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  • 1.
    Andersson, Karin M.
    et al.
    Department of Medical Physics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Medical Physics, Örebro University Hospital, Örebro, Sweden.
    Norrman, Eva
    Department of Medical Physics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Geijer, Håkan
    Örebro University, School of Medical Sciences. Department of Radiology, Örebro University Hospital, Örebro, Sweden.
    Krauss, Wolfgang
    Örebro University, School of Medical Sciences. Department of Radiology, Örebro University Hospital, Örebro, Sweden.
    Cao, Yang
    Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden; Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Jendeberg, Johan
    Örebro University, School of Medical Sciences. Department of Radiology, Örebro University Hospital, Örebro, Sweden.
    Geijer, Mats
    Department of Radiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Clinical Sciences, Lund University, Lund, Sweden.
    Lidén, Mats
    Örebro University, School of Medical Sciences. Department of Radiology, Örebro University Hospital, Örebro, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Medical Physics, Örebro University Hospital, Örebro, Sweden .
    Visual grading evaluation of commercially available metal artefact reduction techniques in hip prosthesis computed tomography2016In: British Journal of Radiology, ISSN 0007-1285, E-ISSN 1748-880X, Vol. 89, no 1063, article id 20150993Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate metal artefact reduction (MAR) techniques from four computed tomography (CT) vendors in hip prosthesis imaging.

    Methods: Bilateral hip prosthesis phantom images, obtained by using MAR algorithms for single energy CT data or dual energy CT (DECT) data and by monoenergetic reconstructions of DECT data, were visually graded by five radiologists using ten image quality criteria. Comparisons between the MAR images and a reference image were performed for each scanner separately. Ordinal probit regression analysis was used.

    Results: The MAR algorithms in general improved the image quality based on the majority of the criteria (up to between 8/10 and 10/10) with a statistically improvement in overall image quality (P<0.001). However, degradation of image quality, such as new artefacts, was seen in some cases. A few monoenergetic reconstruction series improved the image quality (P<0.004) for one of the DECT scanners, but it was only improved for some of the criteria (up to 5/10). Monoenergetic reconstructions resulted in worse image quality for the majority of the criteria (up to 7/10) for the other DECT scanner.

    Conclusions: The MAR algorithms improved the image quality of the hip prosthesis CT images. However, since additional artefacts and degradation of image quality were seen in some cases, all algorithms should be carefully evaluated for every clinical situation. Monoenergetic reconstructions were in general concluded to be insufficient for reducing metal artifacts. Advances in knowledge: Qualitative evaluation of the usefulness of several MAR techniques from different vendors in CT imaging of hip prosthesis.

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    Visual grading evaluation of commercially available metal artefact reduction techniques in hip prosthesis computed tomography
  • 2.
    Andersson, Karin M.
    et al.
    Örebro University, School of Medical Sciences.
    Norrman, Eva
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Metal Artifacts in CT Imaging of Hip Prostheses: Evaluation of Metal Artifact Reduction Techniques Provided by Four Vendors2015Conference paper (Other academic)
    Abstract [en]

    PURPOSE: The aim of this study was to evaluate metal artifact reduction (MAR) techniques, provided by four vendors, in CT imaging of hip prostheses.

    METHOD AND MATERIALS: A water phantom containing hip prostheses mounted in calf bones was scanned with four CT scanners; Philips Ingenuity; Toshiba Aquilion ONE Vision edition; GE Discovery 750 HD and Siemens SOMATOM Definition Flash. An uncorrected (reference) image was obtained for every CT and compared with images acquired with the scanner specific MAR technique; either monoenergetic reconstruction of Dual Energy CT (DECT) data (GE and Siemens) or the use of a MAR algorithm software (Philips and Toshiba), or a combination of the two (GE). The MAR techniques were applied for varying tube voltage, kernel and reconstruction technique. The reference images were quantitatively compared to the MAR images by analyzing the noise and the CT number accuracy in region of interests (ROIs). Visual grading was performed by five radiologists based on ten image quality (IQ) criteria.

    RESULTS: The MAR algorithms implied a general noise reduction (by up to 77%) and improved IQ based on the majority of the visual grading criteria. The use of monoenergetic reconstructions of DECT data, without any MAR algorithm, did not decrease the noise in the ROIs to the same extent as the MAR algorithms (up to 41%) and did even increase the noise in one ROI. The visual grading evaluation showed that monoenergetic reconstructions in general degraded the IQ for one of the DECT scanners and improved the IQ for only a few of the criteria for the other DECT scanner.

    CONCLUSION: The quantitative analysis and the visual grading evaluation showed that the IQ was generally improved when the MAR algorithms were used. However, additional artifacts and degradation of the IQ were noted in some MAR image regions. The use of monoenergetic reconstruction was concluded to not reduce metal artifacts to the same extent as the MAR algorithms and to even degrade the IQ in several image regions.

    CLINICAL RELEVANCE/APPLICATION: This study points out advantages and potential risks of using MAR techniques in CT imaging of hip prostheses and will be useful for clinics when optimizing CT scan protocols and purchasing new CT systems.

  • 3.
    Andersson, Karin M.
    et al.
    Örebro University, School of Medical Sciences.
    Nowik, P.
    Department of Medical Physics, Karolinska University Hospital, Stockholm, Sweden.
    Persliden, Jan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medical Physics, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Thunberg, Per
    Department of Medical Physics, Örebro University Hospital, Örebro, Sweden.
    Norrman, Eva
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medical Physics, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Metal artefact reduction in CT imaging of hip prostheses-an evaluation of commercial techniques provided by four vendors2015In: British Journal of Radiology, ISSN 0007-1285, E-ISSN 1748-880X, Vol. 88, no 1052, article id 20140473Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to evaluate commercial metal artefact reduction (MAR) techniques in X-ray CT imaging of hip prostheses.

    Methods: Monoenergetic reconstructions of dual-energy CT (DECT) data and several different MAR algorithms, combined with single-energy CT or DECT, were evaluated by imaging a bilateral hip prosthesis phantom. The MAR images were compared with uncorrected images based on CT number accuracy and noise in different regions of interest.

    Results: The three MAR algorithms studied implied a general noise reduction (up to 67%, 74% and 77%) and an improvement in CT number accuracy, both in regions close to the prostheses and between the two prostheses. The application of monoenergetic reconstruction, without any MAR algorithm, did not decrease the noise in the regions close to the prostheses to the same extent as did the MAR algorithms and even increased the noise in the region between the prostheses.

    Conclusion: The MAR algorithms evaluated generally improved CT number accuracy and substantially reduced the noise in the hip prostheses phantom images, both close to the prostheses and between the two prostheses. The study showed that the monoenergetic reconstructions evaluated did not sufficiently reduce the severe metal artefact caused by large orthopaedic implants.

    Advances in knowledge: This study evaluates several commercially available MAR techniques in CT imaging of large orthopaedic implants.

  • 4.
    Andersson, Karin M.
    et al.
    Örebro University, School of Medical Sciences. Department of Medical Physics, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Vallhagen Dahlgren, C.
    The Skandion clinic, Uppsala, Sweden.
    Reizenstein, J.
    Department of Oncology, Örebro University Hospital, Örebro, Sweden; , Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Ahnesjö, A.
    Medical Radiation Sciences, Department of Immunology-Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Medical Physics , Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Impact of Metal Artifacts on Proton Therapy Treatment Planning Accuracy2017In: 56th Annual Meeting of the Particle Therapy Cooperative Group (PTCOG) 8-13 May 2017: Proceedings, The Particle Therapy Cooperative Group , 2017, Vol. 4, p. 68-68, article id 1Conference paper (Other academic)
    Abstract [en]

    Purpose: To evaluate for proton therapy treatment planning the feasibility of two commercial metal artifact reduction (MAR) algorithms in CT-imaging.

    Materials and Methods: A head phantom with removable dental fillings and a body phantom with a removable hip prosthesis were scanned to evaluate O-MAR (Philips) and iMAR (Siemens). Reference images (scans without metal) were acquired and subtracted from the uncorrected (no MAR) and MAR-images. CT number-differences were mapped to differences in stopping power ratios to water. In addition, proton treatment plans for a parotid, tonsil and prostate-target were optimized based on uncorrected and MAR images and recalculated on reference images. Beams were arranged to not traverse metal, enabling evaluation of metal artifact impact on target coverage.

    Results: MAR algorithms reduced the most extreme dental filling artifacts, but residual artifacts still remained. iMAR reduced hip prosthesis artifacts to large extent, while considerable artifacts still were present with O-MAR. For parotid and tonsil-plans, D98%to PTV was nearly intact in the reference recalculations for both uncorrected and MAR-based plans, with maximum-difference,0.3%. For uncorrected prostate plans, D98%decreased more than 4% in the reference recalculation. For the iMAR prostate plan, D98%was almost identical in the reference recalculation (97.5% versus 97.4%). A slight D98%-decrease was seen in the reference for the O-MAR based plan (96.8% versus 97.5%).

    Conclusion: Hip prosthesis artifacts reduced target coverage accuracy, but it was substantially improved with MAR algorithms. Dental filling artifacts were moderately reduced with MAR, but did not substantially affect target coverage

  • 5.
    Andersson, Karin M.
    et al.
    Örebro University, School of Medical Sciences.
    Vallhagen Dahlgren, Christina
    The Skandion Clinic, Uppsala, Sweden.
    Reizenstein, Johan
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ahnesjö, Anders
    Medical Radiation Sciences, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences.
    CT image metal artifacts in proton radiotherapy treatment planning: evaluation of two commercial correction algorithmsManuscript (preprint) (Other academic)
  • 6.
    Andersson, Karin M.
    et al.
    Örebro University, School of Medical Sciences. The Skandion Clinic, Uppsala, Sweden.
    Vallhagen Dahlgren, Christina
    The Skandion Clinic, Uppsala, Sweden.
    Reizenstein, Johan
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ahnesjö, Anders
    Medical Radiation Sciences, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Medical Physics.
    Evaluation of two commercial CT metal artifact reduction algorithms for use in proton radiotherapy treatment planning in the head and neck area2018In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 45, no 10, p. 4329-4344Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate two commercial CT metal artifact reduction (MAR) algorithms for use in proton treatment planning in the head and neck (H&N) area.

    METHODS: An anthropomorphic head phantom with removable metallic implants (dental fillings or neck implant) was CT-scanned to evaluate the O-MAR (Philips) and the iMAR (Siemens) algorithms. Reference images were acquired without any metallic implants in place. Water equivalent thickness (WET) was calculated for different path directions and compared between image sets. Images were also evaluated for use in proton treatment planning for parotid, tonsil, tongue base, and neck node targets. The beams were arranged so as to not traverse any metal prior to the target, enabling evaluation of the impact on dose calculation accuracy from artifacts surrounding the metal volume. Plans were compared based on γ analysis (1 mm distance-to-agreement/1% difference in local dose) and dose volume histogram metrics for targets and organs at risk (OARs). Visual grading evaluation of 30 dental implant patient MAR images was performed by three radiation oncologists.

    RESULTS: In the dental fillings images, ΔWET along a low-density streak was reduced from -17.0 to -4.3 mm with O-MAR and from -16.1 mm to -2.3 mm with iMAR, while for other directions the deviations were increased or approximately unchanged when the MAR algorithms were used. For the neck implant images, ΔWET was generally reduced with MAR but residual deviations remained (of up to -2.3 mm with O-MAR and of up to -1.5 mm with iMAR). The γ analysis comparing proton dose distributions for uncorrected/MAR plans and corresponding reference plans showed passing rates >98% of the voxels for all phantom plans. However, substantial dose differences were seen in areas of most severe artifacts (γ passing rates of down to 89% for some cases). MAR reduced the deviations in some cases, but not for all plans. For a single patient case dosimetrically evaluated, minor dose differences were seen between the uncorrected and MAR plans (γ passing rate approximately 97%). The visual grading of patient images showed that MAR significantly improved image quality (P < 0.001).

    CONCLUSIONS: O-MAR and iMAR significantly improved image quality in terms of anatomical visualization for target and OAR delineation in dental implant patient images. WET calculations along several directions, all outside the metallic regions, showed that both uncorrected and MAR images contained metal artifacts which could potentially lead to unacceptable errors in proton treatment planning. ΔWET was reduced by MAR in some areas, while increased or unchanged deviations were seen for other path directions. The proton treatment plans created for the phantom images showed overall acceptable dose distributions differences when compared to the reference cases, both for the uncorrected and MAR images. However, substantial dose distribution differences in the areas of most severe artifacts were seen for some plans, which were reduced by MAR in some cases but not all. In conclusion, MAR could be beneficial to use for proton treatment planning; however, case-by-case evaluations of the metal artifact-degraded images are always recommended.

  • 7.
    Andersén, Christoffer
    et al.
    Örebro University, School of Medical Sciences.
    Rydén, Tobias
    Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Physics.
    H. Lagerlöf, Jakob
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Physics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Medical Physics, Karlstad Central Hospital, Karlstad, Sweden.
    Deep learning based digitisation of prostate brachytherapy needles in ultrasound images2020In: Medical physics, E-ISSN 2473-4209, Vol. 47, no 12, p. 6414-6420Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To develop, and evaluate the performance of, a deep learning based 3D convolutional neural network (CNN) artificial intelligence (AI) algorithm aimed at finding needles in ultrasound images used in prostate brachytherapy.

    METHODS: Transrectal ultrasound (TRUS) image volumes from 1102 treatments were used to create a clinical ground truth (CGT) including 24422 individual needles that had been manually digitised by medical physicists during brachytherapy procedures. A 3D CNN U-net with 128x128x128 TRUS image volumes as input was trained using 17215 needle examples. Predictions of voxels constituting a needle were combined to yield a 3D linear function describing the localisation of each needle in a TRUS volume. Manual and AI digitisations were compared in terms of the root-mean-square distance (RMSD) along each needle, expressed as median and interquartile range (IQR). The method was evaluated on a dataset including 7207 needle examples. A subgroup of the evaluation data set (n=188) was created, where the needles were digitised once more by a medical physicist (G1) trained in brachytherapy. The digitisation procedure was timed.

    RESULTS: The RMSD between the AI and CGT was 0.55 (IQR: 0.35-0.86) mm. In the smaller subset, the RMSD between AI and CGT was similar (0.52 [IQR: 0.33-0.79] mm) but significantly smaller (p<0.001) than the difference of 0.75 (IQR: 0.49-1.20) mm between AI and G1. The difference between CGT and G1 was 0.80 (IQR: 0.48-1.18) mm, implying that the AI performed as well as the CGT in relation to G1. The mean time needed for human digitisation was 10 min 11 sec, while the time needed for the AI was negligible.

    CONCLUSIONS: A 3D CNN can be trained to identify needles in TRUS images. The performance of the network was similar to that of a medical physicist trained in brachytherapy. Incorporating a CNN for needle identification can shorten brachytherapy treatment procedures substantially.

  • 8.
    Andersén, Christoffer
    et al.
    Örebro University, School of Medical Sciences.
    Rydén, Tobias
    Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences.
    Heydorn Lagerlöf, Jakob
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Medical Physics, Karlstad Central Hospital, Karlstad, Sweden.
    Presults for the aI-Brachy study: Utilizing deep learning for needle reconstruction in prostate brachytherapy2019Conference paper (Refereed)
    Abstract [en]

    Purpose To develop a deep neural network for automatic reconstruction of needles in ultrasound images depicting the prostate during brachytherapy treatment of prostate cancer.

    Methods Ultrasound tomographies of the prostate from 907 treatments were used to train the artificial intelligent (AI) algorithm. The image matrices were downsampled to 128x128x128 and were used as in-data when training the AI, a 27 layer convolutional neural network. The needles were identified manually by medical physicists using conventional software. These reconstructions were used as gold standard when training the algorithm. An additional set of examinations were used for validation where the needle reconstructions by the AI were compared to the manual reconstructions. The root mean square deviation (RMSD) of needle position, including the central part (70 slices) of the needle was measured in order to avoid influence from artefacts around the needle tip. The result was also evaluated through visual inspection (see image). The times spent for manual vs. AI reconstruction were compared.

    Results RMSD for manual vs. AI reconstruction is on average (n=170) 1.18±1.0mm, whereas the difference between two manual operators is 0.02±0.06mm, which suggests that the AI is inferior to manual operators. The visual inspection, however, shows AI to be very accurate in positioning the needles. Manual reconstruction took approximately 11.0 minutes, whereas the time for the trained AI is negligible in comparison. Worth noticing regarding RMSD calculations is that, due to limited image resolution, small values may be under-estimated, hence overestimating the difference between the reconstruction methods.

    Conclusions The study implies that an AI may reconstruct needles for brachytherapy treatments of prostate cancer. The larger deviations between AI algorithm and manual operators, compared to between human operators appears to disagree with the high accuracy of the visual evaluation. However, visually, manual needle reconstructions appear to deviate more from the ultrasound image than do the AI reconstructions. This discrepancy is mainly caused by manual reconstruction software assuming straight needles, unlike the AI. We conclude that AI gives the opportunity to save a substantial amount of treatment planning time, when the patient is anesthetised. Further studies are needed to determine whether different reconstruction methods impact treatment plans.

  • 9.
    Bejerot, Susanne
    et al.
    Örebro University, School of Medical Sciences. Faculty of Health and Medical Sciences, University Health Care Research Centre, Örebro University, Örebro, Sweden.
    Eklund, Daniel
    Örebro University, School of Medical Sciences.
    Hesser, Hugo
    Örebro University, School of Behavioural, Social and Legal Sciences.
    Hietala, Max Albert
    Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Kariis, Tarmo
    Karlstad Central Hospital, Region Värmland, Karlstad, Sweden.
    Lange, Niclas
    Örebro University, School of Medical Sciences.
    Lebedev, Alexander
    Center for Psychiatry Research (CPF), Center for Cognitive and Computational Neuropsychiatry (CCNP), Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Nordenskjöld, Axel
    Örebro University, School of Medical Sciences.
    Petrovic, Predrag
    Center for Psychiatry Research (CPF), Center for Cognitive and Computational Neuropsychiatry (CCNP), Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Söderbergh, Annika
    Department of Rheumatology, Örebro University Hospital, Örebro, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Radiology and Medical Physics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Center for Experimental and Biomedical Imaging in Örebro (CEBIO), Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Wikström, Sverre
    Örebro University, School of Medical Sciences. Centre for Clinical Research, County Council of Värmland, Karlstad, Sweden.
    Humble, Mats B.
    Örebro University, School of Medical Sciences.
    Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits)2023In: BMC Psychiatry, E-ISSN 1471-244X, Vol. 23, no 1, article id 771Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years. Autoimmune diseases and severe infections are risk factors for the later development of schizophrenia, elevated inflammatory markers in childhood or adolescence are associated with a greater risk of schizophrenia in adulthood, individuals with schizophrenia have increased levels of pro-inflammatory cytokines compared to healthy controls, and autoimmune diseases are overrepresented in schizophrenia. However, treatments with anti-inflammatory agents are so far of doubtful clinical relevance. The primary objective of this study is to test whether the monoclonal antibody rituximab, directed against the B-cell antigen CD20 ameliorates psychotic symptoms in adults with schizophrenia or schizoaffective disorder and to examine potential mechanisms. A secondary objective is to examine characteristics of inflammation-associated psychosis and to identify pre-treatment biochemical characteristics of rituximab responders. A third objective is to interview a subset of patients and informants on their experiences of the trial to obtain insights that rating scales may not capture.

    METHODS: A proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of B-cell depletion in patients with psychosis. 120 participants with a diagnosis of schizophrenia spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion of rituximab (1000 mg) or saline. Psychiatric measures and blood samples will be collected at baseline, week 12, and week 24 post-infusion. Brief assessments will also be made in weeks 2 and 7. Neuroimaging and lumbar puncture, both optional, will be performed at baseline and endpoints. Approximately 40 of the patients and their informants will be interviewed for qualitative analyses on the perceived changes in well-being and emotional qualities, in addition to their views on the research.

    DISCUSSION: This is the first RCT investigating add-on treatment with rituximab in unselected SSD patients. If the treatment is helpful, it may transform the treatment of patients with psychotic disorders. It may also heighten the awareness of immune-psychiatric disorders and reduce stigma.

    TRIAL REGISTRATION: NCT05622201, EudraCT-nr 2022-000220-37 version 2.1. registered 14th of October 2022.

  • 10.
    Broxvall, Mathias
    et al.
    Örebro University, School of Science and Technology. Centre of Biomedical Engineering Research (MTFC), Örebro University Hospital, Örebro, Sweden.
    Emilsson, Kent
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Physiology, Örebro University Hospital, Örebro, Sweden.
    Thunberg, Per
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medical Physics and Centre of Biomedical Engineering Research (MTFC), Örebro University Hospital, Örebro, Sweden.
    Fast GPU based adaptive filtering of 4D echocardiography2012In: IEEE Transactions on Medical Imaging, ISSN 0278-0062, E-ISSN 1558-254X, Vol. 31, no 6, p. 1165-1172, article id 6099625Article in journal (Refereed)
    Abstract [en]

    Time resolved three-dimensional (3D) echocardiography generates four-dimensional (3D+time) data sets that bring new possibilities in clinical practice. Image quality of four-dimensional (4D) echocardiography is however regarded as poorer compared to conventional echocardiography where time-resolved 2D imaging is used. Advanced image processing filtering methods can be used to achieve image improvements but to the cost of heavy data processing. The recent development of graphics processing unit (GPUs) enables highly parallel general purpose computations, that considerably reduces the computational time of advanced image filtering methods. In this study multidimensional adaptive filtering of 4D echocardiography was performed using GPUs. Filtering was done using multiple kernels implemented in OpenCL (open computing language) working on multiple subsets of the data. Our results show a substantial speed increase of up to 74 times, resulting in a total filtering time less than 30 s on a common desktop. This implies that advanced adaptive image processing can be accomplished in conjunction with a clinical examination. Since the presented GPU processor method scales linearly with the number of processing elements, we expect it to continue scaling with the expected future increases in number of processing elements. This should be contrasted with the increases in data set sizes in the near future following the further improvements in ultrasound probes and measuring devices. It is concluded that GPUs facilitate the use of demanding adaptive image filtering techniques that in turn enhance 4D echocardiographic data sets. The presented general methodology of implementing parallelism using GPUs is also applicable for other medical modalities that generate multidimensional data.

  • 11.
    Dimitriou, Praxitelis
    et al.
    Department of Radiology, Örebro University Hospital , Örebro, Sweden.
    Kähäri, Anders
    Department of Clinical Physiology, Örebro University Hospital , Örebro, Sweden.
    Emilsson, Kent
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Physiology, Örebro University Hospital , Örebro, Sweden.
    Thunberg, Per
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medical Physics, Örebro University Hospital, Örebro, Sweden .
    Cardiovascular magnetic resonance imaging and transthoracic echocardiography in the assessment of stenotic aortic valve area: a comparative study2012In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 53, no 9, p. 995-1003Article in journal (Refereed)
    Abstract [en]

    Background: Magnetic resonance (MR) imaging and echocardiography both allow assessment of aortic valve stenosis. In MR the aortic valve area (AvA) is measured using planimetry while in transthoracic echocardiography (TTE) AvA is usually calculated by applying the continuity equation.

    Purpose: To compare the measured stenotic aortic valve areas using five different MR-acquisition alternatives with the corresponding area values calculated by TTE.

    Material and Methods: The aortic valve was imaged in 14 patients, with diagnosed aortic valve stenosis, using balanced steady state free precession (bSSFP) gradient echo (GE) and phase contrast imaging (PC). Three adjacent slices were planned to encompass the aortic valve and the aortic valve area was measured using planimetry. The two sets of complex valued images generated by the PC sequence formed three kinds of images that could be used for aortic valve area measurements: the magnitude image (PC/Mag), the modulus (PCA/M), and phase difference (PCA/P) between the two complex images, respectively. The valve area from TTE was calculated using the continuity equation. A cut-off of <1.0 cm(2) was used as a criteria for severe stenosis.

    Results: The mean area differences between the different MR acquisitions and TTE method were -0.05 ± 0.37 cm(2) (GE), -0.18 ± 0.46 cm(2) (bSSFP), 0.27 ± 0.43 cm(2) (PC/Mag), 0.15 ± 0.32 cm(2) (PCA/P), and 0.26 ± 0.27 cm(2) (PCA/M). The valve area was significantly overestimated using PCA/M that, in turn, implied a significant underestimation of the aortic valve stenosis severity compared to the assessments using TTE.

    Conclusion: The smallest area valve difference between TTE and an MR-acquisition alternative is obtained with gradient echo images. The use of PCA/M leads to significant differences in planimetry measurements of the aortic valve orifice and the gradation of the stenosis severity compared to TTE.

  • 12.
    Edebol Carlman, Hanna M. T.
    et al.
    Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Rode, Julia
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Radiology and Medical Physics.
    Persson, Jonas
    Örebro University, School of Law, Psychology and Social Work.
    Kiselev, Andrey
    Örebro University, School of Science and Technology. Center for Applied Autonomous Sensor Systems.
    Pruessner, Jens C.
    Douglas Institute, McGill University, Montréal, QC H4H1R3, Canada; Department of Psychology, University of Konstanz, Konstanz, Germany.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses to an Arithmetic Stress Task in Healthy Subjects: A Randomised Clinical Trial and Proof-of-Concept Study2022In: Nutrients, E-ISSN 2072-6643, Vol. 14, no 7, article id 1329Article in journal (Refereed)
    Abstract [en]

    Probiotics are suggested to impact physiological and psychological stress responses by acting on the gut-brain axis. We investigated if a probiotic product containing Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 affected stress processing in a double-blinded, randomised, placebo-controlled, crossover proof-of-concept study (NCT03615651). Twenty-two healthy subjects (24.2 ± 3.4 years, 6 men/16 women) underwent a probiotic and placebo intervention for 4 weeks each, separated by a 4-week washout period. Subjects were examined by functional magnetic resonance imaging while performing the Montreal Imaging Stress Task (MIST) as well as an autonomic nervous system function assessment during the Stroop task. Reduced activation in regions of the lateral orbital and ventral cingulate gyri was observed after probiotic intervention compared to placebo. Significantly increased functional connectivity was found between the upper limbic region and medioventral area. Interestingly, probiotic intervention seemed to predominantly affect the initial stress response. Salivary cortisol secretion during the task was not altered. Probiotic intervention did not affect cognitive performance and autonomic nervous system function during Stroop. The probiotic intervention was able to subtly alter brain activity and functional connectivity in regions known to regulate emotion and stress responses. These findings support the potential of probiotics as a non-pharmaceutical treatment modality for stress-related disorders.

  • 13.
    Edebol-Carlman, Hanna
    et al.
    Örebro University, School of Medical Sciences.
    Rode, Julia
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Kiselev, Andrey
    Örebro University, School of Science and Technology.
    Thunberg, Per
    Örebro University, School of Medical Sciences.
    Lathrop Stern, Lori
    Labus, Jennifer
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Evaluating the effects of probiotic intake on brain activity during an emotional attention task and blood markers related to stress in healthy subjects2019Conference paper (Refereed)
  • 14.
    Edebol-Carlman, Hanna
    et al.
    Örebro University, School of Medical Sciences.
    Rode, Julia
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley N.
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Physics.
    Persson, Jonas
    Örebro University, School of Law, Psychology and Social Work.
    Kiselev, Andrey
    Örebro University, School of Science and Technology.
    Pruessner, Jens C.
    McGill Centre for Studies in Ageing, Department of Psychology, Psychiatry, Neurology and Neurosurgery, Douglas Institute, McGill University, Montréal, Canada.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Probiotic mixture containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum affects brain responses to an arithmetic stress task in healthy subjects: A randomized clinical trialManuscript (preprint) (Other academic)
  • 15.
    Emilsson, Kent
    et al.
    Department of Clinical Physiology Karlskoga Hospital, Karlskoga, Sweden; Department of Clinical Physiology, Örebro University Hospital, Örebro, Sweden.
    Kähäri, Anders
    Department of Radiology, Örebro University Hospital, Örebro, Sweden.
    Bodin, Lennart
    Unit of Statistics Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Thunberg, Per
    Department of Biomedical Engineering Örebro University Hospital, Sweden.
    Comparison between angiographic right coronary artery motion and echocardiographic tricuspid annulus motion2004In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 38, no 2, p. 85-92Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To compare echocardiographic M-mode measurements of tricuspid annulus motion (TAM) with angiographic M-mode measurements of right coronary artery motion (RAM).

    DESIGN: Twenty-four patients were included and examined by echocardiography before the angiographic examination. The amplitudes and the velocities of TAM and the atrial contribution to the total amplitude of TAM were measured. The obtained values were compared with angiographic M-mode measurements of RAM at a proximal and a distal site of the second segment of the right coronary artery.

    RESULTS: There was no significant difference between several of the echocardiographic M-mode measurements of TAM and the angiographic M-mode measurements of RAM. However, the agreement was rather poor for some variables.

    CONCLUSION: Different parameters obtained from echocardiographic TAM are not interchangeable with values from angiographic RAM. If measurements of RAM are to be used in the assessment of right ventricular (RV) function further studies are needed to examine the correlation and agreement between RAM and different methods of measuring RV function, i.e. radionuclide angiography or magnetic resonance imaging.

  • 16.
    Emilsson, Kent
    et al.
    Department of Clinical Physiology Karlskoga Hospital, Karlskoga, Sweden; Department of Clinical Physiology, Örebro University Hospital, Örebro, Sweden.
    Kähäri, Anders
    Department of Radiology, Örebro University Hospital, Sweden.
    Bodin, Lennart
    Unit of Statistics Clinical Research Centre, Örebro University Hospital, ÖrebroSweden.
    Thunberg, Per
    Department of Biomedical Engineering Örebro University Hospital, Sweden.
    Outer contour and radial changes of the cardiac left ventricle: a magnetic resonance imaging study.2007In: Clinical Research in Cardiology, ISSN 1861-0684, E-ISSN 1861-0692, Vol. 96, no 5, p. 272-278Article in journal (Refereed)
    Abstract [en]

    Earlier studies have shown a +/-5% end-systolic decrease in the volume encompassed by the pericardial sack, manifesting as a radial diminution of the pericardial/epicardial contour of the left ventricle (LV). The aim of this study was to measure this radial displacement at different segmental levels of the LV and try to find out were it is as greatest and to calculate regional myocardial volume changes as a reference in healthy subjects. Eleven healthy subjects were examined by magnetic resonance imaging. Images were acquired using an ECG-triggered balanced fast field echo pulse sequence. The epicardial borders of the LV wall were delineated in end-diastole (ED) and end-systole (ES). Regional changes of the LV wall were analysed at three different levels (base, mid and apex) by dividing the myocardium into segments. The volumes obtained as the differences between the outer volume of the left ventricle at ED and ES at different slice levels were found to be greatest at the base of the heart and lowest at apex. The relative inward motion, that is the motion in short-axis direction of the epicardial border of the myocardium from ED to ES towards the centre of the LV, was greatest at the base and lowest at the mid level, something that has to be taken into account when measuring the LV during clinical exams. There was a significant difference in the relative inward motion between the segments at apex (p < 0.0001), mid (p = 0.036) and at base level (p < 0.0001).

  • 17.
    Funk, Eva
    et al.
    Örebro University, School of Health Sciences.
    Anderzen-Carlsson, Agneta
    Örebro University, School of Health Sciences. Örebro University Hospital.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Patient participation in MRI: patient experiences and image quality addressing breath-hold acquisitions2016In: ECR 2016 Book of Abstracts: B. Scientific Sessions and Clinical Trials in Radiology, Springer, 2016, p. S379-S379Conference paper (Other academic)
    Abstract [en]

    Purpose: To investigate two different breath-hold techniques, in terms of patient experience and image quality, and describe patients' experiences of magnetic resonance imaging.

    Methods and Materials: Thirty patients referred for an MRI of the liver conducted two separate breath-hold acquisitions in a randomised order, radiographer-directed and patient-initiated. Semi-structured interviews were held and analysed, and images were reviewed according to image quality.

    Results: The patients' general experiences of the MRI were that they felt a loss of control, and almost half of the patients seemed to prefer the self-initiated breath-hold. About 20 % of the patients preferred to hand over the responsibility to the radiographer, and for some the technique did not matter.The patients empathized in general the importance of achieving the best image quality. There were no significant differences identified between the two breath-hold techniques, in regards to image quality.

    Conclusion: The results show that self-initiated breath-hold acquisitions can be seen as a new alternative worth considering in clinical MRI since it is appreciated by the patients and give similar image quality compared to conventional breath-hold acquisitions. It also offers a possibility to achieve some control over the situation.

  • 18.
    Funk, Eva
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Anderzén-Carlsson, Agneta
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Ingverud, Per
    Department of Diagnostic Radiology, Örebro University Hospital, Örebro, Sweden.
    Leander, Anna
    Department of Diagnostic Radiology, Örebro University Hospital, Örebro, Sweden.
    Thunberg, Per
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Patient-initiated breath-holds in MRI: an alternative for reducing respiratory artifacts and improving image quality2015In: Clinical imaging, ISSN 0899-7071, E-ISSN 1873-4499, Vol. 39, no 4, p. 619-622Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate MRI image quality using two different breath-hold techniques.

    Materials and methods: Thirty patients remitted for MRI, 2D-dual gradient echo acquisition of the liver conducted two separate breath-hold acquisitions in randomized order, operator-instructed and patient-initiated. The images were reviewed by two radiologists.

    Results: There were no significant differences in image quality between the two breath-hold techniques either in overall image quality or respiratory motion artifacts. This assessment was equal and concordant for both radiologists.

    Conclusion: In terms of image quality, the patient self-initiated breath-hold was shown to be an equal alternative to conventional breath-hold imaging.

  • 19.
    Funk, Eva
    et al.
    Örebro University, School of Health Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Anderzen-Carlsson, Agneta
    Örebro University, School of Health Sciences. Örebro University Hospital.
    Instructed or patient-initiated breath holds: what do the patients prefer?2013Conference paper (Other academic)
  • 20.
    Funk, Eva
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Thunberg, Per
    Örebro University Hospital. Department of Medical Physics, Örebro University Hospital, Örebro, Sweden.
    Anderzen-Carlsson, Agneta
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Centre for Health Care Sciences, Örebro University Hospital, Örebro, Sweden.
    Patients' experiences in magnetic resonance imaging (MRI) and their experiences of breath holding techniques2014In: Journal of Advanced Nursing, ISSN 0309-2402, E-ISSN 1365-2648, Vol. 70, no 8, p. 1880-1890Article in journal (Refereed)
    Abstract [en]

    Aims: To describe patients' experiences of magnetic resonance examination of the liver and their experiences of two breath-hold techniques.

    Background: Traditionally, patients are instructed by the radiographer to hold their breath during the examination. Alternatively, the patient can initiate the breath hold and start the image acquisition. Studies have revealed that magnetic resonance examinations can be experienced as challenging.

    Design: Descriptive qualitative.

    Methods: Semi-structured interviews were conducted with 28 patients and analysed using qualitative content analysis. The data collection was carried out from autumn 2010 to spring 2011.

    Results: The patients' main experience was that they felt loss of control. This was described in terms of feeling trapped, being lost in time and lost as a result of uncertainty. They had many questions in their mind that they did not ask. Although their statements often revealed no clear preference regarding the techniques, almost half of the patients seemed to prefer self-initiated breath hold, as it was easier and less stressful. Those who preferred the radiographer-directed technique felt more confident leaving the responsibility to the radiographer. In general, the patients understood the importance of achieving the best quality images possible.

    Conclusion: Magnetic resonance examination can be experienced as being in loss of control. Nevertheless, not all patients wished to actively participate in magnetic resonance examination. Some preferred to hand over the responsibility to the radiographer. These results can form a base for radiographers' reflections of how to individualize and optimize the nursing care of patients undergoing magnetic resonance examinations.

  • 21.
    Hellstrandh Jorstig, Stina
    et al.
    Örebro University, School of Medical Sciences.
    Waldenborg, Micael
    Örebro University, School of Health Sciences. Department of Clinical Physiology, Örebro University Hospital, Örebro, Sweden.
    Lidén, Mats
    Örebro University, School of Medical Sciences. Department of Radiology, Örebro University Hospital, Örebro, Sweden.
    Wodecki, Maciej
    Department of Clinical Physiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Medical Physics, Örebro University Hospital, Örebro, Sweden.
    Determination of Right Ventricular Volume by Combining Echocardiographic Distance Measurements2016In: Echocardiography, ISSN 0742-2822, E-ISSN 1540-8175, Vol. 33, no 6, p. 844-853Article in journal (Refereed)
    Abstract [en]

    Background: The position of the right ventricle (RV), often partly behind the sternum, implies difficulties to image the RV free wall using transthoracic echocardiography (TTE) and consequently limits the possibilities of stroke volume calculations. The aim of this study was to evaluate whether the volume of the right ventricle (RV) can be determined by combining TTE distance measurements that do not need the RV free wall to be fully visualized.

    Methods: The RV volume was approximated by an ellipsoid composed of three distances. Distance measurements, modeled RV stroke volumes (RVSV), and RV ejection fraction (RVEF) were compared to reference values obtained from cardiac magnetic resonance (CMR) imaging for 12 healthy volunteers.

    Results: Inter-modality comparisons showed that distance measurements were significantly underestimated in TTE compared to CMR. The modeled RV volumes using TTE distance measurements were underestimated compared to reference CMR volumes. There was, however, for TTE an agreement between modeled RVSV and left ventricular stroke volumes determined by biplane Simpson's rule. Similar agreement was shown between modeled RVSV based on CMR distance measurements and the CMR reference. Regarding RVEF, further studies including patients with a wider range of RVEF are needed to evaluate the method.

    Conclusion: In conclusion, the ellipsoid model of the RV provides good estimates of RVSVs, but volumes based on distance measurements from different modalities cannot be used interchangeably.

  • 22.
    Humble, Mats B.
    et al.
    Örebro University, School of Medical Sciences.
    Eklund, Daniel
    Örebro University, School of Medical Sciences.
    Fresnais, D.
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Hylén, Ulrika
    Örebro University, School of Health Sciences.
    Sigra, Sofia
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences.
    Bejerot, Susanne
    Örebro University, School of Medical Sciences.
    Rituximab for treatment-resistant schizophrenia and/or obsessive-compulsive disorder (OCD): functional connectivity and cytokines associated with symptomatic improvements2023In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 66, no Suppl. 1, p. S629-S629, article id EPP1035Article in journal (Other academic)
    Abstract [en]

    Introduction: Immunological mechanisms may contribute to the causation of mental illness. Autoimmunity is most convincingly shown for anti-NMDA-R encephalitis and Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS); disorders that overlap clinically with schizophrenia and OCD. Altered inflammatory cytokine production, glial activation and auto-antibodies have also been associated with schizophrenia and OCD. In these disorders, however, the treatment results with anti-inflammatory or immunomodulating drugs have hitherto been limited and inconsistent. Yet other targets within the immune system may still be effective and new options are warranted for treatment-resistant patients. Rituximab targets B-lymphocytes and is often used in autoimmune disorders such as rheumatoid arthritis, multiple sclerosis and anti-NMDA-R encephalitis.

    Objectives: We aimed to investigate whether rituximab is clinically effective, safe and tolerable as add-on therapy in markedly ill, treatment-resistant adult psychiatric patients with schizophrenia or OCD. We also wanted to identify putative mediating mechanisms in treatment responders, such as cytokine changes and functional connectivity (FC).

    Methods: In an open pilot study, adults (18-39 years) with treatment-resistant schizophrenia and/or OCD were included. They received an intravenous infusion of rituximab 1000 mg, once at baseline, in addition to their regular psychiatric medication and were followed for 1 year. The main outcome measures were the Positive and Negative Syndrome Scale (PANSS) or Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Clinical Global Impression-Improvement scale (CGI-I) and the Personal and Social Performance scale (PSP). Treatment response was defined as ≥ 40 % decrease in PANSS or ≥ 35 % decrease in Y-BOCS, and much improved according to CGI-I. Resting-state fMRI was applied at baseline and after 5 months. Plasma cytokines were measured at 0, 3 and 5 months. Cognitive tests and the recently developed PsychoNeuroinflammatory Related Signs and Symptoms Inventory (PNISSI) were used to identify and measure symptoms related to neuro-inflammation and cognitive function.

    Results: Nineteen patients were treated with rituximab. 3-5 months after treatment, 6/9 patients with schizophrenia and 1/10 with OCD responded. One schizophrenia patient continues with rituximab every 6 months and has reportedly done well for almost 3 years. No severe side effects were reported apart from recurrent abdominal pain in a schizophrenia patient and one case of post-COVID-19 syndrome. Significant changes of FC were detected in responders only and correlated with PSP changes.

    Conclusions: Aberrant B-cell activities may contribute to treatment-resistant schizophrenia and be amenable to treatment with rituximab. However, the results of this pilot study need confirmation in placebo-controlled trials.

  • 23.
    Jendeberg, Johan
    et al.
    Örebro University, School of Medical Sciences. Department of Radiology, Örebro University Hospital, Örebro, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Physics.
    Lidén, Mats
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Radiology.
    Differentiation of distal ureteral stones and pelvic phleboliths using a convolutional neural network2021In: Urolithiasis, ISSN 2194-7228, Vol. 49, p. 41-49Article in journal (Refereed)
    Abstract [en]

    The objectives were to develop and validate a Convolutional Neural Network (CNN) using local features for differentiating distal ureteral stones from pelvic phleboliths, compare the CNN method with a semi-quantitative method and with radiologists' assessments and to evaluate whether the assessment of a calcification and its local surroundings is sufficient for discriminating ureteral stones from pelvic phleboliths in non-contrast-enhanced CT (NECT). We retrospectively included 341 consecutive patients with acute renal colic and a ureteral stone on NECT showing either a distal ureteral stone, a phlebolith or both. A 2.5-dimensional CNN (2.5D-CNN) model was used, where perpendicular axial, coronal and sagittal images through each calcification were used as input data for the CNN. The CNN was trained on 384 calcifications, and evaluated on an unseen dataset of 50 stones and 50 phleboliths. The CNN was compared to the assessment by seven radiologists who reviewed a local 5 × 5 × 5 cm image stack surrounding each calcification, and to a semi-quantitative method using cut-off values based on the attenuation and volume of the calcifications. The CNN differentiated stones and phleboliths with a sensitivity, specificity and accuracy of 94%, 90% and 92% and an AUC of 0.95. This was similar to a majority vote accuracy of 93% and significantly higher (p = 0.03) than the mean radiologist accuracy of 86%. The semi-quantitative method accuracy was 49%. In conclusion, the CNN differentiated ureteral stones from phleboliths with higher accuracy than the mean of seven radiologists' assessments using local features. However, more than local features are needed to reach optimal discrimination.

  • 24.
    Jendeberg, Johan
    et al.
    Örebro University, School of Medical Sciences. Department of Radiology.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Medical Physics.
    Popiolek, Marcin
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Lidén, Mats
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Single-energy CT predicts uric acid stones with accuracy comparable to dual-energy CT-prospective validation of a quantitative method2021In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 31, no 8, p. 5980-5989Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To prospectively validate three quantitative single-energy CT (SE-CT) methods for classifying uric acid (UA) and non-uric acid (non-UA) stones.

    METHODS: Between September 2018 and September 2019, 116 study participants were prospectively included in the study if they had at least one 3-20-mm urinary stone on an initial urinary tract SE-CT scan. An additional dual-energy CT (DE-CT) scan was performed, limited to the stone of interest. Additionally, to include a sufficient number of UA stones, eight participants with confirmed UA stone on DE-CT were retrospectively included. The SE-CT stone features used in the prediction models were (1) maximum attenuation (maxHU) and (2) the peak point Laplacian (ppLapl) calculated at the position in the stone with maxHU. Two prediction models were previously published methods (ppLapl-maxHU and maxHU) and the third was derived from the previous results based on the k-nearest neighbors (kNN) algorithm (kNN-ppLapl-maxHU). The three methods were evaluated on this new independent stone dataset. The reference standard was the CT vendor's DE-CT application for kidney stones.

    RESULTS: Altogether 124 participants (59 ± 14 years, 91 men) with 106 non-UA and 37 UA stones were evaluated. For classification of UA and non-UA stones, the sensitivity, specificity, and accuracy were 100% (37/37), 97% (103/106), and 98% (140/143), respectively, for kNN-ppLapl-maxHU; 95% (35/37), 98% (104/106), and 97% (139/143) for ppLapl-maxHU; and 92% (34/37), 94% (100/106), and 94% (134/143) for maxHU.

    CONCLUSION: A quantitative SE-CT method (kNN-ppLapl-maxHU) can classify UA stones with accuracy comparable to DE-CT.

    KEY POINTS:

    • Single-energy CT is the first-line diagnostic tool for suspected renal colic.

    • A single-energy CT method based on the internal urinary stone attenuation distribution can classify urinary stones into uric acid and non-uric acid stones with high accuracy.

    • This immensely increases the availability of in vivo stone analysis.

  • 25.
    Jendeberg, Johan
    et al.
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences.
    Popiolek, Marcin
    Örebro University Hospital, Örebro, Sweden.
    Lidén, Mats
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Single-energy CT predicts uric acid stones with accuracy comparableto dual-energy CT: Prospective validation of a quantitative methodManuscript (preprint) (Other academic)
  • 26.
    Jorstig, Stina
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Emilsson, Kent
    Department of Clinical Physiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Waldenborg, Micael
    Örebro University, School of Health Sciences. Örebro University Hospital. Department of Clinical Physiology, Örebro University Hospital, Örebro, Sweden.
    Lidén, Mats
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Radiology, Örebro University Hospital, Örebro, Sweden.
    Wodecki, M.
    Department of Clinical Physiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Physics, Örebro University Hospital, Örebro, Sweden.
    Distance and area measurement of the right atrium and ventricle by echocardiography and cardiac magnetic resonance imaging: do we measure the same thing?2016Conference paper (Other academic)
    Abstract [en]

    Purpose: It has previously been shown that stroke volumes measured by transthoracic echocardiography (TTE) are underestimated, compared to cardiac magnetic resonance (CMR) imaging. The purpose of this study was to evaluate differences in distance and area measurements of the right atrium (RA) and the right ventricle (RV) by TTE and CMR.

    Methods: TTE examinations and CMR examinations were subsequently performed in 12 healthy volunteers. Three distances (RAL - right atrial length, RVIT3 - right ventricular inflow tract, RVLAX - right ventricular long axis) and one area (RVA - right ventricular area) were measured in TTE and CMR. Stroke volumes were also calculated using conventional methods available on each modality. Both intramodality and intermodality comparisons were performed based on measurements from three observers. One of the observers performed measurements in both TTE and CMR.

    Results: Intermodality comparisons showed that all distance and area measurements were significantly smaller using TTE (Table 1). Two of the measurements, RVIT3 and RVA, differed at about 50%. Calculated stroke volumes showed, consistent with previous results, that the TTE stroke volumes are substantially underestimated compared to CMR volumes. Intramodality variations of distance and area measurements were considerably smaller (Table 1).

    Conclusions: Our results show that RV distances and areas measured by TTE are smaller compared to CMR, probably due to differences in defining the endocardial borders. These differences subsequently result in smaller stroke volumes when using TTE. Caution should be taken when comparing distances, areas and volumes measured by TTE and CMR.

  • 27.
    Jorstig, Stina Hellstrand
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Emilsson, Kent
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Physiology, Örebro University Hospital, Örebro, Sweden.
    Lidén, Mats
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Radiology, Örebro University Hospital, Örebro, Sweden.
    Thunberg, Per
    Örebro University Hospital. Department of Medical Physics, Örebro University Hospital, Örebro, Sweden.
    A study to determine the contribution to right ventricle stroke volume from pulmonary and tricuspid valve displacement volumes2015In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 35, no 4, p. 283-290Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Describing the systolic function of the right ventricle (RV) is a difficult task due to the complex shape and orientation of the RV. The purpose of this study was to investigate the extent to which the volumes encompassed by the pulmonary and tricuspid valve displacements contribute to the total right ventricle stroke volume (RVSV).

    METHODS: Twelve healthy volunteers were examined using cardiac magnetic resonance (CMR). Two series of time-resolved axially rotated MR images were acquired that encompassed the tricuspid valve and the pulmonary valve, respectively. The volume related to each valve movement, the tricuspid plane displacement (TPD) and the pulmonary plane displacement (PPD), was determined by delineation in diastole and systole. These volumes, RVSVTPD and RVSVPPD , were compared to the stroke volume to determine the contributions to the total stroke volume from the TPD and the PPD. The remaining volume of the total RVSV was referred to as RVSVOther . An initial in vitro study was carried out to validate the accuracy of volume measurements using axially rotated images.

    RESULTS: In vitro measurements indicated that the method for volumetric measurements using axially rotated images was a very accurate one, with a mean difference of 0·04 ± 0·10 ml. The in vivo measurements of RVSVTPD , RVSVPPD and RVSVOther were 45 ± 10%, 13 ± 2% and 42 ± 11%, respectively.

    CONCLUSIONS: Right ventricle stroke volume is determined by different individual volume changes as follows: RVSVTPD together with RVSVOther contributes to almost the entire RVSV in nearly equal proportions, while RVSVPPD contributes only a small amount and is approximately 30% of either RVSVTPD or RVSVOther.

  • 28.
    Jorstig, Stina Hellstrandh
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kähäri, Anders
    Department of Radiology, Örebro University Hospital, Örebro, Sweden.
    Emilsson, Kent
    Department of Clinical Physiology, Örebro University Hospital, Örebro, Sweden.
    Thunberg, Per
    Department of Medical Physics, Örebro University Hospital, Örebro, Sweden.
    Calculation of right ventricular stroke volume in short-axis MR images using the equation of the tricuspid plane2012In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 32, no 1, p. 5-11Article in journal (Refereed)
    Abstract [en]

    Short-axis (SA) magnetic resonance (MR) images are commonly planned parallel to the left atrioventricular valve. This orientation leads to oblique slices of the right ventricle (RV) with subsequent difficulties in separating the RV from the right atrium in the SA images. The insertion points of the tricuspid valve (TV) in the myocardium can be clearly identified in the right ventricle long axis (RVLA) and four-chamber (4CH) views. The purpose of this study was to develop a method that transfers the position of the tricuspid plane, as seen in the RVLA and 4CH views, to the SA images to facilitate the separation of the RV from the atrium. This methodology, termed Dissociating the Right Atrium from the Ventricle Volume (DRAW), was applied in 20 patients for calculations of right ventricular stroke volume (RVSV). The RVSV using DRAW (RVSVDRAW) was compared to left ventricular stroke volumes (LVSV) obtained from flow measurements in the ascending aorta. The RVSV was also determined using the conventional method (RVSVCONV) where the stack of images from the SA views are summarized, and a visual decision is made of the most basal slice to be included in the RV. The mean difference between RVSVDRAW and LVSV was 0.1 +/- 12.7 ml, while the mean difference between RVSVCONV and LVSV was 0.33 +/- 14.3 ml. Both the intra- and interobserver variability were small using the DRAW methodology, 0.6 +/- 3.5 and 1.7 +/- 2.7 ml, respectively. In conclusion, the DRAW method can be used to facilitate the separation of the RV and the atrium.

  • 29.
    Jorstig, Stina
    et al.
    Örebro University, School of Medical Sciences.
    Waldenborg, Micael
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lidén, Mats
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences.
    Right ventricular ejection fraction measurements using twodimensional echocardiographyManuscript (preprint) (Other academic)
  • 30.
    Jorstig, Stina
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Faculty of Medicine and Health, Örebro University Biomedical Engineering, Örebro University Hospital, Örebro, Sweden.
    Waldenborg, Micael
    Örebro University Hospital. Örebro University, School of Medical Sciences. Faculty of Medicine and Health and Department of Clinical Physiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lidén, Mats
    Örebro University, School of Medical Sciences. Örebro University Hospital. Faculty of Medicine and Health and Department of Radiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Örebro University Hospital. Faculty of Medicine and Health and Department of Medical Physics, Department of Medical Physics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Right ventricular ejection fraction measurements using two-dimensional transthoracic echocardiography by applying an ellipsoid model2017In: Cardiovascular Ultrasound, E-ISSN 1476-7120, Vol. 15, article id 4Article in journal (Refereed)
    Abstract [en]

    Background: There is today no established approach to estimate right ventricular ejection fraction (RVEF) using 2D transthoracic echocardiography (TTE). The aim of this study was to evaluate a new method for RVEF calculations using 2D TTE and compare the results with cardiac magnetic resonance (CMR) imaging and tricuspid annular plane systolic excursion (TAPSE).

    Methods: A total of 37 subjects, 25 retrospectively included patients and twelve healthy volunteers, were included to give a wide range of RVEF. The right ventricle (RV) was modeled as a part of an ellipsoid enabling calculation of the RV volume by combining three distance measurements. RVEF calculated according to the model, RVEFTTE, were compared with reference CMR-derived RVEF, RVEFCMR. Further, TAPSE was measured in the TTE images and the correlations were calculated between RVEFTTE, TAPSE and RVEFCMR.

    Results: The mean values were RVEFCMR = 43 +/- 12% (range 20-66%) and RVEFTTE = 50 +/- 9% (range 34-65%). There was a high correlation (r = 0.80, p < 0.001) between RVEFTTE and RVEFCMR. Bland-Altman analysis showed a mean difference between RVEFCMR and RVEFTTE of 6 percentage points (ppt) with limits of agreement from -11 to 23 ppt. The mean value for TAPSE was 19 +/- 5 mm and the correlation between TAPSE and RVEFCMR was moderate (r = 0.54, p < 0.001). The correlation between RVEFTTE and RVEFCMR was significantly higher (p < 0.05) than the correlation between TAPSE and RVEFCMR.

    Conclusions: The ellipsoid model shows promise for RVEF calculations using 2D TTE for a wide range of RVEF, providing RVEF estimates that were significantly better correlated to RVEF obtained from CMR compared to TAPSE.

  • 31.
    Karlsson, Leif
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medical Physics, Örebro University Hospital, Örebro, Sweden.
    Thunberg, Per
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medical Physics, Örebro University Hospital, Örebro, Sweden.
    Johansson, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Persliden, Jan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medical Physics, Örebro University Hospital, Örebro, Sweden.
    The impact of activating source dwell positions outside the CTV on the dose to treated normal tissue volumes in TRUS guided 3D conformal interstitial HDR brachytherapy of prostate cancer2014In: Journal of Contemporary Brachytherapy, ISSN 1689-832X, E-ISSN 2081-2841, Vol. 6, no 3, p. 282-288Article in journal (Refereed)
    Abstract [en]

    Purpose: Dose coverage is crucial for successful treatment in mono-brachytherapy. Since few and very high dose fractions are used, there is an important balance between dwell positioning outside the clinical target volume (CTV) and possible damage on adjacent normal tissue. The purpose of this study was to evaluate the possibility of having dwell positions close to the CTV surface, while maintaining an acceptable dose distribution, and to investigate the robustness in terms of known geometrical uncertainties of the implant.

    Material and methods: This study included 37 patients who had received brachytherapy for prostate cancer as a monotherapy with the following schedules: 2 x 14 Gy or 3 x 11 Gy, each fraction separated by two weeks. The source dwell positions were activated 5 mm outside CTV. New optimizations were simulated for dwell positions at 3, 2, 1, and 0 mm. Inverse and graphical optimization were applied according to the relative dose constraints: V-100 CTV >= 97%, D-max,D- urethra <= 110%, and D-10 rectal mucosa <= 65%. The V-100 normal tissue outside CTV was used to evaluate dose variations caused by different dwell positions. Prostate geometries and dose distributions for the different dwell positions outside the CTV were used to investigate the impact on the CTV dose distribution due to geometrical uncertainties.

    Results: Both V-100,V- CTV, and V-100,V- normal tissue decreased, 98.6% to 92.2%, and 17 cm(3) to 9.0 cm(3), for dwell activation from 5 rum to 0 mm. The evaluation of both simulated longitudinal geometrical uncertainties and different source dwell activations implied that V-100,V- CTV ranged from 98.6% to 86.3%.

    Conclusions: It is possible to reduce the V-100,V- normal tissue by decreasing the source dwell positions outside the CTV from 5 to 3 mm, while maintaining dose constraints. In combination with the estimated geometrical uncertainties, however, the source dwell positions need to be 5 mm from the surface in order to maintain a robust implant.

  • 32.
    Karlsson, Leif
    et al.
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Medical Physics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Physics, Örebro University Hospital, Örebro, Sweden.
    With, Anders
    Department of Medical Physics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Mordhorst, Louise Bohr
    Örebro University, School of Medical Sciences. Department of Oncology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Persliden, Jan
    Örebro University Hospital. School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Medical Physics, Örebro University Hospital, Örebro, Sweden.
    3D image-based adapted high-dose-rate brachytherapy in cervical cancer with and without interstitial needles: measurement of applicator shift between imaging and dose delivery2017In: Journal of Contemporary Brachytherapy, ISSN 1689-832X, E-ISSN 2081-2841, Vol. 9, no 1, p. 52-58Article in journal (Refereed)
    Abstract [en]

    Purpose: Using 3D image-guided adaptive brachytherapy for cervical cancer treatment, it often means that patients are transported and moved during the treatment procedure. The purpose of this study was to determine the intra-fractional longitudinal applicator shift in relation to the high risk clinical target volume (HR-CTV) by comparing geometries at imaging and dose delivery for patients with and without needles.

    Material and methods: Measurements were performed in 33 patients (71 fractions), where 25 fractions were without and 46 were with interstitial needles. Gold markers were placed in the lower part of the cervix as a surrogate for HR-CTV, enabling distance measurements between HR-CTV and the ring applicator. Shifts of the applicator relative to the markers were determined using planning computed tomography (CT) images used for planning, and the radiographs obtained at dose delivery. Differences in the physical D-90 for HR-CTV due to applicator shifts were simulated individually in the treatment planning system to provide the relative dose variation.

    Results: The maximum distances of the applicator shifts, in relation to the markers, were 3.6 mm (caudal), and-2.5 mm (cranial). There was a significant displacement of-0.7 mm (SD = 0.9 mm) without needles, while with needles there was no significant shift. The relative dose variation showed a significant increase in D-90 HR-CTV of 1.6% (SD = 2.6%) when not using needles, and no significant dose variation was found when using needles.

    Conclusions: The results from this study showed that there was a small longitudinal displacement of the ring applicator and a significant difference in displacement between using interstitial needles or not.

  • 33.
    Krauss, Wolfgang
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Gunnarsson, Martin
    Örebro University, School of Medicine, Örebro University, Sweden.
    Andersson, Torbjorn
    Örebro University, School of Medicine, Örebro University, Sweden.
    Thunberg, Per
    Department of Medical Physics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Accuracy and reproducibility of a quantitative magnetic resonance imaging method for concurrent measurements of tissue relaxation times and proton density2015In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 33, no 5, p. 584-591Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the accuracy and reproducibility of a quantitative magnetic resonance (qMR) imaging method (QRAPMASTER) for simultaneous measurements of T1 and T2 relaxation times, and proton density (PD).

    Materials and Methods: Measurements of T1, T2, and PD with qMR were performed using phantoms with different relaxation times and concentrations of heavy water. Healthy volunteers were examined with different head coils. Regional measurements were performed in normal-appearing white and gray matter from the healthy control subjects, and in multiple sclerosis (MS) patients.

    Results: In phantom measurements, QRAPMASTER slightly underestimated T1, and T2 variations between repeated measurements were modest. PD was generally overestimated. The overall relative difference was 1.2 5.3% (T1), 6.6 1.9% (12), and 0.7 5.1% (PD). In healthy volunteers, there were no statistically significant differences of T1, T2 or PD using different head coils. Values of T1, T2, and PD obtained in healthy controls and MS patients were within reference ranges. However, significant differences were found in normal-appearing gray and white matter.

    Conclusion: QRAPMASTER can be considered a sufficiently accurate and reproducible method for use in clinical practice. Neuropathology in normal-appearing brain tissue may be revealed using this MR method, with putative implications for quantification of tissue damage in neurological diseases. (C) 2015 Elsevier Inc. All rights reserved.

  • 34.
    Krauss, Wolfgang
    et al.
    Örebro University, School of Medical Sciences. Department of Radiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Gunnarsson, Martin
    Örebro University, School of Medical Sciences. Department of Neurology and Neurophysiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Nilsson, Margareta
    Centre for Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Medical Physics, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Conventional and synthetic MRI in multiple sclerosis: a comparative study2018In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 28, no 4, p. 1692-1700Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To compare the assessment of patients with multiple sclerosis (MS) using synthetic and conventional MRI.

    MATERIALS AND METHODS: Synthetic and conventional axial images were prospectively acquired for 52 patients with diagnosed MS. Quantitative MRI (qMRI) was used for measuring proton density and relaxation times (T1, T2) and then, based on these parameters, synthetic T1W, T2W and FLAIR images were calculated. Image stacks were reviewed blindly, independently and in random order by two radiologists. The number and location for all lesions were documented and categorised. A combined report of lesion load and presence of contrast-enhancing lesions was compiled for each patient. Agreement was evaluated using kappa statistic.

    RESULTS: There was no significant difference in lesion detection using synthetic and conventional MRI in any anatomical region or for any of the three image types. Inter- and intra-observer agreements were mainly higher (p < 0.05) using conventional images but there was no significant difference in any specific region or for any image type. There was no significant difference in the outcome of the combined reports.

    CONCLUSION: Synthetic MR images show potential to be used in the assessment of MS dissemination in space (DIS) despite a slightly lower inter- and intra-observer agreement compared to conventional MRI.

    KEY POINTS:

    • Synthetic MR images may potentially be useful in the assessment of MS.

    • Examination times may be shortened.

    • Inter- and intra-observer agreement is generally higher using conventional MRI.

  • 35.
    Krauss, Wolfgang
    et al.
    Örebro University, School of Medical Sciences. Department of Radiology and Medical Physics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Janusz, Frey
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Heydorn Lagerlöf, Jakob
    Örebro University, School of Medical Sciences. School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Medical Physics, Karlstad Central Hospital, Sweden.
    Lidén, Mats
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Radiology and Medical Physics.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Radiology and Medical Physics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Radiomics from multisite MRI and clinical data to predict clinically significant prostate cancer2023In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, article id 2841851231216555Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Magnetic resonance imaging (MRI) is useful in the diagnosis of clinically significant prostate cancer (csPCa). MRI-derived radiomics may support the diagnosis of csPCa. PURPOSE: To investigate whether adding radiomics from biparametric MRI to predictive models based on clinical and MRI parameters improves the prediction of csPCa in a multisite-multivendor setting.

    MATERIAL AND METHODS: Clinical information (PSA, PSA density, prostate volume, and age), MRI reviews (PI-RADS 2.1), and radiomics (histogram and texture features) were retrieved from prospectively included patients examined at different radiology departments and with different MRI systems, followed by MRI-ultrasound fusion guided biopsies of lesions PI-RADS 3-5. Predictive logistic regression models of csPCa (Gleason score ≥7) for the peripheral (PZ) and transition zone (TZ), including clinical data and PI-RADS only, and combined with radiomics, were built and compared using receiver operating characteristic (ROC) curves.

    RESULTS: In total, 456 lesions in 350 patients were analyzed. In PZ and TZ, PI-RADS 4-5 and PSA density, and age in PZ, were independent predictors of csPCa in models without radiomics. In models including radiomics, PI-RADS 4-5, PSA density, age, and ADC energy were independent predictors in PZ, and PI-RADS 5, PSA density and ADC mean in TZ. Comparison of areas under the ROC curve (AUC) for the models without radiomics (PZ: AUC = 0.82, TZ: AUC = 0.80) versus with radiomics (PZ: AUC = 0.82, TZ: AUC = 0.82) showed no significant differences (PZ: P = 0.366; TZ: P = 0.171).

    CONCLUSION: PSA density and PI-RADS are potent predictors of csPCa. Radiomics do not add significant information to our multisite-multivendor dataset.

  • 36.
    Kähäri, Anders
    et al.
    Department of Radiology, Örebro University Hospital, Örebro, Sweden.
    Thunberg, Per
    Department of Biomedical Engineering, Örebro University Hospital, Örebro, Sweden.
    Emilsson, Kent
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Physiology, Karlskoga Hospital, Karlskoga, Sweden.
    Geijer, Håkan
    Department of Radiology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Torbjörn
    Wandt, Birger
    Assessment of left ventricular function from M-mode measurement of circumflex artery motion recorded by coronary angiography.2003In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 37, no 5, p. 259-265Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the usefulness of M-mode measurement of circumflex artery motion (CAM) for assessment of left ventricular (LV) function.

    DESIGN: Seventy-two patients referred for coronary angiography and LV angiography were included. Ejection fraction (EF) was calculated from LV angiography and systolic and diastolic parameters of CAM were measured by M-mode from coronary angiography. Twenty-three patients, examined by echocardiography of mitral annulus motion (MAM) within 24 h before the angiographic examination, formed a subgroup for comparison between angiographic M-mode of CAM and echocardiographic M-mode of MAM.

    RESULTS: In addition to previous reported CAM amplitude and longitudinal fractional shortening (FSL) the maximal systolic velocity of CAM can be reliably recorded by M-mode. The diastolic indices, atrial contribution to the total amplitude and maximal early and late diastolic velocities, are also well monitored by M-mode of CAM in comparison with echocardiographic MAM.

    CONCLUSION: LV systolic and diastolic function can be assessed by M-mode of CAM.

  • 37.
    Lidén, Mats
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Radiology.
    Adrian, David
    Department of Radiology, Örebro University Hospital, Region Örebro County, Sweden.
    Widell, Jonas
    Department of Radiology, Örebro University Hospital, Region Örebro County, Sweden.
    Uggla, Bertil
    Örebro University, School of Medical Sciences. Department of Medicine.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Medical Physics.
    Quantitative T2* imaging of iron overload in a non-dedicated center - Normal variation, repeatability and reader variation2021In: European journal of radiology open, E-ISSN 2352-0477, Vol. 8, article id 100357Article in journal (Refereed)
    Abstract [en]

    Background: Patients with transfusion dependent anemia are at risk of complications from iron overload. Quantitative T2* magnetic resonance imaging (MRI) is the best non-invasive method to assess iron deposition in the liver and heart and to guide chelation therapy.

    Purpose: To investigate the image quality and inter-observer variations in T2* measurements of the myocardium and the liver, and to obtain the lower limit of cardiac and hepatic quantitative T2* values in patients without suspicion of iron overload.

    Material and methods: Thirty-eight patients referred for cardiac MRI were prospectively included in the study. Three patients were referred with, and 35 without suspicion of iron overload. Quantitative T2* parametric maps were obtained on a 1.5 T MRI system in the cardiac short axis and liver axial view. Two readers independently assessed the image quality and the representative and the lowest T2* value in the myocardium and the liver.

    Results: The normal range of representative T2* values in the myocardium and liver was 24-45 ms and 14-37 ms, respectively. None of the 35 participants (0 %, 95 % confidence interval 0-11 %) in the normal reference group demonstrated representative T2* values below previously reported lower limits in the myocardium (20 ms) or the liver (8 ms). Focal myocardial areas with T2* values near the lower normal range, 19-20 ms, were seen in two patients. The readers generally reported good image quality.

    Conclusion: T2* imaging for assessing iron overload can be performed in a non-dedicated center with sufficient image quality.

  • 38.
    Lidén, Mats
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Radiology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Torbjörn
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Broxvall, Mathias
    Örebro University, School of Science and Technology.
    Thunberg, Per
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medical Physics, Örebro University Hospital, Örebro, Sweden.
    Geijer, Håkan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Urinary stone size estimation: a new segmentation algorithm-based CT method2012In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 22, no 4, p. 731-737Article in journal (Refereed)
    Abstract [en]

    The size estimation in CT images of an obstructing ureteral calculus is important for the clinical management of a patient presenting with renal colic. The objective of the present study was to develop a reader independent urinary calculus segmentation algorithm using well-known digital image processing steps and to validate the method against size estimations by several readers. Fifty clinical CT examinations demonstrating urinary calculi were included. Each calculus was measured independently by 11 readers. The mean value of their size estimations was used as validation data for each calculus. The segmentation algorithm consisted of interpolated zoom, binary thresholding and morphological operations. Ten examinations were used for algorithm optimisation and 40 for validation. Based on the optimisation results three segmentation method candidates were identified. Between the primary segmentation algorithm using cubic spline interpolation and the mean estimation by 11 readers, the bias was 0.0 mm, the standard deviation of the difference 0.26 mm and the Bland-Altman limits of agreement 0.0 +/- 0.5 mm. The validation showed good agreement between the suggested algorithm and the mean estimation by a large number of readers. The limit of agreement was narrower than the inter-reader limit of agreement previously reported for the same data. The size of kidney stones is usually estimated manually by the radiologist. An algorithm for computer-aided size estimation is introduced. The variability between readers can be reduced. A reduced variability can give better information for treatment decisions.

  • 39.
    Lidén, Mats
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Radiology.
    Hjelmgren, Ola
    Department of Molecular and Clinical Medicine, Institute ofMedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Clinical Physiology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Vikgren, Jenny
    Department of Radiology, Sahlgrenska University Hospital and Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Medical Physics.
    Multi-Reader-Multi-Split Annotation of Emphysema in Computed Tomography2020In: Journal of digital imaging, ISSN 0897-1889, E-ISSN 1618-727X, Vol. 33, no 5, p. 1185-1193Article in journal (Refereed)
    Abstract [en]

    Emphysema is visible on computed tomography (CT) as low-density lesions representing the destruction of the pulmonary alveoli. To train a machine learning model on the emphysema extent in CT images, labeled image data is needed. The provision of these labels requires trained readers, who are a limited resource. The purpose of the study was to test the reading time, inter-observer reliability and validity of the multi-reader-multi-split method for acquiring CT image labels from radiologists. The approximately 500 slices of each stack of lung CT images were split into 1-cm chunks, with 17 thin axial slices per chunk. The chunks were randomly distributed to 26 readers, radiologists and radiology residents. Each chunk was given a quick score concerning emphysema type and severity in the left and right lung separately. A cohort of 102 subjects, with varying degrees of visible emphysema in the lung CT images, was selected from the SCAPIS pilot, performed in 2012 in Gothenburg, Sweden. In total, the readers created 9050 labels for 2881 chunks. Image labels were compared with regional annotations already provided at the SCAPIS pilot inclusion. The median reading time per chunk was 15 s. The inter-observer Krippendorff's alpha was 0.40 and 0.53 for emphysema type and score, respectively, and higher in the apical part than in the basal part of the lungs. The multi-split emphysema scores were generally consistent with regional annotations. In conclusion, the multi-reader-multi-split method provided reasonably valid image labels, with an estimation of the inter-observer reliability.

  • 40.
    Lidén, Mats
    et al.
    Örebro University, School of Medical Sciences.
    Jendeberg, Johan
    Örebro University, School of Medical Sciences.
    Längkvist, Martin
    Örebro University, School of Science and Technology.
    Loutfi, Amy
    Örebro University, School of Science and Technology.
    Thunberg, Per
    Örebro University, School of Medical Sciences.
    Discrimination between distal ureteral stones and pelvic phleboliths in CT using a deep neural network: more than local features needed2018Conference paper (Refereed)
    Abstract [en]

    Purpose: To develop a deep learning method for assisting radiologists in the discrimination between distal ureteral stones and pelvic phleboliths in thin slice CT images, and to evaluate whether this differentiation is possible using only local features.

    Methods and materials: A limited field-of-view image data bank was retrospectively created, consisting of 5x5x5 cm selections from 1 mm thick unenhanced CT images centered around 218 pelvis phleboliths and 267 distal ureteral stones in 336 patients. 50 stones and 50 phleboliths formed a validation cohort and the remainder a training cohort. Ground truth was established by a radiologist using the complete CT examination during inclusion.The limited field-of-view CT stacks were independently reviewed and classified as containing a distal ureteral stone or a phlebolith by seven radiologists. Each cropped stack consisted of 50 slices (5x5 cm field-of-view) and was displayed in a standard PACS reading environment. A convolutional neural network using three perpendicular images (2.5D-CNN) from the limited field-of-view CT stacks was trained for classification.

    Results: The 2.5D-CNN obtained 89% accuracy (95% confidence interval 81%-94%) for the classification in the unseen validation cohort while the accuracy of radiologists reviewing the same cohort was 86% (range 76%-91%). There was no statistically significant difference between 2.5D-CNN and radiologists.

    Conclusion: The 2.5D-CNN achieved radiologist level classification accuracy between distal ureteral stones and pelvic phleboliths when only using the local features. The mean accuracy of 86% for radiologists using limited field-of-view indicates that distant anatomical information that helps identifying the ureter’s course is needed.

  • 41.
    Lidén, Mats
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Radiology and Medical Physics.
    Spahr, Antoine
    Department of Biomedical Engineering and Health Systems, KTH Royal Institute of Technology School of Technology and Health, Stockholm, Sweden.
    Hjelmgren, Ola
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Clinical Physiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
    Bendazzoli, Simone
    Department of Biomedical Engineering and Health Systems, KTH Royal Institute of Technology School of Technology and Health, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology - CLINTEC, Karolinska Institutet, Stockholm, Sweden.
    Sundh, Josefin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Respiratory Medicine.
    Sköld, Magnus
    Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden.
    Bergström, Göran
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Clinical Physiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
    Wang, Chunliang
    Department of Biomedical Engineering and Health Systems, KTH Royal Institute of Technology School of Technology and Health, Stockholm, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Radiology and Medical Physics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Machine learning slice-wise whole-lung CT emphysema score correlates with airway obstruction2023In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Quantitative CT imaging is an important emphysema biomarker, especially in smoking cohorts, but does not always correlate to radiologists' visual CT assessments. The objectives were to develop and validate a neural network-based slice-wise whole-lung emphysema score (SWES) for chest CT, to validate SWES on unseen CT data, and to compare SWES with a conventional quantitative CT method.

    MATERIALS AND METHODS: Separate cohorts were used for algorithm development and validation. For validation, thin-slice CT stacks from 474 participants in the prospective cross-sectional Swedish CArdioPulmonary bioImage Study (SCAPIS) were included, 395 randomly selected and 79 from an emphysema cohort. Spirometry (FEV1/FVC) and radiologists' visual emphysema scores (sum-visual) obtained at inclusion in SCAPIS were used as reference tests. SWES was compared with a commercially available quantitative emphysema scoring method (LAV950) using Pearson's correlation coefficients and receiver operating characteristics (ROC) analysis.

    RESULTS: SWES correlated more strongly with the visual scores than LAV950 (r = 0.78 vs. r = 0.41, p < 0.001). The area under the ROC curve for the prediction of airway obstruction was larger for SWES than for LAV950 (0.76 vs. 0.61, p = 0.007). SWES correlated more strongly with FEV1/FVC than either LAV950 or sum-visual in the full cohort (r =  - 0.69 vs. r =  - 0.49/r =  - 0.64, p < 0.001/p = 0.007), in the emphysema cohort (r =  - 0.77 vs. r =  - 0.69/r =  - 0.65, p = 0.03/p = 0.002), and in the random sample (r =  - 0.39 vs. r =  - 0.26/r =  - 0.25, p = 0.001/p = 0.007).

    CONCLUSION: The slice-wise whole-lung emphysema score (SWES) correlates better than LAV950 with radiologists' visual emphysema scores and correlates better with airway obstruction than do LAV950 and radiologists' visual scores.

    CLINICAL RELEVANCE STATEMENT: The slice-wise whole-lung emphysema score provides quantitative emphysema information for CT imaging that avoids the disadvantages of threshold-based scores and is correlated more strongly with reference tests than LAV950 and reader visual scores.

    KEY POINTS: • A slice-wise whole-lung emphysema score (SWES) was developed to quantify emphysema in chest CT images. • SWES identified visual emphysema and spirometric airflow limitation significantly better than threshold-based score (LAV950). • SWES improved emphysema quantification in CT images, which is especially useful in large-scale research.

  • 42.
    Lidén, Mats
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Thunberg, Per
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Kliniskt forskningscentrum (KFC), Univeritetssjukhuset, Örebro, Sverige.
    Broxvall, Mathias
    Örebro University, School of Science and Technology.
    Geijer, Håkan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Two- and three-dimensional CT measurements of urinary calculi length and width: a comparative studyManuscript (preprint) (Other academic)
    Abstract [en]

    The standard imaging procedure for a patient presenting with renal colic is unenhanced CT. The CT measured size has a close correlation to the estimated prognosis for spontaneous passage of a ureteral calculus. Size estimations of urinary calculi in CT images are still based on 2d-reformats. In the present study we developed and validated a calculus oriented 3dmethod for measurements of length and width of urinary calculi and compared those with corresponding 2d measurements in axial and coronal reformats.

    Methods: Fifty unenhanced CT examinations demonstrating urinary calculi were included. A 3d-symmetric segmentation algorithm was validated against reader size estimations. The calculus-oriented size from the segmentation was then compared to the size in axial and coronal reformats.

    Results: The validation showed 0.1±0.7 mm agreement against reference measure. There was a 0.4 mm median bias for 3d-estimated calculus length compared to 2d (p<0.001), but no significant bias for 3d-width compared to 2d.

    Conclusion: The size of the urinary calculus becomes underestimated if its orientation is not aligned to the axial or coronal image plane. Future studies aiming to correlate calculus size with patient outcome should use a calculus oriented size estimation.

  • 43.
    Lidén, Mats
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Radiology, Örebro University Hospital, Örebro, Sweden; Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.
    Thunberg, Per
    Örebro University Hospital. Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Medical Physics, Örebro University Hospital, Örebro, Sweden.
    Broxvall, Mathias
    Modeling and Simulation Research Center, Örebro University, Örebro, Sweden.
    Geijer, Håkan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Radiology, Örebro University Hospital, Örebro, Sweden.
    Two- and three-dimensional CT measurements of urinary calculi length and width: a comparative study2015In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 56, no 4, p. 487-492Article in journal (Refereed)
    Abstract [en]

    Background: The standard imaging procedure for a patient presenting with renal colic is unenhanced computed tomography (CT). The CT measured size has a close correlation to the estimated prognosis for spontaneous passage of a ureteral calculus. Size estimations of urinary calculi in CT images are still based on two-dimensional (2D) reformats.

    Purpose: To develop and validate a calculus oriented three-dimensional (3D) method for measuring the length and width of urinary calculi and to compare the calculus oriented measurements of the length and width with corresponding 2D measurements obtained in axial and coronal reformats.

    Material and Methods: Fifty unenhanced CT examinations demonstrating urinary calculi were included. A 3D symmetric segmentation algorithm was validated against reader size estimations. The calculus oriented size from the segmentation was then compared to the estimated size in axial and coronal 2D reformats.

    Results: The validation showed 0.1 +/- 0.7mm agreement against reference measure. There was a 0.4mm median bias for 3D estimated calculus length compared to 2D (P < 0.001), but no significant bias for 3D width compared to 2D.

    Conclusion: The length of a calculus in axial and coronal reformats becomes underestimated compared to 3D if its orientation is not aligned to the image planes. Future studies aiming to correlate calculus size with patient outcome should use a calculus oriented size estimation.

  • 44.
    Lidén, Mats
    et al.
    Örebro University, School of Medical Sciences.
    Wodecki, Maciej
    Department of Clinical Physiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Medical Physics.
    Rask, Peter
    Örebro University Hospital. Örebro University, School of Medical Sciences.
    Impact of Heart Rate on Flow Measurements in Aortic Regurgitation2017In: Journal of Heart Valve Disease, ISSN 0966-8519, E-ISSN 2053-2644, Vol. 26, no 5, p. 502-508, article id 4562Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Flow measurements using cardiac magnetic resonance imaging (CMRI) enable quantification of the stroke volume, regurgitant volume (RV) and regurgitant fraction (RF) in patients with aortic regurgitation (AR). These variables are used to assess the severity of the valve disease and for the timing of surgery. The aim of the study was to investigate the impact of an increased heart rate on measurement of the RV and RF in patients with AR.

    METHODS: Among 13 patients with known moderate or severe AR, regurgitant flow measurements, using phase-contrast cine magnetic resonance imaging, were obtained in the ascending aorta. Flow measurements were obtained at rest and at increased heart rates after intravenous administration of atropine.

    RESULTS: The mean heart rate was 61 beats per min at rest and 91 beats per min after atropine administration. The RV and RF were 52 ml and 35% at rest, respectively, and 34 ml (p <0.001) and 30% (p = 0.065) at increased heart rate, respectively.

    CONCLUSIONS: An increased heart rate leads to a decreased RV. The RF is more stable and may therefore be preferable for severity grading in AR.

  • 45.
    Längkvist, Martin
    et al.
    Örebro University, School of Science and Technology.
    Jendeberg, Johan
    Örebro University, School of Medical Sciences. Department of Radiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Medical Physics, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Loutfi, Amy
    Örebro University, School of Science and Technology.
    Lidén, Mats
    Örebro University, School of Medical Sciences. Department of Radiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Computer aided detection of ureteral stones in thin slice computed tomography volumes using Convolutional Neural Networks2018In: Computers in Biology and Medicine, ISSN 0010-4825, E-ISSN 1879-0534, Vol. 97, p. 153-160Article in journal (Refereed)
    Abstract [en]

    Computed tomography (CT) is the method of choice for diagnosing ureteral stones - kidney stones that obstruct the ureter. The purpose of this study is to develop a computer aided detection (CAD) algorithm for identifying a ureteral stone in thin slice CT volumes. The challenge in CAD for urinary stones lies in the similarity in shape and intensity of stones with non-stone structures and how to efficiently deal with large high-resolution CT volumes. We address these challenges by using a Convolutional Neural Network (CNN) that works directly on the high resolution CT volumes. The method is evaluated on a large data base of 465 clinically acquired high-resolution CT volumes of the urinary tract with labeling of ureteral stones performed by a radiologist. The best model using 2.5D input data and anatomical information achieved a sensitivity of 100% and an average of 2.68 false-positives per patient on a test set of 88 scans.

  • 46.
    Rode, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Edebol Carlman, Hanna M. T.
    Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    König, Julia
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Radiology and Medical Physics.
    Persson, Jonas
    Örebro University, School of Law, Psychology and Social Work.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Multi-Strain Probiotic Mixture Affects Brain Morphology and Resting State Brain Function in Healthy Subjects: An RCT2022In: Cells, E-ISSN 2073-4409, Vol. 11, no 18, article id 2922Article in journal (Refereed)
    Abstract [en]

    Probiotics can alter brain function via the gut-brain axis. We investigated the effect of a probiotic mixture containing Bifidobacterium longum, Lactobacillus helveticus and Lactiplantibacillus plantarum. In a randomized, placebo-controlled, double-blinded crossover design, 22 healthy subjects (6 m/16 f; 24.2 ± 3.4 years) underwent four-week intervention periods with probiotics and placebo, separated by a four-week washout period. Voxel-based morphometry indicated that the probiotic intervention affected the gray matter volume of a cluster covering the left supramarginal gyrus and superior parietal lobule (p &lt; 0.0001), two regions that were also among those with an altered resting state functional connectivity. Probiotic intervention resulted in significant (FDR &lt; 0.05) functional connectivity changes between regions within the default mode, salience, frontoparietal as well as the language network and several regions located outside these networks. Psychological symptoms trended towards improvement after probiotic intervention, i.e., the total score of the Hospital Anxiety and Depression Scale (p = 0.056) and its depression sub-score (p = 0.093), as well as sleep patterns (p = 0.058). The probiotic intervention evoked distinct changes in brain morphology and resting state brain function alongside slight improvements of psycho(bio)logical markers of the gut-brain axis. The combination of those parameters may provide new insights into the modes of action by which gut microbiota can affect gut-brain communication and hence brain function.

  • 47.
    Rode, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Edebol Carlman, Hanna M. T.
    Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    König, Julia
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Radiology and Medical Physics.
    Andersson, Pernilla
    Örebro University, School of Law, Psychology and Social Work.
    Persson, Jonas
    Örebro University, School of Law, Psychology and Social Work.
    Kiselev, Andrey
    Örebro University, School of Science and Technology.
    Lathrop Stern, Lori
    Global Medical Innovation, Pfizer Consumer Healthcare, Madison, NJ, United States.
    Salomon, Benita
    Örebro University, School of Medical Sciences.
    Mohammed, Ahmed Abdulilah
    Department of Radiology and Medical Physics, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Labus, Jennifer S.
    Integrative Bioinformatics and Biostatistics Core, Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects: A Randomized Clinical Trial2022In: Frontiers in nutrition, E-ISSN 2296-861X, Vol. 9, article id 827182Article in journal (Refereed)
    Abstract [en]

    Background: Evidence from preclinical studies suggests that probiotics affect brain function via the microbiome-gut-brain axis, but evidence in humans remains limited.

    Objective: The present proof-of-concept study investigated if a probiotic product containing a mixture of Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 (in total 3 × 109 CFU/day) affected functional brain responses in healthy subjects during an emotional attention task.

    Design: In this double-blinded, randomized, placebo-controlled crossover study (Clinicaltrials.gov, NCT03615651), 22 healthy subjects (24.2 ± 3.4 years, 6 males/16 females) were exposed to a probiotic intervention and a placebo for 4 weeks each, separated by a 4-week washout period. Subjects underwent functional magnetic resonance imaging while performing an emotional attention task after each intervention period. Differential brain activity and functional connectivity were assessed.

    Results: Altered brain responses were observed in brain regions implicated in emotional, cognitive and face processing. Increased activation in the orbitofrontal cortex, a region that receives extensive sensory input and in turn projects to regions implicated in emotional processing, was found after probiotic intervention compared to placebo using a cluster-based analysis of functionally defined areas. Significantly reduced task-related functional connectivity was observed after the probiotic intervention compared to placebo. Fecal microbiota composition was not majorly affected by probiotic intervention.

    Conclusion: The probiotic intervention resulted in subtly altered brain activity and functional connectivity in healthy subjects performing an emotional task without major effects on the fecal microbiota composition. This indicates that the probiotic effects occurred via microbe-host interactions on other levels. Further analysis of signaling molecules could give possible insights into the modes of action of the probiotic intervention on the gut-brain axis in general and brain function specifically. The presented findings further support the growing consensus that probiotic supplementation influences brain function and emotional regulation, even in healthy subjects. Future studies including patients with altered emotional processing, such as anxiety or depression symptoms are of great interest.

    Clinical Trial Registration: [http://clinicaltrials.gov/], identifier [NCT03615651].

  • 48.
    Rode, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Edebol-Carlman, Hanna
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley N.
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Physics.
    Persson, Jonas
    Örebro University, School of Law, Psychology and Social Work.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Probiotic mixture containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum affects resting state brain function in healthy subjects: A randomized clinical trialManuscript (preprint) (Other academic)
  • 49.
    Rode, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Edebol-Carlman, Hanna
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley N.
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Physics.
    Andersson, Pernilla
    Örebro University, School of Law, Psychology and Social Work.
    Persson, Jonas
    Örebro University, School of Law, Psychology and Social Work.
    Kiselev, Andrey
    Örebro University, School of Science and Technology.
    Lathrop Stern, Lori
    Global Medical Innovation, Pfizer Consumer Healthcare, Madison, NJ, USA.
    Salomon, Benita
    Örebro University, School of Medical Sciences.
    Abdulilah Mohammed, Ahmed
    Faculty of Medicine and Health, Department of Radiology, Örebro University, Örebro, Sweden.
    Labus, Jennifer S.
    Bioinformatics and Neuroimaging Core, Oppenheimer Center for Neurobiology of Stress and Resilience, David Geffen School of Medicine at UCLA, Los Angeles, USA.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Probiotic mixture containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum affects brain responses towards an emotional task in healthy subjects: A randomized clinical trialManuscript (preprint) (Other academic)
  • 50.
    Rode, Julia
    et al.
    Örebro University, School of Medical Sciences. Center for Experimental and Biomedical Imaging in Örebro (CEBIO), Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, 70182, Örebro, Sweden.
    Runnamo, Rebecka
    Örebro University, School of Medical Sciences. Department of Psychiatry, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Center for Experimental and Biomedical Imaging in Örebro (CEBIO), Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department for Radiology and Medical Physics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Msghina, Mussie
    Örebro University, School of Medical Sciences. Department of Psychiatry, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Clinical Neuroscience, Karolinska Institute, 17177, Stockholm, Sweden.
    Salience and hedonic experience as predictors of central stimulant treatment response in ADHD: A resting state fMRI study2023In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 163, p. 378-385Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Roughly 20-30% of patients with Attention-deficit/hyperactivity disorder (ADHD) fail to respond to central stimulant (CS) medication. Genetic, neuroimaging, biochemical and behavioral biomarkers for CS response have been investigated, but currently there are no biomarkers available for clinical use that help identify CS responders and non-responders.

    METHODS: In the present paper, we studied if incentive salience and hedonic experience evaluated after a single-dose CS medication could predict response and non-response to CS medication. We used a bipolar visual analogue 'wanting' and 'liking' scale to gauge incentive salience and hedonic experience in 25 healthy controls (HC) and 29 ADHD patients. HC received 30 mg methylphenidate (MPH) and ADHD patients received either MPH or lisdexamphetamine (LDX) as selected by their clinician, with dosage individually determined for optimal effect. Clinician-evaluated global impression - severity (CGI-S) and improvement (CGI-I) and patient-evaluated improvement (PGI-I) were used to assess response to CS medication. Resting state functional magnetic resonance imaging (fMRI) was conducted before and after single-dose CS to correlate wanting and liking scores to changes in functional connectivity.

    RESULTS: Roughly 20% of the ADHD patients were CS non-responders (5 of 29). CS responders had significantly higher incentive salience and hedonic experience scores compared to healthy controls and CS non-responders. Resting state fMRI showed that wanting scores were significantly associated to changes in functional connectivity in ventral striatum including nucleus accumbens.

    CONCLUSION: Incentive salience and hedonic experience evaluated after a single-dose CS medication segregate CS responders and non-responders, with corresponding neuroimaging biomarkers in the brain reward system.

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