Dynamic contrast-enhanced optical imaging of in vivo organ function

Abstract

Abstract. 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 r 2 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.

Dynamic Contrast Enhanced Fluorescent Molecular Imaging of Vascular Disruption Induced by Combretastatin-A4P in Tumor Xenografts

“…Notably, Amoozegar et al . 28 examined liver damage in nude mice following carbon tetrachloride administration and established correlation between ICG uptake in the liver visualized by DyCE and plasma alanine aminotransferase (ALT) concentration, which is a traditional biomarker. Lee et al 29 presented a preliminary report of dynamic fluorescent imaging to monitor the anti angiogenesis response to bevacizumab in human Ewing sarcoma xenografts in nude mice.…”

Noninvasive measurement of pharmacokinetics by near-infrared fluorescence imaging in the eye of mice

“…Recent studies indicate that this approach is feasible to measure the organ specific uptake dynamics of indocyanine green (ICG) and to assess the liver function after transient damage. 11 In this study, we applied optical imaging in the planar reflectance mode since the NIR excitation light can penetrate into the eye of an animal with low tissue absorption and light scattering and thus illuminates the highly vascularized retina of the eye. This direct and unrestricted access to the blood vessels offers the possibility to noninvasively measure the fluorescence intensity of labeled compounds over the time in the same animal.…”

Early Detection of Acute Drug-Induced Liver Injury in Mice by Noninvasive Near-Infrared Fluorescence Imaging

“…Although imaging of preclinical models of safety/toxicology has not been pursued extensively to date, the ability to use fluorescent imaging probes that detect and quantify a variety of biologic activities has considerable potential in this area as well (Amoozegar et al, 2012; Shuhendler et al, 2014; Peterson, 2016). In this study, three different types of NIR fluorescent probes—Annexin-Vivo 750 (AV-750), MMPSense 645 or 750 (MMP-645 or MMP-750), and Transferrin-Vivo 750 (TfV-750), specific for cell death, matrix metalloprotease (MMP) activity (inflammation), and transferrin receptor (metabolic activity) expression, respectively—were found to be excellent tools for detecting/characterizing drug-induced tissue injury in general and DILI in particular.…”