CAREER: Quantitative Phase Imaging of Cells and Tissues

该提案的重点是扩展定量相位成像（QPI）的边界，该技术具有独特的能力，可以在不使用造影剂的情况下量化细胞和组织结构和动力学的细微变化，并应用于高影响力的应用，包括神经科学、癌症成像和细胞膜生物物理学。PI已经开发的QPI技术包括：1)干涉显微技术，称为琼斯相显微镜（JPM），能够提取与透明和各向异性样品相关的空间分辨琼斯偏振矩阵；2)傅立叶变换光散射（FTLS）实验方法，结合光学显微镜，用于研究非均匀和动态介质的全息摄影和光散射技术；3)一种称为相衬断层扫描（PCT）的相衬成像技术，可以从3D细胞或组织样本中检索亚微米厚的切片。本文介绍了四个方面的研究活动和方法：1)红细胞的纳米细胞膜动力学；2)利用FTLB研究脑细胞的粘弹性；3)活神经元的动态传输和细胞间通信成像；4)健康和病变组织的折射率成像。血红细胞的研究包括与加州大学洛杉矶分校的Alex Levine合作开发一个分析模型，从波动数据中提取膜流变学，以及一项非平衡动力学的研究，重点是确定ATP介导过程的影响。与加州大学洛杉矶分校的玛莎·吉列特合作进行的脑细胞粘弹性研究将重点关注神经元和神经胶质细胞之间的差异。转运研究将集中在非接触测量神经元动作电位和细胞器运输的动态成像。折射率研究建议将cm宽血液涂片的初步工作扩展到整个器官尺度成像。与加州大学洛杉矶分校的Steve Boppart合作，所做的测量将扩展到癌症进展过程中折射率变化的研究。

0846660PopescuThe proposal focuses on extending the boundaries of quantitative phase imaging (QPI), which has the unique ability to quantify subtle changes in both structure and dynamics of cells and tissues without using contrast agents, to high-impact applications, including neuroscience, cancer imaging, and cell membrane biophysics. QPI technologies already developed by the PI include: 1) an interferometric microscopy technique, termed Jones Phase Microscopy (JPM), capable of extracting the spatially-resolved Jones polarization matrix associated with transparent and anisotropic samples, 2) a Fourier transform light scattering (FTLS) experimental approach that combines optical microscopy, holography and light scattering for studying inhomogeneous and dynamic media and 3) a phase contrast imaging technique referred to as phase contrast tomography (PCT) that can retrieve submicron thick sections from a 3D cell or tissue sample. Research activities and methods were described in four areas: 1) nanoscale cell membrane dynamics of red blood cells, 2) viscoelasticity of brain cells using FTLB, 3) imaging dynamic transport and cell-to-cell communication in live neurons, and 4) refractive index mapping of healthy and diseased tissue. The red blood cell studies include developing an analytic model to extract membrane rheology from fluctuation data in collaboration with Alex Levine, UCLA, and a study of out-of-non-equilibrium dynamics focused particularly on determining the effects of ATP mediated processes. The viscoelasticity of brain cells study, in collaboration with Martha Gillete, UIUC, will focus on differences between neuron and glial cells. The transport studies will focus on non-contact measurement of neuronal action potentials and the dynamic imaging of organelle traffic. The refractive index studies proposed extend preliminary work on cm wide blood smears to whole organ scale imaging. The measurements made will be extended to studies of refractive index changes during cancer progression in collaboration with Steve Boppart, UIUC.