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  • 1. Ahlén Bergman, Emma
    et al.
    Hartana, Ciputra Adijaya
    Johansson, Markus
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Urology, Sundsvall Hospital, Sundsvall, Sweden..
    Linton, Ludvig B
    Berglund, Sofia
    Hyllienmark, Martin
    Lundgren, Christian
    Holmström, Benny
    Palmqvist, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgery, Urology Section, Östersund County Hospital, Östersund, Sweden.
    Hansson, Johan
    Alamdari, Farhood
    Huge, Ylva
    Aljabery, Firas
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Winerdal, Malin E
    Krantz, David
    Zirakzadeh, A. Ali
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Unit of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Marits, Per
    Sjöholm, Louise K
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Winqvist, Ola
    Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients2018Ingår i: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 10, artikel-id 102Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4+ T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-γ, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4+ T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.

    RESULTS: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4+ lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4+ lymphocytes in lymph nodes and blood (lymph nodes vs tumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p > 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4+ T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4+ T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.

    CONCLUSION: Increased lineage commitment in CD4+ T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4+ T cell lineages as a useful readout for clinical staging.

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  • 2.
    Andersson, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Granberg, Christoffer
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    A novel system for quality assurance of radiology equipment2018Ingår i: EuroSafe Imaging 2018 / ESI-0064, EuroSafe Imaging , 2018Konferensbidrag (Refereegranskat)
  • 3.
    Andersson, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Karpe, Fredrik
    NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, UK.
    Sjöström, Lars-Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Association of adipose tissue blood flow with fat depot sizes and adipokines in women2012Ingår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 36, nr 6, s. 783-789Artikel i tidskrift (Refereegranskat)
    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.

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  • 4.
    Andersson, Ronny
    et al.
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Hofer, Åke
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Dermatologi och venereologi.
    Riklund-Åhlström, Katrine
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Diagnostisk radiologi.
    Henriksson, Roger
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Effects of interferon-[alpha], verapamil and dacarbazine in the treatment of advanced malignant melanoma2003Ingår i: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 13, nr 1, s. 87-91Artikel i tidskrift (Refereegranskat)
    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.

  • 5. Arheden, Håkan
    et al.
    Aspelin, Peter
    Bajc, Marika
    Damm, Sabine
    Flodmark, Olof
    Friberg, Peter
    Gustafsson, Lars
    Holtås, Stig
    Modin, Agnes
    Riklund, Katrine
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Diagnostisk radiologi.
    Rydh, Anders
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Diagnostisk radiologi.
    Functional imaging medicine: a new specialty with great prospects2006Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, nr 39, s. 2883-2884Artikel i tidskrift (Refereegranskat)
  • 6.
    Asklund, Thomas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergström, Åsa
    Kasper, Maria
    Ögren, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Toftgård, Rune
    Riklund, Katrine Åhlström
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Early and persisting response to vismodegib in a patient with bone metastasizing medulloblastoma2013Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, nr 4, s. 862-865Artikel i tidskrift (Refereegranskat)
  • 7.
    Asklund, Thomas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Sandström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Shahidi, Saeed
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Durable stabilization of three chordoma cases by bevacizumab and erlotinib2014Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, nr 7, s. 980-984Artikel i tidskrift (Refereegranskat)
  • 8. 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 universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    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, Germany2018Ingår i: Molecular Imaging and Biology, ISSN 1536-1632, E-ISSN 1860-2002, Vol. 20, nr 1, s. 4-20Artikel, forskningsöversikt (Refereegranskat)
    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.

  • 9. 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 universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    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, Germany2016Ingår i: Molecular Imaging and Biology, ISSN 1536-1632, E-ISSN 1860-2002, Vol. 18, nr 5, s. 637-650Artikel i tidskrift (Refereegranskat)
    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.

  • 10.
    Bergdahl, Jan
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Nilsson, Lars-Göran
    Riklund Åhlström, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Treatment of chronic stress in employees: subjective, cognitive and neural correlates2005Ingår i: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 46, nr 5, s. 395-402Artikel i tidskrift (Refereegranskat)
    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.

  • 11.
    Björeland, Ulrika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Nyholm, Tufve
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Jonsson, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Skorpil, Mikael
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Blomqvist, Lennart
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Strandberg, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Beckman, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Thellenberg-Karlsson, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Impact of neoadjuvant androgen deprivation therapy on magnetic resonance imaging features in prostate cancer before radiotherapy2021Ingår i: Physics and Imaging in Radiation Oncology, E-ISSN 2405-6316, Vol. 17, s. 117-123Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose: In locally advanced prostate cancer (PC), androgen deprivation therapy (ADT) in combination with whole prostate radiotherapy (RT) is the standard treatment. ADT affects the prostate as well as the tumour on multiparametric magnetic resonance imaging (MRI) with decreased PC conspicuity and impaired localisation of the prostate lesion. Image texture analysis has been suggested to be of aid in separating tumour from normal tissue. The aim of the study was to investigate the impact of ADT on baseline defined MRI features in prostate cancer with the goal to investigate if it might be of use in radiotherapy planning.

    Materials and methods: Fifty PC patients were included. Multiparametric MRI was performed before, and three months after ADT. At baseline, a tumour volume was delineated on apparent diffusion coefficient (ADC) maps with suspected tumour content and a reference volume in normal prostatic tissue. These volumes were transferred to MRIs after ADT and were analysed with first-order -and invariant Haralick -features.

    Results: At baseline, the median value and several of the invariant Haralick features of ADC, showed a significant difference between tumour and reference volumes. After ADT, only ADC median value could significantly differentiate the two volumes.

    Conclusions: Invariant Haralick -features could not distinguish between baseline MRI defined PC and normal tissue after ADT. First-order median value remained significantly different in tumour and reference volumes after ADT, but the difference was less pronounced than before ADT.

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  • 12.
    Björeland, Ulrika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Strandberg, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Söderkvist, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nyholm, Tufve
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Jonsson, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Skorpil, Mikael
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Blomqvist, Lennart
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Beckman, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Thellenberg-Karlsson, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Diffusion-weighted MRI and 11C-acetate-PET/CT imaging in high-risk/very high-risk prostate cancerManuskript (preprint) (Övrigt vetenskapligt)
  • 13. Brolin, Gustav
    et al.
    Edenbrandt, Lars
    Granerus, Goeran
    Olsson, Anna
    Afzelius, David
    Gustafsson, Agneta
    Jonsson, Cathrine
    Hagerman, Jessica
    Johansson, Lena
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. EQUALIS AB, Uppsala, Sweden.
    Ljungberg, Michael
    The accuracy of quantitative parameters in Tc-99m-MAG3 dynamic renography: a national audit based on virtual image data2016Ingår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 36, nr 2, s. 146-154Artikel i tidskrift (Refereegranskat)
    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.

  • 14.
    Bäckström, David C
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper. DeDepartment of Neurology, Yale University, New Haven, CT, USA.
    Granåsen, Gabriel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Jakobson Mo, Susanna
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Trupp, Miles
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Zetterberg, Henrik
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease and UCL Queen Square Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK.
    Blennow, Kaj
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Eriksson Domellöf, Magdalena
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Prediction and early biomarkers of cognitive decline in Parkinson disease and atypical parkinsonism: a population-based study2022Ingår i: Brain Communications, E-ISSN 2632-1297, Vol. 4, nr 2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The progression of cognitive decline is heterogeneous in the three most common idiopathic parkinsonian diseases: Parkinson disease, multiple system atrophy and progressive supranuclear palsy. The causes for this heterogeneity are not fully understood, and there are no validated biomarkers that can accurately identify patients who will develop dementia and when. In this population-based, prospective study, comprehensive neuropsychological testing was performed repeatedly in new-onset, idiopathic parkinsonism. Dementia was diagnosed until 10 years and participants (N = 210) were deeply phenotyped by multimodal clinical, biochemical, genetic and brain imaging measures. At baseline, before the start of dopaminergic treatment, mild cognitive impairment was prevalent in 43.4% of the patients with Parkinson disease, 23.1% of the patients with multiple system atrophy and 77.8% of the patients with progressive supranuclear palsy. Longitudinally, all three diseases had a higher incidence of cognitive decline compared with healthy controls, but the types and severity of cognitive dysfunctions differed. In Parkinson disease, psychomotor speed and attention showed signs of improvement after dopaminergic treatment, while no such improvement was seen in other diseases. The 10-year cumulative probability of dementia was 54% in Parkinson disease and 71% in progressive supranuclear palsy, while there were no cases of dementia in multiple system atrophy. An easy-to-use, multivariable model that predicts the risk of dementia in Parkinson disease within 10 years with high accuracy (area under the curve: 0.86, P < 0.001) was developed. The optimized model adds CSF biomarkers to four easily measurable clinical features at baseline (mild cognitive impairment, olfactory function, motor disease severity and age). The model demonstrates a highly variable but predictable risk of dementia in Parkinson disease, e.g. a 9% risk within 10 years in a patient with normal cognition and CSF amyloid-β42 in the highest tertile, compared with an 85% risk in a patient with mild cognitive impairment and CSF amyloid-β42 in the lowest tertile. Only small or no associations with cognitive decline were found for factors that could be easily modifiable (such as thyroid dysfunction). Risk factors for cognitive decline in multiple system atrophy and progressive supranuclear palsy included signs of systemic inflammation and eye movement abnormalities. The predictive model has high accuracy in Parkinson disease and might be used for the selection of patients into clinical trials or as an aid to improve the prevention of dementia. 

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  • 15.
    Bäckström, David C
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Jakobson Mo, Susanna
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Zetterberg, Henrik
    Blennow, Kaj
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lenfeldt, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Neurofilament concentration in CSF correlates with disease severity, survival and imaging measures of neurodegeneration in incident Parkinson diseaseManuskript (preprint) (Övrigt vetenskapligt)
  • 16.
    Bäckström, David C
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Jakobson Mo, Susanna
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Zetterberg, Henrik
    Blennow, Kaj
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Lenfeldt, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    NfL as a biomarker for neurodegeneration and survival in Parkinson disease2020Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 95, nr 7, s. e827-e838Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To determine whether neurofilament light chain protein in CSF (cNfL), a sensitive biomarker of neuroaxonal damage, reflects disease severity or can predict survival in Parkinson disease (PD).

    METHODS: We investigated whether disease severity, phenotype, or survival in patients with new-onset PD correlates with cNfL concentrations around the time of diagnosis in the population-based New Parkinsonism in Umeå (NYPUM) study cohort (n = 99). A second, larger new-onset PD cohort (n = 194) was used for independent validation. Association of brain pathology with the cNfL concentration was examined with striatal dopamine transporter imaging and repeated diffusion tensor imaging at baseline and 1 and 3 years.

    RESULTS: Higher cNfL in the early phase of PD was associated with greater severity of all cardinal motor symptoms except tremor in both cohorts and with shorter survival and impaired olfaction. cNfL concentrations above the median of 903 ng/L conferred an overall 5.8 times increased hazard of death during follow-up. After adjustment for age and sex, higher cNfL correlated with striatal dopamine transporter uptake deficits and lower fractional anisotropy in diffusion tensor imaging of several axonal tracts.

    CONCLUSIONS: cNfL shows usefulness as a biomarker of disease severity and to predict survival in PD. The present results indicate that the cNfL concentration reflects the intensity of the neurodegenerative process, which could be important in future clinical trials.

    CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with PD, cNfL concentrations are associated with more severe disease and shorter survival.

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  • 17.
    Bäckström, David
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Granåsen, Gabriel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Eriksson Domellöf, Magdalenax
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Jakobson Mo, Susanna
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Zetterberg, Henrik
    Blennow, Kaj
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Early predictors of mortality in parkinsonism and Parkinson disease: A population-based study2018Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 91, nr 22, s. E2045-E2056Artikel i tidskrift (Refereegranskat)
    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.

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  • 18. de Boer, Lieke
    et al.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Chowdhury, Rumana
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Dolan, Raymond J.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Backman, Lars
    Guitart-Masip, Marc
    Dorsal striatal dopamine D1 receptor availability predicts an instrumental bias in action learning2019Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 116, nr 1, s. 261-270Artikel i tidskrift (Refereegranskat)
    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.

  • 19. de Boer, Lieke
    et al.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Dayan, Peter
    Backman, Lars
    Guitart-Masip, Marc
    Attenuation of dopamine-modulated prefrontal value signals underlies probabilistic reward learning deficits in old age2017Ingår i: eLIFE, E-ISSN 2050-084X, Vol. 6, artikel-id e2642Artikel i tidskrift (Refereegranskat)
    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.

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  • 20. de Boer, Lieke
    et al.
    Garzón, Benjamín
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Department of Radiation Sciences, Diagnostic Radiology, University Hospital, Umeå University, Umeå, Sweden.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Department of Radiation Sciences, Diagnostic Radiology, University Hospital, Umeå University, Umeå, Sweden.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Department of Radiation Sciences, Diagnostic Radiology, University Hospital, Umeå University, Umeå, Sweden.
    Bäckman, Lars
    Guitart-Masip, Marc
    Corticostriatal White Matter Integrity and Dopamine D1 Receptor Availability Predict Age Differences in Prefrontal Value Signaling during Reward Learning2020Ingår i: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 30, nr 10, s. 5270-5280Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Probabilistic reward learning reflects the ability to adapt choices based on probabilistic feedback. The dopaminergically innervated corticostriatal circuit in the brain plays an important role in supporting successful probabilistic reward learning. Several components of the corticostriatal circuit deteriorate with age, as it does probabilistic reward learning. We showed previously that D1 receptor availability in NAcc predicts the strength of anticipatory value signaling in vmPFC, a neural correlate of probabilistic learning that is attenuated in older participants and predicts probabilistic reward learning performance. We investigated how white matter integrity in the pathway between nucleus accumbens (NAcc) and ventromedial prefrontal cortex (vmPFC) relates to the strength of anticipatory value signaling in vmPFC in younger and older participants. We found that in a sample of 22 old and 23 young participants, fractional anisotropy in the pathway between NAcc and vmPFC predicted the strength of value signaling in vmPFC independently from D1 receptor availability in NAcc. These findings provide tentative evidence that integrity in the dopaminergic and white matter pathways of corticostriatal circuitry supports the expression of value signaling in vmPFC which supports reward learning, however, the limited sample size calls for independent replication. These and future findings could add to the improved understanding of how corticostriatal integrity contributes to reward learning ability.

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  • 21.
    Ekman, Urban
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Jakobson Mo, Susanna
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Functional brain activity and presynaptic dopamine uptake in patients with Parkinson's disease and mild cognitive impairment: a cross-sectional study2012Ingår i: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 11, nr 8, s. 679-687Artikel i tidskrift (Refereegranskat)
    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.

  • 22.
    Elgh, Eva
    et al.
    Umeå universitet, Medicinsk fakultet, Samhällsmedicin och rehabilitering, Geriatrik.
    Sundström, Torbjörn
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Diagnostisk radiologi.
    Näsman, Birgitta
    Umeå universitet, Medicinsk fakultet, Samhällsmedicin och rehabilitering, Geriatrik.
    Riklund Åhlström, Katrine
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Diagnostisk radiologi.
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskaplig fakultet, Psykologi.
    Memory functions and rCBF (99m)Tc-HMPAO SPET: developing diagnostics in Alzheimer's disease2002Ingår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, ISSN 1619-7070, Vol. 29, nr 9, s. 1140-1148Artikel i tidskrift (Refereegranskat)
    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.

  • 23.
    Eriksson, David
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Blomberg, Jeanette
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Lindgren, Theres
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Löfroth, Per-Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Johansson, Lennart
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Stigbrand, Torgny
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Iodine-131 induces mitotic catastrophes and activates apoptotic pathways in HeLa Hep2 cells2008Ingår i: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 23, nr 5, s. 541-549Artikel i tidskrift (Refereegranskat)
    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.

  • 24.
    Eriksson, David
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Löfroth, Per-Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Johansson, Lennart
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Stigbrand, Torgny
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Apoptotic signalling in HeLa Hep2 cells following 5 Gy of cobalt-60 gamma radiation2009Ingår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 29, nr 11, s. 4361-4366Artikel i tidskrift (Refereegranskat)
    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.

  • 25.
    Eriksson, David
    et al.
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Immunologi/immunkemi.
    Löfroth, Per-Olov
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Radiofysik.
    Johansson, Lennart
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Radiofysik.
    Åhlström Riklund, Katrine
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Diagnostisk radiologi.
    Stigbrand, Torgny
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Immunologi/immunkemi.
    Cell cycle disturbances and mitotic catastrophes in HeLa Hep2 cells following 2.5 to 10 Gy of ionizing radiation.2007Ingår i: Clin Cancer Res, ISSN 1078-0432, Vol. 13, nr 18 Pt 2, s. 5501s-5508sArtikel i tidskrift (Refereegranskat)
    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.

  • 26.
    Eriksson, David
    et al.
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi.
    Mirzaie-Joniani, Homa
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi.
    Sheikholvaezin, Ali
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi.
    Löfroth, Per-Olov
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Radiofysik.
    Johansson, Lennart
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Radiofysik.
    Åhlström-Riklund, Katrine
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Diagnostisk radiologi.
    Stigbrand, Torgny
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi.
    Combined low dose radio- and radioimmunotherapy of experimental HeLa Hep 2 tumours.2003Ingår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 30, nr 6, s. 895-906Artikel i tidskrift (Refereegranskat)
    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.

  • 27.
    Eriksson, Johan
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund Åhlström, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Similar frontal and distinct posterior cortical regions mediate visual and auditory perceptual awareness2007Ingår i: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 17, nr 4, s. 760-765Artikel i tidskrift (Refereegranskat)
    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.

  • 28.
    Eriksson, Johan
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund Åhlström, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Visual consciousness: dissociating the neural correlates of perceptual transitions from sustained perception with fMRI2004Ingår i: Consciousness and Cognition, ISSN 1053-8100, E-ISSN 1090-2376, Vol. 13, nr 1, s. 61-72Artikel i tidskrift (Refereegranskat)
    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.

  • 29.
    Erlandsson, Ann
    et al.
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi.
    Eriksson, David
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi.
    Johansson, Lennart
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Radiofysik.
    Riklund, Katrine
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Diagnostisk radiologi.
    Stigbrand, Torgny
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi.
    Sundström, Birgitta Elisabeth
    In vivo clearing of idiotypic antibodies with antiidiotypic antibodies and their derivatives2006Ingår i: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 43, nr 6, s. 599-606Artikel i tidskrift (Refereegranskat)
    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.

  • 30.
    Farnsworth von Cederwald, Bryn
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Johansson, Jarkko
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Karalija, Nina
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Boraxbekk, Carl-Johan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Danish Research Center for Magnetic Resonance (DRCMR), Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Amager and Hvidovre, Copenhagen, Denmark; Institute of Sports Medicine Copenhagen (ISMC) and Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark; Institute for Clinical Medicine, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark.
    White matter lesion load determines exercise-induced dopaminergic plasticity and working memory gains in aging2023Ingår i: Translational Psychiatry, E-ISSN 2158-3188, Vol. 13, nr 1, artikel-id 28Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Age-related dopamine reductions have been suggested to contribute to maladaptive working memory (WM) function in older ages. One promising intervention approach is to increase physical activity, as this has been associated with plasticity of the striatal dopamine system and WM improvements, however with individual differences in efficacy. The present work focused on the impact of individual differences in white-matter lesion burden upon dopamine D2-like receptor (DRD2) availability and WM changes in response to a 6 months physical activity intervention. While the intervention altered striatal DRD2 availability and WM performance in individuals with no or only mild lesions (p < 0.05), no such effects were found in individuals with moderate-to-severe lesion severity (p > 0.05). Follow-up analyses revealed a similar pattern for processing speed, but not for episodic memory performance. Linear analyses further revealed that lesion volume (ml) at baseline was associated with reduced DRD2 availability (r = −0.41, p < 0.05), and level of DRD2 change (r = 0.40, p < 0.05). Taken together, this study underlines the necessity to consider cerebrovascular health in interventions with neurocognitive targets. Future work should assess whether these findings extend beyond measures of DRD2 availability and WM.

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  • 31.
    Flodin, Pär
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Jonasson, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (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 Adults2017Ingår i: Frontiers in Aging Neuroscience, E-ISSN 1663-4365, Vol. 9, artikel-id 267Artikel i tidskrift (Refereegranskat)
    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.

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  • 32. Garzón, Benjamín
    et al.
    Lövdén, Martin
    de Boer, Lieke
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Bäckman, Lars
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Guitart-Masip, Marc
    Role of dopamine and gray matter density in aging effects and individual differences of functional connectomes2021Ingår i: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 226, nr 3, s. 743-758Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    With increasing age, functional connectomes become dissimilar across normal individuals, reflecting heterogenous aging effects on functional connectivity (FC). We investigated the distribution of these effects across the connectome and their relationship with age-related differences in dopamine (DA) D1 receptor availability and gray matter density (GMD). With this aim, we determined aging effects on mean and interindividual variance of FC using fMRI in 30 younger and 30 older healthy subjects and mapped the contribution of each connection to the patterns of age-related similarity loss. Aging effects on mean FC accounted mainly for the dissimilarity between connectomes of younger and older adults, and were related, across brain regions, to aging effects on DA D1 receptor availability. Aging effects on the variance of FC indicated a global increase in variance with advancing age, explained connectome dissimilarity among older subjects and were related to aging effects on variance of GMD. The relationship between aging and the similarity of connectomes can thus be partly explained by age differences in DA modulation and gray matter structure.

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  • 33. Gatidis, Sergios
    et al.
    Beyer, Thomas
    Becker, Minerva
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nikolaou, Konstantin
    Cyran, Clemens
    Pfannenberg, Christina
    State of affairs of hybrid imaging in Europe: two multi-national surveys from 20172019Ingår i: Insights into Imaging, E-ISSN 1869-4101, Vol. 10, nr 1, artikel-id 57Artikel i tidskrift (Refereegranskat)
    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.

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  • 34. Glimelius, Bengt
    et al.
    Melin, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Enblad, Gunilla
    Alafuzoff, Irina
    Beskow, Anna
    Ahlström, Håkan
    Bill-Axelson, Anna
    Birgisson, Helgi
    Björ, Ove
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Edqvist, Per-Henrik
    Hansson, Tony
    Helleday, Thomas
    Hellman, Per
    Henriksson, Kerstin
    Hesselager, Göran
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Häggman, Michael
    Höglund, Martin
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Larsson, Chatarina
    Lindman, Henrik
    Ljuslinder, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Mindus, Stephanie
    Nygren, Peter
    Pontén, Fredrik
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Rosenquist, Richard
    Sandin, Fredrik
    Schwenk, Jochen M.
    Stenling, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Stålberg, Karin
    Stålberg, Peter
    Sundström, Christer
    Thellenberg Karlsson, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Westermark, Bengt
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Claesson-Welsh, Lena
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Sjöblom, Tobias
    U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden2018Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, nr 2, s. 187-194Artikel i tidskrift (Refereegranskat)
    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.

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  • 35.
    Grefve, Josefine
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Söderkvist, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Gunnlaugsson, Adalsteinn
    Department of Hematology, Oncology and Radiation Physics, Skane University Hospital, Lund University, Lund, Sweden.
    Sandgren, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Jonsson, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Keeratijarut Lindberg, Angsana
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Nilsson, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Zackrisson, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Moreau, Mathieu
    Department of Hematology, Oncology and Radiation Physics, Skane University Hospital, Lund University, Lund, Sweden.
    Thellenberg-Karlsson, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Olsson, Lars.E.
    Department of Translational Medicine, Medical Radiation Physics, Lund University, Malmö, Sweden.
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Blomqvist, Lennart
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Berg Loegager, Vibeke
    Department of Radiology, Copenhagen University Hospital in Herlev, Herlev, Denmark.
    Strandberg, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nyholm, Tufve
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Histopathology-validated gross tumor volume delineations of intraprostatic lesions using PSMA-positron emission tomography/multiparametric magnetic resonance imaging2024Ingår i: Physics and Imaging in Radiation Oncology, E-ISSN 2405-6316, Vol. 31, artikel-id 100633Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose: Dose escalation in external radiotherapy of prostate cancer shows promising results in terms of biochemical disease-free survival. Boost volume delineation guidelines are sparse which may cause high interobserver variability. The aim of this research was to characterize gross tumor volume (GTV) delineations based on multiparametric magnetic resonance imaging (mpMRI) and prostate specific membrane antigen-positron emission tomography (PSMA-PET) in relation to histopathology-validated Gleason grade 4 and 5 regions.

    Material and methods: The study participants were examined with [68Ga]PSMA-PET/mpMRI prior to radical prostatectomy. Four radiation oncologists delineated GTVs in 15 study participants, on four different image types; T2-weighted (T2w), diffusion weighted imaging (DWI), dynamic contrast enhanced (DCE) and PSMA-PET scans separately. The simultaneous truth and performance level estimation (STAPLE) algorithm was used to generate combined GTVs. GTVs were subsequently compared to histopathology. We analysed how Dice similarity coefficient (DSC) and lesion coverage are affected by using single versus multiple image types as well as by adding a clinical target volume (CTV) margin.

    Results: Median DSC (STAPLE) for different GTVs varied between 0.33 and 0.52. GTVPSMA-PET/mpMRI generated the highest median lesion coverage at 0.66. Combining different image types achieved similar lesion coverage as adding a CTV margin to contours from a single image type, while reducing non-malignant tissue inclusion within the target volume.

    Conclusion: The combined use of mpMRI or PSMA-PET/mpMRI shows promise, achieving higher DSC and lesion coverage while minimizing non-malignant tissue inclusion, in comparison to the use of a single image type with an added CTV margin.

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  • 36. Guitart-Masip, Marc
    et al.
    Kurth-Nelson, Zeb
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Bäckman, Lars
    Garzon, Benjamin
    Microscopic Structure of Frontal White Matter Predict Delay Discounting2020Ingår i: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 87, nr 9, s. S197-S197Artikel i tidskrift (Övrigt vetenskapligt)
  • 37. Hartana, C. A.
    et al.
    Ahlén Bergman, E.
    Broomé, A.
    Berglund, S.
    Johansson, M.
    Department of Urology, Sundsvall Hospital, Sundsvall, Sweden.
    Alamdari, F.
    Jakubczyk, T.
    Huge, Y.
    Aljabery, F.
    Palmqvist, K.
    Department of Surgery, Östersund County Hospital, Urology section, Östersund, Sweden..
    Holmström, B.
    Glise, H.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Winqvist, O.
    Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer2018Ingår i: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 194, nr 1, s. 39-53Artikel i tidskrift (Refereegranskat)
    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.

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  • 38. Hartana, Ciputra Adijaya
    et al.
    Bergman, Emma Ahlén
    Zirakzadeh, A. Ali
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Medicine Solna, Unit of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden.
    Krantz, David
    Winerdal, Malin E.
    Winerdal, Max
    Johansson, Markus
    Alamdari, Farhood
    Jakubczyk, Tomasz
    Glise, Hans
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Winqvist, Ola
    Urothelial bladder cancer may suppress perforin expression in CD8+ T cells by an ICAM-1/TGFβ2 mediated pathway2018Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 13, nr 7, artikel-id e0200079Artikel i tidskrift (Refereegranskat)
    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.

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  • 39.
    Holmberg, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Sundström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Ljungberg, Michael
    Department of Medical Radiation Physics, Clinical Sciences Lund, Lund University, Lund, Sweden.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Reducing scanning time to 50% for In-111 pentetreotide SPECT when using model-based compensation2012Ingår i: 2012 IEEE nuclear science symposium and medical imaging conference record (NSS/MIC) / [ed] Bo Yu, IEEE, 2012, s. 2946-2949Konferensbidrag (Refereegranskat)
    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.

  • 40.
    Jakobson Mo, Susanna
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    J. Stiernman, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    af Bjerkén, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Bäckström, David C.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Gabrielsson Kellgren, Therese
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Varrone, Andrea
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet and Stockholm Health Care Services, Stockholm, Sweden.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    VNTR polymorphism in the SLC6A3 gene does not influence dopamine transporter availability measured by [18F]FE-PE2I PET or [123I]FP-Cit SPECT2022Ingår i: Nuclear medicine communications, ISSN 0143-3636, E-ISSN 1473-5628, Vol. 43, nr 3, s. 247-255Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To investigate the potential impact of polymorphism in the 3'-untranslated region (3'UTR) of the SLC6A3 gene (DAT1) on normal variation in dopamine transporter (DAT) imaging with [18F]FE-PE2I PET and [123I]FP-Cit SPECT.

    METHODS: Thirty-six individuals (mean age 70.4±5.4 years) with normal [18F]FE-PE2I PET and [123I]FP-Cit SPECT were genotyped for variable number of tandem repeats (VNTR) in the 3′UTR of the DAT1 gene. The DAT-availability in the caudate and putamen as measured with [18F]FE-PE2I PET and [123I]FP-Cit SPECT, as well as in the substantia nigra with [18F]FE-PE2I PET were compared between the participants carrying one or two 9-repeat alleles (i.e. 9R+10R or 9R+9R; 47%) and the participants without a 9R allele (i.e. 10R+10R or 10R+11R; 53%). Nonparametric tests, linear regression analysis and mixed model analysis were used to assess any statistical difference in measured DAT availability between the two allele groups.

    RESULTS: The measured DAT-availability in PET- and SPECT-imaging tended to be slightly higher in the 9R-group; however, the difference did not reach statistical significance in either the caudate or the putamen or the substantia nigra. Instead, age did have a significant effect on the DAT level (P < 0.05) notwithstanding the genotype.

    CONCLUSION: No significant effect of DAT1-genotype was detectable in imaging with [18F]FE-PE2I PET or [123I]FP-Cit, instead, age accounted for the normal variation in DAT-PET and DAT-SPECT.

  • 41.
    Jakobson Mo, Susanna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Jonasson, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Ögren, Mattias J.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Ögren, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Varrone, Andrea
    Eriksson, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bäckström, David
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    af Bjerkén, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Dopamine transporter imaging with [18F]FE-PE2I PET and [123I]FP-CIT SPECT – a clinical comparison2018Ingår i: EJNMMI Research, E-ISSN 2191-219X, Vol. 8, artikel-id 100Artikel i tidskrift (Refereegranskat)
    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.

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  • 42.
    Jakobson Mo, Susanna
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Jonasson, Lars S.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Validation of dynamic [18F]FE-PE2I PET for estimation of relative regional cerebral blood flow: a comparison with [15O]H2O PET2022Ingår i: EJNMMI Research, E-ISSN 2191-219X, Vol. 12, nr 1, artikel-id 72Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Dopamine transporter (DAT) imaging is used in the diagnostic work-up in suspected parkinsonian syndromes and dementia with Lewy bodies but cannot differentiate between these syndromes, and an extra brain imaging examination of the regional cerebral blood flow (rCBF) or glucose metabolism is often needed for differential diagnosis. The requirement of two different imaging examinations is resource-consuming and inconvenient for the patients. Therefore, imaging of both cortical blood flow and DAT imaging with the same radiotracer would be more convenient and cost-effective. The aim of this study was to test whether relative regional cerebral blood flow (rCBFR) can be measured with the DAT-specific positron emission tomography (PET) tracer [18F]FE-PE2I (FE-PE2I), by validation with cerebral perfusion measured with [15O]H2O PET (H2O).

    Methods: The rCBFR was quantified by kinetic modeling for FE-PE2I (R1) and H2O (F). The R1 was calculated using the simplified reference tissue model, and F was calculated with a modified Koopman double-integration method. The linear relationship and intraclass correlation (ICC) between R1 and F were tested in image data derived from 29 patients with recent onset parkinsonism and 30 healthy controls.

    Results: There was a strong linear correlation across all subjects between R1 and F in the frontal, parietal, temporal, cingulate and occipital cortex as well as in the striatum (r ≥ 0.731–0.905, p < 0.001) with a good-to-excellent ICC, ranging from 0.727 to 0.943 (p < 0.001).

    Conclusions: Our results suggest that FE-PE2I may be used as a proxy for cerebral perfusion, thus potentially serving as a radiotracer for assessment of both DAT availability and rCBFR in one single dynamic scan. This could be valuable in the differential diagnosis of parkinsonian syndromes.

    Trial registration: EUDRA-CT 2015-003045-26. Registered 23 October 2015 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-003045-26

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  • 43.
    Jakobson Mo, Susanna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Johansson, Lennart
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Cross-camera comparison of ROI-based semi-quantitative 123I-IBZM SPECT data in healthy volunteers using an anthropomorphic phantom for calibration2013Ingår i: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 54, nr 5, s. 549-556Artikel i tidskrift (Refereegranskat)
    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.

  • 44.
    Jakobson Mo, Susanna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Edenbandt, Lars
    Göteborgs Universitet, Avdelningen för molekylär och klinisk medicin.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    123I-FP-Cit and 123I-IBZM SPECT uptake in a prospective normal material analysed with two different semi-quantitative image evaluation tools2013Ingår i: Nuclear medicine communications, ISSN 0143-3636, E-ISSN 1473-5628, Vol. 34, nr 10, s. 978-989Artikel i tidskrift (Refereegranskat)
    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.

  • 45.
    Jakobson Mo, Susanna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Holmberg, Henrik
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Pre- and postsynaptic dopamine SPECT in idiopathic parkinsonian diseases: a follow-up study2013Ingår i: BioMed Research International, ISSN 2314-6141, Vol. 2013, s. 143532-Artikel i tidskrift (Refereegranskat)
    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.

    Ladda ner fulltext (pdf)
    Pre- and postsynaptic dopamine SPECT in idiopathic parkinsonian diseases: a follow-up study
  • 46.
    Jakobson Mo, Susanna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Johansson, Lennart
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Pre- and postsynaptic dopamine SPECT in the early phase of idiopathic parkinsonism: a population-based study2010Ingår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 37, nr 11, s. 2154-2164Artikel i tidskrift (Refereegranskat)
    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.

  • 47.
    Jakobson Mo, Susanna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Accuracy of Visual Assessment of Dopamine Transporter Imaging in Early Parkinsonism2015Ingår i: Movement Disorders Clinical Practice, E-ISSN 2330-1619, Vol. 2, nr 1, s. 17-23Artikel i tidskrift (Refereegranskat)
    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.

  • 48.
    Johansson, Amanda
    et al.
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Immunologi/immunkemi.
    Eriksson, David
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Immunologi/immunkemi.
    Ullen, Anders
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Immunologi/immunkemi.
    Löfroth, Per-Olov
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Radiofysik.
    Johansson, Lennart
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Radiofysik.
    Åhlström-Riklund, Katrine
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Diagnostisk radiologi.
    Stigbrand, Torgny
    Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Immunologi/immunkemi.
    The combination of external beam radiotherapy and experimental radioimmunotargeting with a monoclonal anticytokeratin antibody2002Ingår i: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 94, nr S4, s. 1314-1319Artikel i tidskrift (Refereegranskat)
  • 49. Johansson, Amanda
    et al.
    Sandström, Per
    Ullén, Anders
    Erlandsson, Ann
    Sundström, Birgitta
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Johansson, Lennart
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hietala, Sven-Ola
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Stigbrand, Torgny
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Stability and immunoreactivity of the monoclonal anticytokeratin antibody TS1 after different degrees of iodination.1999Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 38, nr 3, s. 329-334Artikel i tidskrift (Refereegranskat)
    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.

  • 50.
    Johansson, Elias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Rydh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Åhlström Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ultrasound, Computed Tomography, and Laboratory Findings in the Diagnosis of Appendicitis2007Ingår i: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 48, nr 3, s. 267-273Artikel i tidskrift (Refereegranskat)
    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.

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