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

基本信息

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
项目类别：
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&apos 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

项目摘要

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（由申请人提供）：摘要：多光子显微镜（MPM）是一种非线性的Lasanning显微镜技术，即三维分辨率，快速成像能力和无标记的分子对比度二核苷酸（NADH），黄素腺苷二核苷酸（FAD），角蛋白stin纤维（通过两光蛋白激发荧光，TPEF），可以产生组织结构的高分辨率图像，并需要用于外源性型号的外源性。适合在体内表征浅表性的，以评估体内多光子显微镜，以提供足够高的预测能力的Opti Cal端点，以可靠地区分三组的色素病变：常见的Nevi结果从15个病变（14名患者）研究中获得，我们确定了与TPEF和信号有关的三个光学生物标志物，并将其与体内Molecualarz Vivo组织病理学标准相关联。区分常见的NEVI（MMI = 0-1），非典型NEVI（MMI = 1-4）和黑色素瘤（MMI = 5-8）（P <0.05），我们现在提出了一项有希望的前瞻性临床试验为了确定MMI或类似的MPM派生指数，我们希望我们的结果将提供经过验证的Decisisiont，以驱除普通Nevi，非典型NEVI和黑色素瘤的iAngnosis。与常规的组织病理学的对比有望导致黑色素瘤的起源和进展。