Validation and Extension of the Theory of Ultrasound Scattering in Tissue

描述（由申请人提供）：我们提出的研究将验证这样一个假设，即由Lizzi及其同事首次发表并随后由Insana和Lizzi及其同事扩展的理论框架准确地将光谱参数值与各向同性、弱散射体、中等聚焦换能器失音的力学和几何特性联系起来。该研究还将超越对原始理论的严格验证，使用原始假设，包括在这些假设之外的散射条件下的光谱行为评估，即非各向同性和密集排列的散射体的散射，强聚焦换能器的散射，以及在广泛频率范围内的散射。本研究的成功将为散射特性在疾病诊断、疾病进展或治疗反应监测以及基础生物学和生理学研究中的组织特性评估等方面的定量测定提供可靠、更广泛的基础。所提出的验证该理论的实验方法将利用分离的、活的和固定的、培养的细胞和细胞核悬浮在已知浓度和已知大小的液体培养基中。超声回波信号的采集将利用宽带、聚焦换能器，其中心频率范围为10mhz至75mhz，每个中心频率的f值范围为2至4。由于现有理论利用了与散射体声阻抗空间分布相关的空间自相关函数和形状因子，我们将根据超声传播速度和使用离心压实成球的细胞测量的质量密度计算每种散射体类型的声阻抗。我们将生成归一化的（系统无关的）光谱为所有实验散射和失谐条件，并将计算光谱与理论比较。然后，我们将扩展我们的分析，包括估计散射特性的替代方法，包括自回归和小波方法，以及常用的傅立叶方法。我们还将比较标准化的替代方法，即基于平面目标的确定性反射和基于定义良好的散射目标的随机返回的方法。本研究将对超声在组织中的散射现象有更深入的了解，并将为基于组织散射体特性的超声评估和成像技术的改进提供坚实的基础。这项研究将由河滨研究所Lizzi生物医学工程中心和康奈尔大学威尔医学院眼科的多学科科学家团队合作进行。该计划将验证超声在软组织中散射的基本理论，但目前尚未完全验证。迄今为止，对现有散射理论的支持只是推断性的。我们提出的直接验证方法将导致散射理论的改进，这将为制定更精确的理论提供基础，并将提高我们对组织之间的差异在其散射行为中表现出来的方式的见解，例如，正常与患病或受损组织之间的差异。

DESCRIPTION (provided by applicant): Our proposed study will test the hypothesis that the theoretical framework first published by Lizzi and co- workers and subsequently expanded by Insana and Lizzi and their co-workers accurately relates spectral-parameter values to mechanical and geometric properties of isotropic, weak scatterers, insonified by moderately focused transducers. The study also will go beyond rigorous validation of the original theory using its original assumptions to include assessment of spectral behavior under scattering conditions that are outside those assumptions, i.e., scattering for non-isotropic and densely-packed scatterers, scattering with strongly-focused transducers, and scattering over a broad range of frequencies. Success in this study will provide a reliable, more-general basis for quantitative determination of scatterer properties in diagnosing disease, monitoring disease progression or response to therapy, and evaluating tissue properties in basic biological and physiological research. The proposed experimental method for validating the theory will utilize isolated, living and fixed, cultured cells and nuclei suspended in a liquid medium in known concentrations and having known sizes. Acquisition of ultrasound echo signals will utilize broadband, focused transducers with center frequencies ranging from 10 MHz to 75 MHz and with f-numbers ranging from 2 to 4 at each center frequency. Because existing theory utilizes spatial autocorrelation functions and form factors related to the spatial distributions of the acoustic impedances of scatterers, we will compute acoustic impedances for each scatterer type from ultrasound propagation velocities and mass densities measured using cells compacted into pellets by centrifugation. We will generate normalized (system-independent) spectra for all experimental scattering and insonification conditions, and will compare computed spectra to theory. We then will extend our analysis to include alternative methods of estimating scatterer properties, including autoregression and wavelet methods, as well as the commonly used Fourier methods. We also will compare alternative methods of normalization, i.e., those based on deterministic reflections from planar targets and those based on stochastic returns from well-defined scattering targets. The proposed study will give greater insight into phenomena related to scattering of ultrasound by tissue, and will provide a firm foundation for improved ultrasonic means of evaluating and imaging tissue based on the properties of its constituent scatterers. The study will be performed collaboratively by a multidisciplinary team of scientists at the Lizzi Center for Biomedical Engineering at Riverside Research Institute and the Department of Ophthalmology at the Weill Medical College of Cornell University. The proposed project will validate fundamental, but currently incompletely validated, theories of scattering of ultrasound in soft tissues. To date, support for existing scattering theories only has been inferential. Our proposed direct validation approach will lead to refinements of scattering theory that will provide a basis for formulating a more-exact theory and will improve our insights into the way differences among tissues are manifested in their scattering behavior, e.g., differences between normal and diseased or damaged tissue.