I-Corps: Chemometric fluorescence microscopic imaging and virtual staining for rapid label-free histopathology

这个i-Corps项目的更广泛的影响/商业潜力是实现稳健、快速和无标签的生物样本评估。癌症是一个世界性的公共卫生问题，目前它的诊断依赖于对生物材料样本的评估。迫切需要具有时效性和客观性的替代方法，以解决现有程序的几个缺点，这些缺点既耗时又费力，而且容易受到口译员变化的影响。拟议的项目是一种经过验证的方法，使用未经处理或最低限度处理的细胞和组织标本上的光。该方法特别适合于外科病房和远程病理实验室对快速准确诊断的要求。这个I-Corps项目是为了促进化学计量学、荧光、显微成像和虚拟染色(CFM-VS)在未染色的细胞和组织标本上的翻译。CFM使用内源性细胞荧光产生2D图像，揭示亚细胞的形态和功能，直观地区分特定的细胞属性，包括结构、细胞新陈代谢和蛋白质生产。CFM的一个独特优势是对内源性荧光生物分子的绝对浓度进行量化，使可靠和准确的诊断成为可能。CFM和衍生的虚拟染色(CFM-VS)已成功地应用于肺癌和前列腺癌的鉴别和诊断。未染色的组织切片的虚拟染色图像不仅与传统的苏木精-伊红(H&Amp；E)染色图像的形态相同，而且还表明了癌症引起的生化变化。CFM-VS的吸引人的功能包括：能够以接近实时的方式对未经处理或最小处理的细胞和组织切片进行成像；产生病理学家熟悉的虚拟H&amp；E染色图像；消除组织处理中引入的扭曲；实现稳健的诊断，并可以通过根据数据的积累学习而调整算法来改进诊断。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is to enable robust, rapid, and label-free biological sample evaluation. Cancer is a worldwide public health problem, and its diagnosis currently depends on evaluation of specimens of biological material. Time-efficient and objective alternative methods are urgently needed to address several shortcomings of the existing process, which is time-consuming, labor-intensive, and subject to interpreter variations. The proposed project is a validated method using light on unprocessed or minimally processed cell and tissue specimens. The proposed method particularly meets the demands of rapid and accurate diagnosis in surgical suites and telepathology laboratories. This I-Corps project is to advance the translation of chemometric fluorescence microscopic imaging and virtual staining (CFM-VS) on unstained cell and tissue specimens. Using endogenous cellular fluorescence, CFM produces 2D images revealing both subcellular morphology and function, visually differentiating specific cell properties including structure, cellular metabolism, and protein production. One unique advantage of CFM is the quantification of the absolute concentration of the endogenous fluorescent biomolecules, enabling reliable and accurate diagnosis. CFM and the derived virtual staining (CFM-VS) have been successfully applied to differentiate and diagnose lung and prostate cancers. The virtually stained images for unstained histological slides not only share the morphology of traditional hematoxylin and eosin (H&E) stained image counterparts, but also indicate the biochemical alterations due to cancer. Attractive features of CFM-VS include: ability to image unprocessed or minimally processed cell and tissue sections in close to real-time; yields virtual H&E stained images familiar to pathologists; eliminates distortions introduced in tissue processing; and robust diagnosis is achieved and may be improved through adaption of the algorithm from learning with the accumulation of data.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.