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  • 1.
    Aalto, Anne
    et al.
    Linköping University, Department of Medicine and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Jaworski, M
    Gustavsson, M
    Tisell, Anders
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Radiation Physics. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL. Linköping University, Faculty of Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Östergötlands Läns Landsting, Sinnescentrum, Department of Neurosurgery UHL. Linköping University, Faculty of Health Sciences.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Radiation Physics. Linköping University, Department of Medicine and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Radiology in Linköping. Linköping University, Faculty of Health Sciences.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Radiology in Linköping. Linköping University, Faculty of Health Sciences.
    Effects of Betainterferon treatment in Multiple Sclerosis Studied by Quantitative 1H MRS2009Conference paper (Other academic)
  • 2.
    Aalto, Anne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Sjoewall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Davidsson, Leif
    Linköping University, Department of Medicine and Care, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Smedby, Örjan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Brain magnetic resonance imaging does not contribute to the diagnosis of chronic neuroborreliosis2007In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 48, no 7, p. 755-762Article in journal (Refereed)
    Abstract [en]

    Background: Borrelia infections, especially chronic neuroborreliosis ( NB), may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive. Purpose: To evaluate brain magnetic resonance imaging ( MRI) in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration. Material and Methods: Sixteen well- characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1- ( with and without gadolinium), T2-, and diffusion- weighted imaging plus fluid- attenuated inversion recovery ( FLAIR) imaging were used. Results: White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls ( no significant difference). Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients ( rho=0.83, P < 0.01) and in controls ( rho=0.61, P < 0.05), but not to the duration of disease. Most lesions were detected with FLAIR, but many also with T2- weighted imaging. Conclusion: A number of MRI findings were detected in patients with chronic NB, although the findings were unspecific when compared with matched controls and did not correlate with disease duration. However, subependymal lesions may constitute a potential finding in chronic NB.

  • 3.
    Dahlqvist Leinhard, Olof
    et al.
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Radiation Physics . Linköping University, Faculty of Health Sciences.
    Jacek, J.
    Aalto, Anne
    Linköping University, Department of Medicine and Health Sciences, Radiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging.
    Grönqvist, A.
    Smedby, Örjan
    Linköping University, Department of Medicine and Health Sciences, Radiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lundberg, Peter
    Linköping University, Department of Medicine and Health Sciences, Radiation Physics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics.
    Is Increased Normal White Matter Glutamate Concentration a Precursor of Gliosis and Disease Progression in Multiple Sclerosis?Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: The multiple sclerosis (MS) severity scale (MSSS) is a new scoring procedure to clinically characterize the rate of disease progression in MS, rather than the disability of the patient. The latter is often characterized using the expanded disability status score (EDSS). The progress rate of the disease, magnetic resonance imaging (MRI)-based measures of ‘black hole lesions’, and atrophy have all been shown to be predicted well by MSSS. In this study we investigated possible relationships between brain metabolite concentrations, measured using proton (1H) magnetic resonance spectroscopy (MRS), and MSSS.

    Purpose: Our aims were to quantitatively investigate the metabolite concentrations in normal appearing white matter (NAWM) in MS-patients, and also to investigate possible correlations between disease subtype, EDSS and MSSS and metabolite concentrations. To minimize the interference from lesion contamination in the MRS measurement, a refined novel analysis procedure had to be developed in order to correct for partial volume effects in tissues near plaques.

    Materials and Methods: Forty eight patients with Clinically Definite MS (CDMS), and 18 normal control subjects (NC) were included retrospectively from several MRS studies. T1, T2, and proton density MRI, and four white matter 1H MRS single voxel PRESS (Point-REsolved SpectroScopy) spectra were acquired in each subject using echo time 35 ms and repetition time 6000 ms on a 1.5 T MR-scanner. A total of 108 examinations were acquired from patients and 18 from NC. Absolutely quantified NAWM metabolite concentrations were determined using a mixed linear model (MLM) analysis that included the degree of T2 lesion contamination in each voxel. The T2 lesion contamination of the MRS voxels was also used as an estimate of ‘lesion load’ at each exam. The corrected metabolite concentrations were then correlated with clinical measures of the patients’ status, including EDSS and MSSS.

    Results: The axonal marker N-acetyl aspartate (NAA) did not correlate with either EDSS or MSSS. The glial cell markers creatine and myo-inositol correlated positively with EDSS. Creatine and glutamate correlated positively with MSSS. The ‘estimated lesion load’ correlated positively not only with EDSS, but also with the number of bouts since disease onset. Importantly, it did not correlate with MSSS.

    Conclusion: The most interesting findings were the unchanged concentrations of NAA, and the concomitant increase of creatine and myo-inositol during the course of disease progression in MSpatients. These not only indicated a constant axonal density, but also that a simultaneous development of gliosis occurred. These processes are most likely linked to demyelination, as well as development of white matter atrophy, a process in which the demyelinated volume is replaced by the surrounding tissue leading to a net loss of white matter. As a consequence of this process, axons in NAWM are probably damaged, which leads to a higher concentration of glia cells relative to the axonal volume. The positive correlation that was found between MSSS, and the glutamate and creatine concentrations in NAWM, in combination with a complete lack of correlation between lesion load and MSSS, suggests that altered glutamate metabolism, and subsequent demyelination and gliosis, is an important pathophysiological mechanism in MS.

  • 4.
    Dahlqvist Leinhard, Olof
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Jaworski, J,
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Aalto, Anne
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Grönkvist, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Tisell, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Faculty of Health Sciences.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Is Increased normal White Matter Glutamate Concentrations a Precursor of Gliosis and Disease Progression in Multiple Sclerosis?2011In: Internationell Society for Magnetic Resonance in Medicin, 2011, 2011, p. 4089-4089Conference paper (Refereed)
  • 5.
    Tisell, Anders
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Warntjes, Jan Bertus Marcel
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Aalto, Arne
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Increased Concentrations of Glutamate and Glutamine in Normal Appearing White Matter of Patients with Multiple Sclerosis and Normal MR Imaging Brain Scans2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 4Article in journal (Refereed)
    Abstract [en]

    In Multiple Sclerosis (MS) the relationship between disease process in normal-appearing white matter (NAWM) and the development of white matter lesions is not well understood. In this study we used single voxel proton ‘Quantitative Magnetic Resonance Spectroscopy’ (qMRS) to characterize the NAWM and thalamus both in atypical ‘Clinically Definite MS’ (CDMS) patients, MRIneg (N = 15) with very few lesions (two or fewer lesions), and in typical CDMS patients, MRIpos (N = 20) with lesions, in comparison with healthy control subjects (N = 20). In addition, the metabolite concentrations were also correlated with extent of brain atrophy measured using Brain Parenchymal Fraction (BPF) and severity of the disease measured using ‘Multiple Sclerosis Severity Score’ (MSSS). Elevated concentrations of glutamate and glutamine (Glx) were observed in both MS groups (MRIneg 8.12 mM, p<0.001 and MRIpos 7.96 mM p<0.001) compared to controls, 6.76 mM. Linear regressions of Glx and total creatine (tCr) with MSSS were 0.16±0.06 mM/MSSS (p = 0.02) for Glx and 0.06±0.03 mM/MSSS (p = 0.04) for tCr, respectively. Moreover, linear regressions of tCr and myo-Inositol (mIns) with BPF were −6.22±1.63 mM/BPF (p<0.001) for tCr and −7.71±2.43 mM/BPF (p = 0.003) for mIns. Furthermore, the MRIpos patients had lower N-acetylaspartate and N-acetylaspartate-glutamate (tNA) and elevated mIns concentrations in NAWM compared to both controls (tNA: p = 0.04 mIns p<0.001) and MRIneg (tNA: p = 0.03 , mIns: p = 0.002). The results suggest that Glx may be an important marker for pathology in non-lesional white matter in MS. Moreover, Glx is related to the severity of MS independent of number of lesions in the patient. In contrast, increased glial density indicated by increased mIns and decreased neuronal density indicated by the decreased tNA, were only observed in NAWM of typical CDMS patients with white matter lesions.

  • 6.
    West, Janne
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Health Sciences.
    Aalto, Anne
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Tisell, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Smedby, Örjan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Normal Appearing and Diffusely Abnormal White Matter in Patients with Multiple Sclerosis, Assessed with Quantitative MR: Optimization for clinical usage2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 4, p. e95161-Article in journal (Refereed)
    Abstract [en]

    Introduction: Magnetic Resonance Imaging is a sensitive technique for detecting white matter (WM) MS lesions, but the relation with clinical disability is low. Because of this, changes in both ‘normal appearing white matter’ (NAWM) and ‘diffusely abnormal white matter’ (DAWM) have been of interest in recent years. MR techniques, including quantitative magnetic resonance imaging (qMRI) and quantitative magnetic resonance spectroscopy (qMRS), have been developed in order to detect and  quantify such changes.

    In this study, a combination of qMRI and qMRS was used to investigate NAWM and DAWM in typical MS patients and in MS patients with low number of WM lesions. Patient data were compared to ‘normal white matter’ (NWM) in healthy controls.

    Methods: QMRI and qMRS measurements were performed on a 1.5T Philips MR-scanner. 35 patients with clinically definite MS and 20 healthy controls were included. Fifteen of the patients showed few WM lesions (‘MRIneg‘) and 20 showed radiologically typical findings (‘MRIpos’). QMRI properties were determined in ROIs of NAWM, DAWM and WM lesions in the MS groups and of NWM in controls. Descriptive statistical analysis and comparisons were performed. Correlations were calculated between qMRI measurements and (1) clinical parameters and (2) WM metabolite concentrations. Regression analyses were performed with brain parenchyma fraction and MSSS.

    Results: NAWM in the MRIneg group was significantly different from NAWM in the MRIpos group and NWM. In addition, R1 and R2 of NAWM in the MRIpos group correlated negatively with EDSS and MSSS. DAWM was significantly different from NWM, but similar in the two MS groups. N-acetyl aspartate correlated negatively with R1 and R2 in MRIneg. Finally, R2 of DAWM was associated with BPF.

    Conclusions: Changes in NAWM and DAWM are independent pathological entities in the disease. Combined qMRI and qMRS measurements of NAWM and DAWM provide important markers for disease status.

  • 7.
    West, Janne
    et al.
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Aalto, Anne
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Radiology in Linköping.
    Warntjes, Marcel
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Clinical Physiology UHL.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Radiology in Linköping.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL.
    Characterizing Normal Appearing White and Diseased Matter in Multiple Sclerosis Using Quantitative MRI2012Conference paper (Other academic)
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