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  • 251.
    Ekström, Magnus Par
    et al.
    Lund Univ, Dept Clin Sci Lund, Fac Med, Resp Med & Allergol, Lund, Sweden.
    Blomberg, Anders
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Bergstrom, Goran
    Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Med, Wallenberg Lab,Dept Mol & Clin Med, Gothenburg, Sweden.
    Brandberg, John
    Univ Gothenburg, Inst Clin Sci, Dept Radiol, Gothenburg, Sweden.
    Caidahl, Kenneth
    Univ Gothenburg, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden.
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci, Malm, Sweden.
    Engvall, Jan
    Linkoping Univ, Dept Clin Physiol, Linkoping, Sweden;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Eriksson, Maria
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Gransbo, Klas
    Lund Univ, Dept Clin Sci Malmo, Lund, Sweden.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Stockholm, Sweden.
    Nilsson, Lars
    Umea Univ, Unit Med, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Nilsson, Ulf
    Umea Univ, Unit Med, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Olin, Anna-Carin
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Sect Occupat & Environm Med, Gothenburg, Sweden.
    Persson, Lennart
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Rosengren, Annika
    Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Med, Wallenberg Lab,Dept Mol & Clin Med, Gothenburg, Sweden.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Skold, Magnus
    Karolinska Inst, Ctr Mol Med, Resp Med Unit, Dept Med, Stockholm, Sweden;Karolinska Inst, Dept Med Solna, Resp Med Unit, Stockholm, Sweden;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.
    Sundstrom, Johan
    Karolinska Inst, Dept Med Solna, Resp Med Unit, Stockholm, Sweden;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.
    Swahn, Eva
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Soderberg, Stefan
    Umea Univ, Unit Med, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Tanash, Hanan A.
    Lund Univ, Skane Univ Hosp, Dept Resp Med & Allergol, Malmo, Sweden.
    Toren, Kjell
    Sahlgrens Univ Hosp, Dept Occupat & Environm, Gothenburg, Sweden.
    Ostgren, Carl Johan
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    The association of body mass index, weight gain and central obesity with activity-related breathlessness: the Swedish Cardiopulmonary Bioimage Study2019In: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 74, no 10, p. 958-964Article in journal (Refereed)
    Abstract [en]

    Introduction Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m2) is rapidly increasing globally and its impact on breathlessness is unclear.

    Methods This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score ≥1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex.

    Results We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m2; and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness.

    Conclusion Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.

  • 252.
    Ekström, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Efficient GPU-based Image Registration: for Detailed Large-Scale Whole-body Analysis2020Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Imaging has become an important aspect of medicine, enabling visualization of internals in a non-invasive manner. The rapid advancement and adoption of imaging techniques have led to a demand for tools able to take advantage of the information that is produced. Medical image analysis aims to extract relevant information from acquired images to aid diagnostics in healthcare and increase the understanding within medical research. The main subject of this thesis, image registration, is a widely used tool in image analysis that can be employed to find a spatial transformation aligning a set of images. One application, that is described in detail in this thesis, is the use of image registration for large-scale analysis of whole-body images through the utilization of the correspondences defined by the resulting transformations. To produce detailed results, the correspondences, i.e. transformations, need to be of high resolution and the quality of the result has a direct impact on the quality of the analysis. Also, this type of application aims to analyze large cohorts and the value of a registration method is not only weighted by its ability to produce an accurate result but also by its efficiency. This thesis presents two contributions on the subject; a new method for efficient image registration with the ability to produce dense deformable transformations, and the application of the presented method in large-scale analysis of a whole-body dataset acquired using an integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) system. In this thesis, it is shown that efficient and detailed image registration can be performed by employing graph cuts and a heuristic where the optimization is performed on subregions of the image. The performance can be improved further by the efficient utilization of a graphics processing unit (GPU). It is also shown that the method can be employed to produce a model on health based on a PET-MRI dataset which can be utilized to automatically detect pathology in the imaging.

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  • 253.
    Ekström, Simon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Deformable Image Registration of Volumetric Whole-body MRI: An EvaluationManuscript (preprint) (Other academic)
    Abstract [en]

    Whole-body imaging presents a variety of interesting applications and combining these information rich images with image registration enables detailed large scale analysis. Whole-body image registration, with the large variability present in human anatomy, introduces a range of challenges that need to be dealt with. This paper aims to present two new extensions to a previously published registration method based on compositive updates and voxel-wise regularization. The new extensions are evaluated against a previously presented pipeline for whole-body registration and a learning-based approach using the Voxel Morph framework. The methods are evaluated on Dice overlap, smoothness of produced displacement fields, and the inverse consistency error. The presented extensions are shown to improve upon previous method both in terms of computation time and registration quality. The voxel-wise regularization produces a mean Dice overlap of 0.828 for the 10 segmented regions and a mean computation time of 320 seconds per subject. The learning-based approach had an inference time of only 3 seconds but a training time of 16 hours per reference subject. This approach produced a mean Dice overlap of only 0.797 but it was shown that the issues in overlap score were limited to the kidneys. In conclusion, both the extensions and VoxelMorph has presented great promise for the task of whole-body registration compared to previous method. However, the choice of method will be highly dependent upon the task. VoxelMorph provides results of lower quality and reduced flexibility but a computation time of only a few seconds.

  • 254.
    Ekström, Simon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, Mölndal, Sweden.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, Mölndal, Sweden.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Fast graph-cut based optimization for practical dense deformable registration of volume images2020In: Computerized Medical Imaging and Graphics, ISSN 0895-6111, E-ISSN 1879-0771, Vol. 84, article id 101745Article in journal (Refereed)
    Abstract [en]

    Deformable image registration is a fundamental problem in medical image analysis, with applications such as longitudinal studies, population modeling, and atlas-based image segmentation. Registration is often phrased as an optimization problem, i.e., finding a deformation field that is optimal according to a given objective function. Discrete, combinatorial, optimization techniques have successfully been employed to solve the resulting optimization problem. Specifically, optimization based on α-expansion with minimal graph cuts has been proposed as a powerful tool for image registration. The high computational cost of the graph-cut based optimization approach, however, limits the utility of this approach for registration of large volume images. Here, we propose to accelerate graph-cut based deformable registration by dividing the image into overlapping sub-regions and restricting the α-expansion moves to a single sub-region at a time. We demonstrate empirically that this approach can achieve a large reduction in computation time - from days to minutes - with only a small penalty in terms of solution quality. The reduction in computation time provided by the proposed method makes graph-cut based deformable registration viable for large volume images. Graph-cut based image registration has previously been shown to produce excellent results, but the high computational cost has hindered the adoption of the method for registration of large medical volume images. Our proposed method lifts this restriction, requiring only a small fraction of the computational cost to produce results of comparable quality.

  • 255.
    Ekström, Simon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pilia, Martino
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Faster dense deformable image registration by utilizing both CPU and GPUManuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: Image registration is an important aspect of medical image analysis and a key component in many analysis concepts. Applications include fusion of multimodal images, multi-atlas segmentation, and whole-body analysis. Deformable image registration is often computationally expensive, and the need for efficient registration methods is highlighted by the emergence of large-scale image databases, e.g., the UK Biobank, providing imaging from 100 000 participants.

    Approach: We present a heterogeneous computing approach, utilizing both the CPU and the GPU, to accelerate a previously proposed image registration method. The parallelizable task of computing the matching criterion is offloaded to the GPU, where it can be computed efficiently, while the more complex optimization task is performed on the CPU. To lessen the impact of data synchronization between the CPU and GPU we propose a pipeline model, effectively overlapping computational tasks with data synchronization. The performance is evaluated on a brain labeling task and compared with a CPU implementation of the same method and the popular Advanced Normalization Tools (ANTs) software.

    Results: The proposed method presents a speed-up by a factor of 4 and 8 against the CPU implementation and the ANTs software respectively. A significant improvement in labeling quality was also observed, with measured mean Dice overlaps of 0.712 and 0.701 for our method and ANTs respectively.

    Conclusions: We showed that the proposed method compares favorably to the ANTs software yielding both a significant speed-up and an improvement in labeling quality. The registration method together with the proposed parallelization strategy is implemented as an open-source software package, deform.

  • 256.
    Ekström, Simon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical AB (Sweden) .
    Pilia, Martino
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical AB (Sweden) .
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical AB (Sweden) .
    Strand, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Faster dense deformable image registration by utilizing both CPU and GPU2021In: Journal of Medical Imaging, ISSN 2329-4302, E-ISSN 2329-4310, Vol. 8, no 1, article id 014002Article in journal (Refereed)
    Abstract [en]

    Purpose: Image registration is an important aspect of medical image analysis and a key component in many analysis concepts. Applications include fusion of multimodal images, multi-atlas segmentation, and whole-body analysis. Deformable image registration is often computationally expensive, and the need for efficient registration methods is highlighted by the emergence of large-scale image databases, e.g., the UK Biobank, providing imaging from 100,000 participants. Approach: We present a heterogeneous computing approach, utilizing both the CPU and the graphics processing unit (GPU), to accelerate a previously proposed image registration method. The parallelizable task of computing the matching criterion is offloaded to the GPU, where it can be computed efficiently, while the more complex optimization task is performed on the CPU. To lessen the impact of data synchronization between the CPU and GPU, we propose a pipeline model, effectively overlapping computational tasks with data synchronization. The performance is evaluated on a brain labeling task and compared with a CPU implementation of the same method and the popular advanced normalization tools (ANTs) software. Results: The proposed method presents a speed-up by factors of 4 and 8 against the CPU implementation and the ANTs software, respectively. A significant improvement in labeling quality was also observed, with measured mean Dice overlaps of 0.712 and 0.701 for our method and ANTs, respectively. Conclusions: We showed that the proposed method compares favorably to the ANTs software yielding both a significant speed-up and an improvement in labeling quality. The registration method together with the proposed parallelization strategy is implemented as an open-source software package, deform.

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  • 257.
    Elf, Kristin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rostedt Punga: Clinical Neurophysiology.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Semnic, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Rostami-Berglund, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Sundblom, Jimmy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Continuous EEG monitoring after brain tumor surgery2019In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 161, no 9, p. 1835-1843Article in journal (Refereed)
    Abstract [en]

    Background

    Prolonged seizures generate cerebral hypoxia and increased intracranial pressure, resulting in an increased risk of neurological deterioration, increased long-term morbidity, and shorter survival. Seizures should be recognized early and treated promptly.

    The aim of the study was to investigate the occurrence of postoperative seizures in patients undergoing craniotomy for primary brain tumors and to determine if non-convulsive seizures could explain some of the postoperative neurological deterioration that may occur after surgery.

    Methods

    A single-center prospective study of 100 patients with suspected glioma. Participants were studied with EEG and video recording for at least 24 h after surgery.

    Results

    Seven patients (7%) displayed seizure activity on EEG recording within 24 h after surgery and another two patients (2%) developed late seizures. One of the patients with early seizures also developed late seizures. In five patients (5%), there were non-convulsive seizures. Four of these patients had a combination of clinically overt and non-convulsive seizures and in one patient, all seizures were non-convulsive. The non-convulsive seizures accounted for the majority of total seizure time in those patients. Non-convulsive seizures could not explain six cases of unexpected postoperative neurological deterioration. Postoperative ischemic lesions were more common in patients with early postoperative seizures.

    Conclusions

    Early seizures, including non-convulsive, occurred in 7% of our patients. Within this group, non-convulsive seizure activity had longer durations than clinically overt seizures, but only 1% of patients had exclusively non-convulsive seizures. Seizures were not associated with unexpected neurological deterioration.

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  • 258. Elfstrand, Erika
    et al.
    Löfvenberg, Christian
    Lundman, Lars
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    A Rare Case of Angiofibroma Presenting as an Endolymphatic Sac Tumor.2023In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995Article in journal (Refereed)
    Abstract [en]

    A 30-year-old man presented with minute-long episodes of vertigo and severe autophony. CVEMP showed a decreased threshold when testing the left side, potentially indicating SSCD. A subsequent MRI demonstrated a multi-lobulated, cystic mass in the temporal bone and the radiological diagnosis at that time was ELST. Tumor excision was performed, and microscopic examination of the excised material revealed fibrovascular tissue without signs of papillary or cystic projections. The conclusion of the histological assessment rendered a diagnosis of angiofibroma. We were unable to find a previous report of ENA originating around the endolymphatic sac. Laryngoscope, 2023.

  • 259.
    Elmsjö, Albert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Engskog, Mikael K R
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Haglöf, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Iggman, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Arvidsson, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Pettersson, Curt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    NMR-based metabolic profiling in healthy individuals overfed different types of fat: links to changes in liver fat accumulation and lean tissue mass.2015In: Nutrition & Diabetes, E-ISSN 2044-4052, Vol. 5, no 19, p. e182-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Overeating different dietary fatty acids influence the amount of liver fat stored during weight gain, however, the mechanisms responsible are unclear. We aimed to identify non-lipid metabolites that may differentiate between saturated (SFA) and polyunsaturated fatty acid (PUFA) overfeeding using a non-targeted metabolomic approach. We also investigated the possible relationships between plasma metabolites and body fat accumulation.

    METHODS: In a randomized study (LIPOGAIN study), n=39 healthy individuals were overfed with muffins containing SFA or PUFA. Plasma samples were precipitated with cold acetonitrile and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Pattern recognition techniques were used to overview the data, identify variables contributing to group classification and to correlate metabolites with fat accumulation.

    RESULTS: We previously reported that SFA causes a greater accumulation of liver fat, visceral fat and total body fat, whereas lean tissue levels increases less compared with PUFA, despite comparable weight gain. In this study, lactate and acetate were identified as important contributors to group classification between SFA and PUFA (P<0.05). Furthermore, the fat depots (total body fat, visceral adipose tissue and liver fat) and lean tissue correlated (P(corr)>0.5) all with two or more metabolites (for example, branched amino acids, alanine, acetate and lactate). The metabolite composition differed in a manner that may indicate higher insulin sensitivity after a diet with PUFA compared with SFA, but this needs to be confirmed in future studies.

    CONCLUSION: A non-lipid metabolic profiling approach only identified a few metabolites that differentiated between SFA and PUFA overfeeding. Whether these metabolite changes are involved in depot-specific fat storage and increased lean tissue mass during overeating needs further investigation.

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  • 260.
    El-Sherif, Ahmed M.
    et al.
    Al Azhar Univ, Fac Med, Nasr City 11651, Cairo, Egypt..
    Rashad, Alaa
    Al Azhar Univ, Fac Med, Nasr City 11651, Cairo, Egypt..
    Rabie, Mohamed M.
    Al Azhar Univ, Fac Med, Nasr City, Egypt..
    Hegazy, Mohammed
    Al Haram Hosp, Minist Hlth, Giza, Egypt..
    Adel, Mostafa
    Al Azhar Univ, Al Hussein Hosp, Fac Med, Nasr City, Egypt..
    Albialy, Mohammad
    Al Azhar Univ, Fac Med, Nasr City 11651, Cairo, Egypt..
    El-Shandawely, Mohammed
    Al Azhar Univ, Fac Med, Nasr City 11651, Cairo, Egypt..
    Mahmoud, Ehab Adel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Resource utilization in management of spontaneous intracerebral hemorrhage without systemic risk factors: Does early surgical decompression matter?2023In: Clinical neurology and neurosurgery, ISSN 0303-8467, E-ISSN 1872-6968, Vol. 231, article id 107829Article, review/survey (Refereed)
    Abstract [en]

    Background: Even though different subtypes of spontaneous ICH are frequently linked to a poor prognosis, their causes, pathological features, and prognoses vary. Atypical intracerebral hemorrhage is the subtype of spontaneous ICH that usually occurs due to an underlying localized vascular lesion. It is unrelated to systemic vascular risk factors, mostly affects children and young adults and is associated with a relatively good outcome. This fact should be considered when planning the evaluation and treatment. Investigating the cause of this subtype is fundamental to providing optimal management. However, if resources do not allow completing the investigations, the cause will be more difficult to discover. Treatment decisions will be made under stress to save the patient's life, especially with rapidly deteriorating patients. Methods: We described three cases of spontaneous ICH without systemic risk factors where the bleeding source could not be determined before surgery due to a lack of resources, preventing preoperative vascular investigation. Knowing that the atypical ICH has a distinct identity, regarding etiology and prognosis, encouraged the surgeons to resort to early surgical decompression as an alternative plan. We reviewed the literature searching for supporting evidence. Results: The results of treatment of the presented cases were satisfactory. The lack of reported similar cases was brought to light by a literature analysis that sought to provide backing for the proposed management strategy. In the end, we supplied two graphic organizers to help readers remember the different types and treatment of hemorrhagic stroke. Conclusion: There isn't enough evidence to show that there are other ways to treat atypical intracerebral haemorrhage when resources are limited. The presented cases highlight the importance of decisionmaking in resource-constrained situations when patient outcomes can be improved.

  • 261.
    Emilsson, Össur Ingi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Respiratory medicine and allergology, Akademiska sjukhuset, Uppsala, Sweden.
    Dessle, Angelica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Physiotherapy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Respiratory, allergy and sleep research, Akademiska Sjukhuset.
    Adeli, Shamisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Different chest HRCT scan protocols change the extent of ground glass opacities2022In: BMC Pulmonary Medicine, E-ISSN 1471-2466, Vol. 22, no 1, article id 430Article in journal (Refereed)
    Abstract [en]

    Background

    Ground glass opacity (GGO) is the main HRCT feature representing alveolitis in systemic sclerosis-associated interstitial lung disease (SSc-ILD), but may also represent other conditions such as atelectasis or edema. It is unclear how much this is affected by the HRCT scan protocol used. We aimed to compare the performance of three different HRCT protocols to evaluate the degree of SSc-ILD related changes.

    Methods

    Eleven patients with SSc underwent chest HRCT scan by three different protocols: First, a supine scan after lying down for 15 minutes, then two scans in alternating order: A prone position scan, and a supine position scan after performing 10 deep breaths using a positive expiratory pressure (PEP) device. The HRCT scans were evaluated by the Warrick score system for ILD-related findings.

    Results

    The three HRCT protocols were compared and resulted in different mean (95% CI) Warrick scores: 9.4 (5.3–13.4) in supine after rest; 7.5 (95% CI 3.8–11.1) in prone and 7.6 (95% CI 4.2–11.1) in supine after PEP. When comparing supine after rest to prone and supine after PEP, the latter two scans had a significantly lower score (p = 0.001 for both comparisons). In all cases, only sub-scores for ground glass opacities differed, while sub-scores for fibrosis-related changes did not change.

    Conclusions

    Different HRCT scan protocols significantly altered the Warrick severity score for SSc-ILD findings, primarily because of changes in ground glass opacities. These differences may be clinically meaningful.

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  • 262. Emmert, Kirsten
    et al.
    Breimhorst, Markus
    Bauermann, Thomas
    Birklein, Frank
    Rebhorn, Cora
    Van De Ville, Dimitri
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Centre de Diagnostic Radiologique de Carouge CDRC, Geneva, Switzerland; Faculty of Medicine of the University of Geneva, Geneva, Switzerland; Department of Neuroradiology, University Hospital Freiburg, Freiburg im Breisgau, Germany.
    Active pain coping is associated with the response in real-time fMRI neurofeedback during pain2017In: Brain Imaging and Behavior, ISSN 1931-7557, E-ISSN 1931-7565, Vol. 11, no 3, p. 712-721Article in journal (Refereed)
    Abstract [en]

    Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback is used as a tool to gain voluntary control of activity in various brain regions. Little emphasis has been put on the influence of cognitive and personality traits on neurofeedback efficacy and baseline activity. Here, we assessed the effect of individual pain coping on rt-fMRI neurofeedback during heat-induced pain. Twenty-eight healthy subjects completed the Coping Strategies Questionnaire (CSQ) prior to scanning. The first part of the fMRI experiment identified target regions using painful heat stimulation. Then, subjects were asked to down-regulate the pain target brain region during four neurofeedback runs with painful heat stimulation. Functional MRI analysis included correlation analysis between fMRI activation and pain ratings as well as CSQ ratings. At the behavioral level, the active pain coping (first principal component of CSQ) was correlated with pain ratings during neurofeedback. Concerning neuroimaging, pain sensitive regions were negatively correlated with pain coping. During neurofeedback, the pain coping was positively correlated with activation in the anterior cingulate cortex, prefrontal cortex, hippocampus and visual cortex. Thermode temperature was negatively correlated with anterior insula and dorsolateral prefrontal cortex activation. In conclusion, self-reported pain coping mechanisms and pain sensitivity are a source of variance during rt-fMRI neurofeedback possibly explaining variations in regulation success. In particular, active coping seems to be associated with successful pain regulation.

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  • 263.
    Emmert, Kirsten
    et al.
    Univ Hosp Geneva, Dept Radiol & Med informat, Switzerland.
    Kopel, Rotem
    Univ Hosp Geneva, Dept Radiol & Med informat, Switzerland.
    Koush, Yury
    Univ Hosp Geneva, Dept Radiol & Med informat, Switzerland.
    Maire, Raphael
    Univ Hosp Lausanne, Neurotol & Audiol Unit, Dept ENT Head & Neck Surg, Switzerland.
    Senn, Pascal
    Univ Hosp Geneva, Dept Clin Neurosci, Switzerland.
    Van De Ville, Dimitri
    Univ Hosp Geneva, Dept Radiol & Med informat, Switzerland.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Continuous vs. intermittent neurofeedback to regulate auditory cortex activity of tinnitus patients using real-time fMRI: A pilot study2017In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 14, p. 97-104Article in journal (Refereed)
    Abstract [en]

    The emerging technique of real-time fMRI neurofeedback trains individuals to regulate their own brain activity via feedback from an fMRI measure of neural activity. Optimum feedback presentation has yet to be determined, particularly when working with clinical populations. To this end, we compared continuous against intermittent feedback in subjects with tinnitus.

    Fourteen participants with tinnitus completed the whole experiment consisting of nine runs (3 runs × 3 days). Prior to the neurofeedback, the target region was localized within the auditory cortex using auditory stimulation (1 kHz tone pulsating at 6 Hz) in an ON-OFF block design. During neurofeedback runs, participants received either continuous (n = 7, age 46.84 ± 12.01, Tinnitus Functional Index (TFI) 49.43 ± 15.70) or intermittent feedback (only after the regulation block) (n = 7, age 47.42 ± 12.39, TFI 49.82 ± 20.28). Participants were asked to decrease auditory cortex activity that was presented to them by a moving bar. In the first and the last session, participants also underwent arterial spin labeling (ASL) and resting-state fMRI imaging. We assessed tinnitus severity using the TFI questionnaire before all sessions, directly after all sessions and six weeks after all sessions. We then compared neuroimaging results from neurofeedback using a general linear model (GLM) and region-of-interest analysis as well as behavior measures employing a repeated-measures ANOVA. In addition, we looked at the seed-based connectivity of the auditory cortex using resting-state data and the cerebral blood flow using ASL data.

    GLM group analysis revealed that a considerable part of the target region within the auditory cortex was significantly deactivated during neurofeedback. When comparing continuous and intermittent feedback groups, the continuous group showed a stronger deactivation of parts of the target region, specifically the secondary auditory cortex. This result was confirmed in the region-of-interest analysis that showed a significant down-regulation effect for the continuous but not the intermittent group. Additionally, continuous feedback led to a slightly stronger effect over time while intermittent feedback showed best results in the first session. Behaviorally, there was no significant effect on the total TFI score, though on a descriptive level TFI scores tended to decrease after all sessions and in the six weeks follow up in the continuous group. Seed-based connectivity with a fixed-effects analysis revealed that functional connectivity increased over sessions in the posterior cingulate cortex, premotor area and part of the insula when looking at all patients while cerebral blood flow did not change significantly over time.

    Overall, these results show that continuous feedback is suitable for long-term neurofeedback experiments while intermittent feedback presentation promises good results for single session experiments when using the auditory cortex as a target region. In particular, the down-regulation effect is more pronounced in the secondary auditory cortex, which might be more susceptible to voluntary modulation in comparison to a primary sensory region.

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  • 264.
    Emmert, Kirsten
    et al.
    Univ Geneva, Dept Radiol & Med Informat, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Lausanne, Switzerland..
    Kopel, Rotem
    Univ Geneva, Dept Radiol & Med Informat, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Lausanne, Switzerland..
    Sulzer, James
    Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA..
    Bruehl, Annette B.
    Univ Zurich, Hosp Psychiat, Dept Psychiat Psychotherapy & Psychosomat, Zurich, Switzerland.;Univ Cambridge, Behav & Clin Neurosci Inst, Dept Psychiat, Cambridge, England..
    Berman, Brian D.
    Univ Colorado, Dept Neurol, Aurora, CO USA..
    Linden, David E. J.
    Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales..
    Horovitz, Silvina G.
    NINDS, NIH, Bethesda, MD 20892 USA..
    Breimhorst, Markus
    Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Neurol, D-55122 Mainz, Germany..
    Caria, Andrea
    Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany..
    Frank, Sabine
    Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany..
    Johnston, Stephen
    Long, Zhiying
    Swansea Univ, Dept Psychol, Swansea, W Glam, Wales.;Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China.;Beijing Normal Univ, IDG McGovern Inst Brain Res, Beijing 100875, Peoples R China..
    Paret, Christian
    Heidelberg Univ Mannheim, Med Fac Mannheim, Cent Inst Mental Hlth Mannheim, Dept Psychosomat Med & Psychotherapy, Mannheim, Germany.;Heidelberg Univ Mannheim, Med Fac Mannheim, Cent Inst Mental Hlth Mannheim, Dept Neuroimaging, Mannheim, Germany..
    Robineau, Fabien
    Univ Geneva, Dept Neurosci, Lab Neurol & Imaging Cognit, CH-1211 Geneva 4, Switzerland..
    Veit, Ralf
    Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany.;Univ Tubingen, Helmholtz Ctr Munich, Inst Diabet Res & Metab Dis, Tubingen, Germany..
    Bartsch, Andreas
    Heidelberg Univ, Dept Neuroradiol, Heidelberg, Germany.;Univ Wurzburg, Dept Neuroradiol, D-97070 Wurzburg, Germany.;Univ Oxford, FMRIB Ctr, Oxford, England.;Bamberg Hosp, Dept Radiol, Bamberg, Germany..
    Beckmann, Christian F.
    Radboud Univ Nijmegen, Ctr Cognit Neuroimaging, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neuroimaging, NL-6525 ED Nijmegen, Netherlands.;Univ Oxford, Oxford Ctr Funct MRI Brain, Nuffield Dept Clin Neurosci, Oxford OX1 2JD, England..
    Van De Ville, Dimitri
    Univ Geneva, Dept Radiol & Med Informat, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Lausanne, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiolog Carouge CDRC, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland..
    Meta-analysis of real-time fMRI neurofeedback studies using individual participant data: How is brain regulation mediated?2016In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 124, no Part A, p. 806-812Article in journal (Refereed)
    Abstract [en]

    An increasing number of studies using real-time fMRI neurofeedback have demonstrated that successful regulation of neural activity is possible in various brain regions. Since these studies focused on the regulated region(s), little is known about the target-independent mechanisms associated with neurofeedback-guided control of brain activation, i.e. the regulating network. While the specificity of the activation during self-regulation is an important factor, no study has effectively determined the network involved in self-regulation in general. In an effort to detect regions that are responsible for the act of brain regulation, we performed a post-hoc analysis of data involving different target regions based on studies from different research groups. We included twelve suitable studies that examined nine different target regions amounting to a total of 175 subjects and 899 neurofeedback runs. Data analysis included a standard first-(single subject, extracting main paradigm) and second-level (single subject, all runs) general linear model (GLM) analysis of all participants taking into account the individual timing. Subsequently, at the third level, a random effects model GLM included all subjects of all studies, resulting in an overall mixed effects model. Since four of the twelve studies had a reduced field of view (FoV), we repeated the same analysis in a subsample of eight studies that had a well-overlapping FoV to obtain a more global picture of self-regulation. The GLM analysis revealed that the anterior insula as well as the basal ganglia, notably the striatum, were consistently active during the regulation of brain activation across the studies. The anterior insula has been implicated in interoceptive awareness of the body and cognitive control. Basal ganglia are involved in procedural learning, visuomotor integration and other higher cognitive processes including motivation. The larger FoV analysis yielded additional activations in the anterior cingulate cortex, the dorsolateral and ventrolateral prefrontal cortex, the temporo-parietal area and the visual association areas including the temporo-occipital junction. In conclusion, we demonstrate that several key regions, such as the anterior insula and the basal ganglia, are consistently activated during self-regulation in real-time fMRI neurofeedback independent of the targeted region-ofinterest. Our results imply that if the real-time fMRI neurofeedback studies target regions of this regulation network, such as the anterior insula, care should be given whether activation changes are related to successful regulation, or related to the regulation process per se. Furthermore, future research is needed to determine how activation within this regulation network is related to neurofeedback success.

  • 265.
    Emmert, Kirsten
    et al.
    Univ Geneva, Fac Med, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Geneva, Switzerland..
    Zoller, Daniela
    Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Geneva, Switzerland.;Univ Geneva, Dept Psychiat, Off Medicopedag, Geneva, Switzerland..
    Preti, Maria Giulia
    Univ Geneva, Fac Med, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Geneva, Switzerland..
    Van De Ville, Dimitri
    Univ Geneva, Fac Med, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Geneva, Switzerland..
    Giannakopoulos, Panteleimon
    Univ Geneva, Dept Psychiat, Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland.;Affidea Ctr Diagnost Radiol Carouge CDRC, Carouge, Switzerland..
    Influence of Vascular Variant of the Posterior Cerebral Artery (PCA) on Cerebral Blood Flow, Vascular Response to CO2 and Static Functional Connectivity2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 8, article id e0161121Article in journal (Refereed)
    Abstract [en]

    Introduction The fetal origin of the posterior cerebral artery (fPCA) is a frequent vascular variant in 11-29% of the population. For the fPCA, blood flow in the PCA originates from the anterior instead of the posterior circulation. We tested whether this blood supply variant impacts the cerebral blood flow assessed by arterial spin labeling (ASL), cerebrovascular reserve as well as resting-state static functional connectivity (sFC) in the sense of a systematic confound. Methods The study included 385 healthy, elderly subjects (mean age: 74.18 years [range: 68.9-90.4]; 243 female). Participants were classified into normal vascular supply (n = 296, 76.88%), right fetal origin (n = 23, 5.97%), left fetal origin (n = 16, 4.16%), bilateral fetal origin (n = 4, 1.04%), and intermediate (n = 46, 11.95%, excluded from further analysis) groups. ASL-derived relative cerebral blood flow (relCBF) maps and cerebrovascular reserve (CVR) maps derived from a CO2 challenge with blocks of 7% CO2 were compared. Additionally, sFC between 90 regions of interest (ROIs) was compared between the groups. Results CVR was significantly reduced in subjects with ipsilateral fPCA, most prominently in the temporal lobe. ASL yielded a non-significant trend towards reduced relCBF in bilateral posterior watershed areas. In contrast, conventional atlas-based sFC did not differ between groups. Conclusions In conclusion, fPCA presence may bias the assessment of cerebrovascular reserve by reducing the response to CO2. In contrast, its effect on ASL-assessed baseline perfusion was marginal. Moreover, fPCA presence did not systematically impact resting-state sFC. Taken together, this data implies that perfusion variables should take into account the vascularization patterns.

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  • 266.
    Engman, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Moby, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fredriksson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hormonal Cycle and Contraceptive Effects on Amygdala and Salience Resting-State Networks in Women with Previous Affective Side Effects on the Pill.2018In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 43, no 3, p. 555-563Article in journal (Refereed)
    Abstract [en]

    The mechanisms linking ovarian hormones to negative affect are poorly characterized, but important clues may come from the examination of the brain's intrinsic organization. Here, we studied the effects of both the menstrual cycle and oral contraceptives (OCs) on amygdala and salience network resting-state functional connectivity using a double-blind, randomized, and placebo-controlled design. Hormone levels, depressive symptoms, and resting-state functional connectivity were measured in 35 healthy women (24.9±4.2 years) who had previously experienced OC-related negative affect. All participants were examined in the follicular phase of a baseline cycle and in the third week of the subsequent cycle during treatment with either a combined OC (30 μg ethinyl estradiol/0.15 mg levonorgestrel) or placebo. The latter time point targeted the midluteal phase in placebo users and steady-state ethinyl estradiol and levonorgestrel concentrations in OC users. Amygdala and salience network connectivity generally increased with both higher endogenous and synthetic hormone levels, although amygdala-parietal cortical connectivity decreased in OC users. When in the luteal phase, the naturally cycling placebo users demonstrated higher connectivity in both networks compared with the women receiving OCs. Our results support a causal link between the exogenous administration of synthetic hormones and amygdala and salience network connectivity. Furthermore, they suggest a similar, potentially stronger, association between the natural hormonal variations across the menstrual cycle and intrinsic network connectivity.

  • 267.
    Engquist, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Johnson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hemodynamic Disturbances in the Early Phase After Subarachnoid Hemorrhage: Regional Cerebral Blood Flow Studied by Bedside Xenon-enhanced CT.2018In: Journal of Neurosurgical Anesthesiology, ISSN 0898-4921, E-ISSN 1537-1921, Vol. 30, no 1, p. 49-58Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The mechanisms leading to neurological deterioration and the devastating course of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) are still not well understood. Bedside xenon-enhanced computerized tomography (XeCT) enables measurements of regional cerebral blood flow (rCBF) during neurosurgical intensive care. In the present study, CBF characteristics in the early phase after severe SAH were explored and related to clinical characteristics and early clinical course outcome.

    MATERIALS AND METHODS: Patients diagnosed with SAH and requiring mechanical ventilation were prospectively enrolled in the study. Bedside XeCT was performed within day 0 to 3.

    RESULTS: Data from 64 patients were obtained. Median global CBF was 34.9 mL/100 g/min (interquartile range [IQR], 26.7 to 41.6). There was a difference in CBF related to age with higher global CBF in the younger patients (30 to 49 y). CBF was also related to the severity of SAH with lower CBF in Fisher grade 4 compared with grade 3. rCBF disturbances and hypoperfusion were common; in 43 of the 64 patients rCBF<20 mL/100 g/min was detected in more than 10% of the region-of-interest (ROI) area and in 17 patients such low-flow area exceeded 30%. rCBF was not related to the localization of the aneurysm; there was no difference in rCBF of ipsilateral compared with contralateral vascular territories. In patients who initially were in Hunt & Hess grade I to III, median global CBF day 0 to 3 was significantly lower for patients who were in poor neurological state at discharge compared with patients in good neurological state, 25.5 mL/100 g/min (IQR, 21.3 to 28.3) versus 37.8 mL/100 g/min (IQR, 30.5 to 47.6).

    CONCLUSIONS: CBF disturbances are common in the early phase after SAH. In many patients, CBF was heterogenic and substantial areas with low rCBF were detected. Age and CT Fisher grade were factors influencing global cortical CBF. Bedside XeCT may be a tool to identify patients at risk of deteriorating so they can receive intensified management, but this needs further exploration.

  • 268. Engström, G.
    et al.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Dekkers, Koen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lin, Yi-Ting
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ahlm, K.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Alfredsson, J.
    Bergström, G.
    Blomberg, A.
    Brandberg, J.
    Caidahl, K.
    Cederlund, K.
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Engvall, J. E.
    Eriksson, M. J.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Gigante, B.
    Gummesson, A.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Hamrefors, V.
    Hedner, J.
    Janzon, M.
    Jernberg, T.
    Johnson, L.
    Lind, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Mannila, M.
    Nilsson, U.
    Persson, A.
    Persson, H. L.
    Persson, M.
    Ramnemark, A.
    Rosengren, A.
    Schmidt, C.
    Skoglund Larsson, L.
    Sköld, C. M.
    Swahn, E.
    Söderberg, S.
    Torén, K.
    Waldenström, A.
    Wollmer, P.
    Zaigham, Suneela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Östgren, C. J.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications2024In: Eur J Epidemiol, ISSN 1573-7284 Electronic 0393-2990 LinkingArticle in journal (Refereed)
    Abstract [en]

    Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

  • 269.
    Eriksson, Barbro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Antonodimitrakis, Pantelis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Streptozocin and 5-fluorouracil treatment of pancreatic neuroendocrine tumors: efficacy, toxicity and prognostic factors2014In: Wiener Klinische Wochenschrift, ISSN 0043-5325, E-ISSN 1613-7671, Vol. 126, no S3, p. S145-S145, article id FP7.1Article in journal (Other academic)
  • 270.
    Eriksson, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Jernberg, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kunskap och säkerhet: Röntgensjuksköterskans syn på kunskap och användande av strålskydd inom nuklearmedicin  - En enkätstudie2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Inom nuklearmedicin är det essentiellt att följa goda strålhygiensrutiner med hjälp av skyddsåtgärder och att tillägna sig kunskaper om strålningsfysik.

    Syfte: Studien riktas mot röntgensjuksköterskor på nuklearmedicinska avdelningar i Sverige, där syftet är att utforska vilka strålskydd som tillämpas, om de är tillräckliga och om det finns ett behov av kunskapsutveckling. Vidare utreds hur röntgensjuksköterskor upplever arbetsrutiner kring strålning och säkerhet.

    Metod: Studien är kvantitativ där röntgensjuksköterskor på nuklearmedicinska avdelningar har tillfrågats att svara på en enkät. Urvalet är anpassat efter exklusions- och inklusionkriterier. Resultatet analyserades via statistikprogrammet SPSS. Svar erhölls från 48 röntgensjuksköterskor från sammanlagt 8 sjukhus.

    Resultat: I resultatet framgår det att 38 deltagare huvudsakligen använder blyförkläde som strålskydd vid arbetet. Motsvarande 38 deltagare använder plasthandskar som skyddsmedel. Utfallet konstaterar att 22 röntgensjuksköterskor alltid använder någon form av strålskydd. Sammanlagt upplever 43 deltagare att befintliga strålskydd är tillräckliga. Av deltagarna anser 36 att kunskapsutveckling om strålning inom arbetet är behövligt. Vidare anser 30 deltagare att kunskapsutveckling inom strålskydd är behövligt. Bland deltagarna svarade 45 att vederbörandes arbetsplats erbjuder arbetsplatskurser. Totalt uttrycker sig 42 röntgensjuksköterskor positivt gentemot rådande arbetsrutiner.

    Slutsats: Enligt resultatet används primärt blyförkläden som strålskydd men även plasthandskar som skyddande komplement. Resultatet fastslår att strålskydd används överlag av studiens röntgensjuksköterskor och att de upplevs som tillräckliga. Det konstateras även att röntgensjuksköterskor i allmänhet anser kunskapsutveckling som nödvändig inom strålning och strålskydd, samt att alla sjukhus i studien erbjuder arbetsplatskurser av olika slag. Slutligen framhåller studien att flertalet röntgensjuksköterskor är positivt inställda till gällande arbetsrutiner. 

  • 271.
    Eriksson, Jan W
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Visvanathar, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, Mölndal, Sweden.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Skrtic, Stanko
    Innovation Strategies & External Liaison, Pharmaceutical Technologies & Development, AstraZeneca, Gothenburg, Sweden;Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden .
    Ekström, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lundqvist, Martin H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Katsogiannos, Petros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, Mölndal, Sweden .
    Tissue-specific glucose partitioning and fat content in prediabetes and type 2 diabetes: whole-body PET/MRI during hyperinsulinemia2021In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 184, no 6, p. 879-889Article in journal (Refereed)
    Abstract [en]

    Objective: To obtain direct quantifications of glucose turnover, volumes and fat content of several tissues in the development of type 2 diabetes (T2D) using a novel integrated approach for whole-body imaging.

    Design and methods: Hyperinsulinemic-euglycemic clamps and simultaneous whole-body integrated [18F]FDG-PET/MRI with automated analyses were performed in control (n = 12), prediabetes (n = 16) and T2D (n = 13) subjects matched for age, sex and BMI.

    Results: Whole-body glucose uptake (Rd) was reduced by approximately 25% in T2D vs control subjects, and partitioning to brain was increased from 3.8% of total Rd in controls to 7.1% in T2D. In liver, subcutaneous AT, thigh muscle, total tissue glucose metabolic rates (MRglu) and their % of total Rd were reduced in T2D compared to control subjects. The prediabetes group had intermediate findings. Total MRglu in heart, visceral AT, gluteus and calf muscle was similar across groups. Whole-body insulin sensitivity assessed as glucose infusion rate correlated with liver MRglu but inversely with brain MRglu. Liver fat content correlated with MRglu in brain but inversely with MRglu in other tissues. Calf muscle fat was inversely associated with MRglu only in the same muscle group.

    Conclusions: This integrated imaging approach provides detailed quantification of tissue-specific glucose metabolism. During T2D development, insulin-stimulated glucose disposal is impaired and increasingly shifted away from muscle, liver and fat toward the brain. Altered glucose handling in the brain and liver fat accumulation may aggravate insulin resistance in several organs.

  • 272.
    Eriksson, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Roy, Tamal
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Sawadjoon, Supaporn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Bachmann, Kim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Sköld, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Larhed, Mats
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Selvaraju, Ramkumar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Odell, Luke R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Synthesis and preclinical evaluation of the CRTH2 antagonist [11C]MK-7246 as a novel PET tracer and potential surrogate marker for pancreatic beta-cell mass2019In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 71, p. 1-10Article in journal (Refereed)
    Abstract [en]

    Introduction: MK-7246 is a potent and selective antagonist for chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Within the pancreas CRTH2 is selectively expressed in pancreatic β-cells where it is believed to play a role in insulin release. Reduction in β-cell mass and insufficient insulin secretion in response to elevated blood glucose levels is a hallmark for type 1 and type 2 diabetes. Reported here is the synthesis of [11C]MK-7246 and initial preclinical evaluation towards CRTH2 imaging. The aim is to develop a method to quantify β-cell mass with PET and facilitate non-invasive studies of disease progression in individuals with type 2 diabetes.

    Methods: The precursor N-desmethyl-O-methyl MK-7246 was synthesized in seven steps and subjected to methylation with [11C]methyl iodide followed by hydrolysis to obtain [11C]MK-7246 labelled in the N-methyl position. Preclinical evaluation included in vitro radiography and immune-staining performed in human pancreatic biopsies. Biodistribution studies were performed in rat by PET-MRI and in pig by PET-CT imaging. The specific tracer uptake was examined in pig by scanning before and after administration of MK-7246 (1 mg/kg). Predicted dosimetry of [11C]MK-7246 in human males was estimated based on the biodistribution in rat.

    Results: [11C]MK-7246 was obtained with activities sufficient for the current investigations (270±120 MBq) and a radiochemical purity of 93±2%. The tracer displayed focal binding in areas with insulin positive islet of Langerhans in human pancreas sections. Baseline uptake in pig was significantly reduced in CRTH2-rich areas after administration of MK-7246; pancreas (66% reduction) and spleen (88% reduction). [11C]MK-7246 exhibited a safe human predicted dosimetry profile as extrapolated from the rat biodistribution data.

    Conclusions: Initial preclinical in vitro and in vivo evaluation of [11C]MK-7246 show binding and biodistribution properties suitable for PET imaging of CRTH2. Further studies are warranted to assess its potential in β-cell mass imaging and CRTH2 drug development.

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  • 273.
    Eriksson, Olle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olsson, Ulf
    Unit of Applied Statistics and Mathematics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    [11C]5HTP-PET in Premenstrual Dysphoria2016Data set
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  • 274.
    Eriksson, Olle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Olsson, Ulf
    Swedish Univ Agr Sci, Unit Appl Stat & Math, Uppsala, Sweden..
    Marteinsdottir, Ina
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Holstad, Maria
    Univ Uppsala Hosp, Dept Neurosci, Psychiat Unit, Uppsala, Sweden..
    Ågren, Hans
    Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden..
    Hartvig, Per
    Univ Copenhagen, Dept Drug Design & Pharmacol, Copenhagen, Denmark..
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Women with Premenstrual Dysphoria Lack the Seemingly Normal Premenstrual Right-Sided Relative Dominance of 5-HTP-Derived Serotonergic Activity in the Dorsolateral Prefrontal Cortices - A Possible Cause of Disabling Mood Symptoms2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 9, article id e0159538Article in journal (Refereed)
    Abstract [en]

    Study Objective To investigate potential quantitative and qualitative differences in brain serotonergic activity between women with Premenstrual Dysphoria (PMD) and asymptomatic controls. Background Serotonin-augmenting drugs alleviate premenstrual mood symptoms in the majority of women with PMD while serotonin-depleting diets worsen PMD symptoms, both indicating intrinsic differences in brain serotonergic activity in women with PMD compared to asymptomatic women. Methods Positron-emission tomography with the immediate precursor of serotonin, 5-hydroxytryptophan (5-HTP), radiolabelled by 11C in the beta-3 position, was performed in the follicular and luteal phases for 12 women with PMD and 8 control women. Brain radioactivity-a proxy for serotonin precursor uptake and synthesis-was measured in 9 regions of interest (ROIs): the right and left sides of the medial prefrontal cortex, dorsolateral prefrontal cortex, putamen and caudate nucleus, and the single "whole brain". Results There were no significant quantitative differences in brain 5-HTP-derived activity between the groups in either of the menstrual phases for any of the 9 ROIs. However, multivariate analysis revealed a significant quantitative and qualitative difference between the groups. Asymptomatic control women showed a premenstrual right sided relative increase in dorsolateral prefrontal cortex 5-HTP derived activity, whereas PMD women displayed the opposite (p = 0.0001). Menstrual phase changes in this asymmetry (premenstrual-follicular) correlated with changes in self ratings of 'irritability' for the entire group (rs = -0.595, p = 0.006). The PMD group showed a strong inverse correlation between phase changes (pre-menstrual-follicular) in plasma levels of estradiol and phase changes in the laterality (dx/sin) of radiotracer activity in the dorsolateral prefrontal ROI (r(s) = -0.635; 0.027). The control group showed no such correlation. Conclusion Absence of increased premenstrual right-sided relative 5-HTP-derived activity of the dorsolateral prefrontal cortices was found to strongly correlate to premenstrual irritability. A causal relationship here seems plausible, and the findings give further support to an underlying frontal brain disturbance in hormonally influenced serotonergic activity in women with PMD. Because of the small number of subjects in the study, these results should be considered preliminary, requiring verification in larger studies.

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  • 275.
    Eriksson, Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Selvaraju, Ramkumar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Eich, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Willny, Mariam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Brismar, Torkel B.
    Karolinska Inst, CLINTEC, Div Med Imaging & Technol, Stockholm, Sweden.
    Carlbom, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Tufvesson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lundgren, Torbjörn
    Karolinska Inst, CLINTEC, Div Transplantat Surg, Stockholm, Sweden.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Positron Emission Tomography to assess the outcome of intraportal islet transplantation2016In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, no 9, p. 2482-2489Article in journal (Refereed)
    Abstract [en]

    There currently exists no imaging methodology to monitor viable islet mass following clinical intraportal islet transplantation. We investigated the potential of the endocrine positron emission tomography (PET) marker [(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP) for this purpose. In a preclinical proof of concept study, the ex vivo and in vivo [(11)C]5-HTP signal was compared to the number of islets transplanted in rats. In a clinical study, human subjects with an intraportal islet graft (n=8) performed two [(11)C]5-HTP PET and MRI examinations 8 months apart. The tracer concentration in the liver as a whole, or in defined hotspots was correlated to measurements of islet graft function. In rat, hepatic uptake of [(11)C]5-HTP correlated with number of transplanted islets. In human subjects, uptake in hepatic hotspots showed a correlation with metabolic assessments of islet function. Change in hotspot SUV predicted loss of graft function in one subject whereas hotspot SUV was unchanged in subjects with stable graft function. The endocrine marker [(11)C]5-HTP thus show correlation between hepatic uptake and transplanted islet function, and show promise as a tool for non-invasive detection of viable islets. The evaluation procedure described herein can be used as benchmark for novel agents targeting intraportally transplanted islets.

  • 276.
    Eriksson, Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Translational PET Imaging. Antaros Med AB, Mölndal, Sweden.;Uppsala Univ, Dept Med Chem, Sci Life Lab, Uppsala, Sweden..
    Velikyan, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Translational PET Imaging.
    Haack, Torsten
    Sanofi Aventis Deutschland GmbH, Frankfurt, Germany..
    Bossart, Martin
    Sanofi Aventis Deutschland GmbH, Frankfurt, Germany..
    Evers, Andreas
    Sanofi Aventis Deutschland GmbH, Frankfurt, Germany..
    Lorenz, Katrin
    Sanofi Aventis Deutschland GmbH, Frankfurt, Germany..
    Laitinen, Iina
    Sanofi Aventis Deutschland GmbH, Frankfurt, Germany..
    Larsen, Philip J.
    Bayer Pharmaceut, Wuppertal, Germany..
    Plettenburg, Oliver
    Helmholtz Zentrum Munchen, Munich, Germany..
    Johansson, Lars
    Antaros Med AB, Mölndal, Sweden..
    Pierrou, Stefan
    Antaros Med AB, Mölndal, Sweden..
    Wagner, Michael
    Sanofi Aventis Deutschland GmbH, Frankfurt, Germany..
    Drug Occupancy Assessment at the Glucose-Dependent Insulinotropic Polypeptide Receptor by Positron Emission Tomography2021In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 70, no 4, p. 842-853Article in journal (Refereed)
    Abstract [en]

    Targeting of the glucose-dependent insulinotropic polypeptide receptor (GIPR) is an emerging strategy in antidiabetic drug development. The aim of this study was to develop a positron emission tomography (PET) radioligand for the GIPR to enable the assessment of target distribution and drug target engagement in vivo. The GIPR-selective peptide S02-GIP was radiolabeled with Ga-68. The resulting PET tracer [Ga-68]S02-GIP-T4 was evaluated for affinity and specificity to human GIPR (huGIPR). The in vivo GIPR binding of [Ga-68]S02-GIP-T4 as well as the occupancy of a drug candidate with GIPR activity were assessed in nonhuman primates (NHPs) by PET. [Ga-68]S02-GIP-T4 bound with nanomolar affinity and high selectivity to huGIPR in overexpressing cells. In vivo, pancreatic binding in NHPs could be dose-dependently inhibited by coinjection of unlabeled S02-GIP-T4. Finally, subcutaneous pretreatment with a high dose of a drug candidate with GIPR activity led to a decreased pancreatic binding of [Ga-68]S02-GIP-T4, corresponding to a GIPR drug occupancy of almost 90%. [Ga-68]S02-GIP-T4 demonstrated a safe dosimetric profile, allowing for repeated studies in humans. In conclusion, [Ga-68]S02-GIP-T4 is a novel PET biomarker for safe, noninvasive, and quantitative assessment of GIPR target distribution and drug occupancy.

  • 277.
    Eriksson, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Science for Life Laboratory, SciLifeLab. Antaros Med AB, Uppsala, Sweden.
    Bossart, M.
    Sanofi Aventis, Frankfurt, Germany..
    Haack, T.
    Sanofi Aventis, Frankfurt, Germany..
    Laitinen, I.
    Sanofi Aventis, Frankfurt, Germany..
    Larsen, P.
    Sanofi Aventis, Frankfurt, Germany..
    Plettenburg, O.
    Helmholtz Zentrum, Munich, Germany..
    Johansson, L.
    Antaros Med AB, Molndal, Sweden..
    Pierrou, S.
    Antaros Med AB, Molndal, Sweden..
    Wagner, M.
    Sanofi Aventis, Frankfurt, Germany..
    Velikyan, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry. Uppsala PET Ctr, Uppsala, Sweden..
    First-in-class PET tracer for the glucagon receptor2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S400-S400Article in journal (Other academic)
  • 278.
    Eriksson, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Berg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Olerud, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Shalabi, Adel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hänni, Mari
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Low-dose CT of postoperative pelvic fractures: a comparison with radiography2019In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 60, no 1, p. 85-91Article in journal (Refereed)
    Abstract [en]

    Background Computed tomography (CT) is superior to conventional radiography (CR) for assessing internal fixation of pelvic fractures, but with a higher radiation exposure. Low-dose CT (LDCT) could possibly have a sufficient diagnostic accuracy but with a lower radiation dose. Purpose To compare postoperative diagnostic accuracy of LDCT and CR after open reduction and internal fixation of pelvic fracture. Material and Methods Twenty-one patients were examined with LDCT and CR 0-9 days after surgery. The examinations were reviewed by two musculoskeletal radiologists. Hardware, degree of fracture reduction, image quality, and reviewing time were assessed, and effective radiation dose was calculated. Inter-reader agreement was calculated. Results LDCT was significantly better than CR in determining whether hardware positioning was assessable ( P < 0.001). Acetabular congruence was assessable in all fractured patients with LDCT. In 12 of the 32 assessments with CR of patients with an acetabular fracture, joint congruence was not assessable due to overlapping hardware ( P = 0.001). Image quality was significantly higher for LDCT. Median time to review was 240 s for LDCT compared to 180 s for CR. Effective dose was 0.79 mSv for LDCT compared to 0.32 mSv for CR ( P < 0.001). Conclusion LDCT is more reliable than CR in assessing hardware position and fracture reduction. Joint congruency is sometimes not possible to assess with CR, due to overlapping hardware. The image quality is higher, but also the effective dose, with LDCT than with CR.

  • 279.
    Eriksson, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Maguire, Gerald Q
    Noz, Marilyn E
    Zeleznik, Michael P
    Olivecrona, Henrik
    Shalabi, Adel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hänni, Mari
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Are low-dose CT scans a satisfactory substitute for stereoradiographs for migration studies?: A preclinical test of low-dose CT scanning protocols and their application in a pilot patient2019In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 60, no 12, p. 1643-1652Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Computed tomography (CT) has the potential to acquire the data needed for migration studies of orthopedic joint implants of patients who have had tantalum beads implanted at the time of joint replacement surgery. This can be accomplished with the same precision as radiostereometric analysis (RSA). Switching to CT would increase availability without the need for the specific facilities required for RSA. However, higher effective dose is a concern.

    PURPOSE: To investigate if migration measurements can be done with CT with an accuracy and effective dose comparable to that of conventional RSA.

    MATERIAL AND METHODS: Fourteen scanning protocols were tested in a hip phantom that incorporated tantalum beads and an uncemented femoral stem. The protocols were graded for clinical practice according to the three parameters of image quality, effective dose, and robustness of numerical data. After grading, the two protocols that graded best overall were applied to a pilot patient.

    RESULTS: All protocols produced scans in which the numerical data were sufficient for a migration analysis at least as precise as would be expected using RSA. A protocol with an effective dose of 0.70 mSv was shown to be applicable in a pilot patient.

    CONCLUSION: Low-dose CT scans with an effective dose comparable to a set of routine plain radiographs can be used for precise migration measurements.

  • 280.
    Espes, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Selvaraju, Ram Kumar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rosestedt, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Cheung, Pierre
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Translational PET Imaging.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical AB, Mölndal, Sweden.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Eriksson, Olof
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Translational PET Imaging.
    Longitudinal Assessment of 11C-5-Hydroxytryptophan Uptake in Pancreas After Debut of Type 1 Diabetes2021In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 70, no 4, p. 966-975Article in journal (Refereed)
    Abstract [en]

    The longitudinal alterations of the pancreatic β-cell and islet mass in the progression of type 1 diabetes (T1D) are still poorly understood. The objective of this study was to repeatedly assess the endocrine volume and the morphology of the pancreas for up to 24 months after T1D diagnosis (n = 16), by 11C-5-hydroxytryptophan (11C-5-HTP) positron emission tomography (PET) and MRI. Study participants were examined four times by PET/MRI: at recruitment and then after 6, 12, and 24 months. Clinical examinations and assessment of β-cell function by a mixed-meal tolerance test and fasting blood samples were performed in connection with the imaging examination. Pancreas volume has a tendency to decrease from 50.2 ± 10.3 mL at T1D debut to 42.2 ± 14.6 mL after 24 months (P < 0.098). Pancreas uptake of 11C-5-HTP (e.g., the volume of the endocrine pancreas) did not decrease from T1D diagnosis (0.23 ± 0.10 % of injected dose) to 24-month follow-up, 0.21 ± 0.14% of injected dose, and exhibited low interindividual changes. Pancreas perfusion was unchanged from diagnosis to 24-month follow-up. The pancreas uptake of 11C-5-HTP correlated with the long-term metabolic control as estimated by HbA1c (P < 0.05). Our findings argue against a major destruction of β-cell or islet mass in the 2-year period after diagnosis of T1D.

  • 281.
    Espes, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Manell, Elin
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Rydén, Anneli
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Carlbom, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Jensen-Waern, Marianne
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Jansson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pancreatic perfusion and its response to glucose as measured by simultaneous PET/MRI2019In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 56, no 10, p. 1113-1120Article in journal (Refereed)
    Abstract [en]

    AIMS: Perfusion of the pancreas and the islets of Langerhans is sensitive to physiological stimuli and is dysregulated in metabolic disease. Pancreatic perfusion can be assessed by both positron emission tomography (PET) and magnetic resonance imaging (MRI), but the methods have not been directly compared or benchmarked against the gold-standard microsphere technique.

    METHODS: Pigs (n = 4) were examined by [15O]H2O PET and intravoxel incoherent motion (IVIM) MRI technique simultaneously using a hybrid PET/MRI scanner. The pancreatic perfusion was measured both at basal conditions and after intravenous (IV) administration of up to 0.5 g/kg glucose.

    RESULTS: Pancreatic perfusion increased by 35%, 157%, and 29% after IV 0.5 g/kg glucose compared to during basal conditions, as assessed by [15O]H2O PET, IVIM MRI, and microspheres, respectively. There was a correlation between pancreatic perfusion as assessed by [15O]H2O PET and IVIM MRI (r = 0.81, R2 = 0.65, p < 0.01). The absolute quantification of pancreatic perfusion (ml/min/g) by [15O]H2O PET was within a 15% error of margin of the microsphere technique.

    CONCLUSION: Pancreatic perfusion by [15O]H2O PET was in agreement with the microsphere technique assessment. The IVIM MRI method has the potential to replace [15O]H2O PET if the pancreatic perfusion is sufficiently large, but not when absolute quantitation is required.

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  • 282.
    Estrada, Sergio
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Thibblin, Alf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Sprycha, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Buchanan, Tim
    UCB Pharma, Brussels, Belgium..
    Mestdagh, Nathalie
    UCB Pharma, Brussels, Belgium..
    Kenda, Benoit
    UCB Pharma, Brussels, Belgium..
    Mercier, Joel
    UCB Pharma, Brussels, Belgium..
    Provins, Laurent
    UCB Pharma, Brussels, Belgium..
    Gillard, Michel
    UCB Pharma, Brussels, Belgium..
    Tytgat, Dominique
    UCB Pharma, Brussels, Belgium.;Sanofi Aventis Deutschland GmbH, Frankfurt, Germany..
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    [C-11]UCB-A, a novel PET tracer for synaptic vesicle protein 2 A2016In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 43, no 6, p. 325-332Article in journal (Refereed)
    Abstract [en]

    Introduction: Development of a selective and specific high affinity PET tracer, [C-11]UCB-A, for the in vivo study of SV2A expression in humans. Radiochemistry and preclinical studies in rats and pigs including development of a tracer kinetic model to determine V-T. A method for the measurement of percent intact tracer in plasma was developed and the radiation dosimetry was determined in rats. Results: 3-5 GBq of [C-11]UCB-A could be produced with radiochemical purity exceeding 98% with a specific radioactivity of around 65 GBq/mu mol. In vitro binding showed high selective binding towards SV2A. [C-11]UCB-A displayed a dose-dependent and reversible binding to SV2A as measured with PET in rats and pigs and the V-T could be determined by Logan analysis. The dosimetry was favorable and low enough to allow multiple administrations of [C-11]UCB-A to healthy volunteers, and the metabolite analysis showed no sign of labeled metabolites in brain. Conclusions: We have developed the novel PET tracer, [C-11]UCB-A, that can be used to measure SV2A expression in vivo. The dosimetry allows up to 5 administrations of 400 MBq of [C-11]UCB-A in humans. Apart from measuring drug occupancy, as we have shown, the tracer can potentially be used to compare SV2A expression between individuals because of the rather narrow range of baseline V-T values. This will have to be further validated in human studies.

  • 283.
    Eyjolfsdottir, Helga
    et al.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Geriatr, S-17176 Stockholm, Sweden..
    Eriksdotter, Maria
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Geriatr, S-17176 Stockholm, Sweden..
    Linderoth, Bengt
    Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Neurosurg, Bldg R3 02, S-17176 Stockholm, Sweden..
    Lind, Goran
    Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Neurosurg, Bldg R3 02, S-17176 Stockholm, Sweden..
    Juliusson, Bengt
    NsGene Inc, 225 Chapman St, Providence, RI 02905 USA..
    Kusk, Philip
    NsGene Inc, 225 Chapman St, Providence, RI 02905 USA..
    Almkvist, Ove
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden..
    Andreasen, Niels
    Karolinska Univ Hosp, Dept Geriatr, S-17176 Stockholm, Sweden..
    Blennow, Kaj
    Univ Gothenburg, Dept Clin Neurosci, Clin Neurochem Lab, S-41345 Gothenburg, Sweden..
    Ferreira, Daniel
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden..
    Westman, Eric
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden..
    Nennesmo, Inger
    Karolinska Univ Hosp, Dept Lab Med, Sect Pathol, S-17176 Stockholm, Sweden..
    Karami, Azadeh
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden..
    Darreh-Shori, Taher
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden..
    Kadir, Ahmadul
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden..
    Nordberg, Agneta
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Geriatr, S-17176 Stockholm, Sweden..
    Sundström, Erik
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;Stiftelsen Stockholms Sjukhem, Mariebergsgatan 22, S-11235 Stockholm, Sweden..
    Wahlund, Lars-Olof
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Geriatr, S-17176 Stockholm, Sweden..
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wiberg, Maria
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Med Imaging & Technol, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Radiol, S-17176 Stockholm, Sweden..
    Winblad, Bengt
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Geriatr, S-17176 Stockholm, Sweden..
    Seiger, Ake
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;Stiftelsen Stockholms Sjukhem, Mariebergsgatan 22, S-11235 Stockholm, Sweden..
    Wahlberg, Lars
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;NsGene Inc, 225 Chapman St, Providence, RI 02905 USA..
    Almqvist, Per
    Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Neurosurg, Bldg R3 02, S-17176 Stockholm, Sweden..
    Targeted delivery of nerve growth factor to the cholinergic basal forebrain of Alzheimer's disease patients: application of a second-generation encapsulated cell biodelivery device2016In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 8, article id 30Article in journal (Refereed)
    Abstract [en]

    Background: Targeted delivery of nerve growth factor (NGF) has emerged as a potential therapy for Alzheimer's disease (AD) due to its regenerative effects on basal forebrain cholinergic neurons. This hypothesis has been tested in patients with AD using encapsulated cell biodelivery of NGF (NGF-ECB) in a first-in-human study. We report our results from a third-dose cohort of patients receiving second-generation NGF-ECB implants with improved NGF secretion. Methods: Four patients with mild to moderate AD were recruited to participate in an open-label, phase Ib dose escalation study with a 6-month duration. Each patient underwent stereotactic implant surgery with four NGF-ECB implants targeted at the cholinergic basal forebrain. The NGF secretion of the second-generation implants was improved by using the Sleeping Beauty transposon gene expression technology and an improved three-dimensional internal scaffolding, resulting in production of about 10 ng NGF/device/day. Results: All patients underwent successful implant procedures without complications, and all patients completed the study, including implant removal after 6 months. Upon removal, 13 of 16 implants released NGF, 8 implants released NGF at the same rate or higher than before the implant procedure, and 3 implants failed to release detectable amounts of NGF. Of 16 adverse events, none was NGF-, or implant-related. Changes from baseline values of cholinergic markers in cerebrospinal fluid (CSF) correlated with cortical nicotinic receptor expression and Mini Mental State Examination score. Levels of neurofilament light chain (NFL) protein increased in CSF after NGF-ECB implant, while glial fibrillary acidic protein (GFAP) remained stable. Conclusions: The data derived from this patient cohort demonstrate the safety and tolerability of sustained NGF release by a second-generation NGF-ECB implant to the basal forebrain, with uneventful surgical implant and removal of NGF-ECB implants in a new dosing cohort of four patients with AD.

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  • 284.
    Ezra, Emmanuel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Siilin, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Gulobovic, Milan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Graf, J. Wilhelm R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Patterns of tined lead migration in sacral nerve modulation2020In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 35, no 6, p. 1163-1166Article in journal (Refereed)
    Abstract [en]

    Aim Lead migration is a common cause of loss of efficacy in sacral nerve modulation. Our aim was to systematically study the migration pattern of tined leads in sacral nerve modulation. Our hypothesis was that tined leads may promote forward migration because of their configuration. Method Consecutive patients treated with sacral nerve modulation with a tined lead electrode, who had experienced loss of efficacy and had radiographs both at baseline and after loss of efficacy between 2005 and 2016 were eligible for inclusion. Results Twenty-five patients out of 70 with loss of efficacy were studied. Lead migration was measured as percent electrode movement in relation to sacral cortex at lateral projection. All had some degree of lead migration, ranging from 35% backward to 74% forward migration. Sixteen (64%) had forward migration while nine (36%) had backward migration. In seven patients (28%), loss of efficacy was associated with an episode of perceived mechanical strain on the electrode. Fifty percent (4/8) who associated their loss of efficacy with an adverse event had forward migration of the electrode. Conclusions Forward lead migration with concomitant loss of efficacy seems to be a common event in patients with tined leads, hence supporting our hypothesis. The retrospective design and that some of the patients with loss of efficacy could not be included because of incomplete data, which is a limitation to the study. Further studies are needed to confirm to what extent the direction and magnitude of the migration relate to loss of efficacy.

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  • 285.
    Fagius, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Feresiadou, Amalia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Severe relapses and rebound activity after natalizumab discontinuation in MS patients with more than five years of treatment with stable disease course2015In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, p. 297-297Article in journal (Other academic)
  • 286.
    Fagius, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Feresiadou, Amalia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Discontinuation of disease modifying treatments in middle aged multiple sclerosis patients: First line drugs vs natalizumab2017In: Multiple Sclerosis and Related Disorders, ISSN 2211-0348, E-ISSN 2211-0356, Vol. 12, p. 82-87, article id S2211-0348(17)30010-XArticle in journal (Refereed)
    Abstract [en]

    BACKGROUND: Several disease-modifying drugs (DMD) are available for the treatment of MS, and most patients with relapsing-remitting disease are currently treated. Data on when and how DMD treatment can be safely discontinued are scarce.

    METHODS: Fifteen MS patients, treated with natalizumab for >5 years without clinical and radiological signs of inflammatory disease activity, suspended treatment and were monitored with MRI examinations and clinical follow-up to determine recurrence of disease activity. This group was compared with a retrospectively analysed cohort comprising 55 MS patients treated with first-line DMDs discontinuing therapy in the time period of 1998-2015 after an analogous stable course.

    RESULTS: Natalizumab discontinuers were followed for on average 19 months, and follow-up data for 56 months were available for first-line DMD quitters. Two-thirds of natalizumab treated patients experienced recurrent inflammatory disease activity, and one third had recurrence of rebound character. In contrast, 35% of first-line DMD quitters had mild recurrent disease activity, and no one exhibited rebound.

    CONCLUSIONS: Withdrawal of a first-line DMD after prolonged treatment in middle-aged MS patients with stable disease appears to be relatively safe, while natalizumab withdrawal in a similar group of patients cannot be safely done without starting alternative therapy.

  • 287.
    Fagman, Erika
    et al.
    Univ Gothenburg, Inst Clin Sci, Dept Radiol, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Radiol, Gothenburg, Sweden..
    Alven, Jennifer
    Univ Gothenburg, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Chalmers Univ Technol, Dept Elect Engn, Comp Vis & Med Image Anal, Gothenburg, Sweden..
    Westerbergh, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Kitslaar, Pieter
    Med Med Imaging Syst BV, Leiden, Netherlands..
    Kercsik, Michael
    Univ Gothenburg, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Alingsas Hosp, Dept Radiol, Alingsas, Sweden..
    Cederlund, Kerstin
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Engvall, Jan
    Linköping Univ, Dept Clin Physiol, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, CMIV Ctr Med Image Sci & Visualizat, Linköping, Sweden..
    Goncalves, Isabel
    Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Markstad, Hanna
    Lund Univ, Cardiovasc Res Translat Studies, Clin Sci Malmö, Lund, Sweden.;Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Diagnost Radiol, Lund, Sweden..
    Ostenfeld, Ellen
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Clin Physiol, Lund, Sweden..
    Bergstrom, Goran
    Univ Gothenburg, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Clin Physiol, Gothenburg, Sweden..
    Hjelmgren, Ola
    Univ Gothenburg, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Clin Physiol, Gothenburg, Sweden..
    High-quality annotations for deep learning enabled plaque analysis in SCAPIS cardiac computed tomography angiography2023In: Heliyon, E-ISSN 2405-8440, Vol. 9, no 5, article id e16058Article in journal (Refereed)
    Abstract [en]

    Background: Plaque analysis with coronary computed tomography angiography (CCTA) is a promising tool to identify high risk of future coronary events. The analysis process is time-consuming, and requires highly trained readers. Deep learning models have proved to excel at similar tasks, however, training these models requires large sets of expert-annotated training data. The aims of this study were to generate a large, high-quality annotated CCTA dataset derived from Swedish CArdioPulmonary BioImage Study (SCAPIS), report the reproducibility of the annotation core lab and describe the plaque characteristics and their association with established risk factors.

    Methods and results: The coronary artery tree was manually segmented using semi-automatic software by four primary and one senior secondary reader. A randomly selected sample of 469 subjects, all with coronary plaques and stratified for cardiovascular risk using the Systematic Coronary Risk Evaluation (SCORE), were analyzed. The reproducibility study (n = 78) showed an agreement for plaque detection of 0.91 (0.84-0.97). The mean percentage difference for plaque volumes was-0.6% the mean absolute percentage difference 19.4% (CV 13.7%, ICC 0.94). There was a positive correlation between SCORE and total plaque volume (rho = 0.30, p < 0.001) and total low attenuation plaque volume (rho = 0.29, p < 0.001).

    Conclusions: We have generated a CCTA dataset with high-quality plaque annotations showing good reproducibility and an expected correlation between plaque features and cardiovascular risk. The stratified data sampling has enriched high-risk plaques making the data well suited as training, validation and test data for a fully automatic analysis tool based on deep learning.

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  • 288.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    On potentials and limitations of perfusion MRI in neurological disorders2020Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cerebral perfusion outlines several parameters which describe the status of cerebral haemodynamics. Numerous neurological diseases affect cerebral perfusion, thus the importance of diagnostic measurements. Perfusion magnetic resonance imaging (MRI) is a collection of non-ionizing magnetic resonance-based perfusion measurement techniques that can be used for clinical assessment of cerebral perfusion. The aim of this thesis was to investigate potentials and limitations of perfusion MRI used for clinical assessment of patients with neurological disorders. Patients with glioblastoma were examined with dynamic susceptibility contrast MRI (DSC-MRI) and dynamic contrast enhanced MRI (DCE-MRI) before/after treatment with fractionated radiotherapy (FRT). Radiation-induced changes in normal-appearing brain tissue were found in the form of decreased cerebral blood volume (CBV) and cerebral blood flow (CBF) measured with DSC-MRI and increased vascular permeability and increased fraction of the extravascular extracellular space measured with DCE-MRI. Papers I–II provide valuable information regarding the possibility that radiation-induced changes could be a confounder in DSC-MRI and that DCE-MRI could potentially act as a biomarker for vascular damage secondary to radiation exposure. Additionally, CBF derived from arterial spin labelling (ASL) was compared to the reference standard 15O-water positron emission tomography (PET). Simultaneous measurements were acquired with an integrated PET/MR scanner using arterial blood sampling and zero-echo time-based attenuation correction in healthy subjects and patients with epilepsy. Correlation- and Bland–Altman analysis showed fair correlation and a negative relationship with wide limits of agreement in several cortical and subcortical regions. Thus, agreement with 15O-water is insufficient for absolute quantification with ASL, but ASL provides reliable relative measures that could potentially be rescaled to absolute values. Moyamoya disease (MMD) is characterized by progressive stenosis/occlusion in large brain arteries. A limitation of ASL is the sensitivity to prolonged arterial transit times, which is common in the collateral vessels of the brain in patients with MMD. Given the non-invasiveness and non-ionizing exposure, ASL has a pronounced potential for use in diagnostic imaging in patients with MMD. ASL was performed before and after administration of acetazolamide; CBF and cerebrovascular reserve capacity were derived for large vascular regions. Artefacts originating from prolonged arterial transit times were found to have negligible effects on CBF and cerebrovascular reserve capacity derived from ASL. This thesis adds to the understanding of potential and limitations of perfusion MRI in neurological diseases. 

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  • 289.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Perfusion MRI of the brain after radiotherapy in patients with glioblastoma – potential and problems2018Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Perfusion Magnetic Resonance Imaging (MRI) is a useful tool in diagnostic evaluation and treatment response assessment in patients with glioblastoma. The standard treatment regimen includes surgical resection, radiotherapy and adjuvant chemotherapy. However, prognosis is poor; relative 5-year survival is 3–5%. Radiotherapy sequelae may have considerable negative effects on the patients’ quality of life. Acute and early delayed radiation-induced injury is primarily considered damage to the cerebral vascular tissue.

     

    The general aim of this study was to evaluate how perfusion MRI evaluation, based on contrast agent administration (DSC- and DCE-MRI), is affected by or can be useful to assess radiation-induced changes in normal appearing brain tissue in patients with glioblastoma after radiotherapy.

     

    Paper I: Dynamic Susceptibility Contrast (DSC)-MRI is a common perfusion MRI method in clinical practice in patients with glioblastoma. Due to inherent limitations, cerebral blood volume (CBV) and cerebral blood flow (CBF) derived from DSC-MRI are normalized to contralateral normal appearing white matter. Ten patients with glioblastoma were examined. Regional and global normalized CBV and normalized CBF in white and gray matter decreased after radiotherapy, followed by a tendency to recover. The response of nCBV and nCBF was dose-dependent in white matter but not in gray matter. In conclusion, radiotherapy effects on normal appearing white matter can confound treatment evaluation with DSC-MRI in patients with glioblastoma.

     

    Paper II: Dynamic Contrast Enhanced (DCE)-MRI may be useful in evaluating radiation-induced damage in normal appearing brain tissue.  DCE-MRI-derived parameters, vascular permeability (Ktrans) and the fractional volume of the extravascular extracellular space (Ve) are potential biomarkers. Twelve patients with glioblastoma were examined. A tendency toward increased Ktrans and Ve was seen, suggesting that these parameters may act as potential biomarkers for acute and early delayed radiation-induced vascular damage

  • 290.
    Fahlström, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Engström, Mathias
    GE Healthcare, Applied Science Laboratory.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Evaluation of Arterial Spin Labeling MRI: Comparison with 15O-Water PET on an Integrated PET/MR Scanner2021In: Diagnostics (Basel), ISSN 2075-4418, Vol. 11, no 5, article id 821Article in journal (Refereed)
    Abstract [en]

    Cerebral blood flow (CBF) measurements are of high clinical value and can be acquired non-invasively with no radiation exposure using pseudo-continuous arterial spin labeling (ASL). The aim of this study was to evaluate accordance in resting state CBF between ASL (CBFASL) and 15O-water positron emission tomography (PET) (CBFPET) acquired simultaneously on an integrated 3T PET/MR system. The data comprised ASL and dynamic 15O-water PET data with arterial blood sampling of eighteen subjects (eight patients with focal epilepsy and ten healthy controls, age 21 to 61 years). 15O-water PET parametric CBF images were generated using a basis function implementation of the single tissue compartment model. Cortical and subcortical regions were automatically segmented using Freesurfer. Average CBFASL and CBFPET in grey matter were 60 ± 20 and 75 ± 22 mL/100 g/min respectively, with a relatively high correlation (r = 0.78, p < 0.001). Bland-Altman analysis revealed poor agreement (bias = −15 mL/100 g/min, lower and upper limits of agreements = −16 and 45 mL/100 g/min, respectively) with a negative relationship. Accounting for the negative relationship, the width of the limits of agreement could be narrowed from 61 mL/100 g/min to 35 mL/100 g/min using regression-based limits of agreements. Although a high correlation between CBFASL and CBFPET was found, the agreement in absolute CBF values was not sufficient for ASL to be used interchangeably with 15O-water PET.

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  • 291.
    Fahlström, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Nyholm, Tufve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Perfusion Magnetic Resonance Imaging Changes in Normal Appearing Brain Tissue after Radiotherapy in Glioblastoma Patients may Confound Longitudinal Evaluation of Treatment Response2018In: Radiology and Oncology, ISSN 1318-2099, E-ISSN 1581-3207, Vol. 52, no 2, p. 143-151Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was assess acute and early delayed radiation-induced changes in normal-appearing brain tissue perfusion as measured with perfusion magnetic resonance imaging (MRI) and the dependence of these changes on the fractionated radiotherapy (FRT) dose level.

    Patients and methods: Seventeen patients with glioma WHO grade III-IV treated with FRT were included in this prospective study, seven were excluded because of inconsistent FRT protocol or missing examinations. Dynamic susceptibility contrast MRI and contrast-enhanced 3D-T1-weighted (3D-T1w) images were acquired prior to and in average (standard deviation): 3.1 (3.3), 34.4 (9.5) and 103.3 (12.9) days after FRT. Pre-FRT 3D-T1w images were segmented into white- and grey matter. Cerebral blood volume (CBV) and cerebral blood flow (CBF) maps were calculated and co-registered patient-wise to pre-FRT 3D-T1w images. Seven radiation dose regions were created for each tissue type: 0-5 Gy, 5-10 Gy, 10-20 Gy, 20-30 Gy, 30-40 Gy, 40-50 Gy and 50-60 Gy. Mean CBV and CBF were calculated in each dose region and normalised (nCBV and nCBF) to the mean CBV and CBF in 0-5 Gy white- and grey matter reference regions, respectively.

    Results: Regional and global nCBV and nCBF in white- and grey matter decreased after FRT, followed by a tendency to recover. The response of nCBV and nCBF was dose-dependent in white matter but not in grey matter.

    Conclusions: Our data suggest that radiation-induced perfusion changes occur in normal-appearing brain tissue after FRT. This can cause an overestimation of relative tumour perfusion using dynamic susceptibility contrast MRI, and can thus confound tumour treatment evaluation.

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  • 292.
    Fahlström, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fransson, Samuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Nyholm, Tufve
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Dynamic Contrast-Enhanced Magnetic Resonance Imaging May Act as a Biomarker for Vascular Damage in Normal Appearing Brain Tissue after Radiotherapy in Patients with Glioblastoma2018In: Acta Radiologica Open, E-ISSN 2058-4601, Vol. 7, no 11Article in journal (Refereed)
    Abstract [en]

    Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a promising perfusion method and may be useful in evaluating radiation-induced changes in normal-appearing brain tissue.

    Purpose: To assess whether radiotherapy induces changes in vascular permeability (Ktrans) and the fractional volume of the extravascular extracellular space (Ve) derived from DCE-MRI in normal-appearing brain tissue and possible relationships to radiation dose given.

    Material and Methods: Seventeen patients with glioblastoma treated with radiotherapy and chemotherapy were included; five were excluded because of inconsistencies in the radiotherapy protocol or early drop-out. DCE-MRI, contrast-enhanced three-dimensional (3D) T1-weighted (T1W) images and T2-weighted fluid attenuated inversion recovery (T2-FLAIR) images were acquired before and on average 3.3, 30.6, 101.6, and 185.7 days after radiotherapy. Pre-radiotherapy CE T1W and T2-FLAIR images were segmented into white and gray matter, excluding all non-healthy tissue. Ktrans and Ve were calculated using the extended Kety model with the Parker population-based arterial input function. Six radiation dose regions were created for each tissue type, based on each patient's computed tomography-based dose plan. Mean Ktrans and Ve were calculated over each dose region and tissue type.

    Results: Global Ktrans and Ve demonstrated mostly non-significant changes with mean values higher for post-radiotherapy examinations in both gray and white matter compared to pre-radiotherapy. No relationship to radiation dose was found.

    Conclusion: Additional studies are needed to validate if Ktrans and Ve derived from DCE-MRI may act as potential biomarkers for acute and early-delayed radiation-induced vascular damages. No dose-response relationship was found.

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  • 293.
    Fahlström, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    High Intravascular Signal Arterial Transit Time Artifacts Have Negligible Effects on Cerebral Blood Flow and Cerebrovascular Reserve Capacity Measurement Using Single Postlabel Delay Arterial Spin-Labeling in Patients with Moyamoya Disease2020In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 41, no 3, p. 430-436Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Arterial spin-labeling-derived CBF values may be affected by arterial transit time artefacts. Thus, our aim was to assess to what extent arterial spin-labeling–derived CBF and cerebrovascular reserve capacity values in major vascular regions are overestimated due to the arterial transit time artifacts in patients with Moyamoya disease.

    MATERIALS AND METHODS: Eight patients with Moyamoya disease were included before or after revascularization surgery. CBF maps were acquired using a 3D pseudocontinuous arterial spin-labeling sequence, before and 5, 15, and 25 minutes after an IV acetazolamide injection and were registered to each patient’s 3D-T1-weighted images. Vascular regions were defined by spatial normalization to a Montreal Neurological Institute–based vascular regional template. The arterial transit time artifacts were defined as voxels with high signal intensity corresponding to the right tail of the histogram for a given vascular region, with the cutoff selected by visual inspection. Arterial transit time artifact maps were created and applied as masks to exclude arterial transit time artifacts on CBF maps, to create corrected CBF maps. The cerebrovascular reserve capacity was calculated as CBF after acetazolamide injection relative to CBF at baseline for corrected and uncorrected CBF values, respectively.

    RESULTS: A total of 16 examinations were analyzed. Arterial transit time artifacts were present mostly in the MCA, whereas the posterior cerebral artery was generally unaffected. The largest differences between corrected and uncorrected CBF and cerebrovascular reserve capacity values, reported as patient group average ratio and percentage point difference, respectively, were 0.978 (95% CI, 0.968–0.988) and 1.8 percentage points (95% CI, 0.3–3.2 percentage points). Both were found in the left MCA, 15 and 5 minutes post-acetazolamide injection, respectively.

    CONCLUSIONS: Arterial transit time artifacts have negligible overestimation effects on calculated vascular region-based CBF and cerebrovascular reserve capacity values derived from single-delay 3D pseudocontinuous arterial spin-labeling.

  • 294.
    Fahlström, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lindskog, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Engström, Mathias
    GE Healthcare, Stockholm, Sweden..
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Correlation between regional cerebral blood flow based on simultaneously acquired arterial spin labelling MRI and 15O-water-PET using zero-echo-time-based attenuation correction2017In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 58, no S1, article id 362Article in journal (Other academic)
    Abstract [en]

    Objectives: Arterial spin labelling (ASL) MRI promises clinical value in several common neurological disorders. Its quantitative accuracy and reproducibility, however, need to be further validated, ideally using simultaneously acquired measurements with 15O-water-PET on an integrated PET-MR scanner. However, so far, few studies have attempted this and the inclusion of bone in MR-based attenuation correction for PET has thus far been a challenge, compromising the quantitative accuracy of PET-MR based 15O-water PET data. The aim of the present work was to assess the correlation of ASL- and 15O-water-PET based regional cerebral blood flow (rCBF) values based on simultaneously acquired data, using zero-echo-time (ZTE)-based attenuation correction, as well as to assess the reproducibility of ASL-based rCBF.

    Methods: Six subjects underwent 10 min PET scans after automated bolus injection of 400 MBq 15O-water (1 mL/s during 5 s followed by 35 mL saline at 2 mL/s) on a time-of-flight integrated PET-MR scanner (Signa PET-MR, GE Healthcare). Arterial blood radioactivity concentrations were monitored using continuous sampling from the radial artery (Swisstrace Twilite Two). Simultaneously, a 3D FSE pseudo-continuous ASL (3D pCASL) with a spiral read-out as supplied by the scanner manufacturer in the commercial software were acquired using an 8 channel head coil (Invivo Hi-Res Head Coil). In addition, 3D T1-w, ZTE and Dixon fat-water MRI were acquired. The ASL procedure was repeated after 2 h (patients remained in the scanner). Quantifiable ASL-based CBF maps were generated. PET images were reconstructed into 26 frames of increasing durations using time-of-flight OSEM (2 iterations, 28 subsets) and a 5 mm post-filter, with ZTE-based attenuation correction. Blood sampler data were corrected for delay and dispersion and 15O-water-based CBF maps were calculated using a basis function implementation of the single tissue compartment model including a fitted blood volume parameter. CBF maps were co-registered to each patient's T1-w image. 3D T1-w images were segmented and normalised to MNI space using SPM12, and anterior, middle and posterior flow territory volumes of interest (VOIs) were created from a standard template in MNI space and inversely transformed for each patient. In addition, a 45-VOI probabilistic template was applied using PVElab software. Correlations between PET- and ASL-based rCBF values were assessed using regression analysis, and reproducibility of ASL using a paired t-test.

    Results: Mean (CI) total brain grey matter CBF values were 67.2 (48.0-86.5) mL/min/100 g for 15O-water-PET and 65.5 (55.7-75.5) mL/min/100 g for ASL. Although correlation and agreement between 15O-water and ASL-based rCBF for individual VOIs in the 45-VOI template were generally poor, significant correlations were found on a grey matter flow territory basis, with R2 ranging from 0.70 in the anterior flow territory to 0.86 in the middle flow territory. rCBF values were significantly reduced between second and first ASL for all flow territories (p<0.01), with a mean decrease of 10%.

    Conclusion: A good correlation between regional flow territory CBF values based on ASL and 15O-water-PET was found, using ZTE-based attenuation correction for PET data which takes bone tissue into account. ASL values for regional flow territories may have potential applications in patients with dementia or cerebrovascular diseases affecting blood flow such as moya moya. The decrease of ASL-based rCBF values in the reproducibility study needs to be investigated further to assess whether this is a methodological issue or reflects a true decrease in rCBF. Research Support: Uppsala County Council

  • 295.
    Fahlström, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Subasic, Irfan
    Teder, Priit
    Åberg, Karin
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Blomström-Lundqvist, Carina
    Pacemaker ingen absolut kontraindikation för MR-undersökning.2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, article id ECLRArticle in journal (Refereed)
    Abstract [sv]

    Cardiac implantable electronic devices (CIED) not an absolute contraindication to MRI Conventional cardiac implantable electronic devices (CIED) are presently not an absolute contraindication to magnetic resonance imaging (MRI), which thus is accessible for device patients depending on risk/benefit assessments. While current literature suggests that MRI can be performed without risk if precautions are taken, adverse events have been reported. The number of MR conditional CIEDs is rapidly increasing, and depending on device and electrode combinations, patients can now undergo advanced MRI at 3.0 T without risk, possibly with restriction, e.g. anatomy coverage. This article describes published guidelines, recommendations and complications that may appear during MRI and precautions to avoid and manage them. The recommendations made are based on a thorough literature review and our own experiences reported with the aim to increase the awareness of healthcare professionals so that device patients no longer are excluded from the advantages of MRI as a diagnostic tool.

  • 296.
    Fahlström, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Svedung-Wettervik, Teodor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurosurgery.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Evaluation of single-delay arterial spin labeling-based spatial coefficient of variation and histogram-based parameters in relation to cerebrovascular reserve in patients with Moyamoya disease.2023In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 14, article id 1137046Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Single-delay Arterial Spin Labeling (ASL)-based spatial coefficient of variation (CoVCBF) has been suggested as a measure of hemodynamic disturbance in patients with cerebrovascular diseases. However, spatial CoVCBF and other histogram-based parameters such as skewness and kurtosis and the volume of the arterial transit time artefact (ATAvol), has not been evaluated in patients with MMD nor against cerebrovascular reserve (CVR). The aim of this study was to assess whether any associations between spatial CoVCBF, skewness, kurtosis, and ATAvol are present and to analyze any potential associations with CVR, derived from single-delay ASL in patients with MMD.

    METHODS: Fifteen MMD patients were included before or after revascularization surgery. Cerebral blood flow (CBF) maps were acquired using pseudo-continuous ASL before, and 5, 15, and 25 min after an intravenous acetazolamide injection. CVRmax was defined as the highest percentual increase in CBF at any of the three post-injection time points. A vascular territory template was spatially normalized to each patient, including the bilateral anterior, middle, and posterior cerebral arteries. All affected anterior and middle cerebral artery regions and all unaffected posterior cerebral artery regions were included, based on Suzuki grading by digital subtraction angiography.

    RESULTS: Significant differences between affected and unaffected regions were found for CBF, CVRmax, and ATAvol. No association was found between CVRmax and any other parameter. High correlations were found between spatial CoVCBF, skewness and ATAvol.

    CONCLUSION: Spatial CoVCBF derived from single-delay ASL does not correlate with CVR in patients with MMD. Moreover, skewness and kurtosis did not provide additional information of clinical value.

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  • 297.
    Fahlström, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Borota, Ljubisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Variable Temporal Cerebral Blood Flow Response to Acetazolamide in Moyamoya Patients Measured Using Arterial Spin Labeling2021In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 12, article id 615017Article in journal (Refereed)
    Abstract [en]

    Cerebrovascular reserve capacity (CVR), an important predictor of ischaemic events and a prognostic factor for patients with moyamoya disease (MMD), can be assessed by measuring cerebral blood flow (CBF) before and after administration of acetazolamide (ACZ). Often, a single CBF measurement is performed between 5 and 20 min after ACZ injection. Assessment of the temporal response of the vasodilation secondary to ACZ administration using several repeated CBF measurements has not been studied extensively. Furthermore, the high standard deviations of the group-averaged CVRs reported in the current literature indicate a patient-specific dispersion of CVR values over a wide range. This study aimed to assess the temporal response of the CBF and derived CVR during ACZ challenge using arterial spin labeling in patients with MMD. Eleven patients with MMD were included before or after revascularisation surgery. CBF maps were acquired using pseudo-continuous arterial spin labeling before and 5, 15, and 25 min after an intravenous ACZ injection. A vascular territory template was spatially normalized to patient-specific space, including the bilateral anterior, middle, and posterior cerebral arteries. CBF increased significantly post-ACZ injection in all vascular territories and at all time points. Group-averaged CBF and CVR values remained constant throughout the ACZ challenge in most patients. The maximum increase in CBF occurred most frequently at 5 min post-ACZ injection. However, peaks at 15 or 25 min were also present in some patients. In 68% of the affected vascular territories, the maximum increase in CBF did not occur at 15 min. In individual cases, the difference in CVR between different time points was between 1 and 30% points (mean difference 8% points). In conclusion, there is a substantial variation in CVR between different time points after the ACZ challenge in patients with MMD. Thus, there is a risk that the use of a single post-ACZ measurement time point overestimates disease progression, which could have wide implications for decision-making regarding revascularisation surgery and the interpretation of the outcome thereof. Further studies with larger sample sizes using multiple CBF measurements post-ACZ injection in patients with MMD are encouraged.

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  • 298.
    Falk Delgado, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Preoperative MRI and PET in suspected low-grade gliomas: Radiological, neuropathological and clinical intersections2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Gliomas are neuroepithelial tumours classified by cell type and grade. In adults, low-grade gliomas are comprised mainly of astrocytomas and oligodendrogliomas grade II. The aim was to non-invasively characterise suspected low-grade gliomas through use of 11C-methionine-PET and physiological MRI in order to facilitate treatment decisions.

    Materials and methods: Patients with suspected low-grade glioma were prospectively and consecutively included after referral to the Neurosurgical Department, Uppsala University Hospital, between February 2010 and February 2014. All patients underwent morphological MRI, perfusion MRI, diffusion MRI and 11C-methionine PET. The institutional review board approved the study, and written informed consent was obtained prior to participation from each patient.

    Results: 11C-methionine PET hot spot regions corresponded spatially with regions of maximum relative cerebral blood volume in dynamic susceptibility contrast (DSC) perfusion MRI. The skewness of the transfer constantin dynamic contrast-enhanced (DCE) perfusion MRI, and the standard deviation of relative cerebral blood flow in DSC perfusion MRI could most efficiently discriminate between glioma grades II and III. In diffusion MRI, tumour fractional anisotropy differed between suspected low-grade gliomas of different neuropathological types. Quantitative diffusion tensor tractography was applicable for the evaluation of tract segment infiltration.

    Conclusion: PET and physiological MRI are able to characterise low-grade gliomas and are promising tools for guiding therapy and clinical decisions before neuropathological diagnosis has been obtained.

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  • 299.
    Falk Delgado, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Markus, Nilsson
    Bioimaging center, Lunds Universitet.
    Ghaderi Berntsson, Shala
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    van Westen, Danielle
    Clinical Sciences, Lunds Universitet.
    Lätt, Jimmy
    MR Department, Center for medical imaging and physiology, Lund University Hospital.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Preoperative diffusion kurtosis imaging in suspected low-grade gliomas: A prospective study of diffusional properties in tumour and perilesional regions with histopathological correlationsManuscript (preprint) (Other academic)
  • 300.
    Falk Delgado, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nilsson, Markus
    Lund Univ, Bioimaging Ctr, Lund, Sweden..
    Berntsson, Shala G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Libard, Sylwia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    van Westen, Danielle
    Lund Univ, Clin Sci Lund, Diagnost Radiol, Lund, Sweden..
    Lätt, Jimmy
    Skane Univ Healthcare, Dept Imaging & Funct, Lund, Sweden..
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Diffusion kurtosis imaging of gliomas grades II and III: a study of perilesional tumor infiltration, tumor grades and subtypes at clinical presentation2017In: Radiology and Oncology, ISSN 1318-2099, E-ISSN 1581-3207, Vol. 51, no 2, p. 121-129Article in journal (Refereed)
    Abstract [en]

    Background. Diffusion kurtosis imaging (DKI) allows for assessment of diffusion influenced by microcellular structures. We analyzed DKI in suspected low-grade gliomas prior to histopathological diagnosis. The aim was to investigate if diffusion parameters in the perilesional normal-appearing white matter (NAWM) differed from contralesional white matter, and to investigate differences between glioma malignancy grades II and III and glioma subtypes (astrocytomas and oligodendrogliomas).

    Patients and methods. Forty-eight patients with suspected low-grade glioma were prospectively recruited to this institutional review board-approved study and investigated with preoperative DKI at 3T after written informed consent. Patients with histologically proven glioma grades II or III were further analyzed (n=35). Regions of interest (ROIs) were delineated on T2FLAIR images and co-registered to diffusion MRI parameter maps. Mean DKI data were compared between perilesional and contralesional NAWM (student's t-test for dependent samples, Wilcoxon matched pairs test). Histogram DKI data were compared between glioma types and glioma grades (multiple comparisons of mean ranks for all groups). The discriminating potential for DKI in assessing glioma type and grade was assessed with receiver operating characteristics (ROC) curves.

    Results. There were significant differences in all mean DKI variables between perilesional and contralesional NAWM (p=< 0.000), except for axial kurtosis (p=0.099). Forty-four histogram variables differed significantly between glioma grades II (n=23) and III (n=12) (p=0.003-0.048) and 10 variables differed significantly between ACs (n=18) and ODs (n=17) (p=0.011-0.050). ROC curves of the best discriminating variables had an area under the curve (AUC) of 0.657-0.815.

    Conclusions. Mean DKI variables in perilesional NAWM differ significantly from contralesional NAWM, suggesting altered microstructure by tumor infiltration not depicted on morphological MRI. Histogram analysis of DKI data identifies differences between glioma grades and subtypes.

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