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

非技术摘要：超声是一种强大的工具，可以对包括癌症、骨科疾病和心脏功能在内的疾病进行成像。超声波的一个局限性是它具有低对比度（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，有大量的研究进入一种特殊的超声称为光声成像。光声成像利用光只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类中广泛使用。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，这项工作将创建具有已知光学和声学特性的专用塑料物体，适用于校准和标准化光声成像设备。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创建光声成像仪器的知识，也可能简化该设备的监管批准。反过来，这将增加患者对这一重要成像技术的使用，最终促进国民健康和生活质量。技术摘要：光声成像提供与超声相似的深层组织成像，但具有增强的光学对比度和附加的功能和分子成像能力。然而，不像成熟的技术，如计算机断层扫描，没有标准化的性能测试方法或幻影存在的光声成像系统的评价。这里要研究的基本限制和科学问题是缺乏在宽范围的光波长和声频上同时模拟组织特性的材料。这使得研究者、仪器制造商和监管机构没有明确的策略来评估器械的安全性和有效性。该项目与美国食品药品监督管理局（FDA）建立了稳定的，生物相关的成像体模，具有良好的光学吸收/散射系数，声阻抗等，广泛模拟组织在广泛的光波长和声频。本研究的目的1是在光声成像过程中，开发具有生物相关异质形态和光散射伪影的体模。使用FDA提供的分光光度计和声脉冲传输设备，对体模材料的光学和声学特性进行严格表征。成像体模包含多层背景材料，其具有不同的光学和声学特性，旨在模拟天然组织（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。夹杂物具有不同大小的规则形状（圆柱体、球体）以及源自图像的曲折血管模拟结构。目标2使用这些体模建立测试方法，以评价三种不同成像系统中通量伪影对器械性能的影响。系统图像的均匀性和平面外的灵敏度进行评估，在机械扫描的探针超过现实的血管模仿夹杂物已知产生体积图像。套幻影包含夹杂物模仿血液吸收在几个氧饱和度水平，但具有不同的背景光学特性和层形态服务于参数研究的设备性能，在面对光谱着色文物。我们的三个光声成像系统的测量精度进行量化，以确定设备的鲁棒性，使用各种通量校正方法（扩散理论，蒙特卡罗模拟）。其成果是一个经过充分验证的组织模拟体模，以支持设备开发人员和通知监管决策，包括作为一个潜在的食品和药物管理局医疗器械开发工具的使用。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

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.