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  • 1. Aguilar, Carlos
    et al.
    Edholm, Kaijsa
    Simmons, Andrew
    Cavallin, Lena
    Muller, Susanne
    Skoog, Ingmar
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Axelsson, Rimma
    Wahlund, Lars-Olof
    Westman, Eric
    Automated CT-based segmentation and quantification of total intracranial volume2015In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 25, no 11, 3151-3160 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To develop an algorithm to segment and obtain an estimate of total intracranial volume (tICV) from computed tomography (CT) images.

    MATERIALS AND METHODS: Thirty-six CT examinations from 18 patients were included. Ten patients were examined twice the same day and eight patients twice six months apart (these patients also underwent MRI). The algorithm combines morphological operations, intensity thresholding and mixture modelling. The method was validated against manual delineation and its robustness assessed from repeated imaging examinations. Using automated MRI software, the comparability with MRI was investigated. Volumes were compared based on average relative volume differences and their magnitudes; agreement was shown by a Bland-Altman analysis graph.

    RESULTS: We observed good agreement between our algorithm and manual delineation of a trained radiologist: the Pearson's correlation coefficient was r = 0.94, tICVml[manual] = 1.05 × tICVml[automated] - 33.78 (R(2) = 0.88). Bland-Altman analysis showed a bias of 31 mL and a standard deviation of 30 mL over a range of 1265 to 1526 mL.

    CONCLUSIONS: tICV measurements derived from CT using our proposed algorithm have shown to be reliable and consistent compared to manual delineation. However, it appears difficult to directly compare tICV measures between CT and MRI.

    KEY POINTS: • Automated estimation of tICV is in good agreement with manual tracing. • Consistent tICV estimations from repeated measurements demonstrate the robustness of the algorithm. • Automatically segmented volumes seem less variable than those from manual tracing. • Unbiased and automated tlCV estimation is possible from CT.

  • 2.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Burgos, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kempton, Matthew J
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Craft, Suzanne
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Impaired Insulin Sensitivity as Indexed by the HOMA Score Is Associated With Deficits in Verbal Fluency and Temporal Lobe Gray Matter Volume in the Elderly2012In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 35, no 3, 488-494 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    Impaired insulin sensitivity is linked to cognitive deficits and reduced brain size. However, it is not yet known whether insulin sensitivity involves regional changes in gray matter volume. Against this background, we examined the association between insulin sensitivity, cognitive performance, and regional gray matter volume in 285 cognitively healthy elderly men and women aged 75 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.

    RESEARCH DESIGN AND METHODS

    Insulin sensitivity was calculated from fasting serum insulin and plasma glucose determinations using the homeostasis model assessment of insulin resistance (HOMA-IR) method. Cognitive performance was examined by a categorical verbal fluency. Participants also underwent a magnetic resonance imaging (MRI) brain scan. Multivariate analysis using linear regression was conducted, controlling for potential confounders (sex, education, serum LDL cholesterol, mean arterial blood pressure, and abdominal visceral fat volume).

    RESULTS

    The HOMA-IR was negatively correlated with verbal fluency performance, brain size (S1), and temporal lobe gray matter volume in regions known to be involved in speech production (Brodmann areas 21 and 22, respectively). No such effects were observed when examining diabetic (n = 55) and cognitively impaired (n = 27) elderly subjects as separate analyses.

    CONCLUSIONS

    These cross-sectional findings suggest that both pharmacologic and lifestyle interventions improving insulin signaling may promote brain health in late life but must be confirmed in patient studies.

  • 3.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Burgos, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Le Grevès, Madeleine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Association between physical activity and brain health in older adults2013In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 34, no 1, 83-90 p.Article in journal (Refereed)
    Abstract [en]

    In the present cross-sectional study, we examined physical activity (PA) and its possible association with cognitive skills and brain structure in 331 cognitively healthy elderly. Based on the number of self-reported light and hard activities for at least 30 minutes per week, participants were assigned to 4 groups representing different levels of PA. The cognitive skills were assessed by the Mini Mental State Examination score, a verbal fluency task, and the Trail-making test as a measure of visuospatial orientation ability. Participants also underwent a magnetic resonance imaging of the brain. Multiple regression analysis revealed that greater PA was associated with a shorter time to complete the Trail-making test, and higher levels of verbal fluency. Further, the level of self-reported PA was positively correlated with brain volume, white matter, as well as a parietal lobe gray matter volume, situated bilaterally at the precuneus. These present cross-sectional results indicate that PA is a lifestyle factor that is linked to brain structure and function in late life.

  • 4.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    O'Daly, Owen G
    Almèn, Markus S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Morell, Arvid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Åberg, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Schultes, Bernd
    Hallschmid, Manfred
    Broman, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Acute Sleep Deprivation Enhances the Brain's Response to Hedonic Food Stimuli: An fMRI Study2012In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 97, no 3, E443-447 p.Article in journal (Refereed)
    Abstract [en]

    Context:

    There is growing recognition that a large number of individuals living in Western society are chronically sleep deprived. Sleep deprivation is associated with an increase in food consumption and appetite. However, the brain regions that are most susceptible to sleep deprivation-induced changes when processing food stimuli are unknown.

    Objective:

    Our objective was to examine brain activation after sleep and sleep deprivation in response to images of food.

    Intervention:

    Twelve normal-weight male subjects were examined on two sessions in a counterbalanced fashion: after one night of total sleep deprivation and one night of sleep. On the morning after either total sleep deprivation or sleep, neural activation was measured by functional magnetic resonance imaging in a block design alternating between high- and low-calorie food items. Hunger ratings and morning fasting plasma glucose concentrations were assessed before the scan, as were appetite ratings in response to food images after the scan.

    Main Outcome Measures:

    Compared with sleep, total sleep deprivation was associated with an increased activation in the right anterior cingulate cortex in response to food images, independent of calorie content and prescan hunger ratings. Relative to the postsleep condition, in the total sleep deprivation condition, the activation in the anterior cingulate cortex evoked by foods correlated positively with postscan subjective appetite ratings. Self-reported hunger after the nocturnal vigil was enhanced, but importantly, no change in fasting plasma glucose concentration was found.

    Conclusions:

    These results provide evidence that acute sleep loss enhances hedonic stimulus processing in the brain underlying the drive to consume food, independent of plasma glucose levels. These findings highlight a potentially important mechanism contributing to the growing levels of obesity in Western society.

  • 5.
    Berntsson, Shala Ghaderi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Falk, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Savitcheva, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Godau, Andrea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Perfusion and diffusion MRI combined with (11)C-methionine PET in the preoperative evaluation of suspected adult low-grade gliomas2013In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 114, no 2, 241-249 p.Article in journal (Refereed)
    Abstract [en]

    Perfusion and diffusion magnetic resonance imaging (pMRI, dMRI) are valuable diagnostic tools for assessing brain tumors in the clinical setting. The aim of this study was to determine the correlation of pMRI and dMRI with (11)C-methionine positron emission tomography (MET PET) in suspected low-grade gliomas (LGG) prior to surgery. Twenty-four adults with suspected LGG were enrolled in an observational study and examined by MET PET, pMRI and dMRI. Histological tumor diagnosis was confirmed in 23/24 patients (18 gliomas grade II, 5 gliomas grade III). The maximum relative cerebral blood volume (rCBVmax) and the minimum mean diffusivity (MDmin) were measured in tumor areas with highest MET uptake (hotspot) on PET by using automated co-registration of MRI and PET scans. A clearly defined hotspot on PET was present in all 23 tumors. Regions with rCBVmax corresponded with hotspot regions in all tumors, regions with MDmin corresponded with hotspot regions in 20/23 tumors. The correlation between rCBVmax (r = 0.19, P = 0.38) and MDmin (r = -0.41, P = 0.053) with MET uptake in the hotspot was not statistically significant. Taken into account the difficulties of measuring perfusion abnormalities in non-enhancing gliomas, this study demonstrates that co-registered MET PET and pMRI facilitates the identification of regions with rCBVmax. Furthermore, the lack of a clear positive correlation between tumor metabolism in terms of MET uptake and tumor vascularity measured as rCBVmax suggests that combined pMRI/PET provides complementary baseline imaging data in these tumors.

  • 6.
    Björkstrand, Johannes
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ågren, Thomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Disruption of Memory Reconsolidation Erases a Fear Memory Trace in the Human Amygdala: An 18-Month Follow-Up.2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 7, e0129393- p.Article in journal (Refereed)
    Abstract [en]

    Fear memories can be attenuated by reactivation followed by disrupted reconsolidation. Using functional magnetic resonance imaging we recently showed that reactivation and reconsolidation of a conditioned fear memory trace in the basolateral amygdala predicts subsequent fear expression over two days, while reactivation followed by disrupted reconsolidation abolishes the memory trace and suppresses fear. In this follow-up study we demonstrate that the behavioral effect persists over 18 months reflected in superior reacquisition after undisrupted, as compared to disrupted reconsolidation, and that neural activity in the basolateral amygdala representing the initial fear memory predicts return of fear. We conclude that disrupting reconsolidation have long lasting behavioral effects and may permanently erase the fear component of an amygdala-dependent memory.

  • 7.
    Björkstrand, Johannes
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ågren, Thomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Department of Clinical Neuroscience, Karolinska Institutet, Tomtebodavägen 18A, 171 77, Stockholm, Sweden.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Department of Clinical Neuroscience, Karolinska Institutet, Tomtebodavägen 18A, 171 77, Stockholm, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hjorth, Olof
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Department of Clinical Neuroscience, Karolinska Institutet, Tomtebodavägen 18A, 171 77, Stockholm, Sweden.
    Think twice, it's all right: Long lasting effects of disrupted reconsolidation on brain and behavior in human long-term fear2017In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 324, 125-129 p.Article in journal (Refereed)
    Abstract [en]

    Memories can be modified when recalled. Experimental fear conditioning studies support that amygdala-localized fear memories are attenuated when reconsolidation is disrupted through extinction training immediately following memory activation. Recently, using functional brain imaging in individuals with lifelong spider fears, we demonstrated that fear memory activation followed by repeated exposure to feared cues after 10 min, thereby disrupting reconsolidation, attenuated activity in the amygdala during later re-exposure, and also facilitated approach behavior to feared cues. In contrast, repeated exposure 6 h after fear memory activation, allowing for reconsolidation, did not attenuate amygdala activity and resulted in less approach behavior as compared to the group that received disrupted reconsolidation. We here evaluated if these effects are stable after 6 months and found that amygdala activity was further reduced in both groups, with a tendency towards greater reductions in the 10 min than the 6 h group. Hence, disrupted reconsolidation results in long lasting attenuation of amygdala activity. The behavioral effect, with more approach towards previously feared cues, in the 10 min than the 6 h group also persisted. Thus, the brain effect of disrupted reconsolidation is stable over 6 months and the behavioral effect also remained. We therefore conclude that disrupted reconsolidation result in a long-lasting diminished fear memory representation in the amygdala which may have clinical importance.

  • 8. Blystad, I
    et al.
    Warntjes, Jbm
    Smedby, Örjan
    Landtblom, A-M
    Lundberg, P
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Synthetic MRI of the brain in a clinical setting2012In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 53, no 10, 1158-1163 p.Article in journal (Refereed)
    Abstract [en]

    Background

    Conventional magnetic resonance imaging (MRI) has relatively long scan times for routine examinations, and the signal intensity of the images is related to the specific MR scanner settings. Due to scanner imperfections and automatic optimizations, it is impossible to compare images in terms of absolute image intensity. Synthetic MRI, a method to generate conventional images based on MR quantification, potentially both decreases examination time and enables quantitative measurements.

    Purpose

    To evaluate synthetic MRI of the brain in a clinical setting by assessment of the contrast, the contrast-to-noise ratio (CNR), and the diagnostic quality compared with conventional MR images.

    Material and Methods

    Twenty-two patients had synthetic imaging added to their clinical MR examination. In each patient, 12 regions of interest were placed in the brain images to measure contrast and CNR. Furthermore, general image quality, probable diagnosis, and lesion conspicuity were investigated.

    Results

    Synthetic T1-weighted turbo spin echo and T2-weighted turbo spin echo images had higher contrast but also a higher level of noise, resulting in a similar CNR compared with conventional images. Synthetic T2-weighted FLAIR images had lower contrast and a higher level of noise, which led to a lower CNR. Synthetic images were generally assessed to be of inferior image quality, but agreed with the clinical diagnosis to the same extent as the conventional images. Lesion conspicuity was higher in the synthetic T1-weighted images, which also had a better agreement with the clinical diagnoses than the conventional T1-weighted images.

    Conclusion

    Synthetic MR can potentially shorten the MR examination time. Even though the image quality is perceived to be inferior, synthetic images agreed with the clinical diagnosis to the same extent as the conventional images in this study.

  • 9. Blystad, Ida
    et al.
    Håkansson, I
    Tisell, A
    Ernerudh, J
    Smedby, Örjan
    Lundberg, P
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Quantitative MRI for Analysis of Active Multiple Sclerosis Lesions without Gadolinium-Based Contrast Agent2016In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 37, no 1, 94-100 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Contrast-enhancing MS lesions are important markers of active inflammation in the diagnostic work-up of MS and in disease monitoring with MR imaging. Because intravenous contrast agents involve an expense and a potential risk of adverse events, it would be desirable to identify active lesions without using a contrast agent. The purpose of this study was to evaluate whether pre-contrast injection tissue-relaxation rates and proton density of MS lesions, by using a new quantitative MR imaging sequence, can identify active lesions.

    MATERIALS AND METHODS: Forty-four patients with a clinical suspicion of MS were studied. MR imaging with a standard clinical MS protocol and a quantitative MR imaging sequence was performed at inclusion (baseline) and after 1 year. ROIs were placed in MS lesions, classified as nonenhancing or enhancing. Longitudinal and transverse relaxation rates, as well as proton density were obtained from the quantitative MR imaging sequence. Statistical analyses of ROI values were performed by using a mixed linear model, logistic regression, and receiver operating characteristic analysis.

    RESULTS: Enhancing lesions had a significantly (P < .001) higher mean longitudinal relaxation rate (1.22 ± 0.36 versus 0.89 ± 0.24), a higher mean transverse relaxation rate (9.8 ± 2.6 versus 7.4 ± 1.9), and a lower mean proton density (77 ± 11.2 versus 90 ± 8.4) than nonenhancing lesions. An area under the receiver operating characteristic curve value of 0.832 was obtained.

    CONCLUSIONS: Contrast-enhancing MS lesions often have proton density and relaxation times that differ from those in nonenhancing lesions, with lower proton density and shorter relaxation times in enhancing lesions compared with nonenhancing lesions.

  • 10.
    Blystad, Ida
    et al.
    Department of Radiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden, Centre for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.
    Warntjes, J B Marcel
    Centre for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden, Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden .
    Smedby, Örjan
    Department of Radiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden, Centre for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden, School of Technology and Health, KTH Royal Institute of Technology, Stockholm, Sweden.
    Lundberg, Peter
    Centre for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden, Department of Radiation Physics and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden .
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Centre for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.
    Tisell, Anders
    Centre for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden, Department of Radiation Physics and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden .
    Quantitative MRI for analysis of peritumoral edema in malignant gliomas.2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, e0177135Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Damage to the blood-brain barrier with subsequent contrast enhancement is a hallmark of glioblastoma. Non-enhancing tumor invasion into the peritumoral edema is, however, not usually visible on conventional magnetic resonance imaging. New quantitative techniques using relaxometry offer additional information about tissue properties. The aim of this study was to evaluate longitudinal relaxation R1, transverse relaxation R2, and proton density in the peritumoral edema in a group of patients with malignant glioma before surgery to assess whether relaxometry can detect changes not visible on conventional images.

    METHODS: In a prospective study, 24 patients with suspected malignant glioma were examined before surgery. A standard MRI protocol was used with the addition of a quantitative MR method (MAGIC), which measured R1, R2, and proton density. The diagnosis of malignant glioma was confirmed after biopsy/surgery. In 19 patients synthetic MR images were then created from the MAGIC scan, and ROIs were placed in the peritumoral edema to obtain the quantitative values. Dynamic susceptibility contrast perfusion was used to obtain cerebral blood volume (rCBV) data of the peritumoral edema. Voxel-based statistical analysis was performed using a mixed linear model.

    RESULTS: R1, R2, and rCBV decrease with increasing distance from the contrast-enhancing part of the tumor. There is a significant increase in R1 gradient after contrast agent injection (P < .0001). There is a heterogeneous pattern of relaxation values in the peritumoral edema adjacent to the contrast-enhancing part of the tumor.

    CONCLUSION: Quantitative analysis with relaxometry of peritumoral edema in malignant gliomas detects tissue changes not visualized on conventional MR images. The finding of decreasing R1 and R2 means shorter relaxation times closer to the tumor, which could reflect tumor invasion into the peritumoral edema. However, these findings need to be validated in the future.

  • 11.
    Bodén, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Persson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Uppsala Univ, Uppsala, Sweden..
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Striatal Phosphodiesterase 10A and Medial Prefrontal Cortical Thickness in Patients with Schizophrenia: A PET and MRI Study2017In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 81, no 10, S386-S387 p.Article in journal (Other academic)
  • 12.
    Bodén, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Persson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Striatal phosphodiesterase 10A and medial prefrontal cortical thickness in patients with schizophrenia: a PET and MRI study2017In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 7, no 3, e1050Article in journal (Refereed)
    Abstract [en]

    The enzyme phosphodiesterase 10A (PDE10A) is abundant in striatal medium spiny neurons and has been implicated in the pathophysiology of schizophrenia in animal models and is investigated as a possible new pharmacological treatment target. A reduction of prefrontal cortical thickness is common in schizophrenia, but how this relates to PDE10A expression is unknown. Our study aim was to compare, we believe for the first time, the striatal non-displaceable binding potential (BPND) of the new validated PDE10A ligand [(11)C]Lu AE92686 between patients with schizophrenia and healthy controls. Furthermore, we aimed to assess the correlation of PDE10A BPND to cortical thickness. Sixteen healthy male controls and 10 male patients with schizophrenia treated with clozapine, olanzapine or quetiapine were investigated with positron emission tomography (PET) and magnetic resonance imaging (MRI). Striatal binding potential (BPND) of [(11)C]Lu AE92686 was acquired through dynamic PET scans and cortical thickness by structural MRI. Clinical assessments of symptoms and cognitive function were performed and the antipsychotic dosage was recorded. Patients with schizophrenia had a significantly lower BPND of [(11)C]Lu AE92686 in striatum (P=0.003) than healthy controls. The striatal BPND significantly correlated to cortical thickness in the medial prefrontal cortex and superior frontal gyrus across patients with schizophrenia and healthy controls. No significant correlation was observed between the BPND for [(11)C]Lu AE92686 in striatum and age, schizophrenia symptoms, antipsychotic dosage, coffee consumption, smoking, duration of illness or cognitive function in the patients. In conclusion, PDE10A may be important for functioning in the striato-cortical interaction and in the pathophysiology of schizophrenia.

  • 13.
    Brooks, Samantha J
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Burgos, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kempton, M J
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Late-life obesity is associated with smaller global and regional gray matter volumes: a voxel-based morphometric study2013In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 37, no 2, 230-236 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: 

    Obesity adversely affects frontal lobe brain structure and function. Here we sought to show that people who are obese versus those who are of normal weight over a 5-year period have differential global and regional brain volumes.

    DESIGN: 

    Using voxel-based morphometry, contrasts were done between those who were recorded as being either obese or of normal weight over two time points in the 5 years prior to the brain scan. In a post-hoc preliminary analysis, we compared scores for obese and normal weight people who completed the trail-making task.

    SUBJECTS: 

    A total of 292 subjects were examined following exclusions (for example, owing to dementia, stroke and cortical infarcts) from the Prospective Investigation of the Vasculature in Uppsala Seniors cohort with a body mass index of normal weight (<25 kg m−2) or obese (30 kg m−2).

    RESULTS: 

    People who were obese had significantly smaller total brain volumes and specifically, significantly reduced total gray matter (GM) volume (GMV) (with no difference in white matter or cerebrospinal fluid). Initial exploratory whole brain uncorrected analysis revealed that people who were obese had significantly smaller GMV in the bilateral supplementary motor area, bilateral dorsolateral prefrontal cortex (DLPFC), left inferior frontal gyrus and left postcentral gyrus. Secondary more stringent corrected analyses revealed a surviving cluster of GMV difference in the left DLPFC. Finally, post-hoc contrasts of scores on the trail-making task, which is linked to DLPFC function, revealed that obese people were significantly slower than those of normal weight.

    CONCLUSION: 

    These findings suggest that in comparison with normal weight, people who are obese have smaller GMV, particularly in the left DLPFC. Our results may provide evidence for a potential working memory mechanism for the cognitive suppression of appetite that may lower the risk of developing obesity in later life.

  • 14.
    Brooks, Samantha J
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Solstrand Dahlberg, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Swenne, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Aronsson, Marianne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Zarei, Sanaz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lundberg, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Jacobsson, Josefin A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Rask-Andersen, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Salonen-Ros, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Rosling, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Obsessive-compulsivity and working memory are associated with differential prefrontal cortex and insula activation in adolescents with a recent diagnosis of an eating disorder2014In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 224, no 3, 246-253 p.Article in journal (Refereed)
    Abstract [en]

    The role of rumination at the beginning of eating disorder (ED) is not well understood. We hypothesised that impulsivity, rumination and restriction could be associated with neural activity in response to food stimuli in young individuals with eating disorders (ED). We measured neural responses with functional magnetic resonance imaging (fMRI), tested working memory (WM) and administered the eating disorders examination questionnaire (EDE-Q), Barratt impulsivity scale (BIS-11) and obsessive-compulsive inventory (OCI-R) in 15 adolescent females with eating disorder not otherwise specified (EDNOS) (mean age 15 years) and 20 age-matched healthy control females. We found that EDNOS subjects had significantly higher scores on the BIS 11, EDE-Q and OCI-R scales. Significantly increased neural responses to food images in the EDNOS group were observed in the prefrontal circuitry. OCI-R scores in the EDNOS group also significantly correlated with activity in the prefrontal circuitry and the cerebellum. Significantly slower WM responses negatively correlated with bilateral superior frontal gyrus activity in the EDNOS group. We conclude that ruminations, linked to WM, are present in adolescent females newly diagnosed with EDNOS. These may be risk factors for the development of an eating disorder and may be detectable before disease onset.

  • 15.
    Ebeling Barbier, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Themudo, Raquel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Prevalence of unrecognized myocardial infarction detected with magnetic resonance imaging and its relationship to cerebral ischemic lesions in both sexes2011In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 58, no 13, 1372-1377 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The purpose of this study was to investigate the prevalence of unrecognized myocardial infarction (UMI) detected with magnetic resonance imaging (MRI) and whether it is related to cerebral ischemic lesions on MRI in an elderly population-based cohort.

    BACKGROUND: There is a correlation between stroke and recognized myocardial infarction (RMI) and between stroke and UMI detected with electrocardiography, whereas the prevalence of stroke in subjects with MRI-detected UMI is unknown.

    METHODS: Cerebral MRI and cardiac late-enhancement MRI were performed on 394 randomly selected 75-year-old subjects (188 women, 206 men). Images were assessed for cerebral ischemic lesions and myocardial infarction (MI) scars. Medical records were scrutinized. Subjects with MI scars, with or without a hospital diagnosis of MI, were classified as RMI or UMI, respectively.

    RESULTS: UMIs were found in 120 subjects (30%) and RMIs in 21 (5%). The prevalence of UMIs (p = 0.004) and RMIs (p = 0.02) was greater in men than in women. Men with RMI displayed an increased prevalence of cortical and lacunar cerebral infarctions, whereas women with UMI more frequently had cortical cerebral infarctions (p = 0.003).

    CONCLUSIONS: MI scars are more frequent in men than in women at 75 years of age. The prevalence of RMI is related to that of cerebral infarctions.

  • 16.
    Engman, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Alaie, Iman
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Björkstrand, Johannes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ågren, Thomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Faria, Vanda
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Wallenquist, Ulrika
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Wahlstedt, Kurt
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Morell, Arvid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Altered Amygdala but not Default Mode Network Functional Connectivity in Social Anxiety Disorder2013In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 73, no 9, 79S-79S p.Article in journal (Other academic)
  • 17.
    Fagius, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Feresiadou, Amalia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Severe relapses and rebound activity after natalizumab discontinuation in MS patients with more than five years of treatment with stable disease course2015In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, 297-297 p.Article in journal (Other academic)
  • 18.
    Fagius, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Feresiadou, Amalia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Discontinuation of disease modifying treatments in middle aged multiple sclerosis patients: First line drugs vs natalizumab2017In: Multiple Sclerosis and Related Disorders, ISSN 2211-0348, E-ISSN 2211-0356, Vol. 12, 82-87 p., S2211-0348(17)30010-XArticle in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 19.
    Fahlström, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lindskog, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Engström, Mathias
    GE Healthcare, Stockholm, Sweden..
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Correlation between regional cerebral blood flow based on simultaneously acquired arterial spin labelling MRI and 15O-water-PET using zero-echo-time-based attenuation correction2017In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 58, no S1, 362Article in journal (Other academic)
    Abstract [en]

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

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

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

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

  • 20.
    Falk, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Rostrup, Egill
    Berntsson, Shala
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Morell, Arvid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, Henrik B W
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Discrimination between glioma grades II and III in suspected low-grade gliomas using dynamic contrast-enhanced and dynamic susceptibility contrast perfusion MR imaging: a histogram analysis approach2014In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 56, no 12, 1031-1038 p.Article in journal (Refereed)
    Abstract [en]

    Introduction

    Perfusion magnetic resonance imaging (MRI) can be used in the pre-operative assessment of brain tumours. The aim of this prospective study was to identify the perfusion parameters from dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) perfusion imaging that could best discriminate between grade II and III gliomas.

    Methods

    MRI (3 T) including morphological ((T2 fluid attenuated inversion recovery (FLAIR) and T1-weighted (T1W)+Gd)) and perfusion (DCE and DSC) sequences was performed in 39 patients with newly diagnosed suspected low-grade glioma after written informed consent in this review board-approved study. Regions of interests (ROIs) in tumour area were delineated on FLAIR images co-registered to DCE and DSC, respectively, in 25 patients with histopathological grade II (n = 18) and III (n  = 7) gliomas. Statistical analysis of differences between grade II and grade III gliomas in histogram perfusion parameters was performed, and the areas under the curves (AUC) from the ROC analyses were evaluated.

    Results

    In DCE, the skewness of transfer constant (k trans) was found superior for differentiating grade II from grade III in all gliomas (AUC 0.76). In DSC, the standard deviation of relative cerebral blood flow (rCBF) was found superior for differentiating grade II from grade III gliomas (AUC 0.80).

    Conclusions

    Histogram parameters from k trans (DCE) and rCBF (DSC) could most efficiently discriminate between grade II and grade III gliomas.

  • 21.
    Falk Delgado, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Markus, Nilsson
    Bioimaging center, Lunds Universitet.
    Ghaderi Berntsson, Shala
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    van Westen, Danielle
    Clinical Sciences, Lunds Universitet.
    Lätt, Jimmy
    MR Department, Center for medical imaging and physiology, Lund University Hospital.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Preoperative diffusion kurtosis imaging in suspected low-grade gliomas: A prospective study of diffusional properties in tumour and perilesional regions with histopathological correlationsManuscript (preprint) (Other academic)
  • 22.
    Falk Delgado, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nilsson, Markus
    Lund Univ, Bioimaging Ctr, Lund, Sweden..
    Berntsson, Shala G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Libard, Sylwia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    van Westen, Danielle
    Lund Univ, Clin Sci Lund, Diagnost Radiol, Lund, Sweden..
    Lätt, Jimmy
    Skane Univ Healthcare, Dept Imaging & Funct, Lund, Sweden..
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Diffusion kurtosis imaging of gliomas grades II and III: a study of perilesional tumor infiltration, tumor grades and subtypes at clinical presentation2017In: Radiology and Oncology, ISSN 1318-2099, E-ISSN 1581-3207, Vol. 51, no 2, 121-129 p.Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 23.
    Falk Delgado, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nilsson, Markus
    Latini, Francesco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Mårtensson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Berntsson, Shala G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Lätt, Jimmy
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Preoperative Quantitative MR Tractography Compared with Visual Tract Evaluation in Patients with Neuropathologically Confirmed Gliomas Grades II and III: A Prospective Cohort Study2016In: Radiology Research and Practice, ISSN 2090-1941, E-ISSN 2090-195X, 7671854Article in journal (Refereed)
    Abstract [en]

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

  • 24. Ferreira, Daniel
    et al.
    Cavallin, Lena
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Muehlboeck, J-Sebastian
    Mecocci, Patrizia
    Vellas, Bruno
    Tsolaki, Magda
    Kłoszewska, Iwona
    Soininen, Hilkka
    Lovestone, Simon
    Simmons, Andrew
    Wahlund, Lars-Olof
    Westman, Eric
    Practical cut-offs for visual rating scales of medial temporal, frontal and posterior atrophy in Alzheimer's disease and mild cognitive impairment2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 278, no 3, 277-290 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Atrophy in the medial temporal lobe, frontal lobe and posterior cortex can be measured with visual rating scales such as the medial temporal atrophy (MTA), global cortical atrophy - frontal subscale (GCA-F) and posterior atrophy (PA) scales, respectively. However, practical cut-offs are urgently needed, especially now that different presentations of Alzheimer's disease (AD) are included in the revised diagnostic criteria.

    AIMS:

    The aim of this study was to generate a list of practical cut-offs for the MTA, GCA-F and PA scales, both for diagnosis of AD and determining prognosis in mild cognitive impairment (MCI), and to evaluate the influence of key demographic and clinical factors on these cut-offs.

    METHODS:

    AddNeuroMed and ADNI cohorts were combined giving a total of 1147 participants (322 AD patients, 480 MCI patients and 345 control subjects). The MTA, GCA-F and PA scales were applied and a broad range of cut-offs was evaluated.

    RESULTS:

    The MTA scale showed better diagnostic and predictive performances than the GCA-F and PA scales. Age, apolipoprotein E (ApoE) ε4 status and age at disease onset influenced all three scales. For the age ranges 45-64, 65-74, 75-84 and 85-94 years, the following cut-offs should be used. MTA: ≥1.5, ≥1.5, ≥2 and ≥2.5; GCA-F, ≥1, ≥1, ≥1 and ≥1; and PA, ≥1, ≥1, ≥1 and ≥1, respectively, with an adjustment for early-onset ApoE ε4 non-carrier AD patients (MTA: ≥2, ≥2, ≥3 and ≥3; and GCA-F: ≥1, ≥1, ≥2 and ≥2, respectively).

    CONCLUSIONS:

    If successfully validated in clinical settings, the list of practical cut-offs proposed here might be useful in clinical practice. Their use might also (i) promote research on atrophy subtypes, (ii) increase the understanding of different presentations of AD, (iii) improve diagnosis and prognosis and (iv) aid population selection and enrichment for clinical trials. This article is protected by copyright. All rights reserved.

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

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

  • 26.
    Frick, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Alaie, Iman
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Björkstrand, Johannes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Faria, Vanda
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Wallenquist, Ulrika
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ågren, Thomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Wahlstedt, Kurt
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Morell, Arvid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Enlargement of visual processing regions in social anxiety disorder is related to symptom severity2014In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 583, 114-119 p.Article in journal (Refereed)
    Abstract [en]

    Social anxiety disorder (SAD) is associated with altered brain function and structure, but most structural studies include small samples and findings are mixed. This study compared regional gray matter volume between 48 SAD patients and 29 healthy controls (HC) as well as the relationship between volume and symptom severity. Structural magnetic resonance images from SAD patients and HC were evaluated using standard voxel-based morphometry (VBM) processing in the SPM8 software package. Social anxiety symptom severity was rated in SAD patients by a clinician using the Liebowitz Social Anxiety Scale (LSAS). SAD patients had greater regional gray matter volume in the lingual gyrus and lateral occipital cortex than the controls, and within the SAD group a positive correlation was found between symptom severity and regional gray matter volume in the lingual gyrus and the retrosplenial cortex. These findings replicate and extend earlier reports of enlarged visual processing areas in SAD. Increased gray matter volume in regions involved in visual processing and self-consciousness could underlie, or be the result of, abnormal emotional information processing and self-focused attention previously demonstrated in patients with SAD.

  • 27.
    Frick, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Alaie, Iman
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Björkstrand, Johannes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Morell, Arvid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wahlstedt, Kurt
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Predicting Outcome of Combined CBT and SSRI Treatment for Social Anxiety Disorder Using a Machine Learning Approach2014In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 75, no 9, 357S-357S p.Article in journal (Other academic)
  • 28.
    Fällmar, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Med Ctr Freiburg, Dept Neuroradiol, Freiburg, Germany.; Univ Geneva, Fac Med, Geneva, Switzerland.; Affidea CDRC Ctr Diagnost Radiol Carouge, Carouge, Switzerland..
    Lilja, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Hermes Med Solut, Stockholm, Sweden.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Tolboom, Nelleke
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.
    Egger, Karl
    Univ Med Ctr Freiburg, Dept Neuroradiol, Freiburg, Germany.
    Kellner, Elias
    Univ Freiburg, Dept Radiol, Med Ctr, Fac Med,Med Phys, Freiburg, Germany.
    Croon, Philip M
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.
    Verfaillie, Sander C J
    Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Med Ctr, Amsterdam, Netherlands.
    van Berckel, Bart N M
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.
    Ossenkoppele, Rik
    Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Med Ctr, Amsterdam, Netherlands.
    Barkhof, Frederik
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.; UCL, Inst Neurol & Healthcare Engn, London, England..
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Arterial spin labeling-based Z-maps have high specificity and positive predictive value for neurodegenerative dementia compared to FDG-PET.2017In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 27, no 10, 4237-4246 p.Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

  • 29.
    Fällmar, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lilja, Johan
    Hermes Medical Solutions, Stockholm, Sweden..
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Validation of true low-dose 18F-FDG PET of the brain2016In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 6, no 5, 269-276 p.Article in journal (Refereed)
    Abstract [en]

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

  • 30.
    Fällmar, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lilja, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Velickaite, Vilma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ahlgren, André
    Lund Univ, Dept Med Radiat Phys, Lund, Sweden.
    van Osch, Matthias J P
    eiden Univ, Med Ctr, Dept Radiol, CJ Gorter Ctr High Field MRI, Leiden, Netherlands.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Visual Assessment of Brain Perfusion MRI Scans in Dementia: a Pilot Study2016In: Journal of Neuroimaging, ISSN 1051-2284, E-ISSN 1552-6569, Vol. 26, no 3, 324-330 p.Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 31. Georgiopoulos, Charalampos
    et al.
    Davidsson, Anette
    Engström, Maria
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Zachrisson, Helene
    Dizdar, Nil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    The diagnostic value of dopamine transporter imaging and olfactory testing in patients with parkinsonian syndromes.2015In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 262, no 9, 2154-2163 p.Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to compare the efficacy of olfactory testing and presynaptic dopamine imaging in diagnosing Parkinson's disease (PD) and atypical parkinsonian syndromes (APS); to evaluate if the combination of these two diagnostic tools can improve their diagnostic value. A prospective investigation of 24 PD patients, 16 APS patients and 15 patients with non-parkinsonian syndromes was performed during an 18-month period. Single photon emission computed tomography with the presynaptic radioligand (123)I-FP-CIT (DaTSCAN(®)) and olfactory testing with the Brief 12-item Smell Identification Test (B-SIT) were performed in all patients. DaTSCAN was analysed semi-quantitatively, by calculating two different striatal uptake ratios, and visually according to a predefined ranking scale. B-SIT score was significantly lower for PD patients, but not significantly different between APS and non-parkinsonism. The visual assessment of DaTSCAN had higher sensitivity, specificity and diagnostic accuracy compared to olfactory testing. Most PD patients (75 %) had visually predominant dopamine depletion in putamen, while most APS patients (56 %) had visually severe dopamine depletion both in putamen and in caudate nucleus. The combination of DaTSCAN and B-SIT led to a higher rate of correctly classified patients. Olfactory testing can distinguish PD from non-parkinsonism, but not PD from APS or APS from non-parkinsonism. DaTSCAN is more efficient than olfactory testing and can be valuable in differentiating PD from APS. However, combining olfactory testing and DaTSCAN imaging has a higher predictive value than these two methods separately.

  • 32.
    Georgiopoulos, Charalampos
    et al.
    Department of Radiology and Department ofMedical and Health Sciences, Linköping University; Center for Medical ImageScience and Visualization (CMIV), Linköping University.
    Warntjes, Marcel
    Center for Medical ImageScience and Visualization (CMIV), Linköping University; SyntheticMR AB .
    Dizdar, Nil
    Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University.
    Zachrisson, Helene
    Center for Medical ImageScience and Visualization (CMIV), Linköping University; Department of Clinical Physiology and Departmentof Medical and Health Sciences, Linköping University, Linköping.
    Engström, Maria
    Center for Medical ImageScience and Visualization (CMIV), Linköping University, Linköping; Department of Medical andHealth Sciences, Linköping University, Linköping.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea CDRC Centre de Diagnostic Radiologiquede Carouge SA, Geneva, Switzerland .
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Olfactory Impairment in Parkinson's Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging.2017In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 7, no 2, 301-311 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Olfactory impairment is an early manifestation of Parkinson's disease (PD). Diffusion Tensor Imaging (DTI) and Magnetization Transfer (MT) are two imaging techniques that allow noninvasive detection of microstructural changes in the cerebral white matter.

    OBJECTIVE: To assess white matter alterations associated with olfactory impairment in PD, using a binary imaging approach with DTI and MT.

    METHODS: 22 PD patients and 13 healthy controls were examined with DTI, MT and an odor discrimination test. DTI data were first analyzed with tract-based spatial statistics (TBSS) in order to detect differences in fractional anisotropy, mean, radial and axial diffusivity between PD patients and controls. Voxelwise randomized permutation was employed for the MT analysis, after spatial and intensity normalization. Additionally, ROI analysis was performed on both the DTI and MT data, focused on the white matter adjacent to olfactory brain regions.

    RESULTS: Whole brain voxelwise analysis revealed decreased axial diffusivity in the left uncinate fasciculus and the white matter adjacent to the left olfactory sulcus of PD patients. ROI analysis demonstrated decreased axial diffusivity in the right orbitofrontal cortex, as well as decreased mean diffusivity and axial diffusivity in the white matter of the left entorhinal cortex of PD patients. There were no significant differences regarding fractional anisotropy, radial diffusivity or MT between patients and controls.

    CONCLUSIONS: ROI analysis of DTI could detect microstructural changes in the white matter adjacent to olfactory areas in PD patients, whereas MT imaging could not.

  • 33.
    Gingnell, Malin
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Alaie, Iman
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Björkstrand, Johannes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Faria, Vanda
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Harvard Med Sch, Boston Childrens Hosp, Ctr Pain & Brain, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA.
    Carlbring, Per
    Stockholm Univ, Dept Psychol, Stockholm, Sweden.
    Andersson, Gerhard
    Linkoping Univ, Dept Behav Sci & Learning, Psychol, Linkoping, Sweden.; Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Reis, Margareta
    Linkoping Univ, Div Drug Res Clin Pharmacol, Dept Hlth Sci, Linkoping, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wahlstedt, Kurt
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Combining escitalopram and cognitive-behavioural therapy for social anxiety disorder: randomised controlled fMRI trial.2016In: British Journal of Psychiatry, ISSN 0007-1250, E-ISSN 1472-1465, Vol. 209, no 3, 229-235 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioural therapy (CBT) are often used concomitantly to treat social anxiety disorder (SAD), but few studies have examined the effect of this combination.

    AIMS: To evaluate whether adding escitalopram to internet-delivered CBT (ICBT) improves clinical outcome and alters brain reactivity and connectivity in SAD.

    METHOD: Double-blind, randomised, placebo-controlled neuroimaging trial of ICBT combined either with escitalopram (n = 24) or placebo (n = 24), including a 15-month clinical follow-up (trial registration: ISRCTN24929928).

    RESULTS: Escitalopram+ICBT, relative to placebo+ICBT, resulted in significantly more clinical responders, larger reductions in anticipatory speech state anxiety at post-treatment and larger reductions in social anxiety symptom severity at 15-month follow-up and at a trend-level (P = 0.09) at post-treatment. Right amygdala reactivity to emotional faces also decreased more in the escitalopram+ICBT combination relative to placebo+ICBT, and in treatment responders relative to non-responders.

    CONCLUSIONS: Adding escitalopram improves the outcome of ICBT for SAD and decreased amygdala reactivity is important for anxiolytic treatment response.

  • 34. Grankvist, J
    et al.
    Fisker, R
    Iyer, V
    Fründ, E T
    Simonsen, C
    Christensen, T
    Stenbygaard, L
    Ewertz, M
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    MRI and PET/CT of patients with bone metastases from breast carcinoma2012In: European Journal of Radiology, ISSN 0720-048X, E-ISSN 1872-7727, Vol. 81, no 1, e13-e18 p.Article in journal (Refereed)
    Abstract [en]

    3.0Tesla magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) was compared with combined 18F-fluorodeoxyglucose positron emission tomography and computed tomography (PET/CT) in patients with suspected bone metastases from breast cancer. A prospective clinical study was performed in 13 female breast cancer patients (mean age 61years; range 45-85 years). The spine was imaged in the sagittal plane with T1-weighted (T1), short tau inversion recovery (STIR), and T2-weighted fat-saturated (T2) sequences. The pelvis was imaged similarly in the coronal plane. Axial DWI was performed from the skull base to the mid-thigh. MRI and PET/CT were performed in all patients at a maximum interval of 10 working days and at least 14 days after chemotherapy. MRI was reviewed by two radiologists, and their consensus on potential metastases in 27 predefined locations was recorded. The predefined locations were the vertebral bodies (24), the left (1) and right (1) pelvic bones, and the sacral bone (1). The PET/CT was reviewed by a radiologists and a nuclear medicine physician. MRI detected 59 of the 60 active metastases found with our gold standard modality PET/CT. T1 had the highest sensitivity (98%) but rather low specificity (77%), but with the addition of STIR and DWI, the specificity increased to 95%. The additional metastases detected with MRI most likely represented postherapeutic residual scars without active tumour. In conclusion, 3.0Tesla MRI with T1, STIR, and DWI is useful for the clinical evaluation of bone metastases from breast cancer and compares well to PET/CT.

  • 35.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Plasma Parathyroid Hormone Is Associated with Vascular Dementia and Cerebral Hyperintensities in Two Community-Based Cohorts2014In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, no 11, 4181-4189 p.Article in journal (Refereed)
    Abstract [en]

    Context:

    In diseases with increased PTH such as hyperparathyroidism and chronic renal failure, dementia is common. Little is known of PTH and dementia in the community.

    Objective:

    We sought to investigate relations between PTH, clinical dementia and cerebral micro-vascular disease.

    Setting and Design:

    The Uppsala Longitudinal Study Of Adult Men (ULSAM) was prospective, baseline, 1991-1995; followup, 15.8 years. The Prospective Investigation Of The Vasculature In Uppsala Seniors (PIVUS) was cross-sectional, baseline, 2001. Both settings were community based.

    Participants and Main Outcome Measure:

    In the ULSAM study of 998 men (age 71) the association between PTH and dementia was investigated. In the PIVUS study of 406 men and women (age 70) the relation between PTH and magnetic resonance imaging signs of cerebral small vascular disease was investigated.

    Results:

    During followup, 56 individuals were diagnosed with vascular, 91 with Alzheimer's, and 59 with other dementias. In Cox-regression analyses, higher PTH was associated with vascular dementia (hazard ratio per 1 SD increase of PTH, 1.41; P < .01), but not with other dementias. The top tertile of PTH accounted for 18.5% of the population-attributable risk for vascular dementia, exceeding all other risk factors. In linear regression analysis in PIVUS, PTH was associated with increasing white matter hyperintensities (WMHI), reflecting increasing burden of cerebral small vessel disease (1 SD PTH increase, 0.31 higher category of WMHI; P = .016). All models were adjusted for vascular risk factors and mineral metabolism.

    Conclusions:

    In two community-based samples, PTH predicted clinically diagnosed and neuroimaging indices of vascular dementia and cerebral small vessel disease. Our data suggest a role for PTH in the development of vascular dementia.

  • 36. Haldorsen, I. S.
    et al.
    Espeland, A.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Central Nervous System Lymphoma: Characteristic Findings on Traditional and Advanced Imaging2011In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 32, no 6, 984-992 p.Article in journal (Refereed)
    Abstract [en]

    SUMMARY: CNS lymphoma consists of 2 major subtypes: secondary CNS involvement by systemic lymphoma and PCNSL. Contrast-enhanced MR imaging is the method of choice for detecting CNS lymphoma. In leptomeningeal CNS lymphoma, representing two-thirds of secondary CNS lymphomas, imaging typically shows leptomeningeal, subependymal, dural, or cranial nerve enhancement. Single or multiple periventricular and/or superficial contrast-enhancing lesions are characteristic of parenchymal CNS lymphoma, representing one-third of secondary CNS lymphomas and almost 100% of PCNSLs. New CT and MR imaging techniques and metabolic imaging have demonstrated characteristic findings in CNS lymphoma, aiding in its differentiation from other CNS lesions. Advanced imaging techniques may, in the future, substantially improve the diagnostic accuracy of imaging, ultimately facilitating a noninvasive method of diagnosis. Furthermore, these imaging techniques may play a pivotal role in planning targeted therapies, prognostication, and monitoring treatment response.

  • 37.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea CDRC Ctr Diagnost Radiol Carouge SA, Clos Fonderie 1, CH-1227 Geneva, Switzerland.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Susceptibility weighted imaging in dementia with Lewy bodies: will it resolve the blind spot of MRI?2016In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 58, no 2, 217-218 p.Article in journal (Refereed)
  • 38. Hansen Pupp, Ingrid
    et al.
    Hövel, Holger
    Hellström, Ann
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Löfqvist, Chatarina
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lazeyras, Francois
    Fellman, Vineta
    Hüppi, Petra S.
    Ley, David
    Postnatal decrease in circulating insulin-like growth factor-I and low brain volumes in very preterm infants2011In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 96, no 4, 1129-1135 p.Article in journal (Refereed)
    Abstract [en]

    Context: IGF-I and IGF binding protein-3 (IGFBP-3) are essential for growth and maturation of the developing brain. Objective: The aim of this study was to evaluate the association between postnatal serum concentrations of IGF-I and IGFBP-3 and brain volumes at term in very preterm infants. Design: Fifty-one infants with a mean (sd) gestational age (GA) of 26.4 (1.9) wk and birth weight (BW) of 888 (288) g were studied, with weekly blood sampling of IGF-I and IGFBP-3 from birth until 35 gestational weeks (GW) and daily calculation of protein and caloric intake. Magnetic resonance images obtained at 40 GW were segmented into total brain, cerebellar, cerebrospinal fluid, gray matter, and unmyelinated white matter volumes. Main Outcome Measures: We evaluated brain growth by measuring brain volumes using magnetic resonance imaging. Results: Mean IGF-I concentrations from birth to 35 GW correlated with total brain volume, unmyelinated white matter volume, gray matter volume, and cerebellar volume [r = 0.55 (P < 0.001); r = 0.55 (P < 0.001); r = 0.44 (P = 0.002); and r = 0.58 (P < 0.001), respectively]. Similar correlations were observed for IGFBP-3 concentrations. Correlations remained after adjustment for GA, mean protein and caloric intakes, gender, severe brain damage, and steroid treatment. Protein and caloric intakes were not related to brain volumes. Infants with BW small for GA had lower mean concentrations of IGF-I (P = 0.006) and smaller brain volumes (P = 0.001-0.013) than infants with BW appropriate for GA. Conclusion: Postnatal IGF-I and IGFBP-3 concentrations are positively associated with brain volumes at 40 GW in very preterm infants. Normalization of the IGF-I axis, directly or indirectly, may support normal brain development in very preterm infants.

  • 39. Heradstveit, Bard E.
    et al.
    Guttormsen, Anne Berit
    Langorgen, Jorund
    Hammersborg, Stig-Morten
    Wentzel-Larsen, Tore
    Fanebust, Rune
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Heltne, Jon-Kenneth
    Capillary leakage in post-cardiac arrest survivors during therapeutic hypothermia: A prospective, randomised study2010In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, Vol. 18, 29- p.Article in journal (Refereed)
    Abstract [en]

    Background: Fluids are often given liberally after the return of spontaneous circulation. However, the optimal fluid regimen in survivors of cardiac arrest is unknown. Recent studies indicate an increased fluid requirement in post-cardiac arrest patients. During hypothermia, animal studies report extravasation in several organs, including the brain. We investigated two fluid strategies to determine whether the choice of fluid would influence fluid requirements, capillary leakage and oedema formation. Methods: 19 survivors with witnessed cardiac arrest of primary cardiac origin were allocated to either 7.2% hypertonic saline with 6% poly (O-2-hydroxyethyl) starch solution (HH) or standard fluid therapy (Ringer's Acetate and saline 9 mg/ml) (control). The patients were treated with the randomised fluid immediately after admission and continued for 24 hours of therapeutic hypothermia. Results: During the first 24 hours, the HH patients required significantly less i.v. fluid than the control patients (4750 ml versus 8010 ml, p = 0.019) with comparable use of vasopressors. Systemic vascular resistance was significantly reduced from 0 to 24 hours (p = 0.014), with no difference between the groups. Colloid osmotic pressure (COP) in serum and interstitial fluid (p < 0.001 and p = 0.014 respectively) decreased as a function of time in both groups, with a more pronounced reduction in interstitial COP in the crystalloid group. Magnetic resonance imaging of the brain did not reveal vasogenic oedema. Conclusions: Post-cardiac arrest patients have high fluid requirements during therapeutic hypothermia, probably due to increased extravasation. The use of HH reduced the fluid requirement significantly. However, the lack of brain oedema in both groups suggests no superior fluid regimen. Cardiac index was significantly improved in the group treated with crystalloids. Although we do not associate HH with the renal failures that developed, caution should be taken when using hypertonic starch solutions in these patients.

  • 40. Heradstveit, Bård E
    et al.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Skeidsvoll, Håvard
    Hammersborg, Stig-Morten
    Wentzel-Larsen, Tore
    Guttormsen, Anne Berit
    Heltne, Jon-Kenneth
    Repeated magnetic resonance imaging and cerebral performance after cardiac arrest: a pilot study2011In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 82, no 5, 549-555 p.Article in journal (Refereed)
    Abstract [en]

    AIM OF THE STUDY:

    Prognostication may be difficult in comatose cardiac arrest survivors. Magnetic resonance imaging (MRI) is potentially useful in the prediction of neurological outcome, and it may detect acute ischemia at an early stage. In a pilot setting we determined the prevalence and development of cerebral ischemia using serial MRI examinations and neurological assessment.

    METHODS:

    Ten witnessed out-of-hospital cardiac arrest patients were included. MRI was carried out approximately 2h after admission to the hospital, repeated after 24h of therapeutic hypothermia and 96 h after the arrest. The images were assessed for development of acute ischemic lesions. Neurophysiological and cognitive tests as well as a self-reported quality-of-life questionnaire, Short Form-36 (SF-36), were administered minimum 12 months after discharge.

    RESULTS:

    None of the patients had acute cerebral ischemia on MRI at admission. Three patients developed ischemic lesions after therapeutic hypothermia. There was a change in the apparent diffusion coefficient, which significantly correlated with the temperature (p < 0.001). The neurophysiological tests appeared normal. The patients scored significantly better on SF 36 than the controls as regards both bodily pain (p = 0.023) and mental health (p = 0.016).

    CONCLUSIONS:

    MRI performed in an early phase after cardiac arrest has limitations, as MRI performed after 24 and 96 h revealed ischemic lesions not detectable on admission. ADC was related to the core temperature, and not to the volume distributed intravenously. Follow-up neurophysiologic tests and self-reported quality of life were good.

  • 41.
    Hogenkamp, Pleunie S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Zhou, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Dahlberg, Linda Solstrand
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Stark, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsen, A. L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Wiemerslage, Lyle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Higher resting-state activity in reward-related brain circuits in obese versus normal-weight females independent of food intake2016In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, no 11, 1687-1692 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals-that is, resting-state brain activity-in the context of food intake are, however, less well studied.

    OBJECTIVE: To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese and normal-weight females, as assessed by functional magnetic resonance imaging (fMRI).

    METHODS: Fractional amplitude of low-frequency fluctuations were measured in the morning following an overnight fast in 17 obese (age: 39±11 years, body mass index (BMI): 42.3±4.8 kg m(-)(2)) and 12 normal-weight females (age: 36±12 years, BMI: 22.7±1.8 kg m(-)(2)), both before and 30 min after consumption of a standardized meal (~260 kcal).

    RESULTS: Compared with normal-weight controls, obese females had increased low-frequency activity in clusters located in the putamen, claustrum and insula (P<0.05). This group difference was not altered by food intake. Self-reported hunger dropped and plasma glucose concentrations increased after food intake (P<0.05); however, these changes did not differ between the BMI groups.

    CONCLUSION: Reward-related brain regions are more active under resting-state conditions in obese than in normal-weight females. This difference was independent of food intake under the experimental settings applied in the current study. Future studies involving males and females, as well as utilizing repeated post-prandial resting-state fMRI scans and various types of meals are needed to further investigate how food intake alters resting-state brain activity in obese humans.International Journal of Obesity advance online publication, 28 June 2016; doi:10.1038/ijo.2016.105.

  • 42.
    Holzgraefe, Bernhard
    et al.
    Karolinska Univ Hosp, ECMO Dept Karolinska, Huddinge, Sweden; Karolinska Univ Hosp, Dept Physiol & Pharmacol, Sect Anesthesiol & Intens Care Med, Huddinge, Sweden.
    Andersson, Christin
    Karolinska Univ Hosp, Dept Psychol, Huddinge, Sweden; Karolinska Univ Hosp, Dept Clin Neurosci, Stockholm, Sweden.
    Kalzén, Håkan
    Karolinska Univ Hosp, ECMO Dept Karolinska, Q9 00, S-17176 Stockholm, Sweden.
    von Bahr, Viktor
    Karolinska Univ Hosp, ECMO Dept Karolinska, Huddinge, Sweden; Karolinska Univ Hosp, Dept Physiol & Pharmacol, Sect Anesthesiol & Intens Care Med, Huddinge, Sweden.
    Mosskin, Mikael
    Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Palmér, Kenneth
    Karolinska Univ Hosp, ECMO Dept Karolinska, Q9 00, S-17176 Stockholm, Sweden.
    Frenckner, Björn
    Karolinska Univ Hosp, ECMO Dept Karolinska, Q9 00, S-17176 Stockholm, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Does permissive hypoxaemia during extracorporeal membrane oxygenation cause long-term neurological impairment?: A study in patients with H1N1-induced severe respiratory failure2017In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 34, no 2, 98-103 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Extracorporeal Life Support Organisation accepts permissive hypoxaemia in adult patients during extracorporeal membrane oxygenation (ECMO). The neurological long-term outcome of this approach has not yet been studied.

    OBJECTIVES: We investigated the prevalence of brain lesions and cognitive dysfunction in survivors from the Influenza A/H1N1 2009 pandemic treated with permissive hypoxaemia during ECMO for severe acute respiratory distress syndrome (ARDS). Our hypothesis was that this method is reasonable if tissue hypoxia is avoided.

    DESIGN: Long-term follow-up study after ECMO.

    SETTING: Karolinska University Hospital, Sweden, from October 2012 to July 2013.

    PATIENTS: Seven patients treated with ECMO for severe influenza A/H1N1-induced ARDS were studied 3.2 years after treatment. Blood lactate concentrations were used as a surrogate for tissue oxygenation.

    INTERVENTIONS: Neurocognitive outcome was studied with standardised cognitive tests and MRI of the brain.

    MAIN OUTCOME MEASURES: Cognitive functioning and hypoxic brain lesions after permissive hypoxaemia during ECMO. The observation period was the first 10 days of ECMO or the entire treatment period if shorter than 10 days.

    RESULTS: Eleven of 13 patients were still alive 3 years after ECMO. We were able to contact seven of these patients (mean age 31 years), who all agreed to participate in this study. Mean +/- SD peripherally measured arterial saturation during the observation period was 79 +/- 10%. Full-scale Intelligence Quotient was within one standard deviation or above from the mean of a healthy population in five patients, and was 1.5 SD below the mean in one patient. In one other patient, it could not be determined because of a lack of formal education. Memory functioning was normal in all patients. MRI showed no changes related to cerebral hypoxia.

    CONCLUSIONS: Permissive hypoxaemia during ECMO might not negatively affect long-term cognitive outcome if adequate organ perfusion is maintained.

  • 43.
    Jiltsova, Elena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Möttönen, Timo
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Haapasalo, Joonas
    Tähtinen, Timo
    Peltola, Jukka
    Öhman, Juha
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kiekara, Tommi
    Lehtimäki, Kai
    Imaging of Anterior Nucleus of Thalamus Using 1.5T MRI for Deep Brain Stimulation Targeting in Refractory Epilepsy2016In: Neuromodulation (Malden, Mass.), ISSN 1094-7159, E-ISSN 1525-1403, Vol. 19, no 8, 812-817 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Deep brain stimulation (DBS) of the anterior nucleus of thalamus (ANT) is an evolving treatment option in refractory focal epilepsy. Due to poor visualization of ANT in traditional MRI sequences used for movement disorder surgery, targeting of ANT is mainly based on stereotactic atlas information. Sophisticated 3T MRI methods enable visualization of ANT, but 1.5T MRI is still preferred or more readily available in a large number of centers performing DBS.

    OBJECTIVE: In the present study, we sought to determine whether ANT could be adequately visualized at 1.5T MRI pre- and postoperatively using imaging techniques similar to the ones visualizing ANT in 3T MRI. A total of 15 MRI examinations with short tau inversion recovery (STIR) and T1-weighted magnetization prepared gradient echo (MPRAGE) images were performed to visualize ANT in nonepileptic subjects (n = 2), patients with vagus nerve stimulator (VNS) (n = 3), stereotactic MRI (n = 3), patients with ANT-DBS (n = 7).

    RESULTS: ANT was distinctly visualized in STIR and T1-weighted MPRAGE images in patients without implanted stimulators, with Leksell stereotactic frame and with fully implanted VNS. Postoperative 1.5T MRI was able to demonstrate some of the anatomical landmarks around ANT enabling assessment of electrode contact locations.

    CONCLUSIONS: The visualization of ANT is possible in preoperative 1.5T MRI enabling direct targeting of ANT all examined situations. The use of indirect targeting and its inherent potential for lead misplacement due to anatomical variation may be avoided using these MRI methods. Furthermore, postoperative MRI with STIR and T1-weighted MPRAGE images enable detailed postoperative assessment of contact locations.

  • 44. Järnum, Hanna
    et al.
    Eskildsen, Simon F
    Steffensen, Elena G
    Lundbye-Christensen, Søren
    Simonsen, Carsten W
    Thomsen, Ib S
    Fründ, Ernst-Torben
    Théberge, Jean
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Longitudinal MRI study of cortical thickness, perfusion, and metabolite levels in major depressive disorder2011In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 124, no 6, 435-446 p.Article in journal (Refereed)
    Abstract [en]

    Objective:  To determine whether patients with major depressive disorder (MDD) display morphologic, functional, and metabolic brain abnormalities in limbic-cortical regions at a baseline magnetic resonance (MR) scan and whether these changes are normalized in MDD patients in remission at a follow-up scan.

    Method:  A longitudinal 3.0-Tesla (T) magnetic resonance imaging (MRI) study was carried out with cortical thickness measurements with a surface-based approach, perfusion measurements with three-dimensional (3D) pseudo-continuous arterial spin labeling (pCASL), and spectroscopy (1H-MRS) measurements in the anterior cingulate cortex (ACC) with water as an internal reference adjusted for cerebrospinal fluid content. We examined 23 MDD patients and 26 healthy controls. MDD patients underwent a baseline MRI at inclusion and were invited to a follow-up scan when they were in remission or after a 6-month follow-up period.

    Results:  Major findings were a significantly thinner posterior cingulate cortex in non-remitters than in remitters, a significant decrease in perfusion in the frontal lobes and the ACC in non-remitters compared with healthy controls at baseline and significantly reduced N-acetylaspartate, myo-inositol, and glutamate levels in MDD patients compared with healthy controls at baseline.

    Conclusion:  Using novel MRI techniques, we have found abnormalities in cerebral regions related to cortical-limbic pathways in MDD patients.

  • 45. Järnum, Hanna
    et al.
    Knutsson, Linda
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Brain tumours: evaluation of perfusion using 3D-FSE-pseudocontinuous arterial spin labelling2011In: Tumors of the Central Nervous system / [ed] M A Hayat, Dordrecht: Springer, 2011, vol 3, part 2, 135-142 p.Chapter in book (Refereed)
  • 46. Järnum, Hanna
    et al.
    Steffensen, Elena G.
    Knutsson, Linda
    Fründ, Ernst-Torben
    Simonsen, Carsten Wiberg
    Lundbye-Christensen, Søren
    Shankaranarayanan, Ajit
    Alsop, David C.
    Jensen, Finn Taagehøj
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Perfusion MRI of brain tumours: a comparative study of pseudo-continuous arterial spin labelling and dynamic susceptibility contrast imaging2010In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 52, no 4, 307-317 p.Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The purpose of this study was to compare the non-invasive 3D pseudo-continuous arterial spin labelling (PC ASL) technique with the clinically established dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC-MRI) for evaluation of brain tumours. METHODS: A prospective study of 28 patients with contrast-enhancing brain tumours was performed at 3 T using DSC-MRI and PC ASL with whole-brain coverage. The visual qualitative evaluation of signal enhancement in tumour was scored from 0 to 3 (0 = no signal enhancement compared with white matter, 3 = pronounced signal enhancement with equal or higher signal intensity than in grey matter/basal ganglia). The extent of susceptibility artefacts in the tumour was scored from 0 to 2 (0 = no susceptibility artefacts and 2 = extensive susceptibility artefacts (maximum diameter > 2 cm)). A quantitative analysis was performed with normalised tumour blood flow values (ASL nTBF, DSC nTBF): mean value for region of interest (ROI) in an area with maximum signal enhancement/the mean value for ROIs in cerebellum. RESULTS: There was no difference in total visual score for signal enhancement between PC ASL and DSC relative cerebral blood flow (p = 0.12). ASL had a lower susceptibility-artefact score than DSC-MRI (p = 0.03). There was good correlation between DSC nTBF and ASL nTBF values with a correlation coefficient of 0.82. CONCLUSION: PC ASL is an alternative to DSC-MRI for the evaluation of perfusion in brain tumours. The method has fewer susceptibility artefacts than DSC-MRI and can be used in patients with renal failure because no contrast injection is needed.

  • 47.
    Latini, Francesco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ryttlefors, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Rapid and Accurate MRI Segmentation of Peritumoral Brain Edema in Meningiomas2017In: Clinical neuroradiology, ISSN 1869-1447, Vol. 27, no 2, 145-152 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    The extent of peritumoral brain edema (PTBE) in meningiomas commonly affects the clinical outcome. Despite its importance, edema volume is usually highly inaccurately approximated to a spheroid shape. We tested the accuracy and the reproducibility of semiautomatic lesion management software for the analysis of PTBE in a homogeneous case series of surgically confirmed intracranial meningiomas.

    METHODS:

    PTBE volume was calculated on magnetic resonance images in 50 patients with intracranial meningiomas using commercial lesion management software (Vue PACS Livewire, Carestream, Rochester, NY, USA). Inter and intraobserver agreement evaluation and a comparison between manual volume calculation, the semiautomatic software and spheroid approximation were performed in 22 randomly selected patients.

    RESULTS:

    The calculation of edema volume was possible in all cases irrespective of the extent of the signal changes. The median time for each calculation was 3 min. Interobserver and intraobserver agreement confirmed the reproducibility of the method. Comparison with standard (fully manual) calculation confirmed the accuracy of this software.

    CONCLUSIONS:

    Our study showed a high level of reproducibility of this semiautomatic computational method for peritumoral brain edema. It is rapid and easy to use after relatively short training and is suitable for implementation in clinical practice.

  • 48. Laustsen, Søren Ravn
    et al.
    Sørensen, Preben
    Fründ, Torben
    Larsson, Henrik B. W.
    Christensen, Thorkil
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Præoperativ funktionel magnetisk resonans-billeddannelse hos patienter med hjernetumor2010In: Ugeskrift for læger, ISSN 0041-5782, E-ISSN 1603-6824, Vol. 172, no 35, 2370-2376 p.Article in journal (Refereed)
    Abstract [da]

    INTRODUCTION: Functional Magnetic Resonance Imaging (fMRI) allows important functions in the brain cortex to be mapped noninvasively. The purpose with this work was to investigate a possible correlation between the distance from the tumour margin to fMRI activity and postoperative neurological deficits by means of a standardised method for measurement of distance. A second purpose was to investigate the influence of preoperative fMRI on the neurosurgical decision-making process. MATERIAL AND METHODS: Retrospective study of 25 patients. The inclusion criteria were surgery or biopsy after fMRI plus a three-month postoperative assessment. A total of 14 patients complied with these requirements (six men and eight women, the mean age was 39 years). fMRI raw data was collected using a three tesla magnetic resonance scanner (Signa HDx R14M5, GE Healthcare). The distance from the tumour margin to fMRI activation was measured using GE-reformat version 4.2 after raw data had been postprocessed using GE BrainwavePA version 1.3.08130. The neurosurgeons valuation of fMRI in the preoperative decision-making process was obtained using a standard questionnaire. RESULTS: There was a trend of association between distance from tumour to eloquent functional areas and the patients' postoperative neurological outcome (Fisher's exact test: distance < 15 mm, p = 0.43; distance < 10 mm, p = 0.14). fMRI proved very useful when deciding whether to operate or not (42%), when deciding the surgical approach (50%) and when deciding the extent of the surgical approach (83%). CONCLUSION: The standardised method for measurement of distance between tumour margin and fMRI activity can contribute to the preoperative risk assessment in patients with brain tumours.

  • 49.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Endothelium-dependent vasodilation is related to the occurrence of cortical brain infarcts at MR imaging: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2017In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 37, no 2, 194-197 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Infarcts in the brain can be divided into larger cortical and smaller deep lacunar infarcts. The pathogenesis differs between these two types of infarctions.

    OBJECTIVE: This study aims to investigate the relationship between measures of endothelium-dependent vasodilation (EDV) and occurrence of cortical and lacunar infarcts in a population-based sample.

    METHODS: In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, 1016 subjects aged 70 were evaluated by the invasive forearm technique with acetylcholine (EDV) and brachial artery ultrasound to assess flow-mediated vasodilation (FMD). Six to seven years later MRI of the brain was performed, and the prevalence of cortical and lacunar infarcts was visually assessed in 407 randomly selected subjects.

    RESULTS: Lacunar infarcts were found in 22% and cortical infarcts in 5·9% of the subjects. EDV and FMD were both significantly related to the occurrence of cortical, but not lacunar infarcts. In a model adjusting for gender, waist circumference, body mass index, fasting blood glucose, systolic and diastolic blood pressure, HDL and LDL cholesterol, serum triglycerides, smoking, antihypertensive treatment and statin use, both EDV and FMD were independent predictors of cortical infarcts (P = 0·035 and P = 0·008, respectively).

    CONCLUSIONS: Endothelium-dependent vasodilation in both forearm resistance vessels and the brachial artery was related to the occurrence of cortical, but not lacunar, infarcts at MRI in a population-based sample independently of traditional risk factors.

  • 50.
    Lubberink, Mark
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Gaging, Johannes
    Uppsala Univ, Uppsala, Sweden..
    Lindskog, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Tracer kinetic analysis of the SV2A ligand 11C-UCBA as a PET marker for synaptic density in humans2017In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 58, no S1, 631Article in journal (Other academic)
    Abstract [en]

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

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

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

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

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