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: 10365803
• 负责人: Mihaela Balu
• 金额: $ 59.3万
• 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/10365803
• 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; Custom; Cutaneous Melanoma; Data Analyses; Dermatology; Dermoscopy; Devices; Diagnosis; Discriminant Analysis; Disease; Early Diagnosis; Elastin Fiber; Environment; Fluorescence; Generations; Germany; Histopathology; Image; Image Analysis; Imaging Device; Imaging Techniques; Institutes; 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; Pigments; Reporting; Research Personnel; Resolution; Safety; Scanning; Side; Signal Transduction; Skin; Skin Tissue; Speed; Standardization; Structure; Superficial Lesion; System; Technology; Testing; Time; Tissues; Training; Treatment Cost; United States; Universities; Validation; application programming interface; base; 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提高患者存活率和减少治疗的关键因素 成本。诊断黑素细胞病变的标准皮肤镜检查的敏感性是 据报道是高度可变的，范围在68%-96%之间，取决于医生的熟练程度和 病变分期。低敏感性反映了假阴性发现的高比率，这延误了诊断和 治疗。因此，医生必须谨慎行事，这会导致过多的不必要的活检和 增加了医疗费用。高准确率鉴别皮肤黑色素瘤与良性黑色素细胞痣 由于这种方法，即使在专家临床医生的手中，皮肤镜检查仍然是一个挑战 只提供病变表面结构的二维图像。最终，活组织检查是必要的 皮肤科医生的明确诊断，但这也可能受到观察者间变异性的影响， 导致了不一致的结论。加州大学旧金山分校黑色素瘤中心进行的一项研究估计 在美国，214,500到643,500例黑素细胞肿瘤的诊断将有所不同 另一位皮肤科医生，每年，这会对患者产生重大后果，无论 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)作为黑色素瘤非侵入性成像和早期检测的工具，以减少假阳性 皮肤镜和组织病理学检查均为假阴性。多光子显微镜(MPM)是一种非线性的 基于内源信号提供独特结构和分子对比度的光学成像技术 例如胶原产生二次谐波和NAD(P)H/FAD+产生双光子激发荧光， 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 (cm2尺度)可以通过光学和光学相结合在~2分钟内以显微分辨率绘制出来 具有深度学习图像恢复的机械扫描机制。根据PAR-20-155我们的要求 学术界和产业界的合作将为临床医生提供强大的MPM成像工具，以实现无创、真实的 在床边进行时间量化评估，不需要专门培训。我们的建议 应用是为了黑色素瘤的早期诊断，但这种方法将产生更广泛的影响，以便快速、活体 患者细胞形态和代谢成像终点的特征。我们的具体目标是： (1)开发一种紧凑、便携的MPM原型系统FLAME，用于快速、深度分辨的活体成像 皮肤，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 实施安全特性并论证技术可行性；(3)通过以下方法测试火焰性能 评估其提供具有足够高的预测能力的体内定量光学端点的能力 可靠地区分良性和早期黑色素瘤病变。我们是一个由多学科调查人员组成的团队， 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。