Quantitative multiphoton microscopy for non-invasive diagnosis of melanoma

定量多光子显微镜用于黑色素瘤的无创诊断

• 批准号: 9355016
• 负责人: KRISTEN M KELLY
• 金额: $ 4.5万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9355016
• 关键词: Actinic keratosis; Adenosine; Appearance; Benign Melanocytic Nevus; Biological Markers; Biopsy; Characteristics; Clinic; Clinical; Clinical Research; Clinical Trials; Collagen; Collagen Fiber; Comprehensive Cancer Center; Data; Decision Making; Dendrites; Dermal; Dermatologic; Dermatology; Dermoscopy; Development; Diagnosis; Diagnostic; Dimensions; Dinucleoside Phosphates; Dysplastic Nevus; Elastin Fiber; Environment; Epithelioid and spindle cell nevus; Excision; Family; Flavin-Adenine Dinucleotide; Flavins; Fluorescence; Generations; Germany; Goals; Gold; Histologic; Histopathology; Hutchinson' s Melanotic Freckle; Hyperplasia; Image; Keratin; Label; Laser Scanning Microscopy; Lead; Lesion; Light; Melanins; Methods; Microscopy; Molecular; Morphology; Nevi and Melanomas; Nevus; Nevus Cell; Nicotinamide adenine dinucleotide; Optics; Patients; Performance; Pigments; Recruitment Activity; Resolution; Sample Size; Signal Transduction; Source; Squamous cell carcinoma; Standardization; Structure; Techniques; Technology; Three-Dimensional Imaging; Time; Tissue imaging; Tissues; base; biomedical referral center; clinical Diagnosis; clinical imaging; design; diagnostic accuracy; effective therapy; experimental study; high resolution imaging; imaging capabilities; improved; in vivo; indexing; insight; melanocyte; melanoma; microscopic imaging; multi-photon; noninvasive diagnosis; novel strategies; patient population; prevent; prospective; public health relevance; quantitative imaging; second harmonic; standard of care; submicron; tool; two-photon

 DESCRIPTION (provided by applicant): Summary: Multiphoton microscopy (MPM) is a nonlinear laser scanning microscopy technique that features high three-dimensional resolution, fast imaging capabilities and label-free molecular contrast. Several endogenous tissue components can be visualized, including collagen (through second-harmonic generation, SHG), reduced nicotinamide adenine dinucleotide (NADH), flavin adenosine dinucleotide (FAD), keratin, melanin and elastin fibers (through two-photon excited fluorescence, TPEF). The ability to generate high- resolution images of tissue structure and composition without the need for exogenous labels makes MPM imaging particularly well-suited for characterizing superficial tissues in vivo. The purpose of this clinical imaging proposal is to evaluate the ability of in viv multiphoton microscopy to provide quantitative optical endpoints with sufficiently high predictive power to reliably distinguish between pigmented lesions in three groups: common nevi, atypical nevi and melanoma. The framework is based on our preliminary results obtained from a 15-lesion (14 patient) study where we identified three optical biomarkers related to TPEF and SHG signals and correlated these in vivo molecular features with conventional ex vivo histopathologic criteria. MPM biomarkers were combined to obtain a quantitative, 9-point numerical index (multi-photon melanoma index, MMI) that distinguished between common nevi (MMI = 0-1), atypical nevi (MMI = 1-4) and melanoma (MMI = 5-8) (p<0.05). We now propose a powered prospective clinical trial that follows on these promising results in order to determine whether the MMI, or similar MPM-derived index, can be reliably used in a clinical setting. We expect our results will provide a validated decision-making endpoint to increase clinical diagnosis accuracy of common nevi, atypical nevi and melanoma. In addition, our effort to correlate in vivo MPM-derived contrast with conventional histopathology is expected to lead to new insight regarding the origins of melanoma appearance and progression. Our long-term goal is to identify the right combination of quantitative clinical endpoints that would improve clinical diagnoses, guide effective treatment, and eliminate unnecessary biopsies while increasing identification of lesions requiring removal.

 描述（应用程序提供）：摘要：多光子显微镜（MPM）是一种非线性激光扫描显微镜技术，具有高三维分辨率，快速成像功能和无标签的分子对比度。可以看到几种内源性组织成分，包括胶原蛋白（通过第二次谐波，SHG），减少烟酰胺腺嘌呤二核苷酸（NADH），黄素腺苷二核苷酸（FAD），角蛋白，黑色素，黑色素和弹性纤维纤维（通过两片弹性纤维激发）。在不需要外源标签的情况下生成组织结构和组成图像的高分辨率图像的能力使得MPM成像特别适合在体内表征浅表时机。该临床成像建议的目的是评估体内多光子显微镜提供具有足够高的预测能力的定量光学终点的能力，以可靠地区分三组的小猪病变：常见的NEVI，非典型NEVI和黑色素瘤。该框架是基于我们从15个病变（14名患者）研究获得的初步结果，在该研究中，我们确定了与TPEF和SHG信号相关的三种光学生物标志物，并将这些体内分子特征与常规的体内组织病理学标准相关联。将MPM生物标志物组合在一起以获得定量的9点数值指数（多光子黑色素瘤指数，MMI），该指数，区分常见的NEVI（MMI = 0-1），非典型NEVI（MMI = 1-4）和黑色素瘤（MMI = 5-8）（MMI = 5-8）（P <0.05）。现在，我们提出了一项有能力的前瞻性临床试验，该试验遵循这些承诺结果，以确定在临床环境中可以可靠地使用MMI或类似MPM衍生的指数。我们预计我们的结果将提供验证的决策终点，以提高常见NEVI，非典型NEVI和黑色素瘤的临床诊断准确性。此外，我们将体内MPM衍生的对比与常规组织病理学相关的努力有望导致有关黑色素瘤外观和进展的起源的新见解。我们的长期目标是确定定量临床终点的正确组合，以改善临床诊断，指导有效治疗并消除不必要的活检，同时增加对需要去除的病变的识别。