Quantitative Phase Imaging Using Digital Holographic Microscopy to Assess the Degree of Intestinal Inflammation in Patients with Ulcerative Colitis

Arne Bokemeyer; Joost Buskermolen; Steffi Ketelhut; Phil-Robin Tepasse; Richard Vollenberg; Jonel Trebicka; Hartmut H Schmidt; Michael Vieth; Dominik Bettenworth; Björn Kemper

doi:10.3390/jcm12124067

Quantitative Phase Imaging Using Digital Holographic Microscopy to Assess the Degree of Intestinal Inflammation in Patients with Ulcerative Colitis

J Clin Med. 2023 Jun 15;12(12):4067. doi: 10.3390/jcm12124067.

Affiliations

¹ Department of Gastroenterology, Hepatology and Transplant Medicine, University Hospital of Essen, University Duisburg-Essen, 45147 Essen, Germany.
² Department of Medicine B for Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Muenster, 48149 Muenster, Germany.
³ Biomedical Technology Center, University of Muenster, 48149 Muenster, Germany.
⁴ Institut für Pathologie, Friedrich-Alexander-University Erlangen-Nürnberg, Klinikum Bayreuth, 95445 Bayreuth, Germany.
⁵ CED Schwerpunktpraxis Münster, 48149 Muenster, Germany.

Abstract

Ulcerative colitis (UC) is characterized by chronic inflammation of the colorectum. Histological remission has emerged as a potential future treatment goal; however, the histopathological assessment of intestinal inflammation in UC remains challenging with a multitude of available scoring systems and the need for a pathologist with expertise in inflammatory bowel disease (IBD). In previous studies, quantitative phase imaging (QPI) including digital holographic microscopy (DHM) was successfully applied as an objective method for stain-free quantification of the degree of inflammation in tissue sections. Here, we evaluated the application of DHM for the quantitative assessment of histopathological inflammation in patients with UC. In our study, endoscopically obtained colonic and rectal mucosal biopsy samples from 21 patients with UC were analyzed by capturing DHM-based QPI images that were subsequently evaluated using the subepithelial refractive index (RI). The retrieved RI data were correlated with established histological scoring systems including the Nancy index (NI) as well as with endoscopic and clinical findings. As a primary endpoint, we found a significant correlation between the DHM-based retrieved RI and the NI (R² = 0.251, p < 0.001). Furthermore, RI values correlated with the Mayo endoscopic subscore (MES; R² = 0.176, p < 0.001). An area under the receiver operating characteristics (ROC) curve of 0.820 confirms the subepithelial RI as a reliable parameter to distinguish biopsies with histologically active UC from biopsies without evidence of active disease as determined by conventional histopathological examination. An RI higher than 1.3488 was found to be the most sensitive and specific cut-off value to identify histologically active UC (sensitivity of 84% and specificity of 72%). In conclusion, our data demonstrate DHM to be a reliable tool for the quantitative assessment of mucosal inflammation in patients with UC.

Keywords: digital holographic microscopy; histopathology; inflammation; inflammatory bowel disease; quantitative phase imaging; refractive index; ulcerative colitis.

Grants and funding

This research received no external funding.