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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要黑色素瘤的早期发现是提高患者生存率和减少治疗的关键因素成本。皮肤镜检查（诊断黑素细胞病变的护理标准）的敏感性为据报道变化很大，范围在 68-96% 之间，具体取决于医生的熟练程度和病变阶段。低敏感性反映了假阴性结果的高发生率，从而延迟了诊断和治疗。因此，医生必须谨慎行事，这会导致过多不必要的活检和增加医疗费用。高精度区分皮肤黑色素瘤和良性黑色素细胞痣即使在专业临床医生手中，基于皮肤镜检查的方法仍然是一个挑战，因为这种方法仅提供病变表面结构的二维图像。最终，需要进行活检皮肤病理学家的明确诊断，但这也可能受到观察者间差异的影响，从而得出不一致的结论。加州大学旧金山分校黑色素瘤中心进行的一项研究估计美国 214,500 至 643,500 例黑素细胞肿瘤病例将被不同地诊断每年另一名皮肤病理学家，无论情况如何，都会对患者产生重大影响病变的性质。我们建议开发一种快速、大面积的多光子外窥镜并进行临床评估 (FLAME) 作为非侵入性成像和黑色素瘤早期检测的工具，以减少误报以及皮肤镜检查和组织病理学的假阴性。多光子显微镜 (MPM) 是一种非线性基于内源信号提供独特的结构和分子对比度的光学成像技术例如胶原蛋白的二次谐波和 NAD(P)H/FAD+ 的双光子激发荧光，角蛋白、黑色素和弹性蛋白纤维。在初步研究中，我们证明了皮肤的宏观区域通过结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，我们的学术与工业合作伙伴关系将为临床医生提供强大的 MPM 成像工具，以实现非侵入性、真实的在床边进行时间定量评估，不需要专门培训。我们提出的应用用于黑色素瘤的早期诊断，但该方法将产生更广泛的影响，用于快速、体内患者细胞形态和代谢成像终点的表征。我们的具体目标是： (1) 开发 FLAME，一种紧凑的便携式 MPM 原型系统，用于快速、深度分辨体内成像皮肤，在宏观区域（cm2 尺度），具有微观分辨率和增强的分子对比度； (2) 至实施安全功能并论证技术可行性； (3) 测试FLAME的性能评估其提供体内定量光学终点的能力，并具有足够高的预测能力可靠地区分良性和早期黑色素瘤病变。我们是一个由来自不同学科的研究人员组成的团队加州大学欧文分校、Vidrio Technologies, LLC 和塔夫茨大学有 3 至 8 年的合作记录。