An integrated coherent anti-Stokes Raman scattering and multiphoton imaging technique for liver disease diagnosis

Abstract

Liver steatosis and fibrosis are two prevalence liver diseases and may eventually develop into hepatocellular carcinoma (HCC) Due to their prevalence and severity, much work has been done to develop efficient diagnostic methods and therapies. Nonlinear optical microscopy has high sensitivity and chemical specificity for major biochemical compounds, making it a powerful tool for tissue imaging without staining. In this study, three nonlinear microscopy imaging modalities are applied to the study of liver diseases in a bile duct ligation rat modal. CARS shows the distributions of fats or lipids quantitatively across the tissue; SHG visualizes the collagens; and TPEF reveals the morphology of hepatic cells. The results clearly show the development of liver steatosis and fibrosis with time, and the hepatic fat and collagen fibrils are quantified. This study demonstrates the ability of multimodal nonlinear optical microscopy for liver disease diagnosis, and may provide new insights into the understanding of the mechanisms of steatosis/fibrosis transformations at the cellular and molecular levels.

Multiphoton microscopy in defining liver function

“…38 Fibrosis is treatable in its early stages; therefore, accurate staging is important for optimal treatment. 39 Liver biopsy is the gold standard in tracking fibrosis, despite sampling error risk, 40 but it is not ideal to perform serial liver biopsies in order to accurately determine disease progression or to monitor treatment effects. 39 Therefore, noninvasive biomedical imaging techniques, such as ultrasonography, computed tomography, and magnetic resonance imaging, are important to detect liver disease.…”

“…This is a major limitation as it cannot predict the eventual timing of liver function loss, onset of portal hypertension, or other complications to determine proper therapeutic intervention. 34,40 Therefore, it is important to develop advanced optical imaging for noninvasive label-free quantitative assessment of early liver disease. 40 Imaging has the potential to extract information over a long period of time and over a larger sampling area.…”

“…34,40 Therefore, it is important to develop advanced optical imaging for noninvasive label-free quantitative assessment of early liver disease. 40 Imaging has the potential to extract information over a long period of time and over a larger sampling area. 39…”

Assessing Steatotic Liver Function after Ischemia-Reperfusion Injury by In Vivo Multiphoton Imaging of Fluorescein Disposition

“…Noninvasive biomedical imaging techniques such as ultrasonography, computed tomography, and magnetic resonance imaging are widely used to detect liver disease, but they do not have sufficient sensitivity, spatial resolution, or specificity to detect or stage liver disease (Lin et al, 2012). By contrast, virtual biopsies obtained via fluorescence imaging can give an overall view of the liver (Goetz et al, 2008a) as well as provide dynamic information (Goetz et al, 2008b).…”

“…Liver biopsies provide only a snapshot image of the liver tissue and do not allow dynamic monitoring of morphologic events (Goetz et al, 2008b). Staining efficiency variation, cost, and the impracticality of mass screening are some further disadvantages of liver biopsy (Lin et al, 2012). Performing serial liver biopsies to accurately determine disease progression or monitor treatment effects is not ideal (He et al, 2010).…”