Toward surface quantification of liver fibrosis progression

Abstract

Monitoring liver fibrosis progression by liver biopsy is important for certain treatment decisions, but repeated biopsy is invasive. We envision redefinition or elimination of liver biopsy with surface scanning of the liver with minimally invasive optical methods. This would be possible only if the information contained on or near liver surfaces accurately reflects the liver fibrosis progression in the liver interior. In our study, we acquired the second-harmonic generation and two-photon excitation fluorescence microscopy images of liver tissues from bile duct-ligated rat model of liver fibrosis. We extracted morphology-based features, such as total collagen, collagen in bile duct areas, bile duct proliferation, and areas occupied by remnant hepatocytes, and defined the capsule and subcapsular regions on the liver surface based on image analysis of features. We discovered a strong correlation between the liver fibrosis progression on the anterior surface and interior in both liver lobes, where biopsy is typically obtained. The posterior surface exhibits less correlation with the rest of the liver. Therefore, scanning the anterior liver surface would obtain similar information to that obtained from biopsy for monitoring liver fibrosis progression.

A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy

“…Compared to microelectromechanical system (MEMS)-based probes (17), the current probe configuration does not involve beam folding optics and thus allows for an overall compact probe size. These features will enable future application of SHG endomicroscopy for clinical evaluation of a wide variety of disorders where collagen architecture is altered (27)(28)(29). In particular, we propose that translation of this emerging technology into the obstetrics clinic could potentially have a dramatic impact on the understanding and prediction of preterm birth risk.…”

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

“…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). The latter technique remains useful regardless of sample preparation (e.g., frozen or paraffin-embedded tissue), is easy and fast, has no sampling bias (Gailhouste et al, 2010), and may potentially quantify liver diseases such as fibrosis (He et al, 2010). However, to provide functional information regarding uptake, metabolism, and excretion, a fluorescent dye must be administered.…”

“…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). In addition, scoring systems to assess fibrosis use qualitative rather than quantitative measures, so it is difficult to obtain highly reproducible results without a high degree of intraobserver and interobserver discrepancy (as high as 35%) (Tai et al, 2009).…”

“…It accounts for 4.4% of all deaths among adults in developed countries (Lim and Kim, 2008), and liver transplantation is the only immediate treatment (Jonas et al, 2001). Fibrosis is treatable in its early stages, so accurate staging of the extent of fibrosis is important for optimal treatment (He et al, 2010). Liver function is traditionally assessed by static measures, which cannot track changes in liver function quickly.…”

“…Noninvasive imaging has the potential to extract extra information over a long period of time, over a larger sampling area, and with minimal morbidity (He et al, 2010). 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).…”