Elastic scattering spectroscopy as an optical marker of inflammatory bowel disease activity and subtypes

Abstract

Background: In 10% to 15% of individuals, inflammatory bowel disease (IBD) is difficult to classify as ulcerative colitis (UC) or Crohn's disease (CD). Previous work has demonstrated that probe-based elastic scattering spectroscopy (ESS) can produce spectra, informed by parameters like tissue ultrastructure and hemoglobin content, capable of differentiating pathologies. This study investigates whether ESS is an in vivo optical biomarker for the presence, activity, and type of IBD in the colon.

Methods: Pilot study, a retrospective data analysis. ESS spectra of endoscopically normal and inflamed colon were obtained from 48 patients with IBD and 46 non-IBD controls. Measurements from patients with IBD were categorized as CD or UC based on clinical diagnosis. Spectra were analyzed using high-dimensional methods. Leave-one-patient-out cross-validation was used to obtain diagnostic performance estimates.

Results: Patients with IBD were distinguishable from non-IBD controls with a sensitivity of 0.93 and specificity of 0.91 based on readings from endoscopically normal mucosa, and 0.94 and 0.93 from inflamed mucosa. In patients with IBD, histologically normal and inflamed colon were distinguishable with per-class accuracies of 0.83 and 0.89, respectively; histologically normal from inactive inflammation with accuracies of 0.73 and 0.89, respectively; and inactive from active colitis with accuracies of 0.87 and 0.84, respectively. The diagnosis of CD versus UC was made with per-class accuracies of 0.92 and 0.87 in normal and 0.87 and 0.85 in inflamed mucosa, respectively.

Conclusions: ESS, a simple, low-cost clinically friendly optical biopsy modality, has the potential to enhance the endoscopic assessment of IBD and its activity in real time and may help to distinguish CD from UC.

FIGURE 1

A 2-dimensional representation of the optical forceps tip is depicted in (A). The optical forceps is a modified traditional endoscopic jaw-type biopsy forceps (left) with a central channel through which our fiberoptic probe is introduced for tissue measurements while the jaws are held open (right). A photograph of a clinically usable unit (B) showing standard biopsy forceps (left) next to our ESS integrated optical forceps (right).

FIGURE 2

Schematic diagram of the ESS system (A) and a photograph of the clinical ESS optical biopsy box used for this study (B).

FIGURE 3

Representative ESS spectra for (A) non-IBD patients versus (+)IBD patients; (B) patients with CD versus UC, measurements from endoscopically inflamed mucosa in (+)IBD patients; (C) inactive versus active colitis in (+)IBD patients, measurements taken from areas of endoscopic inflammation; (D) CD versus UC, measurements from endoscopically normal mucosa in (+)IBD patients.