Thayer School of Engineering at Dartmouth, Hanover, New Hampshire, United States.
Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States.
J Biomed Opt. 2021 Jan;26(1). doi: 10.1117/1.JBO.26.1.010902.
Deep-tissue penetration by x-rays to induce optical responses of specific molecular reporters is a new way to sense and image features of tissue function in vivo. Advances in this field are emerging, as biocompatible probes are invented along with innovations in how to optimally utilize x-ray sources.
A comprehensive review is provided of the many tools and techniques developed for x-ray-induced optical molecular sensing, covering topics ranging from foundations of x-ray fluorescence imaging and x-ray tomography to the adaptation of these methods for sensing and imaging in vivo.
The ways in which x-rays can interact with molecules and lead to their optical luminescence are reviewed, including temporal methods based on gated acquisition and multipoint scanning for improved lateral or axial resolution.
While some known probes can generate light upon x-ray scintillation, there has been an emergent recognition that excitation of molecular probes by x-ray-induced Cherenkov light is also possible. Emission of Cherenkov radiation requires a threshold energy of x-rays in the high kV or MV range, but has the advantage of being able to excite a broad range of optical molecular probes. In comparison, most scintillating agents are more readily activated by lower keV x-ray energies but are composed of crystalline inorganic constituents, although some organic biocompatible agents have been designed as well. Methods to create high-resolution structured x-ray-optical images are now available, based upon unique scanning approaches and/or a priori knowledge of the scanned x-ray beam geometry. Further improvements in spatial resolution can be achieved by careful system design and algorithm optimization. Current applications of these hybrid x-ray-optical approaches include imaging of tissue oxygenation and pH as well as of certain fluorescent proteins.
Discovery of x-ray-excited reporters combined with optimized x-ray scan sequences can improve imaging resolution and sensitivity.
利用 X 射线穿透深层组织以诱导特定分子报告器产生光学响应，是一种用于活体感知和成像组织功能特征的新方法。随着发明出生物相容性探针以及如何优化利用 X 射线源的创新，该领域的进展正在涌现。
全面综述了用于 X 射线诱导光学分子传感的多种工具和技术，涵盖了从 X 射线荧光成像和 X 射线层析成像的基础到这些方法在活体传感和成像中的应用等多个方面。
综述了 X 射线与分子相互作用并导致其光学发光的多种方式，包括基于门控采集和多点扫描的时间方法，以提高横向或轴向分辨率。
虽然一些已知的探针在 X 射线闪烁时可以产生光，但人们已经认识到，X 射线诱导的切伦科夫光也可以激发分子探针。切伦科夫辐射的发射需要 X 射线在高千伏或兆伏范围内的阈值能量，但具有能够激发广泛的光学分子探针的优点。相比之下，大多数闪烁剂更容易被较低能量的 X 射线激活，但由结晶无机成分组成，尽管也设计了一些有机生物相容性试剂。现在，基于独特的扫描方法和/或对扫描 X 射线束几何形状的先验知识，已经可以创建高分辨率结构 X 射线-光学图像的方法。通过仔细的系统设计和算法优化，可以进一步提高空间分辨率。这些混合 X 射线-光学方法的当前应用包括对组织氧合和 pH 以及某些荧光蛋白的成像。
发现 X 射线激发的报告器与优化的 X 射线扫描序列相结合，可以提高成像分辨率和灵敏度。
