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  • 301.
    Falk Delgado, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Falk Delgado, Alberto
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    [In Process Citation].2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112Article in journal (Refereed)
    Abstract [sv]

    Systemic thrombolysis is an established treatment in acute ischemic stroke. Endovascular treatment to reperfuse occluded vessels has been in clinical practice the last decade. The role of neurointervention in acute ischemic stroke has been questioned. Within the last year, several randomized controlled trials have been published, comparing endovascular treatment and systemic thrombolysis with systemic thrombolysis alone. A meta-analysis, using data from six trials treating 1569 patients, was recently published. In this meta-analysis, patients treated with endovascular therapy in addition to IV thrombolysis had a more favourable clinical outcome compared to patients receiving IV thrombolysis alone, after 3 months. Compared to the individ-ual studies, a decreased mortality in the intervention group was shown. Assessing the safety of endovascular treatment, there was no increased risk of intracranial bleed-ing, compared to IV thrombolysis alone. This meta-analysis highlights and summar-izes the scientific evidence for endovascular treatment in acute ischemic stroke.

  • 302.
    Falk Delgado, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Markus, Nilsson
    Bioimaging center, Lunds Universitet.
    Latini, Francesco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Mårtensson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Ghaderi Berntsson, Shala
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Lätt, Jimmy
    MR Department, Center for medical imaging and physiology, Lund University Hospital.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Preoperative quantitative MR tractography analysis compared with visual tract evaluation in patients with suspected low-grade gliomas.Manuscript (preprint) (Other academic)
  • 303.
    Falk Delgado, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nilsson, Markus
    Latini, Francesco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Mårtensson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Berntsson, Shala G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Lätt, Jimmy
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Preoperative Quantitative MR Tractography Compared with Visual Tract Evaluation in Patients with Neuropathologically Confirmed Gliomas Grades II and III: A Prospective Cohort Study2016In: Radiology Research and Practice, ISSN 2090-1941, E-ISSN 2090-195X, article id 7671854Article in journal (Refereed)
    Abstract [en]

    Background and Purpose. Low-grade gliomas show infiltrative growth in white matter tracts. Diffusion tensor tractography can noninvasively assess white matter tracts. The aim was to preoperatively assess tumor growth in white matter tracts using quantitative MR tractography (3T). The hypothesis was that suspected infiltrated tracts would have altered diffusional properties in infiltrated tract segments compared to noninfiltrated tracts. Materials and Methods. Forty-eight patients with suspected low-grade glioma were included after written informed consent and underwent preoperative diffusion tensor imaging in this prospective review-board approved study. Major white matter tracts in both hemispheres were tracked, segmented, and visually assessed for tumor involvement in thirty-four patients with gliomas grade II or III (astrocytomas or oligodendrogliomas) on postoperative neuropathological evaluation. Relative fractional anisotropy (rFA) and mean diffusivity (rMD) in tract segments were calculated and compared with visual evaluation and neuropathological diagnosis. Results. Tract segment infiltration on visual evaluation was associated with a lower rFA and high rMD in a majority of evaluated tract segments (89% and 78%, resp.). Grade II and grade III gliomas had similar infiltrating behavior. Conclusion. Quantitative MR tractography corresponds to visual evaluation of suspected tract infiltration. It may be useful for an objective preoperative evaluation of tract segment involvement.

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  • 304. Falk Delgado, Anna
    et al.
    Van Westen, Danielle
    Nilsson, Markus
    Knutsson, Linda
    Sundgren, Pia C
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Falk Delgado, Alberto
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Diagnostic value of alternative techniques to gadolinium-based contrast agents in MR neuroimaging: a comprehensive overview2019In: Insights into Imaging, E-ISSN 1869-4101, Vol. 10, no 1, article id 84Article, review/survey (Refereed)
    Abstract [en]

    Gadolinium-based contrast agents (GBCAs) increase lesion detection and improve disease characterization for many cerebral pathologies investigated with MRI. These agents, introduced in the late 1980s, are in wide use today. However, some non-ionic linear GBCAs have been associated with the development of nephrogenic systemic fibrosis in patients with kidney failure. Gadolinium deposition has also been found in deep brain structures, although it is of unclear clinical relevance. Hence, new guidelines from the International Society for Magnetic Resonance in Medicine advocate cautious use of GBCA in clinical and research practice. Some linear GBCAs were restricted from use by the European Medicines Agency (EMA) in 2017.

    This review focuses on non-contrast-enhanced MRI techniques that can serve as alternatives for the use of GBCAs. Clinical studies on the diagnostic performance of non-contrast-enhanced as well as contrast-enhanced MRI methods, both well established and newly proposed, were included. Advantages and disadvantages together with the diagnostic performance of each method are detailed. Non-contrast-enhanced MRIs discussed in this review are arterial spin labeling (ASL), time of flight (TOF), phase contrast (PC), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS), susceptibility weighted imaging (SWI), and amide proton transfer (APT) imaging.

    Ten common diseases were identified for which studies reported comparisons of non-contrast-enhanced and contrast-enhanced MRI. These specific diseases include primary brain tumors, metastases, abscess, multiple sclerosis, and vascular conditions such as aneurysm, arteriovenous malformation, arteriovenous fistula, intracranial carotid artery occlusive disease, hemorrhagic, and ischemic stroke.

    In general, non-contrast-enhanced techniques showed comparable diagnostic performance to contrast-enhanced MRI for specific diagnostic questions. However, some diagnoses still require contrast-enhanced imaging for a complete examination.

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  • 305.
    Falk-Delgado, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kuntze Söderqvist, Åsa
    Fransén, Jian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Falk Delgado, Alberto
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Improved clinical outcome 3 months after endovascular treatment, including thrombectomy, in patients with acute ischemic stroke: a meta-analysis2016In: Journal of neurointerventional surgery, ISSN 1759-8486, Vol. 8, no 7Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Intravenous thrombolysis with tissue plasminogen activator is standard treatment in acute stroke today. The benefit of endovascular treatment has been questioned. Recently, studies evaluating endovascular treatment and intravenous thrombolysis compared with intravenous thrombolysis alone, have reported improved outcome for the intervention group. The aim of this study was to perform a meta-analysis of randomized controlled trials comparing endovascular treatment in addition to intravenous thrombolysis with intravenous thrombolysis alone.

    METHODS: Databases were searched for eligible randomized controlled trials. The primary outcome was a functional neurological outcome after 90 days. A secondary outcome was severe disability and death. Data were pooled in the control and intervention groups, and OR was calculated on an intention to treat basis with 95% CIs. Outcome heterogeneity was evaluated with Cochrane's Q test (significance level cut-off value at <0.10) and I(2) (significance cut-off value >50%) with the Mantel-Haenszel method for dichotomous outcomes. A p value <0.05 was regarded as statistically significant.

    RESULTS: Six studies met the eligibility criteria, and data from 1569 patients were analyzed. A higher probability of a functional neurological outcome after 90 days was found for the intervention group (OR 2, 95% CI 2 to 3). There was a significantly higher probability of death and severe disability in the control group compared with the intervention group.

    CONCLUSIONS: Endovascular treatment in addition to intravenous thrombolysis for acute ischemic stroke leads to an improved clinical outcome after 3 months, compared with patients receiving intravenous thrombolysis alone.

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  • 306.
    Fani, Melpomeni
    et al.
    Division of Radiopharmaceutical Chemistry, University Hospital of Basel, 4031 Basel, Switzerland.
    Peitl, Petra Kolenc
    Department of Nuclear Medicine, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.
    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.
    Current Status of Radiopharmaceuticals for the Theranostics of Neuroendocrine Neoplasms2017In: Pharmaceuticals, E-ISSN 1424-8247, Vol. 10, no 1, article id E30Article, review/survey (Refereed)
    Abstract [en]

    Nuclear medicine plays a pivotal role in the management of patients affected by neuroendocrine neoplasms (NENs). Radiolabeled somatostatin receptor analogs are by far the most advanced radiopharmaceuticals for diagnosis and therapy (radiotheranostics) of NENs. Their clinical success emerged receptor-targeted radiolabeled peptides as an important class of radiopharmaceuticals and it paved the way for the investigation of other radioligand-receptor systems. Besides the somatostatin receptors (sstr), other receptors have also been linked to NENs and quite a number of potential radiolabeled peptides have been derived from them. The Glucagon-Like Peptide-1 Receptor (GLP-1R) is highly expressed in benign insulinomas, the Cholecystokinin 2 (CCK2)/Gastrin receptor is expressed in different NENs, in particular medullary thyroid cancer, and the Glucose-dependent Insulinotropic Polypeptide (GIP) receptor was found to be expressed in gastrointestinal and bronchial NENs, where interestingly, it is present in most of the sstr-negative and GLP-1R-negative NENs. Also in the field of sstr targeting new discoveries brought into light an alternative approach with the use of radiolabeled somatostatin receptor antagonists, instead of the clinically used agonists. The purpose of this review is to present the current status and the most innovative strategies for the diagnosis and treatment (theranostics) of neuroendocrine neoplasms using a cadre of radiolabeled regulatory peptides targeting their receptors.

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  • 307.
    Fanni, Giovanni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kagios, Christakis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Roman, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. CIMC—Centre d’Imagerie Médicale de Cornavin, Geneva, Switzerland.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Effects of gastric bypass surgery on brain connectivity responses to hypoglycemia2023In: Endocrine, ISSN 1355-008X, E-ISSN 1559-0100, Vol. 79, no 2, p. 304-312Article in journal (Refereed)
    Abstract [en]

    Introduction

    Roux-en-Y gastric bypass (RYGB) leads to beneficial effects on glucose homeostasis, and attenuated hormonal counterregulatory responses to hypoglycemia are likely to contribute. RYGB also induces alterations in neural activity of cortical and subcortical brain regions. We aimed to characterize RYGB-induced changes in resting-state connectivity of specific brain regions of interest for energy homeostasis and behavioral control during hypoglycemia.

    Method

    Ten patients with BMI > 35 kg/m2 were investigated with brain PET/MR imaging during a hyperinsulinemic normo- and hypoglycemic clamp, before and 4 months after RYGB. Hormonal levels were assessed throughout the clamp. Resting-state (RS) fMRI scans were acquired in the glucose-lowering phase of the clamp, and they were analyzed with a seed-to-voxel approach.

    Results

    RS connectivity during initiation of hypoglycemia was significantly altered after RYGB between nucleus accumbens, thalamus, caudate, hypothalamus and their crosstalk with cortical and subcortical regions. Connectivity between the nucleus accumbens and the frontal pole was increased after RYGB, and this was associated with a reduction of ACTH (r = −0.639, p = 0.047) and cortisol (r = −0.635, p = 0.048) responses. Instead, connectivity between the caudate and the frontal pole after RYGB was reduced and this was associated with less attenuation of glucagon response during the hypoglycemic clamp (r = −0.728, p = 0.017), smaller reduction in fasting glucose (r = −0.798, p = 0.007) and less excess weight loss (r = 0.753, p = 0.012). No other significant associations were found between post-RYGB changes in ROI-to-voxel regional connectivity hormonal responses and metabolic or anthropometric outcomes.

    Conclusion

    RYGB alters brain connectivity during hypoglycemia of several neural pathways involved in reward, inhibitory control, and energy homeostasis. These changes are associated with altered hormonal responses to hypoglycemia and may be involved in the glucometabolic outcome of RYGB.

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  • 308.
    Faria, Vanda
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    M. Hoppe, Johanna
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Hjorth, Olof
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Alaie, Iman
    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 Neuroscience, Child and Adolescent Psychiatry.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hultberg, Sara
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Wahlstedt, Kurt
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Månsson, Kristoffer N.T.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.; Department of Psychology, Stockholm University, Stockholm, Sweden.
    Carlbring, Per
    Department of Psychology, Stockholm University, Stockholm, Sweden.
    Andersson, Gerhard
    Department of Behavioural Sciences and Learning, Linköping University, Linköping, Sweden.
    Reis, Margareta
    Department of Medical and Health Sciences, Division of Drug Research, Linköping University, Linköping, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder: A Randomized Trial2017In: EBioMedicine, E-ISSN 2352-3964, no 24, p. 179-188, article id S2352-3964(17)30385-7Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety, but their efficacy relative to placebo has been questioned. We aimed to test how manipulation of verbally induced expectancies, central for placebo, influences SSRI treatment outcome and brain activity in patients with social anxiety disorder (SAD).

    METHODS: We did a randomized clinical trial, within an academic medical center (Uppsala, Sweden), of individuals fulfilling the DSM-IV criteria for SAD, recruited through media advertising. Participants were 18years or older and randomized in blocks, through a computer-generated sequence by an independent party, to nine weeks of overt or covert treatment with escitalopram (20mg daily). The overt group received correct treatment information whereas the covert group was treated deceptively with the SSRI described, by the psychiatrist, as active placebo. The treating psychiatrist was necessarily unmasked while the research staff was masked from intervention assignment. Treatment efficacy was assessed primarily with the self-rated Liebowitz Social Anxiety Scale (LSAS-SR), administered at week 0, 1, 3, 6 and 9, also yielding a dichotomous estimate of responder status (clinically significant improvement). Before and at the last week of treatment, brain activity during an emotional face-matching task was assessed with functional magnetic resonance imaging (fMRI) and during fMRI sessions, anticipatory speech anxiety was also assessed with the Spielberger State-Trait Anxiety Inventory - State version (STAI-S). Analyses included all randomized patients with outcome data at posttreatment. This study is registered at ISRCTN, number 98890605.

    FINDINGS: Between March 17th 2014 and May 22nd 2015, 47 patients were recruited. One patient in the covert group dropped out after a few days of treatment and did not provide fMRI data, leaving 46 patients with complete outcome data. After nine weeks of treatment, overt (n=24) as compared to covert (n=22) SSRI administration yielded significantly better outcome on the LSAS-SR (adjusted difference 21.17, 95% CI 10.69-31.65, p<0.0001) with more than three times higher response rate (50% vs. 14%; χ(2)(1)=6.91, p=0.009) and twice the effect size (d=2.24 vs. d=1.13) from pre-to posttreatment. There was no significant between-group difference on anticipatory speech anxiety (STAI-S), both groups improving with treatment. No serious adverse reactions were recorded. On fMRI outcomes, there was suggestive evidence for a differential neural response to treatment between groups in the posterior cingulate, superior temporal and inferior frontal gyri (all z thresholds exceeding 3.68, p≤0.001). Reduced social anxiety with treatment correlated significantly with enhanced posterior cingulate (z threshold 3.24, p=0.0006) and attenuated amygdala (z threshold 2.70, p=0.003) activity.

    INTERPRETATION: The clinical and neural effects of escitalopram were markedly influenced by verbal suggestions. This points to a pronounced placebo component in SSRI-treatment of SAD and favors a biopsychosocial over a biomedical explanatory model for SSRI efficacy.

    FUNDING RESOURCES: The Swedish Research Council for Working Life and Social Research (grant 2011-1368), the Swedish Research Council (grant 421-2013-1366), Riksbankens Jubileumsfond - the Swedish Foundation for Humanities and Social Sciences (grant P13-1270:1).

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  • 309. Farid, Karim
    et al.
    Carter, Stephen F
    Rodriguez-Vieitez, Elena
    Almkvist, Ove
    Andersen, Pia
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Blennow, Kaj
    Portelius, Erik
    Zetterberg, Henrik
    Nordberg, Agneta
    Case Report of Complex Amyotrophic Lateral Sclerosis with Cognitive Impairment and Cortical Amyloid Deposition2015In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 47, no 3, p. 661-667Article in journal (Refereed)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS), a fatal disease of unknown origin, affects motor neurons in the primary motor cortex, brainstem, and spinal cord. Cognitive impairment may occur before the motor symptoms. We present a patient who was initially diagnosed with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) but who developed ALS-like symptoms during follow-up and died shortly thereafter. A 60-year-old subject with cognitive impairment underwent neuropsychological testing, cerebrospinal fluid (CSF) analysis, structural imaging (computed tomography and magnetic resonance imaging) and functional imaging [11C]-Pittsburgh compound B (PIB) positron emission tomography (PET), [18F]-fluorodeoxyglucose (FDG) PET, and [11C]-deuterium-L-deprenyl (DED) PET. Neuropsychological testing showed episodic memory impairment. CSF P-tau and T-tau levels were elevated. CSF amyloid-β (Aβ)42 levels were initially normal but became pathological during follow-up. MCI was diagnosed. [18F]-FDG PET showed hypometabolism in the left temporal and prefrontal cortices and [11C]-PIB PET demonstrated amyloid plaque deposition in the prefrontal, posterior cingulate, and parietal cortices. [11C]-DED PET showed high brain accumulation consistent with astrocytosis. The memory impairment progressed and AD was diagnosed. Motor impairments developed subsequently and, following additional neurological evaluation, ALS was diagnosed. The disease progressed rapidly and the patient died with pronounced motor symptoms three years after the initial cognitive assessment. Since relatives refused autopsy, postmortem analysis was not possible.

  • 310. Ferreira, Daniel
    et al.
    Hansson, Oskar
    Barroso, José
    Molina, Yaiza
    Machado, Alejandra
    Hernández-Cabrera, Juan Andrés
    Muehlboeck, J-Sebastian
    Stomrud, Erik
    Nägga, Katarina
    Lindberg, Olof
    Ames, David
    Kalpouzos, Grégoria
    Fratiglioni, Laura
    Bäckman, Lars
    Graff, Caroline
    Mecocci, Patrizia
    Vellas, Bruno
    Tsolaki, Magda
    Kłoszewska, Iwona
    Soininen, Hilkka
    Lovestone, Simon
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wahlund, Lars-Olof
    Simmons, Andrew
    Westman, Eric
    The interactive effect of demographic and clinical factors on hippocampal volume: A multicohort study on 1958 cognitively normal individuals2017In: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 27, no 6, p. 653-667Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.

  • 311. Ferreira, Mjv
    et al.
    Robalo, M M
    Saraiva, T
    Cunha, M J
    Goncalves, L
    Albuquerque, A
    Ramos, D
    Costa, G
    Lima, J
    Pego, M
    Peovska, I
    Davceva Pavlovska, J
    Pop Gorceva, D
    Zdravkovska, M
    Vavlukis, M
    Kostova, N
    Bulugahapitiya, D S
    Feben, A
    Avison, M
    Foley, J
    Martin, J
    De Graaf, M A
    Van Den Hoogen, I J
    Leen, A C
    Kharagjitsingh, A V
    Kroft, L J
    Jukema, J W
    Bax, J J
    Scholte, A J
    Patel, K
    Mahan, M
    Ananthasubramaniam, K
    Durmus Altun, G
    Alpay, M
    Altun, A
    Andreini, D
    Pontone, G
    Mushtaq, S
    Bertella, E
    Conte, E
    Segurini, C
    Volpato, V
    Petulla, M
    Baggiano, A
    Pepi, M
    Van Dijk, J D
    Huizing, E D
    Jager, P L
    Slump, C H
    Ottervanger, J P
    Van Dalen, J A
    Yambao, E
    Calleja, H B
    Sibulo, A S
    Ramirez Moreno, A
    Siles Rubio, J R
    Noureddine, M
    Munoz-Bellido, J
    Bravo, R
    Martinez, F
    Valle, A
    Milan, A
    Inigo-Garcia, L
    Velasco, T
    Ramaiah, V L
    Devanbu, J S
    Taywade, S K
    Hejjaji, V S
    Zafrir, N
    Bental, T
    Gutstein, A
    Solodky, A
    Mats, I
    Kornowski, R
    Lagan, J
    Hasleton, J
    Meah, M
    Mcshane, J
    Trent, R
    Massalha, S
    Israel, O
    Koskosi, A
    Kopelovich, M
    Marai, I
    Venuraju, S
    Jeevarethinam, A
    Dumo, A
    Ruano, S
    Darko, D
    Cohen, M
    Nair, D
    Rosenthal, M
    Rakhit, R
    Lahiri, A
    Pizzi, M N
    Roque, A
    Fernandez-Hidalgo, N
    Cuellar-Calabria, H
    Gonzalez-Alujas, M T
    Oristrell, G
    Rodriguez-Palomares, J
    Tornos, P
    Aguade-Bruix, S
    Smettei, O
    Abazid, R
    Ahmed, W M K
    Samy, W
    Behairy, N
    Tayeh, O
    Hassan, A
    Berezin, A
    Kremzer, A
    Samura, T
    Berezina, T
    Scrima, G
    Bertuccio, G
    Canseco Nadia, Ncl
    Cruz Raul, C R
    Gonzalez Cristian, G C
    Hernandez Salvador, S H
    Alexanderson Erick, Ear
    Zerahn, B
    Shugushev, Z
    Maximkin, D
    Chepurnoy, A
    Volkova, O
    Tsedenova, A
    Faibushevich, A
    Baranovich, V
    Yoshida, H
    Mizukami, A
    Matsumura, A
    Keller, M
    Silber, S
    Falcao, A
    Imada, R
    Azouri, L O
    Giorgi, McP
    Santos, R D
    Mello, S L
    Kalil Filho, R
    Meneghetti, J C
    Chalela, W A
    Kanni, L
    Ohrman, T
    Nygren, A T
    Irabi, R D
    Falcao, A
    Imada, R
    Azouri, L O
    Parisotto, T
    Soares, J
    Kalil Filho, R
    Meneghetti, J C
    Chalela, W A
    Burrell, S
    Burrell, S
    Lo, C
    Zavadovskyi, K
    Gulya, M
    Lishmanov, Y U
    Amin, A
    Kandeel, Ahmed
    Shaban, Mahmud
    Nawito, Zeinab
    Caobelli, F
    Soffientini, A
    Thackeray, J T
    Bengel, F M
    Pizzocaro, C
    Guerra, U P
    Hellberg, S E
    Silvola, Jmu
    Kiugel, M
    Liljenback, H
    Savisto, N
    Thiele, A
    Laine, Vjo
    Knuuti, J
    Roivainen, A
    Saraste, A
    Ismail, B
    Hadizad, T
    Dekemp, Rob
    Beanlands, Rob
    Dasilva, J N
    Hyafil, F
    Sorbets, E
    Duchatelle, V
    Rouzet, F
    Le Guludec, D
    Feldman, L
    Martire, V D
    De Pierris, C
    Martire, M V
    Pis Diez, E R
    Ramaiah, V
    Devanbu, J S
    Hejjaji, V S
    Lebasnier, A
    Legallois, D
    Peyronnet, D
    Desmonts, C
    Zalcman, G
    Bienvenu, B
    Agostini, D
    Manrique, A
    Solomyanyy, V
    Mintale, I
    Zabunova, M
    Narbute, I
    Ratniece, M
    Jakobsons, E
    Kaire, K
    Kamzola, G
    Briede, I
    Jegere, S
    Erglis, A
    Mostafa, S
    Abdelkader, M
    Abdelkader, H
    Abdelkhlek, S
    Khairy, E
    Huidu, S
    Popescu, A
    Lacau, S
    Huidu, A
    Dimulescu, D
    Abazid, R
    Smettei, O
    Sayed, S
    Al Harby, F
    Habeeb, A
    Saqqah, H
    Merganiab, S
    Selvanayagam, J
    Harms, H J
    Tolbod, L P
    Hansson, N H
    Kero, T
    Orndahl, L H
    Kim, W Y
    Bouchelouche, K
    Wiggers, H
    Frokiaer, J
    Sorensen, J
    Hansson, N H
    Tolbod, L
    Harms, H J
    Wiggers, H
    Kim, W Y
    Hansen, E
    Zaremba, T
    Frokiaer, J
    Sorensen, J
    Harms, H J
    Tolbod, L P
    Hansson, N H
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Orndahl, L H
    Kim, W Y
    Bouchelouche, K
    Wiggers, H
    Frokiaer, J
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Poster Session 3: Tuesday 5 May 2015, 082015In: European Heart Journal Cardiovascular Imaging, ISSN 2047-2404, E-ISSN 2047-2412, Vol. 16 Suppl 1Article in journal (Refereed)
  • 312.
    Finnsson, Johannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Radiological studies of LMNB1-related autosomal dominant leukodystrophy and Marinesco-Sjögren syndrome2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    There are approximately 6000 to 8000 rare diseases, each with a prevalence of less than 1 / 10 000, but in aggregate affecting 6 to 8% of the population. It is important to evaluate disease development and progression to know the natural course of any disease. This information can be utilized in diagnostics and in assessing effects of therapeutic interventions as they become available. This thesis describes the natural clinical history and evolution of imaging findings of two rare diseases over approximately two decades.

    Papers I, II and III present clinical, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) findings in LMNB1-related autosomal dominant leukodystrophy (ADLD). MRI was found to be very sensitive in finding pathology in patients with LMNB1-related ADLD, even before the onset of clinical symptoms. However, even patients with widespread MRI changes can have a relatively mild symptomatology and present only slight disturbances in metabolic examinations such as MRS and FDG-PET. This is compatible with relatively intact axons, even as myelin impairment is widespread.

    Paper IV presents clinical and MRI findings in the brain and musculature in SIL1-positive Marinesco-Sjögren syndrome (MSS), and describes a new, mild phenotype of the disease with no intellectual disabilities and only slight motor disabilities. With a 19-year-long radiological follow-up, a slow progressive atrophic process in the cerebellum and brainstem could be demonstrated. MRI of the musculature shows early involvement of the quadriceps and gastrocnemii but not the tibialis anterior, progressing to widespread atrophy in the back and upper and lower limbs at the age of 20 years. In the mildest phenotype, the most severely affected muscles were the m gluteus maximus, m sartorius, m peroneus longus, and the lateral head of the m gastrocnemius.

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  • 313.
    Finnsson, Johannes
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kimber, Eva
    Institute of Clinical Sciences at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Melberg, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Clinical and MRI evaluation of Marinesco-Sjögren syndrome with a 21-year-follow-up and a description of a mild form of the diseaseManuscript (preprint) (Other academic)
  • 314.
    Finnsson, Johannes
    et al.
    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.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Savitcheva, Irina
    Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
    Melberg, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Glucose metabolism in the brain in LMNB1-related autosomal dominant leukodystrophy; a PET studyManuscript (preprint) (Other academic)
  • 315.
    Finnsson, Johannes
    et al.
    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.
    Savitcheva, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Melberg, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Glucose metabolism in the brain in LMNB1-related autosomal dominant leukodystrophy.2019In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 139, no 2, p. 135-142Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: LMNB1-related autosomal dominant leukodystrophy is caused by an overexpression of the protein lamin B1, usually due to a duplication of the LMNB1 gene. Symptoms start in 5th to 6th decade. This slowly progressive disease terminates with death. We studied brain glucose metabolism in this disease using 18 F-fluorodeoxyglucose positron emission tomography (PET).

    METHODS: We examined 8 patients, aged 48-64 years, in varying stages of clinical symptomatology. Two patients were investigated with quantitative PET on clinical indications after which six more patients were recruited. Absolute glucose metabolism was analyzed with the PVElab software in 6 patients and 18 healthy controls. A semiquantitative analysis using the CortexID software was performed in seven investigations, relating local metabolism levels to global glucose metabolism.

    RESULTS: The clinical quantitative PET revealed low global glucose metabolism, with the most marked reduction in the cerebellum. In the PVElab analysis, patients presented low mean glucose metabolism in the cerebellum, brainstem and global grey matter. In the semiquantitative analysis, 2 patients showed a decreased metabolism in the cerebellum and 4 patients a relatively higher metabolism in parts of the temporal lobes. Since none of the patients showed an increased metabolism in the quantitative analysis, we interpret these increases as "pseudo-increases" related to a globally reduced metabolism.

    CONCLUSIONS: Global reduction of grey matter glucose metabolism in this white matter disease most likely depends on a combination of cortical afferent dysfunction and, in later stages, neuronal loss. The lowest metabolism in the cerebellum is consistent with histopathological findings and prominent cerebellar symptoms.

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  • 316.
    Finnsson, Johannes
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sundblom, Jimmy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Dahl, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Melberg, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    LMNB1-related autosomal-dominant leukodystrophy: Clinical and radiological course2015In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 78, no 3, p. 412-25Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Duplication of the LMNB1 gene encoding lamin B1 causes adult-onset autosomal-dominant leukodystrophy (ADLD) starting with autonomic symptoms, which are followed by pyramidal signs and ataxia. Magnetic resonance imaging (MRI) of the brain reveals characteristic findings. This is the first longitudinal study on this disease. Our objective is to describe the natural clinical and radiological course of LMNB1-related ADLD.

    METHODS: Twenty-three subjects in two families with LMNB1 duplications were studied over two decades with clinical assessment and MRI of the brain and spinal cord. They were 29 to 70 years old at their first MRI. Repeated MRIs were performed in 14 subjects over a time period of up to 17 years.

    RESULTS: Pathological MRI findings were found in the brain and spinal cord in all examinations (i.e., even preceding clinical symptoms). MRI changes and clinical symptoms progressed in a definite order. Autonomic dysfunction appeared in the fifth to sixth decade, preceding or together with gait and coordination difficulties. Motor signs developed ascending from spastic paraplegia to tetraplegia and pseudobulbar palsy in the seventh decade. There were clinical, radiological, and neurophysiological signs of myelopathy. Survival lasted more than two decades after clinical onset.

    INTERPRETATION: LMNB1-related ADLD is a slowly progressive neurological disease. MRI abnormalities of the brain and spinal cord can precede clinical symptoms by more than a decade and are extensive in all symptomatic patients. Spinal cord involvement is a likely contributing factor to early autonomic symptoms and spastic paraplegia. Ann Neurol 2015;78:412-425.

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  • 317.
    Flachskampf, Frank A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Biering-Sorensen, Tor
    Solomon, Scott D.
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Smiseth, Otto A.
    Heart Rate Is an Important Consideration for Cardiac Imaging of Diastolic Function Reply2016In: JACC Cardiovascular Imaging, ISSN 1936-878X, E-ISSN 1876-7591, Vol. 9, no 6, p. 758-759Article in journal (Refereed)
  • 318.
    Flachskampf, Frank A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Biering-Sörensen, Tor
    Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div, Boston, MA 02115 USA.
    Solomon, Scott D.
    Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div, Boston, MA 02115 USA.
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Smiseth, Otto A,
    Univ Oslo, Rikshosp, Oslo Univ Hosp,Dept Cardiol, Ctr Cardiol Innovat,KG Jebsen Cardiac Res Ctr,Ctr, N-0027 Oslo, Norway; Univ Oslo, Rikshosp, Oslo Univ Hosp,Inst Surg Res, Ctr Cardiol Innovat,KG Jebsen Cardiac Res Ctr,Ctr, N-0027 Oslo, Norway.
    Cardiac Imaging to Evaluate Left Ventricular Diastolic Function2015In: JACC Cardiovascular Imaging, ISSN 1936-878X, E-ISSN 1876-7591, Vol. 8, no 9, p. 1071-1093Article in journal (Refereed)
    Abstract [en]

    Left ventricular diastolic dysfunction in clinical practice is generally diagnosed by imaging. Recognition of heart failure with preserved ejection fraction has increased interest in the detection and evaluation of this condition and prompted an improved understanding of the strengths and weaknesses of different imaging modalities for evaluating diastolic dysfunction. This review briefly provides the pathophysiological background for current clinical and experimental imaging parameters of diastolic dysfunction, discusses the merits of echocardiography relative to other imaging modalities in diagnosing and grading diastolic dysfunction, summarizes Lessons from clinical trials that used parameters of diastolic function as an inclusion criterion or endpoint, and indicates current areas of research.

  • 319.
    Fojecki, Grzegorz
    et al.
    Hosp Southern Jutland, Dept Urol, Sonderborg, Denmark.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Traxer, Olivier
    Sorbonne Univ, Hop Tenon, Paris, France.
    Baard, Joyce
    Univ Amsterdam, Dept Urol, Amsterdam UMC, Amsterdam, Holland, Netherlands.
    Osther, Palle Jörn Sloth
    Univ Southern Denmark, Lillebaelt Hosp, Urol Res Ctr, Vejle, Denmark.
    Jaremko, Georg
    Karolinska Univ Hosp Solna, Dept Clin Pathol & Cytol, Stockholm, Sweden.
    Seitz, Christian
    Med Univ Vienna, Dept Urol, Vienna, Austria.
    Knoll, Thomas
    Teaching Hosp Univ Tuebingen, Dept Urol, Sindelfingen, Germany.
    Giusti, Guido
    IRCCS San Raffaele Hosp, Dept Urol, Ville Turro Div, Milan, Italy.
    Brehmer, Marianne
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Div Urol, Stockholm, Sweden.
    Consultation on UTUC, Stockholm 2018 aspects of diagnosis of upper tract urothelial carcinoma2019In: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 37, no 11, p. 2271-2278Article in journal (Refereed)
    Abstract [en]

    Purpose: To summarize knowledge on upper urinary tract carcinoma (UTUC) regarding diagnostic procedures, risk factors and prognostic markers.

    Methods: A scoping review approach was applied to search literature in Pubmed, Web of Science, and Embase. Consensus was reached through discussions at Consultation on UTUC in Stockholm, September 2018.

    Results: Tumor stage and grade are the most important prognostic factors. CT urography (CTU) including corticomedullary phase is the preferred imaging modality. A clear tumor on CTU in combination with high-grade UTUC in urine cytology identifies high-risk UTUC, and in some cases indirect staging can be obtained. Bladder urine cytology has limited sensitivity, and in most cases ureterorenoscopy (URS) with in situ samples for cytology and histopathology are mandatory for exact diagnosis. Image-enhancing techniques, Image S1 and narrow-band imaging, may improve tumor detection at URS. Direct confocal laser endomicroscopy may help to define grade during URS. There is strong correlation between stage and grade, accordingly correct grading is crucial. The correlation is more pronounced using the 1999 WHO than the 2004 classification: however, the 1999 system risks greater interobserver variability. Using both systems is advisable. A number of tissue-based molecular markers have been studied. None has proven ready for use in clinical practice.

    Conclusions: Correct grading and staging of UTUC are mandatory for adequate treatment decisions. Optimal diagnostic workup should include CTU with corticomedullary phase, URS with in situ cytology and biopsies. Both WHO classification systems (1999 and 2004) should be used to decrease risk of undergrading or overtreatment.

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  • 320.
    Fors, Felicia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Vanhanen, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Röntgensjuksköterskans roll och ansvar vid trauma CT nivå 1: En intervjustudie2023Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Trauma är den sjätte vanligaste dödsorsaken i världen. Röntgen är en viktig del av traumavården för att snabbt och effektivt kunna diagnostisera skador. Speciell CT-undersökning, kallat whole-body computed tomography (WBCT) har utifrån detta designats och benämns i Sverige som trauma CT, och specificeras utifrån traumanivåerna 1 och 2. Röntgensjuksköterskan blir en del av traumateamet vid ett trauma nivå 1 och är delaktig i att utföra CT-undersökningen. 

    Syfte: Syftet med studien är att studera hur röntgensjuksköterskan upplever sin roll vid en nivå 1 trauma CT-undersökning och vilka utmaningar som finns vid denna typ av undersökning.

    Metod: Studien genomfördes som en kvalitativ intervjustudie med semi-strukturerade intervjufrågor. Nio röntgensjuksköterskor intervjuades på plats i ett avskilt rum. Intervjuerna spelades in, materialet transkriberades och analyserades med en kvalitativ manifest innehållsanalys. 

    Resultat: Röntgensjuksköterskans roll upplevs tydlig och röntgensjuksköterskan har ett ansvar innan, efter och under pågående undersökning att samarbeta med övrig traumapersonal för att kunna utföra CT-undersökningen effektivt. Det finns stressfaktorer och hinder i arbetsflödet som påverkar röntgensjuksköterskans arbete.

    Slutsats: Röntgensjuksköterskans roll följer kompetensbeskrivningen även vid trauma CT nivå 1. Ett samarbete med andra professioner och egna kollegor är avgörande för att utföra trauma CT-undersökningen optimalt. Förbättrade rutiner i förberedelser på traumarummet, inkluderande av röntgen i traumaövningar och placering av CT-kamera på traumarummet kan vara lösningar på de utmaningar röntgensjuksköterskan möter. 

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  • 321.
    Forslund, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Weghuber, D.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Paulmichl, K.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Zsoldos, F.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Widhalm, K.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Vheu, M. D.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Lagler, F.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Cadamuro, J.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Brunner, S.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Hofmann, J.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Dahlbom, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Lidström, M.
    Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Vilen, H.
    Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Ciba, Iris
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    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.
    Kristinsson, Hjalti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Alderborn, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Bergsten, Peter
    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 Women's and Children's Health.
    Exenatide Once Weekly Reduces Weight, Liver Fat And 2-Hour Postprandial Glucose In Obese Adolescents2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 470, p. 14-15Article in journal (Other academic)
  • 322.
    Fragata, Isabel
    et al.
    Ctr Hosp Lisboa Cent, Dept Neuroradiol, Rua Jose Antonio Serrano, P-1150099 Lisbon, Portugal..
    Alves, Marta
    Ctr Hosp Lisboa Cent, Ctr Invest, Lisbon, Portugal..
    Papoila, Ana Lusia
    Ctr Hosp Lisboa Cent, Ctr Invest, Lisbon, Portugal.;Ctr Hosp Lisboa Cent, Unidade Cerebrovasc, Lisbon, Portugal.;NOVA Med Sch, Fac Ciencias Med, Lisbon, Portugal..
    Nunes, Ana Paiva
    Ferreira, Patricia
    Ctr Hosp Lisboa Cent, Unidade Cerebrovasc, Lisbon, Portugal..
    Canto-Moreira, Nuno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Canhao, Patricia
    Ctr Hosp Lisboa Norte, Dept Neurol, Lisbon, Portugal.;Univ Lisbon, Fac Med, Inst Med Mol, Lisbon, Portugal..
    Early Prediction of Delayed Ischemia and Functional Outcome in Acute Subarachnoid Hemorrhage: Role of Diffusion Tensor Imaging2017In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 48, no 8, p. 2091-2097Article in journal (Refereed)
    Abstract [en]

    Background and Purpose-Diffusion tensor imaging (DTI) parameters are markers of cerebral lesion in some diseases. In patients with acute subarachnoid hemorrhage (SAH), we investigated whether DTI parameters measured at < 72 hours might be associated with delayed cerebral ischemia (DCI) and with poor functional outcome at 3 months (modified Rankin Scale score =3).

    Methods-DTI was performed in a prospective cohort of 60 patients with nontraumatic SAH at < 72 hours. Association of fractional anisotropy and apparent diffusion coefficient values at < 72 hours with the occurrence of DCI and outcome at 3 months was evaluated with logistic regression models, adjusting for known predictors of prognosis.

    Results-At < 72 hours after SAH, fractional anisotropy values at the cerebellum were associated with DCI occurrence (78% less odds of DCI for each 0.1 increase in fractional anisotropy; P=0.019). Early apparent diffusion coefficient values were not associated with DCI. After adjusting for confounding variables, an increase of 10 U in apparent diffusion coefficient at the frontal centrum semiovale corresponded to 15% increased odds of poor outcome (P=0.061).

    Conclusions-DTI parameters at < 72 hours post-SAH are independently associated with the occurrence of DCI and functional outcome. These preliminary results suggest the role of DTI parameters as surrogate markers of prognosis in nontraumatic SAH.

  • 323. Fragata, Isabel
    et al.
    Canhão, Patrícia
    Alves, Marta
    Papoila, Ana Luísa
    Canto Moreira, Nuno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Evolution of diffusion tensor imaging parameters after acute subarachnoid haemorrhage: a prospective cohort study2017In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 59, no 1, p. 13-21Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Few studies assessed diffusion tensor imaging (DTI) changes in the acute phase of subarachnoid haemorrhage (SAH). We prospectively evaluated DTI parameters in the acute phase of SAH and 8-10 days after and analysed whether changes could be related to SAH severity or to the development of delayed cerebral ischemia (DCI).

    METHODS: Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) changes over time were assessed in a prospective cohort of patients with acute SAH. Two MRI studies were performed at <72 h (MRI-1) and 8-10 days (MRI-2). DTI parameters were recorded in 15 ROIs. Linear mixed regression models were used.

    RESULTS: Forty-two patients were included. Subtle changes in DTI parameters were found between MRI-1 and MRI-2. At the posterior limb of internal capsule (PLIC), a weak evidence of a 0.02 mean increase in FA (p = 0.064) and a 17.55 × 10(-6) mm(2)/s decrease in ADC (p = 0.052) were found in MRI-2. Both FA and ADC changed over time at the cerebellum (increase of 0.03; p = 0.017; decrease of 34.73 × 10(-6) mm(2)/s; p = 0.002, respectively). Patients with DCI had lower FA values on MRI-1 and lower ADC on MRI-2, although not reaching statistical significance, compared to non-DCI patients. DTI parameters on MRI-1 were not correlated to clinical admission scales.

    CONCLUSION: ADC and FA values show subtle changes over time in acute SAH at the PLIC and cerebellum although not statistically associated with the severity of SAH or the occurrence of DCI. However, DTI changes occurred mainly in DCI patients, suggesting a possible role of DTI as a marker of DCI.

  • 324.
    Fransson, Samuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Dept Med Phys, Uppsala, Sweden..
    Comparing multi-image and image augmentation strategies for deep learning-based prostate segmentation2024In: Physics and Imaging in Radiation Oncology, E-ISSN 2405-6316, Vol. 29, article id 100551Article in journal (Refereed)
    Abstract [en]

    During MR-Linac-based adaptive radiotherapy, multiple images are acquired per patient. These can be applied in training deep learning networks to reduce annotation efforts. This study examined the advantage of using multiple versus single images for prostate treatment segmentation. Findings indicate minimal improvement in DICE and Hausdorff 95% metrics with multiple images. Maximum difference was seen for the rectum in the low data regime, training with images from five patients. Utilizing a 2D U -net resulted in DICE values of 0.80/0.83 when including 1/5 images per patient, respectively. Including more patients in training reduced the difference. Standard augmentation methods remained more effective.

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  • 325.
    Fransson, Samuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Machine Learning in Magnetic Resonance-Guided Adaptive Radiotherapy2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In radiotherapy, treatments are frequently distributed over multiple weeks, and the radiation dose delivered across several sessions. A significant hurdle in this approach is the anatomical changes that occur between the planning stage and subsequent treatment sessions, leading to uncertainties in the treatment. The MR-Linac system, which combines a linear accelerator with an MRI scanner, addresses this issue by allowing for daily adjustments to the treatment plan based on the patient's current anatomy. However, the process for making these adjustments, involving image fusion, re-contouring, and plan re-optimization, can be quite elaborate and time-consuming. This project aimed to identify opportunities within the daily treatment routine where machine learning and deep learning could streamline the process, thereby enhancing efficiency, with a focus on prostate cancer treatments due to their frequent occurrence at our facility. We leveraged deep learning to train patient-specific models for segmenting anatomical structures in daily MRI scans, matching the accuracy of existing deformable image registration techniques. Furthermore, we extended this concept to segmenting structures and predicting radiation dose distributions, offering a swift assessment of potential dose distribution before engaging in the more complex manual workflow. This could aid in selecting the most suitable adaptation method more quickly. Additionally, we developed motion models for intrafractional motion and for segmenting images at lower resolutions to facilitate a target tracking process. Throughout this project, we showed how machine learning and deep learning techniques could contribute to optimizing the daily MR-Linac workflow.

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  • 326.
    Fransson, Samuel
    et al.
    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 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 Vi3.
    Tilly, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine.
    Deep learning-based dose prediction for magnetic resonance-guided prostate radiotherapyManuscript (preprint) (Other academic)
  • 327.
    Fransson, Samuel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Department of Medical Physics, Akademiska Hospital, Uppsala, Sweden.
    Tilly, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science. Department of Medical Physics, Akademiska Hospital, Uppsala, Sweden;Elekta Instruments AB, Stockholm, Sweden.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nyholm, Tufve
    Department of Radiation Sciences, Umeå University, Umeå, Sweden.
    Strand, Robin
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Intrafractional motion models based on principal components in Magnetic Resonance guided prostate radiotherapy2021In: Physics and Imaging in Radiation Oncology, E-ISSN 2405-6316, Vol. 20, p. 17-22Article in journal (Refereed)
    Abstract [en]

    Background and purpose:

    Devices that combine an MR-scanner with a Linac for radiotherapy, referred to as MR-Linac systems, introduce the possibility to acquire high resolution images prior and during treatment. Hence, there is a possibility to acquire individualised learning sets for motion models for each fraction and the construction of intrafractional motion models. We investigated the feasibility for a principal component analysis (PCA) based, intrafractional motion model of the male pelvic region.

    Materials and methods:

    4D-scans of nine healthy male volunteers were utilized, FOV covering the entire pelvic region including prostate, bladder and rectum with manual segmentation of each organ at each time frame. Deformable image registration with an optical flow algorithm was performed for each subject with the first time frame as reference. PCA was performed on a subset of the resulting displacement vector fields to construct individualised motion models evaluated on the remaining fields.

    Results:

    The registration algorithm produced accurate registration result, in general DICE overlap >0.95 across all time frames. Cumulative variance of the eigen values from the PCA showed that 50% or more of the motion is explained in the first component for all subjects. However, the size and direction for the components differed between subjects. Adding more than two components did not improve the accuracy significantly and the model was able to explain motion down to about 1 mm.ConclusionsAn individualised intrafractional male pelvic motion model is feasible. Geometric accuracy was about 1 mm based on 1–2 principal components.

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  • 328.
    Fransson, Samuel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Tilly, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine.
    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 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 Vi3.
    Deep learning segmentation of low-resolution images for prostate magnetic resonance-guided radiotherpy2024Manuscript (preprint) (Other academic)
  • 329.
    Freedman, Nanette
    et al.
    Tel Aviv Sourasky Med Ctr, Inst Nucl Med, 6 Weizman St, IL-64239 Tel Aviv, Israel.
    Sandström, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kuten, Jonathan
    Tel Aviv Sourasky Med Ctr, Inst Nucl Med, 6 Weizman St, IL-64239 Tel Aviv, Israel.
    Shtraus, Natan
    Tel Aviv Sourasky Med Ctr, Inst Radiotherapy, Tel Aviv, Israel.
    Ospovat, Inna
    Tel Aviv Sourasky Med Ctr, Inst Radiotherapy, Tel Aviv, Israel.
    Schlocker, Albert
    Tel Aviv Sourasky Med Ctr, Inst Radiotherapy, Tel Aviv, Israel.
    Even-Sapir, Einat
    Tel Aviv Sourasky Med Ctr, Inst Nucl Med, 6 Weizman St, IL-64239 Tel Aviv, Israel; Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel.
    Personalized radiation dosimetry for PRRT: how many scans are really required?2020In: EJNMMI Physics, E-ISSN 2197-7364, Vol. 7, no 1, article id 26Article in journal (Refereed)
    Abstract [en]

    Purpose

    Over recent years, peptide receptor radiotherapy (PRRT) has been recognized as an effective treatment for patients with metastatic neuroendocrine tumors (NETs). Personalized dosimetry can contribute to improve the outcome of peptide receptor radiotherapy (PRRT) in patients with metastatic NETs. Dosimetry can aid treatment planning, ensuring that absorbed dose to vulnerable normal organs (kidneys and bone marrow) does not exceed safe limits over serial treatments, and that absorbed dose to tumor is sufficient. Absorbed dose is estimated from a series of post-treatment SPECT/CT images. Total self-dose is proportional to the integral under the time activity concentration curve (TACC). Method dependence of image-based absorbed dose calculations has been previously investigated, and we set out here to extend previous work by examining implications of number of data points in the TACC and the numerical integration methods used in estimating absorbed dose.

    Methods

    In this retrospective study, absorbed dose estimates and effective half-lives were calculated by fitting curves to TACCs for normal organs and tumors in 30 consecutive patients who underwent a series of 4 post-treatment SPECT/CT scans at 4 h, 24 h, 4–5 days, and 1 week following 177Lu-DOTATATE PRRT. We examined the effects of including only 2 or 3 rather than all 4 data points in the TACC, and the effect of numerical integration method (mono-exponential alone or in combination with trapezoidal rule) on the absorbed dose and half-life estimates. Our current method is the combination of trapezoidal rule over the first 24 h, with mono-exponential fit thereafter extrapolated to infinity. The other methods were compared to this current method.

    Results

    Differences in absorbed dose and effective half-life between the current method and estimates based only on the second, third, and fourth scans were very small (mean differences < 2.5%), whereas differences between the current method and 4-point mono-exponential fit were higher (mean differences < 5%) with a larger range. It appears that in a 4-point mono-exponential fit the early (4 h) time point may skew results, causing some large errors. Differences between the current method and values based on only 2 time points were relatively small (mean differences < 3.5%) when the 24 h and 1 week scans were used, but when the 24 h and 4–5 days scans, or the 4–5 days and 1 week scans were used, differences were greater.

    Conclusion

    This study indicates that for 177Lu-DOTATATE PRRT, accurate estimates of absorbed dose for organs and tumors may be estimated from scans at 24 h, 72 h, and 1 week post-treatment without an earlier scan. It may even be possible to cut out the 72 h scan, though the uncertainty increases. However, further work on more patients is required to validate this.

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  • 330.
    Frick, Anderas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Palmquist, Åsa M.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Pissiota, A.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Wallenquist, Ulrika
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fernandez, Manuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Jonasson, My
    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.
    Frans, Örjan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    von Knorring, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Alterations in the serotonergic and substance P systems in posttraumatic stress disorder2016In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 21, no 10, p. 1323-1323Article in journal (Other academic)
  • 331.
    Frick, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry.
    Björkstrand, Johannes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Lund Univ, Dept Psychol, Lund, Sweden..
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Allison
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Reproductive Health Research.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Åhs, Fredrik
    Mid Sweden Univ, Dept Psychol & Social Work, Östersund, Sweden..
    Dopamine and fear memory formation in the human amygdala2022In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 27, no 3, p. 1704-1711Article in journal (Refereed)
    Abstract [en]

    Learning which environmental cues that predict danger is crucial for survival and accomplished through Pavlovian fear conditioning. In humans and rodents alike, fear conditioning is amygdala-dependent and rests on similar neurocircuitry. Rodent studies have implicated a causative role for dopamine in the amygdala during fear memory formation, but the role of dopamine in aversive learning in humans is unclear. Here, we show dopamine release in the amygdala and striatum during fear learning in humans. Using simultaneous positron emission tomography and functional magnetic resonance imaging, we demonstrate that the amount of dopamine release is linked to strength of conditioned fear responses and linearly coupled to learning-induced activity in the amygdala. Thus, like in rodents, formation of amygdala-dependent fear memories in humans seems to be facilitated by endogenous dopamine release, supporting an evolutionary conserved neurochemical mechanism for aversive memory formation.

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  • 332.
    Frick, Andreas
    et al.
    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 Neuroscience, Ekselius: Psychiatry.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Alaie, Iman
    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 Neuroscience, Child and Adolescent Psychiatry.
    Björkstrand, Johannes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Univ Southern Denmark, Dept Psychol, Odense, Denmark;Lund Univ, Dept Psychol, Lund, 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 Neuroscience, Ekselius: Psychiatry.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Elias
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Pharmacol, Gothenburg, Sweden.
    Wahlstedt, Kurt
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Neuroimaging, genetic, clinical, and demographic predictors of treatment response in patients with social anxiety disorder2020In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 261, p. 230-237Article in journal (Refereed)
    Abstract [en]

    Background: Correct prediction of treatment response is a central goal of precision psychiatry. Here, we tested the predictive accuracy of a variety of pre-treatment patient characteristics, including clinical, demographic, molecular genetic, and neuroimaging markers, for treatment response in patients with social anxiety disorder (SAD).

    Methods: Forty-seven SAD patients (mean +/- SD age 33.9 +/- 9.4 years, 24 women) were randomized and commenced 9 weeks' Internet-delivered cognitive behavior therapy (CBT) combined either with the selective serotonin reuptake inhibitor (SSRI) escitalopram (20 mg daily [10 mg first week], SSRI+CBT, n= 24) or placebo (placebo+CBT, n= 23). Treatment responders were defined from the Clinical Global Impression-Improvement scale (CGI- I <= 2). Before treatment, patients underwent functional magnetic resonance imaging and the Multi-Source Interference Task taxing cognitive interference. Support vector machines (SVMs) were trained to separate responders from nonresponders based on pre-treatment neural reactivity in the dorsal anterior cingulate cortex (dACC), amygdala, and occipital cortex, as well as molecular genetic, demographic, and clinical data. SVM models were tested using leave-one-subject-out cross-validation.

    Results: The best model separated treatment responders (n= 24) from nonresponders based on pre-treatment dACC reactivity (83% accuracy, P= 0.001). Responders had greater pre-treatment dACC reactivity than nonresponders especially in the SSRI+CBT group. No other variable was associated with clinical response or added predictive accuracy to the dACC SVM model.

    Limitations: Small sample size, especially for genetic analyses. No replication or validation samples were available.

    Conclusions: The findings demonstrate that treatment outcome predictions based on neural cingulate activity, at the individual level, outperform genetic, demographic, and clinical variables for medication-assisted Internet-delivered CBT, supporting the use of neuroimaging in precision psychiatry.

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  • 333.
    Frick, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Use of 5-Hydroxytryptophan Labeled With Carbon 11 in Social Anxiety Disorder Reply2016In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 73, no 2, p. 177-178Article in journal (Refereed)
  • 334.
    Frick, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Jonasson, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wahlstedt, Kurt
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bani, Massimo
    GlaxoSmithKline, Verona, Italy.
    Pich, Emilio Merlo
    GlaxoSmithKline, Verona, Italy.
    Bettica, Paolo
    GlaxoSmithKline, Verona, Italy.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Lubberink, Mark
    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.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Reduced serotonin synthesis and regional cerebral blood flow after anxiolytic treatment of social anxiety disorder2016In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 26, no 11, p. 1775-1783Article in journal (Refereed)
    Abstract [en]

    Abstract Social anxiety disorder (SAD) is associated with increased fear-related neural activity in the amygdala and we recently found enhanced serotonin synthesis rate in the same region. Anxiolytic agents like selective serotonin re-uptake inhibitors (SSRIs) and neurokinin-1 receptor (NK1R) antagonists reduce amygdala activity and may attenuate serotonin formation according to animal studies. Here, we examined the effects of SSRI pharmacotherapy, NK1R antagonism, and placebo on serotonin synthesis rate in relation to neural activity, measured as regional cerebral blood flow (rCBF), and symptom improvement in SAD. Eighteen SAD patients were randomized to receive daily double-blind treatment for six weeks either with the SSRI citalopram (n=6; 40 mg), the NK1R antagonist GR205171 (n=6; 5 mg; 4 weeks following 2 weeks of placebo), or placebo (n=6). Serotonin synthesis rate at rest and rCBF during stressful public speaking were assessed, before and after treatment, using positron emission tomography with the tracers [11C]5-hydroxytryptophan and [15O]water respectively. The Liebowitz Social Anxiety Scale (LSAS-SR) indexed symptom severity. All groups exhibited attenuated amygdala serotonin synthesis rate after treatment, which was associated with reduced amygdala rCBF during public speaking and accompanied by symptom improvement. These results are consistent with the notion that serotonin in the amygdala exerts an anxiogenic influence and, conversely, that anxiolysis is achieved through decreased serotonin formation in the amygdala.

  • 335. Frick, Andreas
    et al.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Jonasson, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Alaie, Iman
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Björkstrand, Johannes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Frans, Örjan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Faria, Vanda
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Linnman, Clas
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wahlstedt, Kurt
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Serotonin Synthesis and Reuptake in Social Anxiety Disorder: A Positron Emission Tomography Study.2015In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 72, no 8, p. 794-802Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: Serotonin is involved in negative affect, but whether anxiety syndromes, such as social anxiety disorder (SAD), are characterized by an overactive or underactive serotonin system has not been established. Serotonin 1A autoreceptors, which inhibit serotonin synthesis and release, are downregulated in SAD, and serotonin transporter availability might be increased; however, presynaptic serotonin activity has not been evaluated extensively.

    OBJECTIVE: To examine the serotonin synthesis rate and serotonin transporter availability in patients with SAD and healthy control individuals using positron emission tomography (PET) with the radioligands 5-hydroxytryptophan labeled with carbon 11 ([11C]5-HTP) and 11C-labeled 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile [11C]DASB.

    DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional study at an academic clinical research center. Eighteen patients with SAD (9 men and 9 women; mean [SD] age, 32.6 [8.2] years) and 18 sex- and age-matched healthy controls (9 men and 9 women; mean [SD] age, 34.7 [9.2] years) underwent [11C]5-HTP PET imaging. We acquired [11C]DASB PET images for 26 additional patients with SAD (14 men and 12 women; mean [SD] age, 35.2 [10.7] years) and the same 18 sex- and age-matched healthy controls. Participants were recruited through newspaper advertisements. Data were acquired from March 12, 2002, through March 5, 2012, and analyzed from March 28, 2013, through August 29, 2014.

    MAIN OUTCOMES AND MEASURES: The influx rate of [11C]5-HTP as a measure of serotonin synthesis rate capacity and [11C]DASB binding potential as an index of serotonin transporter availability were acquired during rest. We used the Liebowitz Social Anxiety Scale to measure severity of social anxiety symptoms.

    RESULTS: The PET data were not available for analysis in 1 control for each scan. Increased [11C]5-HTP influx rate was observed in the amygdala, raphe nuclei region, caudate nucleus, putamen, hippocampus, and anterior cingulate cortex of patients with SAD compared with healthy controls (P < .05 corrected), supporting an enhanced serotonin synthesis rate. Increased serotonin transporter availability in the patients with SAD relative to healthy controls was reflected by elevated [11C]DASB binding potential in the raphe nuclei region, caudate nucleus, putamen, thalamus, and insula cortex (P < .05 corrected).

    CONCLUSIONS AND RELEVANCE: Neurotransmission in SAD is characterized by an overactive presynaptic serotonin system, with increased serotonin synthesis and transporter availability. Our findings could provide important new insights into the etiology of anxiety disorders.

  • 336.
    Frick, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Linnman, Clas
    Jonasson, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. 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 Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. 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 Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Increased neurokinin-1 receptor availability in the amygdala in social anxiety disorder: a positron emission tomography study with [(11)C]GR2051712015In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 5, article id e597Article in journal (Refereed)
    Abstract [en]

    The neurokinin-1 (NK1) receptor is abundantly expressed in the fear circuitry of the brain, including the amygdala, where it modulates stress and anxiety. Despite its proposed involvement in psychopathology, only a few studies of NK1 receptor availability in human subjects with anxiety disorders exist. Here, we compared NK1 receptor availability in patients with social anxiety disorder (SAD; n = 17) and healthy controls (n = 17) using positron emission tomography and the radiotracer [(11)C]GR205171. The Patlak Graphical plot using a cerebellar reference region was used to model the influx parameter, Ki measuring NK1 receptor availability. Voxel-wise statistical parametric mapping analyses revealed increased NK1 receptor availability specifically in the right amygdala in SAD patients relative to controls. Thus, we demonstrate that exaggerated social anxiety is related to enhanced NK1 receptor availability in the amygdala. This finding supports the contribution of NK1 receptors not only in animal models of stress and anxiety but also in humans with anxiety disorders.

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  • 337.
    Frick, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Michelgård Palmquist, Åsa
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Pissiota, Anna
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Wallenquist, Ulrika
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fernandez, Manuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Jonasson, My
    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.
    Frans, Örjan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    von Knorring, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Co-expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder: a multitracer PET studyArticle in journal (Refereed)
  • 338.
    Frick, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Michelgård Palmquist, Åsa
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Pissiota, Anna
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Wallenquist, Ulrika
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fernandez, Manuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Jonasson, My
    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.
    Frans, Örjan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    von Knorring, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder: a multi-tracer PET study2016In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 21, no 10, p. 1400-1407Article in journal (Refereed)
    Abstract [en]

    The brain serotonergic system is colocalized and interacts with the neuropeptidergic substance P/neurokinin-1 (SP/NK1) system. Both these neurochemical systems have independently been implicated in stress and anxiety, but interactions between them might be crucial for human anxiety conditions. Here, we examined the serotonin and substance P/neurokinin-1 (SP/NK1) systems individually as well as their overlapping expression in 16 patients with posttraumatic stress disorder (PTSD) and 16 healthy controls. Participants were imaged with the highly selective radiotracers [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) and [(11)C]GR205171 assessing serotonin transporter (SERT) and NK1 receptor availability, respectively. Voxel-wise analyses in the amygdala, our a priori-defined region of interest, revealed increased number of NK1 receptors, but not SERT in the PTSD group. Symptom severity, as indexed by the Clinician-administered PTSD Scale, was negatively related to SERT availability in the amygdala, and NK1 receptor levels moderated this relationship. Exploratory, voxel-wise whole-brain analyses revealed increased SERT availability in the precentral gyrus and posterior cingulate cortex of PTSD patients. Patients, relative to controls, displayed lower degree of overlapping expression between SERT and NK1 receptors in the putamen, thalamus, insula and lateral orbitofrontal gyrus, lower overlap being associated with higher PTSD symptom severity. Expression overlap also explained more of the symptomatology than did either system individually, underscoring the importance of taking interactions between the neurochemical systems into account. Thus, our results suggest that aberrant serotonergic-SP/NK1 couplings contribute to the pathophysiology of PTSD and, consequently, that normalization of these couplings may be therapeutically important.

  • 339.
    Fridén, Michael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kullberg, Joel
    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 Public Health and Caring Sciences, Geriatrics.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rosqvist, Fredrik
    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.
    Intake of Ultra-Processed Food and Ectopic-, Visceral- and Other Fat Depots: A Cross-Sectional Study.2022In: Frontiers in nutrition, ISSN 2296-861X, Vol. 9, article id 774718Article in journal (Refereed)
    Abstract [en]

    Introduction: The purpose of this study was to investigate associations between intake of ultra-processed food (UPF) and liver fat, pancreas fat and visceral adipose tissue (VAT) but also subcutaneous adipose tissue (SAT), VAT/SAT ratio and total fat mass.

    Materials and Methods: Cross-sectional analysis of n = 286 50-year old men and women. Energy percentage (%E) from UPF was calculated from a semi-quantitative food frequency questionnaire. Food items were categorized according to the NOVA-classification system and fat depots were assessed using magnetic resonance imaging (MRI) and bioelectrical impedance analysis (BIA). Associations were analyzed using linear regression, adjusted for sex, education, physical activity, smoking, dietary factors and BMI.

    Results: Mean intake of UPF was 37.8 ± 10.2 %E and the three largest contributors to this were crisp- and wholegrain breads and spreads, indicating overall healthy food choices. Consumption of UPF was associated with higher intake of energy, carbohydrates and fiber and lower intake of protein and polyunsaturated fat but no differences were observed for total fat, saturated fat (SFA), monounsaturated fat, sugar or alcohol between tertiles of UPF. Intake of UPF was positively associated with liver- and pancreas fat, VAT, VAT/SAT and inversely associated with total fat mass in crude models. The association for VAT remained after full adjustment (β = 0.01 (95% CI: 0.002, 0.02), P = 0.02) and was driven by women.

    Conclusion: Energy intake from UPF is not associated with ectopic fat, SAT or total fat after adjustment for multiple confounders in this population having overall healthy food habits. However, a positive association between UPF and VAT was observed which was driven by women.

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  • 340.
    Fridén, Michael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Martínez Mora, Andrés
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical AB, Mölndal, Sweden.
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Diet composition, nutrient substitutions and circulating fatty acids in relation to ectopic and visceral fat depots2023In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 42, no 10, p. 1922-1931Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Short-term randomized trials have demonstrated that replacing saturated fat (SFA) with polyunsaturated fat (PUFA) causes a reduction or prevention of liver fat accumulation, but population-based studies on diet and body fat distribution are limited. We investigated cross-sectional associations between diet, circulating fatty acids and liver fat, visceral adipose tissue (VAT), intermuscular adipose tissue (IMAT) and other fat depots using different energy-adjustment models.

    METHODS: Sex-stratified analyses of n = 9119 (for serum fatty acids) to 13 849 (for nutrients) participants in UK Biobank were conducted. Fat depots were assessed by MRI, circulating fatty acids by NMR spectroscopy and diet by repeated 24-h recalls. Liver fat, VAT and IMAT were primary outcomes; total adipose tissue (TAT) and abdominal subcutaneous adipose tissue (ASAT) were secondary outcomes. Three a priori defined models were constructed: the all-components model, standard model and leave-one-out model (main model including specified nutrient substitutions). Imiomics (MRI-derived) was used to confirm and visualize associations.

    RESULTS: In women, substituting carbohydrates and free sugars with saturated fat (SFA) was positively associated with liver fat (β (95% CI) = 0.19 (0.02, 0.36) and β (95% CI) = 0.20 (0.05-0.35), respectively) and IMAT (β (95% CI) = 0.07 (0.00, 0.14) and β (95% CI) = 0.08 (0.02, 0.13), respectively), whereas substituting animal fat with plant fat was inversely associated with IMAT, ASAT and TAT. In the all-components and standard models, SFA and animal fat were positively associated with liver fat, IMAT and VAT whereas plant fat was inversely associated with IMAT in women. Few associations were observed in men. Circulating polyunsaturated fatty acids (PUFA) were inversely associated with liver fat, IMAT and VAT in both men and women, whereas SFA and monounsaturated fatty acids were positively associated.

    CONCLUSIONS: Type of dietary fat may be an important determinant of ectopic fat in humans consuming their habitual diet. Plant fat and PUFA should be preferred over animal fat and SFA. This is corroborated by circulating fatty acids and overall consistent through different energy adjustment models.

    TWITTER SUMMARY: In UK Biobank, intake of saturated- and animal fat were positively whereas biomarkers of polyunsaturated fat were inversely associated with liver-, visceral- and intermuscular fat. Type of dietary fat may be a determinant of ectopic fat, a risk factor for cardiometabolic disease.

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  • 341.
    Fridén, Michael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med AB, BioVenture Hub, Mölndal, Sweden..
    Niessen, Heiko G.
    Boehringer Ingelheim Pharma GmbH & Co KG, Dept Translat Med & Clin Pharmacol, Biberach, Germany..
    Schultheis, Christian
    Boehringer Ingelheim Pharma GmbH & Co KG, Dept Translat Med & Clin Pharmacol, Biberach, Germany..
    Hockings, Paul
    Antaros Med AB, BioVenture Hub, Mölndal, Sweden.;Chalmers Univ Technol, MedTech West, Gothenburg, Sweden..
    Hulthe, Johannes
    Antaros Med AB, BioVenture Hub, Mölndal, Sweden..
    Gummesson, Anders
    Sahlgrens Univ Hosp, Dept Clin Genet & Genom, Gothenburg, Sweden..
    Wanders, Alkwin
    Aalborg Univ Hosp, Dept Pathol, Aalborg, Denmark..
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Vessby, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Hepatic Unsaturated Fatty Acids Are Linked to Lower Degree of Fibrosis in Non-alcoholic Fatty Liver Disease2022In: Frontiers in Medicine, E-ISSN 2296-858X, Vol. 8, article id 814951Article in journal (Refereed)
    Abstract [en]

    Background: The hepatic lipidome of patients with early stages of non-alcoholic fatty liver disease (NAFLD) has been fairly well-explored. However, studies on more progressive forms of NAFLD, i.e., liver fibrosis, are limited.

    Materials and methods: Liver fatty acids were determined in cholesteryl esters (CE), phospholipids (PL), and triacylglycerols (TAG) by gas chromatography. Cross-sectional associations between fatty acids and biopsy-proven NAFLD fibrosis (n = 60) were assessed using multivariable logistic regression models. Stages of fibrosis were dichotomized into none-mild (F0–1) or significant fibrosis (F2–4). Models were adjusted for body-mass index (BMI), age and patatin-like phospholipase domain-containing protein 3 (PNPLA3 rs738409) (I148M) genotype. A secondary analysis examined whether associations from the primary analysis could be confirmed in the corresponding plasma lipid fractions.

    Results: PL behenic acid (22:0) was directly associated [OR (95% CI): 1.86 (1.00, 3.45)] whereas PL docosahexaenoic acid (22:6n-3) [OR (95% CI): 0.45 (0.23, 0.89)], TAG oleic acid (18:1n-9) [OR (95% CI): 0.52 (0.28, 0.95)] and 18:1n-9 and vaccenic acid (18:1n-7) (18:1) [OR (95% CI): 0.52 (0.28, 0.96)] were inversely associated with liver fibrosis. In plasma, TAG 18:1n-9 [OR (95% CI): 0.55 (0.31, 0.99)], TAG 18:1 [OR (95% CI): 0.54 (0.30, 0.97)] and PL 22:0 [OR (95% CI): 0.46 (0.25, 0.86)] were inversely associated with liver fibrosis.

    Conclusion: Higher TAG 18:1n-9 levels were linked to lower fibrosis in both liver and plasma, possibly reflecting an altered fatty acid metabolism. Whether PL 22:6n-3 has a protective role, together with a potentially adverse effect of hepatic 22:0, on liver fibrosis warrants large-scale studies.

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  • 342.
    Fridén, Michael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical AB, BioVenture Hub , Mölndal , Sweden.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical AB, BioVenture Hub , Mölndal , Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Associations between fatty acid composition in serum cholesteryl esters and liver fat, basal fat oxidation, and resting energy expenditure: a population-based study2021In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 114, no 5, p. 1743-1751Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We have repeatedly shown in short-term feeding trials that a high intake of dietary n-6 PUFAs, i.e. linoleic acid, prevents liver fat accumulation compared with saturated fat. However, population-based data is lacking and the mechanisms behind such effects are unclear.

    OBJECTIVE: To investigate associations between serum cholesteryl ester (CE) fatty acids and liver fat, basal fat oxidation [respiratory quotient (RQ)], and resting energy expenditure (REE). We hypothesized that PUFA in particular is inversely associated with liver fat and that such a relation is partly explained by a PUFA-induced increase in basal fat oxidation or REE.

    METHODS: Cross-sectional analyses using linear regression models in a population-based cohort with data on serum CE fatty acid composition and liver fat (n = 308).

    RESULTS: Linoleic acid (18:2n-6) (β = -0.03, 95% CI: -0.06, -0.001) and Δ5 desaturase index were inversely associated, whereas, γ-linolenic acid (18:3n-6) (β = 0.59, 95% CI: 0.28, 0.90), dihomo-γ-linolenic acid (20:3n-6) (β = 1.20, 95% CI: 0.65, 1.75), arachidonic acid (20:4n-6) (β = 0.08, 95% CI: 0.002, 0.16), palmitoleic acid (16:1n-7) (β = 0.37, 95% CI: 0.04, 0.70), Δ6 desaturase, and stearoyl CoA desaturase-1 (SCD-1) index were directly associated with liver fat after adjustment for confounders. Several serum CE fatty acids were correlated with both liver fat and REE, but only the association between DHA (22:6n-3) and liver fat was clearly attenuated after adjustment for REE (from β = -0.63 95% CI: -1.24, -0.02 to β = -0.34, 95% CI: -0.95, 0.27). Palmitoleic acid and SCD-1 were weakly inversely correlated with RQ but could not explain a lower liver fat content.

    CONCLUSIONS: Several serum CE fatty acids are associated with liver fat, among them linoleic acid. Although we identified novel associations between individual fatty acids and RQ and REE, our findings imply that PUFAs might prevent liver fat accumulation through mechanisms other than enhanced whole-body energy metabolism.

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  • 343.
    Frithiof, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Rostami, Elham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery. Karolinska institutet.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Ashton, Nicholas
    Blennow, Kaj
    Zetterberg, Henrik
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rostedt Punga: Clinical Neurophysiology.
    Critical illness polyneuropathy, myopathy and neuronal biomarkers in COVID-19 patients: A prospective study2021In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 132, no 7, p. 1733-1740Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim was to characterize the electrophysiological features and plasma biomarkers of critical illness polyneuropathy (CIN) and myopathy (CIM) in coronavirus disease 2019 (COVID-19) patients with intensive care unit acquired weakness (ICUAW).

    METHODS: An observational ICU cohort study including adult patients admitted to the ICU at Uppsala University Hospital, Uppsala, Sweden, from March 13th to June 8th 2020. We compared the clinical, electrophysiological and plasma biomarker data between COVID-19 patients who developed CIN/CIM and those who did not. Electrophysiological characteristics were also compared between COVID-19 and non-COVID-19 ICU patients.

    RESULTS: 111 COVID-19 patients were included, 11 of whom developed CIN/CIM. Patients with CIN/CIM had more severe illness; longer ICU stay, more thromboembolic events and were more frequently treated with invasive ventilation for longer than 2 weeks. In particular CIN was more frequent among COVID-19 patients with ICUAW (50%) compared with a non-COVID-19 cohort (0%, p = 0.008). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp) levels were higher in the CIN/CIM group compared with those that did not develop CIN/CIM (both p = 0.001) and correlated with nerve amplitudes.

    CONCLUSIONS: CIN/CIM was more prevalent among COVID-19 ICU patients with severe illness.

    SIGNIFICANCE: COVID-19 patients who later developed CIN/CIM had significantly higher NfL and GFAp in the early phase of ICU care, suggesting their potential as predictive biomarkers for CIN/CIM.

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  • 344.
    Fritz, Benjamin
    et al.
    Balgrist Univ Hosp, Dept Radiol, Zurich, Switzerland.;Univ Zurich, Fac Med, Zurich, Switzerland..
    Parkar, Anagha P.
    Haraldsplass Deaconess Hosp, Dept Radiol, Bergen, Norway..
    Cerezal, Luis
    Diagnost Med Cantabria, Dept Radiol, Santander, Spain..
    Storgaard, Morten
    Inst Sports Med Copenhagen, Copenhagen Area, Copenhagen, Denmark..
    Boesen, Mikael
    Copenhagen Univ Hosp Bispebjerg & Frederiksberg, Dept Radiol, Copenhagen NV, Denmark.;Copenhagen Univ Hosp Bispebjerg & Frederiksberg, Parker Inst, Frederiksberg, Denmark..
    Åström, Gunnar
    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 Immunology, Genetics and Pathology.
    Fritz, Jan
    NYU, Dept Radiol, Grossman Sch Med, New York, NY USA.;Univ Bergen, Fac Med & Dent, Dept Clin Med, Bergen, Norway..
    Sports Imaging of Team Handball Injuries2020In: Seminars in Musculoskeletal Radiology, ISSN 1089-7860, E-ISSN 1098-898X, Vol. 24, no 03, p. 227-245Article in journal (Refereed)
    Abstract [en]

    Team handball is a fast high-scoring indoor contact sport with>20 million registered players who are organized in>150 federations worldwide. The combination of complex and unique biomechanics of handball throwing, permitted body tackles and blocks, and illegal fouls contribute to team handball ranging among the four athletic sports that carry the highest risks of injury. The categories include a broad range of acute and overuse injuries that most commonly occur in the shoulder, knee, and ankle. In concert with sports medicine, physicians, surgeons, physical therapists, and radiologists consult in the care of handball players through the appropriate use and expert interpretations of radiography, ultrasonography, CT, and MRI studies to facilitate diagnosis, characterization, and healing of a broad spectrum of acute, complex, concomitant, chronic, and overuse injuries. This article is based on published data and the author team's cumulative experience in playing and caring for handball players in Denmark, Sweden, Norway, Germany, Switzerland, and Spain. The article reviews and illustrates the spectrum of common handball injuries and highlights the contributions of sports imaging for diagnosis and management.

  • 345.
    Fröss-Baron, Katarzyna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Garske, Ulrike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Department of Nuclear Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Khan, Tanweera Shaheena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Sandström, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    177Lu-DOTATATE Therapy of Advanced Pancreatic Neuroendocrine Tumors Heavily Pretreated With Chemotherapy: Analysis of Outcome, Safety and Their Determinants2021In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 111, no 4, p. 330-343Article in journal (Refereed)
    Abstract [en]

    Objective: To retrospectively analyze toxicity, progression-free survival (PFS), overall survival (OS) and their determinants in patients with advanced pancreatic neuroendocrine tumors (panNETs), previously pretreated with chemotherapy, undergoing peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE.

    Methods: In total, 102 patients with advanced panNETs, previously pretreated with one (67%) or several (33%) lines of chemotherapy were included, of whom 90 % had progressive disease and the majority (74.5%) with grade 2 tumors. 177Lu-DOTATATE, 7.4 GBq per cycle, was administered with 6 to 8 weeks interval, in 88 % of patients utilizing a dosimetry-guided protocol, until an absorbed dose of 23 Gy to the kidneys was reached.

    Results: Mean 32±10.9 GBq per patient was administered in 1-10 cycles starting median 36 months after panNET diagnosis. Median follow-up was 34 months. Median PFS was 24 months and median OS was 42 months from start of PRRT. Independent risk factors for both progression and death were liver tumor burden >50%, more than one line of previous chemotherapy and elevated alkaline phosphatase (ALP). Resection of the primary tumor was linked to longer survival. Bone marrow toxicity grade 3-4 occurred in 10.8%. One patient (1.0 %) developed acute myeloid leukemia. Bone marrow toxicity was unrelated to type and length of previous chemotherapy, amount of administered activity and absorbed dose to the bone marrow.

    Conclusion: 177Lu-DOTATATE therapy was feasible, highly effective and safe in patients with advanced panNETs heavily pretreated with chemotherapy. More than one line of chemotherapy was a therapy related independent risk factor for shorter PFS and OS.

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  • 346.
    Frühling, Petter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Duraj, Frans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Haglund, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Norén, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Single-center nonrandomized clinical trial to assess the safety and efficacy of irreversible electroporation (IRE) ablation of liver tumors in humans: Short to mid-term results2017In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 43, no 4, p. 751-757Article in journal (Refereed)
    Abstract [en]

    Introduction: A single-center nonrandomized clinical trial was performed to assess the safety and efficacy of IRE ablation of liver tumors in humans.

    Methods: 38 malignant liver tumors on 30 patients were treated with IRE between September 2011 and September 2014. Treatment was with curative intent, and the diagnoses were colorectal cancer with liver metastases (CRLM) (n = 23), hepatocellular carcinoma (HCC) (n = 8) and other metastasis (n = 7). Patients were selected when surgery, radiofrequency ablation (RFA) or microwave ablation (MWA) was not an option, and when they met inclusion criteria (tumor size < 3 cm, 1-2 tumors). Patients were followed-up at 1 and 6 months with a contrast-enhanced computed tomography (CE-CT), and contrast-enhanced ultrasound (CE-US) at 3 months.

    Results: Ablation success was defined as no evidence of residual tumor in the ablated area as confirmed by CE-CT and CE-US. At 3 months ablation success was 78.9%, and 65.8% at 6 months. There was no statistically significant difference between tumor volume (<5 cm(3) vs >5 cm(3), p = 0.518), and between diagnosis (CRLM vs HCC, p = 0.084) in terms of local recurrence. Complications were classified according to the standardized grading system of Society of Interventional Radiology (SIR). A minor complication occurred in six palients (20%), one patient (3.3%) suffered from a major complication (bile duct dilatation and stricture of the portal vein and bile duct). No mortalities occurred at 30 days.

    Conclusions: IRE appears to be a safe treatment modality for a selected group of patients with liver tumors and offers high local tumor control at 3 and 6 months.

  • 347.
    Furmark, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Marteinsdottir, Ina
    Linkoping Univ, Dept Clin & Expt Med, Ctr Social & Affect Neurosci, Linkoping, Sweden.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Heurling, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Tillfors, Maria
    Univ Orebro, Ctr Hlth & Med Psychol, Orebro, Sweden.
    Appel, Lieuwe
    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, Division of Molecular Imaging.
    Hartvig, Per
    Univ Copenhagen, Dept Drug Design & Pharmacol, Copenhagen, Denmark.
    Fischer, Håkan
    Stockholm Univ, Dept Psychol, Stockholm, Sweden.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry. Southern Denmark Univ, Odense Univ Hosp, Odense, Denmark.
    Eriksson, Elias
    Gothenburg Univ, Dept Pharmacol, Gothenburg, Sweden.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Serotonin synthesis rate and the tryptophan hydroxylase-2: G-703T polymorphism in social anxiety disorder.2016In: Journal of Psychopharmacology, ISSN 0269-8811, E-ISSN 1461-7285, Vol. 30, no 10, p. 1028-1035Article in journal (Refereed)
    Abstract [en]

    It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohort, and whether allelic variation in the tryptophan hydroxylase-2 (TPH2) G-703T polymorphism relates to differences in serotonin synthesis assessed with positron emission tomography. Eighteen social anxiety disorder patients and six healthy controls were scanned during 60 minutes in a resting state using positron emission tomography and 5-hydroxy-L-[β -(11)C]tryptophan, [(11)C]5-HTP, a substrate of the second enzymatic step in serotonin synthesis. Parametric images were generated, using the reference Patlak method, and analysed using Statistical Parametric Mapping (SPM8). Blood samples for genotyping of the TPH2 G-703T polymorphism were obtained from 16 social anxiety disorder patients (T carriers: n=5, GG carriers: n=11). A significantly elevated [(11)C]5-HTP accumulation rate, indicative of enhanced decarboxylase activity and thereby serotonin synthesis capacity, was detected in social anxiety disorder patients compared with controls in the hippocampus and basal ganglia nuclei and, at a more lenient (uncorrected) statistical threshold, in the amygdala and anterior cingulate cortex. In patients, the serotonin synthesis rate in the amygdala and anterior cingulate cortex was significantly elevated in TPH2 T carriers in comparison with GG homozygotes. Our results support that social anxiety disorder entails an overactive presynaptic serotonergic system that, in turn, seems functionally influenced by the TPH2 G-703T polymorphism in emotionally relevant brain regions.

  • 348.
    Furthner, Dieter
    et al.
    Salzkammergutklinikum Voecklabruck, Dept Pediat, Voecklabruck, Austria.;Paracelsus Med Univ, Univ Hosp Salzburg, Obes Res Unit, Salzburg, Austria..
    Anderwald, Christian-Heinz
    Paracelsus Med Univ, Univ Hosp Salzburg, Obes Res Unit, Salzburg, Austria.;Med Univ Vienna, Div Endocrinol & Metab, Dept Internal Med 3, Vienna, Austria.;Arnoldstein Healthcare Ctr, Arnoldstein, Austria..
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. 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.
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ciba, Iris
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Mangge, Harald
    Med Univ Graz, Clin Inst Med & Chem Lab Diag, Graz, Austria..
    Maruszczak, Katharina
    Paracelsus Med Univ, Univ Hosp Salzburg, Obes Res Unit, Salzburg, Austria.;Paracelsus Med Univ, Univ Hosp Salzburg, Dept Pediat, Salzburg, Austria..
    Koren, Pia
    Paracelsus Med Univ, Univ Hosp Salzburg, Obes Res Unit, Salzburg, Austria.;Paracelsus Med Univ, Univ Hosp Salzburg, Dept Pediat, Salzburg, Austria..
    Schuetz, Sebastian
    Paracelsus Med Univ, Univ Hosp Salzburg, Obes Res Unit, Salzburg, Austria.;Paracelsus Med Univ, Univ Hosp Salzburg, Dept Pediat, Salzburg, Austria..
    Brunner, Susanne Maria
    Paracelsus Med Univ, Dept Pediat, Res Program Receptor Biochem & Tumor Metab, Univ Hosp, Salzburg, Austria..
    Schneider, Anna Maria
    Paracelsus Med Univ, Univ Hosp Salzburg, Obes Res Unit, Salzburg, Austria.;Paracelsus Med Univ, Univ Hosp Salzburg, Dept Pediat, Salzburg, Austria..
    Weghuber, Daniel
    Paracelsus Med Univ, Univ Hosp Salzburg, Obes Res Unit, Salzburg, Austria.;Paracelsus Med Univ, Univ Hosp Salzburg, Dept Pediat, Salzburg, Austria..
    Moerwald, Katharina
    Paracelsus Med Univ, Univ Hosp Salzburg, Obes Res Unit, Salzburg, Austria.;Paracelsus Med Univ, Univ Hosp Salzburg, Dept Pediat, Salzburg, Austria..
    Single Point Insulin Sensitivity Estimator in Pediatric Non-Alcoholic Fatty Liver Disease2022In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 13, article id 830012Article in journal (Refereed)
    Abstract [en]

    BackgroundAttenuated insulin-sensitivity (IS) is a central feature of pediatric non-alcoholic fatty liver disease (NAFLD). We recently developed a new index, single point insulin sensitivity estimator (SPISE), based on triglycerides, high-density-lipoprotein and body-mass-index (BMI), and validated by euglycemic-hyperinsulinemic clamp-test (EHCT) in adolescents. This study aims to assess the performance of SPISE as an estimation of hepatic insulin (in-)sensitivity. Our results introduce SPISE as a novel and inexpensive index of hepatic insulin resistance, superior to established indices in children and adolescents with obesity. Materials and MethodsNinety-nine pubertal subjects with obesity (13.5 +/- 2.0 years, 59.6% males, overall mean BMI-SDS + 2.8 +/- 0.6) were stratified by MRI (magnetic resonance imaging) into a NAFLD (>5% liver-fat-content; male n=41, female n=16) and non-NAFLD (<= 5%; male n=18, female n=24) group. Obesity was defined according to WHO criteria (> 2 BMI-SDS). EHCT were used to determine IS in a subgroup (n=17). Receiver-operating-characteristic (ROC)-curve was performed for diagnostic ability of SPISE, HOMA-IR (homeostatic model assessment for insulin resistance), and HIRI (hepatic insulin resistance index), assuming null hypothesis of no difference in area-under-the-curve (AUC) at 0.5. ResultsSPISE was lower in NAFLD (male: 4.8 +/- 1.2, female: 4.5 +/- 1.1) than in non-NAFLD group (male 6.0 +/- 1.6, female 5.6 +/- 1.5; P< 0.05 {95% confidence interval [CI]: male NAFLD 4.5, 5.2; male non-NAFLD 5.2, 6.8; female NAFLD 4.0, 5.1, female non-NAFLD 5.0, 6.2}). In males, ROC-AUC was 0.71 for SPISE (P=0.006, 95% CI: 0.54, 0.87), 0.68 for HOMA-IR (P=0.038, 95% CI: 0.48, 0.88), and 0.50 for HIRI (P=0.543, 95% CI: 0.27, 0.74). In females, ROC-AUC was 0.74 for SPISE (P=0.006), 0.59 for HOMA-IR (P=0.214), and 0.68 for HIRI (P=0.072). The optimal cutoff-level for SPISE between NAFLD and non-NAFLD patients was 5.18 overall (Youden-index: 0.35; sensitivity 0.68%, specificity 0.67%). ConclusionSPISE is significantly lower in juvenile patients with obesity-associated NAFLD. Our results suggest that SPISE indicates hepatic IR in pediatric NAFLD patients with sensitivity and specificity superior to established indices of hepatic IR.

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  • 349.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Neuroradiologiska fynd vid Covid-192020In: Neurologi i Sverige, Vol. 3, no 20, p. 62-65Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Under sommaren har en tilltagande ström av artiklar om neuroradiologiska fynd vid covid-19 (härefter benämnt covid) publicerats och ännu fler ogranskade förhandsmanuskript cirkulerar i ett svåröverskådligt flöde. Mycket av innehållet är fallrapporter och opportuna ”short communications” men flera mellanstora studier har hunnit ut. Den här artikeln av David Fällmar syftar till att sammanfatta innehållet i några sådana rapporter som har neuroradiologiskt innehåll. Den är på inget sätt heltäckande, men artiklarnas likheter och skillnader är väl värda en stunds begrundan.

  • 350.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Svensk forskning konsoliderar kunskap om normaltryckshydrocefalus2020In: Neurologi i Sverige, Vol. 3, p. 24-31Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Normaltryckshydrocefalus (NPH) är ettvanligt tillstånd, som orsakar stort lidande, men är behandlingsbart. Det är också otill-räckligt utforskat. Därför är det glädjandeatt svensk NPH-forskning är framgångsrik. David Fällmar, neuroradiolog, berättarmer i denna artkikel.

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