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Theoretical simulation of oxygen tension measurement in the tissue using a microelectrode: II. Simulated measurements in tissues
Umeå University, Faculty of Medicine, Department of Radiation Sciences.
Umeå University, Faculty of Medicine, Department of Radiation Sciences.
Umeå University, Faculty of Medicine, Department of Radiation Sciences.
Umeå University, Faculty of Medicine, Department of Radiation Sciences.
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2002 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 64, no 1, 109-118 p.Article in journal (Refereed) Published
Abstract [en]

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 pO2 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.

Place, publisher, year, edition, pages
2002. Vol. 64, no 1, 109-118 p.
Keyword [en]
Electrode, Oxygen, Tumour, Hypoxia, Eppendorf, Histogram
URN: urn:nbn:se:umu:diva-3940DOI: 10.1016/S0167-8140(02)00148-2PubMedID: 12208581OAI: diva2:142855
Available from: 2004-05-06 Created: 2004-05-06 Last updated: 2010-08-24Bibliographically approved
In thesis
1. Theoretical modelling of tumour oxygenation and influences on treatment outcome
Open this publication in new window or tab >>Theoretical modelling of tumour oxygenation and influences on treatment outcome
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

One of the main problems in curing cancer resides in the different microenvironment existing in tumours compared to the normal tissues. The mechanisms of failure are different for radiotherapy and chemotherapy, but they all relate to the poor blood supply known to exist in tumours. It is therefore very important to know the tumour microenvironmental conditions in order to devise techniques that will overcome the problems and will therefore improve the result of the treatment.

The aims of the thesis were the modelling of tumour oxygenation and the simulation of polarographic oxygen measurements in order to assess and possibly to improve the accuracy of the electrode in measuring tumour oxygenation. It also aimed to evaluate the implications of tumour microenvironment for the radiotherapy outcome.

The project used theoretical modelling as the main tool. The processes of oxygen diffusion and consumption were described mathematically for different conditions, the result being very accurate distributions of oxygen in tissues. A first simple model of tissue oxygenation was based on the oxygen diffusion around a single blood vessel. A more complex model built from the basic physical processes and measurable parameters allowed the simulation of realistical tissues with heterogeneous vasculature. This model also allowed the modelling of the two types of hypoxia known to appear in tumours and their influence on the tumour microenvironment. The computer simulation of tissues was also used for assessing the accuracy of the polarographic technique for measuring tumour oxygenation.

The results of this study have shown that it is possible to model theoretically the tissue oxygenation starting from the basic physical processes. The particular application of our theoretical simulation to the polarographic oxygen electrode has shown that this experimental method does not give the oxygen values in individual cells. Because the electrode measures the average oxygenation in a relatively large tissue volume, the resulting oxygen distributions are different from the real ones and the extreme high and low values are not detected. It has further been found that the polarographic electrode cannot make distinction between various types of hypoxia existing in tumours, the geometrical distribution of the hypoxic cells influencing mostly the accuracy of the measurement.

It was also shown that because of the averaging implied by the measurement process, electrode results should not be used directly to predict the response to radiation. Thus, the differences between the predictions in clinical tumour control obtained from the real or the measured oxygenations are of the order of tens of percents in absolute value. A method to improve the accuracy of the electrode, i.e. to improve the correlation between the results of the measurements and the actual tissue oxygenation, was proposed.

In conclusion, theoretical modelling has been shown to be a very powerful tool for predicting the outcome of radiotherapy and it has the advantage of describing the tumour oxygenation in the least invasive manner. Furthermore it allows the investigation of the invasiveness and the accuracy of various experimental methods.

56 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 897
Radiation sciences, Computer simulation, Electrode, Polarographic measurements, Tumour oxygenation, Hypoxia, Strålningsvetenskap
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
urn:nbn:se:umu:diva-262 (URN)91-7305-667-7 (ISBN)
Public defence
2004-05-28, sal 244, by 7, Norrlands universitetssjukhus, Umeå, 09:00
Available from: 2004-05-06 Created: 2004-05-06Bibliographically approved

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