Rectal Mucosal Microvascular Blood Supply Increase Is Associated with Colonic Neoplasia

Abstract

Purpose: Endoscopic examination has proven effective in both detecting and preventing colorectal cancer; however, only about a quarter of eligible patients undergo screening. Even if the compliance rate increased, limited endoscopic capacity and cost would be prohibitive. There is a need for an accurate method to target colonoscopy to those most at risk of harboring colonic neoplasia. Exploiting field carcinogenesis seems to be a promising avenue. Our group recently reported that an early increase in blood supply (EIBS) is a reliable marker of field carcinogenesis in experimental models. We now investigate whether in situ detection of EIBS in the rectum can predict neoplasia elsewhere in the colon. Experimental Design:We developed a novel polarization-gated spectroscopy fiber-optic probe that allows depth-selective interrogation of microvascular blood content. Using the probe, we examined the blood content in vivo from the rectal mucosa of 216 patients undergoing screening colonoscopy. Results: Microvascular blood content was increased by f50% in the endoscopically normal rectal mucosa of patients harboring advanced adenomas when compared with neoplasia-free patients irrespective of lesion location. Demographic factors and nonneoplastic lesions did not confound this observation. Logistic regression using mucosal oxyhemoglobin concentration and patient age resulted in a sensitivity of 83%, a specificity of 82%, and an area under the receiver operating characteristic curve of 0.88 for the detection of advanced adenomas. Conclusions: Increased microvascular blood supply in the normal rectal mucosa is associated with the presence of clinically significant neoplasia elsewhere in the colon, supporting the development of rectal EIBS as a colon cancer risk-stratification tool.

In vivo measurement of the shape of the tissue-refractive-index correlation function and its applicationto detection of colorectal field carcinogenesis

“…Using polarization-gated spectroscopy, we have previously shown that early increases in bloody supply associated with carcinogenesis are more prominent at superficial tissue layers. 7,26 Low coherence interferometry has been used to demonstrate that the most significant changes in nuclear diameter in the AOM-treated rat occur at a depth of 35 μm. 35 In the present study, both the copolarization and crosspolarization m parameter were statistically significant indicators of concurrent neoplasia, suggesting diffuse alterations throughout mucosa and submucosa in the shape of the index correlation function.…”

“…Methods to separate the absorbance spectrum from the scattering spectrum f ðm; cλ 2m−4 Þ have been further described in detail in previous publications. 7,17,26 The precise functional form of f ðm; cλ 2m−4 Þ was determined using the MC methods described in Secs. 2.1 and 2.2 and is described in the results section.…”

“…Our laboratory has previously employed a suite of biophotonic technologies to demonstrate that changes in rectal optical signatures are indicative of premalignant lesions throughout the colon. [7][8][9] One of the technologies we have used is known as polarization-gated spectroscopy. Interrogation of tissue structure with polarized light has found numerous applications in biomedical optics, particularly for its ability to suppress multiply scattered light.…”

Algorithm for automated selection of application-specific fiber-optic reflectance probes

“…Our optical and histological investigations in human patients and animal models of colon carcinogenesis have shown diagnostic alterations in hemoglobin concentration that are present in the mucosa but attenuated at deeper submucosal depths. [1][2][3][4][5] Studies with angle-resolved low-coherence interferometry demonstrate that elevation of nuclear diameter associated with dysplasia in Barrett's esophagus was only detectable at a depth of 200 to 300 μm and not observable at 0 to 100 μm or 100 to 200 μm. 6 Several fiber-optic probe modalities have been developed to target the mucosal layer with a wide field of view.…”

“…[12][13][14] These methods have proven successful in diagnosing epithelial lesions including those in the colon, oral, and other types of mucosae. 1,2,9,13,[15][16][17][18] On the other hand, diffuse reflectance spectroscopy (DRS) methods typically have a sampling depth on the order of several millimeters and are consequently not very selective to the mucosal layer. However, the deeper sampling depth of DRS may be advantageous for other applications.…”