Fast, large area, multiphoton exoscope (FLAME) for improving early detection of melanoma

快速、大面积、多光子外窥镜 (FLAME) 用于改善黑色素瘤的早期检测

• 批准号: 10687990
• 负责人: Mihaela Balu
• 金额: $ 60.54万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10687990
• 关键词: Adoption; Advanced Development; Affect; Algorithms; Area; Benign; Benign Melanocytic Nevus; Biological Markers; Biopsy; Cellular Morphology; Clinical; Clinical Research; Collaborations; Collagen; Computer software; Connective Tissue; Cutaneous Melanoma; Data Analyses; Dermatology; Dermoscopy; Devices; Diagnosis; Discriminant Analysis; Disease; Early Diagnosis; Elastin Fiber; Electronics; Environment; Fluorescence; Generations; Germany; Histopathology; Image; Image Analysis; Imaging Device; Imaging Techniques; Interobserver Variability; Keratin; Label; Lasers; Lesion; Lesion by Stage; Maps; Mechanics; Medical Care Costs; Melanins; Melanocytic Neoplasm; Metabolism; Methods; Microscope; Microscopic; Modality; Molecular; Morphology; Motion; Nature; Negative Finding; Optics; Pathology; Patients; Performance; Physicians; Physiological; Reporting; Research Personnel; Resolution; Safety; Scanning; Side; Signal Transduction; Skin; Skin Tissue; Specific qualifier value; Speed; Standardization; Structure; Superficial Lesion; System; Technology; Testing; Time; Tissues; Training; Treatment Cost; United States; Universities; Validation; application programming interface; clinical imaging; cost; data acquisition; data standards; deep learning; ex vivo imaging; imaging detection; imaging platform; imaging study; improved; in vivo; in vivo imaging; indexing; industry partner; innovation; instrument; melanocyte; melanoma; metabolic imaging; multi-photon; multidisciplinary; multiphoton microscopy; non-invasive imaging; optical imaging; performance tests; portability; prototype; real-time images; restoration; second harmonic; software development; standard of care; submicron; temporal measurement; tool; translational study; two-dimensional; two-photon

Project Summary Early detection of melanoma is a key factor in improving patient survival and decreasing treatment costs. The sensitivity of dermoscopy, the standard of care in the diagnosis of melanocytic lesions, was reported to be highly variable, ranging between 68-96%, depending on the proficiency of the physician and the stage of the lesion. Low sensitivity reflects high rates of false-negative findings, which delay diagnosis and treatment. Thus doctors must err on the side of caution, which leads to an excess of unnecessary biopsies and increased medical costs. Distinguishing cutaneous melanoma from benign melanocytic nevi with high accuracy based on dermoscopy remains a challenge even when in the hands of expert clinicians since this approach only offers a two-dimensional image of the lesion's superficial structure. Ultimately, a biopsy is necessary for definitive diagnosis by the dermatopathologist, but this too may be affected by inter-observer variability, resulting in discordant conclusions. A study performed at the Melanoma Center, at UCSF estimated that 214,500 to 643,500 cases of melanocytic neoplasms in the United States would be diagnosed differently by another dermatopathologist, annually, which has significant consequences for the patient regardless of the nature of the lesion. We propose to develop and clinically evaluate a fast, large area multiphoton exoscope (FLAME) as a tool for non-invasive imaging and early detection of melanoma in order to reduce false positives and false negatives in both dermoscopy and histopathology. Multiphoton microscopy (MPM) is a nonlinear optical imaging technique that provides unique structural and molecular contrast based on endogenous signals such as second harmonic generation from collagen and two-photon excited fluorescence from NAD(P)H/FAD+, keratin, melanin and elastin fibers. In preliminary studies, we demonstrated that macroscopic areas of skin (cm2 scale) could be mapped out with microscopic resolution within ~2 minutes by combining optical and mechanical scanning mechanisms with deep learning image restoration. As required by PAR-20-155 our academic-industrial partnership will deliver a powerful MPM imaging tool to clinicians for non-invasive, real- time quantitative assessment at the bedside that would not require specialized training. Our proposed application is for early diagnosis of melanoma, but the approach will have wider impact, for rapid, in vivo characterization of cellular morphologic and metabolic imaging endpoints in patients. Our specifics aims are: (1) to develop FLAME, a compact, portable MPM prototype system for rapid, depth-resolved in vivo imaging of skin, over macroscopic areas (cm2-scale) with microscopic resolution and enhanced molecular contrast; (2) to implement safety features and demonstrate the technical feasibility; (3) to test the performance of FLAME by evaluating its ability to provide in vivo quantitative optical endpoints with sufficiently high predictive power to reliably distinguish benign from early melanoma lesions. We are a multi-disciplinary team of investigators from UC Irvine, Vidrio Technologies, LLC and Tufts University with 3 to 8 years record of collaboration.

项目摘要 早期发现黑色素瘤是改善患者存活和减少治疗的关键因素 费用。皮肤镜检查的敏感性是诊断黑素细胞病变的护理标准 据报道是高度可变的，介于68-96％之间，具体取决于医师的熟练程度 病变的阶段。低灵敏度反映了假阴性发现的高率，这会延迟诊断和 治疗。因此，医生必须谨慎行事，这会导致过量不必要的活检和 增加医疗费用。以高精度区分皮肤黑色素瘤和良性黑色素型NEVI 即使在专家临床医生手中，基于皮肤镜检查仍然是一个挑战 仅提供病变浅表结构的二维图像。最终，必须进行活检 皮肤病理学家确定的诊断，但这也可能受到观察者间变异性的影响， 得出不一致的结论。在UCSF的黑色素瘤中心进行的一项研究估计 214,500至643,500例在美国的黑素细胞肿瘤病例将通过不同的诊断 每年的另一位皮肤病理学家，这对患者产生重大影响 病变的性质。我们建议开发和临床评估快速的大面积多光外观 （火焰）作为非侵入性成像和早期检测黑色素瘤的工具，以减少假阳性 以及皮肤镜和组织病理学中的假阴性。多光子显微镜（MPM）是非线性 光学成像技术可根据内源信号提供独特的结构和分子对比度 例如从NAD（P）H/FAD+的胶原蛋白和两光激发荧光的第二次谐波产生， 角蛋白，黑色素和弹性纤维。在初步研究中，我们证明了皮肤的宏观区域 （CM2量表）可以通过组合光学和 具有深度学习图像恢复的机械扫描机制。根据Par-20-155的要求我们的要求 学术工业合作伙伴关系将为临床医生提供强大的MPM成像工具，以实现无创，现实 不需要专门培训的床边的时间定量评估。我们提出的 用于早期诊断黑色素瘤的应用，但该方法将对快速，体内产生更大的影响 患者细胞形态和代谢成像终点的表征。我们的具体目的是： （1）开发火焰，一种紧凑的便携式MPM原型系统，用于快速，深度分辨的体内成像 皮肤，在宏观区域（CM2尺度）上具有微观分辨率和增强的分子对比度； （2）至 实施安全功能并证明技术可行性； （3）测试火焰的性能 评估其提供体内定量光学端点具有足够高的预测能力的能力 可靠地区分良性与早期黑色素瘤病变。我们是来自调查人员的多学科团队 UC Irvine，Vidrio Technologies，LLC和Tufts University拥有3到8年的合作记录。