Researchers have developed a custom Raman spectroscopy system that detected inflammatory bowel disease during colonoscopy with high sensitivity in a recent pilot study.
With further refinement, physicians could use the device for real-time IBD detection, discrimination between Crohn’s disease and ulcerative colitis, and evaluation of treatment response, according to investigators.
“With current methods, ultimately the diagnosis is dependent on how the patient responds to therapy over time, and you often don’t know the diagnosis until it’s been a few years,” Anita Mahadevan-Jansen, PhD, of the department of biomedical engineering at Vanderbilt University in Nashville, said in a press release. “That’s why we decided to use a light-based method to probe the biochemistry of what’s going on in the colon. Our goal is to use Raman spectroscopy to look at the actual inflammatory signals.”
Physicians currently rely on clinical, radiologic, endoscopic and pathologic features to differentiate between ulcerative colitis and Crohn’s disease based on symptoms, and this “inexact” diagnostic process lacks an objective gold standard, investigators wrote. In effect, up to 15% of IBD cases are diagnosed as indeterminate colitis and between 5% to 14% of patients have their IBD subtype reclassified based on their treatment response.
“Accurate differential diagnosis of IBD is critically needed for appropriate medical and surgical care, intervention, and prognosis,” they wrote.
Thus, based on previous findings showing that IBD subtypes differ on the molecular level, the investigators argued that Raman spectroscopy during colonoscopy may be useful for detecting these molecular differences and determining IBD subtype, degree of inflammation and early IBD indicators that precede macroscopic tissue changes.
“Most people go through baseline colonoscopy as part of routine care, and you could imagine using this to get a baseline Raman signal for each person,” Mahadevan-Jansen said in the press release. “If someone presents with IBD symptoms later on, you can use our system again to determine if it’s more likely to be UC or Crohn’s. Then once they are being treated, you have an objective measure to track their response because you can use the device to actually quantify mild, moderate or severe inflammation.”
After using tissue and animal studies to identify preliminary IBD biomarkers and spectral signatures, Mahadevan-Jansen and colleagues developed a custom, portable, Raman spectroscopy system with a 785-nm diode laser and fiber-optic probe that delivers 80 mW to the surface of the colon when coupled with a standard endoscope.
“The customization was both the packaging — to make sure it can fit easily in the endoscopy channel and bend through the turns of the colon — and to probe the right depth in the tissues we are looking at to make sure we can get a robust measurement,” she said in the press release.
Researchers then performed a pilot study involving eight UC patients, 15 Crohn’s patients and eight healthy controls who were scheduled for routine colonoscopy at the Vanderbilt GI Endoscopy lab. They collected spectra samples from normal and/or inflamed sites of the colon, and compared the results with standard diagnostic findings based on endoscopy, histopathology and patient history.
Overall the test could discriminate IBD from normal controls with high sensitivity (86%) but with poor specificity when discriminating between subtypes (39%). However, this varied depending on the degree of inflammation and sample location; for example, the test identified Crohn’s disease with 90% sensitivity and 75% specificity based on samples collected in the right colon in patients with active inflammation.
Moving forward, the researchers are working to refine prediction algorithms for interpreting test results, and to improve the test’s specificity by further investigating the impact of factors like sex, diet, demographics and treatment, according to the press release. They hope the system will eventually be able to deliver patient-specific results in real-time that can guide diagnosis and treatment.
“It’s a unique way of thinking about personalized medicine that takes into account all sorts of information — beyond just the genome — including demographics and many other factors that make a person unique,” Mahadevan-Jansen said in the press release. “Our lab has really pushed to find ways to apply optical technology to support this kind of personalized medicine.” – by Adam Leitenberger
Disclosures: Healio Gastroenterology was unable to confirm the researchers’ relevant financial disclosures at the time of publication.