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Journal of Biomedical Optics • Open Access

Longitudinal optical imaging of tumor metabolism and hemodynamics
Author(s): Melissa C. Skala; Andrew Nicholas Fontanella; Lan Lan; Joseph A. Izatt; Mark W. Dewhirst

Paper Abstract

An important feature of tumor hypoxia is its temporal instability, or "cycling hypoxia." The primary consequence of cycling hypoxia is increased tumor aggressiveness and treatment resistance beyond that of chronic hypoxia. Longitudinal imaging of tumor metabolic demand, hemoglobin oxygen saturation, and blood flow would provide valuable insight into the mechanisms and distribution of cycling hypoxia in tumors. Fluorescence imaging of metabolic demand via the optical redox ratio (fluorescence intensity of FAD/NADH), absorption microscopy of hemoglobin oxygen saturation, and Doppler optical coherence tomography of vessel morphology and blood flow are combined to noninvasively monitor changes in oxygen supply and demand in the mouse dorsal skin fold window chamber tumor model (human squamous cell carcinoma) every 6 h for 36 h. Biomarkers for metabolic demand, blood oxygenation, and blood flow are all found to significantly change with time (p<0.05). These variations in oxygen supply and demand are superimposed on a significant (p<0.05) decline in metabolic demand with distance from the nearest vessel in tumors (this gradient was not observed in normal tissues). Significant (p<0.05), but weak (r ≤0.5) correlations are found between the hemoglobin oxygen saturation, blood flow, and redox ratio. These results indicate that cycling hypoxia depends on both oxygen supply and demand, and that noninvasive optical imaging could be a valuable tool to study therapeutic strategies to mitigate cycling hypoxia, thus increasing the effectiveness of radiation and chemotherapy.

Paper Details

Date Published: 1 January 2010
PDF: 8 pages
J. Biomed. Opt. 15(1) 011112 doi: 10.1117/1.3285584
Published in: Journal of Biomedical Optics Volume 15, Issue 1
Show Author Affiliations
Melissa C. Skala, Vanderbilt Univ. (United States)
Andrew Nicholas Fontanella, Duke Univ. (United States)
Lan Lan, Duke Univ. (United States)
Joseph A. Izatt, Duke Univ. (United States)
Mark W. Dewhirst, Duke Univ. (United States)

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