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.

Endoscopic histological assessment of colonic polyps by using elastic scattering spectroscopy

“…The ESS system and probes have been described previously (38, 43, 45). Briefly, the ESS optical biopsy forceps consist of 2 identical adjacent fibers with 200-μm cores (1 for illumination, the other for detection), with a numerical aperture of 0.22 in air.…”

“…In the gastrointestinal tract, ESS appears to be sensitive to dysplasia in the esophagus (34–39) and to a variety of colonic pathologies including neoplasia (40–45). …”

Optical Spectroscopy as a Method for Skin Cancer Risk Assessment

“…Due to its ability to translate tissue morphology into spectral features at the cellular and sub‐cellular levels, ESS relates directly to the observed tissue architecture and structure of histopathologic features . Different tissue types and histopathological status exhibit specific optical signatures, and ESS has been demonstrated clinically to assess malignancy in multiple tissue types . Spectral correlation with histopathologic diagnosis using variations of ESS has also been reported by other groups .…”

Clinical characterization of in vivo inflammatory bowel disease with Raman spectroscopy

“…4). However, when considering only spectra from active locations from IBD subjects, regardless of disease, the spectra are much weaker, and exhibit peak broadening consistent with increased protein content, potentially from fibrin and collagen and consistent with ulceration and edema [14,17]. While these features themselves do not provide discrimination between CD and UC, there remains the potential that an objective metric for disease activity could be developed; such a metric could be used to evaluate therapeutic response after initiation of medication, for which a relative measure of active inflammation over time could be critical.…”

“…The lack of a definitive, biochemically specific characterization tool that can investigate IBD subtypes directly hinders delivery of appropriate care. Numerous investigations have been pursued to develop tools to improve diagnosis, including computed tomography, magnetic resonance imaging, optical coherence tomography, laser endomicroscopy, wireless capsule endoscopy, and elastic scattering spectroscopy [12][13][14][15][16]. All of these techniques are based on structure either at the macroscopic (appearance under widefield imaging) or microscopic scale (cell morphology and optical scattering properties of tissues).…”