Improving the penetration depth in vivo optical imaging of cancer

描述(申请人提供)：在这项R21探索性计划中，将探索和演示体内多光子显微成像的新概念和系统，以实现前所未有的对散射生物组织的渗透深度。提出的研究包括两个同时推进：第一个包括探索新的光谱窗口，大大减少了多光子显微镜的组织散射；第二个推动集中在照明场的空间和时间分量的同时聚焦，以显著提高成像散射组织的信号背景比。这两个平行的研究组件将各自提高当前多光子显微镜的穿透深度，并根据涉及的应用，可以组合在一起，以实现最大效益。应用这些新的概念和技术，我们的目标是创建一种新的多光子成像系统，提供前所未有的穿透深度，为体内癌症检测和癌症生物学的体内研究提供新的工具。体内光学成像具有高分辨率和分子特异性，在非侵入性癌症检测和诊断方面具有巨大的潜力。然而，由于在大多数生物组织中遇到的强散射，现在光学成像主要限于表层。这种穿透深度的缺乏严重限制了光学技术在癌症研究中的适用性。该计划的目标是创造和开发实用的方法来延长穿透深度，显著增加光学成像技术在癌症检测和诊断中的覆盖范围。为了适应这一提议的广度，该计划涉及国际和平协会和联合国际组织Warren Zipfel博士之间的密切合作。该计划的三个具体目标是：1.探索和展示减少组织散射的多光子显微镜的新光谱窗口。2.提出并论证了空间和时间同时聚焦的概念，以提高成像散射样品的信本底比。3.展示用于癌症研究的多光子显微镜/内窥镜成像的具体目标1和2。

DESCRIPTION (provided by applicant): In this R21 exploratory program, novel concepts and systems for in vivo multiphoton microscopic imaging will be explored and demonstrated to enable unprecedented penetration depth into scattering biological tissues. The proposed research consists of two concurrent thrusts: the first involves the exploration of new spectral windows with much reduced tissue scattering for multiphoton microscopy; the second thrust concentrates on the simultaneous focusing of the spatial and temporal components of the illumination field to significantly enhance the signal to background ratio in imaging scattering tissues. These two parallel research components will each improve the penetration depth of current multiphoton microscopy and, depending on the applications involved, can be combined for maximum benefits. Applying these new concepts and techniques, we aim to create a new multiphoton imaging system that offers unprecedented penetration depth, providing new tools for both in vivo detection of cancer and in vivo studies of cancer biology. With its jam-resolution and molecular specificity, in vivo optical imaging holds tremendous potential for non-invasive cancer detection and diagnostics. Because of the strong scattering encountered in most biological tissues, however, optical imaging is now mostly restricted to the superficial layer. This lack of penetration depth severely limits the applicability of optical techniques for cancer research. The objective of this program is to create and develop practical methods for extending the penetration depth, significantly increasing the reach of optical imaging techniques in cancer detection and diagnostics. To accommodate the breadth of this proposal, this program involves close collaboration between the PI and Co-Pi Dr. Warren Zipfel. The three specific aims of the program are: 1. Explore and demonstrate new spectral windows for multiphoton microscopy with reduced tissue scattering. 2. Develop and demonstrate the concept of simultaneous spatial and temporal focusing for enhancing the signal to background ratio in imaging scattering samples. 3. Demonstrate specific aims 1 and 2 for multiphoton microscopic/endoscopic imaging for cancer research.