WHOLE-BODY SMALL-ANIMAL PHOTOACOUSTIC-ULTRASONIC COMPUTED TOMOGRAPHY

描述（由申请人提供）：本R01申请的目标是开发一种集成的小动物全身光声超声计算机断层扫描系统和相关的图像重建算法，用于同时进行高分辨率解剖和功能成像，并伴有运动跟踪。由于动物模型在人类疾病研究中的广泛应用，小动物全身成像在生物医学研究中发挥着越来越重要的作用。虽然在开发小动物成像系统方面投入了大量的努力，但每种可用的方法都有很大的局限性。光声计算机断层扫描（PACT）最近被认为是一种很有前途的小动物全身成像工具。利用光声效应，PACT可以在远超过光学扩散极限（~1 mm）的组织深度以高空间分辨率成像具有丰富光学吸收对比度的完整生物组织。由于光学吸收对血红蛋白总浓度和氧饱和度等生理参数敏感，PACT可以同时提供解剖和功能成像。在功能化造影剂（分子探针）的帮助下，PACT也可以进行分子成像。迄今为止，大多数PACT系统都假定被成像物体具有均匀的声学特性。这一假设在小动物的全身成像中严重违背，因为存在厚骨或气囊，其声速和质量密度值与周围软组织的声速和质量密度值有很大不同。此外，现有的PACT系统还存在明显的运动伪影。因此，仍然非常需要发展改进的小动物PACT系统和相关的图像重建方法。将PACT和超声计算机断层扫描（USCT）与运动跟踪相结合将带来独特的优势，并使我们能够克服上述两个挑战。首先，利用USCT重建的声学特性分布将被用于PACT图像重建算法，从而提高全身图像质量。超声对比也将补充PACT的光学对比，以准确评估多方面的疾病。其次，为了最大限度地减少运动伪影，在回顾性门控的数据采集过程中，将监测呼吸和心脏运动。因此，USCT和PACT的协同融合将在不使用电离辐射或外源性造影剂的情况下，为全面成像提供自动共同注册的解剖和功能对比。本课题的具体目标是：(1)研制一种集成全身光声-超声计算机断层扫描系统。(2)开发用于双模成像系统的图像重建算法。(3)开发回顾性呼吸门控断层扫描，最大限度地减少运动伪影。(4)用组织幻影和活体动物对成像系统进行测试。

DESCRIPTION (provided by applicant): The objective of this R01 application is to develop an integrated small-animal whole-body photoacoustic- ultrasonic computed tomography system and the associated image reconstruction algorithms for simultaneous high-resolution anatomical and functional imaging with motion tracking. Due to the widespread use of animal models for human disease studies, small-animal whole-body imaging plays an increasingly important role in biomedical research. While much effort has been invested in the development of small-animal imaging systems, each of the available methods possesses significant limitations. Photoacoustic computed tomography (PACT) has recently been recognized as a promising tool for small- animal whole-body imaging. Utilizing the photoacoustic effect, PACT can image intact biological tissues with rich optical absorption contrast at high spatial resolution at tissue depth well beyond the optical diffusion limit (~1 mm). Since optical absorption is sensitive to physiological parameters such as the total concentration and oxygen saturation of hemoglobin, PACT can provide both anatomical and functional imaging. With the aid of functionalized contrast agents (molecular probes), PACT can also permit molecular imaging. Most PACT systems implemented to date assume that the to-be-imaged object possesses uniform acoustic properties. This assumption is strongly violated in whole-body imaging of small animals due to the presence of either thick bones or gas pockets, which possess speed-of-sound and mass density values greatly different from those of the surrounding soft tissues. In addition, the existing PACT systems suffer from significant motion artifacts. Accordingly, there remains an important need for the development of improved small-animal PACT systems and associated image reconstruction methodologies. The proposed integration of PACT and ultrasonic computed tomography (USCT) with motion tracking will bring unique advantages and allow us to overcome the two challenges mentioned above. First, the acoustic property distributions reconstructed by use of USCT will be employed to inform the PACT image reconstruction algorithms and hence improve the whole-body image quality. The ultrasonic contrasts will also complement optical contrasts from PACT for accurate multi-faceted disease assessment. Second, to minimize motion artifacts, respiration and cardiac motions will be monitored during data acquisition for retrospective gating. Therefore, the synergistic fusion of USCT and PACT will provide automatically co-registered anatomical and functional contrasts for comprehensive imaging without using ionizing radiation or exogenous contrast agents. The specific aims of this project are as follows: (1) Develop an integrated whole-body photoacoustic- ultrasonic computed tomography system. (2) Develop image reconstruction algorithms for use with the dual- modality imaging system. (3) Develop retrospectively respiration-gated tomography that minimizes motion artifacts. (4) Test the imaging systems with tissue phantoms and living animals.