Columbia University, Department of Biomedical Engineering and Radiology, Laboratory for Functional Optical Imaging, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, New York 10027, USA.
J Biomed Opt. 2012 Sep;17(9):96003-1. doi: 10.1117/1.JBO.17.9.096003.
Conventional approaches to optical small animal molecular imaging suffer from poor resolution, limited sensitivity, and unreliable quantitation, often reducing their utility in practice. We previously demonstrated that the in vivo dynamics of an injected contrast agent could be exploited to provide high-contrast anatomical registration, owing to the temporal differences in each organ's response to the circulating fluorophore. This study extends this approach to explore whether dynamic contrast-enhanced optical imaging (DyCE) can allow noninvasive, in vivo assessment of organ function by quantifying the differing cellular uptake or wash-out dynamics of an agent in healthy and damaged organs. Specifically, we used DyCE to visualize and measure the organ-specific uptake dynamics of indocyanine green before and after induction of transient liver damage. DyCE imaging was performed longitudinally over nine days, and blood samples collected at each imaging session were analyzed for alanine aminotransferase (ALT), a liver enzyme assessed clinically as a measure of liver damage. We show that changes in DyCE-derived dynamics of liver and kidney dye uptake caused by liver damage correlate linearly with ALT concentrations, with an r2 value of 0.91. Our results demonstrate that DyCE can provide quantitative, in vivo, longitudinal measures of organ function with inexpensive and simple data acquisition.
传统的小动物光学分子成像方法存在分辨率差、灵敏度有限和定量不可靠等问题,这往往降低了它们在实际中的应用。我们之前已经证明,通过利用注射的造影剂的体内动力学,可以提供高对比度的解剖配准,这是由于每个器官对循环荧光团的反应存在时间上的差异。本研究扩展了这种方法,探索动态对比增强光学成像(DyCE)是否可以通过量化健康和受损器官中造影剂的不同细胞摄取或清除动力学,实现对器官功能的非侵入性、体内评估。具体来说,我们使用 DyCE 来可视化和测量吲哚菁绿在诱导短暂性肝损伤前后的器官特异性摄取动力学。DyCE 成像在九天内进行了纵向研究,并在每次成像时收集血样进行丙氨酸氨基转移酶(ALT)分析,这是一种临床上用于评估肝损伤的肝脏酶。我们表明,由肝损伤引起的 DyCE 衍生的肝脏和肾脏染料摄取动力学变化与 ALT 浓度呈线性相关,r2 值为 0.91。我们的研究结果表明,DyCE 可以提供定量的、体内的、纵向的器官功能测量,其数据采集简单且成本低廉。