NSF/FDA SIR: Morphologically Complex Tissue-Mimicking Phantoms for Evaluating Tissue Scattering Artifacts in Photoacoustic Imaging

摘要：超声是诊断癌症、骨科疾病和心脏功能等疾病的有力工具。超声波的一个限制是对比度低（对比度是感兴趣区域和背景组织之间的信号强度差异）。因此，对一种称为光声成像的特殊超声进行了大量的研究。光声成像利用光在感兴趣的区域产生声音，这增加了对比度。不幸的是，光声超声尚未被批准在人体中广泛使用。这可能部分是由于缺乏设备和方法来验证和标准化光声成像所需的新型成像设备。因此，这项工作将创造出具有已知光学和声学特性的专门塑料物体，适合于光声成像设备的校准和标准化。该提案结合了学术界和食品和药物管理局的专业知识，以确定具有与人体组织相似的光学和声学特性的材料。我们将创建对仪器制造商和医生有用的测试对象和方法。由此产生的测试对象将提高如何最好地制造光声成像仪器的知识，并可能简化该设备的监管批准。反过来，这将增加患者获得这一重要成像技术的机会，最终促进国民健康和生活质量。技术摘要：光声成像提供了类似于超声的深层组织成像，但具有增强的光学对比度和额外的功能和分子成像能力。然而，与计算机断层扫描等成熟技术不同，光声成像系统评估没有标准化的性能测试方法或模型。这里要研究的基本限制和科学问题是缺乏在广泛的光学波长和声学频率范围内同时模拟组织特性的材料。这使得研究人员、仪器制造商和监管机构没有明确的策略来评估设备的安全性和有效性。该项目与美国食品和药物管理局（FDA）合作，建立了稳定的、与生物相关的成像模型，具有良好的光学吸收/散射系数、声阻抗等特征，可以在广泛的光学波长和声学频率范围内广泛模拟组织。本研究的目的1是在光声成像过程中开发具有生物学相关的异质形态和光散射伪影的幻影。幻影材料的光学和声学特性是严格表征使用分光光度法和声波脉冲传输设备可在FDA。成像模型包含多层具有不同光学和声学特性的背景材料，旨在模拟自然组织（例如乳房脂肪和腺体组织或肌肉和脂肪层）以及目标内含物。这些内含物具有不同大小的规则形状（圆柱体、球体）以及图像衍生的、弯曲的容器模拟结构。目标2使用这些幻影建立测试方法，评估影响伪影对三种不同成像系统中设备性能的影响。系统图像均匀性和面外灵敏度评估在机械扫描的探头在现实的血管模拟内含物已知产生体积图像。在几种氧饱和度水平下，包含模拟血液吸收的内含物的幻影集-但具有不同的背景光学特性和层形态-在面对光谱着色伪影时用于设备性能的参数化研究。我们的三个光声成像系统的测量精度是量化的，以确定设备鲁棒性使用各种影响校正方法（扩散理论，蒙特卡罗模拟）。结果是一个经过良好验证的组织模拟模型，以支持设备开发人员并为监管决策提供信息，包括用作潜在的食品和药物管理局医疗设备开发工具。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

NON-TECHNICAL ABSTRACT:Ultrasound is a powerful tool to image diseases including cancer, orthopedic disorders, and heart function. One limitation of ultrasound is that it suffers from low contrast (contrast is the difference in signal intensity between the region of interest and the background tissue). Therefore, there is a large body of research into a special kind of ultrasound known as photoacoustic imaging. Photoacoustic imaging uses light to generate sound only in the area of interest-this increases the contrast. Unfortunately, photoacoustic ultrasound is not yet approved for widespread use in people. This might be partially due to a lack of devices and methods to validate and standardize the novel imaging equipment needed for photoacoustic imaging. Therefore, this work will create specialized plastic objects with known optical and acoustic properties suitable for calibrating and standardizing photoacoustic imaging equipment. This proposal combines expertise from academia and the Food and Drug Administration to identify materials that have optical and acoustic properties similar to human tissue. We will create test objects and methods that will be useful to instrument manufacturers and physicians. The resulting test objects will improve knowledge of how to best create photoacoustic imaging instrumentation and might also streamline regulatory approval of this equipment. In turn, this will increase patient access to this important imaging technique to ultimately advance the national health and quality of life. TECHNICAL ABSTRACT:Photoacoustic imaging provides deep tissue imaging similar to ultrasound but with enhanced optical contrast and additional functional and molecular imaging capabilities. However, no standardized performance test methods or phantoms exist for photoacoustic imaging system evaluation unlike mature techniques such as computed tomography. The fundamental limitation-and scientific problem to be studied here is a lack of materials to simultaneously simulate tissue properties over a broad range of optical wavelengths and acoustic frequencies. This leaves investigators, instrument manufacturers, and regulatory agencies without clear strategies to evaluate device safety and effectiveness. This project with the Food and Drug Administration (FDA) builds stable, biologically relevant imaging phantoms with well-characterized optical absorption/scattering coefficients, acoustic impedance, etc. that broadly simulate tissue over a wide range of optical wavelengths and acoustic frequencies. Objective 1 of this research develops phantoms with biologically relevant heterogeneous morphologies and light scattering artifacts during photoacoustic imaging. Phantom material optical and acoustic properties are rigorously characterized using spectrophotometry and acoustic pulse-transmission equipment available at FDA. The imaging phantoms contain multiple layers of background material with different optical and acoustic properties designed to mimic natural tissue (e.g. breast fat and glandular tissue or muscle and fat layers) as well as target inclusions. The inclusions have regular shapes (cylinders, spheres) of varying sizes as well as image-derived, tortuous vessel-mimicking structures. Objective 2 uses these phantoms to establish test methods that evaluate the impact of fluence artifacts on device performance in three different imaging systems. System image uniformity and out-of-plane sensitivity are evaluated during mechanical scanning of probes over realistic vessel-mimicking inclusions known to produce volumetric images. Sets of phantoms containing inclusions mimicking blood absorption at several oxygen saturation levels-but with different background optical properties and layer morphologies-serve in parametric studies of device performance in the face of spectral coloring artifacts. The measurement accuracy of our three photoacoustic imaging systems is quantified to determine device robustness using various fluence correction methods (diffusion theory, Monte Carlo simulations). The outcome is a well-validated tissue-mimicking phantom to support device developers and inform regulatory decision-making including use as a potential Food and Drug Administration Medical Device Development Tool.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.