Validation and Extension of the Theory of Ultrasound Scattering in Tissue

描述(申请人提供)：我们提议的研究将测试这样一个假设，即理论框架首先由Lizzi及其同事发表，随后由Insana和Lizzi及其同事扩展，准确地将光谱参数值与各向同性、弱散射体的机械和几何属性联系起来，这些散射体被中等聚焦的换能器电离。这项研究还将超越使用原始假设对原始理论进行严格验证的范围，包括在这些假设之外的散射条件下评估光谱行为，即非各向同性和密集填充的散射体的散射、强聚焦换能器的散射以及在广泛频率范围内的散射。这项研究的成功将为定量测定散射体特性提供可靠的、更普遍的基础，以诊断疾病、监测疾病进展或对治疗的反应，以及在基础生物和生理研究中评估组织特性。拟议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，悬浮在液体介质中，浓度已知，大小已知。超声回波信号的采集将使用中心频率从10 MHz到75 MHz的宽带聚焦换能器，每个中心频率的f数从2到4。由于现有的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，所以我们将根据超声传播速度和质量密度来计算每种散射体类型的声阻抗，这些散射体是使用离心法压实成颗粒的细胞来测量的。我们将为所有实验的散射和电离条件产生归一化(系统无关)光谱，并将计算的光谱与理论进行比较。然后，我们将扩展我们的分析，以包括估计散射体属性的替代方法，包括自回归和小波方法，以及常用的傅立叶方法。我们还将比较其他归一化方法，即基于平面目标的确定性反射的归一化方法和基于明确定义的散射目标的随机返回的归一化方法。这项拟议的研究将使人们更深入地了解与组织散射有关的现象，并将为改进基于组织成分散射体的属性来评估和成像组织的超声手段提供坚实的基础。这项研究将由河滨研究所利齐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。拟议中的项目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。到目前为止，对现有散射理论的支持只是推论。我们提出的直接验证方法将导致对散射理论的改进，这将为制定更精确的理论提供基础，并将改进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洞察，例如，正常组织和病变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.