Search PubMed⌕ Search

Biomedical subjects

A Brahme

Publications and source records attributed to A Brahme.

At least 55 records · Page 3Linked to original sources

Optimization of 3D conformal electron beam therapy in inhomogeneous media by concomitant fluence and energy modulation.

The possibilities of using simultaneous fluence and energy modulation techniques in electron beam therapy to shape the dose distribution and almost eliminate the influences of tissue inhomogeneities have been investigated. By using a radiobiologically based optimization algorithm the radiobiological properties of the tissues can be taken into account when trying to find the best possible dose delivery. First water phantoms with differently shaped surfaces were used to study the effect of surface irregularities. We also studied water phantoms with internal inhomogeneities consisting of air or cortical bone. It was possible to improve substantially the dose distribution by fluence modulation in these cases. In addition to the fluence modulation the most suitable single electron energy in each case was also determined. Finally, the simultaneous use of several preselected electron beam energies was also tested, each with an individually optimized fluence profile. One to six electron energies were used, resulting in a slow improvement in complication-free cure with increasing number of beam energies. To apply these techniques to a more clinically relevant situation a post-operative breast cancer patient was studied. For simplicity this patient was treated with only one anterior beam portal to clearly illustrate the effect of inhomogeneities like bone and lung on the dose distribution. It is shown that by using fluence modulation the influence of dose inhomogeneities can be significantly reduced. When two or more electron beam energies with individually optimized fluence profiles are used the dose conformality to the internal target volume is further increased, particularly for targets with complex shapes.

Algorithms↗

Monte Carlo and analytical calculation of proton pencil beams for computerized treatment plan optimization.

Proton pencil beams in water, in a format suitable for treatment planning algorithms and covering the radiotherapy energy range (50-250 MeV), have been calculated using a modified version of the Monte Carlo code PTRAN. A simple analytical model has also been developed for calculating proton broad-beam dose distributions which is in excellent agreement with the Monte Carlo calculations. Radial dose distributions are also calculated analytically and narrow proton pencil-beam dose distributions derived. The physical approximations in the Monte Carlo code and in the analytical model together with their limitations are discussed. Examples showing the use of the calculated set of proton pencil beams as input to an existing photon treatment planning algorithm based on biological optimization are given for fully 3D scanned proton pencil beams; these include intensity modulated beams with range shift and scanning in the transversal plane.

Algorithms↗

An estimation of the relative biological effectiveness of 50 MV bremsstrahlung beams by microdosimetric techniques.

An efficient algorithm has been developed to estimate the relative biological effectiveness (RBE) from experimental RBE data and measured single-event energy deposition spectra. As benchmarks for the calculations well established RBE data for crypt cell survival and associated microdosimetric distributions from a number of therapeutic high- and low-LET beams was used. As a by-product of the calculations the RBE for this system was determined for the lineal energy range 0.1-5000 keV microns-1 in very good agreement with experimental data. These data have been applied to estimate the biological effectiveness of therapeutic high-energy bremsstrahlung beams characterized by microdosimetric measurements with a wall-less proportional counter. The absorbed dose component due to photoneutrons and charged particles from photonuclear reactions in scanned 50 MV bremsstrahlung beams was measured to be about 2% of the total absorbed dose. The RBE of 50 MV scanned bremsstrahlung beams was estimated to be 1.09 for jejunum crypt cell survival as the biological endpoint at absorbed doses of the order of 10 Gy, in fair agreement with reported results based on radiobiological experiments. The RBE is fairly independent of the bremsstrahlung target used. Using the estimated increase in the RBE of neutrons compared to photons for absorbed dose levels applied in clinical fractionation schedules increases the RBE further to 1.13 at absorbed doses per fraction of the order of 2 Gy.

Algorithms↗

The role of phantom and treatment head generated bremsstrahlung in high-energy electron beam dosimetry.

An analytical expression has been derived for the phantom generated bremsstrahlung photons in plane-parallel monoenergetic electron beams normally incident on material of any atomic number (Be, H2O, Al, Cu and U). The expression is suitable for the energy range from 1 to 50 MeV and it is solely based on known scattering power and radiative and collision stopping power data for the material at the incident electron energy. The depth dose distribution due to the bremsstrahlung generated by the electrons in the phantom is derived by convolving the bremsstrahlung energy fluence produced in the phantom with a simple analytical energy deposition kernel. The kernel accounts for both electrons and photons set in motion by the bremsstrahlung photons. The energy loss by the primary electrons, the build-up of the electron fluence and the generation, attenuation and absorption of bremsstrahlung photons are all taken into account in the analytical formula. The longitudinal energy deposition kernel is derived analytically and it is consistent with both the classical biexponential relation describing the photon depth dose distribution and the exponential attenuation of the primary photons. For comparison Monte Carlo calculated energy deposition distributions using ITS3 code were used. Good agreement was found between the results with the analytical expression and the Monte Carlo calculation. For tissue equivalent materials, the maximum total energy deposition differs by less than 0.2% from Monte Carlo calculated dose distributions. The result can be used to estimate the depth dependence of phantom generated bremsstrahlung in different materials in therapeutic electron beams and the bremsstrahlung production in different electron absorbers such as scattering foils, transmission monitors and photon and electron collimators. By subtracting the phantom generated bremsstrahlung from the total bremsstrahlung background the photon contamination generated in the treatment head can be determined to allow accurate dosimetry of heavily photon contaminated electron beams.

Electrons↗

Effective source size, yield and beam profile from multi-layered bremsstrahlung targets.

Modern conformal radiotherapy benefits from heterogeneous dose delivery using scanned narrow bremsstrahlung beams of high energy in combination with dynamic double focused multi-leaf collimation and purging magnets. When using a purging magnet to remove electrons and positrons the target space is limited and unorthodox thin multi-layered targets are needed. A computational technique has therefore been developed to determine the forward yield and the angular distributions of the bremsstrahlung beam as well as the size and location of the effective and the virtual photon point source for arbitrary multi-layer bremsstrahlung targets. The Gaussian approximation of the diffusion equation for the electrons has been used and convolved with the bremsstrahlung production process. For electrons with arbitrary emittance impinging on targets of any multi-layer and atomic number combination, the model is well applicable, at least for energies in the range 1-100 MeV. The intrinsic bremsstrahlung photon profile has been determined accurately by deconvolving the electron multiple scattering process from thin experimental beryllium target profiles. For electron pencil beams incident on a target of high density and atomic number such as tungsten, the size of the effective photon source stays at around a tenth of a millimetre. The effective photon source for low-Z materials such as Be, C and Al is located at depths from 3-7 mm in the target, decreasing with increasing atomic number. The effective photon source at off-axis positions then moves out considerably from the central axis, which should be considered when aligning collimators. For high-Z materials such as tungsten, the location of the effective photon source is at a few tenths of a millimetre deep. The virtual photon point source is located only a few tenths of a millimetre upstream of the effective photon source both for high- and low-Z materials. For 50 MeV electrons incident on multi-layered full range targets the radial energy fluence distributions will have a full width at half maximum (FWHM) of 80 to 100 mm at 1 m from the target. The best target composition made of two layers when the space is limited to 15 mm was found to be 9 mm-Be followed by 6 mm W. A thin beryllium target (approximately 3 mm) results in a high-intensity bremsstrahlung lobe with a FWHM of about 35 mm at the isocentre. Interestingly, the forward dose rate in such a beam is as high as 62% of the maximum achievable with an optimal target design, even if on average only 1 MeV is lost by the electrons.

Biophysical Phenomena↗

Optimization of conformal electron beam therapy using energy- and fluence-modulated beams.

Fluence modulation of multiple electron beams of various energies has been used to optimize the delivered dose distribution during electron beam radiation therapy. By maximizing the probability of achieving tumor control without causing severe complications electron beam fluence profiles have been optimized for superficial target volumes. It is possible to use several equiportal fluence-modulated electron beams to modify the energy deposition with depth in a controlled manner making it possible to use the technique as an alternative to bolus. The technique was tested in two representative phantom geometries and in three clinical patient geometries using a set of five and two different energies. The local maxima in dose for the plans with five energies were typically lower than with the conventional or advanced bolus techniques. The principles for how the technique could be carried out in the future with a fourth generation radiotherapy accelerator are also indicated.

Electrons↗

Recent developments in radiation therapy planning and treatment optimization.

Radiation therapy of cancer is today going through a very dynamic development with the introduction of a large number of new treatment principles, new types of treatment units and new radiobiologically based optimization algorithms for treatment planning. All of these make use of the recent developments in three dimensional tumor diagnostics, molecular biology of cancer, the fractionation sensitivity of different tissues and most recently predictive assays of radiation sensitivity. The most efficient but also least developed area of treatment optimization is to use a few (approximately 3) non uniform radiation beams directed towards the tumor. Today patient individual collimation with beam blocks or multileaf collimators protect organs at risk laterally outside the tumor volume. Non uniform dose delivery also allows protection of normal tissues anterior, posterior and even inside the target volume by shaping the isodoses tightly around the tumor tissues and thereby also allowing longitudinal protection of normal tissues. Some of the most advanced new algorithms are even treating therapy optimization as an inverse problem where the optimal incident beam shapes are determined directly from the location of gross disease, presumed microscopic tumor spread and organs at risk. The optimization is then performed such that the probability, P+, to eradicate all clonogenic tumor cells without severely damaging healthy normal tissues is as high as possible. Already with a few non uniform beams the treatment outcome is within a few percent of what can be achieved with infinitely many co-planar beams in a dynamic mood. With such optimized non uniform treatments it should be possible to improve the treatment outcome by as much as 20% and more, particularly in patients with a local complex spread of the disease or several organs at risk.

Algorithms↗

Which is the most suitable number of photon beam portals in coplanar radiation therapy?

PURPOSE: Computer-controlled milling machines for compensator manufacture, dynamic multileaf collimators, and narrow scanned electron or bremsstrahlung photon beams have opened up new possibilities to shape nonuniform fluence profiles and have thus, paved the road for truly three dimensional (3D) dose delivery. The present paper investigates the number of beam portals required to optimize coplanar radiation therapy using uniform and nonuniform dose delivery. METHODS AND MATERIALS: A recently developed algorithm has been used for optimization of the dose delivery in such a way that the probability of achieving tumor control without causing severe reactions in healthy normal tissues becomes as high as possible. This method has been used to optimize the delivered dose distribution for an increasing number of beam portals to determine how many coplanar beam portals are desirable to safely achieve a good treatment outcome. Target volumes in the head and neck, thorax, and abdomen have been investigated. RESULTS: Nonuniform dose delivery allows a considerable improvement in the treatment outcome compared to uniform dose delivery. This is evident both from the probability of achieving complication-free tumor control and the value of relevant properties of the dose distribution, such as the mean value and the standard deviation of the mean dose to target volume and organs at risk. The results also show a close relationship between the dose distribution parameters and the probability of achieving complication-free tumor control. The level of complication-free tumor control first increases rapidly when the number of beam portals is increased, but already reaches a level of saturation after three to five beam portals. When the saturation level has been reached, the standard deviation of the mean dose to the target volume is around 3%. CONCLUSIONS: To achieve optimal expectation value of the treatment outcome, within an accuracy of a few percent as measured by the probability of achieving complication-free tumor control, it is generally sufficient to use three nonuniform beam portals. A very large number of coplanar beams may only raise the probability of achieving complication-free tumor control by 1 to 2%. However, good treatment outcome with three beam portals requires that the directions of incidence of the coplanar nonuniform beams are optimally selected. If, on the other hand, the treatment is performed using uniform beams, it is not possible, even with an infinite number of fields, to obtain as high a level of complication-free tumor control as with a few nonuniform beams. From an optimization point of view, it is sufficient to reach a relative standard deviation of the mean dose to the target volume of around 3%. Improved dose homogeneity beyond this level will, in general, not significantly improve the complication-free tumor control.

Algorithms↗

An improved energy-range relationship for high-energy electron beams based on multiple accurate experimental and Monte Carlo data sets.

A theoretically based analytical energy-range relationship has been developed and calibrated against well established experimental and Monte Carlo calculated energy-range data. Only published experimental data with a clear statement of accuracy and method of evaluation have been used. Besides published experimental range data for different uniform media, new accurate experimental data on the practical range of high-energy electron beams in water for the energy range 10-50 MeV from accurately calibrated racetrack microtrons have been used. Largely due to the simultaneous pooling of accurate experimental and Monte Carlo data for different materials, the fit has resulted in an increased accuracy of the resultant energy-range relationship, particularly at high energies. Up to date Monte Carlo data from the latest versions of the codes ITS3 and EGS4 for absorbers of atomic numbers between four and 92 (Be, C, H2O, PMMA, Al, Cu, Ag, Pb and U) and incident electron energies between 1 and 100 MeV have been used as a complement where experimental data are sparse or missing. The standard deviation of the experimental data relative to the new relation is slightly larger than that of the Monte Carlo data. This is partly due to the fact that theoretically based stopping and scattering cross-sections are used both to account for the material dependence of the analytical energy-range formula and to calculate ranges with the Monte Carlo programs. For water the deviation from the traditional energy-range relation of ICRU Report 35 is only 0.5% at 20 MeV but as high as -2.2% at 50 MeV. An improved method for divergence and ionization correction in high-energy electron beams has also been developed to enable use of a wider range of experimental results.

Electrons↗

Simultaneous optimization of dynamic multileaf collimation and scanning patterns or compensation filters using a generalized pencil beam algorithm.

A very flexible iterative method for simultaneous optimization of dynamic multileaf collimation, scanning patterns and compensation filters has been developed. The algorithm can account for and optimize almost all the degrees of freedom available in a modern radiation therapy clinic. The method has been implemented for three dimensional treatment planning. The algorithm has been tested for a number of cases where both traditional wedge filters and block collimators, and modern equipment such as scanned beams and multileaf collimators are available. It is shown that the algorithm can improve heavily on traditional uniform dose plans with respect to the probability of achieving tumor control without causing severe complications (P+) simply by finding the optimal beam weights and block collimator settings. By allowing more complex equipment to deliver the dose and by accounting for their increased flexibility during the optimization, the dose plan can be substantially improved with respect to the applied objective functions. It is demonstrated that flexible lateral collimation combined with compensators or scanned beams in most cases allow close to optimal dose delivery. Here both the calculation time and the amount of primary computer memory needed has been reduced by performing the dose calculations in a cone beam coordinate system allowing the use of approximately spatially invariant energy deposition kernels. A typical calculation time for optimization of a two-field technique in a three dimensional volume is about 20 s per iteration step on a Hewlett-Packard 735 workstation. A well converged solution is normally obtained within about 50-100 iterations or within 15-30 min.

Algorithms↗

Volume and heterogeneity dependence of the dose-response relationship for head and neck tumours.

Based on the Poisson statistics of cell kill a model for the response of heterogeneous tumours to non-uniform dose delivery have been developed. The five parameters required to characterize the response are the 50% response dose, D50, the normalized dose-response gradient, gamma, the tumour heterogeneity factor, h, the relative volume, v and the extra daily dose required to counteract the tumour cell proliferation, delta. The model has been fitted to data from a number of clinical investigations to allow the derivation of clinically relevant radiation response parameters for head and neck tumours. The D50 value for T2 larynx cancers is 59.9 Gy in 41 days with a relative standard deviation of 2.1 Gy and the gamma value is 2.9 with a relative standard deviation of 0.3. The value of delta, which is most consistent with the clinical data for laryngeal tumours, is 0.35 Gy/day and this value should be used if the treatment time is changed from the 41 days normalization. The heterogeneity factor, h, is close to zero for laryngeal tumours which indicates that their response is basically governed by Poisson statistics. Nasopharyngeal tumours, on the other hand, exhibit h values around 0.2 which indicates that these tumours are more heterogeneous in their internal organization and so are their responses to radiation.

Algorithms↗

An analytical solution for the dynamic control of multileaf collimators.

All current optimization techniques in radiation therapy benefit from the use of strongly non-uniform radiation beams. The most flexible way of generating these fields under real time control is by elementary beam scanning and/or dynamic multileaf collimation. In this work general analytical expressions are derived for the required motion of the collimator leaves to achieve a desired energy fluence distribution or collimator opening density in the patient in the shortest possible time. By simplification of the general expressions the equations of motion have been derived for both the shrinking field and the curtain shutter techniques with the associated approximations clearly quantified. The mechanical limitations on leaf motion, caused by the finite velocity and acceleration, are taken into account. It is shown that almost any desired energy fluence distribution can be created even when the limitations on velocity and acceleration are considered. The basic rule with the curtain shutter technique is that when the energy fluence gradient along the direction of motion of the leaves is positive, the leading leaf should move at maximum speed and the lagging leaf should modulate the field. In regions where the gradient is negative the lagging leaf should instead move at full speed and the leading leaf should modulate the field. The overall treatment time is then proportional to the total increment in energy fluence or opening density between consecutive minima and maxima. For energy fluence profiles with numerous high peaks the treatment time may therefore increase considerably over that for conventional uniform dose delivery. However, in general the treatment time is prolonged by a factor of about two compared to a traditional uniform treatment. Obviously the method developed here for multileaf collimators is also suitable for simple block collimators since it can be used to deliver arbitrary regular or irregular 'dynamic wedge' profiles along the direction of motion of the collimator blocks.

Humans↗

A general solution to charged particle beam flattening using an optimized dual-scattering-foil technique, with application to proton therapy beams.

This paper describes a dual-scattering-foil technique for flattening of radiotherapeutic charged particle beams. A theory for optimization of shapes and thicknesses of the scattering foils is presented. The result is a universal optimal secondary-scatterer profile, which can be adapted to any charged particle beam by a simple scaling procedure. The calculation of the mean square scattering angle of the beam after passing through the scattering foils is done using the generalized Fermi-Eyges model for charged particle transport. It is shown that the fluence profile in the plane of interest can be made flat to better than 1% inside a predefined beam radius provided the shaped secondary scatterer has the universal radial thickness profile. The thicknesses of the two foils are optimized to minimize the total energy loss. The theory has been tested experimentally in an 180 MeV clinical proton beam. The measured distributions agree well with the calculations.

Electrons↗

An accurate energy-range relationship for high-energy electron beams in arbitrary materials.

A general analytical energy-range relationship has been derived to relate the practical range, Rp, to the most probable energy, Ep, of incident electron beams in the range 1 to 50 MeV and above, for absorbers of any atomic number. The expression is cubic in energy and requires as input parameters the total stopping power, So, the ratio of the scattering power and the total specific stopping power, T0/epsilon0, both taken at 10 MeV, and the radiation length for the material involved, X0. In addition to these parameters, five of the derived parameters are used to 'fine tune' the equation and minimize the mean square deviation from experimental and/or Monte Carlo data by means of non-linear regression. In the present study only Monte Carlo data determined with the new ITS.3 code have been employed. The standard deviations of the mean deviation from the Monte Carlo data at any energy are about 0.10, 0.12, 0.04, 0.11, 0.04, 0.03, 0.02 mm for Be, C, H2O, Al, Cu, Ag and U, respectively, and the relative standard deviation of the mean is about 0.5% for all materials. The fitting program gives some priority to water-equivalent materials, which explains the low standard deviation for water. A small error in the fall-off slope can give a different value for Rp. We describe a new method which reduces the uncertainty in the Rp determination, by fitting an odd function to the descending portion of the depth-dose curve in order to accurately determine the tangent at the inflection point, and thereby the practical range. An approximate inverse relation is given expressing the most probable energy of an electron beam as a function of the practical range. The resultant relative standard error of the energy is less than 0.7%, and the maximum energy error deltaEp is less than 0.3 MeV.

Algorithms↗

A generalized pencil beam algorithm for optimization of radiation therapy.

An iterative pencil beam algorithm for optimization of multidimensional radiation therapy dose plans has been developed. The algorithm allows the use of both physical and radiobiological treatment objective functions and allows arbitrary sampling such as straight Cartesian grids with linear or nonlinear sampling functions or random sampling. The algorithm can account for and optimally combine almost all the degrees of freedom at an advanced radiotherapy clinic, such as different beam modalities and spectra, beam directions, beam fluence distributions, and time-dose fractionations. The algorithm allows for external charged and neutral beams as well as intracavitary and interstitial sources to be optimally combined. A quantity termed the generalized fluence vector is introduced, combining fluences and energy fluences from external beams as well as the radiation source densities of intracavitary and interstitial sources or external source distributions. The positivity constraint on the generalized fluence can therefore be applied directly during the optimization procedure. The convergence properties and the required iteration time of the algorithm are discussed. Several examples with combinations of photon and electron beams of different energies and directions of incidence are presented. The optimization has been made with the treatment objective to maximize the probability of achieving tumor control without causing severe complications in healthy normal tissues.

Algorithms↗