Development and experimental validation of methods for quantitative photoacoustic tomography of blood oxygen saturation in vivo

光声层析成像是一种新兴的生物医学成像方式，它利用组织生色团对短光脉冲的吸收来产生宽带超声波。这些波传播到皮肤，换能器阵列在那里检测到时间分辨的PA信号。从这些信号中，使用图像重建算法获得高分辨率(几十微米)的3-D图像。由于在可见光和近红外波长区域的主要组织吸收物质是血红蛋白，这些图像通常代表血管系统。PA成像结合了许多强大的属性，例如多尺度成像能力和血管软组织中由于被血红蛋白吸收而产生的强烈对比度，而其他方式，如MRI、x射线CT和超声波缺乏敏感性。它最强大的属性是有可能对绝对发色团浓度和衍生参数进行空间分辨测量，如血氧饱和度，这对生理和分子成像应用是必不可少的。然而，这一潜力尚未得到利用。由于逆问题的规模，深层组织3-D定量PA断层成像仍然具有很高的挑战性，到目前为止还没有在体内得到证实。为了使PA层析成像在生命科学中得到广泛的应用，需要开发出准确可靠的方法来解决qPAT的逆问题。本项目的目的是开发和实验验证从活体多波长三维PA断层图像中确定绝对血氧饱和度的实用方法。将解决的挑战包括1)开发有效的3-D PA正演模型，2)开发基于模型的易处理的反演的计算和实验方法，3)测量组织模体中血液氧合的可行方法的实验验证，以及4)在组织再生的小动物模型中的体内实验验证。该项目将提供第一个经过实验验证的方法，用于非侵入性测量深层组织的绝对血氧含量，这是在生命科学中应用定量PA断层扫描的重要一步。此外，在该项目中获得的知识有望为分子PA断层扫描定量方法的长期发展做出重大贡献。

Photoacoustic (PA) tomography is an emerging biomedical imaging modality in which the absorption of short optical pulses by tissue chromophores is used to generate broadband ultrasonic waves. These waves propagate to the skin where time-resolved PA signals are detected by transducer arrays. From these signals, high resolution (tens of microns) 3-D images are then obtained using image reconstruction algorithms. Since the main tissue absorber in the visible and near-infrared wavelength region is haemoglobin, these images typically represent the vasculature. PA imaging combines a number of powerful attributes, such as multiscale imaging capabilities and strong contrast in vascularised soft tissues due to the absorption by haemoglobin where other modalities, such as MRI, x-ray CT, and ultrasound lack sensitivity. Its most powerful attribute is the potential for making spatially resolved measurements of absolute chromophore concentrations and derived parameters, such as blood oxygen saturation, which is essential for physiological and molecular imaging applications. However, this potential has yet to be harnessed. Deep tissue 3-D quantitative PA tomography in particular remains highly challenging due to the scale of the inverse problem, and has not been demonstrated in vivo to date. To translate PA tomography to a broad range of applications in the life sciences, the development of accurate and reliable methods for the solution of the inverse problem of qPAT is required. The aim of this project is the development and experimental validation of practicable methods for determining the absolute blood oxygen saturation from in vivo multiwavelength 3-D PA tomography images. The challenges that will be addressed are 1) the development of an efficient 3-D PA forward model, 2) the development of computational and experimental methods for a tractable model-based inversion, 3) the experimental validation of practicable methods for the measurement of blood oxygenation in tissue phantoms, and 4) experimental validation in vivo in a small animal model of tissue regeneration. This project will deliver the first experimentally validated methodology for the non-invasive measurement of absolute blood oxygenation in deep tissue, a major step towards the application of quantitative PA tomography in the life sciences. In addition, the knowledge gained during this project is expected to contribute substantially to the long-term development of quantitative methods for molecular PA tomography.