| 1. |
- Daşu, Alexandru, et al.
(författare)
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Should single or distributed parameters be used to explain the steepness of tumour control probability curves?
- 2003
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 48:3, s. 387-397
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Tidskriftsartikel (refereegranskat)abstract
- Linear quadratic (LQ) modelling allows easy comparison of different fractionation schedules in radiotherapy. However, estimating the radiation effect of a single fractionated treatment introduces many questions with respect to the parameters to be used in the modelling process. Several studies have used tumour control probability (TCP) curves in order to derive the values for the LQ parameters that may be used further for the analysis and ranking of treatment plans. Unfortunately, little attention has been paid to the biological relevance of these derived parameters, either for the initial number of cells or their intrinsic radiosensitivity, or both. This paper investigates the relationship between single values for the TCP parameters and the resulting dose-response curve. The results of this modelling study show how clinical observations for the position and steepness of the TCP curve can be explained only by the choice of extreme values for the parameters, if they are single values. These extreme values are in contradiction with experimental observations. This contradiction suggests that single values for the parameters are not likely to explain reasonably the clinical observations and that some distributions of input parameters should be taken into consideration.
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| 2. |
- Daşu, Alexandru, et al.
(författare)
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Theoretical simulation of tumour oxygenation and results from acute and chronic hypoxia
- 2003
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 48:17, s. 2829-2842
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Tidskriftsartikel (refereegranskat)abstract
- The tumour microenvironment is considered to be responsible for the outcome of cancer treatment and therefore it is extremely important to characterize and quantify it. Unfortunately, most of the experimental techniques available now are invasive and generally it is not known how this influences the results. Non-invasive methods on the other hand have a geometrical resolution that is not always suited for the modelling of the tumour response. Theoretical simulation of the microenvironment may be an alternative method that can provide quantitative data for accurately describing tumour tissues. This paper presents a computerized model that allows the simulation of the tumour oxygenation. The model simulates numerically the fundamental physical processes of oxygen diffusion and consumption in a two-dimensional geometry in order to study the influence of the different parameters describing the tissue geometry. The paper also presents a novel method to simulate the effects of diffusion-limited (chronic) hypoxia and perfusion-limited (acute) hypoxia. The results show that all the parameters describing tissue vasculature are important for describing tissue oxygenation. Assuming that vascular structure is described by a distribution of inter-vessel distances, both the average and the width of the distribution are needed in order to fully characterize the tissue oxygenation. Incomplete data, such as distributions measured in a non-representative region of the tissue, may not give relevant tissue oxygenation. Theoretical modelling of tumour oxygenation also allows the separation between acutely and chronically hypoxic cells, a distinction that cannot always be seen with other methods. It was observed that the fraction of acutely hypoxic cells depends not only on the fraction of collapsed blood vessels at any particular moment, but also on the distribution of vessels in space as well. All these suggest that theoretical modelling of tissue oxygenation starting from the basic principles is a robust method that can be used to quantify the tissue oxygenation and to provide input parameters for other simulations.
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| 3. |
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| 4. |
- Toma-Dasu, Iuliana, et al.
(författare)
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The relationship between temporal variation of hypoxia, polarographic measurements and predictions of tumour response to radiation
- 2004
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 49:19, s. 4463-4475
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Tidskriftsartikel (refereegranskat)abstract
- The polarographic oxygen sensor is one of the most used devices for in vivo measurements of oxygen and many other measurement techniques for measuring tumour hypoxia are correlated with electrode measurements. Little is known however about the relationship between electrode measurements and the real tissue oxygenation. This paper investigates the influence of the temporal change of the hypoxic pattern on the electrode measurements and the tumour response. Electrode measurements and tumour response were simulated using a computer program that allows both the calculation of the tissue oxygenation with respect to the two types of hypoxia that might arise in tumours and the virtual insertion of the electrode into the tissue. It was therefore possible to control the amount of each type of hypoxia in order to investigate their influence on the measurement results. Tissues with several vascular architectures ranging from well oxygenated to poorly oxygenated were taken into consideration as might be seen in practice. The influence of the electrode measurements on the treatment outcome was estimated by calculating the tumour control probability for the tumours characterized either by the real or by the measured tumour oxygenation. We have simulated electrode oxygen measurements in different types of tissues, covering a wide range of tumour oxygenations. The results of the simulations showed that the measured distribution depends on the details of the vascular network and not on the type of hypoxia. We have also simulated the effects of the temporal change of the acute hypoxic pattern due to the opening and the closure of different blood vessels during a full fractionated treatment. The results of this simulation suggested that the temporal variation of the hypoxic pattern does not lead to significantly different results for the electrode measurements or the predicted tumour control probabilities. In conclusion, it was found that the averaging effect of the electrode leads to a systematic deviation between the actual oxygen distribution and the measured distribution. However, as the electrode reflects the general trends of the tissue oxygenation it has the potential of being used for the general characterization of tumour hypoxia even if the actual type of hypoxia measured by the electrode cannot be determined. Indeed, the change in time of the acute hypoxic region does not compensate for the lack of oxygenation at a specific moment and therefore does not influence the polarographic oxygen measurements.
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| 5. |
- Toma-Dasu, Iuliana, et al.
(författare)
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Theoretical simulation of oxygen tension measurement in the tissue using a microelectrode: II. Simulated measurements in tissues
- 2002
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Ingår i: Radiotherapy and Oncology. - 0167-8140 .- 1879-0887. ; 64:1, s. 109-118
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
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| 7. |
- Toma-Dasu, Iuliana, et al.
(författare)
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Theoretical simulation of oxygen tension measurement in tissues using a microelectrode: I. The response function of the electrode
- 2001
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Ingår i: Physiological Measurement. - : IOP Publishing. - 0967-3334 .- 1361-6579. ; 22:4, s. 713-725
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this article is to determine the correlation between the actual oxygen distribution in tissues and the distribution of oxygen measured by microelectrodes. This correlation is determined by the response function of the electrode, which depends on the oxygen consumed by the electrode. In tissue it is necessary to consider the gradients resulting from cellular respiration. A computer program has been used to simulate the vascular structure of various tissues and also the measurements of oxygen tension using a polarographic electrode. The electrode absorption process is described using a theoretical model. The gradient of oxygen in tissue is described by a mathematical model that takes into consideration both diffusion and cellular consumption of oxygen. We have compared the results obtained using the response function of the electrode and some simplifications of it. The results of these comparisons show that there are some differences in the 'observed' distributions of the oxygen tension in tissues predicted using different formulae for the electrode response function. Also, there are considerable differences between the input oxygen distribution and the measured values in all cases. All the results of the simulations of the oxygen tension 'observed' by a 12 microm polarographic electrode, using different response functions of the electrode, show that the electrode averages the values from many cells. Care should be taken in using a simplification for the response function of the electrode, especially if the results are going to be used as input values in modelling the tumour response to new treatments and/or as a basis of selecting patients for treatments. A computer simulation of measurement of oxygen tensions in regions of steep pO2 gradients shows that extremely high and extremely low pO2 values will not be detected.
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