Tumor oxygen dynamics: Comparison of 19F MR EPI and frequency domain NIR spectroscopy

Joint Graduate Program in Biomedical Engineering, Department of Radiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Advances in Experimental Medicine and Biology (Impact Factor: 1.96). 02/2003; 530:225-36. DOI: 10.1007/978-1-4615-0075-9_22
Source: PubMed


Oxygen plays a key role in tumor therapy and may be related to tumor development: e.g., angiogenesis and metastasis. Using noninvasive techniques to accurately measure tumor oxygenation could assist in developing novel therapies. Here, we have used the FREDOM (Fluorocarbon Relaxometry using Echo planar imaging for Dynamic Oxygen Mapping) approach based on hexafluorobenzene (HFB) to monitor tissue oxygen tension (pO2) of rat breast and prostate tumors and compared the results with changes in tumor vascular hemoglobin saturation (sO2) and concentration observed using a new dual wavelength homodyne near-infrared (NIR) system. The dynamic changes in pO2 and sO2 were assessed while rats were breathing various gases. NIR showed significant changes in vascular oxygenation accompanying respiratory interventions. 19F MR-EPI also showed significant changes in tissue pO2 and revealed considerable regional heterogeneity in both absolute values and rate of change accompanying interventions. Generally, changes in vascular sO2 preceded tissue pO2, particularly for smaller tumors.

3 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: The first pathologists, oncologists, and medical physicists were aware that tumors were populated by an aberrant vasculature. The classic observations of Thomlinson and Gray in the 1950’s established that O2 diffusion distances caused tumor to grow in cords. Tumor necrosis was observed surrounding a Krogh cylinder of viable tumor. That work helped explain earlier work by Warburg, who demonstrated a predisposition for tumors to favor anaerobic respiration, and it became the basis for 5 decades of subsequent research aimed at improving tumor oxygenation at the time of radiation. The role of O2 in modifying radiation response was attributed exclusively to the reactive free radicals that can be formed when O2 is present. These radicals produce approximately three-fold more irreparable double strand breaks in DNA. Subsequently it became clear that tumor had nutritional insufficiencies in addition to hypoxia. Ischemic regions are hypoglycemic, acidotic, have poor penetration of drugs, increased interstitial pressure, and altered immunological states. Ischemic regions can have intermittent reflow and associated redox stress. The relative impact of O2 compared to these associated phenomenon, and the degree to which hypoxia causes or follows these associated physiologic stresses, have been studied in detail. ISOTT scientists are responsible for much of the elucidation of the specific effects of O2, ADP/ATP ratios, hypoglycemia, and acidosis on tumor responses to radiation and hyperthermia. Many questions still remain.
    No preview · Article · Feb 2005 · Advances in Experimental Medicine and Biology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the effect of the vascular targeting agent, combretastatin A4 phosphate, on tumor oxygenation compared with vascular perfusion/permeability. (19)F MRI oximetry and dynamic contrast-enhanced (DCE)-MRI were used to monitor tumor oxygenation and perfusion/permeability in syngeneic 13762NF rat breast carcinoma. A significant drop was found in the mean tumor pO(2) (23 to 9 mm Hg, p <0.05) within 90 min after treatment (30 mg/kg of combretastatin A4 phosphate) and a further decrease was observed at 2 h (mean 2 mm Hg; p <0.01). The initial changes in pO(2) in the central and peripheral regions were parallel, but by 24 h after treatment, a significant difference was apparent: the pO(2) in the periphery had improved significantly, and the center remained hypoxic. These data are consistent with DCE-MRI, which revealed an approximately 70% decrease in perfusion/permeability (initial area under signal-intensity curve) at 2 h (p <0.001). The initial area under signal-intensity curve recovered fully after 24 h in a thin peripheral region, but not in the tumor center. The response observed by DCE-MRI, indicating vascular shutdown, paralleled the pO(2) measurements as expected, but quantitative pO(2) measurements are potentially important for optimizing the therapeutic combination of vascular targeting agents with radiotherapy.
    Preview · Article · Aug 2005 · International Journal of Radiation OncologyBiologyPhysics
  • [Show abstract] [Hide abstract]
    ABSTRACT: Near-infrared (NIR) spectroscopy is being applied to the solution of problems in many areas of biomedical and pharmaceutical research. The need for modern medical diagnostics to develop small portable instruments that enable fast and effective monitoring of the biological properties of the human body is apparent. We have developed a portable and robust spectrometer that consists of a two beam interferometer operating in the near-infrared wavelength range for real-time measurements. The device has limited spectral resolution and so methods of computational intelligence and advanced signal processing have been applied to the NIR data to produce more precise and informative diagnostic information. Our target application concerns blood and tissue status in a form that can be interpreted directly by the user, without special knowledge of spectral analysis. More specifically, theories and methods from the field of machine intelligence (learning algorithms, neural networks, etc.) were first applied to classify in vitro urea samples of different concentrations. The results are encouraging, with overall mean squared prediction errors of less than 10-4, and in vivo trials will follow to further develop the device. Non-intrusive diagnostics of this kind are suitable for point-of-care screening.
    No preview · Article · Sep 2005 · Proceedings of SPIE - The International Society for Optical Engineering
Show more