Raman spectroscopy accurately differentiates mucosal healing from non-healing and biochemical changes following biological therapy in inflammatory bowel disease

PLoS One. 2021 Jun 2;16(6):e0252210. doi: 10.1371/journal.pone.0252210. eCollection 2021.

Abstract

Background: Mucosal healing (MH) is a key treatment target in the management of inflammatory bowel disease (IBD) and is defined in endoscopic terms by the newly published PICaSSO score. Raman Spectroscopy (RS) is based on the scattering of inelastic light giving spectra that are highly specific for individual molecules. We aimed to establish spectral changes before and after treatment and whether Raman Spectroscopy is able to accurately differentiate between inflammation and MH.

Methods: Biopsies were taken for ex vivo RS analysis alongside biopsies for histological analysis from IBD patients undergoing optical diagnosis endoscopic assessment. We compared pre- vs. post-biological treatment in IBD patients and healthy controls and active vs. MH in UC and CD. For spectral analysis, we used supervised self-organising maps for separation and classification.

Results: A total of 23 patients (14 IBD, 9 HC) were recruited for comparison of pre- vs. post-biologic treatment and 74 IBD patients were included for the assessment of MH in IBD, giving 9700 Raman Spectra. Spectral differences were seen between pre- and post-treatment which were observed comparing MH vs. active inflammation. Reductions in intensity at 1003cm-1 and 1252cm-1 when a reduction in inflammation was seen post-treatment and when MH was present. MH was associated with an increase in intensity at 1304cm-1. The trained neural network differentiated MH from active inflammation with a sensitivity, specificity, PPV, NPV and accuracy in UC of 96.29% (sd 0.94), 95.03% (sd 1.52), 94.89% (sd 1.59), 96.33 (sd 0.97) and 95.65 (sd 0.99) and 96.19% (sd 1.46), 88% (sd 4.20), 86.60% (sd 5.39), 96.55% (sd 1.32) and 91.6% (sd 2.75) in CD respectively.

Conclusion: We demonstrated RS can demonstrate biochemical changes following treatment of IBD and accurately differentiates MH from active inflammation in IBD and might be a future tool to personalise therapeutic management in IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biological Therapy / methods*
  • Biomarkers / analysis
  • Biomarkers / metabolism*
  • Case-Control Studies
  • Female
  • Humans
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / pathology*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology*
  • Male
  • Middle Aged
  • Spectrum Analysis, Raman / methods*
  • Wound Healing*

Substances

  • Biomarkers

Grants and funding

MI and SG are funded by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. CB acknowledges funding from EPSRC through a studentship from the Sci-Phy-4-Health Centre for Doctoral Training.