Table of contents

Intravascular coronary thermography is a method that may detect vulnerable, atherosclerotic plaques and is currently evaluated in a clinical setting. Active macrophages or enzymatic heat releasing processes in vulnerable plaques may act as heat sources. To better understand the parameters of influence on thermographic measurements, numerical simulations have been performed on a model of a coronary artery segment containing a heat source. Heat source parameters and flow were varied to study their influence on temperatures at the lumen wall. Maximal temperature differences at the lumen wall increased when the source volume increased and they differ with the source geometry. The simulations showed that blood flow acts as a coolant to the lumen wall. Blood flow decreased maximal temperatures depending on the source geometry, source volume and the maximal flow velocity. Influence of flow was highest for circumferentially extended sources, up to a factor 3.7, and lowest for longitudinally extended sources, down to a factor 1.9. When cap thickness increased, maximal temperatures decreased and the influence of flow increased. This study shows that correct interpretation of intravascular thermographic measurements requires data on the flow and on the morphologic characteristics of the atherosclerotic plaque.

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.

Parallel in vitro and in vivo studies provide insight into the relationship between clinical response and intrinsic cellular radiosensitivity and may aid in the development of predictive assays. Compilations of radiosensitivity parameters from in vitro experiments can also be used to examine the potential effectiveness of alternative or new treatment plan designs until enough clinical data become available to directly estimate the requisite radiosensitivity parameters. In this work, survival data for six prostate cancer cell lines (ten datasets total) have been extracted from the literature and re-analysed using the linear-quadratic (LQ) survival model. The paired bootstrap technique for regression is used to compute 95% confidence intervals for the estimated radiosensitivity parameters. LQ radiosensitivity parameters derived from the in vitro data are then compared to radiosensitivity parameters derived from clinical data for prostate cancer. Estimates of α range from 0.09 to 0.35 Gy⁻¹ (all cell lines), and the α/β ratio ranges from 1.09 to 6.29 Gy (all cell lines). Point estimates of the repair half-time (PPC-1, TSU-Pr1, PC-3 and DU-145 cell lines) range from 5.7 to 8.9 h (95% confidence interval from 0.26 h to 10.7 h). Differences in the radiosensitivity parameters determined from the data reported by different laboratories are as large as or larger than the differences in radiosensitivity parameters observed among the various prostate cell lines. The reported studies demonstrate that even seemingly small corrections for dose rate effects, such as those expected in high dose rate (HDR) experiments, can sometimes have a significant impact on estimates of α and α/β. By neglecting dose rate effects in the analysis of HDR experiments, estimates of the α/β ratio may be too high by factors as large as 1.3 to 6.2. The half-time for repair derived from the in vitro experiments appears significantly larger (slower repair rate) than estimates derived from the clinical data. However, the prostate radiosensitivity parameters α and α/β may be approximately the same in vitro and in vivo. Most of the in vitro data are consistent with an α/β ratio for prostate cancer less than 3 or 4 Gy.

The aim of the present study was to investigate three different detector types (a parallel-plate ionization chamber, a p-type silicon diode and a diamond detector) with regard to output factor measurements in degraded electron beams, such as those encountered in small-electron-field radiotherapy and intraoperative radiation therapy (IORT). The Monte Carlo method was used to calculate mass collision stopping-power ratios between water and the different detector materials for these complex electron beams (nominal energies of 6, 12 and 20 MeV). The diamond detector was shown to exhibit excellent properties for output factor measurements in degraded beams and was therefore used as a reference. The diode detector was found to be well suited for practical measurements of output factors, although the water-to-silicon stopping-power ratio was shown to vary slightly with treatment set-up and irradiation depth (especially for lower electron energies). Application of ionization-chamber-based dosimetry, according to international dosimetry protocols, will introduce uncertainties smaller than 0.3% into the output factor determination for conventional IORT beams if the variation of the water-to-air stopping-power ratio is not taken into account. The IORT system at our department includes a 0.3 cm thin plastic scatterer inside the therapeutic beam, which furthermore increases the energy degradation of the electrons. By ignoring the change in the water-to-air stopping-power ratio due to this scatterer, the output factor could be underestimated by up to 1.3%. This was verified by the measurements. In small-electron-beam dosimetry, the water-to-air stopping-power ratio variation with field size could mostly be ignored. For fields with flat lateral dose profiles (>3 × 3 cm²), output factors determined with the ionization chamber were found to be in close agreement with the results of the diamond detector. For smaller field sizes the lateral extension of the ionization chamber hampers its use. We therefore recommend that the readily available silicon diode detector should be used for output factor measurements in complex electron fields.

When irradiating a polymer gel dosimeter to relatively high doses, edge enhancing effects (overshoots) may be noticed near dose gradients, resulting in a loss of spatial dose integrity. These overshoots are believed to be a consequence of monomers diffusing into the high-dose region, where they react with long-living macroradicals. Macroradicals may also be responsible for the temporal chemical instability of post-irradiation polymerization that occurs in the polymer gel dosimeter. In this study, a mathematical model is proposed that simulates the edge enhancing effect. The model is based on the hypothesis that the macroradicals are responsible for both the temporal instability and loss of spatial dose integrity. All input parameters for the model are obtained from independent experiments. The edge enhancing effect is studied both experimentally and theoretically for polymer gel dosimeters with various gelatin concentrations. The change in the edge enhancement is also investigated over post-irradiation time. Comparisons between polymer gel measurements and simulations confirm the hypothesis that there is a strong relation between the spatial and temporal instabilities.

The double-differential cross sections for (n, px), (n, dx), (n, tx), (n, ³Hex) and (n, αx) reactions in carbon have been measured at 96 MeV incident neutron energy. The various charged particles (inclusive spectra) were identified using ΔE–E techniques. From the experimental data, energy- and angle-differential as well as production cross sections were determined, and subsequently the partial and total kerma coefficients. The deduced partial and total kerma coefficients were compared to previous experimental results and theoretical calculations. The findings indicate that the deduced kerma coefficients for the hydrogen isotopes are in good agreement with those deduced from a previous measurement, and that the kerma coefficient values, in particular of the hydrogen isotopes, are systematically higher than values obtained from recent model calculations, which consequently resulted in a total kerma coefficient which is up to 30% higher than predicted by the calculations.

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. This paper gives a detailed description of the design and development of GATE by the OpenGATE collaboration, whose continuing objective is to improve, document and validate GATE by simulating commercially available imaging systems for PET and SPECT. Large effort is also invested in the ability and the flexibility to model novel detection systems or systems still under design. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at http://www-lphe.epfl.ch/GATE/. Two benchmarks developed for PET and SPECT to test the installation of GATE and to serve as a tutorial for the users are presented. Extensive validation of the GATE simulation platform has been started, comparing simulations and measurements on commercially available acquisition systems. References to those results are listed. The future prospects towards the gridification of GATE and its extension to other domains such as dosimetry are also discussed.

We present a pragmatic approach to image reconstruction for data from the micro crystal elements system (MiCES) fully 3D mouse imaging positron emission tomography (PET) scanner under construction at the University of Washington. Our approach is modelled on fully 3D image reconstruction used in clinical PET scanners, which is based on Fourier rebinning (FORE) followed by 2D iterative image reconstruction using ordered-subsets expectation-maximization (OSEM). The use of iterative methods allows modelling of physical effects (e.g., statistical noise, detector blurring, attenuation, etc), while FORE accelerates the reconstruction process by reducing the fully 3D data to a stacked set of independent 2D sinograms. Previous investigations have indicated that non-stationary detector point-spread response effects, which are typically ignored for clinical imaging, significantly impact image quality for the MiCES scanner geometry. To model the effect of non-stationary detector blurring (DB) in the FORE+OSEM(DB) algorithm, we have added a factorized system matrix to the ASPIRE reconstruction library. Initial results indicate that the proposed approach produces an improvement in resolution without an undue increase in noise and without a significant increase in the computational burden. The impact on task performance, however, remains to be evaluated.

Exciting new SPECT systems can be created by combining pinhole imaging with compact high-resolution gamma cameras. These new systems are able to solve the problem of the limited sensitivity-resolution trade-off that hampers contemporary small animal SPECT. The design presented here (U-SPECT-III) uses a set of detectors placed in a polygonal configuration and a cylindrical collimator that contains 135 pinholes arranged in nine rings. Each ring contains 15 gold pinhole apertures that focus on the centre of the cylinder. A non-overlapping projection is acquired via each pinhole. Consequently, when a mouse brain is placed in the central field-of-view, each voxel in the cerebrum can be observed via 130 to 135 different pinholes simultaneously. A method for high-resolution scintillation detection is described that eliminates the depth-of-interaction problem encountered with pinhole cameras, and is expected to provide intrinsic detector resolutions better than 150 µm. By means of simulations U-SPECT-III is compared to a simulated dual pinhole SPECT (DP-SPECT) system with a pixelated array consisting of 2.0 × 2.0 mm NaI crystals. Analytic calculations indicate that the proposed U-SPECT-III system yields an almost four times higher linear and about sixty times higher volumetric system resolution than DP-SPECT, when the systems are compared at matching system sensitivity. In addition, it should be possible to achieve a 15 up to 30 times higher sensitivity with U-SPECT-III when the systems are compared at equal resolution. Simulated images of a digital mouse-brain phantom show much more detail with U-SPECT-III than with DP-SPECT. In a resolution phantom, 0.3 mm diameter cold rods are clearly visible with U-SPECT-III, whereas with DP-SPECT the smallest visible rods are about 0.6–0.8 mm. Furthermore, with U-SPECT-III, the image deformations outside the central plane of reconstruction that hamper conventional pinhole SPECT are strongly suppressed. Simulation results indicate that future pinhole SPECT systems are likely to bring about significant improvements in radio-molecular imaging of small animals.

The main thrust for this work is the investigation and design of a whole-body PET scanner based on new lanthanum bromide scintillators. We use Monte Carlo simulations to generate data for a 3D PET scanner based on LaBr₃ detectors, and to assess the count-rate capability and the reconstructed image quality of phantoms with hot and cold spheres using contrast and noise parameters. Previously we have shown that LaBr₃ has very high light output, excellent energy resolution and fast timing properties which can lead to the design of a time-of-flight (TOF) whole-body PET camera. The data presented here illustrate the performance of LaBr₃ without the additional benefit of TOF information, although our intention is to develop a scanner with TOF measurement capability. The only drawbacks of LaBr₃ are the lower stopping power and photo-fraction which affect both sensitivity and spatial resolution. However, in 3D PET imaging where energy resolution is very important for reducing scattered coincidences in the reconstructed image, the image quality attained in a non-TOF LaBr₃ scanner can potentially equal or surpass that achieved with other high sensitivity scanners. Our results show that there is a gain in NEC arising from the reduced scatter and random fractions in a LaBr₃ scanner. The reconstructed image resolution is slightly worse than a high-Z scintillator, but at increased count-rates, reduced pulse pileup leads to an image resolution similar to that of LSO. Image quality simulations predict reduced contrast for small hot spheres compared to an LSO scanner, but improved noise characteristics at similar clinical activity levels.

IMRT optimization is an iterative process in which many dose calculations may be necessary. A fast and accurate dose calculation engine is essential for the optimization program to converge to a reliable solution in a reasonable time. Previously we developed a fast dose calculation method for IMRT optimization based on the table lookup (TLP). The TLP kernel is constructed from the dose distributions computed from an accurate superposition/convolution (SC) algorithm at the beginning. Dose calculations at subsequent iterations are performed by looking up the kernel in memory, therefore are very fast. However, it is assumed by the TLP that the beamlet only deposits doses to the voxels on its path. In this paper, we propose an improved table lookup based dose calculation method that includes the scatter contribution (TLPS). The intensity map for each beam is decomposed into an even and an odd checkbox-type pattern for the construction of the kernel for primary and scatter components. The performance of this algorithm is compared with the methods of SC only and TLP without scatter on a few clinical cases and the advantages of speed and accuracy are demonstrated. This method is especially useful for those optimizations that utilize the IMRT optimization as an inner loop, such as the beam angle optimization.

DOSSCORE is an accelerated version of DOSXYZnrc that allows photons to cross voxel boundaries of the same medium and utilizes a separate scoring grid superimposed on the geometrical grid. Two different stepping algorithms, the hownear method and the scaling method are implemented in DOSSCORE.

The hownear method allows particles to travel larger distances in homogeneous regions where there is no interest in the dose deposition of these particles, whilst the scaling method utilizes a stepping algorithm in which particles are only slowed down by the boundaries of the geometrical voxels and not by the boundaries of the scoring voxels.

For CT-based phantoms, only photon ray tracing is applied, which results in a rather modest speed gain of factor 1.2 compared to DOSXYZnrc. The hownear method and scaling method do not increase the speed for CT-based phantoms, but only for homogeneous phantoms and phantoms with a limited number of small heterogeneities. In cases where a small number of scoring voxels are needed, the hownear method performs better than the scaling method, whilst the opposite is true for cases when many scoring voxels are needed.

The photon transport is accelerated by almost a factor of 2 for all phantoms (homogeneous, heterogeneous with much homogeneity and CT-based phantoms) compared to DOSXYZnrc. For a small number of scoring voxels, the hownear method is up to a factor of 2.6 and 1.9 faster than DOSXYZnrc for homogeneous and heterogeneous phantoms in the case of photon beams. For an electron beam, a speed gain of factor 2.4 is obtained. For a full scoring grid like the one used in DOSXYZnrc, the scaling method is up to a factor of 2.2 and 1.7 faster than DOSXYZnrc for homogeneous and heterogeneous phantoms in the case of photon beams. For an electron beam, a speed gain of factor 2 is obtained.

A speed increase without biasing the results is very relevant. The use of two separate grids, the more efficient stepping algorithms and the accelerated photon transport can be applied to every EGS-based or other Monte Carlo code.

The availability at the Paul Scherrer Institute (PSI) of a spot-scanning technique with an isocentric beam delivery system (gantry) allows the realization of intensity-modulated proton therapy (IMPT). The development of 3D dosimetry is an important tool for the verification of IMPT therapy plans based on inhomogeneous 3D conformal dose distributions. For that purpose new dosimeters are being developed. The concept is to use a system of many millimetre sized scintillating volumes distributed in a polyethylene block, which are read on a CCD camera over a bundle of optical fibres and which can be irradiated from any direction orthogonal to the fibre axis. The purpose of this work is to investigate the composition of such small sensitive volumes. A mixture of inorganic phosphors and optical cement allows an optimal coupling between the scintillating volume and the optical fibre. Five different inorganic phosphors, available as powder, have been examined by considering their response along the Bragg curve. In particular, two phosphors have shown interesting behaviours: Gd₂O₂S:Tb and (Zn, Cd)S:Ag. Both phosphors have a high emission efficiency but contrasting behaviour in the Bragg peak region. The efficiency of Gd₂O₂S:Tb decreases with increasing stopping power (quenching of luminescence) while that of (Zn, Cd)S:Ag increases. Because of these contrasting behaviours it is possible to prepare a mixture of the two scintillating powders in a certain ratio in order to modulate the height of the measured Bragg peak relative to the entrance value so that it is in agreement with the ionization chamber measurements. We propose to use a mixture for the sensitive volume consisting of the following weight fractions: 48% Gd₂O₂S:Tb, 12% (Zn, Cd)S:Ag and 40% optical cement.

Extensive use of models in pharmacology, in physiology and in radiotherapy raises some questions on the nature and utility of models in general and of compartmental models in particular. In this paper I will define in a simple and logical way a set of useful pharmacokinetic parameters and show how their estimation depends on the assumed model. A special problem arises when some parameters are not identifiable; in that case I will show how it is possible to determine a range for them. Two examples are used to illustrate how to compute the value of the identifiable parameters and the range of the non-identifiable ones, when the available experimental data are not sufficient to identify a model.

A single large dose of megavoltage x-rays delivered through a grid is currently being utilized by some centres for palliative radiotherapy treatments of large tumours. In this note, we investigate the dosimetry of grid therapy using two-dimensional film dosimetry and three-dimensional gel dosimetry. It is shown that the radiation dose is attenuated more rapidly with depth in a grid field than an open field, and that even shielded regions receive approximately 25% of the dose to the unshielded areas.

Two sets of phantoms have been used to calibrate a ¹⁰⁹Cd γ-ray induced K-XRF bone-lead measurement system. Both sets of phantoms are made of plaster of Paris, but the calibration lines are significantly different. This results in a significant difference for the derived concentrations of bone lead for the same person using these two sets of phantoms. This study shows that the different calibration lines are due to the different compositions of the phantoms, which can then be accounted for by adjusting the parameters related to the phantom composition in spectral analysis. Bone-lead concentrations for ten lead-exposed smelter workers were computed before and after analysis modification, and the results show that the bone-lead concentrations for the same person calculated from two sets of phantoms are not significantly different, only after the modifications are incorporated. Through these investigations, it was discovered that a common practice of setting the ratio of the calcium edge amplitude to the coherent scatter amplitude as a constant is only valid when all spectra are acquired at the same system resolution. When there is a change in the resolution between spectra, it has been determined that the ratio of the calcium edge amplitude to the coherent area should instead be used as the constant factor in the analysis program.

Inaccuracy in seed placement during permanent prostate implants may lead to significant dosimetric deviations from the intended plan. In two recent publications (Todor et al 2002 Phys. Med. Biol.47 2031–48, Todor et al 2003 Phys. Med. Biol.48 1153–71), methodology was described for identifying intraoperatively the positions of seeds already implanted, thus allowing re-optimization of the treatment plan and correcting for such seed misplacement. Seed reconstruction is performed using fluoroscopic images and an important (and non-trivial) component of this approach is the ability to accurately determine the position of the gantry relative to the treatment volume. We describe the methodology for acquiring this information, based on the known geometry of six markers attached to the ultrasound probe. This method does not require the C-arm unit to be isocentric and films can be taken with the gantry set at any arbitrary position. This is significant because the patient positioning on the operating table (in the lithotomy position) restricts the range of angles at which films can be taken to a quite narrow (typically ±10°) interval and, as a general rule, the closer the angles the larger the uncertainty in the seed location reconstruction along the direction from the x-ray source to the film.

The visible absorption spectra of Gafchromic XR type-T radiochromic film have been investigated to analyse the dosimetry characteristics of the film with visible light densitometers. Common densitometers can use photo-spectrometry, fluorescent light (broad-band visible), helium neon (632 nm), light emitting diode (LED) or other specific bandwidth spectra. The visible absorption spectra of this film when exposed to photon radiation show peaks at 676 nm and 618 nm at 2 Gy absorbed doses which shift to slightly lower wavelengths (662 nm and 612 nm at 8 Gy absorbed dose) at higher doses. This is similar to previous models of Gafchromic film such as MD-55-2 and HS but XR type-T also includes a large absorption at lower visible wavelengths due to 'yellow' dyes placed within the film to aid with visible recognition of the film exposure level. The yellow dye band pass is produced at approximately 520 nm to 550 nm and absorbs wavelengths lower than this value within the visible spectrum. This accounts for the colour change from yellow to brown through the added absorption in the red wavelengths with radiation exposure. The film produces a relatively high dose sensitivity with up to 0.25 OD units per Gy change at 672 nm at 100 kVp x-ray energy. Variations in dose sensitivity can be achieved by varying wavelength analysis.