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  • 1.
    Appel, Lieuwe
    et al.
    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.
    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.
    Danfors, Torsten
    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.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    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.
    Sörensen, Jens
    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.
    Use of C-11-PE2I PET in Differential Diagnosis of Parkinsonian Disorders2015In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 56, no 2, p. 234-242Article in journal (Refereed)
    Abstract [en]

    In idiopathic Parkinson disease and atypical parkinsonian disorders, central dopaminergic and overall brain functional activity are altered to different degrees, causing difficulties in achieving an unambiguous clinical diagnosis. A dual examination using I-123-FP-CIT (I-123-N-omega-fluoropropyl- 2 beta-carbomethoxy-3 beta-(4-iodophenyl) nortropane, or I-123-ioflupane) SPECT and F-18-FDG PET provides complementary information on dopamine transporter (DAT) availability and overall brain functional activity, respectively. Parametric images based on a single, dynamic C-11-PE2I (N-(3-iodoprop-2E-enyl)-2 beta-carbomethoxy-3 beta-(4-methyl-phenyl) nortropane) scan potentially supply both DAT availability (nondisplaceable binding potential [BPND]) and relative cerebral blood flow (relative delivery [R-1]) at voxel level. This study aimed to evaluate the validity of C-11-PE2I PET against the dual-modality approach using I-123-FP-CIT SPECT and F-18-FDG PET.

    Methods: Sixteen patients with parkinsonian disorders had a dual examination with F-18-FDG PET and I-123-FP-CIT SPECT following clinical routines and additionally an experimental C-11-PE2I PET scan. Parametric BPND and R-1 images were generated using receptor parametric mapping with the cerebellum as a reference. T1-weighted MR imaging was used for automated definition of volumes of interest (VOI). The DAT VOIs included the basal ganglia, whereas the overall brain functional activity was examined using VOIs across the brain. BPND and R-1 values were compared with normalized I-123-FP-CIT and F-18-FDG uptake values, respectively, using Pearson correlations and regression analyses. In addition, 2 masked interpreters evaluated the images visually, in both the routine and the experimental datasets, for comparison of patient diagnoses.

    Results: Parametric C-11-PE2I BPND and R-1 images showed high consistency with I-123-FP-CIT SPECT and F-18-FDG PET images. Correlations between C-11-PE2I BPND and I-123-FP-CIT uptake ratios were 0.97 and 0.76 in the putamen and caudate nucleus, respectively. Regional C-11-PE2I R-1 values were moderately to highly correlated with normalized F-18-FDG values (range, 0.61-0.94). Visual assessment of DAT availability showed a high consistency between C-11-PE2I BPND and I-123-FP-CIT images, whereas the consistency was somewhat lower for appraisal of overall brain functional activity using I-123-FP-CIT and F-18-FDG images. Substantial differences were found between clinical diagnosis and both neuro-imaging diagnoses.

    Conclusion: A single, dynamic C-11-PE2I PET investigation is a powerful alternative to a dual examination with I-123-FP-CIT SPECT and F-18-FDG PET for differential diagnosis of parkinsonian disorders. A large-scale patient study is, however, needed to further investigate distinct pathologic patterns in overall brain functional activity for various parkinsonian disorders.

  • 2.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    11C Molecular Imaging in Focal Epilepsy2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Epilepsy is a common neurological disease affecting 6 million people in Europe. Early prevention and accurate diagnosis and treatment are of importance to obtain seizure freedom. In this thesis new applications of carbon-11-labelled tracers in PET and autoradiographic studies were explored in focal epilepsy.

    Patients with low-grade gliomas often experience epileptic seizures. A retrospective PET-study assessing seizure activity, metabolic rate measured with 11C-methionine and other known prognostic factors was performed in patients with glioma. No correlation was found between seizure activity and uptake of methionine. The presence and termination of early seizures was a favourable prognostic factor.

    Activation of the neurokinin-1 (NK1) receptor by substance P (SP) induces epileptic activity. PET with the NK1 receptor antagonist GR205171 was performed in patients with temporal lobe epilepsy (TLE) and healthy controls. In TLE patients an increased NK1 receptor availability was found in both hemispheres, most pronounced in anterior cingulate gyrus ipsilateral to seizure onset. A positive correlation between NK1 receptors and seizure frequency was observed in ipsilateral medial structures consistent with an intrinsic network using the NK1-SP receptor system for transmission of seizure activity.

    The uptake of 18F-fluoro-deoxy-glucose (FDG) is related to cerebral blood flow (CBF). Previously, methods to estimate blood flow from dynamic PET data have been described. A retrospective study was conducted in 15 patients undergoing epilepsy surgery investigation, including PET with 11C-FDG and 11C-Flumazenil (FMZ). The dynamic FMZ dataset and pharmacokinetic modeling with a multilinear reference tissue model were used to determine images of relative CBF. Agreement between data of FDG and CBF was analyzed showing a close association between interictal brain metabolism and relative CBF.

    Epilepsy often occurs after traumatic brain injuries. Changes in glia and inhibitory neuronal cells contribute to the chain of events leading to seizures. Autoradiography with 11C-PK11195, 11C-L-deprenyl and 11C-Flumazenil in an animal model of posttraumatic epilepsy studied the temporal and spatial distribution of microglia, astrocytes and GABAergic neurons. Results showed an instant increase in microglial activity that subsequently normalized, a late formation of astrogliosis and an instant and prolonged decease in GABA binding. The model can be used to visualize pathophysiological events during the epileptogenesis.

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  • 3.
    Danfors, Torsten
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Fagius, Ja
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Akutneurologi2006In: Neurologi, Liber AB, Stockholm , 2006, p. 568-Chapter in book (Other scientific)
  • 4.
    Danfors, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Ribom, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Berntsson, Shala G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Epileptic seizures and survival in early disease of grade 2 gliomas2009In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 16, no 7, p. 823-831Article in journal (Refereed)
    Abstract [en]

    Background and purpose

    The aims of this study were (i) to determine the correlation between seizure activity and the metabolic rate of the tumour measured by 11Cmethionine PET (MET PET) in patients with grade 2 gliomas, and (ii) to assess the prognostic impact of early seizure manifestations on patient survival.

    Methods

    In this retrospective review, early seizure manifestations were studied in 101 patients with supratentorial grade 2 gliomas subjected to MET PET as part of the pretreatment tumour investigation. Seizure manifestations as a variable was then used in multivariate survival analyses, together with established prognostic factors for this patient group.

    Results

    Of all 101 cases, 88 patients had seizures at tumour presentation. Fortyseven were seizure free at the early stage of the disease, whereas 54 had recurrent seizures. Patients with seizures at tumour presentation had a more favourable outcome before and after (P = 0.006) adjustment for conventional prognostic factors. However, for those who continued to have seizures early in the disease, the outcome was worse (P = 0.003). We found no significant correlation between MET PET and the seizure manifestations of the patients.

    Conclusion

    The presence and termination of early seizure manifestations may be favourable prognostic factors in patients with low-grade gliomas.

     

  • 5.
    Danfors, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Samuelsson, Carolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Estrada, Sergio
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Mats, Bergström
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    11C-autoradiographic studies of dynamic changes in glial cells and benzodiazepine receptor binding in a model of posttraumatic epilepsyManuscript (preprint) (Other academic)
  • 6.
    Danfors, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Relative Cerbral Blood Flow Measurement using dynamic Flumazenil-PET may Replace Fluorodeoxyglucose-PET in Epilepsy Surgical Investigations2012In: Article in journal (Other academic)
  • 7.
    Danfors, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Velickaite, Vilma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Canto Moreira, Nuno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    The role of methionine positron emission tomography in the evaluation of central nervous system tumors in children2016In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 36, no Suppl. 1, p. 394-395, article id 538Article in journal (Other academic)
  • 8.
    Danfors, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. neurologi.
    von Knorring, Anne-Liis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. BUP.
    Hartvig, Per
    Hospital Pharmacy.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Moulder, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Strömberg, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Torstenson, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Wester, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Watanabe, Yasuyoshi
    Department of Physiology, Osaka City University Graduate School of Medicine, Japan.
    Eeg-Olofsson, Orvar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Tetrahydrobiopterin in the treatment of children with autistic disorder. A double-blind placebo-controlled crossover study2005In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 25, no 5, p. 485-489Article in journal (Refereed)
    Abstract [en]

    Twelve children, all boys, aged 4 to 7 years, with a diagnosis of autistic disorder and low concentrations of spinal 6R-l-erythro-5,6,7,8-tetrahydrobiopterin (tetrahydrobiopterin) were selected to participate in a double-blind, randomized, placebo-controlled, crossover study. The children received a daily dose of 3 mg tetrahydrobiopterin per kilogram during 6 months alternating with placebo. Treatment-induced effects were assessed with the Childhood Autism Rating Scale every third month. The results showed small nonsignificant changes in the total scores of Childhood Autism Rating Scale after 3- and 6-month treatment. Post hoc analysis looking at the 3 core symptoms of autism, that is, social interaction, communication, and stereotyped behaviors, revealed a significant improvement of the social interaction score after 6 months of active treatment. In addition, a high positive correlation was found between response of the social interaction score and IQ. The results indicate a possible effect of tetrahydrobiopterin treatment.

  • 9.
    Danfors, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    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.
    Linnman, Clas
    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.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Increased neurokinin-1 receptor availability in temporal lobe epilepsy: A positron emission tomography study using [(11)C]GR2051712011In: Epilepsy Research, ISSN 0920-1211, E-ISSN 1872-6844, Vol. 97, no 1-2, p. 183-189Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Activation of the neurokinin-1 (NK1) receptor by neuropeptide substance P (SP) induces and maintains epileptic activity in various experimental models of epilepsy. The primary objective of this study was to investigate whether neurobiological changes linked to NK1-SP receptor system are associated with hyperexcitability in patients with temporal lobe epilepsy (TLE). A secondary objective was to investigate the relationship between seizure frequency and NK1 receptor availability.

    METHODS: A positron emission tomography study was conducted with the selective NK1 receptor antagonist [(11)C]GR205171 in nine patients with TLE and 18 healthy control participants. Parametric PET images were generated using the Patlak graphical method, with cerebellum as reference region. Data analyses including group comparisons were performed using statistical parametric mapping.

    RESULTS: Patients with TLE showed increased NK1 receptor availability in both hemispheres with the most pronounced increase in anterior cingulate gyrus ipsilateral to seizure onset. A positive correlation between NK1 receptor availability and seizure frequency was observed in the medial temporal lobe and in the lentiform nucleus ipsilateral to the seizure onset.

    CONCLUSION: Our results suggest that there is an intrinsic network using the NK1-SP receptor system for synaptic transmission and epileptiform activity in TLE.

  • 10.
    de la Vega, Maria Pagnon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Michno, Wojciech
    Univ Gothenburg, Dept Psychiat & Neurochem, S-43180 Gothenburg, Sweden.;UCL, Dept Neurosci, London WC1E 6BT, England..
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Guener, Goekhan
    Tech Univ Munich, German Ctr Neurodegenerat Dis DZNE & Neuroprote, Sch Med, Klinikum Rechts Isar, D-81377 Munich, Germany..
    Zielinski, Mara
    Forschungszentrum Julich, Inst Biol Informat Proc, Julich Ctr Struct Biol, Struct Biochem IBI 7, D-52425 Julich, Germany.;Forschungszentrum Julich, JuStruct, Julich Ctr Struct Biol, D-52425 Julich, Germany..
    Degerman Gunnarsson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Brundin, RoseMarie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Soderberg, Linda
    BioArctic AB, S-11251 Stockholm, Sweden..
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Nilsson, Lars N. G.
    Univ Oslo, Dept Pharmacol, N-0316 Oslo, Norway.;Oslo Univ Hosp, N-0316 Oslo, Norway..
    Erlandsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Willbold, Dieter
    Forschungszentrum Julich, Inst Biol Informat Proc, Julich Ctr Struct Biol, Struct Biochem IBI 7, D-52425 Julich, Germany.;Forschungszentrum Julich, JuStruct, Julich Ctr Struct Biol, D-52425 Julich, Germany.;Heinrich Heine Univ Dusseldorf, Inst Phys Biol, D-40225 Dusseldorf, Germany.;State Univ, Res Ctr Mol Mech Aging & Age Related Dis, Moscow Inst Phys & Technol, Dolgoprudnyi 141701, Russia..
    Mueller, Stephan A.
    Tech Univ Munich, German Ctr Neurodegenerat Dis DZNE & Neuroprote, Sch Med, Klinikum Rechts Isar, D-81377 Munich, Germany..
    Schroeder, Gunnar F.
    Forschungszentrum Julich, Inst Biol Informat Proc, Julich Ctr Struct Biol, Struct Biochem IBI 7, D-52425 Julich, Germany.;Forschungszentrum Julich, JuStruct, Julich Ctr Struct Biol, D-52425 Julich, Germany.;Heinrich Heine Univ Dusseldorf, Phys Dept, D-40225 Dusseldorf, Germany..
    Hanrieder, Jorg
    Univ Gothenburg, Dept Psychiat & Neurochem, S-43180 Gothenburg, Sweden.;UCL, Dept Neurodegenerat Dis, Queen Sq Inst Neurol, London WC1N 3BG, England..
    Lichtenthaler, Stefan F.
    Tech Univ Munich, German Ctr Neurodegenerat Dis DZNE & Neuroprote, Sch Med, Klinikum Rechts Isar, D-81377 Munich, Germany.;Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany..
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sehlin, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    The Uppsala APP deletion causes early onset autosomal dominant Alzheimer's disease by altering APP processing and increasing amyloid beta fibril formation2021In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 13, no 606, article id eabc6184Article in journal (Refereed)
    Abstract [en]

    Point mutations in the amyloid precursor protein gene (APP) cause familial Alzheimer's disease (AD) by increasing generation or altering conformation of amyloid beta (A beta). Here, we describe the Uppsala APP mutation (Delta 690-695), the first reported deletion causing autosomal dominant AD. Affected individuals have an age at symptom onset in their early forties and suffer from a rapidly progressing disease course. Symptoms and biomarkers are typical of AD, with the exception of normal cerebrospinal fluid (CSF) A beta 42 and only slightly pathological amyloid-positron emission tomography signals. Mass spectrometry and Western blot analyses of patient CSF and media from experimental cell cultures indicate that the Uppsala APP mutation alters APP processing by increasing beta-secretase cleavage and affecting alpha-secretase cleavage. Furthermore, in vitro aggregation studies and analyses of patient brain tissue samples indicate that the longer form of mutated A beta, A beta Upp1-42(Delta 19-24), accelerates the formation of fibrils with unique polymorphs and their deposition into amyloid plaques in the affected brain.

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

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

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  • 12.
    Fällmar, David
    et al.
    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. Univ Med Ctr Freiburg, Dept Neuroradiol, Freiburg, Germany.; Univ Geneva, Fac Med, Geneva, Switzerland.; Affidea CDRC Ctr Diagnost Radiol Carouge, Carouge, Switzerland..
    Lilja, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Hermes Med Solut, Stockholm, Sweden.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Tolboom, Nelleke
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.
    Egger, Karl
    Univ Med Ctr Freiburg, Dept Neuroradiol, Freiburg, Germany.
    Kellner, Elias
    Univ Freiburg, Dept Radiol, Med Ctr, Fac Med,Med Phys, Freiburg, Germany.
    Croon, Philip M
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.
    Verfaillie, Sander C J
    Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Med Ctr, Amsterdam, Netherlands.
    van Berckel, Bart N M
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.
    Ossenkoppele, Rik
    Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Med Ctr, Amsterdam, Netherlands.
    Barkhof, Frederik
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.; UCL, Inst Neurol & Healthcare Engn, London, England..
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Arterial spin labeling-based Z-maps have high specificity and positive predictive value for neurodegenerative dementia compared to FDG-PET.2017In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 27, no 10, p. 4237-4246Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Cerebral perfusion analysis based on arterial spin labeling (ASL) MRI has been proposed as an alternative to FDG-PET in patients with neurodegenerative disease. Z-maps show normal distribution values relating an image to a database of controls. They are routinely used for FDG-PET to demonstrate disease-specific patterns of hypometabolism at the individual level. This study aimed to compare the performance of Z-maps based on ASL to FDG-PET.

    METHODS: Data were combined from two separate sites, each cohort consisting of patients with Alzheimer's disease (n = 18 + 7), frontotemporal dementia (n = 12 + 8) and controls (n = 9 + 29). Subjects underwent pseudocontinuous ASL and FDG-PET. Z-maps were created for each subject and modality. Four experienced physicians visually assessed the 166 Z-maps in random order, blinded to modality and diagnosis.

    RESULTS: Discrimination of patients versus controls using ASL-based Z-maps yielded high specificity (84%) and positive predictive value (80%), but significantly lower sensitivity compared to FDG-PET-based Z-maps (53% vs. 96%, p < 0.001). Among true-positive cases, correct diagnoses were made in 76% (ASL) and 84% (FDG-PET) (p = 0.168).

    CONCLUSION: ASL-based Z-maps can be used for visual assessment of neurodegenerative dementia with high specificity and positive predictive value, but with inferior sensitivity compared to FDG-PET.

    KEY POINTS: • ASL-based Z-maps yielded high specificity and positive predictive value in neurodegenerative dementia. • ASL-based Z-maps had significantly lower sensitivity compared to FDG-PET-based Z-maps. • FDG-PET might be reserved for ASL-negative cases where clinical suspicion persists. • Findings were similar at two study sites.

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  • 13.
    Fällmar, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lilja, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Iyer, Victor
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Z-score maps from low-dose 18F-FDG PET of the brain in neurodegenerative dementia.2018In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 8, no 4, p. 239-246Article in journal (Refereed)
    Abstract [en]

    Neuroimaging is a central part of diagnostic work-up of patients with suspected neurodegenerative disease. FDG-PET can reveal pathological changes earlier and more reliably than morphological imaging. Diagnostic accuracy can be improved by constructing 3D SSP Z-score maps, showing patterns of significant deficits. During FDG-PET, the subject receives a moderate but not insignificant dose of ionizing radiation, and a dose reduction with retained image quality is desirable. With lower dose, repeated examinations can become a useful tool for monitoring disease progress and potential effects of disease-modifying interventions. The aim of this study was to evaluate Z-maps created from low-dose and normal-dose FDG-PET of the brain, with quantitative and qualitative methods. Nine patients with neurodegenerative disorders were prospectively enrolled and nine age-matched controls were recruited through advertising. All subjects (n=18) underwent two FDG-PET scans on separate occasions; a routine and a low-dose scan. The routine dosage of FDG was 3 MBq/kg, and low dosage was 0.75 MBq/kg. 3D-SSP images showing Z-scores of < -1.96 were created from 10-minute summations. The study was comprised of a quantitative part comparing the Z-scores, and a qualitative part where experienced nuclear medicine specialists visually assessed the images. Regarding the quantitative part, Bland-Altman analysis showed a slight constant bias (0.206). Regarding qualitative discrimination between patients and controls, the performance between normal- and low-dose were equal, both showing 72% sensitivity, 83% specificity and 78% accuracy. In this study, visual assessment of 3D-SSP Z-score maps from low-dose FDG-PET provided diagnostic information highly comparable to normal-dose, with minor quantitative discrepancies.

  • 14.
    Fällmar, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lilja, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Hermes Medical Solutions, Stockholm, Sweden..
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Validation of true low-dose 18F-FDG PET of the brain2016In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 6, no 5, p. 269-276Article in journal (Refereed)
    Abstract [en]

    The dosage of F-18-FDG must be sufficient to ensure adequate PET image quality. For younger patients and research controls, the lowest possible radiation dose should be used. The purpose of this study was to find a protocol for FDG-PET of the brain with reduced radiation dose and preserved quantitative characteristics. Eight patients with neurodegenerative disorders and nine controls (n= 17) underwent FDG-PET/ CT twice on separate occasions, first with normal-dose (3 MBq/ kg), and second with low-dose (0.75 MBq/ kg, 25% of the original). Five additional controls (total n= 22) underwent FDG-PET twice, using normal-dose and ultra-low-dose (0.3 MBq/ kg, 10% of original). All subjects underwent MRI. Ten-minute summation images were spatially normalized and intensity normalized. Regional standard uptake value ratios (SUV-r) were calculated using an automated atlas. SUV-r values from the normal-and low-dose images were compared pairwise. No clinically significant bias was found in any of the three groups. The mean absolute difference in regional SUV-r values was 0.015 (1.32%) in controls and 0.019 (1.67%) in patients. The ultra-low-dose protocol produced a slightly higher mean difference of 0.023 (2.10%). The main conclusion is that 0.75 MBq/ kg (56 MBq for a 75-kg subject) is a sufficient FDG dose for evaluating regional SUV-ratios in brain PET scans in adults with or without neurodegenerative disease, resulting in a reduction of total PET/ CT effective dose from 4.54 to 1.15 mSv. The ultra-low-dose (0.5 mSv) could be useful in research studies requiring serial PET in healthy controls or children.

  • 15.
    Fällmar, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lilja, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Velickaite, Vilma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ahlgren, André
    Lund Univ, Dept Med Radiat Phys, Lund, Sweden.
    van Osch, Matthias J P
    eiden Univ, Med Ctr, Dept Radiol, CJ Gorter Ctr High Field MRI, Leiden, Netherlands.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Visual Assessment of Brain Perfusion MRI Scans in Dementia: a Pilot Study2016In: Journal of Neuroimaging, ISSN 1051-2284, E-ISSN 1552-6569, Vol. 26, no 3, p. 324-330Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Functional imaging is becoming increasingly important for the detection of neurodegenerative disorders. Perfusion MRI with arterial spin labeling (ASL) has been reported to provide promising diagnostic possibilities but is not yet widely used in routine clinical work. The aim of this study was to compare, in a clinical setting, the visual assessment of subtracted ASL CBF maps with and without additional smoothing, to FDG-PET data.

    METHODS: Ten patients with a clinical diagnosis of dementia and 11 age-matched cognitively healthy controls were examined with pseudo-continuous ASL (pCASL) and 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET). Three diagnostic physicians visually assessed the pCASL maps after subtraction only, and after postprocessing using Gaussian smoothing and GLM-based beta estimate functions. The assessment scores were compared to FDG PET values. Furthermore, the ability to discriminate patients from healthy elderly controls was assessed.

    RESULTS: Smoothing improved the correlation between visually assessed regional ASL perfusion scores and the FDG PET SUV-r values from the corresponding regions. However, subtracted pCASL maps discriminated patients from healthy controls better than smoothed maps. Smoothing increased the number of false-positive patient identifications. Application of beta estimate functions had only a marginal effect.

    CONCLUSION: Spatial smoothing of ASL images increased false positive results in the discrimination of hypoperfusion conditions from healthy elderly. It also decreased interreader agreement. However, regional characterization and subjective perception of image quality was improved.

  • 16.
    Jonasson, My
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Frick, Andreas
    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.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Sörensen, Jens
    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.
    Development of a clinically feasible [11C]PE2I PET method for differential diagnosis of parkinsonism using reduced scan duration and automated reference region extraction.2017In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 7, no 6, p. 263-274Article in journal (Refereed)
    Abstract [en]

    [11C]PE2I is a highly selective dopamine transporter PET ligand. Parametric images based on dynamic [11C]PE2I scans, showing dopamine transporter availability (BPND) and relative cerebral blood flow (R1), can be used in differential diagnosis of parkinsonism. This work aimed to investigate a shortened scan duration and automated generation of parametric images which are two prerequisites for routine clinical application. Twelve subjects with parkinsonism and seventeen healthy controls underwent 80 min dynamic [11C]PE2I PET scans. BPND and R1 images were generated using cerebellum reference region defined on a co-registered MRI, as well as a supervised cluster analysis (SVCA)-based reference. Initial 20, 30 and 40 min of the scans were extracted and images of standardized uptake value ratio (SUVR) and R1 were computed using MRI- and SVCA-based reference. Correlation was high between striatal 80 min MRI-based BPND and 40 min SVCA-based SUVR-1 (R2=0.95). High correlation was also found between R1 values in striatal and limbic regions (R2≥0.91) whereas correlation was moderate for cortical regions (R2=0.71). The results indicate that dynamic [11C]PE2I scans can be restricted to 40 min and that SVCA can be used for automatic extraction of a reference region. These outcomes will support routine applications of [11C]PE2I PET in clinical settings.

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  • 17.
    Jonasson, My
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    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.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Furmark, Tomas
    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 Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Parametric methods for [11C]PE2I positron emission tomography2012In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 32, no S1, p. S155-S155Article in journal (Other academic)
  • 18.
    Jonasson, My
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    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.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Furmark, Tomas
    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 Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Validation of parametric methods for [(11)C]PE2I positron emission tomography2013In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 74, p. 172-178Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES

    The radioligand [(11)C]PE2I is highly selective for dopamine transporter (DAT) and can be used in vivo for investigation of changes in DAT concentration, progression of disease and validation of treatment using positron emission tomography (PET). DAT is an important protein for regulation of central dopamine concentration and DAT deficiency has been associated with several neurodegenerative and neuropsychiatric disorders. Accurate parametric images are a prerequisite for clinical application of [(11)C]PE2I. The purpose of this study was to evaluate different methods for producing [(11)C]PE2I parametric images, showing binding potential (BPND) and relative delivery (R1) at the voxel level, using clinical data as well as simulations.

    METHODS

    Investigations were made in twelve subjects either with social anxiety disorder (n=6) or parkinsonian syndrome (n=6), each receiving an 80min dynamic PET scan. All subjects underwent a T1-weighted MRI scan which was co-registered to the PET images and used for definition of regions of interest using a probabilistic template (PVElab). Two basis function implementations (receptor parametric mapping: RPM, RPM2) of the simplified reference tissue model (SRTM) and three multilinear reference tissue models (MRTMo, MRTM and MRTM2) were used for computation of parametric BPND and R1 images. In addition, reference Logan and standard uptake value ratio (SUVr) were investigated. Evaluations of BPND and R1 images were performed using linear regression to compare the parametric methods to region-based analyses with SRTM and cerebellar gray matter as reference region. Accuracy and precision of each method were assessed by simulations.

    RESULTS

    Correlation and slope of linear regression between parametric and region-based BPND and R1 values in both striatum and extra-striatal regions were optimal for RPM (R(2)=0.99 for both BPND and R1; slopes 0.99 and 0.98 for BPND and R1, respectively, in striatum). In addition, accuracy and precision were best for RPM and RPM2.

    CONCLUSION

    The basis function methods provided more robust estimations of the parameters compared to the other models and performed best in simulations. RPM, a basis function implementation of SRTM, is the preferred method for voxel level analysis of [(11)C]PE2I PET studies.

  • 19.
    Jonasson, My
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Medical Physics, Uppsala University Hospital, Uppsala, Sweden.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry.
    Fazio, Patrik
    Hjorth, Olof
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Medical Imaging Centre, Uppsala University Hospital, Uppsala, Sweden.
    Axelsson, Jan
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Medical Imaging Centre, Uppsala University Hospital, Uppsala, Sweden.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Varrone, Andrea
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Medical Imaging Centre, Uppsala University Hospital, Uppsala, Sweden.
    Striatal dopamine transporter and receptor availability correlate with relative cerebral blood flow measured with [11C]PE2I, [18F]FE-PE2I and [11C]raclopride PET in healthy individuals2023In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 43, no 7, p. 1206-1215Article in journal (Refereed)
    Abstract [en]

    The aim of this retrospective study was to investigate relationships between relative cerebral blood flow and striatal dopamine transporter and dopamine D2/3 availability in healthy subjects. The data comprised dynamic PET scans with two dopamine transporter tracers [11C]PE2I (n = 20) and [18F]FE-PE2I (n = 20) and the D2/3 tracer [11C]raclopride (n = 18). Subjects with a [11C]PE2I scan also underwent a dynamic scan with the serotonin transporter tracer [11C]DASB. Binding potential (BPND) and relative tracer delivery (R1) values were calculated on regional and voxel-level. Striatal R1 and BPND values were correlated, using either an MRI-based volume of interest (VOI) or an isocontour VOI based on the parametric BPND image. An inter-tracer comparison between [11C]PE2I BPND and [11C]DASB R1 was done on a VOI-level and simulations were performed to investigate whether the constraints of the modeling could cause correlation of the parameters. A positive association was found between BPND and R1 for all three dopamine tracers. A similar correlation was found for the inter-tracer correlation between [11C]PE2I BPND and [11C]DASB R1. Simulations showed that this relationship was not caused by cross-correlation between parameters in the kinetic model. In conclusion, these results suggest an association between resting-state striatal dopamine function and relative blood flow in healthy subjects.

  • 20.
    Jonasson, My
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Langaas, G.
    Uppsala University.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fazio, P.
    Karolinska Inst, Stockholm, Sweden.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Varrone, A.
    Karolinska Inst, Stockholm, Sweden.
    Blood Flow Dependence of Early [C-11]PE2I and [F-18]FE-PE2I PET SUVR Measurements Used In the Differential Diagnosis of Parkinsonian Disorders2018In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, p. S303-S304Article in journal (Other academic)
  • 21.
    Lindström, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Med Phys, Uppsala, Sweden..
    Lindsjö, Lars
    Uppsala Univ Hosp, PET Ctr, Uppsala, Sweden..
    Ilan, Ezgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Med Phys, Uppsala, Sweden..
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, PET Ctr, Uppsala, Sweden..
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala Univ Hosp, PET Ctr, Uppsala, Sweden..
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, PET Ctr, Uppsala, Sweden..
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging. Uppsala Univ Hosp, PET Ctr, Uppsala, Sweden..
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Med Phys, Uppsala, Sweden..
    Optimisation of penalized likelihood estimation reconstruction (Q.Clear) on a digital time-of-flight PET-CT scanner for four different PET tracers2017In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 58, no S1, article id 1355Article in journal (Other academic)
    Abstract [en]

    Objectives: The penalized likelihood estimation reconstruction algorithm Q.Clear (GE Healthcare) allows for full convergence and edge preservation through a block sequential regularized expectation maximization technique. In this study the performance of Q.Clear was investigated for different penalization factors (β) with the aim to optimize its clinical use for four different tracers.

    Methods: Q.Clear reconstructions with β values of 200, 400, 600 and 800 were compared to time-of-flight ordered subset expectation maximization (TF-OSEM) (3 iterations, 16 subsets and 5 mm Gaussian filter) with point spread function recovery. Clinical whole-body PET/CT (Discovery MI, GE Healthcare) scans with 68Ga-DOTATOC, 18F-FDG, 11C-acetate or 18F-fluoride were analyzed for level of noise in healthy liver tissue, signal to noise ratio (SNR), signal to background ratio (SBR) and maximum standardized uptake value (SUVmax). In addition, acquisition times per bed position and transaxial field of view (FOV) of the reconstructed images were varied. For each tracer, images from 10 patients were included, with a mean of 30 lesions per tracer. A spherical reference volume of interest (VOI) was placed in the liver and lesions were delineated employing a 41% threshold of the maximum voxel.

    Results: The lowest levels of noise were reached with the highest beta factor resulting in the highest SNR, but this in turn gave the lowest SBR. Noise equivalence to OSEM was found with β 600 for 68Ga-DOTATOC, 18F-FDG and 18F-fluoride, and β 400 for 11C-acetate with a resulting significant increase of SUVmax (19.4%, 9.7%, 22.5% and 19.0% respectively) (P < 0.0001, paired t-test), SNR (22.1%, 22.6%, 9.5% and 33.6%) and SBR (19.5%, 11.7%, 21.3% and 18.5%) compared to OSEM. SNR decreased while SBR increased for all tracers when extending FOV from 500 to 700 mm, but only significantly for 18F-fluoride. Decreasing image acquisition time gave no statistical difference of SUVmax for 68Ga-DOTATOC, 18F-fluoride (2 to 1.5 min) for any reconstruction method nor for 11C-acetate (3 to 2 min) with β 蠅 400. Decreasing time for 18F-FDG (3 to 2 min) resulted in a change of optimal beta to β 800 in order to reach noise equivalence to OSEM along with maintaining a higher SNR than OSEM.

    Conclusion: Images reconstructed by Q.Clear result in a tracer-dependent increase in tumour SUVmax values compared to OSEM at matched levels of noise, and an improved SNR. The optimal penalization factor, both in terms of noise-equivalence to OSEM and in terms of absolute SNR, is tracer dependent.

  • 22.
    Lindström, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Oddstig, J.
    Skane Univ Hosp, Malmo, Sweden.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Lindsjö, L.
    Uppsala Univ Hosp, Uppsala, Sweden.
    Hansson, O.
    Lund Univ, Malmo, Sweden.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Flutemetamol and FDG Brain-PET Image Reconstruction Methods Affect Software-Aided Diagnosis in Patients with Neurodegenerative Diseases2018In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, p. S305-S305Article in journal (Other academic)
  • 23.
    Lindström, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Oddstig, Jenny
    Radiation Physics, Skåne University Hospital, SE-221 85 Lund, Sweden.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Jögi, Jonas
    Clinical Physiology and Nuclear Medicine, Skåne University Hospital, SE-221 85 Lund, Sweden.
    Hansson, Oskar
    Clinical Memory Research Unit, Lund University, SE-221 00 Lund, Sweden;Memory Clinic, Skåne University Hospital, SE-205 02 Malmö, Sweden.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Image reconstruction methods affect software-aided assessment of pathologies of [18F]flutemetamol and [18F]FDG brain-PET examinations in patients with neurodegenerative diseases2020In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 28, article id 102386Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To assess how some of the new developments in brain positron emission tomography (PET) image reconstruction affect quantitative measures and software-aided assessment of pathology in patients with neurodegenerative diseases.

    METHODS: PET data were grouped into four cohorts: prodromal Alzheimer's disease patients and controls receiving [18F]flutemetamol, and neurodegenerative disease patients and controls receiving [18F]FDG PET scans. Reconstructed images were obtained by ordered-subsets expectation maximization (OSEM; 3 iterations (i), 16/34 subsets (s), 3/5-mm filter, ±time-of-flight (TOF), ±point-spread function (PSF)) and block-sequential regularized expectation maximization (BSREM; TOF, PSF, β-value 75-300). Standardized uptake value ratios (SUVR) and z-scores were calculated (CortexID Suite, GE Healthcare) using cerebellar gray matter, pons, whole cerebellum and whole brain as reference regions.

    RESULTS: In controls, comparable results to the normal database were obtained with OSEM 3i/16 s 5-mm reconstruction. TOF, PSF and BSREM either increased or decreased the relative uptake difference to the normal subjects' database within the software, depending on the tracer and chosen reference area, i.e. resulting in increased absolute z-scores. Normalizing to pons and whole brain for [18F]flutemetamol and [18F]FDG, respectively, increased absolute differences between reconstructions methods compared to normalizing to cerebellar gray matter and whole cerebellum when applying TOF, PSF and BSREM.

    CONCLUSIONS: Software-aided assessment of patient pathologies should be used with caution when employing other image reconstruction methods than those used for acquisition of the normal database.

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  • 24.
    Lindström, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Department of Medical Physics, Uppsala University Hospital, Uppsala, Sweden.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Trampal, Carlos
    Lindsjö, Lars
    Ilan, Ezgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Department of Medical Physics, Uppsala University Hospital, Uppsala, Sweden .
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. PET Centre, Uppsala University Hospital, Uppsala, Sweden.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Department of Medical Physics, Uppsala University Hospital, Uppsala, Sweden .
    Evaluation of penalized likelihood estimation reconstruction on a digital time-of-flight PET/CT scanner for 18F-FDG whole-body examinations2018In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 59, no 7, p. 1152-1158Article in journal (Refereed)
    Abstract [en]

    The resolution and quantitative accuracy of PET are highly influenced by the reconstruction method. Penalized-likelihood estimation algorithms allow for fully convergent iterative reconstruction, generating a higher image contrast than ordered-subsets expectation maximization (OSEM) while limiting noise. In this study, a type of penalized reconstruction known as block-sequential regularized expectation maximization (BSREM) was compared with time-of-flight OSEM (TOF OSEM). Various strengths of noise penalization factor β were tested along with various acquisition durations and transaxial fields of view (FOVs) with the aim of evaluating the performance and clinical use of BSREM for 18F-FDG PET/CT, both quantitatively and in a qualitative visual evaluation. Methods: Eleven clinical whole-body 18F-FDG PET/CT examinations acquired on a digital TOF PET/CT scanner were included. The data were reconstructed using BSREM with point-spread function recovery and β-factors of 133, 267, 400, and 533—and using TOF OSEM with point-spread function—for various acquisition times per bed position and various FOVs. Noise level, signal-to-noise ratio (SNR), signal-to-background ratio (SBR), and SUV were analyzed. A masked evaluation of visual image quality, rating several aspects, was performed by 2 nuclear medicine physicians to complement the analysis. Results: The lowest levels of noise were reached with the highest β-factor, resulting in the highest SNR, which in turn resulted in the lowest SBR. A β-factor of 400 gave noise equivalent to TOF OSEM but produced a significant increase in SUVmax (11%), SNR (22%), and SBR (12%). BSREM with a β-factor of 533 at a decreased acquisition duration (2 min/bed position) was comparable to TOF OSEM at a full acquisition duration (3 min/bed position). Reconstructed FOV had an impact on BSREM outcome measures; SNR increased and SBR decreased when FOV was shifted from 70 to 50 cm. The evaluation of visual image quality resulted in similar scores for reconstructions, although a β-factor of 400 obtained the highest mean whereas a β-factor of 267 was ranked best in overall image quality, contrast, sharpness, and tumor detectability. Conclusion: In comparison with TOF OSEM, penalized BSREM reconstruction resulted in an increased tumor SUVmax and an improved SNR and SBR at a matched level of noise. BSREM allowed for a shorter acquisition than TOF OSEM, with equal image quality.

  • 25.
    Lubberink, Mark
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Gaging, Johannes
    Uppsala Univ, Uppsala, Sweden..
    Lindskog, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Tracer kinetic analysis of the SV2A ligand 11C-UCBA as a PET marker for synaptic density in humans2017In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 58, no S1, article id 631Article in journal (Other academic)
    Abstract [en]

    Objectives: Quantitative imaging of the synaptic vesicle glycoprotein 2A (SV2A) with PET can be used as a measure of synaptic density in the human brain (Finnema et al, Science Tr Med 2016), changes of which occur in many neurodegenerative diseases. 11C-UCBA has previously been validated as an SV2A tracer in pigs (Estrada et al, Nucl Med Biol 2016), showing dose-dependent blocking and reversible binding. The aim of the present work was to evaluate tracer kinetic models and simplified methods for quantification of synaptic density using 11C-UCBA in humans.

    Methods: Eight subjects (6 epilepsy patients, 2 controls) underwent 90 min PET scans starting with injection of 5 MBq/kg 11C-UCBA on a time-of-flight integrated PET-MR scanner (Signa PET-MR, GE Healthcare). Arterial blood was withdrawn for measurements of whole blood and plasma concentrations and metabolite analysis. Images were reconstructed using zero-echo-time MR-based attenuation correction, accounting for bone attenuation. A probabilistic VOI template was defined on a T1-MRI image, acquired during the PET scan, and transferred to the dynamic PET images. A centrum semiovale VOI was drawn as potential reference tissue. Data were analysed using single-tissue (1T2k), two-tissue irreversible (2T3k) and reversible (2T4k) models, as well as the simplified reference tissue model (SRTM) and plasma- and reference-Logan methods, resulting in total distribution volume (VT) and binding potential (BPND) values, with binding potential both estimated directly and as distribution volume ratio to centrum semiovale (DVR). The optimal compartment model was determined using the Akaike information criterion (AIC). Standardized uptake value ratios (SUVR) at various time points were compared to modelling outcomes using regression analysis.

    Results: Plasma and brain kinetics of 11C-UCBA were slow, with peak activity in brain at 70-80 min. Parent fraction was approximately 50% at 90 min. Plasma-input data were best described using the 2T4k model, but this could often not provide robust VT or BPND values. Mean plasma-Logan VT was 24±17. Plasma-Logan DVR using centrum semiovale as reference tissue correlated well with 2T4k DVR (R2 0.94) for those regions where robust DVR values could be determined. Reference-Logan DVR showed good correlation with plasma-Logan DVR (R2 0.72). Plasma-Logan DVR-1 and SUVR-1 images are shown in Figure 1. SUVR for the 40-60 and 70-90 min intervals correlated well with reference-Logan DVR (R2 0.92 and 0.98).

    Conclusion: Slow kinetics of 11C-UCBA resulted in poor robustness of outcome parameters of reversible compartment models. However, reference-Logan DVR correlated well with plasma-Logan DVR. SUVR at 70-90 min p.i. correlated well with DVR and may be used as a simplified measure of synaptic density using 11C-UCBA. Research Support: Uppsala County Council

  • 26.
    Lubberink, Mark
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Med Phys..
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Med Imaging Ctr..
    Lindskog, K.
    Uppsala Univ Hosp, Med Phys..
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Med Imaging Ctr..
    Sprycha, M.
    Uppsala Univ Hosp, Med Imaging Ctr..
    Daging, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala Univ Hosp, Neurol..
    Eriksson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry. Uppsala Univ Hosp, Med Imaging Ctr..
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Med Imaging Ctr..
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala Univ Hosp, Neurol..
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging. Uppsala Univ Hosp, Med Imaging Ctr..
    Quantitative assessment of synaptic density using the SV2A ligand C-11-UCBA in humans2017In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, p. 74-74Article in journal (Other academic)
  • 27.
    Lubberink, Mark
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Widström, Charles
    Uppsala Univ Hosp, Uppsala, Sweden.
    Jonasson, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Appel, Lieuwe
    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. Uppsala Univ Hosp, Uppsala, Sweden.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala Univ Hosp, Uppsala, Sweden.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Uppsala, Sweden.
    Differential diagnosis of patients with parkinsonian syndrome using multilinear regression to disease-specific C-11-PE2I-PET templates and classification tree learning2018In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, p. S409-S409Article in journal (Other academic)
  • 28.
    Niemelä, Valter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Salih, Ammar
    Västerås Hosp, Dept Neurol, Västerås, Sweden..
    Solea, Daniela
    Gävle Cent Hosp, Dept Neurol, Gävle, Sweden..
    Lindvall, Bjoern
    Univ Hosp, Dept Neurol, Örebro, Sweden..
    Weinberg, Jan
    Karolinska Univ Hosp, Dept Neurol, Stockholm, Sweden..
    Miltenberger, Gabriel
    Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany..
    Granberg, Tobias
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Radiol, Stockholm, Sweden..
    Tzovla, Aikaterini
    Karolinska Univ Hosp, Dept Radiol, Stockholm, Sweden..
    Nordin, Love
    Karolinska Univ Hosp Solna, Dept Diagnost Med Phys, Stockholm, Sweden.;Karolinska Inst, Div Clin Geriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Savitcheva, Irina
    Karolinska Univ Hosp, Dept Med Radiat Phys & Nucl Med, Stockholm, Sweden..
    Dahl, Niklas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden..
    Paucar, Martin
    Karolinska Univ Hosp, Dept Neurol, Stockholm, Sweden.;Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Phenotypic variability in chorea-acanthocytosis associated with novel VPS13A mutations2020In: NEUROLOGY-GENETICS, ISSN 2376-7839, Vol. 6, no 3, article id e426Article in journal (Refereed)
    Abstract [en]

    ObjectiveTo perform a comprehensive characterization of a cohort of patients with chorea-acanthocytosis (ChAc) in Sweden.MethodsClinical assessments, targeted genetic studies, neuroimaging with MRI, [F-18]-fluorodeoxyglucose (FDG) PET, and dopamine transporter with I-123 FP-CIT (DaTscan) SPECT. One patient underwent magnetic resonance spectroscopy (MRS).ResultsFour patients living in Sweden but with different ethnical backgrounds were included. Their clinical features were variable. Biallelic VPS13A mutations were confirmed in all patients, including 3 novel mutations. All tested patients had either low or absent chorein levels. One patient had progressive caudate atrophy. Investigation using FDG-PET revealed severe bilateral striatal hypometabolism, and DaTscan SPECT displayed presynaptic dopaminergic deficiency in 3 patients. MRS demonstrated reduced N-acetylaspartate/creatine (Cr) ratio and mild elevation of both choline/Cr and combined glutamate and glutamine/Cr in the striatum in 1 case. One patient died during sleep, and another was treated with deep brain stimulation, which transiently attenuated feeding dystonia but not his gait disorder or chorea.ConclusionsLarger longitudinal neuroimaging studies with different modalities, particularly MRS, are needed to determine their potential role as biomarkers for ChAc.

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  • 29.
    Pagnon de la Vega, María
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Michno, Wojciech
    Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden .
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Güner, Gökhan
    German Center for Neurodegenerative Diseases (DZNE) and Neuroproteomics, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany .
    Zielinski, Mara
    Institute of Biological Information Processing, Structural Biochemistry (IBI-7) and JuStruct, Jülich Center for Structural Biology, Forschungszentrum Jülich, 52425 Jülich, Germany.
    Löwenmark, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Brundin, RoseMarie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Söderberg, Linda
    BioArctic AB, Stockholm, Sweden.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Nilsson, Lars
    Department of Pharmacology, University of Oslo and Oslo University Hospital, Oslo, Norway.
    Erlandsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Willbold, Dieter
    Institute of Biological Information Processing, Structural Biochemistry (IBI-7) and JuStruct, Jülich Center for Structural Biology, Forschungszentrum Jülich, 52425 Jülich, Germany .
    Müller, Stephan A.
    German Center for Neurodegenerative Diseases (DZNE) and Neuroproteomics, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany .
    Schöder, Gunnar F.
    Institute of Biological Information Processing, Structural Biochemistry (IBI-7) and JuStruct, Jülich Center for Structural Biology, Forschungszentrum Jülich, 52425 Jülich, Germany .
    Hanrieder, Jörg
    Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden .
    Lichtenthaler, Stefan F.
    German Center for Neurodegenerative Diseases (DZNE) and Neuroproteomics, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany .
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sehlin, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    The Uppsala APP deletion causes early onset autosomal dominant Alzheimer’s disease by altering APP processing and increasing amyloid-β fibril formationIn: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Science Translational MedicineArticle in journal (Other academic)
  • 30.
    Romanos Zapata, Romina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Differential diagnosis of therapy-related changes and recurrent intracranial tumours using perfusion MRI and methionine PET2014In: Insights into Imaging, E-ISSN 1869-4101, Vol. 5, no Suppl 1, p. S239-, article id B-0485Article in journal (Refereed)
  • 31.
    Roodakker, Kenney Roy
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Alhuseinalkhudhur, Ali
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Al-Jaff, Mohammed
    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.
    Georganaki, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    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.
    Danfors, Torsten
    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, 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.
    Edqvist, Per-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dimberg, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Region-by-region analysis of PET, MRI, and histology in en bloc-resected oligodendrogliomas reveals intra-tumoral heterogeneity2019In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 46, no 3, p. 569-579Article in journal (Refereed)
  • 32.
    Ryttlefors, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Latini, Francesco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Montelius, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Gudjonsson, Olafur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Long-term evaluation of the effect of hypofractionated high-energy proton treatment of benign meningiomas by means of (11)C-L-methionine positron emission tomography2016In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, no 8, p. 1432-1443Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To determine if (11)C-L-methionine PET is a useful tool in the evaluation of the long-term effect of proton beam treatment in patients with meningioma remnant.

    METHODS: Included in the study were 19 patients (4 men, 15 women) with intracranial meningioma remnants who received hypofractionated high-energy proton beam treatment. Patients were examined with (11)C-L-methionine PET and MRI prior to treatment and after 6 months, and 1, 2, 3, 5, 7 and 10 years. Temporal changes in methionine uptake ratio, meningioma volume, meningioma regrowth and clinical symptoms throughout the follow-up period were evaluated.

    RESULTS: In 17 patients the tumour volume was unchanged throughout the follow-up. The methionine uptake ratio on PET decreased over the years in most patients. In two patients the tumour remnant showed progression on MRI. In these patients, prior to the volume increase on MRI, the methionine uptake ratio increased. One patient experienced transient clinical symptoms and showed radiological evidence of a radiation-induced reaction close to the irradiated field.

    CONCLUSION: Proton beam treatment is a safe and effective treatment for achieving long-term growth arrest in meningioma remnants. Follow-up with (11)C-L-methionine PET may be a valuable adjunct to, but not a replacement for, standard radiological follow-up.

  • 33.
    Sousa, Joao M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Papadimitriou, S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Delso, G.
    GE Healthcare, Zurich, Switzerland..
    Wiesinger, F.
    GE Healthcare, Zurich, Switzerland..
    Ahlström, Håkan
    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.
    Validation of Zero-Echo Time PET-MR against stand-alone PET using dynamic dopamine transporter imaging2016In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, p. S79-S79Article in journal (Refereed)
  • 34.
    Stanisic, Milo
    et al.
    Oslo Univ Hosp, Rikshosp, Dept Neurosurg, N-0027 Oslo, Norway..
    Coello, Christopher
    Oslo Univ Hosp, PET Core Facil, PET Ctr, N-0027 Oslo, Norway..
    Ivanovic, Jugoslav
    Oslo Univ Hosp, Rikshosp, Dept Neurosurg, N-0027 Oslo, Norway..
    Egge, Arild
    Oslo Univ Hosp, Rikshosp, Dept Neurosurg, N-0027 Oslo, Norway..
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hald, John
    Oslo Univ Hosp, Dept Radiol, N-0027 Oslo, Norway..
    Heminghyt, Einar
    Oslo Univ Hosp, Dept Clin Psychol & Neuropsychol, Natl Ctr Epilepsy, N-0027 Oslo, Norway..
    Mikkelsen, Marjan Makki
    Oslo Univ Hosp, Dept Adult Epilepsy, Natl Ctr Epilepsy, N-0027 Oslo, Norway..
    Krossnes, Bard Kronen
    Oslo Univ Hosp, Dept Pathol, N-0027 Oslo, Norway..
    Pripp, Are Hugo
    Oslo Univ Hosp, Oslo Ctr Biostat & Epidemiol, Res Support Serv, N-0027 Oslo, Norway..
    Larsson, Pal Gunnar
    Oslo Univ Hosp, Dept Neurosurg, Clin Neurophysiol Labs, N-0027 Oslo, Norway..
    Seizure outcomes in relation to the extent of resection of the perifocal fluorodeoxyglucose and flumazenil PET abnormalities in anteromedial temporal lobectomy2015In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 157, no 11, p. 1905-1916Article in journal (Refereed)
    Abstract [en]

    The area of predominant perifocal [F-18]fluorodeoxyglucose (F-18-FDG) hypometabolism and reduced [C-11]flumazenil (C-11-FMZ) -binding on PET scans is currently considered to contain the epileptogenic zone and corresponds anatomically to the area localizing epileptogenicity in patients with temporal lobe epilepsy (TLE). The question is whether the volume of the perifocal pre-operative PET abnormalities, the extent of their resection, and the volume of the non-resected abnormalities affects the post-operative seizure outcome. The sample group consisted of 32 patients with mesial temporal sclerosis who underwent anteromedial temporal lobe resection for refractory TLE. All patients had pathologic perifocal findings on both of the PET modalities as well as on the whole-brain MRI. The volumetric data of the PET and MRI abnormalities within the resected temporal lobe were estimated by automated quantitative voxel-based analysis. The obtained volumetric data were investigated in relation to the outcome subgroups of patients (Engel classification) determined at the 2-year post-operative follow-up. The mean volume of the pre-operative perifocal F-18-FDG- and C-11-FMZ PET abnormalities in the volumes of interest (VOI) of the epileptogenic temporal lobe, the mean resected volume of these PET abnormalities, the mean volume of the non-resected PET abnormalities, and the mean MRI-derived resected volume were not significantly related to the outcome subgroups and had a low prediction for individual freedom from seizures. The extent of pre-surgical perifocal PET abnormalities, the extent of their resection, and the extent of non-resected abnormalities were not useful predictors of individual freedom from seizures in patients with TLE.

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  • 35.
    Syk, Mikaela
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Malmström, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Gallwitz, Maike
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Amandusson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rostedt Punga: Clinical Neurophysiology.
    Rothkegel, Holger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rostedt Punga: Clinical Neurophysiology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Thulin, Måns
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics.
    Rasmusson, Annica J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Cervenka, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Nilsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Cunningham, Janet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Biological markers for CNS damage in a patient cohort with suspected autoimmune psychiatric diseaseManuscript (preprint) (Other academic)
    Abstract [en]

    Background: This study describes the prevalence of CNS damage biomarkers and other CNS pathology in a psychiatric patient cohort enriched for clinical red flags of suspected autoimmune psychiatric disease. The study further explores how CNS damage biomarkers relate to clinical red flags and psychiatric features. 

    Methods: 127 patients were included in the study. A routine cerebrospinal fluid (CSF) analysis was performed and anti-neuronal antibodies were measured.  CNS damage biomarkers (neurofilament light chain protein (NfL), glial fibrillary acidic protein (GFAp) and total Tau (t-Tau)) in CSF were related to proposed clinical red flags for autoimmune psychiatric disease, other psychiatric features and MRI and EEG findings. 

    Results: Twenty-seven per cent had elevated levels of CNS damage biomarkers and 21% had basic CSF analysis alterations. Six per cent had anti-neuronal antibodies in serum and 2% in CSF. Fifty percent of patients examined with MRI (n=88) had signs of atrophy and 41% had white matter changes. Twenty-five percent of patients with EEG recordings (n=70) had pathological EEG findings. Elevated NfL, GFAp and t-Tau levels were associated with the presence of clinical red flags. Elevated GFAp and t-Tau were also associated with higher psychiatric symptom ratings.

    Conclusions: Pre-selection based on clinical red flags for autoimmune psychiatric disease identifies a population where 27% have CSF signs of CNS tissue damage, 21% have CSF alterations suggesting neuroinflammation or blood-brain barrier dysfunction and 6% have anti-neuronal antibodies. Moreover, pathological levels of NfL, GFAp or t-Tau in CSF may be related to distinctive red flags and patterns of psychiatric manifestations. 

  • 36.
    Syk, Mikaela
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry.
    Tornvind, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry.
    Gallwitz, Maike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry.
    Fällmar, David
    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 Surgical Sciences, Neuroradiology.
    Amandusson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Neurophysiology.
    Rothkegel, Holger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Neurophysiology.
    Danfors, Torsten
    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 Surgical Sciences, Molecular imaging and medical physics.
    Thulin, Måns
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics.
    Rasmusson, Annica J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry.
    Cervenka, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry. Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden.;Stockholm Hlth Care Serv, Stockholm, Sweden..
    Pollak, Thomas A.
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychosis Studies, London, England..
    Endres, Dominique
    Univ Freiburg, Fac Med, Med Ctr, Dept Psychiat & Psychotherapy, Freiburg, Germany..
    van Elst, Ludger Tebartz
    Univ Freiburg, Fac Med, Med Ctr, Dept Psychiat & Psychotherapy, Freiburg, Germany..
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry.
    Nilsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cunningham, Janet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry.
    An exploratory study of the damage markers NfL, GFAP, and t-Tau, in cerebrospinal fluid and other findings from a patient cohort enriched for suspected autoimmune psychiatric disease2024In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 14, no 1, article id 304Article in journal (Refereed)
    Abstract [en]

    There is growing evidence suggesting that immunological mechanisms play a significant role in the development of psychiatric symptoms in certain patient subgroups. However, the relationship between clinical red flags for suspected autoimmune psychiatric disease and signs of central nervous system (CNS) pathology (e.g., routine cerebrospinal fluid (CSF) alterations, CNS damage markers, neurophysiological or neuroimaging findings) has received limited attention. Here, we aimed to describe the prevalence and distribution of potential CNS pathologies in psychiatric patients in relation to clinical red flags for autoimmune psychiatric disease and psychiatric symptoms. CSF routine findings and CNS damage markers; neurofilament light chain protein (NfL), glial fibrillary acidic protein (GFAP) and total Tau (t-Tau), in CSF from 127 patients with psychiatric disease preselected for suspected immunological involvement were related to recently proposed clinical red flags, psychiatric features, and MRI and EEG findings. Twenty-one percent had abnormal routine CSF findings and 27% had elevated levels of CNS damage markers. Six percent had anti-neuronal antibodies in serum and 2% had these antibodies in the CSF. Sixty-six percent of patients examined with MRI (n = 88) had alterations, mostly atrophy or nonspecific white matter lesions. Twenty-seven percent of patients with EEG recordings (n = 70) had abnormal findings. Elevated NfL levels were associated with comorbid autoimmunity and affective dysregulation symptoms. Elevated t-Tau was associated with catatonia and higher ratings of agitation/hyperactivity. Elevated GFAP was associated with acute onset, atypical presentation, infectious prodrome, tics, depressive/anxiety symptom ratings and overall greater psychiatric symptom burden. In conclusion, preselection based on suspected autoimmune psychiatric disease identifies a population with a high prevalence of CSF alterations suggesting CNS pathology. Future studies should examine the value of these markers in predicting treatment responses.

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  • 37.
    Tolf, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Experimental neurology.
    Hedman, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Experimental neurology.
    Granberg, Tobias
    Department of Clinical Neuroscience, Karolinska Institutet.
    Fagius, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Experimental neurology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Experimental neurology.
    Cerebral blood flow in multiple sclerosis: an 15O-water PET studyManuscript (preprint) (Other academic)
  • 38.
    Xiong, Mengfei
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Molecular imaging and medical physics. 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, Molecular imaging and medical physics. 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, Molecular imaging and medical physics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fang, Xiaotian Tsong
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Molecular imaging and medical physics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Julius Clin BV, Zeist, Netherlands..
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Molecular imaging and medical physics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Evaluation of [11C]UCB-A positron emission tomography in human brains2024In: EJNMMI Research, E-ISSN 2191-219X, Vol. 14, no 1, article id 56Article in journal (Refereed)
    Abstract [en]

    Background: In preclinical studies, the positron emission tomography (PET) imaging with [C-11]UCB-A provided promising results for imaging synaptic vesicle protein 2A (SV2A) as a proxy for synaptic density. This paper reports the first-in-human [C-11]UCB-A PET study to characterise its kinetics in healthy subjects and further evaluate SV2A-specific binding.

    Results: Twelve healthy subjects underwent 90-min baseline [C-11]UCB-A scans with PET/MRI, with two subjects participating in an additional blocking scan with the same scanning procedure after a single dose of levetiracetam (1500 mg). Our results indicated abundant [C-11]UCB-A brain uptake across all cortical regions, with slow elimination. Kinetic modelling of [C-11]UCB-A PET using various compartment models suggested that the irreversible two-tissue compartment model best describes the kinetics of the radioactive tracer. Accordingly, the Patlak graphical analysis was used to simplify the analysis. The estimated SV2A occupancy determined by the Lassen plot was around 66%. Significant specific binding at baseline and comparable binding reduction as grey matter precludes the use of centrum semiovale as reference tissue.

    Conclusions: [C-11]UCB-A PET imaging enables quantifying SV2A in vivo. However, its slow kinetics require a long scan duration, which is impractical with the short half-life of carbon-11. Consequently, the slow kinetics and complicated quantification methods may restrict its use in humans.

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    FULLTEXT01
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