Sven Bäck

Real-time optical-fibre luminescence dosimetry for radiotherapy: physical characteristics and applications in photon beams

A new optical-fibre radiation dosimeter system, based on radioluminescence and optically stimulated luminescence from carbon-doped aluminium oxide, was developed and tested in clinical photon beams. This prototype offers several features, such as a small detector (1 x 1 x 2 mm3), high sensitivity, real-time read-out and the ability to measure both dose rate and absorbed dose. The measurements describing reproducibility and output dependence on dose rate, field size and energy all had standard deviations smaller than 1%. The signal variation with the angle of incidence was smaller than 2% (1 SD). Measurements performed in clinical situations suggest the potential of using this real-time system for in vivo dosimetry in radiotherapy.

Dose resolution in radiotherapy polymer gel dosimetry: effect of echo spacing in MRI pulse sequence

In polymer gel dosimetry using magnetic resonance imaging, the uncertainty in absorbed dose is dependent on the experimental determination of T2. The concept of dose resolution (Dpdelta) of polymer gel dosimeters is developed and applied to the uncertainty in dose related to the uncertainty in T2 from a range of T4 encountered in polymer gel dosimetry. Dpdelta is defined as the minimal separation between two absorbed doses such that they may be distinguished with a given level of confidence, p. The minimum detectable dose (MDD) is Dpdelta as the dose approaches zero. Dpdelta and the minimum detectable dose both give a quantifiable indication of the likely practical limitations and usefulness of the dosimeter. Dpdelta of a polyacrylamide polymer gel dosimeter is presented for customized 32-echo and standard multiple-spin-echo sequences on a clinical MRI scanner. In evaluating uncertainties in T2, a parameter of particular significance in the pulse sequence is the echo spacing (ES). For optimal results, ES should be selected to minimize Dpdelta over a range of doses of interest in polymer gel dosimetry.

MAGIC-type polymer gel for three-dimensional dosimetry: Intensity-modulated radiation therapy verification

A new type of polymer gel dosimeter, which responds well to absorbed dose even when manufactured in the presence of normal levels of oxygen, was recently described by Fong et al. [Phys. Med. Biol. 46, 3105-3113 (2001)] and referred to by the acronym MAGIC. The aim of this study was to investigate the feasibility of using this new type of gel for intensity-modulated radiation therapy (IMRT) verification. Gel manufacturing was carried out in room atmosphere under normal levels of oxygen. IMRT inverse treatment planning was performed using the Helios software. The gel was irradiated using a linear accelerator equipped with a dynamic multileaf collimator, and intensity modulation was achieved using sliding window technique. The response to absorbed dose was evaluated using magnetic resonance imaging. Measured and calculated dose distributions were compared with regard to in-plane isodoses and dose volume histograms. In addition, the spatial and dosimetric accuracy was evaluated using the gamma formalism. Good agreement between calculated and measured data was obtained. In the isocenter plane, the 70% and 90% isodoses acquired using the different methods are mostly within 2 mm, with up to 3 mm disagreement at isolated points. For the planning target volume (PTV), the calculated mean relative dose was 96.8 +/- 2.5% (1 SD) and the measured relative mean dose was 98.6 +/- 2.2%. Corresponding data for an organ at risk was 34.4 +/- 0.9% and 32.7 +/- 0.7%, respectively. The gamma criterion (3 mm spatial/3% dose deviation) was fulfilled for 94% of the pixels in the target region. Discrepancies were found in hot spots the upper and lower parts of the PTV, where the measured dose was up to 11% higher than calculated. This was attributed to sub optimal scatter kernels used in the treatment planning system dose calculations. Our results indicate great potential for IMRT verification using MAGIC-type polymer gel.

Linear energy transfer dependence of a normoxic polymer gel dosimeter investigated using proton beam absorbed dose measurements

Three-dimensional dosimetry with good spatial resolution can be performed using polymer gel dosimetry, which has been investigated for dosimetry of different types of particles. However, there are only sparse data concerning the influence of the linear energy transfer (LET) properties of the radiation on the gel absorbed dose response. The purpose of this study was to investigate possible LET dependence for a polymer gel dosimeter using proton beam absorbed dose measurements. Polymer gel containing the antioxidant tetrakis(hydroxymethyl)phosphonium (THP) was irradiated with 133 MeV monoenergetic protons, and the gel absorbed dose response was evaluated using MRI. The LET distribution for a monoenergetic proton beam was calculated as a function of depth using the Monte Carlo code PETRA. There was a steep increase in the Monte Carlo calculated LET starting at the depth corresponding to the front edge of the Bragg peak. This increase was closely followed by a decrease in the relative detector sensitivity (Srel = Dgel/Ddiode), indicating that the response of the polymer gel detector was dependent on LET. The relative sensitivity was 0.8 at the Bragg peak, and reached its minimum value at the end of the proton range. No significant effects in the detector response were observed for LET < 4.9 keV microm(-1), thus indicating that the behaviour of the polymer gel dosimeter would not be altered for the range of LET values expected in the case of photons or electrons in a clinical range of energies.

Modelling of post-irradiation events in polymer gel dosimeters

The nuclear magnetic resonance (NMR) spin-spin relaxation time (T2) is related to the radiation-dependent concentration of polymer formed in polymer gel dosimeters manufactured from monomers in an aqueous gelatin matrix. Changes in T2 with time post-irradiation have been reported in the literature but their nature is not fully understood. We investigated those changes with time after irradiation using FT-Raman spectroscopy and the precise determination of T2 at high magnetic field in a polymer gel dosimeter. A model of fast exchange of magnetization taking into account ongoing gelation and strengthening of the gelatin matrix as well as the polymerization of the monomers with time is presented. Published data on the changes of T2 in gelatin gels as a function of post-manufacture time are used and fitted closely by the model presented. The same set of parameters characterizing the variations of T2 in gelatin gels and the increasing concentration of polymer determined from FT-Raman spectroscopy are used successfully in the modelling of irradiated polymer gel dosimeters. Minimal variations in T2 in an irradiated PAG dosimeter are observed after 13 h.

Ferrous sulphate gel dosimetry and MRI for proton beam dose measurements.

Ferrous sulphate gel dosimetry has the potential for measurement of absorbed dose distributions in proton therapy. The chemical properties of the gel are altered according to the radiation dose and these changes can be evaluated in three dimensions using MRI. The purpose of this work was to investigate the properties of a ferrous gel used with clinical proton beams. The gel was irradiated with both monoenergetic and range-modulated proton beams. It was then evaluated using MRI. The depth dose by means of the 1/T1 distribution was studied and compared with data from a plane-parallel plate ionization chamber. 1/T1 was shown to be proportional to the dose at a mean proton energy of approximately 90 MeV. The dose response was no different from that obtained using photon beams. However, on normalization at the entrance, the relative 1/T1 at the Bragg peak was 15-20% lower than the corresponding ionization chamber data for the monoenergetic proton beam. Better agreement was found for the modulated beam, but with significant differences close to the distal edge of the 1/T1 distribution. The change in sensitivity with depth was explained by means of a linear energy transfer dependence. This property was further studied using Monte Carlo methods.

RapidArc treatment verification in 3D using polymer gel dosimetry and Monte Carlo simulation

The aim of this study was to verify the advanced inhomogeneous dose distribution produced by a volumetric arc therapy technique (RapidArc) using 3D gel measurements and Monte Carlo (MC) simulations. The TPS (treatment planning system)-calculated dose distribution was compared with gel measurements and MC simulations, thus investigating any discrepancy between the planned dose delivery and the actual delivery. Additionally, the reproducibility of the delivery was investigated using repeated gel measurements. A prostate treatment plan was delivered to a 1.3 liter nPAG gel phantom using one single arc rotation and a target dose of 3.3 Gy. Magnetic resonance imaging of the gel was carried out using a 1.5 T scanner. The MC dose distributions were calculated using the VIMC-Arc code. The relative absorbed dose differences were calculated voxel-by-voxel, within the volume enclosed by the 90% isodose surface (VOI(90)), for the TPS versus gel and TPS versus MC. The differences between the verification methods, MC versus gel, and between two repeated gel measurements were investigated in the same way. For all volume comparisons, the mean value was within 1% and the standard deviation of the differences was within 2.5% (1SD). A 3D gamma analysis between the dose matrices were carried out using gamma criteria 3%/3 mm and 5%/5 mm (% dose difference and mm distance to agreement) within the volume enclosed by the 50% isodose surface (VOI(50)) and the 90% isodose surface (VOI(90)), respectively. All comparisons resulted in very high pass rates. More than 95% of the TPS points were within 3%/3 mm of both the gel measurement and MC simulation, both inside VOI(50) and VOI(90). Additionally, the repeated gel measurements showed excellent consistency, indicating reproducible delivery. Using MC simulations and gel measurements, this verification study successfully demonstrated that the RapidArc plan was both accurately calculated and delivered as planned.

Radiation enteropathy and leucocyte-endothelial cell reactions in a refined small bowel model

BackgroundLeucocyte recruitment and inflammation are key features of high dose radiation-induced tissue injury. The inflammatory response in the gut may be more pronounced following radiotherapy due to its high bacterial load in comparison to the response in other organs. We designed a model to enable us to study the effects of radiation on leucocyte-endothelium interactions and on intestinal microflora in the murine ileum. This model enables us to study specifically the local effects of radiation therapy.MethodA midline laparotomy was performed in male C57/Bl6 mice and a five-centimetre segment of ileum is irradiated using the chamber. Leucocyte responses (rolling and adhesion) were then analysed in ileal venules 2 – 48 hours after high dose irradiation, made possible by an inverted approach using intravital fluorescence microscopy. Furthermore, intestinal microflora, myeloperoxidase (MPO) and cell histology were analysed.ResultsThe highest and most reproducible increase in leucocyte rolling was exhibited 2 hours after high dose irradiation whereas leucocyte adhesion was greatest after 16 hours. Radiation reduced the intestinal microflora count compared to sham animals with a significant decrease in the aerobic count after 2 hours of radiation. Further, the total aerobic counts, Enterobacteriaceae and Lactobacillus decreased significantly after 16 hours. In the radiation groups, the bacterial count showed a progressive increase from 2 to 24 hours after radiation.ConclusionThis study presents a refinement of a previous method of examining mechanisms of radiation enteropathy, and a new approach at investigating radiation induced leucocyte responses in the ileal microcirculation. Radiation induced maximum leucocyte rolling at 2 hours and adhesion peaked at 16 hours. It also reduces the microflora count, which then starts to increase steadily afterwards. This model may be instrumental in developing strategies against pathological recruitment of leucocytes and changes in intestinal microflora in the small bowel after radiotherapy.

Local radiotherapy of exposed murine small bowel: Apoptosis and inflammation

BackgroundPreoperative radiotherapy of the pelvic abdomen presents with complications mostly affecting the small bowel. The aim of this study was to define the features of early radiation-induced injury on small bowel.Methods54 mice were divided into two groups (36 irradiated and 18 sham irradiated). Animals were placed on a special frame and (in the radiated group) the exteriorized segment of ileum was subjected to a single absorbed dose of 19 or 38 Gy radiation using 6 MV high energy photons. Specimens were collected for histology, immunohistochemistry (IHC) and ELISA analysis after 2, 24 and 48 hours. Venous blood was collected for systemic leucocyte count in a Burker chamber.ResultsHistology demonstrated progressive infiltration of inflammatory cells with cryptitis and increased apoptosis. MIP-2 (macrophage inflammatory protein) concentration was significantly increased in irradiated animals up to 48 hours. No significant differences were observed in IL-10 (interleukin) and TNF-α (tumour necrosis factor) levels. IHC with CD45 showed a significant increase at 2 hours of infiltrating leucocytes and lymphocytes after irradiation followed by progressive decrease with time. Caspase-3 expression increased significantly in a dose dependent trend in both irradiated groups up to 48 hours.ConclusionAcute small bowel injury caused by local irradiation is characterised by increased apoptosis of crypt epithelial cells and by lymphocyte infiltration of the underlying tissue. The severity of histological changes tends to be dose dependent and may affect the course of tissue damage.

Dosimetric verification of breathing adapted radiotherapy using polymer gel

In radiation therapy patient movement caused by respiration can be a major challenge to the ambition to deliver a high absorbed dose to the target volume while minimizing the dose to normal tissues. Large respiratory motion requires increased margins, which implies an increased risk of morbidity from late toxicity. It is therefore important to take respiratory motion into account when treating targets in the thorax region. The aim of this study was to investigate the feasibility of using a 3D gel dosimeter for dose verification of breathing adapted radiotherapy