Quantitative Ultrasound Imaging for Noninvasive Assessment of Engineered Tissues

描述(申请人提供)：工程化组织的非侵入性成像和表征将极大地促进新疗法的开发、测试和商业化。超声成像和显微技术已被用来表征组织结构的某些方面，但传统的超声技术受到仪器依赖性的限制，仅限于对形态的定性评估。这个为期两年的探索性项目的目标是开发一种定量成像技术，用于快速和高分辨率地表征矿化工程组织的成分、结构和机械性能。它应用高频频谱超声成像(SUSI)来创建含矿物组织的高分辨率图像和功率谱。功率谱的参数分析提供了有关矿物成分的位置、密度和粒度的信息。利用声辐射力(ARF)弹性成像技术对SUSI进行增强，可以测量局部和整体机械性能。该项目有三个具体目标(SA)。在SA1中，我们将演示如何使用SUSI来定量描述三维(3D)工程骨科组织中矿物相的时空发展。在SA2中，我们将实施ARF弹性成像，用于非接触式测量3D工程骨科组织的组织力学特性。最后，在SA3中，我们将SA1的组成和结构信息与SA2的机械性能数据相关联。用组织发育的非侵入性、时空表征取代目前使用的破坏性生化和组织学方法，将极大地促进组织工程学的研究。此外，这种方法将有助于工程组织产品的质量控制和监测。随着时间的推移，将发育中的组织的成分和机械性能联系起来的能力也可能导致对结构-功能关系和机械生物学的新见解。

DESCRIPTION (provided by applicant): Noninvasive imaging and characterization of engineered tissues would greatly enable the development, testing, and commercialization of new therapies. Ultrasound imaging and microscopy have been used to characterize some aspects of tissue structure, but conventional ultrasound techniques are hampered by instrument-dependence and are limited to qualitative assessment of morphology. The objective of this two-year exploratory project is to develop a quantitative imaging technique for the rapid and high resolution characterization of the composition, structure and mechanical properties of mineralized engineered tissues. It applies high frequency spectral ultrasound imaging (SUSI) to create high resolution images and power spectra of mineral-containing tissues. Parametric analysis of the power spectra provides information on the location, density, and particle size of the mineral component. Augmentation of SUSI with acoustic radiation force (ARF) elastography allows measurement of the local and bulk mechanical properties. The project has three Specific Aims (SA). In SA1 we will demonstrate the use of SUSI to quantitatively characterize the spatiotemporal development of a mineral phase in three dimensional (3D) engineered orthopaedic tissues. In SA2 we will implement ARF elastography for noncontact measurement of tissue mechanical properties in 3D engineered orthopaedic tissues. Finally, in SA3 we will correlate the composition and structure information from SA1 with the mechanical property data from SA2. Replacing the currently used destructive biochemical and histological methods of tissue characterization with noninvasive, spatiotemporal characterization of tissue development would greatly enhance research in tissue engineering. In addition, such methods would facilitate quality control and monitoring of engineered tissue products. The ability to correlate composition and mechanical properties in developing tissues over time also could lead to new insights into structure-function relationships and mechanobiology.