Masteruppsatser / Medicinsk strålningsvetenskap
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Item Accumulation of 63Ni, 106Ru and 125Sb in phytoplankton(2022-08-22) Ali, Yusuf; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperBackground: Nuclear Power Plants (NPPs) release small amounts of radionuclides which contribute with a low radiation dose to the environment as well as humans and animals. In this context, marine ecosystems are critical, since most NPPs in Sweden are located by the sea. The Concentration Factor (CF) is a model parame ter that is used to study the transport and uptake of these radionuclides. However, the published CF values for many elements range across several orders of magnitude. Aims: The aim of this project was to experimentally determine phytoplankton CF for some of the radionuclides released from various nuclear facilities in Sweden, in order to improve their uncertainties and to enable a more realistic dose assessment. The elements analyzed in this study were nickel, ruthenium and antimony. Materials and Methods: Seawater samples from two separate stations (Anholt E and Karlsödjupet) near NPP in Sweden, were collected by SMHI. Phytoplankton were then cultured in these seawater samples with addition of relevant radionuclides and nutrients. The cultures were filtered when the phytoplankton concentration reached around 1·106 cells/mL. A HPGe-detector was used to measure the activity of the filtrates and filters from 106Ru and 125Sb. Likewise, a liquid scintillation counter (LSC) was used to measure the activity of the samples containing 63Ni. Results and Discussion: The mean calculated phytoplankton dry weight were 33 ± 8 and 26 ± 4 pg for Anholt E and Karlsödjupet, respectively. The phytoplankton growth rates and dry weights in the different seawater samples were not significantly different. The mean calculated phytoplankton CF for the respective elements were as follows: 4000 and 3800 L/kg for Ni; 15000 and 20000 L/kg for Ru and 250 and 700 L/kg for Sb. The obtained values are in good agreement with published data. Conclusion: The phytoplankton CF for the elements studied were as follows: 4000 and 3800 L/kg for Ni; 15000 and 20000 L/kg for Ru and 250 and 700 L/kg for Sb. The CF obtained in this study, had a smaller variation compared to the literature data, thus the uncertainties in the CF have been improved considerably. These CF will therefore provide a more realistic dose assessment. Keywords: concentration factor (CF), phytoplankton, phaeodactylum tricornutum, uptake, radioactive releases, nickel, ruthenium, antimony, gamma spectroscopy, liquid scintillation counting.Item Age-Related Late Effects in Rat Thyroids After Internal 131I Exposure(2024-09-23) Parling, Ludwig; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperThe Chernobyl nuclear accident left many questions in its wake. One of these questions was why children affected by the radioactive fallout seemed to have a higher incidence of thyroid cancer compared with adults in the same area. The purpose of this study was to compare proteomic changes in internally 131I irradiated rats of two age groups, one young and one adult. This was performed through analysis of fresh frozen thyroid tissue from a previous animal study where young and adult rats were exposed internally to various amounts of 131I. Analysis of the rats’ thyroid proteome was achieved through liquid chromatography tandem mass spectrometry and analysed with Welch’s t-test with Benjamini-Hochberg correction. Protein functional analysis and gene ontology (GO) term analysis were done with UniProt. Large variations in mainly the control group’s data made comparison at the group level difficult. One protein’s relative abundance, TRXR3, was found significantly changed in the young population at 0.5 kBq. TRXR3 is the rat equivalent to the TRXR3 found in humans and is a part of cellular oxidant detoxification and redox homeostasis. This would imply that oxidative stress had taken place, but the lack of other markers makes it difficult to draw a solid conclusion. Due to the lacking appearance at other doses, TRXR3 was not considered a good candidate biomarker for 131I radiation exposure or absorbed doseItem Anatomical segmentation of the human brain: comparative assessment of two automatic methods(2023-08-22) von Dorrien, Carl; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperMagnetic Resonance Imaging (MRI) is a robust and versatile imaging modality and an integral component of a lot of studies, especially when performing quantitative analysis. MRI is the preferred method of imaging the brain because of its excellent soft tissue contrast. Accurate segmentation of the brain into its anatomical regions enables accurate quantitative analysis of the brain. Three software programs that perform automatic anatomical segmentation of the human brain are FreeSurfer, FastSurfer and MAPER. The purpose of this study was to use FreeSurfer as a baseline, and to investigate how well FastSurfer and MAPER segmentations conform to FreeSurfer’s outputs on the same dataset. 185 T1-weighted 3D MR images from the IXI Dataset were segmented using FreeSurfer, FastSurfer, and MAPER. Default training checkpoints were used for FastSurfer and FreeSurfer outputs of the IXI Dataset, along with corresponding brain MR images, were used as a source atlas for MAPER. The FastSurfer and MAPER segmentations were then compared with the FreeSurfer segmentations using the Jaccard Similarity Coefficient. MAPER performed better than FastSurfer at replicating FreeSurfer-conform outputs for subcortical regions. MAPER and FastSurfer performed similarly for the cortical regions.Item Apoptosis induction in breast cancer cells after radiotherapy and potential radiosensitizers(2023-06-27) Simonsson, Klara; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperBackground. Today breast cancer is the foremost cancer death type amongst women around the world. At present some of the toughest challenges in the clinic is recurrent, radioresistant breast cancer, and metastatic breast cancer where low cure rates are observed after surgery and radiotherapy. One way to possibly increase survival rates, is combining radiotherapy and systemic therapy that doubles as a radiosensitizer. The aim of this thesis was to identify pathways that increase radiosensitivity in breast cancer cells after combination treatment with external irradiation and anti-cancer drugs, specifically through increased apoptosis. Method. Three different human breast cancer cell lines were cultured: MCF-7, MDA-MB-453 and HCC-1806. A dose-response study with irradiation was performed on the cells to determine a radiation absorbed dose and time-point after irradiation for the following combination treatment. Lastly, cells were treated with anti-cancer drugs +/– irradiation, and then stained with the fluorescent dyes Annexin V-DyLight 650 (apoptosis marker) and Hoechst 33342 (cell viability marker) whereafter flow cytometry was performed. Results. A dose and time dependency was observed in the dose-response study. In total, 29 of 31 anti-cancer drugs exhibited a synergistic effect with radiation on any cell line at any concentration. The drugs birinapant (with target IAP) and ganetespib (with target HSP90) showed statistically significant radiosensitizing effects on all three cell lines. Conclusions. Possible radiosensitizing targets for all three cell types included in this study are HSP90 and IAP. In addition, BH3 mimetics are potential radiosensitizing targets for cell lines MDA-MB-453 and HCC-1806, and the DNA repair machinery was a radiosensitizing target for cell line HCC-1806.Item APOPTOTIC EFFECTS IN RENAL CORTEX AFTER TREATMENT WITH 177LU-OCTREOTATE(2021-05-10) Andersson, Michelle; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperPurpose: The purpose of this project was to investigate gene regulation of a predetermined panel of apoptotic genes in murine renal cortex after treatment with 177Lu-octreotate after one day and seven days. Theory: The kidneys and bone marrow are the risk organs in 177Lu-octreotate treatment, but by fractioning the treatment the bone marrow recovers. This leads to the kidneys being the dose-limiting risk organ. Apoptosis is a known effect after irradiation of cells and can result in nephrotoxicity after treatment. Whether apoptosis is initiated or inhibited after irradiation depends on a balance of pro-apoptotic and anti-apoptotic signals in the cells and is controlled by many genes divided into gene families. By analysing the expression of apoptotic genes, information about the induction or inhibition of apoptosis can be obtained. The absorbed dose is calculated in order to relate the responses in the tissue to irradiation by 177Lu. The renal cortex receives a higher absorbed dose after treatment with 177Lu-octreotate and is therefore of high interest when studying apoptosis. Method: RNA from the kidney cortex of 12 different mice was used for the analysis. The mice were divided into two irradiated and two control groups and killed at one or seven days after administration of 150 MBq 177Lu-octreotate or physiological saline, respectively. A panel of both pro-apoptotic and anti-apoptotic genes was investigated with a quantitative real-time polymerase chain reaction (QPCR) array. Prior to this, the RNA-concentration was determined with the Qubit ® assay in order to use the same amount of RNA in the QPCR assay. The absorbed dose in the kidney cortex was calculated for each mouse in the irradiated groups and the transcriptional response was related to the absorbed dose and time of irradiation. Result: The group that received a lower absorbed dose and was killed after one day (group 1) showed a higher increase in transcriptional response to irradiation than the group killed after seven days (group 2). The regulation in group 1 indicated pro-apoptotic responses in the renal cortex, wheras in group 2, a shift to anti-apoptotic responses was observed.Item Assessment of bioaccessibility of naturally occurring radionuclides from snus to consumers(2025-03-05) Sanderson, Emma; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperPurpose: Naturally occuring radionuclides can be found in everything we consume, including the tobacco used to make snus. This study aimed to investigate the presence of naturally occurring radionuclides in snus, their bioaccessibility during consumption, and the associated radiological risks to consumers. Methods: A total of 16 samples were sourced from Swedish stores to reflect the national market. A radiological characterization of the samples was conducted through digestion, radiochemical processing, and alpha spectrometry analysis, focusing on 210Po, 232Th, 234U, and 238U. The activity concentrations of these radionuclides in the snus were calculated. A bioaccessibility study analyzed the same radionuclides, simulating real-life snus use to estimate the fraction extracted by saliva. Both used snus and saliva were processed and analyzed using alpha spectrometry. The committed effective dose from annual snus consumption was then calculated. Results: The characterization revealed that 210Po ranged from 2.4–3.0 mBq/g in loose snus and 1.2–5.1 mBq/pouch in pouched snus. For 232Th, levels varied between 0.22–0.42 mBq/g in loose snus and 0.1–0.66 mBq/pouch in pouched snus. 234U ranged from 0.22–0.27 mBq/g in loose snus and 0.07–0.21 mBq/pouch in pouched snus, while 238U was between <0.04–0.23 mBq/g in loose snus and 0.08–0.26 mBq/pouch in pouched snus. Minimal or no activity was detected in tobacco-free snus. The bioaccessibility study demonstrated that all samples transferred 210Po into saliva, with leaching values ranging from 9 ± 3% to 34 ± 7%. Only a limited number of samples showed leaching of other radionuclides, and just one sample appeared to have transferred all radionuclides into saliva. The committed effective dose from one year of snus consumption attributed to 210Po ranged between 1.3 - 8.3 μSv, averaging at 4.55 μSv. Discussion and conclusion: This study conclusively demonstrates that snus use contributes to the annual radiation dose, providing a basis for future research. However, it has limitations, including unexplored factors such as the packaging and design of pouched snus. While the contribution to the annual dose is present, its specific implications for human health remain uncertain. Addressing these knowledge gaps by refining the study design, the inclusion of additional variables, and further investigation into the radiological risks of snus could enhance understanding and potentially lead to strategies that mitigate associated risks in the future.Item ATLAS DATABASES OF HUMAN BRAIN ANATOMY: QUALITATIVE AND QUANTITATIVE COMPARISON(2021-01-11) Philipsson Franzén, Amanda; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperThe purpose of this study was to quantitatively and qualitatively compare the two brain atlases databases, Hammersmith and 2012 MICCAI Multi-Atlas Labelling Challenge data, by developing a quantitative method. Theory Anatomical atlases of the human brain provide reference information about its structure. Researchers and practitioners use them for varied purposes such as automatic image segmentation, biomarker discovery, and identification of relationships between brain structure and function. There is no worldwide agreement on how to segment the human brain, which gives rise to difficulties and differences in the description of brain structures: the brain atlas concordance problem. Two widely used atlas databases are investigated in this study: the Hammersmith (HM) and the 2012 MICCAI Multi-Atlas Labelling Challenge Data (MGC). Both consist of T1-weigthed 3D magnetic resonance (MR) brain images of 30 study participants, with corresponding anatomical label sets. Method The study data consisted of 60 MR brain images (30 from each database) with 120 corresponding segmentations (30 manual and 30 automatically generated, times two databases). The automatic segmentations of the MGC images were based on the HM atlas, and the automatic segmentations of the HM images were based on the MGC atlas. The study was composed of two main parts, a qualitative comparison and a quantitative comparison. The quantitative comparison was developed during the study and was evaluated by juxtaposition with the qualitative results. The quantitative method included calculation of the most frequent coinciding regions, the Jaccard coefficient, and the volume ratio between corresponding regions from each database. The qualitative comparison was composed of predicting differences based on a comparison between the delineation protocols for a subset of regions, a visual analysis of overlaps and a global comparison of region names included in the protocols.Result: Conclusion The main difference between the protocols is that cortical regions only include the actual cortical grey matter in the MGC, whereas HM includes adjacent white matter as part of the region. 73 of the HM regions had matching region names with the MGC regions and 86 of the MGC regions had matching region names with the HM regions. The main differences between the defined regions from the databases were the subdivisions of regions and inclusion of different gyri. 40 and 43 of the HM regions had the matching MGC region as the most frequent coinciding region in the HM images respective the MGC images, and 76 of the MGC regions had the matching HM region as the most frequent coinciding region in both the HM and MGC images. Both atlas databases leave certain brain regions unclassified (assigned the background label). The Jaccard coefficient showed that the greatest overlap occurred between the regions that had matching names with regions in the other protocol. The HM regions generally had larger volumes compared to the corresponding MGC regions, although there were exceptions where MGC regions were almost twice the size of the corresponding HM regions. The quantitative comparison confirmed most of the predictions and revealed multiple additional overlaps and insights that could not be predicted just based on studying the protocols. The two atlas databases differ systematically, reflecting the differences in purpose and priorities that guided the underlying manual segmentation procedures. The quantitative method developed in this project showed to be able to confirm the most important predictions and reveal additional insight that the qualitative analysis could not predict.Item ATLAS-BASED SEGMENTATION OF ULTRAHIGH-RESOLUTION STRUCTURAL MR HEAD IMAGES ACQUIRED AT 7 TESLA(2022-01-13) Johansson, Frida; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperPurpose: The purpose of this work was to find out how the existing brain atlases and segmentation algorithms perform when applied to ultrahigh-resolution MR brain images, acquired with a 7-Tesla scanner. Also to make adaptations to deal with the potential challenges and evaluate the quality of the anatomical segmentations of the 7- Tesla images. Materials: A dataset of MR brain images with various resolutions (1mm, 500 m, 250 m non averaged & 250 m averaged) shared by Lüsebrink et al. from the 7 Tesla scanner in Magdeburg was used. Methods: Two atlas-based anatomical image segmentation algorithms were applied: Pincram for brain extraction and MAPER for labelling multiple brain regions. The resulting brain masks and label maps were assessed qualitatively and quantitatively. Visual evaluation of the quality of the segmentations was made by the auther and external experts. To quantify the consistency of segmentations at the highest resolution, the Jaccard overlap coefficient were calculated. Shape base averaging (SBA) has been implemented on the MAPER-segmented atlases and applied to a 500 m resolution image to improve the appearance of the segmentation. It was then compared to Vote Rule decision Fusion (VRF) that is the standard method of fusing atlas labels in MAPER. Conclusion: MAPER and Pincram work on brain images obtained with a 7-Tesla scanner even though the algorithms have been designed for and validated on 1.5 and 3 Tesla. The data size at the highest resolution exceed available computational resources, therefore images had to be downsampled to 500 m. The segment boundaries were smoother with SBA than with VRF and they got more pleasant to look at. Some boundaries do get misplaced, so the volume estimation of the structures might not be better than with VRF.Item Automatic exposure control for digital radiography without a physical anti-scatter grid(2025-09-04) Ring, Louise; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperPurpose: This study aimed to find a factor R for different parameter settings that can be used to adjust the AEC preset value, in order to maintain a constant amount of primary radiation to the detector when the anti-scatter grid is removed. Method and materials: A factor R was calculated as the fraction between dose-area product (DAP) with and without an anti-scatter grid, from each exposure on polymethylmethacrylate (PMMA) phantoms, multiplied with a primary transmission factor Tp. These measurements lead to a deeper understanding of how varying PMMA thickness, kV and field size would influence R. Second, anthropomorphic phantoms were examined, with a built-in AEC assistance detector (BiAA), while increasing their thicknesses and using different kV and field sizes. An adult chest phantom were examined in anteroposterior (AP) and lateral (LAT) projections (AP/LAT thickness: 21/29, 27/35, 32/39 cm). An adult pelvis and hip phantom (thickness: 23, 29, 35 cm) was examined in AP projection. A pediatric chest phantom (thickness: 15 cm) was examined in AP projection. Results: The Rs from examination of the PMMA resulted in an increase as the thickness increased. This trend was also observed when the field size increased. However, as the kV increased, R decreased. The adult chest (thickness: 21, 27 and 32 cm) AP examination resulted in Rs of 1.13, 1.36 and 1.59. The adult chest (thickness: 29, 35, 39 cm) LAT examination resulted in Rs of 1.20, 1.36 and 1.51, with 141 kV. The adult pelvis (thickness: 23, 29, 35 cm) AP examination resulted in Rs of 2.89, 3.49 and 4.13 with 70 kV. The Rs for the hip examination were 2.34, 2.95 and 2.62. The pediatric chest (thickness: 15 cm) AP examination resulted in an R of 1.08. Discussion and conclusion: R had a similar relative increase for the examination of the adult chest and pelvis with increasing thickness, but R was higher for the pelvis. The change in R between the different thicknesses and phantoms was substantial, which implies the importance of optimizing the examination protocol according to patient size during a gridless examination with AEC. The difference in R also means that the protocol should include a combination of R for a specific anatomic region and patient size, for a finer adjustment of the AEC preset dose. The results of the pediatric phantom measurement, where two different mA were used, the lower mA increased the exposure time. However, the exposure time remained shorter than the minimum recommended by the generator manufacturer. This implies that for smaller thicknesses, the AEC may not be reliable. This study can be used as a base for further studies, and the performance of virtual anti-scatter grids and its impact on image quality needs to be investigated.Item Brain morphometry in Parkinson’s disease(2023-03-02) Olivia, Lönkvist; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperAbstract Purpose The purpose of this brain morphometry study was to examine the volumes of different regions of the brain by research participants with Parkinson’s disease. Method To carry out the study, MR (magnetic resonance) images from 956 research participants from the Parkinson’s Progression Markers Initiative (PPMI) were used. The research participants were divided into 6 different cohorts. Before the MR images were used in this study, they had gone through preprocessing and segmentation using MAPER, where 121 regions including background were segmented. Once the data were obtained, the segmented regions were converted to volumes. The investigation was divided into two parts, first it was studied whether ICV (intracranial volume) differed between the different cohorts. This was done with the help of a violin plot and two-sided t-tests for each cohort. In the second part of the study, the individual volumes in the brain were examined. To accomplish this, hypothesis generation was used on half of each group’s subjects and then the hypotheses were tested on the other half. Two-tailed t-tests were performed to examine statistical differences and similarities between the cohorts. Result In the study, it was seen that the ICV differed between the different cohorts and thus on the imaged person’s head. None of the tested regions in the PD (Parkinsons disease) and SWEDD (scans without evidence for dopaminergic deficit) cohort showed any significant volume difference. The other three cohorts had two to five brain regions that showed a significant volume difference Conclusion In this brain morphometry study, it was shown that a correction for ICV is needed to get comparable results for the different cohorts. For the individual volumes, the results obtained in this study do not agree with previously obtained results. In further studies, it would therefore have been interesting to divide the brain into fewer regions, to add together regions that belong together.Item Can cooking practices affect dietary exposure to 210Po in seafood?(2024-11-13) Nordqvist, Timmy; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperBackground: The estimated yearly worldwide average exposure to radiation is about three mSv, with 2.4 mSv coming from natural radiation sources. 210Po is a highly radiotoxic decay product of 238U and a major contributor to internal radiation dose in humans, especially from seafood consumption. Swedish dietary guidelines recommend frequent seafood consumption, and thus, monitoring 210Po levels is important due to significant dose contributions and lack of guidelines on intake restrictions. Studies show that the Swedish population's yearly average radiation dose from seafood is about 100 μSv, with high consumption groups receiving above 500 μSv for children and 300 μSv for adults. The choice of method to cook seafood can influence the 210Po levels, which impacts the dose assessments from seafood ingestion. Aim: The aim of this master thesis was to determine the impact of cooking on the activity concentration of 210Po in seafood, and to calculate a committed effective dose to humans for consumption of seafood purchased in Sweden. Method: Blue mussels and Norwegian lobsters were bought from selected fish stores in Gothenburg, Sweden. Blue mussels were cooked by boiling, steaming, roasting, or by heating in a microwave. Norwegian lobsters were cooked by boiling, steaming, roasting, or pan-frying. 210Po in blue mussels and Norwegian lobsters was separated using a radiochemical separation method and then measured using alpha spectrometry. The committed effective dose per kg of blue mussels or Norwegian lobster tail meat for an adult was calculated based on the activity concentration of 210Po measured in said seafood. Results: The activity concentration of 210Po varied by cooking method for mussels and lobster. For raw mussels, the average committed effective dose was 44 ± 6 μSv per edible kg, and for boiled mussels 68 ± 8 μSv per edible kg. For raw lobster tail, the committed effective dose ranged from 3.1 ± 1.1 μSv per edible kg to an average of 5 ± 1 μSv per edible kg. The higher doses are likely due to the water content lost during cooking. Discussion and Conclusion: The study observed some variation in 210Po activity concentrations between replicates for blue mussels and Norwegian lobsters for all cooking methods. Raw blue mussels had 210Po levels consistent with previous studies, but more replicates are needed for greater accuracy and to compare different cooking methods. Boiling transferred more of 210Po to the water compared to steaming. Future studies should include more replicates and study e.g., how cooking time affects the activity concentration of 210Po.Item CHARACTERIZATION AND EVALUATION OF A NIPAM POLYMER GEL MRI DOSIMETER SYSTEM(2022-11-08) Waldenberg, Christian; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperPurpose: The normoxic polymer gel dosimeter based on N-isopropyl acrylamide (NiPAM) is a promising full 3D-dosimeter with high spatial resolution and near tissue equivalency. However, limited work have been done in vestigating this dosimeter. The dose response and reproducibility of a NiPAM dosimeter was investigated. The dose rate dependence and the effect of sequential irradiation was studied. Furthermore, the homogene ity of the R2 values across the MRI field of view was examined. Theory: Polymer gel dosimeters are mostly composed of water and when exposed to ionizing radiation, radicals are formed in the process of radiolysis which in turn polymerize the gel via propagation reactions. The gels dose response is related to the degree of monomer polymerization. As the gel polymerize, the spin-lattice relaxation rate changes, making it possible to evaluate the 3D dose distribution within the gel with magnetic resonance imaging. Method: The chemicals for the gel were mixed under controlled conditions and was left to set over night. The NiPAM gel samples were irradiated to different doses using a TrueBeam™ linear accelerator. The absorbed dose was evaluated using a FSE-based MRI sequence and statistical significance of the analyzed data was calculated. The analysis of the DICOM images was carried out using an in house developed software for image processing and data handling. Result: The gel dosimeter was found to respond linearly to the absorbed dose. The reproducibility analysis of the NiPAM gel did not generate a conclu sive result and need to be investigated further. The gel exhibited a dose rate dependence, as well as a dependence on the sequential irradiation scheme. A higher dose rate as well as a higher per sequence dose resulted in a lower dose response. Homogeneity analysis of the calculated R2 val ues across the MRI field of view demonstrated a maximum difference of 4.3% between calculated R2-values.Item Characterization of discrepancies between manual and automatic segmentation to improve anatomical brain atlases(2021-05-10) Sörensson, Anna; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperPurpose: To characterize discrepancies between expert manually segmented brain images from Hammers Atlas Database and automatically generated segmentations of the same images; to decide whether they can be attributed to flaws in the automatic segmentation or in the manual segmentation; and to determine general rules that enable these decisions. Theory: Image segmentation plays an important role in clinical neuroscience and experimental medicine for extraction of information from medical images, and it is a fundamental image processing step in medical image analysis. Another important image processing step is image registration that enables quantitative comparison between datasets of different subjects by geometrically aligning one dataset with another. The scientific underpinning of the project is descriptive science combined with inductive reasoning. Method: The study data consisted of 30 T1-weighted 3D MR images along with manual region label volumes from Hammers Atlas Database, and automatically MAPER-generated segmentations of the same images. The comparison of manual and automatic anatomical (semantic) segmentations involves quantitative and qualitative analyses. Image registration was performed with MIRTK to normalize all images into a common space. Discrepancies were then extracted using a custom-designed image analysis process by the program Convert3D. Result: Conclusion: The work has resulted in a model that enables extraction of discrepancies between manual and automatic segmentation into an individual component for quantitative characterization on a per-label basis. A total of 706 465 surface discrepancies were labelled while 1009 holes were found in both manual and automatic segmentations. Probability maps of the discrepancies have been created and can be used as a basis for determining the probability that certain discrepant voxels have been segmented correctly or not. The study yielded insights into how differences between manual and automatic segmentations arise, and how these can be used to develop an improved segmentation that incorporates information from both models.Item Characterization of spinal tissue in lumbar spinal stenosis by advanced image analysis of MR images(2025-03-24) Nilsfors, Ella; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperBackground. Lumbar spinal stenosis (LSS) is known for causing back and leg pain due to nerve compression but the impact on structures such as intervertebral discs (IVDs), vertebrae, and ligaments is still poorly understood. This knowledge gap may limit the diagnostics and the optimization of the treatment plans for patients with LSS. The aim of the present study was to investigate whether patients with LSS exhibit tissue changes at index levels and at lumbar levels designated for surgery. Method. In 350 LSS-patients awaiting surgery, the IVDs (L1/L2 – L5/S1) and vertebrae (L1 – S1) in both T1- and T2-weighted MR images were segmented. Mean signal intensities (SIs) and standard deviations (SDs) of the means were determined globally and regionally within the segmented IVDs and globally within the vertebrae. Additionally, Δμ (a metric of disc degeneration) was determined and the entropy of the vertebral SI was introduced as a novel metric to evaluate disorganization. All metrics were analyzed for index level and levels planned for surgery and compared between groups. Additionally, Δμ and entropy were correlated to age. Results. Statistical differences in the metrics mean SI and SD were observed between index and non-index levels, as well as between segments planned and not planned for surgery. The largest differences were found in the nucleus pulposus, located in the central regions of the IVD and including subregion 2,3 and 4 (p <0.04). For vertebrae statistical differences were observed in SD and entropy for both index- and surgery level. Vertebral entropy demonstrated the strongest correlation with index levels (r = -0.166; p= 0.002). While Δμ did not display a statistical difference at a specific index level, it displayed an age dependence (e.g., IVD L1/L2; r = 0.399, p <0.001) at most lumbar levels, except at L4/L5 (r = -0.0975, p= 0.070). Δμ did also depend on specific lumbar level. In contrast, vertebral entropy displayed an age dependence at all levels, but no level-specific variation. Conclusions. This explorative study shows distinct differences in tissue characteristics in patients with LSS that correlate with index level and levels planned for surgery. As expected, Δμ was found to depend on both age and spine level. In IVDs at level L4/L5, however, an age-dependency could not statistically be established. Notably, vertebral tissue seemed to display a more homogenous pattern with age, as determined by a decreased entropy. This may reflect the transition in the bone marrow composition in older individuals. Further research is needed to explore the combined impact of multiple metrics and develop predictive tools for earlier intervention and improved clinical decision-making.Item COMPARISON OF MULTI-CRITERIA OPTIMIZATION IN TWO DIFFERENT TREATMENT PLANNING SYSTEMS(2021-05-10) Lindström, Anna; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperPurpose: The purpose with this study was to compare multi-criteria optimization (MCO) for volumetric modulated arc therapy (VMAT) treatment plans in two different treatment planning systems. Theory: When performing treatment planning prior to radiation therapy it is important to prioritize between absorbed dose to target and absorbed dose to organs at risk (OAR). A treatment plan where one treatment goal cannot be improved without impairing another treatment goal is called a Pareto optimal plan. MCO has been proposed as an alternative optimization method for VMAT treatment plans, which will provide several solutions of alternative treatment plans that is at, or close to the Pareto front. The treatment planning system will make it possible for the user to navigate between the possible solutions that the optimization has created and choose the plan that best fulfils the treatment planning goals. Method: Five patients with prostate cancer and five patients with head and neck (H&N) tonsil cancer have been anonymously selected consecutively from the clinical database at Sahlgrenska University Hospital. New VMAT treatment plans were made with MCO in Eclipse (Varian Medical Systems) and RayStation (RaySearch Laboratories). The aim was to give both treatment planning systems (TPS) the same conditions in order to compare the plans fairly. The MCO created Pareto plans and generated a slider for each objective selected. The sliders were thereafter moved to reduce the dose to the organs at risk as much as possible, but at the same time maintain the target dose coverage. Evaluation of the treatment plans was made by evaluating chosen points in the calculated dose-volume histogram but also by evaluating conformity index, heterogeneity index and the complexity of the treatment plans. Result: Conclusion: Dosimetrically, treatment plans created in Eclipse MCO usually provided lower values to the OARs than the treatment plans created in RayStation MCO, but after post processing, RayStation usually provided lower values to the OARs than the treatment plans created in Eclipse MCO. The mean value of the conformity index for Eclipse MCO and RayStation MCO with post processing was 0.9 and 0.78 respectively for the prostate cases and 0.87 and 0.81 respectively for the H&N cases. The values for the heterogeneity index were similar in both TPSs. The calculated complexity index was, in most cases, similar for the prostate cases, however the treatment plans for the H&N cases created in RayStation had generally a lower value of complexity than those created in Eclipse. MCO has proven to be a useful tool for VMAT treatment planning. The management procedure differed for the two TPSs, however, it was in most cases dosimetrically possible to achieve the same treatment planning goals.Item Compartment model for radon-induced absorbed dose in lungs(2024-04-23) Hosseini, Sofia; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperInhalation of radon gas and radon daughters has since a long time been reported as the second leading cause of lung cancer after smoking. The biological hazards make it therefore important to quantify the absorbed doses from radon and radon daughters. The first aim of the study was to reconstruct the Human Respiratory Tract Model, presented by ICRP, to describe the biokinetics, i.e. movement of radon and radon daughters after inhalation for members of the public. The biokinetic model was implemented in the software tool Ecolego and was supplemented with Human Alimentary Tract Model and systemic models of radon, polonium, lead, and bismuth for a complete description of internal exposure. The final biokinetic model enables the user to acquire time-integrated activity (Ã) for combinations of 1) radon and radon daughters, 2) different modes of particle size distribution of radon daughters in air, 3) for members of the public of ages 3 months old, 1 year old, 5 years old, 10 years old, 15 years old and adults defined by ICRP and 4) genders for 15 years old and adults. The model was in a first step bench-marked against the internal dose calculation software Taurus, through comparison of à in the lungs, which resulted in approximately 20% relative bias between the implemented biokinetic model and Taurus. For an overall evaluation of the biokinetic model, the effective dose for radon daughters was calculated to be 18.22 mSv per WLM, which is in the range of values (7–21.1 mSv per WLM) obtained by other researchers. A secondary aim was to study how absorbed doses from emitted α-and β particles following the decay of radon and radon daughters are distributed between tissues of the lungs. Absorbed doses were generated using the software program IDAC-Dose 2.1. In addition, values of S coefficients for combinations of source regions and target tissues inside the respiratory tract were incorporated in the software giving approximative values on absorbed doses and associated uncertainties. The absorbed dose from inhaled radon gas were found to be two orders of magnitude smaller than absorbed doses from inhaled radon daughters. The highest absorbed doses were, as expected, found to be from emitted α particles from 218Po- and 214Po-decay in nearly all tissues of the lungs.Item Deep Neural Networks for Noise Reduction and Bias Removal in MR Diffusion Signal(2022-03-22) Berisha, Beqir; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperThe purpose of this study is to assess the potential of deep neural networks, trained by unsupervised learning, for diffusion weighted imaging (DWI) data modeling and denoising. DWI data were modeled by a biexponential model and Rician bias was corrected for. Deep neural networks that estimate the magnetic resonance (MR) diffusion-weighted signal decay were trained on simulated signal data. Results for simulated data with known σg and estimated σg were compared, where known σg was the most suitable method. Furthermore, a deep neural network trained directly on patient prostate data was used to denoise images. The method of using deep neural networks was compared with OBSIDIAN, which is a model-based, iterative fitting procedure. The deep neural network showed an improvement of image quality with respect to the raw data, but did not have the same quality as OBSIDIAN. Using the trained deep neural network on the same patient data resulted in a runtime of 1.9 ms. The results showed that there is some potential in using deep neural networks for DWI data modelling and denoising, but further optimization is needed.Item DEFORMABLE IMAGE REGISTRATION OF SPINE MAGNETIC RESONANCE IMAGES WITH ELASTIX FOR DETAILED CHARACTERIZATION OF DISC LOADING BEHAVIORS(2021-05-10) Sirat, Zainab; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperPurpose: This work aimed to develop an optimized strategy for registration of spine magnetic resonance (MR) images acquired with and without spinal loading, as well as evaluate the quality of the registration strategy with commonly used quality assessment methods. Method: Previously collected MR images of the lumbar spine of 37 individuals were re analyzed. Multi-echo T2-mapping had been obtained from the subjects in both unloaded and axial-loaded condition. The signal intensity-based registration software Elastix were selected for the registrations between the two image data sets. To facilitate automatic and advanced image analysis, the MICE Toolkit was used as a graphical user interface for Elastix. The registration was done in two steps using the short echo-time raw data images: (1) rigid registration and (2) deformable registration (i.e. non-rigid) with the first registration as input. For comparison, registration was also performed using the long echo-time raw data images. To reduce the calculation time and possibly improve the quality of the image registration, the image was limited by a binary image mask that was applied over the spinal column. To optimize the registration, the parameters FinalGridSpacingInVoxels and BSplineInterpolationOrder were varied. The registration quality was evaluated with Dice similarity coefficient (DSC) and Jaccard coefficient, where a semi-automatic software based on region-growing was used for the delineation of the intervertebral discs (IVDs). The Jacobian determinant was also calculated to ensure that the deformation was realistic with non-zero positive values. The intra- and inter-observer reliability between readers were also determined. Result: The DSC (0.845 ± 0.059) and the Jaccard coefficient (0.735 ± 0.084) were high for all individuals. The mean of the Jacobian determinant was close to one (1.035 ± 0.043). Analysis based on the whole image stack, also showed high DSC (0.845 ± 0.057) and the Jaccard coefficient (0.736 ± 0.081). Significant difference was neither observed between registration with short and long TE images (p = 0.205), nor between registration with or without mask (p = 0.247). A slightly higher accuracy was obtained with less final B-spline grid spacing. The inter- and intra-observer agreement were excellent (ICC = 0.99) Conclusion: Deformable image registration of spine MR images with the optimized registration strategy seems feasible and useful for detailed characterization of disc loading behaviours. The registration using the strategy showed high quality evaluated with DSC and Jaccard coefficient. The evaluation of the Jacobian determinant indicated a preserved topology of the deformed image.Item Developing an Energy Resolution Model for Monte Carlo-Based SPECT Simulation and Reconstruction Using a GE Discovery NM/CT 670 Pro System(2024-09-23) Andelin, Alexandra; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperAim: In order to apply Monte Carlo (MC)-based algorithms for simulations of gamma camera acquisitions, the intrinsic characteristics of the system must be properly defined. This study aimed to determine the energy resolution of a GE Discovery NM/CT 670 Pro gamma camera system, and to develop a nonlinear model for integration in the MC-based program Sahlgrenska Academy Reconstruction Code (SARec). A part of the study also aimed to evaluate different measuring conditions, such as dead time, source geometry, and set-up geometry, and their effect on the energy resolution. Methods and materials: Measurements were performed using said gamma camera system. Spectra were retrieved by extracting listmode data. A MATLAB script was created to determine the full-width half-maximum (FWHM) of the recorded photopeaks using a Gaussian fitting technique. To determine optimal measurement conditions, variations in FWHM under different acquisition circumstances were studied. The effects of dead time were examined by measuring a 131I source at various distances and at different time points. The impact of source geometry and measurement set-up were evaluated using 177Lu, in a syringe and a vial. An evaluation of count statistics was performed by measuring a 241Am source as well as a 177Lu syringe using different acquisition times. To develop the energy resolution model, intrinsic measurements were performed using 241Am, 177Lu, 99mTc, 133Ba, and 131I. The recorded FWHM was fitted as a nonlinear function of photon energy, thus obtaining the energy resolution model. Results: Significant dead time effects arose at counts rates over 180 kcps. Set-up geometry did not affect the measured energy resolution. A small difference in FWHM was observed between the 177Lu syringe and vial (0.11 and 0.43 percentage points at 113 and 208 keV, respectively). Calculated FWHM values did not change significant after acquiring 1,500 kcounts in the photopeak window. The measured energy resolution was 11–8.3% at E = 59–364 keV. The resulting energy resolution relationship was "FWHM = 0.1239 + 0.5428" √(E+0.021E^2 ) with a R2 of 0.89. Conclusion: The evaluated measurement conditions did not affect the energy resolution, although a connection between low count statistics and variations in the calculated FWHM of the peak was observed. The established nonlinear relationship between photon energy and energy resolution provided a better fit to the measured energy resolution, compared to the linear model employed in SARec today, and would thus provide better perquisites for accurate MC-based simulation and reconstruction. However, validation of the model should be performed to evaluate performance.Item DEVELOPMENT, VALIDATION AND APPLICATION OF A METHOD FOR DETERMINATION OF METABOLITE CONCENTRATIONS WITH PRECLINICAL MAGNETIC RESONANCE SPECTROSCOPY(2021-05-10) Lundholm, Lukas; University of Gothenburg/Institute of Clinical Sciences; Göteborgs universitet/Institutionen för kliniska vetenskaperBackground: Information on the metabolic content in tissue has diagnostic and prognostic value when examining for example cancer and diseases of the brain. MR spectroscopy is a non-invasive method that allows quantification of metabolite concentrations in vivo, without the use of ionizing radiation, which makes the method highly attractive for both research and clinical applications. However, specialized software is required for generation of so called basis sets, which consist of information on the individual metabolites that are under investigation, and which are required for quantification. Furthermore, method- and MR vendor-specific information must be provided as the basis sets are being generated in order to yield reliable quantification results. A software for generation of basis sets was recently developed at the University of Gothenburg and validated for a preclinical MR system in a previous master thesis project. However, a standardized method for calculation of metabolite concentrations in vivo in the preclinical setting has not yet been developed. Therefore, the purpose of this work was to adapt, validate and apply a method for non-invasive quantification of metabolites from in vivo MR spectroscopy at the preclinical facility at the University of Gothenburg. Method: The software, implemented in MATLAB and previously developed to simulate basis sets for the clinical MR system, was programmatically adapted to import pulse sequence parameters from the preclinical MR system. Validation of the adapted MATLAB software was done by MR spectroscopy measurements on a phantom solution with known concentrations of certain metabolites, followed by metabolite quantification using the LCModel software. Two in vivo experiments were performed to assess the applicability of the method in the preclinical setting: one on the healthy mouse brain and one on a mouse model of human cancer. The point resolved spectroscopy (PRESS) pulse sequence was used for all measurements and simulations.3 Results: The adaption of the software to the preclinical MR system was successful, resulting in simulated basis sets that could be well fitted to the spectra measured in the validation which, in turn, resulted in accurate determination of metabolite concentrations in the phantom. The in vivo experiments resulted in metabolic profiles of the cancer model and the healthy mouse brain that were in agreement with what has been found in previous studies. The method developed in this work will thus enable metabolite quantification of existing and future MR spectroscopy studies at the preclinical MR facility at the University of Gothenburg.
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