FDA Scholar Program: Blood-Mimicking Phantoms for Assessing Oximetry Performance of Photoacoustic Imaging Systems

非技术性超声是对癌症、骨科疾病和心脏功能等疾病进行成像的有力工具。超声的一个局限性是它的对比度低(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，人们对一种特殊的超声波进行了大量的研究，这种超声波被称为光声成像。光声成像仅在感兴趣的区域使用光产生声音--这增加了对比度。不幸的是，光声超声还没有被批准在人体内广泛使用。这可能部分是由于缺乏验证和标准化光声成像所需的新型成像设备的设备和方法。因此，这项工作将创造出具有光学和声学特性的特殊塑料物体，模仿具有不同组织氧气量的人体组织。这些物体可用于校准和标准化光声成像设备。这项建议结合了学术界和食品和药物管理局的专业知识，以识别与人体组织具有相似光学和声学特性的材料。然后我们将加入吸收光谱类似于血红蛋白的染料。由此产生的测试对象将提高关于如何最好地创建测量组织氧合的光声成像仪器的知识，并可能简化对该设备的监管批准。反过来，这将增加患者使用这一重要成像技术的机会，最终提高美国纳税人的健康和生活质量。技术总结光声成像提供类似于超声波的深层组织成像，但具有增强的光学对比度以及额外的功能和分子成像能力。然而，与计算机断层成像等成熟技术不同，目前还没有标准的性能测试方法或模体用于光声成像系统的评估。基本的限制--也是这里要研究的科学问题--是缺乏能够同时在广泛的光学波长和声频范围内模拟组织特性的材料。这使得调查人员、仪器制造商和监管机构没有明确的战略来评估设备的安全性和有效性。我们之前与美国食品和药物管理局(FDA)的合作建立了稳定的、具有生物相关性的成像模体，具有良好的光学吸收/散射系数、声阻抗等特性，可以在广泛的光学波长和声频范围内广泛模拟组织。我们现在将整合发色团来模拟一系列氧饱和度/灌注值的组织氧合(SO2)。这项研究的目标1将开发模拟血液氧依赖光声光谱的体模。将选择染料的组合来开发可调配方，以在通常用于光声血氧仪的离散光学波长集上再现类似血液的多光谱光声信号。光声二氧化硫测量结果将与地面真实值以及含有可变二氧化硫的牛血中的光声测量结果进行比较。将用血氧计测量牛血中的二氧化硫。目的2利用模体建立血氧定量检测方法。这些方法将在加州大学圣迭戈分校和FDA的三个不同的光声系统上进行。具有不同背景光学性质的模体以及在不同深度和模拟SO2水平下含有模拟血液的包裹体将被用于光声器件血氧测量性能的参数研究。我们的三个光声系统使用各种通量校正算法在二氧化硫测量精度方面的改进将被量化，以确定设备对组织属性和形态的敏感度。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

NON-TECHNICAL SUMMARYUltrasound 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 optical and acoustic properties that mimic human tissue with different amounts of tissue oxygenation. These objects can be used to calibrate and standardize photoacoustic imaging equipment. This proposal combines expertise from academia and the Food and Drug Administration to identify materials that have similar optical and acoustic properties as human tissue. We will then add dyes that have absorption spectra similar to hemoglobin. The resulting test objects will improve knowledge of how to best create photoacoustic imaging instrumentation that measures tissue oxygenation 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 health and quality of life of US taxpayers. TECHNICAL SUMMARYPhotoacoustic 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. Our prior work with the Food and Drug Administration (FDA) built 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. We will now integrate chromophores to simulate tissue oxygenation (SO2) over a range of oxygen saturation/perfusion values. Objective 1 of this research will develop phantoms that simulate blood oxygen-dependent photoacoustic spectra. Combinations of dyes will be selected to develop tunable formulations that reproduce blood-like multispectral photoacoustic signals at sets of discrete optical wavelengths commonly used for photoacoustic oximetry. Photoacoustic-derived SO2 measurements will be compared against ground truth values as well as against photoacoustic measurements in bovine blood with variable SO2. Ground truth SO2 of bovine blood will be measured by oximetry. Objective 2 will use the phantoms to establish quantitative oximetry test methods. These methods will be performed on three different photoacoustic systems located at UCSD and FDA. Phantoms with different background optical properties and containing blood-mimicking inclusions at different depths and mimicked SO2 levels will be used for parametric study of photoacoustic device oximetry performance. Improvements in the SO2 measurement accuracy of our three photoacoustic systems using various fluence correction algorithms will be quantified to determine device sensitivity to tissue properties and morphology.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.