Quantitative diffuse reflectance and fluorescence spectroscopy: tool to monitor tumor physiology in vivo.

This study demonstrates the use of optical spectroscopy for monitoring tumor oxygenation and metabolism in response to hyperoxic gas breathing. Hemoglobin saturation and redox ratio were quantified for a set of 14 and 9 mice, respectively, measured at baseline and during carbogen breathing (95% O(2), 5% CO(2)). In particular, significant increases in hemoglobin saturation and fluorescence redox ratio were observed upon carbogen breathing. These data were compared with data obtained concurrently using an established invasive technique, the OxyLite partial oxygen pressure (pO(2)) system, which also showed a significant increase in pO(2). It was found that the direction of changes were generally the same between all of the methods, but that the OxyLite system was much more variable in general, suggesting that optical techniques may provide a better assessment of global tumor physiology. Optical spectroscopy measurements are demonstrated to provide a reliable, reproducible indication of changes in tumor physiology in response to physiologic manipulation.

[1]  T. K. Goldstick,et al.  Oxygen electrode design criteria and performance characteristics: recessed cathode. , 1978, Journal of applied physiology: respiratory, environmental and exercise physiology.

[2]  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.

[3]  T. K. Goldstick,et al.  Oxygen fields induced by recessed and needle oxygen microelectrodes in homogeneous media. , 1976, Advances in Experimental Medicine and Biology.

[4]  Karthik Vishwanath,et al.  Fluorescence Spectroscopy In Vivo , 2011 .

[5]  V. Grégoire,et al.  Preconditioning of the tumor vasculature and tumor cells by intermittent hypoxia: implications for anticancer therapies. , 2006, Cancer research.

[6]  Hanli Liu,et al.  Near-infrared spectroscopy and imaging of tumor vascular oxygenation. , 2004, Methods in enzymology.

[7]  M. Dewhirst,et al.  Human recombinant erythropoietin significantly improves tumor oxygenation independent of its effects on hemoglobin. , 2003, Cancer research.

[8]  Nirmala Ramanujam,et al.  Monte Carlo-based inverse model for calculating tissue optical properties. Part II: Application to breast cancer diagnosis. , 2006, Applied optics.

[9]  Karthik Vishwanath,et al.  A Robust Monte Carlo Model for the Extraction of Biological Absorption and Scattering In Vivo , 2009, IEEE Transactions on Biomedical Engineering.

[10]  Nirmala Ramanujam,et al.  Experimental proof of the feasibility of using an angled fiber-optic probe for depth-sensitive fluorescence spectroscopy of turbid media. , 2004, Optics letters.

[11]  Nirmala Ramanujam,et al.  Monte-Carlo-based model for the extraction of intrinsic fluorescence from turbid media. , 2008, Journal of biomedical optics.

[12]  E. Rofstad,et al.  Fluctuations in pO2 in Irradiated Human Melanoma Xenografts , 2006, Radiation research.

[13]  E. Hull,et al.  An evaluation of near infrared spectroscopy and cryospectrophotometry estimates of haemoglobin oxygen saturation in a rodent mammary tumour model. , 2000, Physics in medicine and biology.

[14]  N. Ramanujam,et al.  Monte Carlo-based inverse model for calculating tissue optical properties. Part I: Theory and validation on synthetic phantoms. , 2006, Applied optics.

[15]  B. Chance,et al.  Mitochondrial NADH as the bellwether of tissue O2 delivery. , 2005, Advances in experimental medicine and biology.

[16]  B. Chance,et al.  Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals. , 1979, The Journal of biological chemistry.

[17]  Hanli Liu,et al.  Tumour oxygen dynamics measured simultaneously by near-infrared spectroscopy and 19F magnetic resonance imaging in rats , 2006, Physics in medicine and biology.

[18]  M. Dewhirst,et al.  Comparison of tumor and normal tissue oxygen tension measurements using OxyLite or microelectrodes in rodents. , 2001, American journal of physiology. Heart and circulatory physiology.

[19]  P. Antich,et al.  Tumor oximetry: demonstration of an enhanced dynamic mapping procedure using fluorine-19 echo planar magnetic resonance imaging in the Dunning prostate R3327-AT1 rat tumor. , 2001, International journal of radiation oncology, biology, physics.

[20]  P. Vaupel,et al.  Tumor hypoxia: causative factors, compensatory mechanisms, and cellular response. , 2004, The oncologist.

[21]  Hanli Liu,et al.  Interplay of tumor vascular oxygenation and tumor pO2 observed using near-infrared spectroscopy, an oxygen needle electrode, and 19F MR pO2 mapping. , 2003, Journal of biomedical optics.