Rectal Mucosal Microvascular Blood Supply Increase Is Associated with Colonic Neoplasia

Biomedical Engineering Department, Northwestern University, IL, USA.
Clinical Cancer Research (Impact Factor: 8.72). 05/2009; 15(9):3110-7. DOI: 10.1158/1078-0432.CCR-08-2880
Source: PubMed


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.
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.
Microvascular blood content was increased by approximately 50% 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.
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.

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Available from: Laura K Bianchi, Sep 04, 2014
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    • "Another critical aspect of the measurements is depth selectivity, because microvascular alterations are the most pronounced in the pericryptal plexus of the mucosa, which supplies blood to colonocytes. A number of depth-selective optical spectroscopy techniques have been implemented to detect field carcinogenesis including polarization gating and low-coherence enhanced backscattering (LEBS) spectroscopy20-22, 35. "
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    ABSTRACT: The process of neoplastic transformation of the colon involves a progression through hyperproliferative epithelium through the aberrant crypt foci→small adenoma→large adenoma→invasive cancer→metastatic disease. These are orchestrated by sequential genetic and epigenetic events which provide the underpinnings of cellular alterations such as early induction in proliferation/suppression of apoptosis, along with the late stage increase in invasiveness. Colorectal cancer (CRC) averages 49-111 mutations per tumor encompassing 10-15 critical signaling pathways[1]. Accumulating such a high number of mutations requires a fertile mutational field, which is the hallmark of colon carcinogenesis. While genetic susceptibility to colorectal cancer is well-known, at least half of the risk is believed to be due to exogeneous factors (e.g., obesity, diet, exercise). Understanding these risk factors represents a promising mode of tailoring screening modality and intensity. However, previous attempts using these factors (i.e., NCI risk calculator) have only been modestly successful with an area under receiver operating characteristics (ROC) curve (AUC) of just 0.61. One of the most important concepts is that risk is the interaction between these genetic and environmental components and is driven by the variety of polymorphisms. Thus, predicting risk is difficult given the complexity. On the other hand, the colonic mucosa represents the end product of the complex interplay between these multiple factors. The power of field carcinogenesis is that it reflects this interplay between genetics and environment.
    Preview · Article · Mar 2013 · Journal of Cancer
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    • "Applying the reconstruction method towards measurements of colonic tissue from the 10 week AOM-treated rat model of colon carcinogenesis we report an increase in blood supply at a depth corresponding to the base of the colonic crypt. These results are consistent with our previous findings [14,19–22]. "
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    ABSTRACT: Low-coherence enhanced backscattering (LEBS) spectroscopy is a light scattering technique which uses partial spatial coherence broadband illumination to interrogate the optical properties at sub-diffusion length scales. In this work, we present a post-processing technique which isolates the hemoglobin concentration at different depths within a sample using a single spectroscopic LEBS measurement with a fixed spatial coherence of illumination. We verify the method with scattering (spectralon reflectance standard and polystyrene microspheres) and absorbing (hemoglobin) phantoms. We then demonstrate the relevance of this method for quantifying hemoglobin content as a function of depth within biological tissue using the azoxymethane treated animal model of colorectal cancer.
    Full-text · Article · Nov 2010 · Biomedical Optics Express
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    • "In each experiment, measurements were normalized to our perceived ideal operating conditions which included applying a gentle pressure and the probe axis normal to the tissue surface. From each tissue measurement, five parameters were extracted from the algorithm used in previous in vivo analysis [2,13–16]: (1) total hemoglobin (Hb) concentration, (2) oxygen saturation, (3) packaging length scale (PLS) which is proportional to blood vessel diameter, (4) shape parameter, m, which describes the distribution of length scales, and (5) total scattering intensity. The parameter m characterizes the shape of the refractive index correlation function and is used to model the distribution of scattering length scales. "
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    ABSTRACT: Noninvasive optical techniques for tissue characterization, in particular, light scattering properties and blood supply quantification of mucosa, is useful in a wide variety of applications. However, fiber-optic probes that require contact with the tissue surface can present a challenging problem in the variability of in vivo measurements due the nature of interactions, for example affects due to variations in pressure applied to the probe tip. We present an in vivo evaluation of pressure, angle, and temporal effects on tissue properties for polarization-gated spectroscopy at superficial depths (within 100 to 200 microns of tissue surface) for oral mucosa.
    Full-text · Article · Sep 2010 · Biomedical Optics Express
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