Diagnostics & Imaging Week National Editor

A new proof-of-concept study out of NorthShore University HealthSystem (Evanston, Illinois) and Northwestern University (also Evanston) highlights the role that advanced imaging might play in personalized medicine, in this case potentially ferreting out the precancerous stage of colon cancer.

Underline "potentially."

Risk assessment has become a central principle of personalized medicine, sometimes called theranostics — diagnostics to guide therapy, its implementation often a rather large gamble concerning individual healthcare. But the researchers in the new study acknowledge that they are developing a "premise," yet to be proven true.

The study analyzes the ability of an advanced fiber optic technology to assess abnormal types of blood in the outer layers of the colon and that this measurement may be shown to indicate risk for colon cancer, thus providing its "fingerprint."

The attempt at this fingerprinting derives from the researchers' use of a system called Four Dimensional Elastic Light Scattering Fingerprinting (4D-ELF), an advanced fiber optic system, developed by Dr. Vadim Backman, professor of biomedical engineering at Northwestern University's McCormick School of Engineering and Applied Science.

Underpinning the study is the researchers' analysis of what they term EIBS, for early increase in blood supply, and its ability to be used as an identifier of early polyps leading to cancer. The researchers hypothesize that 4D-ELF measurement of EIBS may be a valid biomarker signaling colon cancer risk, with further validation by means of its continuing studies.

The study was carried out by combining the 4D-ELF system with colonoscopies in 220 patients in 2006-2007.

Headed by Hemant Roy, MD, director of gastroenterology research at NorthShore University HealthSystem, the researchers began with the hypothesis that abnormal blood levels in the outer layers of the colon signal the development of polyps, those polyps becoming the signature lesion, the ultimate revealing fingerprint, of colon cancer. Their hope is that this detection can be made before even those changes detectable by microscopy can be seen.

Roy told Diagnostics & Imaging Week that the 4D-ELF system essentially measures the wave lengths of light bouncing off of blood cells, with the innovative aspect of the technology its ability to do this in the outer layers of the intestine. "It's able to specifically target the most superficial part of the lining," he said.

"Our premise is that since the lining of the large intestine — rectum and colon — is contiguous, if you see an abnormality in one part of the colon, then somewhere else in the colon you have a higher likelihood of harboring an adenoma [benign tumor] or carcinoma [malignant tumor]," said Roy. And he credited the "unique and accurate ability" of 4D-ELF to do this.

"We are not determining whether an abnormality is cancer or not cancer," he said. "What we are doing is using optical technology to determine if we can assess risk through looking at field carcinogenesis [cancer formation]. The potential clinical applications included enhance polyp detection during colonoscopy."

Researchers used the optic probe to measure oxygenated (Ohb) and deoxygenated (Dhb) hemoglobin (Hb), specifically in the colonic lining where small blood vessels circulate.

The study found that the total Hb concentration was elevated 75.3% above control levels (comparable region from patients with no adenomas) at the adenoma site and persisted in the uninvolved mucosa (microscopically normal) area. Moreover, tissue sites located within 10 and 30 cm away from an adenoma also manifested a highly statistically significant increase in total Hb, OHb and DHb concentration.

Of the 220 patients in the study, 175 had no adenomas detected, 35 had non-advanced adenomas and 12 had advanced adenomas (polyps larger than one cm). The mean age was 56.6 years and 40% were female. There were no significant differences in gender. The groups did not significantly differ in tobacco or alcohol history.

"It's fascinating," Roy said, "to very precisely know that you're looking at the most superficial layer of tissue — which is where all polyps and cancer start — and the accuracy with which these things can be measured."

Backman, developer of the technique, also is using this light-scattering system to attempt to identify the earliest symptoms of pancreatic cancer by looking at nanoscale cellular changes in the duodenum.

"No one can detect these changes earlier than we can," Backman has said in a website publication from Northwestern University. And he calls this a "field effect" phenomenon.

Roy told D&IW that it is likely to take up to five years to further validate the ability of the technology to assess EIBS and to demonstrate that EIBS is an accurate assessment of risk for this disease. If successful, this would enable more careful guidance of patients with this risk and might further advance to becoming a critical adjunct to colonoscopy.

But he says it should not threaten colonoscopy, as other technologies currently are doing.

"This partnership with Dr. Backman at Northwestern University has the potential of bringing a suite of technologies that is not meant to replace colonoscopy," said Roy, "but rather to more precisely determine risk and thereby help to individualize recommendations on the timing of colonoscopy for colon cancer screening. This improved efficiency and accuracy may aid in cancer prevention efforts."

The study is reported in the October issue of Gastroenterology, the journal of the American Gastroenterological Association (Bethesda, Maryland).