Quantitative in-vivo and clinical imaging (Boppart)

摘要 在实验室开发的成像技术进步找到直接的平移路径是至关重要的 为了快速证明它们在患者中的临床效用，并建立改进检测的潜力， 疾病的诊断和监测。虽然基于标签的光学成像模式已经显示出潜力 在术中癌症检测中，绘制微血管图，并对改变的部位进行定位 新陈代谢和病理学，举几个例子，这些方法往往需要大量的时间和财务成本 由于相关的安全风险和FDA批准任何新对比所需的冗长审查过程 代理或探测器。重要的是，任何新的靶向造影剂或探头都不可避免地会有某种程度的非 特定结合或靶外标记，以及靶细胞或靶细胞的摄取或标记的可变程度 地点。最后，测量或成像的信号电平总是受到质疑。信号是否很低是因为 靶向病理是最小的，还是因为标记的靶向效率低？无标签的重要性 因此，成像是很高的，并且对跨尺寸尺度的无标签成像的需求很大。通过确定可靠的 无标记信号或生物标记物，指示结构、分子组成、代谢和 功能、定量临床和活体成像不仅成为基于标记的方法的可行替代方案， 而且还为临床人体研究提供了一条直接和快速的转换途径，因为监管部门的批准不是 此外还需要造影剂或探头。这使得在活体内实现了第一次到人类的快速和有限规模的 将使用新的光学仪器进行人体研究研究(以及随后的更大规模的临床试验) 成像技术，并及早确定这些技术和新光学技术的临床应用 它们产生的生物标记物。TRD通过四个具体目标关注技术发展 从1)亚细胞和细胞尺度，识别光学生物标记物和签名 在先进的数字病理平台中显示更多系统性疾病过程，以2)组织切片 人工智能，到3)扩展深度和性能的计算光学成像算法 厚组织的光学成像，最后到工程化的光束传输系统，以广泛扩展组织 这些无标签光学成像模式的访问和应用。总而言之，这个项目将展示 新的技术进步将发现无数的应用来推动生物和医学 科学，提高临床医学的诊断和监测能力。

SUMMARY It is essential that technological advances in imaging developed in the laboratory find direct translational paths to rapidly demonstrate their clinical utility in patients, and establish the potential for improving detection, diagnosis, and monitoring of disease. While label-based optical imaging modalities have demonstrated potential in intraoperative cancer detection, mapping the microvasculature, and site-specifically targeting of altered metabolism and pathology, to name a few, these approaches often come at a significant time and financial cost due to the associated safety risks and lengthy review processes required for FDA approval of any new contrast agent or probe. Importantly, any new targeted contrast agent or probe inevitably will have some degree of non- specific binding or off-target labeling, as well as a variable degree of uptake or labeling of the targeted cell or site. In the end, the measured or imaged signal levels are always questioned. Is the signal low because the targeted pathology is minimal, or because the targeted efficiency of labeling is low? The importance of label-free imaging is therefore high, and the need for label-free imaging across size scales is great. By identifying robust label-free signals or biomarkers that indicate changes in structure, molecular composition, metabolism, and function, quantitative clinical and in vivo imaging not only becomes a feasible alternative to label-based methods, but also provides a direct and rapid translational path to clinical human studies, since regulatory approval is not additionally needed for a contrast agent or probe. This enables rapid in vivo first-to-human and limited-scale human subjects research studies (and subsequently larger clinical trials) to be performed with the new optical imaging technologies, and make early determination of the clinical utility of the technologies and the new optical biomarkers that they generate. This TRD focuses on the technological development through four specific aims that progress from 1) the sub-cellular and cellular scale, identifying optical biomarkers and signatures that would indicate more systemic disease processes, to 2) tissue sections in an advanced digital pathology platform with artificial intelligence, to 3) computational optical imaging algorithms that extend the depth and performance of optical imaging in thick tissues, and finally to 4) engineered beam delivery systems to widely expand tissue access and application for these label-free optical imaging modalities. Collectively, this project will demonstrate novel technological advances that will find a myriad of applications to advance the biological and medicine sciences, and improve diagnostic and monitoring capabilities in clinical medicine.