Diffuse reflectance spectroscopy detects increased hemoglobin concentration and decreased oxygenation during colon carcinogenesis from normal to malignant tumors.

Blood content and tumor oxygen level are important biomarkers and prognostic indicators in patients with colorectal cancer (CRC). However, noninvasive measurements of both quantities in human colon are limited. In this study, we extracted the total hemoglobin concentration (THC) and oxygen saturation (StO(2)) of normal, premalignant, and malignant colonic tissues in 27 patients using a diffuse reflectance instrument and algorithms based on the diffusion equation. The mean+/-standard error of THC and StO(2) from all normal sites (n=26) is 93.4+/-17.1microM and 67.2+/-3.7%, respectively. THC increased to 136.9+/-23.8microM and 153.8+/-38.6microM and StO(2) decreased to 51.3+/-7.0% and 26.4+/-6.1% for premalignant and malignant tissues, respectively. The disease-to-normal THC ratios are 3.2+/-1.1 and 4.4+/-1.9 and the disease-to-normal StO(2) ratios are 0.7+/-0.1 and 0.5+/-0.1 for pr alignant and malignant tissues, respectively. These results demonstrate the feasibility of a robust optical method to assess colon THC and StO2 at all stages of carcinogenesis in vivo so that the angiogenesis and hypoxia of the disease and the therapeutic role can be studied in CRC patients.

[1]  R. Gatenby,et al.  Oxygen tension in human tumors: in vivo mapping using CT-guided probes. , 1985, Radiology.

[2]  A. Wree,et al.  Lack of Correlation between Expression of HIF-1α Protein and Oxygenation Status in Identical Tissue Areas of Squamous Cell Carcinomas of the Uterine Cervix , 2004, Cancer Research.

[3]  Pablo R. Ros,et al.  Normal Colonic Wall Thickness at CT and Its Relation to Colonic Distension , 2002, Journal of computer assisted tomography.

[4]  Shoko Nioka,et al.  Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors: a pilot study. , 2006, Journal of biomedical optics.

[5]  R. Cerutti,et al.  Up-regulation of the hypoxia-inducible factor-1 transcriptional pathway in colorectal carcinomas. , 2008, Human pathology.

[6]  Timothy C Zhu,et al.  Broadband reflectance measurements of light penetration, blood oxygenation, hemoglobin concentration, and drug concentration in human intraperitoneal tissues before and after photodynamic therapy. , 2005, Journal of biomedical optics.

[7]  Jarod C Finlay,et al.  Quantitative comparison of tissue oxygen and motexafin lutetium uptake by ex vivo and noninvasive in vivo techniques in patients with intraperitoneal carcinomatosis. , 2007, Journal of biomedical optics.

[8]  J. K. Fisher Abnormal Colonic Wall Thickening on Computed Tomography , 1983, Journal of computer assisted tomography.

[9]  Jarod C Finlay,et al.  Hemoglobin oxygen saturations in phantoms and in vivo from measurements of steady-state diffuse reflectance at a single, short source-detector separation. , 2004, Medical physics.

[10]  J. Berlin,et al.  Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. , 2004, The New England journal of medicine.

[11]  Peter T. Nelson,et al.  Hypoxia Is Important in the Biology and Aggression of Human Glial Brain Tumors , 2004, Clinical Cancer Research.

[12]  J. Detre,et al.  Diffuse optical measurement of blood flow, blood oxygenation, and metabolism in a human brain during sensorimotor cortex activation. , 2004, Optics letters.

[13]  G. Zonios,et al.  Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo. , 1999, Applied optics.

[14]  F. Ciardiello,et al.  Elevated perioperative serum vascular endothelial growth factor levels in patients with colon carcinoma , 2004, Cancer.

[15]  B. Chance,et al.  Time-dependent blood flow and oxygenation in human skeletal muscles measured with noninvasive near-infrared diffuse optical spectroscopies. , 2005, Journal of biomedical optics.

[16]  Vadim Backman,et al.  Spectroscopic microvascular blood detection from the endoscopically normal colonic mucosa: biomarker for neoplasia risk. , 2008, Gastroenterology.

[17]  A. Harris,et al.  Hypoxia-Inducible Factor 1α Expression as an Intrinsic Marker of Hypoxia , 2004, Clinical Cancer Research.

[18]  Xiaowen Zhang,et al.  Deleted in pancreatic carcinoma locus 4/Smad4 participates in the regulation of apoptosis by affecting the Bcl-2/Bax balance in non-small cell lung cancer. , 2008, Human pathology.

[19]  David A Boas,et al.  Assessing the future of diffuse optical imaging technologies for breast cancer management. , 2008, Medical physics.

[20]  Thomas H. Foster,et al.  Steady-state reflectance spectroscopy in the P 3 approximation , 2001 .

[21]  P. Okunieff,et al.  Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. , 1989, Cancer research.

[22]  D. Hanahan,et al.  The Hallmarks of Cancer , 2000, Cell.

[23]  Samuel Valable,et al.  Assessment of blood volume, vessel size, and the expression of angiogenic factors in two rat glioma models: a longitudinal in vivo and ex vivo study , 2008, NMR in biomedicine.

[24]  Weibo Cai,et al.  Multimodality Molecular Imaging of Tumor Angiogenesis , 2008, Journal of Nuclear Medicine.

[25]  D. Chung,et al.  Hypoxia Inducible Factor-1–Independent Pathways in Tumor Angiogenesis , 2007, Clinical Cancer Research.

[26]  David A. Benaron,et al.  Measurement of mucosal capillary hemoglobin oxygen saturation in the colon by reflectance spectrophotometry. , 2003 .

[27]  S. Groshen,et al.  Polymorphisms in VEGF and IL-8 predict tumor recurrence in stage III colon cancer. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[28]  M G Nichols,et al.  Quantitative broadband near-infrared spectroscopy of tissue-simulating phantoms containing erythrocytes. , 1998, Physics in medicine and biology.

[29]  Michael J. Emanuele,et al.  Hypoxia and Photofrin Uptake in the Intraperitoneal Carcinomatosis and Sarcomatosis of Photodynamic Therapy Patients , 2004, Clinical Cancer Research.

[30]  C. Koch,et al.  Measurement of absolute oxygen levels in cells and tissues using oxygen sensors and 2-nitroimidazole EF5. , 2002, Methods in enzymology.

[31]  David Benaron,et al.  Diagnosis of chronic mesenteric ischemia by visible light spectroscopy during endoscopy. , 2006, Gastrointestinal endoscopy.

[32]  J. K. Fisher Normal colon wall thickness on CT. , 1982, Radiology.

[33]  Y Usson,et al.  In vivo assessment of tumoral angiogenesis , 2004, Magnetic resonance in medicine.