Background: This is a retrospective study of patients treated with stereotactic body radiation therapy (SBRT) with the stereotactic body frame for centrally located lung tumours. The purpose was to investigate the doses to the different structures of the tracheobronchial tree and to relate these doses to the incidence of atelectasis. The goal was to estimate a tolerance dose for the bronchi. Materials: The patient material consisted of 71 patient treated at the Karolinska University Hospital for a total of 102 tumours between November 1993 and March 2004. The patient group consisted of 36 men and 35 women with a mean age at the treatment of 67 years (range 34-87). The group was a mixture of patients with primary lung cancer and pulmonary metastases. Methods: After rereading and reactivating the dose plans for the patients in the treatment planning system (TPS) the different tracheobronchial structures (trachea, right mainstem bronchus, right superior bronchus, right intermedius bronchus, right medius bronchus, right inferior bronchus, left mainstem bronchus, left superior bronchus, left intermedius bronchus, left inferior bronchus) were outlined. The dose distribution in each structure was calculated and a dose-volume histogram (DVH) was created. Patients were allocated to four groups, i.e. patients with right sided tumours (22), left sided tumours (14), mediastinal tumours (23) and bilateral tumours (10). After that the maximum and mean doses to all structures were analysed. An oncologist reviewed the medical records for the patients and especially looked for atelectasis. The doses were related to the incidence of atelectasis. Results and Conclusions: For the patient group with right sided tumours it seems like the maximum doses to the bronchi are higher for the patients with atelectasis in comparison with patients without atelectasis. A better correlation between atelectasis and maximum doses rather than mean doses was observed for these patients. At this moment the results are too preliminary, so it is not possible to suggest a tolerance dose for the bronchi. What can be said is that the maximum doses to the bronchi for patients with right sided tumours without atelectasis are below 250 Gy3 expressed in biologically equivalent dose (BED) with α/β=3Gy, while at least one bronchi structure in the atelectasis patients received a maximum dose above 250 Gy3.

Background: Stereotactic body radiation therapy (SBRT) is a relatively new method which has been employed e.g. in the treatment of liver tumours. Little dosimetric data has been published for SBRT in the liver. The aim of this retrospective study was to quantify the dosimetric parameters that influence the toxicity of the healthy liver, and the effect on the tumour, for SBRT to liver tumours in patients treated at Karolinska University Hospital. A comparison was made to relating published studies. Patients and Methods: The patient group to be studied were treated at Karolinska University Hospital for liver metastases with SBRT between July 1993 and October 2004. There were 64 patients treated with 71 treatment plans for 81 tumours. Differential dose volume histograms were collected for the clinical target volume (CTV), the planning target volume (PTV) and the liver excluding the CTV, from all dose plans. Since different fractionation schedules were used, the doses were normalised using the linear quadratic model, to be comparable. The doses to the uninvolved liver were evaluated with the mean liver dose, the Lyman-Kutcher-Burman (LKB) effective volume normal tissue complication probability (NTCP) model as well as the critical volume NTCP-model. A comparison was made to the studies of Dawson et al (2002) and Schefter et al (2005). The doses to the CTV were evaluated using the equivalent uniform dose tumour control probability (TCP) model, and related to target size and date of treatment. Results: When the mean doses to the uninvolved liver (the liver volume without tumour tissue) were compared to Dawson and Ten Haken’s results (2005), 20 treatments out of 71 were predicted to give a risk of radiation induced liver disease (RILD) higher than 50%. The effective volume calculations predicted that 18 treatments gave a risk of RILD higher than 50%, when compared to the results of Dawson et al (2002). According to the critical volume model and the parameter values of Schefter et al (2005), our data predict that 10 of the treatments gave a risk of liver function failure, to an unspecified risk level. Treatments of large tumours resulted in higher doses to the liver. The doses to the CTV showed that the maximum prescribed dose decreased with increasing CTV. Discussion and Conclusions: An evaluation of clinical data is necessary to make a full analysis of the treatments of this study. Such an analysis is planned for the future.

The accuracy and precision of measurements of pulsating flow obtained with phase contrast magnetic resonance imaging (PC MRI) was studied. Measurements were carried out using known flow rates through a phantom connected to a pump that created pulsation in the flow. Repeated measurements were made in both the negative and positive encoding direction, using both breath-hold and non breath hold sequences. The obtained data was analyzed using code written in MATLAB and also using the FLOW software that is offered by the manufacturer of the MRI system. A range of different flow velocities was scanned, and results show that the overall accuracy of the measurements is relatively good, with an average error of between 1.2% to 5.7% using the clinically employed flow calculation software. There is however indication of a systematic phase offset in the data that influences the measurements. The effect of the offset on the results depends on the direction of flow and the sequence used. The results also show the importance of properly selecting the area over which the flow rate is calculated.

The dose distribution around brachytherapy (BT) sources is characterized by steep dose gradients and an energy spectrum varying rapidly with depth in water around the source. These two properties make experimental verification of the dose distribution difficult, and put high demands on the dosimetry system in use regarding precision, size and energy dependence. The American Association of Physicists in Medicine (AAPM) recommends lithium fluoride (LiF) thermo-luminescence dosimetry (TLD) to be used for verification measurements, as it is the only dosimetry system meeting the requirements, but still the total combined uncertainty in dose-rate determination is as high as 7-9 % (1 σ). Lithium formate is a new dosimetry material that is less energy dependent than LiF, but more sensitive than the most common EPR (electron paramagnetic resonance) dosimetry material, alanine. In order to evaluate lithium formate EPR for BT dosimetry, dosimeters were produced for experimental dose determination around BT source 192Ir. The dosimeters were calibrated against an ionization chamber in a high energy photon beam. Dose to water was determined at 1, 3 and 5 cm radial distance from the source, which was stepped along a straight line in a PMMA phantom. The experiments were performed twice using 4 dosimeters per distance and experiment. Methods to correct for energy dependence were developed and evaluated. The uncertainty in measured dose was estimated. The experimental dose values agreed with the values from the treatment planning system with a maximum deviation of 3.3 %, and an average 1 σ uncertainty of 3 % at 3 and 5 cm and 5 % at 1cm. Uncertainty in radial distance from the source as well as source calibration were the dominating contributions to the total combined uncertainty. Lithium formate EPR has been shown to be a promising alternative to LiF TLD for BT dosimetry.

The technique of ESR-dosimetry and strategies for investigation of new materials as in regard to their applicability as ESR-dosimeters for radiotherapy has been reviewed. As an example six salts of formic and lactic acid has been evaluated. The applicability of the dosimeter has been judged by evaluating the tissue equivalence, radical yield, radical stability, spectral suitability, optimal readout parameters, dose response and sensitivity of the dosimetric system. Dependence of material characteristics and influence parameters has been analysed. The reviewed methods have been successfully used for evaluation of the new materials. Lithium formate has been shown to be a good candidate relative to the state of the art dosimeter of alanine. Using optimal readout parameters lithium formate has been shown to be nine times as sensitive but even at moderate settings lithium formate is more sensitive. The results for lithium formate are in accordance to those of previous studies. The signal intensity of sodium formate has also proved to be high but unfortunately the signal fades rapidly. Two new methods have been proposed as synthesis of the reviewed methods. The first allows flexible, effective and objective baseline correction of the ESR-spectrum. The second deals with dose response measurement by linear regression of the entire spectrum and was found to be successful in separating the spectral peaks of the induced radicals from the background signal.

The daily uncertainty concerning tumor localization is one of the major problems during the course of radiation therapy. Image guided-radiation therapy (IGRT) can be used to improve the localization and adjustment of the planning target volume. The aim of this work was to evaluate both the IGRT technique used for prostate cancer patients at the department of the Karolinska University Hospital and an alternative on-line adaptive radiation therapy (ART) method with an On-Board Imager (OBI). In the first part of the thesis 2D and 3D image registration with an OBI were compared. Ten prostate cancer patients were involved in the analyses. Two different statistical tests were used to determine significant systematic deviations between the two methods. The second part concerns daily dose verifications and dose plan reoptimization of one intensity modulated radiation therapy (IMRT) prostate cancer patient treated with IGRT. The study was based on cone-beam computed tomography (CBCT) images acquired at 6 different treatment fractions. The risk of developing late rectal and bladder toxicity was quantified using normal tissue complication probability (NTCP) calculations. Additional measurements on an Alderson phantom were performed to verify the accuracy of using the CBCT images for dose calculations. A statistically significant difference between the 2D-2D and the 3D-3D match applications could be observed in lateral and longitudinal direction. However, the effect differed among the patients. The phantom measurements showed small dose deviations between the CT and CBCT image, with a mean dose increase to the prostate and seminal vesicles (SV) of 2.5 %. The daily dose to the prostate and SV of the IMRT patient showed to be satisfactory. The daily dose to the rectum did not exceed the prescribed rectal dose except at one treatment fraction and the highest risk of developing late rectal toxicity was about 10.4 %. Large daily bladder dose variations were observed and at two treatment fractions the bladder dose restrictions were exceeded. With a reoptimization process of the dose plan, the dose to the bladder could be reduced while conserving the dose to the target. This work shows that for these specific patient cases appropriate doses to the prostate and SV can be delivered with IGRT. However, introducing a suitable ART method could lead to a reduction of inter-fractional rectal and bladder dose variations.

Dosimetric characteristics of a CVD single crystal diamond detector have been evaluated. Detector stability, linearity, optimal bias, temperature dependence, directional dependence, priming and pre-irradiation behaviour, depth dose curves and dose profiles were investigated. The optimal bias was determined to be 50 V. The detector stability measurement showed a too large variation for absolute dosimetry in a day to day measurement, but acceptable variation during one and the same day. The linearity constant, , in the relation between signal and dose rate, (Fowler 1966), was determined to 0.978 and 0.953 for two detectors. The sub-linearity was also observed in the depth dose curves and could be eliminated with a correction method. The diamond detector showed smaller temperature dependence than the EFD silicon diode. The directional dependency was, <1 %, up to at least ± 15˚ and therefore no angular correction is needed. A priming dose of 0.6 Gy was determined, which is considerably smaller than for existing detectors on the market. After pre-irradiation with electrons (8 and 18 MeV) a large and permanent desensitization of up to 31 % / 500 Gy was detected. This is in contradiction to what previous published articles claim. 15 MV photons also reduced the sensitivity of the detector, but no evidence that 5 MV photons do has been found. A 50 Gy dose of 180 MeV protons did not reduce the sensitivity either. The detector dose rate linearity was improved by electron pre-irradiation. The dose profile penumbras of the diamond detector were, for the most part, smaller than the RK ionization chamber, indicating a better spatial resolution.

In this thesis, a two-dimensional pixel-wise deconvolution method for partial volume correction (PVC) for combined Positron Emission Tomography and Computer Tomography (PET/CT) imaging has been developed. The method is based on Van Cittert's deconvolution algorithm and includes a noise reduction method based on adaptive smoothing and median filters. Furthermore, a technique to take into account the position dependent PET point spread function (PSF) and to reduce ringing artifacts is also described. The quantitative and qualitative performance of the proposed PVC algorithm was evaluated using phantom experiments with varying object size, background and noise level. PVC results in an increased activity recovery as well as image contrast enhancement. However, the quantitative performance of the algorithm is impaired by the presence of background activity and image noise. When applying the correction on clinical PET images, the result was an increase in standardized uptake values, up to 98% for small tumors in the lung. These results suggest that the PVC described in this work significantly improves activity recovery without producing excessive amount of ringing artifacts and noise amplification. The main limitations of the algorithm are the restriction to two dimensions and the lack of regularization constraints based on anatomical information from the co-registered CT images.

Det har tidigare uppmärksammats att magnetfältsnivåerna kan vara relativt höga i kuvöser, framförallt på grund av den värmebädd som barnet ligger på. I epidemiologiska studier av barnleukemi och association till magnetfältsexponering har man funnit en antydan till överrisk bland för tidigt födda barn som legat i inkubatorer med höga magnetfältsnivåer. Man har även funnit påverkan på hjärtfrekvensvariabilitet hos barn som vårdats i kuvöser och här misstänker man förhöjda magnetfältsnivåer som en möjlig förklaring. Syftet med denna studie var att genom noggranna mätningar kartlägga lågfrekventa magnetfält i och kring två sorters kuvöser (Dräger 8000 IC och Giraffe OmniBed) samt kringutrustning till dessa. Vidare har långtidsregistreringar av magnetfältet utförts i båda kuvöstyperna. I den äldre kuvösmodellen, Dräger 8000 IC, uppmättes värden mellan 1.0 och 8.1 µT vid kartläggning av magnetfältet inne i kuvösen. De högsta värdena var lokaliserade ovanför värmeelementet, en bit från centrum av kuvösen. Magnetfältet i den nyare modellen, Giraffe OmniBed, varierade vid kartläggningen mellan 0.2 och 5.8 µT, där de högsta värdena uppmättes mot ena kortändan av kuvösen. Medelvärdet från långtidsregistreringarna i kuvöserna beräknades till 1.9 µT för Dräger-kuvösen och 0.2 µT för Giraffe-kuvösen. Medelvärden från långtidsregistreringarna användes även till att beräkna en medeldos för sju veckors heltidsvård av barn i kuvös, uttryckt i mikroteslatimmar. Medeldosen för Dräger blev för huvudet 2.9∙103 µT∙h och för resten av kroppen 2.4∙103 µT∙h. För Giraffe blev medeldosen för huvudet 4.4∙102 µT∙h och för resten av kroppen 2.7∙102 µT∙h. Långtidsregistrering av magnetfält i hemmiljö mättes också i ett äldre hus och i en nyare lägenhet för jämförelse. Medeldosen för sju veckor i hemmiljö blev 10 – 60 µT∙h. Sammanfattningsvis kan man konstatera att magnetfälten i den nyare kuvösen (Giraffe OmniBed) var betydligt lägre än för den äldre kuvösmodellen (Dräger 8000 IC), men är fortfarande något förhöjda jämfört med normal hemmiljö. / It has previously been observed that the magnetic fields in infant incubators can be relatively high, particularly due to the heating bed the child is lying on. In epidemiologic studies of childhood leukaemia in association with exposure to magnetic fields, an inclination to excess risk has been found amongst premature children that have been lying in infant incubators with high magnetic field levels. Influence on the heart rate variability has also been found in children that have been treated in incubators, where elevated magnetic field levels are seen as a possible explanation. The purpose of this study was to map the magnetic field exposure in two different infant incubators (Dräger 8000 IC and Giraffe OmniBed) and the peripheral equipment. Furthermore, the magnetic field was logged over time in both incubator models. In the older model, Dräger 8000 IC, magnetic field levels between 1.0 µT and 8.1 µT were measured during the mapping of the magnetic field distribution over the bed. The highest value was localized above the heater, a short distance from the centre of the bed. The magnetic field in the newer model, Giraffe OmniBed, varied between 0.2 µT and 5.8 µT during the mapping, where the highest value was localized towards one of the short ends of the incubator. The mean value from the long term registration was calculated to 1.9 µT for the Dräger incubator and 0.2 µT for the Giraffe incubator. The average magnetic field level from the long-term registrations was used to calculate a dose for the baby, expressed in microtesla hours. The average dose for seven weeks of full time treatment in an incubator was 2.9∙103 µT∙h for the head and 2.4∙103 µT∙h for the remaining body in the Dräger incubator. Corresponding values for the Giraffe incubator was 4.4∙102 µT∙h for the head and 2.7∙102 µT∙h for the body. Long-time registration in home environment was also conducted in an older house and in a newer apartment. The average dose for seven full weeks was then 10 – 60 µT∙h. The conclusion from all this is that the magnetic field levels in the newer incubator model (Giraffe OmniBed) was significantly lower than in the older model (Dräger 8000 IC) but still higher than in an average home environment.

<p>Radiation quality is described by the RBE (relative biological effectiveness) that varies with the ionizing ability of the radiation. Microdosimetric quantities describe distributions of energy imparted to small volumes and can be related to RBE. This has made microdosimetry a powerful tool for radiation quality determinations in both radiation protection and radiation therapy. The variance-covariance method determines the dose-average of the distributions and has traditionally been used with two detectors to correct for beam intensity variations. Methods to separate dose components in mixed radiation fields and to correct for beam variations using only one detector have been developed in this thesis. Quality factor relations have been optimized for different neutron energies, and a new algorithm that takes single energy deposition events from densely ionizing radiation into account has been formulated. The variance-covariance technique and the new methodology have been shown to work well in the cosmic radiation field onboard aircraft, in the mixed photon and neutron fields in the nuclear industry and in pulsed fields around accelerators.</p><p>The method has also been used for radiation quality characterization in therapy beams. The biological damage is related to track-structure and ionization clusters and requires descriptions of the energy depositions in nanometre sized volumes. It was shown that both measurements and Monte Carlo simulation (condensed history and track-structure) are needed for a reliable nanodosimetric beam characterization. The combined experimental and simulated results indicate that the dose-mean of the energy imparted to an object in the nanometre region is related to the clinical RBE in neutron, proton and photon beams. The results suggest that the variance-covariance technique and the dose-average of the microdosimetric quantities could be well suited for describing radiation quality also in therapy beams.</p>