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

光声成像是一种新兴的生物医学成像方式，利用组织发色团吸收短光脉冲来产生宽带超声波。这些波传播到皮肤，在那里时间分辨PA信号被传感器阵列检测到。从这些信号中，利用图像重建算法获得高分辨率（几十微米）的三维图像。由于可见光和近红外波长区域的主要组织吸收剂是血红蛋白，因此这些图像通常代表脉管系统。PA成像结合了许多强大的属性，如多尺度成像能力和血管化软组织的强对比度，这是由于血红蛋白的吸收，而其他方式，如MRI、x线CT和超声缺乏敏感性。它最强大的特性是有可能对绝对发色团浓度和衍生参数（如血氧饱和度）进行空间分辨测量，这对生理和分子成像应用至关重要。然而，这种潜力尚未得到利用。由于逆问题的规模，深层组织3-D定量PA断层扫描尤其具有挑战性，并且迄今尚未在体内得到证实。为了使PA层析成像在生命科学中得到广泛的应用，需要开发准确可靠的方法来解决qPAT的反问题。本项目的目的是开发和实验验证从体内多波长三维断层扫描图像确定绝对血氧饱和度的可行方法。将要解决的挑战是1)开发一个高效的3- d PA正演模型，2)开发一种易于处理的基于模型的反演的计算和实验方法，3)对组织模型中血氧测量的可行方法进行实验验证，以及4)在小动物体内组织再生模型中的实验验证。该项目将提供第一个经过实验验证的方法，用于无创测量深层组织中的绝对血氧，这是向定量PA断层扫描在生命科学中的应用迈出的重要一步。此外，在这个项目中获得的知识有望为分子PA断层成像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.