In-Vivo Microscopy for Tissue Engineering

描述(申请人提供)：随着组织工程学在过去十年中的巨大成功，迫切需要对工程化的活组织进行定性和定量的成像。我们研究计划的总体目标是开发一种先进的活体成像技术，即结合超声波、光声和弹性显微镜，能够可视化活组织的结构和功能属性，如组织内部的微观和宏观结构、表面形貌、构象、转变、顺应性、均质性、生长速度、生物力学甚至组织内的细胞功能。该项目的基本假设是，远程、非侵入性、高频、高分辨率的活体显微镜是可能的，并将提供比现有组织工程师可用的成像工具明显的优势。我们研究计划的基本前提是开发一种先进的活体显微镜，它融合了三种互补的成像方式-超声、光声和弹性成像-并充分利用这些系统的许多协同功能，从而为组织工程师提供急需的定量成像工具。事实上，基于微观尺度的超声成像为组织工程提供了一种概念和技术上都很新颖的成像工具。这项应用的主要目标是为组织工程师开发一种高分辨率、多功能显微镜的原型。为了实现我们的目标，我们将设计和建造基于机械扫描的、与激光源接口的单元件换能器的组合超声显微系统。我们还将开发超声、光声和弹性成像算法，以优化组合系统的性能。然后，我们将使用组织模拟模型测试开发的显微镜以及相应的信号和图像处理算法。最后，基于在项目期间收集到的见解，我们将概述活体显微镜系统的设计和技术规格。我们研究计划的长期目标是为组织工程师开发一种基于超声的联合显微系统。

DESCRIPTION (provided by applicant): With the great success of tissue engineering over the past decade, there is a definite and urgent need to image the engineered living tissues in a qualitative and quantitative manner. The overall goal of our research program is to develop an advanced in-vivo imaging technology; namely, combined ultrasound, photoacoustic and elasticity microscopy, capable of visualizing both the structural and functional properties of living tissue such as internal micro- and macro-architecture, surface topography, conformation, transformation, compliance, homogeneity, growth rate, biomechanics and even cell function within tissues. The underlying hypothesis of this project is that remote, non-invasive, high-frequency, high-resolution, in-vivo microscopy is possible and will provide marked advantages over existing imaging tools available for tissue engineers. The fundamental premise of our research program is to develop an advanced in-vivo microscopy based on the fusion of three complementary imaging modalities - ultrasound, photoacoustics, and elastography - and to take full advantage of the many synergistic features of these systems, thus providing a much needed quantitative imaging tool to tissue engineers. Indeed, ultrasound-based imaging on the microscopic scale offers a conceptually and technically novel imaging tool for tissue engineering. The main objective of this application is to develop a prototype of the high-resolution, multifunctional microscope for tissue engineers. To achieve our objective, we will design and build the combined ultrasound- based microscopy system based on a mechanically scanned, single element transducer interfaced with a laser source. We will also develop algorithms for ultrasound, photoacoustic and elasticity imaging to optimize the performance of the combined system. We will then test the developed microscope and corresponding signal and image processing algorithms using tissue mimicking phantoms. Finally, based on the insights gathered during the project, we will outline the design and technical specifications of an in-vivo microscopy system. The long-range goal of our research program is to develop a combined ultrasound-based microscopy system for tissue engineers.