Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Harvard Medical School, Boston, MA 02115, USA.
Sci Rep. 2017 Apr 12;7:46306. doi: 10.1038/srep46306.
A central effort of today's neuroscience is to study the brain's 'wiring diagram'. The nervous system is believed to be a network of neurons interacting with each other through synaptic connection between axons and dendrites, therefore the neuronal connectivity map not only depicts the underlying anatomy, but also has important behavioral implications. Different approaches have been utilized to decipher neuronal circuits, including electron microscopy (EM) and light microscopy (LM). However, these approaches typically demand extensive sectioning and reconstruction for a brain sample. Recently, tissue clearing methods have enabled the investigation of a fully assembled biological system with greatly improved light penetration. Yet, most of these implementations, still require either genetic or exogenous contrast labeling for light microscopy. Here we demonstrate a high-speed approach, termed as Clearing Assisted Scattering Tomography (CAST), where intact brains can be imaged at optical resolution without labeling by leveraging tissue clearing and the scattering contrast of optical frequency domain imaging (OFDI).
当今神经科学的一个主要研究方向是研究大脑的“连接图”。人们认为神经系统是一个通过轴突和树突之间的突触连接相互作用的神经元网络，因此神经元连接图不仅描绘了潜在的解剖结构，而且具有重要的行为意义。已经有不同的方法被用于破译神经元回路，包括电子显微镜（EM）和光学显微镜（LM）。然而，这些方法通常需要对脑组织样本进行广泛的切片和重建。最近，组织透明化方法使得对完全组装的生物系统进行研究成为可能，其光穿透能力得到了极大的提高。然而，这些实现方法中的大多数仍然需要遗传或外源性对比标记来进行光学显微镜检测。在这里，我们展示了一种高速方法，称为 Clearing Assisted Scattering Tomography（CAST），它利用组织透明化和光频域成像（OFDI）的散射对比度，无需标记即可在不降低分辨率的情况下对完整的大脑进行成像。
