Jedrzkiewicz J, Bronner MP, Salama ME, Kohan J, Rowe LR, et al. (2018) Liver Fibrosis Quantification by Digital Whole Slide Imaging and Two Photon Microscopy with Second Harmonic Generation. Int J Pathol Clin Res 4:078.


© 2018 Jedrzkiewicz J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ORIGINAL ARTICLE | OPEN ACCESS DOI: 10.23937/2469-5807/1510078

Liver Fibrosis Quantification by Digital Whole Slide Imaging and Two Photon Microscopy with Second Harmonic Generation

Jolanta Jedrzkiewicz1*, Mary P Bronner1, Mohamed E Salama1, Jessica Kohan2, Leslie R Rowe2, Dean Tai3, Elisabeth Malmberg2 and Erinn Downs-Kelly1

1Department of Pathology, University of Utah, USA

2ARUP Laboratories, USA

3Histoindex Pte. Ltd, Institute of Bioengineering and Nanotechnology, Singapore



The progression of fibrosis in liver disease is the single most important pathologic process guiding patient prognosis and treatment decisions. Unfortunately, its histologic assessment is subjective, descriptive and non-quantitative. A more objective and uniform method is needed to assess fibrosis in order to optimize patient care. To that end, we employed two new quantitative imaging technologies to evaluate fibrosis.


49 non-fragmented liver core needle biopsies from patients with a variety of etiologies inciting injury, focusing on hepatitis C and steatohepatitis patients were evaluated histologically by three hepatopathologists generating a Fleiss kappa value of 0.59. Histologic scores were compared with two different quantitative technologies: 1) Aperio Technologies 2 scanner (Leica, Vista, CA) using a color deconvolution algorithm (ScanScope V9), and 2) Genesis®100 (Histoindex Pte Ltd, Singapore/Singapore) using two photon excitation microscopies with second harmonic generation.


Positive correlation was demonstrated between the average histologic scores and fibrosis percentages obtained by Aperio Technologies 2 digital scanner (r = 0.75), along with the two photon microscopy measures of total fibrosis percent (r = 0.59), aggregated fiber percentage (r = 0.58), total number of fibers (r = 0.62), and number of fiber cross-links (r = 0.52).


Only moderate interobserver agreement was demonstrated for histologic scoring, highlighting the need for a more objective fibrosis scoring system. Both quantitative imaging technologies examined reveal strong correlation to histologic scoring and therefore show great promise as a means to quantify fibrosis more objectively.