A method to establish the boundaries of the sensitive volume for a chosen detector to within 50µm (as specified by Elekta Instuments AB) was investigated and is presented in this project. The detector studied was fixed to a positioning system with possibility to move with sub micrometer increments, and scanned in a narrow photon field. The detectors used for the experiment were silicon diodes and a pair of diamond detectors. The silicon diodes showed great promise for future study; two radiotherapy silicon diodes and one electrical component silicon diode were used. The electrical component silicon diode produced a surprisingly sharp dose profile compared with the medical silicon diodes. The diamond detectors gave no stable results at all. As a radiation source 60Co proved most feasible, but a diagnostic x-ray source was also tested as well as a 99mTc source. These radiation sources were also examined with a modified Penelope code, i.e. Monte Carlo simulations. What became very obvious with the Monte Carlo simulations was the importance of the line up, which was never satisfactory. To limit the sensitive volume of these detectors to within the desired boundaries showed great difficulty and was not achieved in this project.

Positron-Emission-Tomography (PET) is a modern imaging technique in nuclear medicine providing quantitative 3D distribution of a radioactive tracer substance in the human body. The gamma-detector is the first link in the chain of components that constitutes a PET. It converts incoming radiation into optical light pulses, which are detected by photo multiplier tubes. Here the light is converted into electric pulses, to be further processed by the acquisition electronics. Improving detector sensitivity and resolution is of great value in research and in clinical practice. The focus of this work is to improve the detector to give it time-of-flight (TOF) capabilities, in order to further improve sensitivity, which in turn leads to increased image quality, faster scan time and/or reduced dose exposure for the patient. Image quality has improved over the years, but losses in image quality have been reported for heavy patients, due to increased attenuation, and more dispersed counts over a larger volume. Instrumentation limits are still significant in heavy patient images, but the incorporation of TOF information promises to alleviate some of the limitations. In order to improve the timing resolution of the detector fast photo-multipliers and a novel scheme to extract the event timing trigger from a detector by using the summed dynode signal were investigated. When designing new PET detectors, it is important to have detailed understanding and control of the light sharing mechanisms in the crystal arrays. Therefore it was necessary to perform optical simulations and single crystal light output measurements to derive a model for an LSO block detector. Another way to improve the image quality is to use the depth-of-interaction (DOI) of the gamma ray within the detector. It is shown that a multi-layer phoswich detector comprised of LSO with different decay times and TOF capability, combines the benefits of TOF and DOI in one detector, maximizing the effective sensitivity gain. / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 7: Submitted.

This thesis presents techniques constructed to aid the radiologists in detecting breast cancer, the second largest cause of cancer deaths for western women. In the first part of the thesis, a computer-aided detection (CAD) system constructed for the detection of stellate lesions is presented. Different segmentation methods and an attempt to incorporate contra-lateral information are evaluated. In the second part, a new method for evaluating such CAD systems is presented based on constructing credible regions for the number of false positive marks per image at a certain desired target sensitivity. This method shows that the resulting regions are rather wide and this explains some of the difficulties encountered by other researchers when trying to compare CAD algorithms on different data sets. In this part an attempt to model the clinical use of CAD as a second look is also made and it shows that applying CAD in sequence to the radiologist in a routine manner, without duly altering the decision criterion of the radiologist, might very well result in suboptimal operating points. Finally, in the third part two dual-energy imaging methods optimized for contrast-enhanced imaging of breast tumors are presented. The first is based on applying an electronic threshold to a photon-counting digital detector to discriminate between high- and low-energy photons. This allows simultaneous acquisition of the high- and low-energy images. The second method is based on the geometry of a scanned multi-slit system and also allows single-shot contrast-enhanced dual-energy mammography by filtering the x-ray beam that reaches different detector lines differently. / QC 20100819

Purpose: The aim of this thesis is to study the European (ESTRO/EAU/EORTC) and American (ABS) guidelines how to report the permanent seed implant and the most significant dosimetric parameters. It will also report on the permanent seed implant at Södersjukhuset, Karolinska University Hospital according to the guidelines. A large number of studies on pre- and post-implant dosimetry on permanent seed implants have recently been published but none is considered a standard. This makes it difficult, if not impossible, to compare data from different centres. The differences in reporting will also be discussed in this thesis. Another part of the study is to investigate how the morbidity correlates with the dose. The results in this report will give an overview of the experience at Södersjukhuset. Matherials and Methods: This study includes 198 patients who received implants between 2004-2007 with I-125 seeds under transperineal ultrasound at Södersjukhuset (to a prescribed dose of 145 Gy). The dose-planning system VariSeed 7.1 was used with an online connection to the ultrasound system with real-time verification. Dose constraints for the planning system are V(100)>99%, V(150)>60%, V(200)>25%, UrD(10)<130% and UrD(30)<125%. Outer and inner wall of rectum was outlined for 55 patients as recommended by ESTRO/EAU/EORTC and doses to rectum were also computed. Results: The median value for dosimetric parameters at Södersjukhuset, Karolinska University Hospital are for the prostate; D(90)=174Gy (153-194Gy), V(100)= 99% (93-100%), V(150)= 57% (40-74%), for the urethra; UrD(30) = 130% (112-147%), UrD(10) = 124% (107-142%) and for the rectum; RD2cc= 98Gy (73-128Gy), RD0.1cc=164Gy (119-240Gy), RV(100)=0.3cc (0.0-1.3cc), RV(150)=0.0cc (0.0-0.2cc). These values correspond to recommended data, except for the V(150) value. Regarding the clinically observed results, 3 patients had a relapse in their cancer, 2 patients had mild proctitis and 15 patients had urinary problems. Discussion and Conclusions: The significant dosimetric parameters for reporting according to ESTRO/EAU/EORTC and ABS for prostate are D90[Gy], V(100)[%] and V(150)[%], for urethra are D(30) and D(10), and for rectum RD2cc and RD0.1cc. These parameters consider as a minimum to use and they further recommend secondary parameters to report. Other authors have also recommended to report RV(100) and RV(150) for rectum. This study did not show any relationship between UrD(10), UrD(30) and urinary morbidity. According to the recommendations every patient should undergo a CT-based evaluation. Further investigations are needed on whether a post-implant CT-study is necessary for real-time implantation, as there is not enough published data on this aspect.

One of the most used irradiation techniques in modern radiation therapy is step-and-shoot IMRT. The accuracy of this technique when delivering complex dose distributions strongly depends on the size of the subfields. The aims of this study is to determine the minimum size of subfields that can be used efficiently in Step-and-Shoot IMRT, to investigate the validation process for beam delivery and treatment planning dose calculations, and to find recommendations for practical clinical implementations. Two different detectors, a CC04 ion chamber and a SFD stereotactic diode, have been used for measuring head scatter factors in air (Sc), total output factors (Scp) and dose profiles in water for a wide range of field sizes. The measurements were compared to calculations done with a pre-release version of the Nucletron MasterPlanTM v 3.1 treatment planning system that employs a novel, high resolution fluence modelling for both its pencil beam and collapsed cone dose calculation algorithms. Collimator settings were explicitly checked using FWHM film measurements with a build-up sheet of tungsten placed close to the treatment head to reduce the influence from lateral electron transport and geometrical penumbra. An analysis of the influence and sensitivity of Scp for small fields with respect to the linear accelerator source size and shape was also made. The measurements with the ionization chamber and the stereotactic diode showed good agreements with each other and with the treatment planning system calculations for field sizes larger than 2×2 cm2. For small field sizes, measurements with different detectors yielded different results. Calculations showed agreements with measurements with the smallest detector, provided careful field size calibration and commissioning of calculation parameters. Uncertainties in collimator settings and source characteristics were shown to yield large uncertainties in Scp for fields smaller than 2×2 cm2. The treatment planning system was found to properly handle small subfields but results were very sensitive to uncertainties in source size, as well as calibration and reproducibility of the collimator settings. Therefore if subfields smaller than 2×2 cm2 are to be used in IMRT extra care should be taken to determine the source characteristics and to calibrate the collimators. The volume of the detectors used for validation of such small fields and the loss of charged particle equilibrium conditions also have to be taken into consideration.

Patient dose in diagnostic radiology is usually expressed in terms of organ dose and effective dose. The latter is used as a measure of the stochastic risk. Determinations of these doses are obtained by measurements (Thermoluminescent dosemeters) or by calculations (Monte Carlo simulation). Conversion factors for the calculation of effective dose from dose-area product (DAP) values are commonly used to determine radiation dose in conventional x-ray imaging to realize radiation risks for different investigations, and for different ages. The exposure can easily be estimated by converting the DAP into an effective dose. The aim of this study is to determine the conversion factor in procedures by computing the ratio between effective dose and DAP for fluoroscopic cardiac procedures in adults and for conventional lung and urography examinations in children. Thermoluminescent dosemeters (TLD) were placed in an anthropomorphic phantom (Alderson Rando phantom) and child phantom (one year old) in order to measure the organ dose and compute the effective dose. A DAP meter was used to measure dose-area product. MC calculations of radiation transport in mathematical anthropomorphic phantoms were used to obtain the effective dose for the same conditions with DAP as input data. The deviation between the measured and calculated data was less than 10 %. The conversion factor for cardiac procedures varies between 0.19 mSvGy-1 cm-2 and 0.18 mSvGy-1 cm-2, for TLD respective MC. For paediatric simulation of a one year old phantom the average conversion factor for urography was 1.34 mSvGy-1 cm-2 and 1,48 mSvGy-1cm-2 for TLD respective MC. This conversion factor will decrease to 1.07 mSvGy-1 cm-2 using the TLD method, if the new ICRP (ICRP Publication 103) weighting factors were used to calculate the effective dose. For lung investigations, the conversion factor for children was 1.75 mSvGy-1 cm-2 using TLD, while this value was 1.62 mSvGy-1 cm-2 using MC simulation. The conversion value increased to 2.02 mSvGy-1 cm-2 using ICRP’s new recommendation for tissue weighting factors and child phantom.

Abstract   Background Semi-automated segmentation using deformable registration of atlases consisting of pre-segmented patient images can facilitate the tedious task of delineating structures and organs in patients subjected to radiotherapy planning. However, a generic atlas based on a single patient may not function well enough due to the anatomical variation between patients. Fusion of segmentation proposals from multiple atlases has the potential to provide a better segmentation due to a more complete representation of the anatomical variation. Purpose The main goal of the present study was to investigate potential operator timesavings from use of atlas-based segmentation compared to manual segmentation of patients with prostate cancer. It was also anticipated that, and evaluated if, the use of semi-automated segmentation workflows would reduce the operator dependent variations in delineation. Materials and Methods A commercial atlas-based segmentation software (VelocityAI from Nucletron AB) was used with several atlases of consistently, protocol based, delineated CT images to create multiple-atlas segmentation proposals through deformable registration. The atlas that was considered most representative was selected to construct single generic atlas segmentation proposals. For fusion of the multiple-atlas segmentations an in-house developed algorithm, which includes information of local registration success was used in a MATLAB-environment[1]. The algorithm used weighted distance map calculations where weights represent probabilities of improving the segmentation results. Based on results from Sjöberg and Ahnesjö the probabilities were estimated using the cross correlation image similarity measure evaluated over a region within a certain distance from the segmentation. 10 patients were included in the study. Each patient was delineated three times, (a) manually by the radiation oncologist, (b) with a generic single-atlas segmentation and (c) with a fusion of multiple-atlas segmentations. For the methods (b) and (c) the radiation oncologist corrected the proposed segmentations blindly without using the result from method (a) as reference. The total number of atlases used for case (c) was 15. The operator time spent by the radiation oncologist was recorded separately for each method. In addition a grading was used to score how helpful the segmentation proposals were for the delineations. The Dice Similarity Coefficient, the Hausdorff distance and the segmented volumes were used to evaluate the similarity between the delineated structures and organs. Results An average time reduction of 26% was found when the radiation oncologist corrected the multiple atlas-based segmentation proposals as compared to manual segmentations. Due to more accurate segmentations and more time saved, segmentation with fused multiple-atlases (c) was superior to the generic single-atlas (b) method, which showed a time reduction of 17%. Hints of an affected intra- and inter-operator variability were seen. Conclusions Atlas-based segmentation saves time for the radiation oncologist but the segmentation proposals always need editing to be approved for dose planning. The atlases, the fusion of these and the software implementation needs to be improved for optimal results and to extend the clinically usefulness.

Background Semi-automated segmentation using deformable registration of atlases consisting of pre-segmented patient images can facilitate the tedious task of delineating structures and organs in patients subjected to radiotherapy planning. However, a generic atlas based on a single patient may not function well enough due to the anatomical variation between patients. Fusion of segmentation proposals from multiple atlases has the potential to provide a better segmentation due to a more complete representation of the anatomical variation. Purpose The main goal of the study was to investigate potential operator timesaving from editing of atlas-based segmentation compared to manual segmentation for head & neck cancer. Materials and Methods A commercial atlas-based segmentation software (VelocityAI from Nucletron AB) was used together with several expert generated and protocol-based atlases of delineated CT images to create multiple atlas segmentations through deformable registration. The atlas that was considered most universal was selected to construct single atlas segmentation proposals. For fusion of the multiple atlas segmentations an in-house developed algorithm, including information of local registration success was used in a MATLAB-environment1. The algorithm uses weighted distance map calculations where weights represent probabilities of improving the segmentation results. Based on previous results1 the probabilities were estimated using the cross correlation image similarity measure evaluated over a region within a certain distance from the segmentation. Ten patients were incorporated in the study. Each patient was delineated three times, (a) manually by the radiation oncologist, (b) with a single atlas segmentation and (c) with a fusion of multiple atlas segmentations. For the methods (b) and (c) the radiation oncologist corrected the proposed segmentations blindly without using the result from method (a) as reference. For case (c) a total number of 11 atlas segmentations were used. The time spent for segmenting or editing the segmentation proposals by the radiation oncologist was recorded separately for each method and each individual ROI. In addition a grading was used to score how helpful the candidate segmentation proposals were for the structure delineations. The Dice Similarity Coefficient, the Hausdorff distance and the volume were used to evaluate the similarity between the delineated structures. Results The results show a time reduction in the order of 40% when the radiation oncologist only has to correct the multiple atlas-based segmentation proposal compared to manual segmentation. When using single atlas the corresponding figure is 21%. Conclusions Using atlas-based segmentation can reduce the time needed for delineation in the head and neck area of patients admitted for radiotherapy. 1C. Sjöberg and A. Ahnesjö, Evaluation of atlas-based segmentation using probabilistic weighted distance maps, Manuscript, Uppsala University, 2011 / Bakgrund Atlasbaserad, semiautomatisk segmentering skulle kunna användas för att underlätta den för onkologen tidskrävande uppgiften med att manuellt segmentera strukturer och organ i patienter vid behandlingsplanering inför strålbehandling. Tidigare segmenterade atlaspatienter ger med hjälp av deformeringsalgoritmer segmenteringsförslag för strukturer i den aktuella patienten. Dessa kan sedan kontrolleras och editeras av onkologen med en tidsbesparing gentemot manuell segmentering som följd. En atlas som baserats på en enstaka individ (singelatlas) kan dock ha begränsningar när det gäller att täcka de anatomiska variationer som finns mellan olika patienter. Därför har metoder med fusionering av multipla segmenteringsförslag från en databas bestående av ett antal sedan tidigare segmenterade patienter (fusionerad multipelatlas) potential att ge ett bättre segmenteringsresultat. Syfte Huvudsyftet med arbetet var att undersöka de möjliga tidsbesparingar för onkologen som kan åstadkommas när editering av atlasbaserad segmentering används vid planering inför strålbehandling i huvud- och halsområdet istället för manuell segmentering Material och metoder En kommersiell, atlasbaserad segmenteringsprogramvara (VelocityAI från Nucletron AB) användes i studien. Genom att låta en erfaren onkolog segmentera ett antal CT-studier (11 st) enligt ett vedertaget protokoll skapades en databas av atlaser som sedan, via deformerbara registreringar, kunde generera lika många segmenteringsförslag för en nytillkommen patient. Den enskilda atlas som ansågs mest representativ valdes till att framställa segmenteringsförslaget för metoden med singelatlas. Till metoden med fusionerade multipla atlaser användes en lokalt utvecklad MATLAB-algoritm baserad på viktade    distansmappar. Vikterna representerar sannolikheten för förbättrat segmenteringsresultat och baseras på tidigare resultat1 där sannolikheterna bestämts utifrån en beräkning av likheterna mellan bilderna i ett visst område från den specifika segmenteringen. Tio patienter har inkluderats i studien. Varje patient segmenterades tre gånger, (a) manuellt, (b) med singelatlas och (c) med fusionerade multipla atlaser. För metoderna (b) och (c) editerades sedan segmenteringsförslagen av onkologen utan att denne fick använda resultatet från metod (a) som referens. För fallet med fusionerade multipla atlaser, (c), användes databasen med 11 atlaser. Tiden onkologen behövde för segmentering respektive editering av segmenteringsförslaget uppmättes i varje enskilt fall för jämförelse. Onkologen fick även göra en bedömning av hur hjälpsamt segmenteringsförslaget var i samband med editeringen. För utvärdering av resultaten användes Dice’s similaritetskoefficient, Hausdorff’s distansmått samt strukturernas volym. Resultat Resultaten visar på att en tidsbesparing i storleksordningen 40 % är rimlig när onkologen editerar förslag från fusioneringen av multipla atlassegmenteringar i jämförelse med manuell segmentering. Vid användning av singelatlas är motsvarande siffra 21 %. Slutsatser Användandet av atlasbaserad segmentering kan reducera tidsåtgången för segmentering av patienter inför strålbehandling i huvud-halsområdet. 1C. Sjöberg and A. Ahnesjö, Evaluation of atlas-based segmentation using probabilistic weighted distance maps, Manuscript, Uppsala University, 2011

Physicians often utilize different imaging techniques to provide clear, visual information about internal parts of the patient. Since the different imaging modalities give different types of information, the combination of them serves as a powerful tool while determining the diagnosis, planning of treatment or during therapy follow-up. To simplify the interpretation of the image information, image registration is often used. The goal of the registration is to put different images in a common coordinate system. It is essential that the registration between the images is accurate. Normalized Mutual Information (NMI) is a metric that quantifies the conformity between images. Even though NMI is a robust method it is often dominated by large structures as the external contour of the patient as well as by the structures of the bones. The prostate is an organ that does not have a fixed position relative to the other organs and host small amounts of image information. The accuracy of the registration is therefore limited with respect to the prostate when using the whole image volume. This master thesis investigates the possibility to restrict the part of the image used for registration to a small volume around the prostate with goal to receive a better registration of the prostate than if full sized images are used. A registration program, utilizing NMI, was written and optimized in MatLab. Four Magnetic Resonance (MR) series and one Computed Tomographic (CT) series where taken over the pelvic area of five patients with the diagnosis prostate cancer. The prostate were delineated by a physician. By adding margin to the delineations five different sized Regions of Interest (ROI) where created.  The smallest ROI precisely covered the prostate while the largest covered the whole image. The deviation in Center of Mass (CoM) between the images and the Percentage Volume Overlap (PVO) were calculated and used as a measure of alignment. The registrations performed with sub-volumes showed an improvement compared to those that used full-volume while registering a MR image to another MR image. In one third of the cases a 2 cm margin to the prostate is preferable. A 3 cm margin is the most favorable option in another third of the cases. The use of sub-volumes to register MR images to CT series turned out to be unpredictable with poor accuracy. Full sized image registration between two MR image pairs has a high precision but, due to the motion of the prostate, poor accuracy. As a result of the high information content in the MR images both high precision as well as high accuracy can be achieved by the use of sub-volume registration. CT images do not contain the same amount of image information around the prostate and the sub-volume based registrations between MR and CT images are hence inconsistent with a low precision.  

The air kerma area product PKA is an important quantity used by hospital physicists in quality assurance and optimization processes in diagnostic radiology and is recommended by national authorities for setting of diagnostic reference levels. PKA can be measured using a transmission ionization chamber (kerma area product (KAP) meter) mounted on the collimator housing. Its signal QKAP must be calibrated to give values of PKA. The objective of this thesis is to analyze the factors influencing the accuracy of the calibration coefficients k= PKA/QKAP and of reported PKA-values. Due to attenuation and scatter in the KAP-meter and presence of extra-focal radiation, values of PKA depend on the choice of integration area A and the distance of the reference plane from the focal spot yielding values of PKA that may differ by as much as 23% depending on this choice. The two extremes correspond to (1) PKA=PKA,o integrated over the exit surface of the KAP-meter resulting in geometry independent calibration coefficients and (2) PKA=PKA,Anom integrated over the nominal beam area in the patient entrance plane resulting in geometry dependent calibration coefficients. Three calibration methods are analysed. Method 1 aims at determine PKA,Anom, for clinical use at the patient entrance plane. At standard laboratories, the method is used to calibrate with respect to radiation incident on the KAP-meter. Problems with extra-focal and scattered radiation are then avoided resulting in calibration coefficients with low standard uncertainty (±1.5 %, coverage factor 2). Method 2 was designed in this work to approach determination of PKA,o using thermoluminescent detectors to monitor contributions from extra-focal radiation and account for the heel effect. The uncertainty in derived calibration coefficients was ± 3% (coverage factor 2). Method 3 uses a Master KAP-meter calibrated at a standard laboratory for incident radiation to calibrate clinical KAP-meters. It has potential to become the standard method in the future replacing the tedious method 2 for calibrations aiming at determination of PKA,o. Commercially available KAP-meters use conducting layers of indium oxide causing a strong energy dependence of their calibration coefficients. This dependence is investigated using Monte Carlo simulations and measurements. It may introduce substantial uncertainties in reported PKA– values since calibration coefficients as obtained from standard laboratories are often available only at one filtration (2.5 mm Al) as function of tube voltage or HVL. This is not sufficient since higher filtrations are commonly used in practice, including filters of Cu. In extreme cases, calibration coefficients for the same value of HVL but using different tube voltages and filtrations can deviate by as much as 30%. If standardised calibration methods are not used and choice of calibration coefficients not carefully chosen with respect to beam quality, the total uncertainty in reported PKA–values may be as large as 40-45%. Conversion of PKA-values to risk related quantities is briefly discussed. The large energy dependence of the conversion coefficients, ε/PKA, for determination of energy imparted,ε, to the patient reduces to a lower energy dependence of calibration coefficients CQ,ε = ε/QKAP for determination of ε from the KAP-meter signal.