Microvascular Blood Content Research Articles

Depth-resolved measurement of mucosal microvascular blood content using low-coherence enhanced backscattering spectroscopy

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.

OC-077 Field effect identification via spectroscopic rectal microvasculature enables accurate proximal neoplasia detection by flexible sigmoidoscopy

Introduction Flexible sigmoidoscopy (flex sig) remains a cornerstone for colorectal cancer (CRC) screening in the UK although concerns have been raised about about isolated proximal neoplasia which is especially common in women.1 Our group has demonstrated using novel polarisation-gated spectroscopy (4D-ELF) that peri-cryptal microvascular blood supply is elevated in the histologically normal mucosa of patients harboring neoplasia elsewhere in their colon (marker of field effect).2–4 We, therefore, wanted to investigate whether this could serve as an adjunct to flex sig. Methods Subjects undergoing colonoscopy were recruited. Microvascular readings were taken from the endoscopically normal rectum with a fibreoptic probe and analysed by an investigator blinded to colonoscopic findings. Specifically, superficially (within 100 micron of tissue surface) oxygenated hemoglobin (SupOxyHb) was calculated. Proximal lesions were defined at the level of the spenic flexure. The performance of distal adenoma and microvascular blood content was calculated. Advanced adenomas (AAs) were defined as size ≥1.0 cm or presence of high-grade dysplasia. Results Our initial data set consisted of 366 patients (age 58±10, 50% female, 28 with AA). Distal adenoma performed poorly at identifying risk proximal AA (sensitivity 11%). Rectal SupOxyHb was elevated by approximately 50% in patients harboring proximal AA (when compared to neoplasia free patients) with an area under receiver operator characteric curve (AUROC) of 0.83. On a separate data set (n=172), the results were validated with an AUROC of 0.84. With regards to gender, the performance in females was excellent. (AUROC=0.88). SupOxyHb was not confounded by demographic factors or benign colonic disease (including hyperplastic polyps) and was insensitive to non-advanced adenomas. Conclusion We demonstrate, for the first time, that evaluation of rectal microvascular hemoglobin was able to sense proximal advanced adenomas with excellent accuracy, markedly outperforming the sentinel adenoma (a conventional marker of field effect). We replicated these results with an independent data set. Furthermore, SupOxyHb worked well in women, a group in which flex sig performs relatively poorly. Our data suggest that rectal EIBS measurement may provide an accurate and inexpensive means of improving performance of flex sig for CRC screening.

Rectal Mucosal Microvascular Blood Supply Increase Is Associated with Colonic Neoplasia

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.

Spectroscopic Microvascular Blood Detection From the Endoscopically Normal Colonic Mucosa: Biomarker for Neoplasia Risk

We previously used a novel biomedical optics technology, 4-dimensional elastically scattered light fingerprinting, to show that in experimental colon carcinogenesis the predysplastic epithelial microvascular blood content is increased markedly. To assess the potential clinical translatability of this putative field effect marker, we characterized the early increase in blood supply (EIBS) in human beings in vivo. We developed a novel, endoscopically compatible, polarization-gated, spectroscopic probe that was capable of measuring oxygenated and deoxygenated (Dhb) hemoglobin specifically in the mucosal microcirculation through polarization gating. Microvascular blood content was measured in 222 patients from the endoscopically normal cecum, midtransverse colon, and rectum. If a polyp was present, readings were taken from the polyp tissue along with the normal mucosa 10-cm and 30-cm proximal and distal to the lesion. Tissue phantom studies showed that the probe had outstanding accuracy for hemoglobin determination (r(2) = 0.99). Augmentation of microvasculature blood content was most pronounced within the most superficial ( approximately 100 microm) layer and dissipated in deeper layers (ie, submucosa). EIBS was detectable within 30 cm from the lesion and the magnitude mirrored adenoma proximity. This occurred for both oxygenated hemoglobin and DHb, with the effect size being slightly greater for DHb. EIBS correlated with adenoma size and was not engendered by nonneoplastic (hyperplastic) polyps. We show, herein, that in vivo microvascular blood content can be measured and provides an accurate marker of field carcinogenesis. This technological/biological advance has numerous potential applications in colorectal cancer screening such as improved polyp detection and risk stratification.

Biophotonic Detection of Increased Microvascular Blood Content (EIBS) As a Marker of Field Carcinogenesis Detection: Potential Adjunctive Technology for Colonoscopy

Biophotonic Detection of Increased Microvascular Blood Content (EIBS) As a Marker of Field Carcinogenesis Detection: Potential Adjunctive Technology for Colonoscopy

A New Biomarker for Colonic Neoplasia

The investigators in this study previously used a probe-based, endoscopic, scattered-light fingerprinting technique to measure microvascular blood content in the colonic mucosa. They showed that, in animal models, normal mucosa near colon polyps and near cancer has an early increase in blood supply (EIBS). Now, the same investigators have measured the microvascular …

Inducible nitric oxide synthase (iNOS) mediates the early increase of blood supply (EIBS) in colon carcinogenesis

We have recently demonstrated that dramatic alteration in mucosal microvascular blood content termed early increase in blood supply (EIBS) is a hallmark of early colon carcinogenesis. In the current study, we elucidate the mechanism of EIBS by assessing iNOS/nitric oxide axis in the histologically normal colonic mucosa of rats treated with the colon-specific carcinogen, azoxymethane. We demonstrate that there was a strong temporal correlation between EIBS and iNOS expression/activity. Importantly, we also observed that short-term treatment with nitric oxide inhibitor abrogated EIBS. These data indicate that iNOS induction may have a critical role in augmenting the predysplastic mucosal blood supply and thereby fostering colon carcinogenesis.

Regional blood flow, microvascular blood content and tissue haematocrit in canine myocardium.

Regional myocardial blood flow, myocardial microvascular blood content and tissue haematocrit were determined in mongrel dogs. In nine dogs the intramyocardial distribution volumes of 99Tcm-albumin and 125I-fibrinogen were examined. Tracer equilibration times of 5, 10 and 30 min were used. The 125I-fibrinogen distribution volume was significantly lower than the distribution volume of 99Tcm-albumin. The 125I-fibrinogen distribution volume was not found to change with time and was thus taken to be a measure of the plasma volume. In 10 dogs intramyocardial distribution of 51Cr-labelled red cells and 125I-fibrinogen was estimated and regional myocardial blood flow was measured by 15 microns 99Tcm-albumin spheres. Plasma and red cell volumes, interpreted as myocardial microvascular blood content, ranged from 3.66 to 4.93 cm3-100 g-1. The distribution volumes indicated gradients with higher endocardial and longitudinal microvascular blood content in the left ventricular free wall and the septum. The intramyocardial haematocrits calculated from the plasma and red cell volumes were uniformly 0.3 all over the heart and amounted to 0.75 of arterial haematocrit. The mean right ventricular blood flow of 46.80 cm3 . min-1 . 100 g-1 amounted to 0.6 of a mean left ventricular blood flow of 86.65 cm3 . min-1 . 100 g-1. Transmural and longitudinal gradients of regional myocardial blood flow within the ventricular wall were observed. The patterns of transmural and longitudinal gradients of regional blood flow and microvascular blood content implies higher flow rates through more or larger vessels indicating a greater endocardial and apical vascular conductance in the vicinity of the left ventricular cavity.