成微透镜的新物镜 16个摄像头，提供RCM成像位置周围皮肤表面的并发宽场图像； 17 (ii) 一种新的软件算法，用于基于宽场图像跟踪皮肤镜内 RCM 图像的位置 18视野； (iii) 一种新的诊断方法，将主动使用宽场成像来定位 RCM 图像 19张皮肤镜图像。我们打算提供这种集成的宽视野临床、皮肤镜和 RCM 成像应用程序 20 进入临床，迈向更准确、一致和更快 RCM 成像的新标准，以指导 21 病人护理。在台式装置上使用“模拟”物镜和微型相机进行初步研究 22 展示了 RCM 成像的出色光学切片 (~2 µm) 和分辨率 (~1 µm)，以及准确和 23 宽视场图像中 RCM 视场的可重复位置。 RCM 图像显示出色的细胞 24和体内形态学细节。我们的具体目标是（1）开发手持式反射共焦微 25 瞄准镜，带集成宽视场相机； (2) 开发实时宽场成像的图像处理算法 26 皮肤镜视野内 RCM 图像位置的老化引导跟踪； (3) 测试和验证性能 27 对 100 名患者。虽然我们的主张是针对皮肤病变，但这项研究肯定会对以下领域产生更广泛的影响： 28 在其他环境下成像，特别是使用微型共焦显微镜和内窥镜，它们具有 29 非常小的视野。我们是一支来自蒙大拿州立大学纪念斯隆管理学院的高度协同团队 30 凯特林癌症中心、东北大学和 Calibre Imaging and Diagnostics（前身为 Lucid Inc.）。