Quantitative phase microscopy for evaluation of intestinal inflammation and wound healing utilizing label-free biophysical markers

Dominik Bettenworth¹*, Arne Bokemeyer¹*, Christopher Poremba², Nik Sheng Ding³, Steffi Ketelhut⁴, Philipp Lenz^1,5# and Björn Kemper⁴#

¹Department of Medicine B, University Hospital Muenster, Muenster, ²Department of Pathology, Pathology Munich-North, Munich, Germany, ³Department of Medicine, University of Melbourne, Melbourne, Vic, Australia, ⁴Biomedical Technology Center, University of Muenster and ⁵Institute of Palliative Care, University Hospital Muenster, Muenster, Germany
*: these authors contributed equally and share first authorship
#: these authors contributed equally and share last authorship

Offprint requests to: Dr. Björn Kemper, PhD, Biomedical Technology Center, University of Muenster, Mendelstraße 17, D-48149 Muenster, Germany. e-mail: bkemper@uni-muenster.de

Summary. Inflammatory bowel diseases (IBD) are inflammatory disorders of the gastrointestinal tract characterized by a chronic relapsing disease course. As uncontrolled intestinal inflammation can result in severe disease complications, recent treatment targets of IBD evolved toward seeking the absence of mucosal and histological inflammation. However, this approach requires adequate histological evaluation of IBD disease activity. The diagnostic challenge of histological examination of intestinal inflammation is documented by the multitude of proposed histological scoring systems. In this context, we review quantitative phase imaging (QPI) techniques such as digital holographic microscopy (DHM) for characterizing intestinal inflammation. DHM determines optical path-length delays in a stain-free manner, thereby providing the tissue refractive index as a biophysical marker that directly correlates to tissue density. Recently, DHM has been successfully applied in cell biology, cancer cell research and infectious-induced cellular alterations. We summarized the capabilities of DHM and related QPI techniques to assess the severity of intestinal inflammation in experimental colitis as well as in colonic samples from human IBD patients. Moreover, we illustrate major advantages of DHM facilitated multimodal evaluation of epithelial wound healing processes as assessed by physical parameters like cell volume, density, thickness and dry mass in vitro. Furthermore, potential limitations of DHM and future utilities of QPI are discussed. In conclusion, DHM represents a promising, easy-to-use quantitative tool to provide accurate and objective assessment of intestinal inflammation and may pave the way towards automated label-free digital pathology and related in vitro cell culture analysis in future. Histol Histopathol 33, 417-432 (2018)

Key words: Inflammatory bowel disease, Histological healing, Digital holographic microscopy, Quanitative phase microscopy

DOI: 10.14670/HH-11-937