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  • 1.
    Andersson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Karpe, Fredrik
    NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, UK.
    Sjöström, Lars-Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Association of adipose tissue blood flow with fat depot sizes and adipokines in women2012In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 36, no 6, p. 783-789Article in journal (Refereed)
    Abstract [en]

    Objective: To explore possible associations between adipose tissue (AT) blood flow (ATBF), AT depot sizes and adipocyte-derived hormones (adipokines) in women.

    Subjects: In all, 43 healthy women were divided into four groups: normal-weight (n=11) and obese (n=11) pre-menopausal women and normal-weight (n=10) and obese (n=11) post-menopausal women.

    Methods: Fasting levels of adipokines were obtained, and a single-slice computed tomography scan at the level of L4-L5 was used to estimate fat depot sizes. ATBF was assessed by xenon washout while in a fasting state and after oral glucose load. We also measured glucose, insulin and non-esterified fatty acids.

    Results: Total, subcutaneous and visceral AT areas strongly correlated with ATBF (all P<0.001). Circulating leptin levels strongly and inversely correlated with ATBF (P=0.001), but this association did not remain after adjustment for body mass index. Adiponectin was not associated with blood flow.

    Conclusion: ATBF is closely linked to subcutaneous and visceral AT size. Further analyses are needed to determine possible mediators of this association, including mechanistic studies to assess a putative role for leptin as a significant modulator of blood flow. International Journal of Obesity advance online publication, 26 July 2011; doi:10.1038/ijo.2011.152.

  • 2.
    Andersson, Ronny
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Hofer, Åke
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Dermatology and Venerology.
    Riklund-Åhlström, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Effects of interferon-[alpha], verapamil and dacarbazine in the treatment of advanced malignant melanoma2003In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 13, no 1, p. 87-91Article in journal (Refereed)
    Abstract [en]

    Treatment of patients with metastatic melanoma with either dacarbazine (DTIC) or interferon-[alpha] (IFN[alpha]) as single drugs, or in combination, results in a response rate of approximately 15–20%. This study evaluated the activity and toxicity following treatment with a combination of DTIC, IFN[alpha]2b and verapamil (VPL). Thirty patients with disseminated metastatic melanoma received DTIC 250 mg/m2 on days 1–5 of a 4 week schedule, IFN[alpha]2b 3 MIU on days 1–5 each week, and VPL 80 mg three times a day throughout the cycle, until either disease progression or serious toxicity was observed. Among the 28 evaluable patients, there were four complete responses (CRs), five partial responses (PRs) and eight patients with stable disease (SD). The overall response rate (CR + PR) was 32%. Two patients with a CR were long-term survivors (45 and 34 months) and a third is still in complete remission after 49 months. The fourth CR patient relapsed and died with progressive brain metastases after 8 months. Among the eight patients with SD, one survived for 22 months and another for 34 months. Despite one toxic death, these results suggest that this treatment regimen is well tolerated and seems to be more effective than DTIC alone in a subset of patients. A controlled randomized study would be required to determine the value of adding VPL and IFN[alpha]2b to DTIC.

  • 3. Arheden, Håkan
    et al.
    Aspelin, Peter
    Bajc, Marika
    Damm, Sabine
    Flodmark, Olof
    Friberg, Peter
    Gustafsson, Lars
    Holtås, Stig
    Modin, Agnes
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Rydh, Anders
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Functional imaging medicine: a new specialty with great prospects2006In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, no 39, p. 2883-2884Article in journal (Refereed)
  • 4.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergström, Åsa
    Kasper, Maria
    Ögren, Margareta
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Toftgård, Rune
    Riklund, Katrine Åhlström
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Early and persisting response to vismodegib in a patient with bone metastasizing medulloblastoma2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 4, p. 862-865Article in journal (Refereed)
  • 5.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Shahidi, Saeed
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Durable stabilization of three chordoma cases by bevacizumab and erlotinib2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 7, p. 980-984Article in journal (Refereed)
  • 6. Bailey, D. L.
    et al.
    Pichler, B. J.
    Gueckel, B.
    Antoch, G.
    Barthel, H.
    Bhujwalla, Z. M.
    Biskup, S.
    Biswal, S.
    Bitzer, M.
    Boellaard, R.
    Braren, R. F.
    Brendle, C.
    Brindle, K.
    Chiti, A.
    la Fougere, C.
    Gillies, R.
    Goh, V.
    Goyen, M.
    Hacker, M.
    Heukamp, L.
    Knudsen, G. M.
    Krackhardt, A. M.
    Law, I.
    Morris, J. C.
    Nikolaou, K.
    Nuyts, J.
    Ordonez, A. A.
    Pantel, K.
    Quick, H. H.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Sabri, O.
    Sattler, B.
    Troost, E. G. C.
    Zaiss, M.
    Zender, L.
    Beyer, Thomas
    Combined PET/MRI: Global Warming-Summary Report of the 6th International Workshop on PET/MRI, March 27-29, 2017, Tubingen, Germany2018In: Molecular Imaging and Biology, ISSN 1536-1632, E-ISSN 1860-2002, Vol. 20, no 1, p. 4-20Article, review/survey (Refereed)
    Abstract [en]

    The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tubingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we are in a position to describe the in vivo nature of disease processes, metabolism, evolution of cancer and the monitoring of response to pharmacological interventions and therapies. As such, PET/MRI is a key to advancing medicine and patient care.

  • 7. Bailey, D. L.
    et al.
    Pichler, B. J.
    Gueckel, B.
    Barthel, H.
    Beer, A. J.
    Botnar, R.
    Gillies, R.
    Goh, V.
    Gotthardt, M.
    Hicks, R. J.
    Lanzenberger, R.
    la Fougere, C.
    Lentschig, M.
    Nekolla, S. G.
    Niederdraenk, T.
    Nikolaou, K.
    Nuyts, J.
    Olego, D.
    Åhlstrom Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Signore, A.
    Schaefers, M.
    Sossi, V.
    Suminski, M.
    Veit-Haibach, P.
    Umutlu, L.
    Wissmeyer, M.
    Beyer, T.
    Combined PET/MRI: from Status Quo to Status Go. Summary Report of the Fifth International Workshop on PET/MR Imaging; February 15-19, 2016; Tubingen, Germany2016In: Molecular Imaging and Biology, ISSN 1536-1632, E-ISSN 1860-2002, Vol. 18, no 5, p. 637-650Article in journal (Refereed)
    Abstract [en]

    This article provides a collaborative perspective of the discussions and conclusions from the fifth international workshop of combined positron emission tomorgraphy (PET)/magnetic resonance imaging (MRI) that was held in Tubingen, Germany, from February 15 to 19, 2016. Specifically, we summarise the second part of the workshop made up of invited presentations from active researchers in the field of PET/MRI and associated fields augmented by round table discussions and dialogue boards with specific topics. This year, this included practical advice as to possible approaches to moving PET/MRI into clinical routine, the use of PET/MRI in brain receptor imaging, in assessing cardiovascular diseases, cancer, infection, and inflammatory diseases. To address perceived challenges still remaining to innovatively integrate PET and MRI system technologies, a dedicated round table session brought together key representatives from industry and academia who were engaged with either the conceptualisation or early adoption of hybrid PET/MRI systems. Discussions during the workshop highlighted that emerging unique applications of PET/MRI such as the ability to provide multi-parametric quantitative and visual information which will enable not only overall disease detection but also disease characterisation would eventually be regarded as compelling arguments for the adoption of PET/MR. However, as indicated by previous workshops, evidence in favour of this observation is only growing slowly, mainly due to the ongoing inability to pool data cohorts from independent trials as well as different systems and sites. The participants emphasised that moving from status quo to status go entails the need to adopt standardised imaging procedures and the readiness to act together prospectively across multiple PET/MRI sites and vendors.

  • 8.
    Bergdahl, Jan
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nilsson, Lars-Göran
    Riklund Åhlström, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Treatment of chronic stress in employees: subjective, cognitive and neural correlates2005In: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 46, no 5, p. 395-402Article in journal (Refereed)
    Abstract [en]

    This study reports the effect of an affect-focused intervention program, the Affect School, on stress, psychological symptoms, cognitive functioning and neural activity. Fifty employees in social service and education, with high levels of chronic stress, were randomly divided into a treatment (N= 27) and control (N= 23) group. Complete sets of data were available in 20 participants in the treatment group and 17 in the control group. The Perceived Stress Questionnaire assessed stress and the Symptom Check List-90 psychological symptoms before and after treatment. Episodic-memory functioning under focused and divided attention conditions was also assessed. Prior and after the Affect School, seven participants in the treatment group were studied with functional magnetic resonance imaging (fMRI) during episodic memory processing. After the Affect School there was a reduction in stress and psychological symptoms for the treatment group but not in the control group. The controls showed a reduction in episodic memory functioning whereas the performance of the treatment group remained intact. The fMRI scanning indicated a qualitative change in the neural network subserving episodic memory. These preliminary results suggest that the Affect School is effective on individuals with high stress.

  • 9. Brolin, Gustav
    et al.
    Edenbrandt, Lars
    Granerus, Goeran
    Olsson, Anna
    Afzelius, David
    Gustafsson, Agneta
    Jonsson, Cathrine
    Hagerman, Jessica
    Johansson, Lena
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. EQUALIS AB, Uppsala, Sweden.
    Ljungberg, Michael
    The accuracy of quantitative parameters in Tc-99m-MAG3 dynamic renography: a national audit based on virtual image data2016In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 36, no 2, p. 146-154Article in journal (Refereed)
    Abstract [en]

    Assessment of image analysis methods and computer software used in Tc-99m-MAG3 dynamic renography is important to ensure reliable study results and ultimately the best possible care for patients. In this work, we present a national multicentre study of the quantification accuracy in Tc-99m-MAG3 renography, utilizing virtual dynamic scintigraphic data obtained by Monte Carlo-simulated scintillation camera imaging of digital phantoms with time-varying activity distributions. Three digital phantom studies were distributed to the participating departments, and quantitative evaluation was performed with standard clinical software according to local routines. The differential renal function (DRF) and time to maximum renal activity (T-max) were reported by 21 of the 28 Swedish departments performing Tc-99m-MAG3 studies as of 2012. The reported DRF estimates showed a significantly lower precision for the phantom with impaired renal uptake than for the phantom with normal uptake. The T-max estimates showed a similar trend, but the difference was only significant for the right kidney. There was a significant bias in the measured DRF for all phantoms caused by different positions of the left and right kidney in the anterior-posterior direction. In conclusion, this study shows that virtual scintigraphic studies are applicable for quality assurance and that there is a considerable uncertainty associated with standard quantitative parameters in dynamic Tc-99m-MAG3 renography, especially for patients with impaired renal function.

  • 10.
    Bäckström, David C
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Jakobson Mo, Susanna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Zetterberg, Henrik
    Blennow, Kaj
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lenfeldt, Niklas
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Neurofilament concentration in CSF correlates with disease severity, survival and imaging measures of neurodegeneration in incident Parkinson diseaseManuscript (preprint) (Other academic)
  • 11.
    Bäckström, David
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Eriksson Domellöf, Magdalenax
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Jakobson Mo, Susanna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Zetterberg, Henrik
    Blennow, Kaj
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Early predictors of mortality in parkinsonism and Parkinson disease: A population-based study2018In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 91, no 22, p. E2045-E2056Article in journal (Refereed)
    Abstract [en]

    Objective To examine mortality and associated risk factors, including possible effects of mild cognitive impairment, imaging, and CSF abnormalities, in a community-based population with incident parkinsonism and Parkinson disease. Methods One hundred eighty-two patients with new-onset, idiopathic parkinsonism were diagnosed from January 2004 through April 2009, in a catchment area of 142,000 inhabitants in Sweden. Patients were comprehensively investigated according to a multimodal research protocol and followed prospectively for up to 13.5 years. A total of 109 patients died. Mortality rates in the general Swedish population were used to calculate standardized mortality ratio and expected survival, and Cox proportional hazard models were used to investigate independent predictors of mortality. Results The standardized mortality ratio for all patients was 1.84 (95% confidence interval 1.50-2.22, p < 0.001). Patients with atypical parkinsonism (multiple system atrophy or progressive supranuclear palsy) had the highest mortality. In early Parkinson disease, a mild cognitive impairment diagnosis, freezing of gait, hyposmia, reduced dopamine transporter activity in the caudate, and elevated leukocytes in the CSF were significantly associated with shorter survival. Conclusion Although patients presenting with idiopathic parkinsonism have reduced survival, the survival is highly dependent on the type and characteristics of the parkinsonian disorder. Patients with Parkinson disease presenting with normal cognitive function seem to have a largely normal life expectancy. The finding of a subtle CSF leukocytosis in patients with Parkinson disease with short survival may have clinical implications.

  • 12. de Boer, Lieke
    et al.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Chowdhury, Rumana
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Dolan, Raymond J.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Backman, Lars
    Guitart-Masip, Marc
    Dorsal striatal dopamine D1 receptor availability predicts an instrumental bias in action learning2019In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 116, no 1, p. 261-270Article in journal (Refereed)
    Abstract [en]

    Learning to act to obtain reward and inhibit to avoid punishment is easier compared with learning the opposite contingencies. This coupling of action and valence is often thought of as a Pavlovian bias, although recent research has shown it may also emerge through instrumental mechanisms. We measured this learning bias with a rewarded go/no-go task in 60 adults of different ages. Using computational modeling, we characterized the bias as being instrumental. To assess the role of endogenous dopamine (DA) in the expression of this bias, we quantified DA D1 receptor availability using positron emission tomography (PET) with the radioligand [11C]SCH23390. Using principal-component analysis on the binding potentials in a number of cortical and striatal regions of interest, we demonstrated that cortical, dorsal striatal, and ventral striatal areas provide independent sources of variance in DA D1 receptor availability. Interindividual variation in the dorsal striatal component was related to the strength of the instrumental bias during learning. These data suggest at least three anatomical sources of variance in DA D1 receptor availability separable using PET in humans, and we provide evidence that human dorsal striatal DA D1 receptors are involved in the modulation of instrumental learning biases.

  • 13. de Boer, Lieke
    et al.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Dayan, Peter
    Backman, Lars
    Guitart-Masip, Marc
    Attenuation of dopamine-modulated prefrontal value signals underlies probabilistic reward learning deficits in old age2017In: eLIFE, E-ISSN 2050-084X, Vol. 6, article id e2642Article in journal (Refereed)
    Abstract [en]

    Probabilistic reward learning is characterised by individual differences that become acute in aging. This may be due to age-related dopamine (DA) decline affecting neural processing in striatum, prefrontal cortex, or both. We examined this by administering a probabilistic reward learning task to younger and older adults, and combining computational modelling of behaviour, fMRI and PET measurements of DA D1 availability. We found that anticipatory value signals in ventromedial prefrontal cortex (vmPFC) were attenuated in older adults. The strength of this signal predicted performance beyond age and was modulated by D1 availability in nucleus accumbens. These results uncover that a value-anticipation mechanism in vmPFC declines in aging, and that this mechanism is associated with DA D1 receptor availability.

  • 14.
    Ekman, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Jakobson Mo, Susanna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Functional brain activity and presynaptic dopamine uptake in patients with Parkinson's disease and mild cognitive impairment: a cross-sectional study2012In: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 11, no 8, p. 679-687Article in journal (Refereed)
    Abstract [en]

    Background: Many patients with Parkinson's disease have mild cognitive impairment (MCI). Deficits in executive functions and working memory suggest dysfunctional frontostriatal brain circuitry. We aimed to assess brain responses during a working memory task in a cohort of newly diagnosed drug-naive patients with Parkinson's disease with and without MCI.

    Methods: Participants were recruited within a prospective cohort study of incident patients with idiopathic parkinsonism, including Parkinson's disease. Between Jan 1, 2004, and April 30, 2009, all physicians in the Umea catchment area were requested to refer all individuals with suspected parkinsonism to the Department of Neurology at lima University. Included patients fulfilled the UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria for Parkinson's disease. Control individuals were matched on the basis of age and sex with the first 50 patients included in the study. Participants who scored 1.5 SDs or more below the population mean on at least two cognitive measures were diagnosed with MCI. The primary outcome measures were functional MRI blood-oxygen-level-dependent signal and SPECT presynaptic uptake. Functional MRI was done during a verbal two-back working memory task. Presynaptic dopamine SPECT was done to assess presynaptic striatal dopaminergic system integrity. Event-related transient analyses of functional MRI data were done for the whole brain and for frontostriatal regions of interest, and semi-quantitative SPECT analyses were done for striatal regions of interest.

    Findings: Compared with controls (n=24), patients with Parkinson's disease (n=77) had under-recruitment in an extensive brain network including bilateral striatal and frontal regions (p<0.001). Within the Parkinson's disease group, patients with Parkinson's disease and MCI (n=30) had additional under-recruitment in the right dorsal caudate nucleus (p=0.005) and the bilateral anterior cingulate cortex (p<0.001) compared with patients with Parkinson's disease without MCI (n=26). In patients with Parkinson's disease and MCI, SPECT uptake in the right caudate was lower than in patients with Parkinson's disease without MCI (p=0.008) and correlated with striatal functional MRI blood-oxygen-level-dependent signal (r=0.32, p=0.031).

    Interpretation: These altered brain responses in patients with Parkinson's disease and MCI suggest that cognitive impairment is linked to frontostriatal dysfunction.

  • 15.
    Elgh, Eva
    et al.
    Umeå University, Faculty of Medicine, Community Medicine and Rehabilitation, Geriatric Medicine.
    Sundström, Torbjörn
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Näsman, Birgitta
    Umeå University, Faculty of Medicine, Community Medicine and Rehabilitation, Geriatric Medicine.
    Riklund Åhlström, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Memory functions and rCBF (99m)Tc-HMPAO SPET: developing diagnostics in Alzheimer's disease2002In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, ISSN 1619-7070, Vol. 29, no 9, p. 1140-1148Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease (AD) is a primary degenerative disease of the brain. The prevalence increases with age, with devastating consequences for the individual and society. The aim of this study was to evaluate whether patients with early AD show an altered regional cerebral blood flow (rCBF) compared with control persons. Furthermore, we aimed to investigate the correlation between rCBF in sublobar volumes of the brain and performance on memory tests. Memory tests were chosen to evaluate episodic and semantic memory. Fourteen patients (aged 75.2+/-8.8 years) with early AD and 15 control persons (aged 71.4+/-3.2 years) were included. rCBF measurements with single-photon emission tomography (SPET) using technetium-99m hexamethylpropylene amine oxime (HMPAO) were performed. The rCBF (99m)Tc-HMPAO SPET images were spatially transformed to fit a brain atlas and normalised for differences in rCBF (Computerised Brain Atlas software). Cortical and subcortical volumes of interest (VOIs) were analysed and compared. Compared with the controls, AD patients showed a significantly lower rCBF ratio in temporoparietal regions, including the left hippocampus. The diagnostic sensitivity and specificity for AD were high in temporoparietal regions. AD patients had significantly reduced performance on semantic and, in particular, episodic memory tests compared with age-matched normative data, and their performance on several episodic tests correlated with rCBF ratios in parietal and temporal regions, including the left hippocampus. The correlation between rCBF ratio and level of episodic memory performance suggests that abnormalities in rCBF pattern underlie impaired episodic memory functioning in AD.

  • 16.
    Eriksson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Blomberg, Jeanette
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Lindgren, Theres
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Löfroth, Per-Olov
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Iodine-131 induces mitotic catastrophes and activates apoptotic pathways in HeLa Hep2 cells2008In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 23, no 5, p. 541-549Article in journal (Refereed)
    Abstract [en]

    Iodine-131 (131I) has been used both in unconjugated form and conjugated to antibody derivates (i.e., radioimmunotherapy; RIT) to treat malignant diseases. The mechanisms by which 131I-irradiation causes growth retardation are, however, inadequately understood. The aim of this study was to elucidate the sequential molecular and cellular events that initiate cell death in HeLa Hep2 cells exposed to 131I. In this paper, HeLa Hep2 cells were found to display a transient G2-M arrest following irradiation, but then reentered the cell cycle still containing unrepaired cellular damage. An increase of multipolar mitotic spindles, as well as a significant increase in centrosome numbers from 8.8% +/- 1.9% in controls to 54.7% +/- 2.2% in irradiated cells, was observed (p < 0.0001). A subsequent failure of cytokinesis caused the cells to progress into mitotic catastrophe. This was accompanied by the formation of giant cells with multiple nuclei, multilobulated nuclei, and an increased frequency of polyploidy cells. A fraction of the cells also displayed apoptotic features, including the activation of initiator caspases-2, -8, -9, and effector caspase-3, as well as cleavage of poly(ADP-ribose) polymerase, a cell-death substrate for active caspase-3. These findings demonstrate that mitotic catastrophes and the activation of a delayed type of apoptosis might be important mechanisms involved in cell death following the RIT of solid tumors with -emitting radionuclides, such as 131I.

  • 17.
    Eriksson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Löfroth, Per-Olov
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Apoptotic signalling in HeLa Hep2 cells following 5 Gy of cobalt-60 gamma radiation2009In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 29, no 11, p. 4361-4366Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The apoptotic signalling pathways involved in the delayed type of apoptosis occurring in HeLa Hep2 cells following radiation were investigated. MATERIALS AND METHODS: HeLa Hep2 cells were exposed to 5 Gy of cobalt-60 radiation. The activation of caspase-2, caspase-8, caspase-9 and effector caspase-3 was investigated by caspase assay plates and Western blots. Cleavage of poly (ADP-ribose) polymerase (PARP) was analysed on Western blots. HeLa Hep2 cells were irradiated with or without preincubation with inhibitors of protein synthesis (cycloheximide, CHX) and caspases, followed by TUNEL staining and caspase assay plate evaluation. RESULTS: Initiator caspases-2, -8, -9, and effector caspase-3, were found to be activated and PARP cleaved following irradiation. CHX completely inhibited the caspase activation and the associated apoptosis. Pretreatment with caspase-2 inhibitor indicated that caspase-2 was involved in the execution of the apoptosis. CONCLUSION: Activation of the apoptotic signalling pathways following irradiation of HeLa Hep2 cells includes components from the intrinsic as well as the extrinsic pathways and seems to require de novo protein synthesis.

  • 18.
    Eriksson, David
    et al.
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    Löfroth, Per-Olov
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Åhlström Riklund, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    Cell cycle disturbances and mitotic catastrophes in HeLa Hep2 cells following 2.5 to 10 Gy of ionizing radiation.2007In: Clin Cancer Res, ISSN 1078-0432, Vol. 13, no 18 Pt 2, p. 5501s-5508sArticle in journal (Refereed)
    Abstract [en]

    PURPOSE: Experimental radioimmunotherapy delivering absorbed doses of 2.5 to 10 Gy has been shown to cause growth retardation of tumors. The purpose of this study was to elucidate the sequential molecular and cellular events occurring in HeLa Hep2 cells exposed to such doses. METHODS: Dose-response curves, activation of cell cycle checkpoints, and mitotic behavior were investigated in HeLa Hep2 cells following 2.5- to 10-Gy irradiation by carrying out 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, Western blots, fluorescence-activated cell sorting analysis, and immunofluorescence stainings. Terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling staining was used to detect apoptosis. RESULTS: A G2-M arrest was shown by fluorescence-activated cell sorting analysis. p53 and p21 were found to be up-regulated but were not immediately related to the arrest. The G2-M arrest was transient and the cells reentered the cell cycle still containing unrepaired cellular damage. This premature entry caused an increase of anaphase bridges, lagging chromosomal material, and multipolar mitotic spindles as visualized by propidium iodide staining and immunofluorescence staining with alpha-tubulin and gamma-tubulin antibodies. Furthermore, a dose-dependent significant increase in centrosome numbers from 12.6+/-6.6% to 67+/-5.3% was identified as well as a dose-dependent increase of polyploid cells from 2.8+/-1.3% to 17.6+/-2.1% with the highest absorbed dose of 10 Gy. These disturbances caused the cells to progress into mitotic catastrophe and a fraction of these dying cells showed apoptotic features as displayed by terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling staining 5 to 7 days after irradiation. CONCLUSION: An absorbed dose of 2.5 to 10 Gy was shown to force HeLa Hep2 cells into mitotic catastrophe and delayed apoptosis. These might be important cell death mechanisms involved in tumor growth retardation following radioimmunotherapy of solid tumors.

  • 19.
    Eriksson, David
    et al.
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Mirzaie-Joniani, Homa
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Sheikholvaezin, Ali
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Löfroth, Per-Olov
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Åhlström-Riklund, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Combined low dose radio- and radioimmunotherapy of experimental HeLa Hep 2 tumours.2003In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 30, no 6, p. 895-906Article in journal (Refereed)
    Abstract [en]

    Radiation therapy of malignant tumours can be delivered by external beam radiation (RT) or radioimmunotherapy (RIT), using nuclides attached to monoclonal antibodies (mAbs). These treatment modalities have now been combined in order to investigate putative therapeutic advantages and elucidate the biological responses involved. Nude mice were transplanted subcutaneously on the back with human HeLa Hep2 tumour cells. RT (3x5 Gy) and/or 100 microg (131)I-labelled mAb H7, against placental alkaline phosphatase, or (131)I-labelled mAb TS1, against cytokeratin, was administered separately or in combination (specific activity of 120-200 MBq/mg antibody). Significant tumour growth retardation was observed both with RT alone and with RIT alone. Combining these regimens enhanced the therapeutic effects further, and a significant reduction in tumour volume could be demonstrated. The tumours were subjected to extensive histochemical and immunohistochemical investigations in order to elucidate changes in biology and histology within them. The following stainings were used: haematoxylin-eosin (morphology), Ki67 (proliferation), M30 (apoptosis), TUNEL (apoptosis) and endoglin (vascularisation). Tumours in the control group grew fast, with an average tumour doubling time of 9 days. These tumours contained large viable tumour cell masses displaying vast proliferation zones of Ki67-positive tumour cells, as well as necrotic regions and small amounts of connective tissue. Apoptotic cells could be identified both with M30 and TUNEL staining. When RT was applied, the growth rate was significantly reduced (doubling time 19 days) and typical alterations in morphology were seen, with a relative increase in connective tissue and a decrease in necrotic regions. Apoptotic cells were identified and a decrease in cell density was also observed. When RIT alone was applied, the growth parameters indicated a longer lasting growth reduction, especially when TS1 was used separately or in combination with H7. The histological appearances of these tumours were somewhat different from the RT-treated tumours, with a larger portion of intratumoural cysts. These tumours also presented a reduced tumour cell density. Dramatic effects were observed when RT was combined with RIT, with a pronounced growth reduction seen in all combination treatment groups. Pronounced tumour volume reduction was also evident in both the RT + RIT ((131)I-TS1) group and RT + RIT ((131)I-TS1/(131)I-H7) group, and in some animals no tumour remained at all. The morphology of the tumour remnants at day 22 was chaotic with a drastically changed histology, with presence of abundant cysts, low fractions of Ki67-positive cells, reduction in cell density, increased amounts of connective tissue and a decrease in necrotic regions. Again, apoptotic cells could be identified, scattered throughout the viable regions. Combining RT and RIT seems to generate an efficient treatment with convincing and long-lasting tumour growth inhibition, which is reflected in a highly aberrant histology within the tumour. Results obtained in this study indicate that both necrosis and apoptosis may be involved in the process leading to this efficient therapy of epithelially derived tumours.

  • 20.
    Eriksson, Johan
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund Åhlström, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Similar frontal and distinct posterior cortical regions mediate visual and auditory perceptual awareness2007In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 17, no 4, p. 760-765Article in journal (Refereed)
    Abstract [en]

    Activity in ventral visual cortex is a consistent neural correlate of visual consciousness. However, activity in this area seems insufficient to produce awareness without additional involvement of frontoparietal regions. To test the generality of the frontoparietal response, neural correlates of auditory awareness were investigated in a paradigm that previously has revealed frontoparietal activity during conscious visual perception. A within-experiment comparison showed that frontal regions were related to both visual and auditory awareness, whereas parietal activity was correlated with visual awareness and superior temporal activity with auditory awareness. These results indicate that frontal regions interact with specific posterior regions to produce awareness in different sensory modalities.

  • 21.
    Eriksson, Johan
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund Åhlström, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Visual consciousness: dissociating the neural correlates of perceptual transitions from sustained perception with fMRI2004In: Consciousness and Cognition, ISSN 1053-8100, E-ISSN 1090-2376, Vol. 13, no 1, p. 61-72Article in journal (Refereed)
    Abstract [en]

    To investigate the possible dichotomy between the neurophysiological bases of perceptual transitions versus sustaining a particular percept over time, an fMRI study was conducted with subjects viewing fragmented pictures. Unlike most other perceptually unstable stimuli, fragmented pictures give rise to only one perceptual transition and a continuous period of sustained perception. Earlier research is inconclusive on the subject of which anatomical regions should be attributed to what temporal aspect of perception, and the aim of the present study was to shed more light on the subject. In this study occipitotemporal and fronto-parietal regions were found to be activated for both aspects. However, regions in the medial-temporal lobe were activated specifically for transitions, whereas medial and dorsolateral prefrontal regions were activated specifically for sustained perception. These results provide further support for the theory that the initial creation of perceptual awareness and upholding perceptual awareness over time are separate processes involving different brain regions.

  • 22.
    Erlandsson, Ann
    et al.
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Eriksson, David
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Sundström, Birgitta Elisabeth
    In vivo clearing of idiotypic antibodies with antiidiotypic antibodies and their derivatives2006In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 43, no 6, p. 599-606Article in journal (Refereed)
    Abstract [en]

    At immunolocalization of experimental tumors, idiotypic monoclonal antibodies, such as TS1 against cytokeratin 8, can be used to carry and deposit in vivo terapeutics in the tumor. These carriers also remain in the circulation and may cause negative side-effects in other tissues. In this report, several derivatives of the antiidiotypic antibody alphaTS1 were produced and tested for their clearing capacity of the idiotypic carrier antibody TS1. Intact monoclonal alphaTS1, scFv of a alphaTS1 and alphaTS1 Fab'2 and fragments were produced by recombinant technology or by cleavage with Ficin. The scFv was tailored by use of the variable domain genes of the light and heavy chain from the hybridoma clone in combination with a (Gly4Ser)3-linker, followed by expression in E. coli. When tested for clearing capacity, the intact divalent antiidiotypic IgG was found to be the most efficient. The divalent and the monovalent Fab fragment also demonstrated significant clearing, but lower than the intact antiidiotypic IgG. The alphaTS1 scFv antibody when injected separately was not found to clear the idiotype, but could do so when preincubated with the idiotype. Rapid excretion and in vivo instability of this low molecular weight antibody fragment may be the major reasons. Similar results were obtained when the system was reversed and the 131I-labeled antiidiotype IgG was cleared with the idiotype fragment. It is concluded that both intact antiidiotypic IgG, and Fab'2 fragments are able to clear the idiotypic antibodies. The experimental data support the conclusion that the Fc parts from both the idiotype and the antiidiotype may contribute to this elimination.

  • 23.
    Flodin, Pär
    et al.
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Jonasson, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.
    Does Aerobic Exercise Influence Intrinsic Brain Activity? An Aerobic Exercise Intervention among Healthy Old Adults2017In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 9, article id 267Article in journal (Refereed)
    Abstract [en]

    Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64–78 years) were randomized into either an aerobic exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). Additionally, a comprehensive battery of cognitive tasks assessing, e.g., executive function and episodic memory was administered. Both the aerobic and the control group improved in aerobic capacity (VO2-peak) over 6 months, but a significant group by time interaction confirmed that the aerobic group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings. At baseline, VO2-peak was negativly related to BOLD-signal fluctuations (BOLDSTD) in mid temporal areas. Over 6 months, improvements in aerobic capacity were associated with decreased connectivity between left hippocampus and contralateral precentral gyrus, and positively to connectivity between right mid-temporal areas and frontal and parietal regions. Independent component analysis identified a VO2-related increase in coupling between the default mode network and left orbitofrontal cortex, as well as a decreased connectivity between the sensorimotor network and thalamus. Extensive exploratory data analyses of global efficiency, connectome wide multivariate pattern analysis (connectome-MVPA), as well as ASL, did not reveal any relationships between aerobic fitness and intrinsic brain activity. Moreover, fitness-predicted changes in functional connectivity did not relate to changes in cognition, which is likely due to absent cross- sectional or longitudinal relationships between VO2-peak and cognition. We conclude that the aerobic exercise intervention had limited influence on patterns of intrinsic brain activity, although post hoc analyses indicated that individual changes in aerobic capacity preferentially influenced mid-temporal brain areas.

  • 24. Gatidis, Sergios
    et al.
    Beyer, Thomas
    Becker, Minerva
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Nikolaou, Konstantin
    Cyran, Clemens
    Pfannenberg, Christina
    State of affairs of hybrid imaging in Europe: two multi-national surveys from 20172019In: Insight into Imaging, ISSN 1869-4101, E-ISSN 1869-4101, Vol. 10, no 1, article id 57Article in journal (Refereed)
    Abstract [en]

    Objectives: To assess the current state of hybrid imaging in Europe with respect to operations, reading and reporting, as well as qualification and training.

    Methods: The first survey (LOCAL) was sent to the heads of the departments of radiology and nuclear medicine in Europe in 2017, including 15 questions regarding the organisation of hybrid imaging operations, reporting strategies for PET/CT and the existence of relevant training programmes. The second survey (NATIONAL) consisted of 10 questions and was directed to the national ministries of health of 37 European countries addressing combined training options in radiology and nuclear medicine.

    Results: In the LOCAL survey, 61 valid responses from 26 European countries were received. In almost half of the institutions, hybrid imaging was performed within a single department, mainly in nuclear medicine departments (31%). In half of the centres (51%), PET/CT reports were performed jointly, while in 20% of the centres, reporting was performed by nuclear medicine physicians. Radiologists were responsible for presenting hybrid imaging results in clinical boards in 34% of responding sites. Integrated hybrid imaging training was available in 41% sites. In the NATIONAL survey, responses from 34 countries were received and demonstrated a heterogeneous landscape of official training possibilities in radiology and nuclear medicine with limited opportunities for additional qualifications in hybrid imaging.

    Conclusions: The results of these surveys demonstrate a notable heterogeneity in the current practice of hybrid imaging throughout Europe. This heterogeneity exists despite the general consensus that strong professional cooperation is required in order to ensure high clinical quality and to strengthen the clinical role of hybrid imaging.

  • 25. Glimelius, Bengt
    et al.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Enblad, Gunilla
    Alafuzoff, Irina
    Beskow, Anna
    Ahlström, Håkan
    Bill-Axelson, Anna
    Birgisson, Helgi
    Björ, Ove
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Edqvist, Per-Henrik
    Hansson, Tony
    Helleday, Thomas
    Hellman, Per
    Henriksson, Kerstin
    Hesselager, Göran
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Häggman, Michael
    Höglund, Martin
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Larsson, Chatarina
    Lindman, Henrik
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Mindus, Stephanie
    Nygren, Peter
    Pontén, Fredrik
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Rosenquist, Richard
    Sandin, Fredrik
    Schwenk, Jochen M.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Stålberg, Karin
    Stålberg, Peter
    Sundström, Christer
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Westermark, Bengt
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Claesson-Welsh, Lena
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sjöblom, Tobias
    U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 187-194Article in journal (Refereed)
    Abstract [en]

    Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umea Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.

    Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.

    Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.

    Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

  • 26. Hartana, C. A.
    et al.
    Ahlén Bergman, E.
    Broomé, A.
    Berglund, S.
    Johansson, M.
    Alamdari, F.
    Jakubczyk, T.
    Huge, Y.
    Aljabery, F.
    Palmqvist, K.
    Holmström, B.
    Glise, H.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Winqvist, O.
    Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer2018In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 194, no 1, p. 39-53Article in journal (Refereed)
    Abstract [en]

    Tissue-resident memory T (TRM ) cells are CD8+ T lymphocytes that reside in the tissues, including tumours. This T cell subset possesses a magnitude of cytotoxicity, but its epigenetic regulation has not been studied. Here, we investigate the impact of perforin DNA methylation in TRM cells and correlate it with their functional potential. Fifty-three urothelial urinary bladder cancer (UBC) patients were recruited prospectively. The DNA methylation status of the perforin gene (PRF1) locus in TRM cells was investigated by pyrosequencing. Flow cytometry with ViSNE analysis and in-vitro stimulation were used to evaluate TRM cell phenotypes. We discovered that tumour TRM cells have low DNA methylation in the PRF1 locus (32·9% methylation), which corresponds to increased numbers of perforin-expressing TRM cells. Surprisingly, programmed cell death 1 (PD-1) expression is high in tumour TRM cells, suggesting exhaustion. Following interleukin-15 and T cell receptor stimulation, perforin and T-bet expressions are enhanced, indicating that TRM cells from tumours are not terminally exhausted. Moreover, a high number of TRM cells infiltrating the tumours corresponds to lower tumour stage in patients. In conclusion, TRM cells from UBC tumours are epigenetically cytotoxic with signs of exhaustion. This finding identifies TRM cells as potential new targets for cancer immunotherapy.

  • 27. Hartana, Ciputra Adijaya
    et al.
    Bergman, Emma Ahlén
    Zirakzadeh, A. Ali
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Krantz, David
    Winerdal, Malin E.
    Winerdal, Max
    Johansson, Markus
    Alamdari, Farhood
    Jakubczyk, Tomasz
    Glise, Hans
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Winqvist, Ola
    Urothelial bladder cancer may suppress perforin expression in CD8+ T cells by an ICAM-1/TGFβ2 mediated pathway2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 7, article id e0200079Article in journal (Refereed)
    Abstract [en]

    The immune system plays a significant role in urothelial bladder cancer (UBC) progression, with CD8+ T cells being capable to directly kill tumor cells using perforin and granzymes. However, tumors avoid immune recognition by escape mechanisms. In this study, we aim to demonstrate tumor immune escape mechanisms that suppress CD8+ T cells cytotoxicity. 42 patients diagnosed with UBC were recruited. CD8+ T cells from peripheral blood (PB), sentinel nodes (SN), and tumor were analyzed in steady state and in vitro-stimulated conditions by flow cytometry, RT-qPCR, and ELISA. Mass spectrometry (MS) was used for identification of proteins from UBC cell line culture supernatants. Perforin was surprisingly found to be low in CD8+ T cells from SN, marked by 1.8-fold decrease of PRF1 expression, with maintained expression of granzyme B. The majority of perforin-deficient CD8+ T cells are effector memory T (TEM) cells with exhausted Tc2 cell phenotype, judged by the presence of PD-1 and GATA-3. Consequently, perforin-deficient CD8+ T cells from SN are low in T-bet expression. Supernatant from muscle invasive UBC induces perforin deficiency, a mechanism identified by MS where ICAM-1 and TGFβ2 signaling were causatively validated to decrease perforin expression in vitro. Thus, we demonstrate a novel tumor escape suppressing perforin expression in CD8+ T cells mediated by ICAM-1 and TGFβ2, which can be targeted in combination for cancer immunotherapy.

  • 28.
    Holmberg, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Sundström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ljungberg, Michael
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Reducing Scanning Time to 50% for In-111 Pentetreotide SPECT When Using Model-Based Compensation2012In: 2012 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE RECORD (NSS/MIC) / [ed] B. Yu, 2012, p. 2946-2949Conference paper (Refereed)
    Abstract [en]

    In In-111-pentetreotide SPECT, it can be difficult to detect small tumors because of high noise levels and low spatial resolution. The aim of this study was to perform optimization of tumor detection in the liver, with regards to the acquisition and reconstruction protocol for In-111-pentetreotide SPECT with model-based compensation included in the OSEM reconstruction. We were also interested in the effect of performing the examination in half of the time or with half the administered activity. Image reconstruction without model-based compensation was also included for comparison. The study concentrates on the acquired number of projections and the subset size in the OSEM reconstruction, and evaluates contrast as a function of noise for a range of OSEM iterations. The raw-data projections are produced using Monte Carlo simulations of a patient-like anthropomorphic phantom with realistic In-111 pentetreotide uptake, including spherical tumors in the liver. Two collimators are evaluated, the extended low-energy general-purpose (ELEGP) and the medium-energy general-purpose (MEGP) collimator. ELEGP proved to be a better collimator when using model-based compensation. The results also indicate that a relatively low number of subsets is advantageous, and that 60 projection angles or even lower is a better choice than 120. For both collimators the time-reduced scan including model-based compensation was better compared to the full-time reconstructions without model-based compensation.

  • 29.
    Jakobson Mo, Susanna
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Jonasson, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Ögren, Mattias J.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Ögren, Margareta
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Varrone, Andrea
    Eriksson, Linda
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Bäckström, David
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    af Bjerkén, Sara
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Dopamine transporter imaging with [18F]FE-PE2I PET and [123I]FP-CIT SPECT – a clinical comparison2018In: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 8, article id 100Article in journal (Refereed)
    Abstract [en]

    Background: Dopamine transporter (DAT) imaging may be of diagnostic value in patients with clinically suspected parkinsonian disease. The purpose of this study was to compare the diagnostic performance of DAT imaging with positron emission computed tomography (PET), using the recently developed, highly DAT-selective radiopharmaceutical [18F]FE-PE2I (FE-PE2I), to the commercially available and frequently used method with [123I]FP-CIT (FP-CIT) single-photon emission computed tomography (SPECT) in early-stage idiopathic parkinsonian syndrome (PS).

    Methods: Twenty-two patients with a clinical de novo diagnosis of PS and 28 healthy controls (HC) participating in an on-going clinical trial of FE-PE2I were analyzed in this study. Within the trial protocol, participants are clinically reassessed 2 years after inclusion. A commercially available software was used for automatic calculation of FP-CIT-specific uptake ratio (SUR). MRI-based volumes of interest combined with threshold PET segmentation were used for FE-PE2I binding potential relative to non-displaceable binding (BPND) quantification and specific uptake value ratios (SUVR).

    Results: PET with FE-PE2I revealed significant differences between patients with a clinical de novo diagnosis of PS and healthy controls in striatal DAT availability (p < 0.001), with excellent accuracy of predicting dopaminergic deficit in early-stage PS. The effect sizes were calculated for FE-PE2I BPND (Glass’s Δ = 2.95), FE-PE2I SUVR (Glass’s Δ = 2.57), and FP-CIT SUR (Glass’s Δ = 2.29). The intraclass correlation (ICC) between FE-PE2I BPND FP-CIT SUR was high in the caudate (ICC = 0.923), putamen (ICC = 0.922), and striatum (ICC = 0.946), p < 0.001. Five of the 22 patients displayed preserved striatal DAT availability in the striatum with both methods. At follow-up, a non-PS clinical diagnosis was confirmed in three of these, while one was clinically diagnosed with corticobasal syndrome. In these patients, FE-PE2I binding was also normal in the substantia nigra (SN), while significantly reduced in the remaining patients. FE-PE2I measurement of the mean DAT availability in the putamen was strongly correlated with BPND in the SN (R = 0.816, p < 0.001). Olfaction and mean putamen DAT availability was correlated using both FE-PE2I BPND and FP-CIT SUR (R ≥ 0.616, p < 0.001).

    Conclusion: DAT imaging with FE-PE2I PET yields excellent basic diagnostic differentiation in early-stage PS, at least as good as FP-CIT SPECT.

  • 30.
    Jakobson Mo, Susanna
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Cross-camera comparison of ROI-based semi-quantitative 123I-IBZM SPECT data in healthy volunteers using an anthropomorphic phantom for calibration2013In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 54, no 5, p. 549-556Article in journal (Refereed)
    Abstract [en]

    Background In (123)I-Iolopride (IBZM) SPECT reference values may diverge between camera systems. If multicenter pooling of normal material databases is needed, differences in measured semi-quantitative data due to equipment performance and reconstruction parameters have to be investigated in each instance to determine the comparability.

    Purpose To explore the differences in (123)I-IBZM measured uptake ratios between two different gamma cameras in healthy controls, the intra-rater reproducibility of the image evaluation method and the possibility to equalize uptake ratios by calibration through an anthropomorphic phantom.

    Material and Methods Differences in ROI-based semi-quantitative data from two different gamma camera systems, the three-headed brain dedicated Neurocam and the two-headed multipurpose hybrid system Infinia Hawkeye, were studied using image data from a group of healthy volunteers and an anthropomorphic brain-phantom scanned with both cameras. Several reconstruction methods and corrections were applied. To test the reliability of the ROI method, the intra-observer reproducibility was determined for the ROI method in this study.

    Results The ROI method had a high reliability. Differences in mean measured uptake (123)I-IBZM ratios in healthy controls varied between 2.9% and 6.5% depending on reconstruction and correction for attenuation and scatter. After calibration, the differences decreased. There were no statistically significant differences between corrected ratios from the two camera systems in the study when images were reconstructed with attenuation correction.

    Conclusion The conformity of uptake ratios in attenuation corrected (123)I-IBZM images derived from the two different cameras was improved by using an anthropomorphic phantom for calibration.

  • 31.
    Jakobson Mo, Susanna
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Edenbandt, Lars
    Göteborgs Universitet, Avdelningen för molekylär och klinisk medicin.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    123I-FP-Cit and 123I-IBZM SPECT uptake in a prospective normal material analysed with two different semi-quantitative image evaluation tools2013In: Nuclear medicine communications, ISSN 0143-3636, E-ISSN 1473-5628, Vol. 34, no 10, p. 978-989Article in journal (Refereed)
    Abstract [en]

    Objective: The need for age-adjusted and/or sex-adjusted reference values in dopamine transporter (DAT) and dopamine D2 receptor (D2R) imaging with single-photon emission computed tomography (SPECT) in a longitudinal study of parkinsonian diseases was investigated. We used two different image evaluation tools with a cross-sectional and longitudinal statistical approach.

    Materials and methods: Baseline DAT and/or D2R SPECT were performed in 51 healthy controls (HC), age-matched to patients in an ongoing prospective study on idiopathic parkinsonism. Twenty-four HC were re-examined after 3 years and 21 HC were examined again after 5 years. SPECT was performed with I-123-FP-Cit and I-123-IBZM on a two-headed hybrid gamma camera. Regions of interest and volumes of interest (VOIs) were used for image evaluation. A cross-sectional and longitudinal statistical analysis was carried out.

    Results: Fewer sex-based differences and less age dependency were seen in DAT SPECT uptake ratios compared with D2R SPECT uptake ratios and when comparing uptake ratios obtained with regions of interest against those with VOIs. In the cross-sectional analysis, a significant age-dependent decline was seen in women in both DAT and D2R uptakes with the VOI method but not in men with either evaluation method. In the longitudinal dataset, both a slight decline and increase over time were seen in DAT uptake; however, a general pattern of decrease was seen in both men and women in D2R uptake.

    Conclusion: The choice of the image evaluation method can influence the pattern of sex-based and age-related differences. The results speak for the use of age-stratified reference values for women, in particular when using a VOI method.

  • 32.
    Jakobson Mo, Susanna
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Holmberg, Henrik
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Pre- and postsynaptic dopamine SPECT in idiopathic parkinsonian diseases: a follow-up study2013In: BioMed Research International, ISSN 2314-6141, Vol. 2013, p. 143532-Article in journal (Refereed)
    Abstract [en]

    We prospectively evaluated the diagnostic contribution of 123I-FP-Cit (DAT) and 123I-IBZM (IBZM) SPECT in 29 patients with Parkinson’s disease (PD) (74.4 ± 4.2 years) and 28 patients with atypical parkinsonian diseases (APD) (74.3 ± 9.2 years). Twelve had multiple system atrophy (MSA) and 16 progressive supranuclear palsy (PSP). Sixteen age-matched healthy controls (HC) were included. DAT and IBZM SPECTs were made at baseline and after 1 year in all PD patients and in 20 (DAT) and 18 (IBZM) of the APD patients, and after 3 years in 22 (DAT) and 17 (IBZM) of the PD patients and in 10 (DAT) and 10 (IBZM) of the APD patients. The relative DAT uptake decrease was faster in PD and PSP than in HC and MSA. In PSP the DAT uptake was lower than in MSA after 1 year but not after 3 years. Baseline IBZM uptake was not significantly different between patients and HC or between PD and APD. One year after initiated dopaminergic treatment the mean IBZM uptake in the MSA patients remained high compared to PSP and after 3 years compared to PD, PSP, and HC.Thus, the pattern of uptake of these ligands over time may be of value in discriminating between these diagnoses.

  • 33.
    Jakobson Mo, Susanna
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Pre- and postsynaptic dopamine SPECT in the early phase of idiopathic parkinsonism: a population-based study2010In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 37, no 11, p. 2154-2164Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was to assess the diagnostic contribution of pre- and postsynaptic dopamine SPECT in drug-naïve patients with early idiopathic parkinsonism and to investigate possible differences between idiopathic Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) and possible differences in motor subtypes of parkinsonism.

    METHODS: A group of 128 newly diagnosed idiopathic parkinsonian patients and 48 healthy controls was studied. Presynaptic baseline SPECT with (123)I-FP-CIT was performed in all patients and in 120 patients also a baseline postsynaptic SPECT with (123)I-IBZM. Clinical diagnoses were reassessed after 12 months.

    RESULTS: Presynaptic uptake in the putamen and caudate was significantly reduced in patients compared to controls. Presynaptic uptake ratios were not different between PD patients and patients with APS, and postsynaptic uptake in APS was not significantly reduced compared to PD or controls. In half of the APS patients both pre- and postsynaptic uptake ratios were reduced on the same side in the striatum. Impaired motor performance was associated with decreased presynaptic uptake in the putamen in PD. The postural instability and gait difficulty (PIGD) subtype of PD had lower presynaptic uptake ratios than patients with tremor-dominated (TD) symptoms.

    CONCLUSION: Not only presynaptic putamen uptake ratios, but also caudate ratios were reduced in a majority of the patients in our study. At baseline scan, i.e. in an early stage of the disease, the accuracy of excluding APS in the whole study population was 85% using a combination of pre- and postsynaptic SPECT. Already at baseline, lower presynaptic SPECT ratios were seen in PD with PIGD at onset compared to those with TD subtype.

  • 34.
    Jakobson Mo, Susanna
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Accuracy of Visual Assessment of Dopamine Transporter Imaging in Early Parkinsonism2015In: Movement Disorders Clinical Practice, ISSN 2330-1619, Vol. 2, no 1, p. 17-23Article in journal (Refereed)
    Abstract [en]

    Dopamine transporter (DaT) imaging may be supportive in the initial clinical diagnostic workup in patients with suspected parkinsonian diseases, given that the method has the potential to detect dopaminergic degeneration. We investigated the diagnostic accuracy of visual assessment of the initial DaT single-photon emission CT (DaT-SPECT) with 123I-FP-CIT in a large group of early-stage parkinsonian patients. After inclusion in a long-term multidisciplinary population-based prospective study, a baseline DaT-SPECT was done in 171 incidental, L-dopa-naïve, parkinsonian patients (102 men and 69 women) and 37 healthy controls (19 men and 18 women). The results of the DaT-SPECTs were linked to criteria-based clinical diagnoses, which were set after a mean follow-up of 4.6 (±1.7) years. The outcome of the visual assessment was also compared with that of a semiquantitative evaluation method using regions of interest to measure uptake ratios in the caudate and putamen. We found that visual assessment of DaT-SPECT in clinically diagnosed incidental Parkinson's disease patients had a sensitivity of 94% and a specificity of 92%, rendering a positive likelihood ratio of 11.75 and a negative likelihood ratio of 0.07. The proportion of false positives was 1.4% and false negatives 4.8% at baseline. These figures were comparable to those of the semiquantitative method. This study demonstrates that visual interpretation of presynaptic dopamine imaging with 123I-FP-CIT offers reliable support in the diagnostic procedure of early parkinsonian diseases.

  • 35.
    Johansson, Amanda
    et al.
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    Eriksson, David
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    Ullen, Anders
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    Löfroth, Per-Olov
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Åhlström-Riklund, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    The combination of external beam radiotherapy and experimental radioimmunotargeting with a monoclonal anticytokeratin antibody2002In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 94, no S4, p. 1314-1319Article in journal (Refereed)
  • 36. Johansson, Amanda
    et al.
    Sandström, Per
    Ullén, Anders
    Erlandsson, Ann
    Sundström, Birgitta
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hietala, Sven-Ola
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Stability and immunoreactivity of the monoclonal anticytokeratin antibody TS1 after different degrees of iodination.1999In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 38, no 3, p. 329-334Article in journal (Refereed)
    Abstract [en]

    The immunoreactivity, stability and in vivo kinetics of an anticytokeratin 8 monoclonal antibody, TS1, were investigated following different degrees of labeling with 125I (0.2, 1 and 2-3 125I/TS1 MAb). By testing with ELISA, it was demonstrated that a high degree of iodination, i.e. > 2 125I/TS1, caused a rapid decrease in immunoreactivity to almost zero within 10 days. Furthermore, a complete degradation to low molecular weight fragments and free iodine was seen, as shown by SDS PAGE and autoradiography. The differently labeled radionuclide conjugates were injected into nude mice inoculated with HeLa Hep2 cells and tumor doses (estimated by MIRD formalism), tumor:non-tumor dose ratios, % I.D./gram tissue, Gy/MBq and in vivo kinetics of the differently labeled MAbs were determined. Despite the in vitro instability of the highest iodinated radionuclide conjugate, it was possible to deliver high doses to the tumors if the conjugate was injected into the animal immediately after completion of the iodination procedure. Increases from 1.4 Gy to 15.2 Gy delivered tumor dose were obtained with a tenfold increase in the specific activity, without alterations in the tumor:non-tumor tissue dose ratios. There is room for significant improvements in efficacy at radioimmunotherapy, which can be gained by optimizing the degree of iodination. For therapeutical applications a high degree of iodination may be an advantage.

  • 37.
    Johansson, Elias
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Rydh, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Åhlström Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ultrasound, Computed Tomography, and Laboratory Findings in the Diagnosis of Appendicitis2007In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 48, no 3, p. 267-273Article in journal (Refereed)
    Abstract [en]

    Purpose: To determine the diagnostic accuracy and the clinical impact of ultrasound (US) and computed tomography (CT) in diagnosing appendicitis, and to evaluate the impact of laboratory tests on the treatment of acute appendicitis.

    Material and Methods: All patients who, during 2005, underwent an acute ultrasound or CT investigation due to suspected appendicitis, or were diagnosed and/or surgically treated for appendicitis at Umeå University Hospital, Umeå, were included. The type of radiological investigation, its findings, the choice of treatment, final diagnosis, C-reactive protein (CRP), leukocyte particle count (LPC), body temperature, age, and sex were recorded for each patient. The histological result from surgery was considered the gold standard.

    Results: The material included 305 cases with an overall appendicitis prevalence of 58%. Fifty-two percent of the patients were female. The mean age was 29 years, with a total range of 2–94 years. Twenty percent (60/305) underwent a CT investigation, 40% (123/305) underwent an US investigation, 5% (14/305) underwent both a CT and an US investigation, and 35% (108/305) of patients did not undergo any radiological investigation at all. The sensitivities and specificities were 91% and 94% for CT, and 83% and 98% for US, respectively. The positive likelihood ratio was 15.1 and 45.5 for CT and US, and the negative likelihood ratio was 0.09 and 0.18 for CT and US, respectively. It was not possible to visualize the appendix in 31% of patients examined with US. The prevalence of appendicitis in this group was the same as the prevalence among patients where it was possible to see the appendix, i.e., 35%. The mean CRP for all patients with appendicitis was 59 (95% CI 10–491) mg/l, and the mean LPC was 11.1 (95% CI 2.6–28.1) ×10−9/l. The mean LPC level was significantly higher for the appendicitis patients. Body temperature could not significantly verify or exclude appendicitis. The overall negative appendectomy rate was 9% (16/176), and it was higher in women, i.e., 11% (9/79). The negative appendectomy rate was slightly higher in the group that was examined by CT and/or US, i.e., 12% (8/69) compared to 7% (8/107) in the group not examined radiologically.

    Conclusion: Diagnostic accuracy was high for US as well as for CT. US was better for diagnosing positive findings, while CT was better for excluding diagnosis of appendicitis. The diagnostic accuracy of LPC, CRP, and body temperature was low. By combining findings from the radiological examination with the results from the clinical examination and laboratory values, a low negative appendectomy rate can be achieved.

  • 38.
    Jonasson, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.
    Simulating effects of brain atrophy in longitudinal PET imaging with an anthropomorphic brain phantom2017In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 62, no 13, p. 5213-5227Article in journal (Refereed)
    Abstract [en]

    In longitudinal positron emission tomography (PET), the presence of volumetric changes over time can lead to an overestimation or underestimation of the true changes in the quantified PET signal due to the partial volume effect (PVE) introduced by the limited spatial resolution of existing PET cameras and reconstruction algorithms. Here, a 3D-printed anthropomorphic brain phantom with attachable striata in three sizes was designed to enable controlled volumetric changes. Using a method to eliminate the non-radioactive plastic wall, and manipulating BP levels by adding different number of events from list-mode acquisitions, we investigated the artificial volume dependence of BP due to PVE, and potential bias arising from varying BP. Comparing multiple reconstruction algorithms we found that a high-resolution ordered- subsets maximization algorithm with spatially variant point-spread function resolution modeling provided the most accurate data. For striatum, the BP changed by 0.08% for every 1% volume change, but for smaller volumes such as the posterior caudate the artificial change in BP was as high as 0.7% per 1% volume change. A simple gross correction for striatal volume is unsatisfactory, as the amplitude of the PVE on the BP differs depending on where in the striatum the change occurred. Therefore, to correctly interpret age-related longitudinal changes in the BP, we must account for volumetric changes also within a structure, rather than across the whole volume. The present 3D-printing technology, combined with the wall removal method, can be implemented to gain knowledge about the predictable bias introduced by the PVE differences in uptake regions of varying shape.

  • 39.
    Jonasson, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Kramer, Arthur F
    Departments of Psychology and Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark..
    Aerobic fitness influences working memory updating via the striatal dopaminergic system in older adultsManuscript (preprint) (Other academic)
    Abstract [en]

    There is much evidence that dopamine is vital for cognitive functioning in aging. Here we tested the hypothesis that aerobic exercise and fitness influences dopaminergic neurotransmission in the striatum as measured by positron emission tomography (PET) and the non-displacable binding potential (BPND ) of [11C]raclopride, and in turn performance on offline working-memory updating tasks. In a sample of 58 older sedentary adults undergoing a six-months exercise intervention, aerobic exercise compared to stretching, toning, and resistance training did not have a differential effect on BPND . At baseline, higher aerobic fitness levels (VO2peak ) were associated with higher BPND  in the striatum. Following the intervention, for both forms of training, we found reduced BPND , indicating increased dopamine (DA), in a cluster in the anterior striatum in individuals with larger improvements in VO2peak . This reduction in BPND  mediated a positive indirect effect of VO2peak  on working-memory updating performance. Collectively these findings implicate DA as a neurocognitive mechanism explaining the positive effects of staying physically active at an old age for working memory.

  • 40.
    Jonasson, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Kramer, Arthur
    Departments of Psychology and Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA.
    Lundquist, Anders
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.
    Aerobic Exercise Intervention, CognitivePerformance, and Brain Structure: results from the Physical Influences on Brain in Aging (PHIBRA) Study2017In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 8, p. 1-15, article id 336Article in journal (Refereed)
    Abstract [en]

    Studies have shown that aerobic exercise has the potential to improve cognition and reduce brain atrophy in older adults. However, the literature is equivocal with regards to the specificity or generality of these effects. To this end, we report results on cognitive function and brain structure from a 6-month training intervention with 60 sedentary adults (64–78 years) randomized to either aerobic training or stretching and toning control training. Cognitive functions were assessed with a neuropsychological test battery in which cognitive constructs were measured using several different tests. Freesurfer was used to estimate cortical thickness in frontal regions and hippocampus volume. Results showed that aerobic exercisers, compared to controls, exhibited a broad, rather than specific, improvement in cognition as indexed by a higher “Cognitive score,” a composite including episodic memory, processing speed, updating, and executive function tasks (p = 0.01). There were no group differences in cortical thickness, but additional analyses revealed that aerobic fitness at baseline was specifically related to larger thickness in dorsolateral prefrontal cortex (dlPFC), and hippocampus volume was positively associated with increased aerobic fitness over time. Moreover, “Cognitive score” was related to dlPFC thickness at baseline, but changes in “Cognitive score” and dlPFC thickness were associated over time in the aerobic group only. However, aerobic fitness did not predict dlPFC change, despite the improvement in “Cognitive score” in aerobic exercisers. Our interpretation of these observations is that potential exercise-induced changes in thickness are slow, and may be undetectable within 6-months, in contrast to change in hippocampus volume which in fact was predicted by the change in aerobic fitness. To conclude, our results add to a growing literature suggesting that aerobic exercise has a broad influence on cognitive functioning, which may aid in explaining why studies focusing on a narrower range of functions have sometimes reported mixed results.

  • 41.
    Jonasson, Lars S.
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Social Sciences, Centre for Population Studies (CPS).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Braver, Todd S.
    Department of Psychology,Washington University, St Louis, MO 63130, USA.
    Ögren, Mattias
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bäckman, Lars
    Aging Research Center, Karolinska Institute, SE-113 30 Stockholm, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Dopamine release in nucleus accumbens during rewarded task switching measured by [11C]raclopride2014In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 99, p. 357-364Article in journal (Refereed)
    Abstract [en]

    Reward and motivation have positive influences on cognitive-control processes in numerous settings. Models of reward implicate corticostriatal loops and the dopamine (DA) system, with special emphasis on D2 receptors in nucleus accumbens (NAcc). In this study, 11 right-handed males (35-40 years) were scanned with positron emission tomography (PET) in a single [(11)C]raclopride dynamic scan during rewarded and non-rewarded task switching. Rewarded task switching (relative to baseline task switching) decreased [(11)C]raclopride binding in NAcc. Decreasing NAcc [(11)C]raclopride binding was strongly associated with task reaction time measures that reflect individual differences in effort and control strategies. Voxelwise analyses additionally revealed reward-related DA release in anterodorsal caudate, a region previously associated with task-switching. These PET findings provide evidence for striatal DA release during motivated cognitive control, and further suggest that NAcc DA release predicts the task reaction time benefits of reward incentives.

  • 42.
    Jonasson, Lars S.
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Kramer, Arthur F.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.
    Higher striatal D2-receptor availability in aerobically fit older adults but non-selective intervention effects after aerobic versus resistance training2019In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 202, article id 116044Article in journal (Refereed)
    Abstract [en]

    There is much evidence that dopamine is vital for cognitive functioning in aging. Here we tested the hypothesis that aerobic exercise and fitness influence dopaminergic neurotransmission in the striatum, and in turn performance on offline working-memory updating tasks. Dopaminergic neurotransmission was measured by positron emission tomography (PET) and the non-displacable binding potential (BPND) of [11C]raclopride, i.e. dopamine (DA) D2-receptor (D2R) availability. Fifty-four sedentary older adults underwent a six-months exercise intervention, performing either aerobic exercise or stretching, toning, and resistance active control training. At baseline, higher aerobic fitness levels (VO2peak) were associated with higher BPND in the striatum, providing evidence of a link between an objective measure of aerobic fitness and D2R in older adults. BPND decreased substantially over the intervention in both groups but the intervention effects were non-selective with respect to exercise group. The decrease was several times larger than any previously estimated annual decline in D2R, potentially due to increased endogenous DA. Working-memory was unrelated to D2R both at baseline and following the intervention. To conclude, we provide partial evidence for a link between physical exercise and DA. Utilizing a PET protocol able to disentangle both D2R and DA levels could shed further light on whether, and how, aerobic exercise impacts the dopaminergic system in older adults.

  • 43.
    Jonsson, Håkan
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Orthopaedics.
    Riklund-Åhlström, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Lind, Jonas
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
    Positive pivot shift after ACL reconstruction predicts later osteoarthrosis: 63 patients follewed 5-9 years after surgery2004In: Acta Orthop Scand, ISSN 0001-6470, Vol. 75, no 5, p. 594-599Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Rupture of the anterior cruciate ligament (ACL) may cause osteoarthrosis (OA) and functional impairment. We wanted to find out whether the degree of knee stability obtained after ACL reconstruction correlates with radiographic and clinical outcome. PATIENTS AND METHODS: We examined 63 patients 2 and 5-9 years after anterior cruciate ligament (ACL) reconstruction. Knee stability was assessed 2 years after surgery by recording AP laxity using radiostereometric technique (RSA) and by performing the pivot shift test. Degeneration of the knee joint was evaluated with bone scintigraphy, and radiographically. Functional outcome was assessed with Lysholm score, Tegner activity scale and with the one-leg hop test. RESULTS: Radiographic signs of osteoarthrosis at the most recent follow-up (5-9 years) did not correlate with knee stability. Patients with positive pivot shift test 2 years after surgery showed increased scintigraphic activity of the subchondral bone at the most recent follow-up, and inferior subjective functional outcome 2 years after surgery. Knees having had meniscus resections had more often OA. Radiographical signs of OA were associated with higher scintigraphic uptake in the operated knee relative to the contralateral knee. INTERPRETATION: The ability to obliterate the pivoting by ACL reconstruction appears to be more important than normalizing the AP laxity in order to prevent later OA.

  • 44.
    Karalija, Nina
    et al.
    Umeå University.
    Papenberg, Goran
    Wåhlin, Anders
    Umeå University.
    Johansson, Jarkko
    Umeå University.
    Andersson, Micael
    Umeå University.
    Axelsson, Jan
    Umeå University.
    Riklund, Katrine
    Umeå University.
    Lövdén, Martin
    Lindenberger, Ulman
    Bäckman, Lars
    Nyberg, Lars
    Umeå University.
    C957T-mediated Variation in Ligand Affinity Affects the Association between C-11-raclopride Binding Potential and Cognition2019In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 31, no 2, p. 314-325Article in journal (Refereed)
    Abstract [en]

    The dopamine (DA) system plays an important role in cognition. Accordingly, normal variation in DA genes has been found to predict individual differences in cognitive performance. However, little is known of the impact of genetic differences on the link between empirical indicators of the DA system and cognition in humans. The present work used PET with C-11-raclopride to assess DA D2-receptor binding potential (BP) and links to episodic memory, working memory, and perceptual speed in 179 healthy adults aged 64-68 years. Previously, the T-allele of a DA D2-receptor single-nucleotide polymorphism, C957T, was associated with increased apparent affinity of C-11-raclopride, giving rise to higher BP values despite similar receptor density values between allelic groups. Consequently, we hypothesized that C-11-raclopride BP measures inflated by affinity rather than D2-receptor density in T-allele carriers would not be predictive of DA integrity and therefore prevent finding an association between C-11-raclopride BP and cognitive performance. In accordance with previous findings, we show that C-11-raclopride BP was increased in T-homozygotes. Importantly, C-11-raclopride BP was only associated with cognitive performance in groups with low or average ligand affinity (C-allele carriers of C957T, n = 124), but not in the high-affinity group (T-homozygotes, n = 55). The strongest C-11-raclopride BP-cognition associations and the highest level of performance were found in C-homozygotes. These findings show that genetic differences modulate the link between BP and cognition and thus have important implications for the interpretation of DA assessments with PET and C-11-raclopride in multiple disciplines ranging from cognitive neuroscience to psychiatry and neurology.

  • 45. Koehncke, Ylva
    et al.
    Papenberg, Goran
    Jonasson, Lars S.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Karalija, Nina
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Salami, Alireza
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bäckman, Lars
    Lindenberger, Ulman
    Lövdén, Martin
    Self-rated intensity of habitual physical activities is positively associated with dopamine D-2/3 receptor availability and cognition2018In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 181, p. 605-616Article in journal (Refereed)
    Abstract [en]

    Between-person differences in cognitive performance in older age are associated with variations in physical activity. The neurotransmitter dopamine (DA) contributes to cognitive performance, and the DA system deteriorates with advancing age. Animal data and a patient study suggest that physical activity modulates DA receptor availability, but data from healthy humans are lacking. In a cross-sectional study with 178 adults aged 64-68 years, we investigated links among self-reported physical activity, D(2/3)DA receptor (D2/3DR) availability, and cognitive performance. D2/3DR availability was measured with [C-11]raclopride positron emission tomography at rest. We used structural equation modeling to obtain latent factors for processing speed, episodic memory, working memory, physical activity, and D2/3DR availability in caudate, putamen, and hippocampus. Physical activity intensity was positively associated with D2/3DR availability in caudate, but not putamen and hippocampus. Frequency of physical activity was not related to D2/3DR availability. Physical activity intensity was positively related to episodic memory and working memory. D2/3DR availability in caudate and hippocampus was positively related to episodic memory. Taken together, our results suggest that striatal DA availability might be a neurochemical correlate of episodic memory that is also associated with physical activity.

  • 46. Krantz, David
    et al.
    Hartana, Ciputra Adijaya
    Winerdal, Malin E
    Johansson, Markus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Sundsvall Hospital, Sundsvall, Sweden.
    Alamdari, Farhood
    Jakubczyk, Tomasz
    Huge, Ylva
    Aljabery, Firas
    Palmqvist, Karin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Urology Section, Department of Surgery, Östersund County Hospital, Östersund, Sweden.
    Zirakzadeh, A Ali
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Holmström, Benny
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Division of Urology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Winqvist, Ola
    Neoadjuvant Chemotherapy Reinforces Antitumour T cell Response in Urothelial Urinary Bladder Cancer2018In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, no 6, p. 688-692Article in journal (Refereed)
    Abstract [en]

    Evidence indicates that neoadjuvant chemotherapy (NAC) may promote antitumour immune responses by activating T cells. The tumour-draining sentinel node (SN) is a key site to study tumour-specific T cell activation, being the primary immunological barrier against the tumour. In this prospective study, we set out to elucidate the effects of NAC on T cell subsets in the SNs of patients with muscle-invasive urothelial bladder cancer. We found that CD8+ effector T (Teff) cell exhaustion was reduced after NAC treatment, while cytotoxicity was increased. Additionally, in complete responders (CR patients), these cells were functionally committed effectors, as displayed by epigenetic analysis. In CD4+ Teffs, NAC treatment was associated with increased clonal expansion of tumour-specific SN-derived cells, as demonstrated by a specific cell reactivity assay. In contrast, we observed an attenuating effect of NAC on regulatory T cells (Tregs) with a dose-dependent decrease in Treg frequency and reduced effector molecule expression in the remaining Tregs. In addition, multicolour flow cytometry analysis revealed that CR patients had higher Teff to activated Treg ratio, promoting antitumoural T cell activation. These results suggest that NAC reinforces the antitumour immune response by activating the effector arm of the T cell compartment and diminishing the influence of suppressive Tregs.

    PATIENT SUMMARY: In this report, we analysed the effect of chemotherapy on immune cell subsets of 40 patients with advanced bladder cancer. We found that chemotherapy has a positive effect on immune effector T cells, whereas an opposite, diminishing effect was observed for immune-suppressive regulatory T cells. We conclude that chemotherapy reinforces the antitumour immune response in bladder cancer patients.

  • 47. Kruse, J.
    et al.
    Lehto, N.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Tegner, Y.
    Engström, A.
    Scrutinized with inadequate control and support: Interns' experiences communicating with and writing referrals to hospital radiology departments - A qualitative study2016In: Radiography, ISSN 1078-8174, E-ISSN 1532-2831, Vol. 22, no 4, p. 313-318Article in journal (Refereed)
    Abstract [en]

    Introduction: Interns' experiences communicating with and writing referrals to hospital radiology departments are important for patient safety, image quality, and decision-making in the diagnostic process. Understanding roles within the department and in the diagnostic process is important for communication. This study aimed to describe interns' experiences communicating with and writing referrals to their hospital's radiology department. Method: A qualitative study design was used. Data was collected from focus discussions with ten interns in three focus groups in Northern Sweden during 2012. The data were subjected to qualitative content analysis. Results: One theme, "a feeling of being scrutinized and lacking control", was identified in the final categories. The interns experienced that the radiology department placed high demands on them and desired more diagnostic skills training, resources and feedback. The interns suggested the following improvements: enhanced dialogue and feedback, improved education, handy guidelines, and practice writing referrals. Conclusion: Interns need more feedback from, and dialogue with, members of the Department of Radiology. They also need more knowledge of referral guidelines, appropriateness criteria and more practice to develop their knowledge and skill for writing referrals. They describe feelings of inadequate support and feel scrutinized in demanding work conditions and need more collaboration. They also need more time and more control of radiology outcomes, and they are eager to learn. 

  • 48.
    Larsson, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Holmberg, Daniel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Sundström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Optimal contrast as a function of noise for Butterworth filtering of 111 In-pentetreotide SPECT when using model-based compensation2013In: 2013 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE (NSS/MIC), 2013Conference paper (Refereed)
    Abstract [en]

    In 111 In-pentetreotide SPECT, it can be difficult to detect small tumors because of low spatial resolution and high noise levels. For an efficient cancer treatment, it is however important to detect the tumors at an early stage. The aim of this study was to perform optimization of Butterworth post-filtering of In-111-pentetreotide SPECT, with regard to small tumor detection in the liver. All images were reconstructed with model-based OSEM reconstruction. Two collimators are evaluated, the extended low-energy general-purpose (ELEGP) and the medium-energy general-purpose (MEGP) collimator. The raw-data projection images are produced using Monte Carlo simulations of an anthropomorphic phantom with realistic In-111-pentetreotide uptake, including seven spherical tumors in the liver. Evaluation was performed using tumor contrast as a function of background noise. According to the results, the detection of the smallest tumors is facilitated by not applying a filter. For somewhat larger tumors, a Butterworth filter of critical frequencies of 0.5-0.6 cm(-1) and an order of 10-12 is more appropriate. ELEGP proved to be better than MEGP for small tumor detection. The study is a continuation of a previous project where collimator choice, acquisition time, number of projection angles and OSEM settings were studied for the same geometry.

  • 49.
    Larsson, Anne
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Jakobson Mo, Susanna
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Ljungberg, Michael
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Dopamine D2 receptor SPECT with (123)I-IBZM: evaluation of collimator and post-filtering when using model-based compensation-a Monte Carlo study.2010In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 55, no 7, p. 1971-1988Article in journal (Refereed)
    Abstract [en]

    In (123)I-IBZM brain SPECT, the main interest is the activity uptake in the striatum relative to the background, and semi-quantitative techniques using regions of interest are typically used for this purpose. Uncertainties in the measured uptakes can however be a problem due to low contrasts and high noise levels. Like SPECT in general, IBZM SPECT should benefit from reconstruction methods that include model-based compensation, but it is important that image acquisition is optimized for this technique. An important factor is the choice of collimator. In this study we compare four different parallel-hole collimators for IBZM SPECT regarding overall quantitative accuracy and measured uptake ratio as a function of image noise and uncertainty. The collimators are low-energy high-resolution (LEHR), low-energy general-purpose (LEGP), extended LEGP (ELEGP) and medium-energy general-purpose (MEGP). The effect of three Butterworth post-filters with cut-off frequencies of 0.3, 0.45 and 0.6 cm(-1) (power factor 8) is also studied. All raw-data projections are produced using Monte Carlo simulations. Of the investigated collimators, the one that is most sensitive to the primary photons, ELEGP, proved to be the most optimal for realistic noise levels. Butterworth post-filtering is advantageous, and the cut-off frequency 0.45 cm(-1) was the best compromise in this study.

  • 50.
    Larsson, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jakobson Mo, Susanna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Rotation radius dependence of 123I-FP-CIT and 123I-IBZM SPECT uptake ratios: a Monte Carlo study2012In: Journal of Nuclear Medicine Technology, ISSN 0091-4916, E-ISSN 1535-5675, Vol. 40, no 4, p. 249-254Article in journal (Refereed)
    Abstract [en]

    In dopamine brain SPECT, semiquantitative techniques are in use, mostly for research purposes, to calculate activity uptake in the striatum relative to the background. The measured uptake ratios depend on both acquisition and reconstruction, and one important parameter is the rotation radius of the γ-camera detectors, which affects spatial resolution. In brain SPECT research studies, the rotation radius is typically set to a constant value to maintain a constant resolution, but because of variations in patient anatomy and compliance, this is not always possible.

    METHODS: In this study, correction factors as a function of rotation radius are developed to correct the uptake ratios where the rotation radius has deviated from the reference value, 15 cm. Monte Carlo simulations of a digital brain phantom were used to produce images with a high and a low uptake ratio, and for both studies the rotation radius was varied between 14 and 23 cm. Two different methods, one based on 2-dimensional (2D) regions of interest of constant shape and size, and one based on predefined 3-dimensional (3D) volumes of interest, were used to calculate the semiquantitative uptake ratios.

    RESULTS: For the 2D method, the change in uptake ratio was 1.2%/cm for the high uptake ratio and 0.9%/cm for the low uptake ratio. The corresponding results for the 3D method were 2.1% and 1.7%, respectively.

    CONCLUSION: The 3D method was found to be more dependent on rotation radius than the 2D method, which was expected because of the 3D nature of the partial-volume effect. The correction factors were, however, less dependent on which of the 2 uptake ratios was simulated, which is positive for the application of the correction equations on patient data.

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