Abstract：
Imaging whole brains is one of the central efforts of biophotonics. While the established imaging modalities used in radiology, such as MRI and CT, have enabled in vivo investigations of various cognitive and affective processes, the prevailing resolution of one-cubic-millimeter has limited their use in studying the \"ground-truth\" of neuronal activities. On the other hand, electron microscopy (EM) visualizes the finest anatomic structures at a resolution of around 30 nm. However, the extensive tissue preparation process and the required large-scale morphological reconstruction restrict this method to small sample volumes. Light microscopy (LM) has the potential to bridge the above two spatial scales, with a resolution ranging from a few hundred nanometers to a few micrometers. Recent advances in tissue clearing have paved the way for optical investigation of large intact tissue volumes. However, most of these LM studies rely on fluorescence-a nonlinear optical process to provide contrast. This chapter introduces an alternative type of LM that is solely based on a linear optical process-elastic scattering, which has some unique advantages over conventional LM methods for the investigation of large-scale biological systems, such as intact murine brains. Here, we will first lay out the background and the motivation of developing this scattering-based method. Then, the basic principle of this approach will be introduced, including controlling tissue scattering and coherent imaging. Next, we explore current implementation and practical considerations. Up-to-date results and the utility of this method will also be demonstrated. Finally, we discuss current limitations and future directions in this promising field.
摘要：
对整个大脑成像是生物光子学的中心工作之一。虽然在放射学中使用的已建立的成像模式，比如MRI和CT,已经实现了各种认知和情感过程的体内研究，一立方毫米的普遍分辨率限制了它们在研究神经元活动的“真相”中的使用。另一方面,电子显微镜（EM）在30nm左右的分辨率下显示最精细的解剖结构。然而,广泛的组织制备过程和所需的大规模形态学重建限制了这种方法的小样品体积。光学显微镜（LM）具有桥接上述两个空间尺度的潜力，分辨率从几百纳米到几微米不等。组织清除的最新进展为大型完整组织体积的光学研究铺平了道路。然而,这些LM研究中的大多数依赖于荧光-一种非线性光学过程来提供对比度。本章介绍了一种替代类型的LM，它仅基于线性光学过程-弹性散射，与传统的LM方法相比，在大规模生物系统的研究中具有一些独特的优势，比如完整的鼠脑.这里,我们将首先阐述开发这种基于散射的方法的背景和动机。然后，将介绍这种方法的基本原理，包括控制组织散射和相干成像。接下来,我们探讨当前的实施和实际考虑。还将展示最新结果和该方法的实用性。最后,我们讨论了这个有前途的领域的当前局限性和未来方向。
