Reconstruction of high resolution MLC leaf positions using a low resolution detector for accurate 3D dose reconstruction in IMRT.

In pre-treatment dose verification, low resolution detector systems are unable to identify shifts of individual leafs of high resolution multi leaf collimator (MLC) systems from detected changes in the dose deposition. The goal of this study was to introduce an alternative approach (the shutter technique) combined with a previous described iterative reconstruction method to accurately reconstruct high resolution MLC leaf positions based on low resolution measurements. For the shutter technique, two additional radiotherapy treatment plans (RT-plans) were generated in addition to the original RT-plan; one with even MLC leafs closed for reconstructing uneven leaf positions and one with uneven MLC leafs closed for reconstructing even leaf positions. Reconstructed leaf positions were then implemented in the original RT-plan for 3D dose reconstruction. The shutter technique was evaluated for a 6 MV Elekta SLi linac with 5 mm MLC leafs (Agility™) in combination with the MatriXX Evolution detector with detector spacing of 7.62 mm. Dose reconstruction was performed with the COMPASS system (v2.0). The measurement setup allowed one row of ionization chambers to be affected by two adjacent leaf pairs. Measurements were obtained for various field sizes with MLC leaf position errors ranging from 1.0 mm to 10.0 mm. Furthermore, one clinical head and neck IMRT treatment beam with MLC introduced leaf position errors of 5.0 mm was evaluated to illustrate the impact of the shutter technique on 3D dose reconstruction. Without the shutter technique, MLC leaf position reconstruction showed reconstruction errors up to 6.0 mm. Introduction of the shutter technique allowed MLC leaf position reconstruction for the majority of leafs with sub-millimeter accuracy resulting in a reduction of dose reconstruction errors. The shutter technique in combination with the iterative reconstruction method allows high resolution MLC leaf position reconstruction using low resolution measurements with sub-millimeter accuracy.

Development of an iterative reconstruction method to overcome 2D detector low resolution limitations in MLC leaf position error detection for 3D dose verification in IMRT.

The objective of this study was to introduce a new iterative method to reconstruct multi leaf collimator (MLC) positions based on low resolution ionization detector array measurements and to evaluate its error detection performance. The iterative reconstruction method consists of a fluence model, a detector model and an optimizer. Expected detector response was calculated using a radiotherapy treatment plan in combination with the fluence model and detector model. MLC leaf positions were reconstructed by minimizing differences between expected and measured detector response. The iterative reconstruction method was evaluated for an Elekta SLi with 10.0 mm MLC leafs in combination with the COMPASS system and the MatriXX Evolution (IBA Dosimetry) detector with a spacing of 7.62 mm. The detector was positioned in such a way that each leaf pair of the MLC was aligned with one row of ionization chambers. Known leaf displacements were introduced in various field geometries ranging from -10.0 mm to 10.0 mm. Error detection performance was tested for MLC leaf position dependency relative to the detector position, gantry angle dependency, monitor unit dependency, and for ten clinical intensity modulated radiotherapy (IMRT) treatment beams. For one clinical head and neck IMRT treatment beam, influence of the iterative reconstruction method on existing 3D dose reconstruction artifacts was evaluated. The described iterative reconstruction method was capable of individual MLC leaf position reconstruction with millimeter accuracy, independent of the relative detector position within the range of clinically applied MU's for IMRT. Dose reconstruction artifacts in a clinical IMRT treatment beam were considerably reduced as compared to the current dose verification procedure. The iterative reconstruction method allows high accuracy 3D dose verification by including actual MLC leaf positions reconstructed from low resolution 2D measurements.

Efficient and reliable 3D dose quality assurance for IMRT by combining independent dose calculations with measurements.

PURPOSE: Advanced radiotherapy treatments require appropriate quality assurance (QA) to verify 3D dose distributions. Moreover, increase in patient numbers demand efficient QA-methods. In this study, a time efficient method that combines model-based QA and measurement-based QA was developed; i.e., the hybrid-QA. The purpose of this study was to determine the reliability of the model-based QA and to evaluate time efficiency of the hybrid-QA method. METHODS: Accuracy of the model-based QA was determined by comparison of COMPASS calculated dose with Monte Carlo calculations for heterogeneous media. In total, 330 intensity modulated radiation therapy (IMRT) treatment plans were evaluated based on the mean gamma index (GI) with criteria of 3%∕3mm and classification of PASS (GI ≤ 0.4), EVAL (0.4 < GI > 0.6), and FAIL (GI ≥ 0.6). Agreement between model-based QA and measurement-based QA was determined for 48 treatment plans, and linac stability was verified for 15 months. Finally, time efficiency improvement of the hybrid-QA was quantified for four representative treatment plans. RESULTS: COMPASS calculated dose was in agreement with Monte Carlo dose, with a maximum error of 3.2% in heterogeneous media with high density (2.4 g∕cm(3)). Hybrid-QA results for IMRT treatment plans showed an excellent PASS rate of 98% for all cases. Model-based QA was in agreement with measurement-based QA, as shown by a minimal difference in GI of 0.03 ± 0.08. Linac stability was high with an average GI of 0.28 ± 0.04. The hybrid-QA method resulted in a time efficiency improvement of 15 min per treatment plan QA compared to measurement-based QA. CONCLUSIONS: The hybrid-QA method is adequate for efficient and accurate 3D dose verification. It combines time efficiency of model-based QA with reliability of measurement-based QA and is suitable for implementation within any radiotherapy department.

Reconstruction of high-resolution 3D dose from matrix measurements: error detection capability of the COMPASS correction kernel method.

The COMPASS system (IBA Dosimetry) is a quality assurance (QA) tool which reconstructs 3D doses inside a phantom or a patient CT. The dose is predicted according to the RT plan with a correction derived from 2D measurements of a matrix detector. This correction method is necessary since a direct reconstruction of the fluence with a high resolution is not possible because of the limited resolution of the matrix used, but it comes with a blurring of the dose which creates inaccuracies in the dose reconstruction. This paper describes the method and verifies its capability to detect errors in the positioning of a MLC with 10 mm leaf width in a phantom geometry. Dose reconstruction was performed for MLC position errors of various sizes at various locations for both rectangular and intensity-modulated radiotherapy (IMRT) fields and compared to a reference dose. It was found that the accuracy with which an error in MLC position is detected depends on the location of the error relative to the detectors in the matrix. The reconstructed dose in an individual rectangular field for leaf positioning errors up to 5 mm was correct within 5% in 50% of the locations. At the remaining locations, the reconstruction of leaf position errors larger than 3 mm can show inaccuracies, even though these errors were detectable in the dose reconstruction. Errors larger than 9 mm created inaccuracies up to 17% in a small area close to the penumbra. The QA capability of the system was tested through gamma evaluation. Our results indicate that the mean gamma provided by the system is slightly increased and that the number of points above gamma 1 ensures error detection for QA purposes. Overall, the correction kernel method used by the COMPASS system is adequate to perform QA of IMRT treatment plans with a regular MLC, despite local inaccuracies in the dose reconstruction.

Impact of simple tissue inhomogeneity correction algorithms on conformal radiotherapy of lung tumours.

BACKGROUND AND PURPOSE: Conformal radiotherapy requires accurate dose calculation at the dose specification point, at other points in the planning target volume (PTV) and in organs at risk. To assess the limitations of treatment planning of lung tumours, errors in dose values, calculated by some simple tissue inhomogeneity correction algorithms available in a number of currently applied treatment planning systems, have been quantified. MATERIALS AND METHODS: Single multileaf collimator-shaped photon beams of 6, 8, 15 and 18 MV nominal energy were used to irradiate a 50 mm diameter spherical solid tumour, simulated by polystyrene, which was located centrally inside lung tissue, simulated by cork. The planned dose distribution was made conformal to the PTV, which was a 15 mm three-dimensional expansion of the tumour. Values of both the absolute dose at the International Commission on Radiation Units and Measurement (ICRU) reference point and relative dose distributions inside the PTV and in the lung were calculated using three inhomogeneity correction algorithms. The algorithms investigated in this study are the pencil beam algorithm with one-dimensional corrections, the modified Batho algorithm and the equivalent path length algorithm. The calculated data were compared with measurements for a simple beam set-up using radiographic film and ionization chambers. RESULTS: For this specific configuration, deviations of up to 3.5% between calculated and measured values of the dose at the ICRU reference point were found. Discrepancies between measured and calculated beam fringe values (distance between the 50 and 90% isodose lines) of up to 14 mm have been observed. The differences in beam fringe and penumbra width (20-80%) increase with increasing beam energy. Our results demonstrate that an underdosage of the PTV up to 20% may occur if calculated dose values are used for treatment planning. The three algorithms predict a considerably higher dose in the lung, both along the central beam axis and in the lateral direction, compared with the actual delivered dose values. CONCLUSIONS: The dose at the ICRU reference point of such a tumour in lung geometry is calculated with acceptable accuracy. Differences between calculated and measured dose distributions are primarily due to changes in electron transport in the lung, which are not adequately taken into account by the simple tissue inhomogeneity correction algorithms investigated in this study. Particularly for high photon beam energies, clinically unacceptable errors will be introduced in the choice of field sizes employed for conformal treatments, leading to underdosage of the PTV. In addition, the dose to the lung will be wrongly predicted which may influence the choice of the prescribed dose level in dose-escalation studies.

Detector line spread functions determined analytically by transport of Compton recoil electrons.

To achieve the maximum benefit of conformal radiation therapy it is necessary to obtain accurate knowledge of radiation beam penumbras based on high-resolution relative dosimetry of beam profiles. For this purpose there is a need to perform high-resolution dosimetry with well-established routine dosimeters, such as ionization chambers or diodes. Profiles measured with these detectors must be corrected for the dosimeter's nonideal response, caused by finite dimensions and, in the case of an ionization chamber, the alteration of electron transport and a contribution of electrons recoiled in the chamber wall and the central electrode. For this purpose the line spread function (LSF) of the detector is needed. The experimental determination of LSFs is cumbersome and restricted to the specific detector and beam energy spectrum used. Therefore, a previously reported analytical model [Med. Phys. 27, 923-934 (2000)] has been extended to determine response profiles of routine dosimeters: shielded diodes and, in particular, ionization chambers, in primary dose slit beams. The model combines Compton scattering of incident photons, the transport of recoiled electrons by Fermi-Eyges small-angle multiple scattering theory, and functions to limit electron transport. It yields the traveling direction and the energy of electrons upon incidence on the detector surface. In the case of ionization chambers, geometrical considerations are then sufficient to calculate the relative amount of ionization in chamber air, i.e., the detector response, as a function of the detector location in the slit beam. In combination with the previously reported slit beam dose profiles, the LSF can then readily be derived by reconstruction techniques. Since the spectral contributions are preserved, the LSF of a dosimeter is defined for any beam for which the effective spectrum is known. The detector response profiles calculated in this study have been verified in a telescopic slit beam geometry, and were found to correspond to experimental profiles within 0.2 and 0.3 mm (full width at half-maximum) for a Wellhoefer IC15 chamber in a 6 and 25 MV-X x-ray beam, respectively. For a shielded diode these figures were found to be 0.2 and 0.1 mm, respectively. It is shown that a shielded diode in a primary beam needs only a small size-based correction of measured profiles. The effect of the LSF of an IC15 chamber on penumbra width has been determined for a set of model penumbras. The LSFs calculated by the application of the analytical model yield a broadening by 2 mm of a 3 mm wide penumbra (20%-80%). This is 0.5 mm (6 MV-X) to 1 mm (25 MV-X) smaller than found with the experimental LSFs. With a spatial correction based on the LSFs that were determined in this study, this broadening of up to 2 mm is eliminated, so that ionization chambers like the IC15 can be used for high-resolution relative dosimetry on a routine basis.

Collimator scatter and 2D dosimetry in small proton beams.

Monte Carlo simulations have been performed to determine the influence of collimator-scattered protons from a 150 MeV proton beam on the dose distribution behind a collimator. Slit-shaped collimators with apertures between 2 and 20 mm have been simulated. The Monte Carlo code GEANT 3.21 has been validated against one-dimensional dose measurements with a scintillating screen, observed by a CCD camera. In order to account for the effects of the spatial response of the CCD/scintillator system, the line-spread function was determined by comparison with measurements made with a diamond detector. The line-spread function of the CCD/scintillator system is described by a Gaussian distribution with a standard deviation of 0.22 mm. The Monte Carlo simulations show that protons that hit the collimator on the entrance face and leave it through the wall of the aperture make the largest scatter contribution. Scatter on air is the major contribution to the extent of the penumbra. From the energy spectra it is derived that protons with a relative biological effectiveness greater than 1 cause at most 1% more damage in tissue than what would be expected from the physical dose.

Slit x-ray beam primary dose profiles determined by analytical transport of Compton recoil electrons.

Accurate measurement of radiation beam penumbras is essential for conformal radiotherapy. For this purpose a detailed knowledge of the dosimeter's spatial response is required. However, experimental determination of detector spatial response is cumbersome and restricted to the specific detector type and beam spectrum used. A model has therefore been developed to calculate in slit beam geometry both dose profiles and detector response profiles. Summations over representative photon beam spectra yield profiles for polyenergetic beams. In the present study the model is described and resulting dose profiles verified. The model combines Compton scattering of incident photons, transport of resulting electrons by Fermi-Eyges small-angle multiple scattering theory, and functions to limit electron transport. This analytic model thus yields line spread kernels of primary dose in a water phantom. It is shown that the spatial response of an ideal point detector to a primary photon beam can be well described by the model; the calculations are verified by measurements with a diamond detector in a telescopic slit geometry in which all dose contributions except for the primary dose can be excluded. Effects of photon detector behavior, source size of the linear accelerator (linac) and detector size are studied. Measurements show that slit dose profiles calculated by means of the kernel are accurate within 0.1 mm of the full-width at half-maximum. For a theoretical point source and point detector combined with a 0.2 mm wide slit, the full-width half-maximum values of the slit beam dose profiles are calculated as 0.37 mm and 0.42 mm in a 6 MV and 25 MV x-ray beam, respectively. The present study shows that the model is adequate to calculate local dose effects that are dominated by approximately mono-directional, primary photon fluence. The analytic model further provides directional electron fluence information and is designed to be applied to various detectors and linac beam spectra.

Radiological and functional assessment of radiation-induced lung injury in the rat.

The purpose of this study is to develop an experimental model to measure localized radiation-induced lung injury using multiple end-points including breathing frequency, high-resolution computed tomography (CT), and radionuclide perfusion. The rats were anesthetized and the right lung irradiated with a single dose of 18 Gy using 200-kVp x-rays. The lung function of the animals was measured every 2 weeks after irradiation with the breathing rate assay. CT scanning and radionuclide lung perfusion assay were performed prior to and 2, 4, 10, 16, and 34 weeks after irradiation. Significant elevation in breathing rate occurred after 16 weeks, with a maximal increase between 22 and 28 weeks. An increase in the right lung density started 4 weeks after irradiation. Regional measurements indicated a relatively uniform increase in density at 4 and 10 weeks, while foci of high-density areas were observed at the later time points. Changes in rat lung volume indicated shrinkage of the irradiated right lung and accompanying compensatory hypertrophy of the shielded left lung. Radionuclide perfusion assay showed significant decrease in relative blood flow in the irradiated right lung 4 weeks after hemithoracic irradiation. Changes in breathing rate provide an index of overall lung function while changes in lung density, volume, and perfusion are of particular importance for evaluating loco-regional differences in lung sensitivity. This study is the first demonstration that CT can be used to measure volume changes after thoracic irradiation in rats.

Analysis of accuracy in dose and position in calculations of a treatment planning system for blocked photon fields.

Accuracy in dose and position, defined as complementary criteria, was determined for blocked photon field calculations with a pencil beam based treatment planning system. The concept of field accuracy has been defined as a combination of deviations in dose and position. Absolute dose deviations were measured including the deviations in beam output (monitor units), depth doses and dose profiles. Based on this verification work it was concluded that the pencil beam model is capable of calculating dose distributions in blocked photon fields (6 MV and 25 MV) with a high degree of accuracy. The measurements and calculations mostly agreed within 3% or 3 mm, whichever was less, relative to a reference dose at 10 cm depth. Furthermore, the model behaves consistently because a substantial part of the discrepancies found could be ascribed to fundamental assumptions in the model related to electron contamination and primary block transmission. The concept 'field accuracy' allows an easy, quantitative and comprehensive comparison to common quality requirements giving, for example, equal weight to percent dose difference and to millimetre isodose distance. The method offers the possibility to focus on calculation accuracy which excludes some experimental sources of error.

Influence of shape on the accuracy of grid-based volume computations.

The influence of the shape of a region of interest (ROI) on the uncertainty in the sampled volume of the ROI is investigated for computations with regular Cartesian grids. Both mathematically defined volumes and clinically relevant ROIs were studied. The sampling uncertainty is shown to depend on the compactness of the ROI and on effects of grid matching and translational symmetry. In clinical ROIs without translational symmetry the estimate of the sampling uncertainty is improved up to a factor of 2.3 by taking the compactness of the ROI into account. In a spherical ROI grid-matching effects were demonstrated by means of Fourier transforms. In this type of ROI, grid-matching effects decrease as well as increase the sampling uncertainty up to a factor of 1.6. Translational symmetry is shown to cause a decrease in the sampling uncertainty convergence power from 2/3 for spherical ROIs, to 1/2 for stringlike or 1/3 for pancakelike cylinders. For clinical ROIs with translational symmetry, similar decreases were found. With the theory derived and these symmetry effects taken into account the experimental uncertainty of volume computation can be estimated for most clinical ROIs within a factor of 2.5. Special care should be taken in grid sampling of volumes inside isodose surfaces of rectangular field techniques. For the volume of a prostate an uncertainty level of 1% or 5% is obtained with less than 1050 or 80 grid points, respectively, while for such an isodose surface up to 16,000 or 500 grid points are required for the same uncertainty levels.

Structural and dynamic effects of oxidatively modified phospholipids in unsaturated lipid membranes.

Phospholipid hydroperoxides and phospholipid alcohols are two of the major forms of oxidatively modified phospholipids produced during oxidant stress and lipid peroxidation. The process of lipid peroxidation is known to affect the physiological function of membranes. We, therefore, investigated the effects of lipid peroxidation products on the molecular interactions in membranes. Our study was specifically focused on the effects of lipid peroxidation products on static membrane structure (molecular orientational order) and on the reorientational dynamics of the probe molecules in lipid bilayers. The study was done by performing angle-resolved fluorescence depolarization measurements (AFD) on the fluorescent probe diphenylhexatriene (DPH) and by performing angle-resolved electron spin resonance (A-ESR) measurements on cholestane (CSL) nitroxide spin probes embedded in macroscopically oriented planar bilayers consisting of 2-10% 1-palmitoyl-2-(9/13-hydroperoxylinoleoyl)phosphatidylcholine (PLPC-OOH) or 1-palmitoyl-2-(9/13-hydroxylinoleoyl)phosphatidylcholine (PLPC-OH) in 1-palmitoyl-2-linoleoylphosphatidylcholine (PLPC) or dilinoleoylphosphatidylcholine (DLPC). Both probe molecules have rigid cylindrical geometries and report on the overall molecular order and dynamics. However, being more polar, the nitroxide spin probe CSL is preferentially located near the surface of the membrane, while the less polar fluorescent probe DPH reports preferentially near the central hydrophobic region of the lipid bilayers. The results show that the presence of relatively small amounts of oxidatively modified phospholipids within the PLPC or DLPC membranes causes pronounced structural effects as the molecular orientational order of the probe molecules is strongly decreased. In contrast, the effect on membrane reorientational dynamics is minimal.

A temporal red-green opponent mechanism.

A mechanistic model is presented that describes the temporal behaviour of a red-green colour opponent channel such as has been investigated for the macaque monkey. The model incorporates luminance- and chromaticity-adaptation mechanisms. Receptive field properties such as retardation and attenuation of the surround signals with respect to the center signals of the colour opponent channel are also included. The model predicts temporal psychophysical chromaticity thresholds and temporal electrophysiological red-green colour opponent ganglion cell behaviour with a reasonable degree of success.