Search PubMed⌕ Search

Biomedical subjects

A Brahme

Publications and source records attributed to A Brahme.

At least 19 recordsLinked to original sources
PubMed2003

Repairable-conditionally repairable damage model based on dual Poisson processes.

The advent of intensity-modulated radiation therapy makes it increasingly important to model the response accurately when large volumes of normal tissues are irradiated by controlled graded dose distributions aimed at maximizing tumor cure and minimizing normal tissue toxicity. The cell survival model proposed here is very useful and flexible for accurate description of the response of healthy tissues as well as tumors in classical and truly radiobiologically optimized radiation therapy. The repairable-conditionally repairable (RCR) model distinguishes between two different types of damage, namely the potentially repairable, which may also be lethal, i.e. if unrepaired or misrepaired, and the conditionally repairable, which may be repaired or may lead to apoptosis if it has not been repaired correctly. When potentially repairable damage is being repaired, for example by nonhomologous end joining, conditionally repairable damage may require in addition a high-fidelity correction by homologous repair. The induction of both types of damage is assumed to be described by Poisson statistics. The resultant cell survival expression has the unique ability to fit most experimental data well at low doses (the initial hypersensitive range), intermediate doses (on the shoulder of the survival curve), and high doses (on the quasi-exponential region of the survival curve). The complete Poisson expression can be approximated well by a simple bi-exponential cell survival expression, S(D) = e(-aD) + bDe(-cD), where the first term describes the survival of undamaged cells and the last term represents survival after complete repair of sublethal damage. The bi-exponential expression makes it easy to derive D(0), D(q), n and alpha, beta values to facilitate comparison with classical cell survival models.

Cell Line↗
PubMed2002

Comparison of Monte Carlo calculated electron slowing-down spectra generated by 60Co gamma-rays, electrons, protons and light ions.

When analysing the factors affecting the relative biological effectiveness (RBE) of different radiation qualities, it is essential to consider particularly the low-energy slowing-down electrons (around 100 eV to 1 keV) since they have the potential of inflicting severe damage to the DNA. We present a modified and extended version of the Monte Carlo code PENELOPE that enables scoring of slowing-down spectra. mean local energy imparted spectra and average intra-track nearest-neighbour energy deposition distances of the secondary electrons generated by different radiation qualities, such as electrons, photons, protons and light ions in general. The resulting spectra show that the low-linear energy transfer (LET) beams, 60Co gamma-rays and electrons with initial energies of 0.1 MeV and higher, have as expected approximately the same electron slowing-down fluence per unit dose in the biologically important low-energy interval. Consistent with the general behaviour of the RBE of low-energy electrons, protons and light ions, the low-energy electron slowing-down fluence per unit dose is larger than for low-LET beams, and it increases with decreasing initial projectile energy.

Cobalt Radioisotopes↗
PubMed2002

RBE of 50 MV scanned bremsstrahlung beams determined using clonogenic assay.

PURPOSE: In order to compare the biological effectiveness of a 50 MV scanned bremsstrahlung beam to (60)Co and 6 MV photons, the survival of Chinese hamster cells (V79-379A), human normal fibroblasts cells (GSH(+/+)) and human small cell lung cancer cells (U-1690) were analysed. MATERIALS AND METHODS: Cells were irradiated in vitro under aerobic conditions in a plastic phantom. Dose to the cells was determined using ferrous sulphate and ionization chamber dosimetry. A number of cell survival models were fitted to the experimental data, including the standard LQ model with and without the induced repair. In particular, a new model treating damage and repair separately was used in combination with a new technique for accurate RBE determination. RESULTS: The measured RBE for the three cell lines were 0.988 (0.984-0.992), 0.999 (0.996-1.002) and 1.013 (1.009-1.016) for V79-379A, GSH(+/+) and U-1690 respectively and thus 50 MV scanned beams did not differ more than a fraction of a per cent from conventional therapy beams. CONCLUSIONS: The present study gives RBE consistent with previously calculated RBEs based on photonuclear reaction cross-sections of high-energy photons.

Animals↗
PubMed2002

Radiation response of hypoxic and generally heterogeneous tissues.

PURPOSE: Biologically based treatment optimisation can be based on the local mean values of the number of clonogenic cells and the cellular radiation response taken over macroscopic tissue voxels. Steep oxygen gradients in tumours may often lead to microscopic distributions of radiation resistance at the cellular level, far beyond the geometrical resolution of current diagnostic and radiotherapeutic methods. The present work focuses on quantifying the radiobiological effect of such microscopic distributions through tissue-oxygenation modelling and on calculating the corresponding radiation response on both micro- and macroscopic scales. MATERIALS AND METHODS: A simple model of tissue vasculature was developed with microvascular density and heterogeneity as its main parameters. New analytical expressions are presented for calculating the effective radiation response of tissues with generally heterogeneous radiation resistance and clonogen density. RESULTS: The oxygen distributions derived for different parameter sets agree very well with clinically measured oxygen distributions for both tumours and normal tissues. In addition to the vascular density, vascular heterogeneity is an important factor while estimating the hypoxic fraction in tissue. It is shown that both the local and global dose-response relation for tissues with heterogeneous radiation resistance can be accurately calculated from the effective initial clonogen number N(0,eff) and the effective radiation resistance D(0,eff). New equations are derived for calculating these quantities, for instance, from measured oxygen distributions. CONCLUSIONS: With the new methods presented here, existing techniques to measure the micro- and macroscopic oxygen distribution either using standard tumour-type or patient-specific oxygenation data can be used for biologically based treatment plan optimisation.

Cell Survival↗
PubMed2002

Relative biological effectiveness of boron ions on human melanoma cells.

PURPOSE: To compare the difference in relative biological effectiveness (RBE) between (10)B ions and a (60)Co gamma-ray beam for human melanoma cells using in vitro cell survival based on a clonogenic assay. MATERIALS AND METHODS: Cells were irradiated in vitro under aerobic conditions with (60)Co and (10)B ions with different linear energy transfer (LET) (40, 80 and 160 eV nm(-1)). The dose to the cells was determined using ferrous sulphate dosimetry and an ionisation chamber. The standard linear-quadratic model and the newly proposed repairable conditionally repairable damage (RCR) model were used to calculate the RBE. RESULTS: The RBE at 10% cell survival for 40, 80 and 160 eV nm(-1) boron ions compared with (60)Co were 1.98 (1.83-2.22), 2.85 (2.64-3.11) and 3.37 (3.17-3.58), respectively, of almost independence of the model used in the calculation. CONCLUSIONS: Different cell survival models may generate different RBE, especially at low doses and high cell survival levels.

Apoptosis↗
PubMed2001

Individualizing cancer treatment: biological optimization models in treatment planning and delivery.

PURPOSE: During the last 30 years radiation therapy has developed from classical rectangular beams via conformation therapy with largely uniform dose delivery, but irregular field shapes, to fully intensity modulated dose delivery where the total dose distribution in the tumor can be fully controlled in three dimensions. This last step has been developed during the last 15-20 years and has opened up the possibilities for truly optimized radiation therapy. METHODS AND MATERIALS: Today it is not only possible to produce almost any desired dose distribution in the tumor volume. It is also possible to deliver the dose distribution, which has the highest probability to cure the patient without inducing severe complications in normal tissues. To fully exploit the advantages of intensity-modulated radiation therapy, quality of life or radiobiologic objectives have to be used, preferably combined with predictive assay of radiation sensitivity. RESULTS: This article will briefly discuss the biologic objective functions and the associated advantages in the treatment outcome using new approaches such as consideration of stochastic variations in sensitivity and optimization of the angle of incidence and fractionation schedule with intensity-modulated beams. Finally, different possibilities for realizing general three-dimensional intensity-modulated dose delivery will be discussed. CONCLUSIONS: Once accurate genetically and/or cell survival based predictive assays become available, radiation therapy will become an exact science allowing truly individual optimization considering also the panorama of side-effects that the patient is willing to accept.

Cell Survival↗
PubMed2001

Generalization of the normalized dose-response gradient to non-uniform dose delivery.

A generalization of the standard dose-response gradient to arbitrarily heterogeneous dose distributions has been developed. The generalized dose-response gradient is the scalar product of the vector representing the dose distribution and the gradient of the dose-response relation with respect to that dose vector. It is shown that, for a tumor, the individual gamma-values for each portion of the tumor divided by the corresponding local tumor control probability should be added to get the total value for the heterogeneously irradiated tumor. This corresponds to summing up the contributions of all tumor volumes so that the total value of the gradient is related to the logarithm of the total tumor clonogen number. General expressions are also derived for the change in the dose-response relation as a function of a change in the delivered dose distribution.

Dose Fractionation, Radiation↗
PubMed2001

Biologically optimized radiation therapy.

Advanced treatment optimization is possible using quantitative radiobiological dose response models. Although all present models are necessarily linked to a certain degree of uncertainty, this will only have a small influence on the relative shape of the resultant optimal dose distribution. However the exact dose level should perferably be determined clinically by dose escalation with the optimized dose plan as a control arm. It is shown that a large part of the biological effect of high linear energy transfer radiation is due to the spectrum of low-energy delta-electrons that can generate dense clusters of complex DNA damage. Such electrons are efficiently generated by low-energy photons or densely ionizing ion beams and to a considerably smaller degree by high-energy electrons, photons and protons. A new analytical expression is developed for the effective radiation resistance of heterogeneous tumors, making it possible to approximate the response of such tumors by the effective clonogen number N0,eff and the effective D0 value D0,eff. It is shown that a relatively small number of resistant tumor cells may well be sufficient to dominate the response of hypoxic or otherwise heterogeneous tumors. Finally, several examples are given of intensity-modulated dose distributions generated by multiple radiation modalities, the total effect of which is biologically optimized.

Cell Survival↗
PubMed2001

Cellular effects of high-intensity focused continuous wave ultrasound alone and in combination with X-rays.

PURPOSE: To investigate the cellular effects of 1.1 MHz high-intensity focused continuous wave (CW) ultrasound alone and in combination with X-rays. MATERIALS AND METHODS: V79 cells were exposed to ultrasound of different intensities for 30s (non-hyperthermic conditions). In the combined treatments, cells were exposed to ultrasound (63 W/cm2) either before or after 2 Gy X-irradiation. Cellular effects studied were clonogenic survival, DNA strand breaks (pulsed-field gel electrophoresis, DNA precipitation assay) and membrane integrity (morphological analysis). RESULTS: With increasing ultrasound intensity, cell survival decreased in a dose-dependent manner as the induction of DNA strand breaks, the fraction of cells with lost membrane integrity and cell lysis increased. In the treatments with combined exposures, the regimen with X-rays before ultrasound had a nearly additive effect on cell kill, whereas the reverse regimen with ultrasound exposure before X-irradiation resulted in a synergistic effect (p<0.012). CONCLUSIONS: High-intensity focused CW ultrasound induces an intensity-dependent reduction in clonogenic survival in V79 cells, which seems to depend on both DNA and membrane damage. Combined exposures of ultrasound and X-rays resulted in a synergistic reduction in cell survival when cells were exposed to ultrasound before X-rays but not for the reverse regimen. Thus, a larger fraction of the repairable sublethal cell damage induced by an initial ultrasound exposure was rendered non-repairable by a subsequent X-ray exposure than if the reverse treatment order was used.

Animals↗
PubMed2001

Biologically effective uniform dose (D) for specification, report and comparison of dose response relations and treatment plans.

Developments in radiation therapy planning have improved the information about the three-dimensional dose distribution in the patient. Isodose graphs, dose volume histograms and most recently radiobiological models can be used to evaluate the dose distribution delivered to the irradiated organs and volumes of interest. The concept of a biologically effective uniform dose (D) assumes that any two dose distributions are equivalent if they cause the same probability for tumour control or normal tissue complication. In the present paper the D concept both for tumours and normal tissues is presented, making use of the fact that probabilities averaged over both dose distribution and organ radiosensitivity are more relevant to the clinical outcome than the expected number of surviving clonogens or functional subunits. D can be calculated in complex target volumes or organs at risk either from the 3D dose matrix or from the corresponding dose volume histograms of the dose plan. The value of the D concept is demonstrated by applying it to two treatment plans of a cervix cancer. Comparison is made of the D concept with the effective dose (Deff ) and equivalent uniform dose (EUD) that have been suggested in the past. The value of the concept for complex targets and fractionation schedules is also pointed out.

Dose Fractionation, Radiation↗
PubMed2001

Photon scatter kernels for intensity modulating radiation therapy filters.

The most important beam property while optimizing photon therapy is the ability to modulate the intensity of the beam. The use of photon absorbers for intensity modulation of beam profiles requires special attention to be paid to the alteration of beam properties due to scatter and spectral changes, in addition to the desired intensity modulation. In this study the influence of photon scatter in high-density filters irradiated with very narrow photon pencil beams was investigated. A simple analytical relation is developed to quantify the contribution by scattered photons. A scatter kernel was derived by convolving the first Compton scatter distribution with an approximate expression for the second-order scattered photons. The calculations were validated experimentally with film dosimetry and also by using Monte Carlo simulations. Results show that the difference in photon scatter estimation by different methods is relatively small when higher order scattering is accounted for. At 6 MV x-rays the agreement is slightly better than that for 18 MV x-rays results. The simple relation presented in this paper can be used to account for the scattered photon contribution in filter optimization codes to deliver biologically or physically optimized intensity modulated treatments.

Models, Statistical↗
PubMed2000

Development of radiation therapy optimization.

The principal radiobiological problems in the treatment of advanced tumors and the solution of many of them by radiobiologically optimized intensity-modulated radiation therapy are presented. Considerable improvements of the treatment outcome using radiobiologically optimized intensity-modulated treatments are achieved by: (a) increasing the tumor dose and dose per fraction; (b) keeping constant or even reducing slightly the dose and dose per fraction to organs at risk, (c) reducing the overall treatment time and the number of treatment fractions. The merits of the new radiation modalities and advanced intensity-modulated treatment techniques are compared in terms of equipment costs per patient cured. It is predicted that the new development of radiobiologically optimized intensity-modulated radiation therapy will rapidly become an important clinical tool, increasing the efficiency of the collaboration between radiation physicists, radiation biologists and radiation oncologists. Not only does it allow the optimal treatment of every patient, but it also promotes an efficient feedback of treatment outcome and complication data to improve the accuracy of known dose response relations to further augment future treatment results. Equipment costs may go up during a transition period until efficient interfaces between new diagnostic equipment, treatment-planning systems and intensity-modulated treatment units are fully developed. From then onwards the cost of high quality biologically optimized intensity-modulated treatments will decrease and so will the treatment time and personnel requirements, at the same time as the treatment quality is greatly improved particularly for more advanced tumors.

Dose Fractionation, Radiation↗
PubMed2000

Photon scatter in intensity modulating filters evaluated by first Compton scatter and Monte Carlo calculations and experiments in broad beams.

High-atomic-number materials may be used as intensity modulating filters for inverse radiation treatment planning with photon beams. Such filters, when placed in a bremsstrahlung beam, attenuate the primary fluence, but also produce scattered photons that will reach the patient. To account for such effects in the optimization of photon beam intensities a semiempirical method based on narrow and broad beam transmission measurements was used to quantify the number of scattered photons produced in these filters. The method was verified by performing analytical calculations based on first scatter and a Monte Carlo simulation in 6 and 18 MV photon beams. The resultant experimental transmission ratios agree with calculations by these methods within 2 per cent under the experimental conditions investigated. The semiempirical method can thus be used as a basis for preliminary decision-making to select the proper material for intensity modulating filters and can provide a fast method to perform independent quality checks of the calculation accuracy of dose planning systems. Change in beam penetration is of less concern when treatments of target volumes at smaller depths are of interest. A 10 g cm(-2) thick filter made of low-melting-point alloy produces a change in percentage depth dose of less than 2 per cent for depths larger than 10 cm independent of field size. Similarly the scatter correction modifies the dose distribution by less than 5-10 per cent in most cases.

Models, Statistical↗
PubMed2000

Comparative dosimetry in narrow high-energy photon beams.

A comparison of the response of different dosimeters in narrow photon beams (phi > or = 4 mm) of 6 and 18 MV bremsstrahlung has been performed. The detectors used were a natural diamond detector, a liquid ionization chamber, a plastic scintillator and two dedicated silicon diodes. The diodes had a very small detection volume and one was a specially designed double diode using two parallel opposed active volumes with compensating interface perturbations. The characteristics of the detectors were investigated both for dose distribution measurements, such as depth-dose curves and lateral beam profiles, and for output factors. The dose rate and angular dependence of the diamond and the two diodes were also studied separately. The depth-dose distributions for small fields agree well for the diamond, the scintillator and the single diode, while the measured dose maximum for the double diode is about 1% higher and for the liquid chamber about 1% lower than the mean of the others when normalized at a depth of 10 cm. The plastic scintillator and the liquid ionization chamber detect a penumbra width that is slightly broadened due to the influence of their finite size, while the double diode may even underestimate the penumbra width due to its small size and high density. When corrected for the extension of the detector volume a good agreement with Monte Carlo calculated beam profiles was obtained for the plastic scintillator and the liquid ionization chamber. Profiles measured with the diamond show an asymmetry when positioned with the smallest dimension facing the beam, while the double diode, the scintillator and the liquid chamber measure symmetric profiles irrespective of positioning. Significant differences in the output factors were obtained with the different detectors. The natural diamond detector measures output factors close to those with an ionization chamber (less than 1% difference) for field sizes between 3 x 3 and 15 x 15 cm2, but overestimates the output factors for large fields and underestimates the output factors for the smallest field sizes. The single and double diodes overestimated the output factor for large field sizes by up to 7 and 12% respectively due to the high content of low-energy photons. The double diode, and to some extent the single diode, also showed a relative increase in response compared with the more water equivalent liquid chamber and plastic scintillator at the smallest fields where there is a lack of lateral electron equilibrium. Both the plastic scintillator and the liquid chamber also show responses that deviate from the ionization chamber for larger field sizes. The major deviations can be explained based on the characteristics of the sensitive materials and the construction of the detectors.

Dose-Response Relationship, Radiation↗
PubMed2000

Comparison of conformal radiation therapy techniques within the dynamic radiotherapy project 'Dynarad'.

The objective of the dynamic radiotherapy project 'Dynarad' within the European Community has been to compare and grade treatment techniques that are currently applied or being developed at the participating institutions. Cervical cancer was selected as the tumour site on the grounds that the involved organs at risk, mainly the rectum and the bladder, are very close to the tumour and partly located inside the internal target volume. In this work, a solid phantom simulating the pelvic anatomy was used by institutions in Belgium, France, Greece, Holland, Italy, Sweden and the United Kingdom. The results were evaluated using both biological and physical criteria. The main purpose of this parallel evaluation is to test the value of biological and physical evaluations in comparing treatment techniques. It is demonstrated that the biological objective functions allow a much higher conformality and a more clinically relevant scoring of the outcome. Often external beam treatment techniques have to be combined with intracavitary therapy to give clinically acceptable results. However, recent developments can reduce or even eliminate this need by delivering more conformal dose distributions using intensity modulated external dose delivery. In these cases the reliability of the patient set-up procedure becomes critical for the effectiveness of the treatment.

European Union↗
PubMed1999

Optimized radiation therapy based on radiobiological objectives.

In the broad field of radiation therapy optimization, both simple and complex problems have their origins in the interaction of the radiation beams with the biological structures of normal and malignant tissues of the human body. Therefore, it is no great surprise that many treatment optimization problems are best handled by the use of well-designed radiobiological models. The classic way of quantifying dose-response relations for tumors and normal tissues as well as their cross-correlation with each other and their dependence on the underlying genetic and molecular biology of the cell are first briefly reviewed. Radiobiological objective functions, such as the probability of achieving complication-free cure and its expectation value under influence of stochastic processes during the course of treatment, are defined and shown to solve many of the problems of radiation therapy planning. Finally, it is shown through the use of these quantifiers that, simply by introducing biologically optimal intensity modulated dose delivery, the treatment outcome can be improved by about 20% or more in cases with a complex spread of the disease. Once radiobiological optimal plans have been developed, they can be approximated by ordinary physical planning, but the biological objective functions are still needed to have a figure of merit for the quality of the treatment.

Dose-Response Relationship, Radiation↗
PubMed1999

Aspects on the optimal photon beam energy for radiation therapy.

The selection of optimal photon beam energy is investigated both for realistic clinical bremsstrahlung beams and for monoenergetic photon beams. The photon energies covered in this investigation range from 60Co to bremsstrahlung and monoenergetic beams with maximum energies up to 50 MeV. One head and neck tumor and an advanced cervix tumor are investigated and the influence of beam direction is considered. It is shown that the use of optimized intensity modulated photon beams significantly reduces the need of beam energy selection. The most suitable single accelerator potential will generally be in the range 6-15 MV for both superficially located and deep-seated targets, provided intensity-modulated dose delivery is employed. It is also shown that a narrow penumbra region of a photon beam ideally should contain low-energy photons (< or =4 MV), whereas the gross tumor volume, particularly when deep-seated targets are concerned, should be irradiated by high-energy photons. The regions where low photon energies are most beneficial are where organs at risk are laterally close to the target volume. The situation is completely changed when uniform or wedged beams are used. The selection of optimal beam energy then becomes a very important task in line with the experience from traditional treatment techniques. However, even with a large number of uniform beam portals, the treatment outcome is substantially lower than with a few optimized intensity-modulated beams.

Female↗