Ultrasound and LED-based photoacoustic system for preclinical imaging of liver fibrosis

Abstract

Histopathological analysis remains a gold standard in preclinical research, which can only be performed as an end-stage analysis. In small animal studies, in order to improve the outcome, it is important to study the disease progression and treatment response over time without sacrificing animals at different time points thereby reducing the number of animals. Photoacoustic imaging with its ability to probe endogenous chromophores in the tissue and being non-invasive has great potential in this aspect. In this work, we aim to use ultrasound and photoacoustic imaging for assessment of liver fibrosis, in particular, to monitor the disease progression. We have used ultrasound and LED-based photoacoustic (US/LED-PA) imaging system, both in its handheld and tomographic mode. In the tomographic mode, the transducer and LED arrays were scanned around the animal for imaging. The imaging was performed on healthy (control) mice and mice with carbon tetrachloride (CCl4) induced liver fibrosis. The control and fibrotic mice were followed over a duration of eight weeks using US/LEDPA imaging. The animals were euthanized, imaged and histopathological analysis were performed at the end of 8-weeks. An increase in photoacoustic contrast and ultrasound echogenicity were observed progressively in the fibrotic livers compared to the control livers. The histological analysis also validated the severity of the fibrosis in the mice. The proposed approach using longitudinal monitoring of disease progression using US/LEDPA imaging can improve the outcome of the study. Since the LED-based system is compact, eye-safe, and easy-to-use, it can be of great benefit in small animal research.