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1.	Kattge, Jens, et al. (author) TRY plant trait database - enhanced coverage and open access 2020 In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188 Journal article (peer-reviewed)abstract Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
2.	2019 Journal article (peer-reviewed)
3.	Bernhardt, Peter, 1966, et al. (author) A novel quantitative image-based method for evaluating cranial symmetry and its usefulness in patients undergoing surgery for unicoronal synostosis. 2013 In: The Journal of craniofacial surgery. - 1536-3732. ; 24:1, s. 166-9 Journal article (peer-reviewed)abstract Background: Unicoronal synostosis presents with cranial asymmetry. Fixed points are difficult to identify; surgical results are therefore difficult to evaluate. The aim of this study was to develop a computer-based method for evaluation of forehead symmetry to enable evaluation of surgical results in unicoronal synostosis. Methods: The MATLAB tool was programmed to segment computed tomographic images, leaving the outermost contour. Cephalometric images were segmented manually due to lower contrast. A center-point (O) and an end-point were manually defined in the midline of the forehead and at the nonfused coronal suture, respectively. The program then found a point (p) on the fused side, at the same distance from the O as the end-point. The contours of the left and right side of the forehead were thereafter superimposed, and the position of minimal area mismatch of the sides was identified. To correct for growth between preoperative images and follow-up, the number of mismatching pixels was related to the area outlined by the contour of the forehead, the end-point and p. Two quantities, the relative symmetry change and the absolute symmetry change, were defined and evaluated by repeated measurements on spherical and elliptical phantoms and 15 patients. Results: Measurements with the MATLAB program were reliable with an SD of 0.26% to 5.39% for the expected range of differences. The SD was lower for measurements on computed tomographic images than for measurements on cephalometric images. The SD was also lower in patients with large surgical improvement than in patients with little improvement. The results support the use of relative symmetry change to evaluate surgical results. Conclusions: Our new computer-based method is capable of measuring forehead symmetry with good precision. This method can be used for systematic evaluation of surgical outcome for unicoronal synostosis and other asymmetric skull deformities.
4.	Fischer, Sara, et al. (author) Comparison of Intracranial Volume and Cephalic Index After Correction of Sagittal Synostosis With Spring-assisted Surgery or Pi-plasty. 2016 In: The Journal of craniofacial surgery. - 1536-3732. ; 27:2, s. 410-3 Journal article (peer-reviewed)abstract The aim of the current study was to determine the intracranial volume (ICV) and cephalic index (CI) in patients operated for sagittal synostosis, and to compare the outcome of 2 different surgical techniques: craniotomy combined with springs and modified pi-plasty.
5.	Fischer, Sara, et al. (author) Intracranial volume is normal in infants with sagittal synostosis. 2015 In: Journal of plastic surgery and hand surgery. - 2000-6764. ; 49:1, s. 62-64 Journal article (peer-reviewed)abstract Abstract Premature sagittal synostosis results in an elongated, narrow skull shape, scaphocephaly. It has been unclear whether the intracranial volume (ICV) of these children is different from that of normal children. The aim of the present study was to precisely determine the ICV in a large cohort of children with premature sagittal synostosis and to compare it to the ICV of a sex- and age-matched control group. All patients (n = 143) with isolated sagittal synostosis registered in the Göteborg Craniofacial Registry until the end of 2012 with a preoperative CT examination were identified. For each case, a sex- and age- (±30 days) matched control was identified from children who had undergone CT for post-traumatic or neurological reasons. The ICV was measured in a semi-automatic MATLAB program with functions such as region growing, watershed, and thresholding in axial CT slices. The ICV was calculated using the Cavalieri principle. The mean (± SEM) values of ICV for children with sagittal synostosis and for corresponding controls were 866 ± 13 ml and 870 ± 15 ml, respectively. The mean ages of these groups were 173 ± 8 days and 172 ± 8 days, respectively. Subgroup analysis of sex and age at CT (≤180 days and >180 days) did not reveal any differences in ICV between cases and controls. Precise determination of ICV in addition to the use of adequate controls has made it possible to conclude that children with premature isolated sagittal synostosis have a normal ICV.
6.	Hagmarker, Linn, et al. (author) A new quantitative image-based method for evaluation of bony temporal hollowing in metopic synostosis 2016 In: Journal of Plastic Surgery and Hand Surgery. - : Medical Journals Sweden AB. - 2000-656X .- 2000-6764. ; 50:6, s. 343-348 Journal article (peer-reviewed)abstract Objective: Premature craniosynostosis is a congenital disorder causing a skull deformity. For both functional and cosmetic reasons, the deformity is surgically treated with a cranioplasty before the age of 1 year. Temporal hollowing is a common and undesirable remaining deformity after cranioplasty for metopic synostosis. The most common method to determine the degree of temporal hollowing is subjective judgement of the temporal region. The aim of the present project was to develop a quantitative semi-automatic computer tool for objective measurement of bony temporal hollowing. Methods: Using MATLAB, a tool was developed to segment computed tomography images, defining the outermost contour. The images were dorsally limited to the widest point of the head. In each case, a sex-and age-matched control was identified and the contours compared. The bony temporal hollowing of the cases was calculated. Results: The intra-user coefficient of variation (CV) was 5.0% (95% CI = 4.2%-6.2%) and the inter-user CV was 3.0% (95% CI = 2.1%-8.6%). For clinical testing purposes, the tool was used in 14 patients, seven of whom had been operated on with a spring-assisted cranioplasty and seven with a cranioplasty using a bone graft. Conclusions: In summary, this study presents a new tool for objective measurement of the surgical result after cranioplasty for metopic synostosis.
7.	Hagmarker, Linn, et al. (author) Characterisation of a planar dosimetry method estimating the absorbed dose to the bone marrow during 177Lu-DOTATATE treatment 2016 In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. Conference paper (other academic/artistic)abstract Aim: An image based method for bone marrow dosimetry, earlier presented by our research group, has shown a significant correlation between the absorbed dose to the bone marrow and haematological toxicity in 177Lu-DOTATATE treatment. The aim of this study was to further evaluate and optimise the method. Materials and Methods: 46 patients with advanced neuroendocrine tumours were treated with 177Lu -DOTATATE on 2-6 occasions. The patients were evaluated using the 4 planar gamma camera images collected at 2, 24, 48 and 168 hours after injection. The whole body was divided into a high- and a low uptake compartment, using a threshold based segmentation tool in the image platform PhONSAi, developed in-house. The segmentation tool starts by including the highest uptake focus and then gradually includes foci with lower and lower uptakes until a threshold is reached where the number of foci escalates. The threshold determines the proportion of the foci that is included in the two compartments. Visual inspection was used to determine the threshold valuewhere all high uptake tissues (i.e. kidney, spleen, liver and tumours) were included in the high uptake compartment. For thresholds around this value the activity in the two compartments was determined by the conjugate view method and the bonemarrow dose was calculated as a sum of the self and cross dose in the low uptake compartment and the cross dose from the high uptake compartment. Results: The visual analysis implies a threshold value of 10%of the maximum number of foci. A correlation was found between the absorbed bone marrow dose and haematological toxicity with p-values ranging from 0.001 to 0.02 for thresholds between 2 % and 25 %, the strongest correlation was found at 15 %. The mean absorbed bone marrow dose were 0.20-0.22 Gy per 7.4 GBq for threshold values between 10-25 %, and increased to 0.28 Gy for the lower values. No significant difference was observed in coefficient of variation (8.2-8.7 %) for the individual mean absorbed doses when varying the threshold value. Conclusion: The individual variation in absorbed dose is maintained at a low level when varying the threshold value for the determination of the compartment sizes. This implies that the method is stable for estimation of bone marrow doses and its correlation to haematological toxicity.
8.	Hagmarker, Linn, et al. (author) Evaluation of planar versus hybrid SPECT image methodology for bone marrow dosimetry during 177Lu-DOTATATE treatments reveals the obstacles with bone marrow metastases and cross-irradiation for the SPECT activity concentration quantification 2018 In: 31st Annual Congress of the European Association of Nuclear Medicine (EANM’18). 13-17 October, Dusseldorf, Germany. Conference paper (other academic/artistic)abstract Introduction. The aim of this study is to compare the recently developed planar image-based method for bone marrow dosimetry with a hybrid method using SPECT/CT imaging at 24 h.p.i. of 177Lu-DOTATATE. Predictive ability of the methods is compared by investigating correlations of determined absorbed bone marrow dose, with haematological toxicity during the course of four treatment cycles. The aim is also to investigate the activity distribution in the vertebral column, and how the hybrid methodology can be optimized. Methods and Materials. 45 patients with advanced neuroendocrine tumours treated with 177Lu-DOTATATE at Sahlgrenska University Hospital in 2011-2016 (ILUMINET-study, EUDRACT nr 2011-etc) were included in this study. Absorbed bone marrow doses were calculated as the sum of the cross-doses from high-uptake organs and the remainder of the body, and the self-dose. Cross-doses were determined by time-activity curves created using planar images and a two-compartment method in the image platform PhONSAi. The self-dose was calculated using the time-activity concentration curve for the remainder of the body adjusted with the activity concentration determined in spheres placed in the vertebral bodies in SPECT-images. To improve recovery and reduce cross-irradiation of false counts in the SPECT-image, we utilized the Monte Carlo based reconstruction code SARec. Three activity concentrations were calculated to represent the activity concentration in the bone marrow; one mean (mean SPECT) and one median (median SPECT) activity concentration based on all visible vertebras and one where vertebras enclosing metastases were manually excluded (w/o Mets SPECT). Results. The planar method, the hybrid methods mean SPECT, median SPECT, and w/o Mets SPECT, yielded absorbed bone marrow doses after treatment cycle one at 0.19 (0.12-0.32), 0.35 (0.12-1.25), 0.29 (0.11-0.92) and 0.29 (0.15-0.81) Gy/7.4 GBq, respectively. A significant dose-response relationship was established after treatment cycle one between decreased platelet counts and absorbed bone marrow dose using the planar method (p=0.025, r=-0.16). With hybrid methods, a significant correlation was firstly found after treatment cycle two between absorbed dose and decreased platelet counts using median SPECT (p=0.018, r=-0.35). Conclusion. Early significant dose-response relationships were established. Despite using SARec-reconstructed SPECT-imaging for specific measurement of activity concentration in bone marrow cavities, the hybrid methods were not able to perform better than the planar method. The hybrid methods yielded higher absorbed bone marrow doses compared to the planar method as both bone metastases and cross-irradiation will influence the activity quantification. Further studies on minimizing influence of bone metastases and cross-irradiation are on-going.
9.	Hemmingsson, Jens, 1986, et al. (author) Autoradiography and biopsy measurements of a resected hepatocellular carcinoma treated with 90 yttrium radioembolization demonstrate large absorbed dose heterogeneities 2018 In: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 3:3, s. 439-446 Journal article (peer-reviewed)abstract © 2018 The Authors Purpose: Radioembolization is an alternative palliative treatment for hepatocellular carcinoma. Here, we examine the uptake differences between tumor tissue phenotypes and present a cross-section of the absorbed dose throughout a liver tissue specimen. Methods and materials: A patient with hepatocellular carcinoma was treated with90Y radioembolization followed by liver tissue resection. Gamma camera images and autoradiographs were collected and biopsy tissue samples were analyzed using a gamma well counter and light microscopy. Results: An analysis of 25 punched biopsy tissue samples identified 4 tissue regions: Normal tissue, viable tumor tissue with and without infarcted areas, and tumor areas with postnecrotic scar tissue. Autoradiography and biopsy tissue sample measurements showed large dose differences between viable and postnecrotic tumor tissue (159 Gy vs 23 Gy). Conclusions: Radioembolization of 90 yttrium with resin microspheres produces heterogeneous-absorbed dose distributions in the treatment of unifocal hepatic malignancies that could not be accurately determined with current gamma camera imaging techniques.
10.	Hemmingsson, Jens, 1986, et al. (author) Autoradiography of a resected hepatocellular carcinoma treated with 90Y radioembolization illustrates uptake differences between viable and infarcted areas 2017 In: European Journal of Nuclear Medicine and Molecular Imaging. 44 (Supplement 2), s. 802 (EP-0871). - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. Conference paper (other academic/artistic)
11.	Högberg, Jonas, 1976, et al. (author) Bremsstrahlung imaging of 90Y microspheres shows poor resemblance with distributions of 99mTc-MAA in liver 2010 In: Journal of the European Society of Therapeutic Radiology and Oncology. - 0167-8140. ; 94:1, s. 25-26 Conference paper (other academic/artistic)abstract PURPOSE To study the resemblance between the distributions of pre- therapeutic 99mTc-MAA and therapeutic 90Y-microspheres, used for ra- dioembolization of liver tumours, making use of gamma- and bremsstrahlung imaging. Furthermore, to establish the accuracy of this method by compar- isons of spatial resolution and radioactivity, performed on line source in water phantom and on resected tumour and normal liver from patients previously treated with 90Y-microspheres. MATERIALS 3 patients diagnosed with liver tumours and planned for surgery; 1 with hepatocellular carcinoma and 2 with cholangiocarcinoma, were treated with SIRTEX R © 90Y-microspheres after standard diagnostic SPECT/CT imag- ing with 99mTc-MAA. The images acquired with gamma camera were com- pared regarding distributions of radioactivity; gamma radiation from the 99mTc-MAA distributions and bremsstrahlung from the distributions of 90Y- microspheres (the latter with a wide bremsstrahlung energy window). Resec- tions of tumour- and some normal liver tissues were performed on all three patients; the resected tissues were sliced, smaller samples were punched out and the radioactivity was measured with a NaI-detector. Furthermore, autoradiography was performed on some slices. A line source with the in- ner diameter 1 mm was positioned in a cylindrical water phantom with the diameter 20 cm; first the line source was filled with 99mTc, then emptied and filled with 90Y. SPECT/CT imaging was performed on both line source se- tups. The spatial resolutions for both radionuclides were then compared. The results from the imaging comparisons performed on the patients were then evaluated with the complementary radiological methods described above. RESULTS The comparison of images from 99mTc-MAA and 90Y showed a considerable deviance in activity distribution for two of the patients. One ex- ample is shown in the figure, the upper image showing 99mTc-MAA and the lower showing 90Y-microspheres. The moderate difference in spatial resolu- tions for 99mTc and 90Y, (15 vs 18 mm FWHM) confirmed the accuracy of these findings. The other radiological methods did also confirm the macro- scopic activity distribution as shown with bremsstrahlung imaging. CONCLUSIONS Bremsstrahlung imaging is a satisfying and reliable method in showing the actual macroscopic distribution of therapeutic 90Y-microspheres used for radioembolization of liver tumours. The results further demonstrate the need for a better diagnostic method than the one currently used, with 99mTc-MAA, thereby providing a better pre-dosimetry; hopefully with a better selection of patients, regarding tumour regression and a lower risk of liver failure.
12.	Högberg, Jonas, 1976, et al. (author) Heterogeneity of microsphere distribution in resected liver and tumour tissue following selective intrahepatic radiotherapy 2014 In: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 4:48 Journal article (peer-reviewed)abstract BACKGROUND Selective arterial radioembolisation of liver tumours has increased, because of encouraging efficacy reports; however, therapeutic parameters used in external beam therapy are not applicable for understanding and predicting potential toxicity and efficacy, necessitating further studies of the physical and biological characteristics of radioembolisation. The aim was to characterise heterogeneity in the distribution of microspheres on a therapeutically relevant geometric scale considering the range of yttrium-90 (90Y) β-particles. METHODS Two patients with intrahepatic cholangiocarcinoma, marginally resectable, were treated by selective arterial embolisation with 90Y resin microspheres (SIRTEX®), followed 9 days post-infusion by resection, including macroscopic tumour tissue and surrounding normal liver parenchyma. Formalin-fixed, sectioned resected tissues were exposed to autoradiographic films, or tissue biopsies of various dimensions were punched out for activity measurements and microscopy. RESULTS Autoradiography and activity measurements revealed a higher activity in tumour tissue compared to normal liver parenchyma. Heterogeneity in activity distribution was evident in both normal liver and tumour tissue. Activity measurements were analysed in relation to the sample mass (5 to 422 mg), and heterogeneities were detected by statistical means; the larger the tissue biopsies, the smaller was the coefficient of variation. The skewness of the activity distributions increased with decreasing biopsy mass. CONCLUSIONS The tissue activity distributions in normal tissue were heterogeneous on a relevant geometric scale considering the range of the ionising electrons. Given the similar and repetitive structure of the liver parenchyma, this finding could partly explain the tolerance of a relatively high mean absorbed dose to the liver parenchyma from β-particles. Keywords: Radioembolisation; Y-90; SIR; Surgery; Activity heterogeneity
13.	Högberg, Jonas, 1976, et al. (author) Increased absorbed liver dose in Selective Internal Radiation Therapy (SIRT) correlates with increased sphere-cluster frequency and absorbed dose inhomogeneity 2015 In: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 2:1 Journal article (peer-reviewed)abstract Background The higher tolerated mean absorbed dose for selective internal radiation therapy (SIRT) with intra-arterially infused 90Y microspheres compared to external beam therapy is speculated to be caused by absorbed dose inhomogeneity, which allows for liver regeneration. However, the complex liver microanatomy and rheology makes modelling less valuable if the tolerance doses are not based on the actual microsphere distribution. The present study demonstrates the sphere distribution and small-scale absorbed dose inhomogeneity and its correlation with the mean absorbed dose in liver tissue resected after SIRT. Methods A patient with marginally resectable cholangiocarcinoma underwent SIRT 9 days prior to resection including adjacent normal liver tissue. The resected specimen was formalin-fixed and sliced into 1 to 2-mm sections. Forty-one normal liver biopsies 6-8 mm in diameter were punched from these sections and the radioactivity measured. Sixteen biopsies were further processed for detailed analyses by consecutive serial sectioning of 15 30-μm sections per biopsy, mounted and stained with haematoxylin-eosin. All sections were scrutinised for isolated or conglomerate spheres. Small-scale dose distributions were obtained by applying a 90Y-dose point kernel to the microsphere distributions. Results A total of 3888 spheres were found in the 240 sections. Clusters were frequently found as strings in the arterioles and as conglomerates in small arteries, with the largest cluster comprising 453 spheres. An increased mean absorbed dose in the punch biopsies correlated with large clusters and a greater coefficient of variation. In simulations the absorbed dose was 5–1240 Gy; 90% were 10-97 Gy and 45% were <30 Gy, the assumed tolerance in external beam therapy. Conclusions Sphere clusters were located in both arterioles and small arteries and increased in size with increasing sphere concentration, resulting in increased absorbed dose inhomogeneity, which contradicts earlier modelling studies.
14.	Högberg, Jonas, 1976, et al. (author) On the dose heterogeneity in normal liver tissue due to treatment of liver tumors with yttrium-90 microspheres 2012 In: 25th Annual Congress on European Association of Nuclear Medicine, Milano, Italy, October 27-31, 2012. European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 39:suppl 2 Conference paper (other academic/artistic)abstract Aim: When treating patients with primary or metastatic liver cancer, applying external radiotherapy, an absorbed dose of 30 - 35 Gy to the whole normal liver tissue volume is associated with a 5 % risk of radiation-induced hepatitis. If less than half of the normal liver volume is being exposed, the threshold for a 5 % risk of hepatitis is increased to above 60 Gy for both primary and metastatic liver cancer. Experience with patients treated with SIR-Spheres® (Sirtex Medical Ltd.), resin microspheres aggregated with yttrium-90, has shown that most patients tolerate an average absorbed dose to normal liver tissue higher than 60 Gy. The high tolerance for this treatment procedure can probably be explained by the resulting heterogenic distribution of radioactivity. It is of interest to study the degree of heterogeneity in the distribution of radioactivity in normal liver tissue, in order to explain or even predict the tolerance to radiation. The aim of this study was to describe the degree of heterogeneity by comparing the relative standard deviations of the radioactivity concentration for different sample mass categories. Materials and Methods: Two patients with cholangiocarcinoma were planned for a combined treatment with yttrium-90-aggregated SIR-Spheres followed by surgery 9 days after radiotherapy. According to standard protocol for treatments with SIR-Spheres, the therapies were preceded by Tc-99m-labled Macro aggregated albumin (Tc-99m-MAA) distribution studies for pre-therapeutic dosimetry and lung shunting evaluations. After surgery the resected tissue, containing both tumour and normal tissue, was studied regarding the distribution of radioactivity. Several small circular samples of normal liver tissue were punched out from 2 mm thick slices of resected tissue, deliberately varying the sizes, and thus the masses of the tissue samples (from 6 to 102 mg). The samples were weighed and categorized in two (first patient) and three (second patient) groups, depending on sample mass. After this the radioactivity was measured with a NaI(Tl) detector. The relative standard deviations (SD/Median) for the radioactivity concentration for each sample mass group were determined and compared. Results: The relative standard deviation for the radioactivity concentration was decreasing rapidly with increasing sample mass. Conclusion: The results indicate a considerable degree of heterogeneity in the distribution of microspheres. One probable explanation for this heterogeneity is clustering of microspheres in the blood vessels.
15.	Högberg, Jonas, 1976, et al. (author) Radiation exposure during liver surgery after treatment with (90)Y microspheres, evaluated with computer simulations and dosimeter measurements. 2012 In: Journal of radiological protection : official journal of the Society for Radiological Protection. - : IOP Publishing. - 1361-6498. ; 32:4, s. 439-46 Journal article (peer-reviewed)abstract Purpose. Two patients with liver tumours were planned for a combined treatment, including surgery with preceding injections of β(-) radiation emitting (90)Y microspheres (SIRTEX(®)). The aim of this paper is to present a method of pre-surgical computer simulations of the absorbed dose rate on the surface of tumour tissue, combined with measurements of the actual absorbed dose rate on resected tissue, in order to estimate the absorbed dose to a surgeon's fingers during such surgery procedures. Methods and Materials. The dose rates from β(-) radiation on the surface of tumour tissue were simulated with the software VARSKIN(®)Mod2. The activity concentrations in tumours were estimated, based on SPECT/CT distribution studies of (99m)Tc-MAA and confirmed by SPECT/CT bremsstrahlung studies of (90)Y microspheres. The activity distributions were considered as homogeneous within the tumour regions. The absorbed dose rates at different tumour tissue spots were calculated based on measurements with thermo-luminescent dosimeters (TLD) fastened on resected tissue. Results. The simulations showed a good agreement with the averaged absorbed dose rates based on TLD measurements performed on resected tissue, differing by 13% and 4% respectively. The absorbed dose rates at the measured maximum hotspots were twice as high as the average dose rates for both patients. Conclusion. The data is not sufficient in order to draw any general conclusions about dose rates on tumour tissue during similar surgeries, neither about the influence of dose rate heterogeneities nor about average dose rates. However, the agreement between simulations and measurements on these limited data indicate that this approach is a promising method for estimations of the radiation exposure to the surgeons' fingers during this kind of surgery procedure. More data from similar surgeries are necessary in order to validate the method.
16.	Högberg, Jonas, 1976, et al. (author) Simulation Model of Microsphere Distribution for Selective Internal Radiation Therapy Agrees With Observations 2016 In: International Journal of Radiation Oncology Biology Physics. - : Elsevier BV. - 0360-3016. ; 96:2, s. 414-421 Journal article (peer-reviewed)abstract Purpose: To perform a detailed analysis of microsphere distribution in biopsy material from a patient treated with 90 Y-labeled resin spheres and characterize microsphere distribution in the hepatic artery tree, and to construct a novel dichotomous bifurcation model for microsphere deposits and evaluate its accuracy in simulating the observed microsphere deposits. Methods and Materials: Our virtual model consisted of arteries that successively branched into 2 new generations of arteries at 20 nodes. The artery diameter exponentially decreased from the lowest generation to the highest generation. Three variable parameters were optimized to obtain concordance between simulations and measure microsphere distributions: an artery coefficient of variation (ACV) for the diameter of all artery generations and the microsphere flow distribution at the nodes; a hepatic tree distribution volume (HDV) for the artery tree; and an artery diameter reduction (ADR) parameter. The model was tested against previously measured activity concentrations in 84 biopsies from the liver of 1 patient. In 16 of 84 biopsies, the microsphere distribution regarding cluster size and localization in the artery tree was determined via light microscopy of 30-mm sections (mean concentration, 14 microspheres/mg; distributions divided into 3 groups with mean microsphere concentrations of 4.6, 14, and 28 microspheres/mg). Results: Single spheres and small clusters were observed in terminal arterioles, whereas large clusters, up to 450 microspheres, were observed in larger arterioles. For 14 microspheres/mg, the optimized parameter values were ACV = 0.35, HDV = 50 cm(3), and ADR = 6 mu m. For 4.6 microspheres/mg, ACV and ADR decreased to 0.26 and 0 mu m, respectively, whereas HDV increased to 130 cm(3). The opposite trend was observed for 28 microspheres/mg: ACV = 0.49, HDV = 20 cm(3), and ADR = 8 mu m. Conclusion: Simulations and measurements reveal that microsphere clusters are larger and more common in volumes with high microsphere concentrations and indicate that the spatial distribution of the artery tree must be considered in estimates of microsphere distributions.
17.	Magnander, Tobias, et al. (author) A fast GPU code for full Monte Carlo based SPECT reconstruction 2016 In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. Conference paper (other academic/artistic)abstract To improve image quality in SPECT/CT reconstructions, various approximate recovery resolution techniques have been developed and implemented in clinical practice. However, optimal image reconstruction requires accounting for all physical interactions of the emitted photons in the individual patient. The objectives for this study were to develop a novel Monte Carlo (MC) code for fast simulation of individual image projections, and to implement these projections in ordered subset expectation maximum (OSEM) reconstructions of SPECT/CTimages.Method: The MC code was written in Compute Unified Device Architecture language for a computer with four graphic processing units (GeForce GTX Titan X, Nvidia, USA). This enables simulations of parallel photon emission from the voxels matrix (1283 or 2563). Each CT number was converted to attenuation coefficients for photo absorption, coherent scattering and incoherent scattering. The type of interaction was determined by the ratio of attenuation coefficients in the CT voxels. For photon scattering the deflection angle was determined by the differential scattering cross sections. The accepted angle for photon interaction with the crystal was determined from the diameter and height of the collimator hole. Predefined energy and spatial resolution kernels for the crystal were used. TheMCcode was implemented intoOSEMreconstruction of 177Lu, 111In and 99mTc SPECT/CT images. The National Electrical Manufacturers Association (NEMA) image quality phantom was used to evaluate the performance of the MC reconstruction in comparison with clinical standard OSEM reconstructions and clinical state-of-the-art OSEM reconstructions with recovery resolution corrections. Results and conclusion: The performance of the MC code was 500 millions photons/s. The required number of photons emitted per voxel for obtaining low noise in the simulated image was 400 for a 1283 voxel matrix. With this number of emitted photons/voxel the MC-based OSEM reconstruction with 10 subsets was performed within 60 s/iteration. The images converged after 2-4 iterations, depending on the sphere sizes in the NEMAphantom. Thereby, the reconstruction time was <4 minutes. The contrast-to-noise level was slightly improved with increased number of emitted photons/voxel, and the reconstruction time was linearly depending on the number of emitted photons/voxel. The signal-to-background for the spheres in the NEMA phantom was clearly improved with MC-based OSEM reconstruction: e.g. for 177Lu the improvement was 37% compared to standard OSEM and 20 % compared to state-of-the-art OSEM. Furthermore, visual inspection of clinical investigations revealed clearly improved resolution and contrast with MC-based reconstruction.
18.	Magnander, Tobias, et al. (author) A novel statistical analysis method to improve the detection of hepatic foci of (111)In-octreotide in SPECT/CT imaging. 2016 In: EJNMMI physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 3:1 Journal article (peer-reviewed)abstract Low uptake ratios, high noise, poor resolution, and low contrast all combine to make the detection of neuroendocrine liver tumours by (111)In-octreotide single photon emission tomography (SPECT) imaging a challenge. The aim of this study was to develop a segmentation analysis method that could improve the accuracy of hepatic neuroendocrine tumour detection.
19.	Magnander, Tobias, et al. (author) Automatic method for improved detection rate and visualization of liver uptake foci in diagnostic 111In-octreotide SPECT/CT investigations 2014 In: XI Congress of World Federation of Nuclear Medicine and Biology, 27-31 August 2014, Cancun, Mexico. Conference paper (other academic/artistic)
20.	Magnander, Tobias, et al. (author) Comparison of the accuracy in kidney activity concentration estimates by the conjugate view and posterior view methods 2015 In: Optimisation in X-ray and Molecular Imaging 2015 - the Fourth Malmö Conference on Medical Imaging, Gothenburg, Sweden, 28-30 May 2015. Conference paper (other academic/artistic)abstract Purpose: In nuclear medicine the conjugate view method (CV) is the most common method for activity quantifications in planar images. The advantage with the CV method is its depth independence, i.e. the activity concentrations can be calculated from two opposite planar images without the knowledge of depth. However, one disadvantage of the method that the signal to background ratio is dependent on the location of the object. This effect might increase the inaccuracy in the activity concentration estimates. Therefore, the activity in off-center objects might be better estimated by the camera projection with the shortest camera to object distance. The aim of the present study was to compare the CV method with a posterior-anterior (PA) projection method for estimation of 177Lu activity concentrations in the kidneys. Methods: The two methods were used to retrospectively determine and compare the left and right kidney activity concentration in 20 patients treated with 177Lu-DOTA-octreotate at Sahlgrenska University Hospital. The kidney was segmented in the SPECT or CT image using an appropriate segmentation algorithm. An attenuation map for 177Lu was created from the CT. Attenuated planar AP and PA projections were created from the SPECT and the attenuation map. The kidney VOI was projected onto the AP and PA projections. The activity concentration in the kidney was calculated using both the PA projection method (ACPA) and the CV method (ACCV) and the results were compared to the concentration in the kidney VOI in the SPECT. Results: The mean ratio between ACCV and the SPECT determined activity concentration was 1.99 with a standard deviation (SD) equal to 1.03 and the mean ratio between ACPA and the SPECT determined concentration was 1.66 with SD=0.80. Both methods demonstrated that the main problems with activity estimates from planar images are the influences of attenuation and the activity concentration in the under and overlying tissues. Conclusions: The present study shows that a true background estimate cannot be accurately performed with neither the CV nor the PA method and that the difficulties in obtaining a true background affect the CV method more than the PA method. The study indicates that the PA method gives a more accurate estimate of the kidney activity concentration than the CV method.
21.	Magnander, Tobias, et al. (author) Improved detection rate and visualization of liver uptake foci in diagnostic 111In-octreotide SPECT/CT investigations with a novel segmentation analysis 2015 In: Optimisation in X-ray and Molecular Imaging 2015 - the Fourth Malmö Conference on Medical Imaging, Gothenburg, Sweden, 28-30 May 2015. Conference paper (other academic/artistic)abstract Purpose: Detection of liver tumors will change the course of treatment of neuroendocrine tumours. In nuclear medicine 111In-octreoscan is of high value for detection of neuroendocrine tumours. However, neuroendocrine tumours disseminated to the livers is often challenging to detect from 111In-octreoscan SPECT images due to low uptake, high noise, poor resolution and low contrast. The aim of the present study was to develop a segmentation analysis method for increased diagnostic accuracy of neuroendocrine liver tumours. Methods: For the SPECT reconstruction 120 projections are acquired with 3 degrees spacing around the patient injected with 111In-octreoscan. The projections are reconstructed into a 128x128x128 voxel matrix using OSEM with CT based attenuation correction. The liver is segmented from the SPECT or CT using either an isosurface, region growing or a GPU accelerated level set algorithm. Manual editing finishes the segmentation of the liver. The segmented liver volume of interest, liver VOI, is thresholded at 125 equidistant threshold values between 0 and the maximum voxel value. At each threshold value a connected component labeling algorithm is used to calculate the number of uptake foci (NUF). The normalized NUF (nNUF) is then plotted against the threshold index (ThI), defined as ThI=(cmax-cthr)/cmax, where cmax is the maximal voxel value in the VOI, and cthr is the voxel threshold value. The method is named nNUFTI - normalized Number of Uptake Foci vs ThI. The ThI at 0.25 nNUF was used for analysis of liver tumour involvement. SPECT images from 53 patients without tumour involvement (i.e SPECT negative) in the liver were analysed with nNUFTI. A three year follow up with MRI, SPECT, PET/CT and CT was used to separate the patients into two groups: the healthy group, with still no liver tumours, and the malignant group, shown to have developed tumours in the liver. Results: 40 patients ended up in the healthy group and 13 in the malignant group. The ThI at 0.25 nNUF was significantly different between the groups (p<0.01). A probability function for the ThI values was constructed from the obtained data. This relationship might be a useful guide in the diagnostic decision making. Conclusions: Our new developed method nNUFTI has been shown to perform well. More studies on the nNUFTI method are needed.
22.	Magnander, Tobias, et al. (author) IMPROVED PLANAR KIDNEY ACTIVITY CONCENTRATION ESTIMATE BY THE POSTERIOR VIEW METHOD IN 177LU-DOTATATE TREATMENTS. 2016 In: Radiation protection dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; 169:1-4, s. 259-266 Journal article (peer-reviewed)abstract The aims of this study were to determine how different background regions of interest (ROIs) around the kidney represent true background activity in over- and underlying tissues in(177)Lu-DOTA-octreatate ((177)Lu-DOTATATE) treatments and to determine the influence of the background positions on the kidney activity concentration estimates by the conjugate view (ConjV) and posterior view (PostV) methods. The analysis was performed in single-photon emission computed tomography (SPECT) images of 20 patients, acquired 24 h post injection of a(177)Lu-DOTATATE treatment, by a computer algorithm that created planar images from the SPECT data. The ratio between the activity concentration in the background and the true background varied from 0.36 to 2.08 [coefficient of variation (CV) = 25-181 %] and from 0.44 to 1.52 (CV = 16-70 %) for the right and left kidneys, respectively. The activity concentration estimate in the kidneys was most accurate with the PostV method using a background ROI surrounding the whole kidney, and this combination might be an alternative planar method for improved kidney dosimetry in the(177)Lu-DOTATATE treatments.
23.	Maltese, Giovanni, 1974, et al. (author) Intracranial volume before and after surgical treatment for isolated metopic synostosis. 2014 In: The Journal of craniofacial surgery. - 1536-3732. ; 25:1, s. 262-266 Journal article (peer-reviewed)abstract Metopic synostosis results in a keel-shaped forehead, hypotelorism, and an increased interparietal width. This study aimed to measure the frontal and total intracranial volume in patients with metopic synostosis before and after surgery and to compare the effect of 2 different operation methods. All patients operated for isolated metopic synostosis between 2002 and 2008 at Sahlgrenska University Hospital who had undergone preoperative and/or postoperative computed tomographic examination (at 3 y of age) were included. The patients were grouped according to operation method: (1) forehead remodeling in combination with a bone graft or (2) forehead remodeling in combination with a spring. Sex- and age-matched controls were identified. A previously developed MATLAB computer program was used to measure the frontal and total intracranial volumes. Sixty patients and 198 controls were included. Preoperatively, the patients with metopic synostosis had significantly lower frontal volumes than those of the controls (P < 0.001) but equal total intracranial volumes. The operations redistributed the intracranial volume and resulted in an improved, frontal-total intracranial volume ratio. However, at 3 years of age, the frontal volume (P < 0.001), total intracranial volume (P ≤ 0.002), and ratio between the 2 (P < 0.001) were significantly lower in the patients than in the controls. The 2 operation methods were equally efficient in creating an improved frontal-total ratio. Surgery for metopic synostosis improves the distribution of the intracranial volume but does not result in normal total intracranial volume or frontal volume at 3 years of age.
24.	Maltese, Giovanni, 1974, et al. (author) New objective measurement of forehead symmetry in unicoronal craniosynostosis - comparison between fronto-orbital advancement and forehead remodelling with a bone graft. 2014 In: Journal of plastic surgery and hand surgery. - 2000-6764. ; 48:1, s. 59-62 Journal article (peer-reviewed)abstract Abstract Patients with unicoronal synostosis (UCS) present with ipsilateral forehead flattening, contralateral frontal bossing, and rotation of the facial midline. Uni- or bilateral fronto-orbital advancement (FOA) techniques are the most common surgical approaches for correction of UCS. The purpose of this study was to objectively evaluate the surgical outcome in patients for UCS, using a new MATLAB computer tool programmed to measure the symmetry of the two halves of the forehead.Files were reviewed from a consecutive series of patients treated for UCS at the unit, from 1979-2008. The patients were grouped according to the method of operation used. The computer tool evaluated preoperative and postoperative cephalograms and CT scans. Eighty-eight patients were included. The male-to-female ratio was 1:2.4. Forty-six patients had been operated on with FOA and 42 with forehead remodelling using a calvarial bone graft. Forehead symmetry was significantly improved by both techniques (p < 0.001 for both), but the postoperative forehead symmetry was significantly better after forehead remodelling (p = 0.025). The reoperation rate was much lower for the second group (6.5 vs 37.2%, p < 0.001). It is concluded that forehead remodelling with a calvarial bone graft creates a more symmetrical forehead than FOA and may, therefore, be a better alternative for treatment of unicoronal synostosis.
25.	Sundin, Maria, 1965, et al. (author) Mars - a target for teachers and science students 2020 In: Contribution to IAU 367S, Education and Heritage in the Era of Big Data in Astronomy, 8-12 December 2020.. Conference paper (other academic/artistic)abstract A case study is here presented of an interdisciplinary course about Mars for teachers and science students. We aim to share the experience of creating an interdisciplinary approach with lecturers spanning physics, geology, radiation physics and philosophy. Issues in ethics, morality, rights and obligations, conflict management and human psychology as well as rocket orbits, fuel economy, radiation hazards and knowledge of the solar system have proven to be a valued and successful initiative for the further training of teachers and science students. The focus of the course is on planning for a journey with humans to the planet Mars. This provides a great opportunity to package complex societal problems in a physics context. The course is offered with a special sustainability content mark. Mankind has always had a strong and dependent relationship with the physical landscape. The land has given us food and shelter but also imposed challenges and disasters. Understanding the physical environment has been crucial for our survival and development. The same will be equally, or more important for Mars where life conditions are much more extreme. We highlight similarities and differences in the geologic processes that have shaped Earth and Mars. What conditions do the future explorers on Mars have to manage? We then enter the modern era and explore the dynamic Martian landscape of today. Also, by learning to read the landscape we may find locations of shelter such as vast systems of lava tubes, or locations of essential resources such as preserved glacial ice etc. A journey to Mars will cause substantially higher personal irradiation than obtained on Earth. The radiation part of the course lectures starts with defining the different radiation types and the biological effects these different types of radiation will cause. Then, the difference between the irradiation on Earth to the elevated irradiation in space and on Mars is described. Thereafter, it is discussed if this elevated radiation burden can cause acute biological effects, e.g. fatigue, vomiting and death, and late biological effects as cancer induction. Last, possible radiation protection strategies are described and discussed. The philosophy of space exploration consists of philosophical approaches to ethics, presently applied to the topic of Mars exploration and colonization, with environmental ethics (anthropocentric vs ecocentric) and value theory at its core. Four main uses of philosophy are distinguished: ethics, aesthetics, cognition and existentialism. Research has shown that visual representation is an important part for students to be able to create a deeper understanding of concepts as well as context about the material that is taught. Interdisciplinary and complex societal problems have also been shown to be important in science teaching. One way for the teacher to develop his/her teaching is to take further education courses in universities whose focus is to seek and discuss the complex societal problems as well as its solutions from a physics and teacher perspective. Future research could be done on the impact of this course on the education in different levels.
26.	Sundin, Maria, 1965, et al. (author) Mars – a target for teachers and science students 2021 In: Proceedings of the International Astronomical Union, Vol 15, Symposium 367S. - 1743-9213 .- 1743-9221. Conference paper (peer-reviewed)abstract An interdisciplinary course about Mars for teachers and science students is presented. The focus of the course is on planning for a journey with humans to the planet Mars. Issues in ethics, morality, rights and obligations, conflict management and human psychology as well as rocket orbits, fuel economy, radiation hazards and knowledge of the solar system are included. Examination of the teacher students include interpretation of the course material for future pedagogical usage.
27.	Sundin, Maria, 1965, et al. (author) Mars — Education of Ethics and Planetary Processes 2021 In: Lunar and Planetary Science Conference 52. Conference paper (other academic/artistic)
28.	Söfteland, Madiha Bhatti, 1977, et al. (author) Temporal Deformity Objectively Measured before and after Surgery for Metopic Synostosis: Retrusion Rather than Hollowing 2017 In: Journal of Craniofacial Surgery. - 1049-2275. ; 28:7, s. 1757-1760 Journal article (peer-reviewed)abstract The temporal contour deformity typical of metopic synostosis is often referred to as temporal hollowing, but has not been quantitatively defined. This deformity is present before surgery and remains to a varying extent at long-term follow-up. The present study aimed to objectively evaluate the degree of this contour deformity in metopic synostosis before and after surgical correction. All children surgically treated for metopic synostosis at Sahlgrenska University Hospital between 2002 and 2014 (n = 120) with appropriate computed tomography scans (n = 160) performed preoperatively and/or at follow-up at 3 years of age were included. Depending on age, 1 of 2 surgical techniques was used. Children presenting before the age of 6 months were treated with frontal remodeling in combination with a spring (S group), whereas children older than 6 months were treated with a bone transplant (BT group). The bony temporal deformity was measured with a semiautomatic MATLAB program and patients were compared to sex-and age-matched controls. The deformity was significantly reduced in both groups (P < 0.001). In the S group, it was reduced from a mean ± standard deviation of 3.6 ± 1.9% to 1.0 ± 1.2% and in the BT group, it was reduced from 3.3% ± 1.4% to 1.1% ± 0.8%. The contour deformity in metopic synostosis is present both before and after surgery and should therefore be termed temporal retrusion (TR). This assessment method enables objective comparison of TR before and after surgical correction and is a potential tool to evaluate TR in metopic synostosis. © 2017 by Mutaz B. Habal, MD.
29.	Söfteland, Madiha Bhatti, 1977, et al. (author) The Degree of Surgical Frontal Volume Correction in Metopic Synostosis Determines Long-Term Outcomes 2017 In: Journal of Craniofacial Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 1049-2275. ; 28:5, s. 1161-1163 Journal article (peer-reviewed)abstract Metopic synostosis results in a keel-shaped forehead, reduced frontal intracranial volume (ICV), and lower frontal to total volume ratio. The ratio improves with cranioplasty, but at 3 years of age, the ratio is still not normalized when compared to that in normal children. The aim of the present study was to investigate whether a low frontal to total ICV ratio at 3 years of age was due to relapse or insufficient correction.All children surgically treated for metopic synostosis in combination with a spring at Sahlgrenska University Hospital with subsequent spring extraction between 2002 and 2008 (n=20) were included. A MATLAB program was used to measure frontal and total ICV.Preoperatively, the frontal to total ICV ratio was 9.81.3% (mean +/- standard deviation). At spring removal, 6 months after cranioplasty, the ratio had increased to 11.8 +/- 2.4%. At 3 years of age, the ratio was 11.6 +/- 1.9%. In age-matched normal children, the ratio was 14.4 +/- 1.9% preoperatively, 15.3 +/- 2.2% at time of spring extraction, and 13.4 +/- 1.4% at 3 years of age.Cranioplasty thus improved the frontal to total ICV ratio, but did not normalize it. The ratio did not change from 6 months after the cranioplasty to 3 years of age. These results indicate that a more pronounced frontal volume correction during cranioplasty is necessary to achieve a normalized distribution of ICV in metopic synostosis.
30.	Tovetjärn, Robert, 1982, et al. (author) Intracranial volume in 15 children with bilateral coronal craniosynostosis. 2014 In: Plastic and reconstructive surgery. Global open. - 2169-7574. ; 2:11 Journal article (peer-reviewed)abstract Intracranial volume (ICV) growth in patients with bilateral coronal craniosynostosis (BCS) is not well described. It is therefore important to evaluate the consequences of cranial surgery in children with this condition. The aim of the present study was to evaluate ICVs in patients operated on for BCS.
31.	Wikberg, Emma, et al. (author) A new computer tool for systematic evaluation of intracranial volume and its capacity to evaluate the result of the operation for metopic synostosis. 2012 In: Journal of plastic surgery and hand surgery. - 2000-6764. ; 46:6, s. 393-8 Journal article (peer-reviewed)abstract Abstract The aim of this project was to develop a tool for systematic evaluation of volumetric changes after surgery for craniosynostosis. A computer program using MATLAB was developed to measure total intracranial volume and frontal volume, anterior to the coronary sutures, by multiplying the area with slice thickness of each slice from just above foramen magnum to just beneath the vertex in CT examinations. The ratio between frontal volume and total volume was used for evaluation of the clinical result in 12 patients operated on for metopic synostosis. In 0.625 and 5 millimetre slices the coefficients of variation were 0.00049 and 0.00058, respectively, for measurements of total volume. The highest coefficient of variation was found in postoperative measurements of the frontal volume and was 0.014 in 0.625 millimetre slices. Measurements in 5 millimetre slices resulted in 3.8% ± 1.5% (mean ± SD) lower total volumes and 5.8% ± 5.3% lower frontal volumes than measurements in 0.625 millimetre slices. In patients operated on for metopic synostosis the ratio between frontal volume and total volume increased 25% ± 16% for patients operated on with cranioplasty in combination with a spring (n = 6) and 20% ± 13% for patients operated on with cranioplasty in combination with a bone transplant (n = 6). In summary, this study has developed a tool that can determine frontal and total intracranial volume with little variation. This tool can be used for systematic evaluation of the result of the operation for metopic synostosis.
32.	Wikberg, Emma, et al. (author) Comparison of a statistical analysis method and a visual assessment of Monte Carlo based SPECT reconstruction concerning liver metastases in 111In-octreotide diagnosis. 2017 In: 30th Annual Congress of the European Association of Nuclear Medicine. Conference paper (other academic/artistic)
33.	Wikberg, Emma, et al. (author) Evaluation of Monte Carlo based reconstruction concerning visual assessment of simulated liver metastases in 111In-octreotide SPECT imaging 2020 In: 33th Annual Congress of the European Association of Nuclear Medicine. Conference paper (other academic/artistic)
34.	Wikberg, Emma, et al. (author) Evaluation of reconstruction methods and image noise levels concerning visual assessment of simulated liver lesions in In-111-octreotide SPECT imaging 2023 In: EJNMMI Physics. - 2197-7364. ; 10:1 Journal article (peer-reviewed)abstract Background: Early cancer detection is crucial for patients' survival. The image quality in In-111-octreotide SPECT imaging could be improved by using Monte Carlo (MC)-based reconstruction. The aim of this observational study was to determine the detection rate of simulated liver lesions for MC-based ordered subset expectation maximization (OSEM) reconstruction compared to conventional attenuation-corrected OSEM reconstruction.MethodsThirty-seven SPECT/CT examinations with In-111-octreotide were randomly selected. The inclusion criterion was no liver lesions at the time of examination and for the following 3 years. SPECT images of spheres representing lesions were simulated using MC. The raw data of the spheres were added to the raw data of the established healthy patients in 26 of the examinations, and the remaining 11 examinations were not modified. The images were reconstructed using conventional OSEM reconstruction with attenuation correction and post filtering (fAC OSEM) and MC-based OSEM reconstruction without and with post filtering (MC OSEM and fMC OSEM, respectively). The images were visually and blindly evaluated by a nuclear medicine specialist. The criteria evaluated were liver lesion yes or no, including coordinates if yes, with confidence level 1-3. The percentage of detected lesions and accuracy (percentage of correctly classified cases), as well as tumor-to-normal tissue concentration (TNC) ratios and signal-to-noise ratios (SNRs), were evaluated.ResultsThe detection rates were 30.8% for fAC OSEM, 42.3% for fMC OSEM, and 50.0% for MC OSEM. The accuracies were 45.9% for fAC OSEM, 45.9% for fMC OSEM, and 54.1% for MC OSEM. The number of false positives was higher for fMC and MC OSEM. The observer's confidence level was higher in filtered images than in unfiltered images. TNC ratios were significantly higher, statistically, with MC OSEM and fMC OSEM than with AC OSEM, but SNRs were similar due to higher noise with MC OSEM.ConclusionOne in two lesions were found using MC OSEM versus one in three using conventional reconstruction. TNC ratios were significantly improved, statistically, using MC-based reconstruction, but the noise levels increased and consequently the confidence level of the observer decreased. For further improvements, image noise needs to be suppressed.
35.	Wikberg, Emma, et al. (author) Improvements of 177Lu SPECT images from sparsely acquired projections by reconstruction with deep-learning-generated synthetic projections 2024 In: EJNMMI PHYSICS. - 2197-7364. ; 11:1 Journal article (peer-reviewed)abstract Background For dosimetry, the demand for whole-body SPECT/CT imaging, which require long acquisition durations with dual-head Anger cameras, is increasing. Here we evaluated sparsely acquired projections and assessed whether the addition of deep-learning-generated synthetic intermediate projections (SIPs) could improve the image quality while preserving dosimetric accuracy. Methods This study included 16 patients treated with Lu-177-DOTATATE with SPECT/CT imaging (120 projections, 120P) at four time points. Deep neural networks (CUSIPs) were designed and trained to compile 90 SIPs from 30 acquired projections (30P). The 120P, 30P, and three different CUSIP sets (30P + 90 SIPs) were reconstructed using Monte Carlo-based OSEM reconstruction (yielding 120P_rec, 30P_rec, and CUSIP_recs). The noise levels were visually compared. Quantitative measures of normalised root mean square error, normalised mean absolute error, peak signal-to-noise ratio, and structural similarity were evaluated, and kidney and bone marrow absorbed doses were estimated for each reconstruction set. Results The use of SIPs visually improved noise levels. All quantitative measures demonstrated high similarity between CUSIP sets and 120P. Linear regression showed nearly perfect concordance of the kidney and bone marrow absorbed doses for all reconstruction sets, compared to the doses of 120P_rec (R-2 >= 0.97). Compared to 120P_rec, the mean relative difference in kidney absorbed dose, for all reconstruction sets, was within 3%. For bone marrow absorbed doses, there was a higher dissipation in relative differences, and CUSIP_recs outperformed 30P_rec in mean relative difference (within 4% compared to 9%). Kidney and bone marrow absorbed doses for 30P_rec were statistically significantly different from those of 120_rec, as opposed to the absorbed doses of the best performing CUSIP_rec, where no statistically significant difference was found. Conclusion When performing SPECT/CT reconstruction, the use of SIPs can substantially reduce acquisition durations in SPECT/CT imaging, enabling acquisition of multiple fields of view of high image quality with satisfactory dosimetric accuracy.
36.	Wild, Damian, et al. (author) Exendin-4-Based Radiopharmaceuticals for Glucagonlike Peptide-1 Receptor PET/CT and SPECT/CT 2010 In: JOURNAL OF NUCLEAR MEDICINE. - 0161-5505. ; 51:7, s. 1059-1067 Journal article (peer-reviewed)
37.	Andersson, Jonas, 1975-, et al. (author) Artificial intelligence and the medical physics profession-A Swedish perspective 2021 In: Physica Medica-European Journal of Medical Physics. - : Elsevier BV. - 1120-1797 .- 1724-191X. ; 88, s. 218-225 Journal article (peer-reviewed)abstract Background: There is a continuous and dynamic discussion on artificial intelligence (AI) in present-day society. AI is expected to impact on healthcare processes and could contribute to a more sustainable use of resources allocated to healthcare in the future. The aim for this work was to establish a foundation for a Swedish perspective on the potential effect of AI on the medical physics profession. Materials and methods: We designed a survey to gauge viewpoints regarding AI in the Swedish medical physics community. Based on the survey results and present-day situation in Sweden, a SWOT analysis was performed on the implications of AI for the medical physics profession. Results: Out of 411 survey recipients, 163 responded (40%). The Swedish medical physicists with a professional license believed (90%) that AI would change the practice of medical physics but did not foresee (81%) that AI would pose a risk to their practice and career. The respondents were largely positive to the inclusion of AI in educational programmes. According to self-assessment, the respondents' knowledge of and workplace preparedness for AI was generally low. Conclusions: From the survey and SWOT analysis we conclude that AI will change the medical physics profession and that there are opportunities for the profession associated with the adoption of AI in healthcare. To overcome the weakness of limited AI knowledge, potentially threatening the role of medical physicists, and build upon the strong position in Swedish healthcare, medical physics education and training should include learning objectives on AI.
38.	Arvidsson, Jonathan, et al. (author) Image Fusion of Reconstructed Digital Tomosynthesis Volumes From a Frontal and a Lateral Acquisition 2016 In: Radiation protection dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; 169:1-4, s. 410-415 Journal article (peer-reviewed)abstract Digital tomosynthesis (DTS) has been used in chest imaging as a low radiation dose alternative to computed tomography (CT). Traditional DTS shows limitations in the spatial resolution in the out-of-plane dimension. As a first indication of whether a dual-plane dual-view (DPDV) DTS data acquisition can yield a fair resolution in all three spatial dimensions, a manual registration between a frontal and a lateral image volume was performed. An anthropomorphic chest phantom was scanned frontally and laterally using a linear DTS acquisition, at 120 kVp. The reconstructed image volumes were resampled and manually co-registered. Expert radiologist delineations of the mediastinal soft tissues enabled calculation of similarity metrics in regard to delineations in a reference CT volume. The fused volume produced the highest total overlap, implying that the fused volume was a more isotropic 3D representation of the examined object than the traditional chest DTS volumes.
39.	Baum, R. P., et al. (author) First-in-Humans Application of Tb-161: A Feasibility Study Using Tb-161-DOTATOC 2021 In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 62:10, s. 1391-1397 Journal article (peer-reviewed)abstract Tb-161 has decay properties similar to those of Lu-177 but, additionally, emits a substantial number of conversion and Auger electrons. The aim of this study was to apply Tb-161 in a clinical setting and to investigate the feasibility of visualizing the physiologic and tumor biodistributions of Tb-161-DOTATOC. Methods: Tb-161 was shipped from Paul Scherrer Institute, Villigen-PSI, Switzerland, to Zentralklinik Bad Berka, Bad Berka, Germany, where it was used for the radiolabeling of DOTATOC. In 2 separate studies, 596 and 1,300 MBq of Tb-161-DOTATOC were administered to a 35-y-old male patient with a metastatic, well-differentiated, nonfunctional malignant paraganglioma and a 70-y-old male patient with a metastatic, functional neuroendocrine neoplasm of the pancreatic tail, respectively. Whole-body planar g-scintigraphy images were acquired over a period of several days for dosimetry calculations. SPECT/CT images were reconstructed using a recently established protocol and visually analyzed. Patients were observed for adverse events after the application of Tb-161-DOTATOC. Results: The radiolabeling of DOTATOC with Tb-161 was readily achieved with a high radiochemical purity suitable for patient application. Planar images and dosimetry provided the expected time-dependent biodistribution of Tb-161-DOTATOC in the liver, kidneys, spleen, and urinary bladder. SPECT/CT images were of high quality and visualized even small metastases in bones and liver. The application of Tb-161-DOTATOC was well tolerated, and no related adverse events were reported. Conclusion: This study demonstrated the feasibility of imaging even small metastases after the injection of relatively low activities of Tb-161-DOTATOC using g-scintigraphy and SPECT/CT. On the basis of this essential first step in translating Tb-161 to clinics, further efforts will be directed toward the application of Tb-161 for therapeutic purposes.
40.	Benjegård, S A, et al. (author) Evaluation of three gamma detectors for intraoperative detection of tumors using 111In-labeled radiopharmaceuticals. 1999 In: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 40:12, s. 2094-101 Journal article (peer-reviewed)abstract Attempts to detect tumors with intraoperative scintillation using tumor-binding radiopharmaceuticals have intensified recently. In some cases previously unknown lesions were found, but in most cases no additional lesions were detected. In this study the physical characteristics of three detector systems and their ability to detect tumors through accumulation of an 111In-labeled radiopharmaceutical were investigated. The first was a sodium iodide (NaI[TI]) detector; the second, a cesium iodide (CsI[TI]) detector; and the third, a cadmium telluride (CdTe) detector.
41.	Bernhardt, Peter, 1966, et al. (author) Dosimetric analysis of the short-ranged particle emitter161 tb for radionuclide therapy of metastatic prostate cancer 2021 In: Cancers. - : MDPI AG. - 2072-6694. ; 13:9 Journal article (peer-reviewed)abstract The aim of this study was to analyze the required absorbed doses to detectable metastases (Dreq ) when using radionuclides with prostate specific membrane antigen (PSMA)-targeting radioligands to achieve a high probability for metastatic control. The Monte Carlo based analysis was performed for the clinically-used radionuclides yttrium-90, iodine-131, lutetium-177, and actinium-225, and the newly-proposed low-energy electron emitter terbium-161. It was demonstrated that metastatic formation rate highly influenced the metastatic distribution. Lower values generated few large detectable metastases, as in the case with oligo metastases, while high values generated a distribution of multiple small detectable metastases, as observed in patients with diffused visualized metastases. With equal number of detectable metastases, the total metastatic volume burden was 4–6 times higher in the oligo metastatic scenario compared to the diffusely visualized scenario. The Dreq was around 30% higher for the situations with 20 detectable metastases compared to one detectable metastasis. The Dreq for iodine-131 and yttrium-90 was high (920–3300 Gy). The Dreq for lutetium-177 was between 560 and 780 Gy and considerably lower Dreq were obtained for actinium-225 and terbium-161, with 240–330 Gy and 210–280 Gy, respectively. In conclusion, the simulations demonstrated that terbium-161 has the potential for being a more effective targeted radionuclide therapy for metastases using PSMA ligands. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
42.	Bernhardt, Peter, 1966, et al. (author) Effects of treatment with (177)Lu-DOTA-Tyr(3)-octreotate on uptake of subsequent injection in carcinoid-bearing nude mice. 2007 In: Cancer biotherapy & radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 22:5, s. 644-53 Journal article (peer-reviewed)abstract PURPOSE: The aim of this study was to analyze the effect therapeutic injections of (177)Lu-DOTA(0)-Tyr(3)]-octreotate (DOTATATE) had on the tumor uptake of a subsequent injection with (111)In-DOTATATE in GOT1-bearing nude mice. METHODS AND MATERIALS: Nude mice, xenografted with the human midgut carcinoid, GOT1, were first intravenously injected with a curative (30 MBq) or a suboptimal (7.5 MBq) amount of (177)Lu-DOTATATE. At various intervals thereafter (4-13 days), a second injection with (111)In-DOTATATE (0.5 MBq) was given. One (1) day after the second injection, the animals were sacrificed, tumor tissues collected, the tumor (111)In and (177)Lu activity concentration determined, and tumor regression/cell density was recorded. RESULTS: In animals given curative amounts, the uptake of (111)In was lower than in untreated animals. On the other hand, a second late injection (3-13 days) after suboptimal amounts resulted in a twofold higher tumor activity concentration versus untreated animals. When the uptake of the curative injection was corrected for tumor cell density, which decreased from 66% to 4% over 2 weeks, an enhanced uptake per tumor cell was observed. The curative and suboptimal amounts resulted in a different uptake and retention of (177)Lu in tumors. The suboptimal amount resulted in a constant activity concentration, while the curative amount resulted in an increased activity concentration over time. CONCLUSIONS: Our results, as presented in this paper, describe how the second injection in a fractionation protocol will be affected by the first therapeutic amount. This new information might be useful in the optimization of radionuclide therapy.
43.	Bernhardt, Peter, 1966, et al. (author) Estimation of metastatic cure after radionuclide therapy. 2007 In: The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of Radiopharmaceutical Chemistry and Biology. - 1824-4785. ; 51:4, s. 297-303 Journal article (peer-reviewed)abstract Targeted radionuclide therapy of disseminated tumor disease involves many factors that will affect the therapeutic outcome. For optimization of such therapy, it is important to know how these factors affect the therapeutic outcome. In this paper, the metastatic cure probability (MCP) model is described. The MCP model is a valuable tool for analyses of the various factors influencing the metastatic cure. The factors discussed are: 1) the physical parameters (the energy and range of emitted particles, absorbed dose-distributions, and cross-irradiation of tumors from the surrounding normal tissue) and 2) the biological parameters (radiosensitivity of tumors, tumor distributions, tumor growth rate, metastasis formation rate, variable tumor activity concentration and non-homogeneous tumor activity distributions).
44.	Bernhardt, Peter, 1966, et al. (author) Model of metastatic growth valuable for radionuclide therapy 2003 In: Medical physics. - 0094-2405. ; 30:12, s. 3227-32 Journal article (peer-reviewed)abstract The aim was to make a Monte Carlo simulation approach to estimate the distribution of tumor sizes and to study the curative potential of three candidate radionuclides for radionuclide therapy: the high-energy electron emitter 90Y, the medium-energy electron emitter 177Lu and the low-energy electron emitter 103mRh. A patient with hepatocellular carcinoma with recently published serial CT data on tumor growth in the liver was used. From these data the growth of the primary tumor, and the metastatis formation rate, were estimated. Assuming the same tumor growth of the primary and all metastases and the same metastatis formation rate from both primary and metastases the metastatic size distribution was simulated for various time points. Tumor cure of the metastatic size distribution was simulated for uniform activity distribution of three radionuclides; the high-energy electron emitter 90Y, the mean-energy electron emitter 177Lu and the low-energy electron emitter 103mRh. The simulation of a tumor cure was performed for various time points and tumor-to-normal tissue activity concentrations, TNC. It was demonstrated that it is important to start therapy as early as possible after diagnosis. It was of crucial importance to use an optimal radionuclide for therapy. These simulations demonstrated that 90Y was not suitable for systemic radionuclide therapy, due to the low absorbed fraction of the emitted electrons in small tumors (< 1 mg). If TNC was low 103mRh was slightly better than 177Lu. For high TNC values low-energy electron emitters, e.g., 103mRh was the best choice for tumor cure. However, the short half-life of 103mRh (56 min) might not be optimal for therapy. Therefore, other low-energy electron emitters, or alpha emitters, should be considered for systemic targeted therapy.
45.	Bernhardt, Peter, 1966, et al. (author) Modelling of metastatic cure after radionuclide therapy: influence of tumor distribution, cross-irradiation, and variable activity concentration 2004 In: Medical physics. - : Wiley. - 0094-2405. ; 31:9, s. 2628-35 Journal article (peer-reviewed)abstract The objective was to study the influence of tumor number and size, cross-irradiation from normal tissue, and of variable activity concentration on metastatic cure after radionuclide therapy. A model to calculate the metastatic cure probability (MCP) was developed, in which it was assumed that the tumor response was an exponential function of the absorbed dose. All calculations were performed for monoenergetic electron emitters with different energies (10-1000 keV). The influence of tumor size and number of tumors were investigated with different log uniform distributions; the basic tumor distribution consisted of tumors with 1, 10, ..., 10(11) cells. The influence of cross-irradiation was assessed by calculating MCP for various tumor-to-normal tissue activity concentration ratios (TNC). The influence of variable activity concentration between tumors was calculated by assuming that the activity concentration in tumors was an inverse power law function of tumor mass. The required activity concentration (C0.9) and absorbed dose (D0.9) to obtain MCP=0.9 was calculated in the different models. The C0.9 and D0.9 needed to obtain MCP were very high; more than 25 MBq/g and 80 Gy, respectively. The lowest C0.9 and D0.9 for equal activity concentration in the different tumor sizes were obtained for electron energies less than 80 keV. For higher energies the low absorbed energy fraction in small tumors will increase the required C0.9 and D0.9 markedly. Cross-irradiation from normal cells surrounding the tumor will cause sterilization of the smallest tumors and decrease the required C0.9 and D0.9 for higher electron energies. Assuming that the activity concentration decreased with increased tumor mass caused a marked increase in C0.9 and D0.9 in favor of higher electron energies. With the MCP model we demonstrated significant influence of the number of tumors, their size, TNC and variable activity concentration on MCP. The results are valuable when evaluating optimal choices for radionuclides for internal-emitter therapy.
46.	Bernhardt, Peter, 1966, et al. (author) Modelling the systemic cure in radionuclide therapy. 2010 In: Targeted radionuclide therapy.Speer T (Eds). - : Lippincott Williams & Wilkins. - 0781796938 Book chapter (other academic/artistic)
47.	Bernhardt, Peter, et al. (author) Molecular basis of perhydrolase activity in serine hydrolases 2005 In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 44:18, s. 2742-2746 Journal article (peer-reviewed)abstract (Chemical Equation Presented) Changing substrates: A mutation that forms a cis-proline-peptide bond in a loop structure close to the active site of an aryl esterase from Pseudomonas fluorescens converts the enzyme into a perhydrolase (see picture). The switch in activity is explained by a new hydrogen bond formed between a backbone carbonyl oxygen atom and the peroxy deacylation intermediate.
48.	Bernhardt, Peter, 1966 (author) Pharmacokinetics and dosimetry of radiolabelled octreotide for tumour therapy 2000 Doctoral thesis (other academic/artistic)abstract Somatostatin (SS) receptors (sstr) are usually highly expressed on neuroendocrine (NE) tumours. The radiolabelled SS analogue 111In-DTPA-D-Phe1-octreotide is today widely used to scintigraphically visualise NE tumours, and high 111In activity concentrations are obtained in tumour vs. normal tissues. The main aim was to investigate the possibility to use radiolabelled SS analogues for systemic therapy.Binding and internalisation of 111In was demonstrated in primary NE tumour cell cultures after incubation with 111In-DTPA-D-Phe1-octreotide. After pulse incubation a rapid release of 50 % of 111In from the cells occurred and the remaining 111In was maintained within the cells over time, mainly located in the cytoplasm and to some extent also in the cell nucleus. The pharmacokinetics of different amounts of i.v. injected 111In-DTPA-D-Phe-octreotide in a patient with disseminated midgut carcinoid tumour was followed by scintigraphy up to 550 h. The uptake in the tumours were long-lasting and the uptake in tumour and most tissues was lower when higher amounts were administered. The pharmacokinetics of i.v. injected 111In-DTPA-D-Phe1-octreotide in nude mice transplanted with tumour cells from the patient (GOT1) was similar to that for the patient, indicating that the animal model could be useful for experimental therapeutic studies.A mathematical model was constructed to calculate the tumour-to-normal-tissue mean absorbed dose ratios (TND) for different radionuclides and tumour sizes. Using the pharmacokinetics of 111In-DTPA-D-Phe1-octreotide from the patient and the mice, the TND was calculated for radionuclides proposed for therapy. 161Tb obtained the highest TND values both in the human and in the mouse model. For therapy of small tumours (< 1 g), suitable electron emitters should, e.g., emit few photons (photon-to-electron energy ratio < 2) and many electrons with low energy (< 40 keV). Five radionuclides fulfilled the criteria: 103mRh, 189mOs, 119Sb, 161Ho and 58mCo.The technique of radiolabelled SS analogues for tumour therapy has great potential for future development. Factors that could increase TND values should be optimised. The major advantage of this type of therapy is that unknown tumours and micrometastases, e.g. in disseminated cancers, may be treated.
49.	Birkemeyer, Ralf, et al. (author) Sealing of coronary perforations with a second-generation covered stent graft - Results from the PAST-PERF registry 2021 In: Cardiovascular Revascularization Medicine. - : Elsevier BV. - 1553-8389. ; 25, s. 20-26 Journal article (peer-reviewed)abstract Background: The PAST-PERF registry was initiated to collect data on the PK Papyrus covered stent, a second-generation device for the treatment of coronary artery perforations with enhanced mechanical properties, but with limited available data. Methods: Patients treated for coronary artery perforations with the PK Papyrus stent at 14 international centers were retrospectively identified. The primary effectiveness outcome was successful sealing of the perforation. The primary safety outcome was a composite of all-cause mortality, definite or probable stent thrombosis, myocardial infarction and target lesion revascularization. Results: Among the 94 included patients, 72.3% (68/94) had Ellis type III and cavity spilling perforations. Complete sealing was achieved in 93.6% (n = 88), and no sealing could be achieved in 3.2% (n = 3, including one patient with a geographical miss and one patient in whom the device could not be implanted). Pericardiocentesis was required in 25.0% (n = 23), emergency cardiac surgery was needed in 7.6% (n = 7), acute stent thrombosis was observed in 1.1% (n = 1), and in-hospital mortality occurred in 11.7% (n = 11). The median follow-up duration was 283 (IQR:40;670) days. At 6 and 12 months, the incidence of the primary safety endpoint was 26.6% [95%CI:18.6;37.1] and 32.0% [95%CI:22.8;43.4], mortality 15.0% [95%CI:9.0;24.6] and 19.0% [95%CI:11.3;30.0], and target lesion revascularization 5.5% [95%CI:2.0;14.6] and 7.7% [95%CI:3.1;18.2]. Two definite stent thrombosis occurred, one during the procedure and one on post-procedure day 233. Conclusions: The registry demonstrates favorably high rates of successful stent delivery and sealing of coronary perforations using a second-generation covered stent with low target lesion revascularization and stent thrombosis rates. Annotated table of content: The PAST-PERF registry demonstrates favorably high rates of successful stent delivery and sealing of coronary perforations using a second-generation covered stent with low target lesion revascularization and stent thrombosis rates. Specifically, complete sealing was achieved in 93.6% of patients (n = 88/94), and no sealing could be achieved in 3.2% (n = 3, including one patient with a geographical miss and one patient in whom the device could not be implanted). The 12-month mortality was 19.0% [95%CI:11.3;30.0], the rate of target lesion revascularization was 7.7% [95%CI:3.1;18.2], and two definite stent thromboses occurred (one during procedure and one on post-procedure day 233).
50.	Båth, Magnus, et al. (author) OPTIMISATION in X-RAY and MOLECULAR IMAGING 2020 2021 In: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 195:3-4, s. 133-133 Journal article (other academic/artistic)

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