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

光声层析成像技术是一种新兴的生物医学成像技术，它利用生物组织中的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，在皮肤处，换能器阵列检测到时间分辨的PA信号。从这些信号，高分辨率（几十微米）的三维图像，然后获得使用图像重建算法。由于可见光和近红外波长区域中的主要组织吸收体是血红蛋白，因此这些图像通常表示脉管系统。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化软组织中的强对比度，这是由于血红蛋白的吸收，而其他模态，例如MRI，X射线CT和超声缺乏灵敏度。其最强大的属性是空间分辨绝对生色团浓度和衍生参数，如血氧饱和度，这是必不可少的生理和分子成像应用的测量的潜力。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断层扫描特别是仍然具有高度挑战性，并且迄今为止尚未在体内得到证实。为了将PA层析成像转化为生命科学中的广泛应用，需要开发精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的实用方法，用于确定绝对血氧饱和度在体内多波长3-D PA断层扫描图像。将解决的挑战是：1）一个有效的3-D PA正演模型的发展，2）一个易于处理的基于模型的反演的计算和实验方法的发展，3）在组织幻影血氧测量的可行方法的实验验证，和4）在体内的实验验证在一个小动物模型的组织再生。该项目将提供第一个经过实验验证的方法，用于无创测量深部组织中的绝对血氧，这是定量PA断层扫描在生命科学中应用的重要一步。此外，在这个项目中获得的知识，预计将大大有助于长期发展的定量方法的分子PA断层扫描。

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.