ST-ODT: Spatiotemporal Optical Diffraction Tomography

生物细胞和组织的高分辨率三维光学成像工具的开发对于生物学和医学的基础和应用研究是非常必要的。它使定量生物学成为可能：通过定量测量了解生物系统的复杂相互作用和功能特性，例如监测神经元网络中的时空活动模式。由于细胞和组织对光是透明的，现有的成像方法通常依赖于外来的造影剂和荧光标记。基于光折射的无标记三维成像，即测量折射率的空间分布，消除了化学清洗的需要，从而保留了功能信息。然而，细胞和组织的无标记折射率成像是困难的，因为它们是高度散射的。这个项目将利用超短激光脉冲的光学衍射层析成像技术，结合数字全息技术和为通信系统开发的处理工具来解决这一挑战。我们提出的时空光学衍射层析成像方法结合了弹道成像和光学衍射层析成像。光学衍射层析成像不能直接应用于高散射目标的折射率成像，因为它是基于一次出生/瑞托夫近似的。光学衍射层析成像不能使用脉冲照明，因为其反演算法是基于连续波的绕射。我们证明了在脉冲照明下，时间积分脉冲响应场与在连续波照明下的衍射场完全相同。因此，通过调整脉冲平面波照明相干探测衍射场的时间积分窗口，不仅得到了等效的连续波衍射场，而且抑制了多次散射和漫射光，使高散射三维位相物体的折射率连续映射成为可能。我们的研究包括以下几个部分：1)通过模拟确定适合于时空光学衍射层析成像的三维物体的类别；2)优化时空光学衍射层析成像的性能，并研究其性能极限；3)时空光学衍射层析成像的实验演示。时空光学衍射层析成像是基于时间积分脉冲响应场和连续波衍射场的等价性，这一特性迄今还没有被应用于成像。时间和空间传播效应之间的相互作用代表了层析成像的一种范式转变，它特别适合于在存在多次散射的情况下进行三维成像。这个问题类似于多输入多输出通信系统，可以从这一知识体系中受益。以足够的精度描述非均匀介质以解决反向传播问题的想法也是最有趣和最具挑战性的，并可应用于其他学科。由于时空光学衍射层析成像可以提供连续的三维折射率图，它还能够将光聚焦到高度散射的三维位相物体内的特定位置。其影响是深远的。

The development of tools for high-resolution three-dimensional optical imaging of biological cells and tissues is highly desirable for fundamental and applied research in biology and medicine. It enables quantitative biology: understanding complex interactions and functional properties of biological systems through quantitative measurements, for example monitoring of spatiotemporal activity patterns in neuronal networks. Since cells and tissues are transparent to light, existing imaging methods have often relied on foreign contrast agents and fluorescent markers. Label-free three-dimensional imaging based on light refraction, i.e., measurement of the spatial distribution of the refractive index, obviates the need of chemical clearing, thereby preserving the functional information. However, label-free refractive-index imaging of cells and tissues is difficult because they are highly scattering. This challenge will be addressed in this project by use of optical diffraction tomography with ultrashort laser pulses, together with techniques from digital holography and processing tools developed for communication systems. Our proposed approach, called spatiotemporal optical diffraction tomography combines ballistic imaging and optical diffraction tomography. Optical diffraction tomography cannot be directly applied to refractive-index imaging of highly-scattering objects because it is based on the first-Born/Rytov approximation. Optical diffraction tomography cannot use pulsed illumination because the inversion algorithm is based on continuous-wave diffraction. We show that with pulsed illumination, the time-integrated impulse response field is exactly the same as the diffracted field with continuous-wave illumination. Therefore, by adjusting the time-integration window for coherently-detected diffraction of pulsed plane-wave illumination, we not only obtain the equivalent continuous-wave diffraction field but also reject multiply-scattered and diffuse light, making continuous mapping of the refractive index of highly-scattering three-dimensional phase objects possible. Our proposed research includes the following components: 1) Determining classes of three-dimensional objects suitable for spatiotemporal optical diffraction tomography through simulation; 2) Optimizing performance of spatiotemporal optical diffraction tomography and, investigating the performance limits; and 3) Experimental demonstration of spatiotemporal optical diffraction tomography. Spatiotemporal optical diffraction tomography is based on the equivalence of the time-integrated impulse response field and the continuous-wave diffracted field, a property that has not been heretofore applied to imaging. The interplay between temporal and spatial propagation effects represents a paradigm shift in tomography that is uniquely suitable for three-dimensional imaging in the presence of multiple scattering. The problem is similar to multiple-input-multiple-output communication systems and can benefit from that body of knowledge. The idea of characterizing an inhomogeneous medium with sufficient accuracy to solve an inverse propagation problem is also most interesting and challenging, and has applications to other disciplines. Since spatiotemporal optical diffraction tomography can provide continuous three-dimensional maps of the refractive index, it also enables focusing light onto specific locations within a highly-scattering three-dimensional phase object. The implications are far reaching.