Theoretical simulation of oxygen tension measurement in the tissue using a microelectrode: II. Simulated measurements in tissues.

BACKGROUND AND PURPOSE The objectives of this study were to make a computer simulation of tissues with different vascular structures and to simulate measurements of oxygen tension using an Eppendorf-like electrode in these tissues and to compare the response to radiation of the tissues with the real oxygen distributions (called input distribution) with the response to radiation of the tissues in which the oxygen distribution is given by the results of the simulated measurements (called output distribution). MATERIALS AND METHODS The structure of various tissues and the measurements of oxygen tension using a microelectrode were simulated using a computer program. The mathematical model used combines the description of a gradient of tissue oxygenation and the electrode absorption process. RESULTS We have compared the oxygen distributions resulting from diffusion (input) with those obtained from a simulation of measurements (output) for various tissues in the same points. Because the electrode measurement is an averaging process, the calculated oxygen distributions are different from the expected ones and the extreme high and low values are not detected. We have then calculated the survival curves describing the response to radiation if there is a small fraction of truly hypoxic cells (expected values) or a large fraction of cells at intermediate values (observed results) in order to determine the differences between them. CONCLUSIONS The results of our study show that oxygen electrode measurements do not give the true distribution of pO(2) values in the tissue. However, our results do not contradict the numerous empirical correlations between the Eppendorf measurements of tumour oxygenation and the outcome of treatments. Measurement results will be misleading for modelling purposes since they do not reflect the actual distributions of oxygen tensions in the measured tissue. Decisions based on such modelling could be very dangerous, especially with respect to the clinical response of tumours to new treatments.

[1]  M A Konerding,et al.  Evidence for characteristic vascular patterns in solid tumours: quantitative studies using corrosion casts , 1999, British Journal of Cancer.

[2]  S M Evans,et al.  Hypoxia and necrosis in rat 9L glioma and Morris 7777 hepatoma tumors: comparative measurements using EF5 binding and the Eppendorf needle electrode. , 2000, International journal of radiation oncology, biology, physics.

[3]  B. Vojnovic,et al.  Measurement of tumor oxygenation: a comparison between polarographic needle electrodes and a time-resolved luminescence-based optical sensor. , 1997, Radiation research.

[4]  J Denekamp,et al.  Theoretical simulation of oxygen tension measurement in tissues using a microelectrode: I. The response function of the electrode. , 2001, Physiological measurement.

[5]  S M Evans,et al.  Interlaboratory variation in oxygen tension measurement by Eppendorf “Histograph” and comparison with hypoxic marker , 1997, Journal of surgical oncology.

[6]  D. Hedley,et al.  A comparison in individual murine tumors of techniques for measuring oxygen levels. , 1999, International journal of radiation oncology, biology, physics.

[7]  I. Tannock,et al.  Oxygen diffusion and the distribution of cellular radiosensitivity in tumours. , 1972, The British journal of radiology.

[8]  TIKVAH ALPER,et al.  Role of Oxygen in Modifying the Radiosensitivity of E. Coli B. , 1956, Nature.

[9]  O. S. Nielsen,et al.  Tumour oxygenation assessed by polarographic needle electrodes and bioenergetic status measured by 31P magnetic resonance spectroscopy in human soft tissue tumours. , 1997, Acta oncologica.