Molecular and cellular imaging of bone biopsies using AI augmented deep UV Raman microscopy

一个探索性的研究项目将发展分子的深紫外拉曼显微高光谱成像 和/或生物组织的细胞分析，目的是早期发现、改进筛查和临床 癌症诊断学。拉曼显微镜经常用于癌症生物学，以识别正在发生的化学变化； 然而，检测的敏感性和特异性仍然是一个挑战。这种基础知识的鸿沟 关于如何通过利用深紫外光激发来改善这种图像的信息上下文， 通过对特定分子的共振激发，将提高分子检测的特异性和 通过在背景中增强信号来提高灵敏度。要进一步提高基于图像的 分析和筛选，将开发一种新型的高光谱图像分析平台。拟议的研究 该计划通过开发一种至少能够进行拉曼成像的仪器来填补技术空白 速度提高100倍，通过评估低频拉曼模式获取新信息，同时减少 成本和占地面积，以加快该仪器的广泛应用。新的成像系统 将应用新的高光谱成像算法来处理多维成像数据 推进骨肿瘤的活检具有挑战性，骨肿瘤是许多癌症最具破坏性的后果之一 目标是达到95%的特异性。在目标1中，一种正在申请专利的新型广域深紫外高光谱 拉曼成像平台将针对癌症组织样本进行优化。将建造一个工作原型，并将其 性能将进行实验表征。在Aim 2中，一个具有机器和深度的数据分析平台 将开发骨组织病理学的学习算法。先进的成像算法，将 考虑到许多小的变化，除了传统的拉曼光谱分析外，还将使用拉曼光谱。机器学习 将开发深度学习技术，以自动确定当前是/否之外的异常 肿瘤范例。在目标3中，开发的平台将被验证为一种新的分析策略。研究将会 重点研究骨转移癌动物模型中肿瘤的鉴别和一套光学检测方法 能够快速识别肿瘤的标记。建议的战略提供了一种新的使能技术 阐明癌症发生和发展的基本机制，有助于癌症的早期发现， 筛查和/或癌症风险评估，通过区分、评估和/或观察癌症分期和 进步。整体方法的目标是广泛传播这项技术，其相对低成本和无缝 过渡到临床环境。R33期将提高检测的灵敏度，并识别路径 走向商业化。研究性研究还将为开发新的先进方法提供路线图 用于研究各种与骨相关的肿瘤，并确定新的临床前和临床检测方法。

An exploratory research project will develop deep-UV Raman microscopic hyperspectral imaging for molecular and/or cellular analysis of biological tissues with a goal of the early detection, improved screening, and clinical diagnostics of cancer. Raman microscopy is often used in cancer biology to identify occurring chemical changes; however, the sensitivity and specificity of detection remain to be a challenge. This gap of fundamental knowledge on how to improve the information context of such images will be addressed by utilizing deep UV excitation, which, through resonance excitation of specific molecules will enhance specificity of molecular detection and improve the sensitivity by enhancing the signal against the background. To further improve the image-based analysis and screening, a novel hyperspectral image analysis platform will be developed. The proposed research program fills the technology gaps by developing an instrument, capable of performing Raman imaging at least 100 times faster, acquire new information through assessing low-frequency Raman modes, while reducing the cost and the footprint to accelerate the wide-spread availability of the instrument. The new imaging system augmented with novel hyperspectral imaging algorithms to handle multidimensional imaging data will be applied to advance a challenging biopsy of bone tumors, one of the most devastating consequences of many cancers with the goal to achieve 95% specificity. In Aim 1, a novel, patent-pending, wide-field deep UV hyperspectral Raman imaging platform will be optimized for cancer tissue samples. A working prototype will be built, and its performance will be experimentally characterized. In Aim 2, a data analysis platform with machine and deep learning algorithms for pathology of bone tissue will be developed. Advanced imaging algorithms that take into account many small changes in addition to a traditional analysis of Raman spectra will be used. Machine learning and deep learning techniques will be developed to automatically determine abnormalities beyond current yes/no tumor paradigm. In Aim 3, the developed platform will be validated as a novel analysis strategy. Research will focus on distinguishing tumors in the animal model of metastatic bone cancer and developing a set of optical markers to enable rapid identification of tumors. The proposed strategy offers a novel enabling technology to elucidate basic mechanisms underlying cancer initiation and progression and will facilitate early cancer detection, screening, and/or cancer risk assessment, by differentiating, evaluating and/or observing cancer stages and progression. The overall approach targets the wide spread of the technology, its relatively low-cost and seamless transition to clinical setting. The R33 phase will improve the sensitivity of detection and identify the pathways toward commercialization. The research study will also provide a roadmap to develop a new advanced approach for studying a variety of bone-related tumors and identify novel preclinical and clinical assays.