liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Reduced thalamic N-acetylaspartate in idiopathic normal pressure hydrocephalus: a controlled (1)H-magnetic resonance spectroscopy study of frontal deep white matter and the thalamus using absolute quantification
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.
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.
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.
University of Gothenburg.
Show others and affiliations
2011 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 82, no 7, 772-778 p.Article in journal (Refereed) Published
Abstract [en]

Introduction Patients with idiopathic normal pressure hydrocephalus (INPH) frequently have a reduction in cerebral blood flow in the subcortical frontal lobe/basal ganglia/thalamic areas. With magnetic resonance spectroscopy, the metabolism in the brain can be examined. The aim of this study was to investigate if there was a compromised metabolism in the thalamus and in the subcortical frontal areas in INPH patients. This was done by measuring total creatine, myo-inositol, total choline, N-acetylaspartate (NAA), total N-acetylaspartate (tNA), glutamate and lactate levels. A comparison was made with healthy individuals (HI). Subjects and methods 16 patients (nine males, seven females, mean age 74 years, range 49-83) diagnosed as INPH and 15 HI (nine males, six females, mean age 74 years, range 62-89) were examined. 1 H magnetic resonance spectroscopy (1.5 T, point-resolved spectroscopy, echo time/relaxation time 30/3000 ms, volume of interest 2.5-3 ml) was performed in frontal deep white matter and in the thalamus. Absolute quantification with internal water as a reference was used. Results INPH patients had lower NAA (p = 0.02) and lower tNA (p = 0.05) concentrations in the thalamus compared with HI. NAA and tNA in the frontal deep white matter did not differ between patients and HI. The absolute metabolic concentrations of total creatine, myoinositol total choline, tNA, lactate and Cr ratios in frontal deep white matter and in the thalamus were similar in INPH patients and HI. Conclusion Reduced thalamic NAA and tNA in INPH patients suggest a compromised metabolic neuronal function in these regions. Thus, the thalamus might have an important role in the pathogenesis of INPH.

Place, publisher, year, edition, pages
BMJ Publishing Group , 2011. Vol. 82, no 7, 772-778 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-69842DOI: 10.1136/jnnp.2010.223529ISI: 000291429200016OAI: oai:DiVA.org:liu-69842DiVA: diva2:433456
Note

Original Publication: Fredrik Lundin, Anders Tisell, Olof Dahlqvist Leinhard, M. Tullberg, C. Wikkelso, Peter Lundberg and Göran Leijon, Reduced thalamic N-acetylaspartate in idiopathic normal pressure hydrocephalus: a controlled (1)H-magnetic resonance spectroscopy study of frontal deep white matter and the thalamus using absolute quantification, 2011, Journal of Neurology, Neurosurgery and Psychiatry, (82), 7, 772-778. http://dx.doi.org/10.1136/jnnp.2010.223529 Copyright: BMJ Publishing Group http://group.bmj.com/

Available from: 2011-08-10 Created: 2011-08-08 Last updated: 2017-12-08
In thesis
1. Idiopathic Normal Pressure Hydrocephalus: Aspects on Pathophysiology, Clinical Characteristics and Evaluation Methods
Open this publication in new window or tab >>Idiopathic Normal Pressure Hydrocephalus: Aspects on Pathophysiology, Clinical Characteristics and Evaluation Methods
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction. Idiopathic normal pressure hydrocephalus (iNPH) is a condition with enlargement of the cerebral ventricular system and an intracranial pressure (ICP) within normal limits. Cerebrospinal fluid circulation is disturbed but the mechanisms behind the symptoms: gait and balance difficulties, cognitive dysfunction and micturition problems, are as yet mostly unexplained.

Aim. In Studies I and II the aim was to investigate cerebral metabolism in the frontal deep white matter (FDWM) and the thalamus in iNPH using Magnetic Resonance Spectroscopy (MRS) before and after shunt surgery and to compare this with healthy individuals (HI). In Study III the aim was, by use of actigraphy, to measure motor function, energy expenditure and resting/sleeping time in iNPH patients before and after shunt surgery, in comparison with HI. In Study IV the aim was to study postural function using computerised dynamic posturography (CDP) before and after shunt surgery as well as in comparison with HI.

Patients and Methods. In all studies the patients had a neurological examination and baseline bedside assessments of motor, balance and cognitive function were performed. Motor function was assessed using a motor score (MOS) consisting of the following items: 10 metre walk time in seconds and number of steps and TUG time in seconds and number of steps. MOS was considered significant if there was an increase of 5% or more. The HI were also tested for motor, balance and cognitive function. In Study I the patients (n=16) and the HI (n=15) were examined with MRS (absolute quantification) with voxels placed in the thalamus and in FDWM and compared with one another. In Studies III and IV the preoperative results of actigraphy and CDP respectively in patients (Study III n=33; study IV n=35) were compared with the HI: Study III, n=17; Study IV, n=16. The HI performed these examinations twice and the average was calculated. In Study II, 14 patients, and in Studies III and IV, 20 patients underwent shunt surgery and new MRS/actigraphy/CDP examinations were performed three months postoperatively and compared with the preoperative results.

Results. In the patients decreased total N-acetyl compounds (tNA) and N-acetyl aspartate (NAA) were found in the thalamus compared to the HI. No metabolic differences were seen in the FDWM between the groups. Postoperatively there were no metabolic changes in the thalamus but an increased total Choline (tCho) and a borderline significant decrease in myo-inositol (mIns).During the day the patients took fewer steps and had also lower total energy expenditure (TEE) than the HI. There was no difference concerning resting/sleeping time between patients and the HI. Postoperatively there were no differences of either number of steps, TEE or time spent resting or sleeping compared with the preoperative state. Postural function was worse in the patients compared to the HI, this difference being more pronounced in tests measuring vestibular function, where loss of balance (LOB) was frequent. There was only a slight improvement in balance after shunt surgery. A positive response to the shunt operation was seen in 86% in Study II, 85% in Study III and 90% in Study IV.

Conclusions. Our results suggest that the thalamus may be involved in the pathogenesis of iNPH. In contrast to others, we did not find any metabolic abnormalities in the FDWM, nor detect an increment of tNA or NAA postoperatively in the thalamus. The postoperative increase in tCho and borderline decrease in mIns in the FDWM might reflect a state of metabolic recovery since high tCho, a major component of the cell membrane, may be a sign of increased membrane turnover, and a decrease in mIns may indicate diminished gliosis.

The low gait capacity seen in the iNPH patients was not surprising but well that time spent resting/sleeping did not differ from the HI. Another unexpected finding was the unchanged ambulatory activity after shunt surgery despite improvement in a point test to determine capacity to walk a short distance. We believe this could be due to strong habits that are difficult to break and/or shortage of rehabilitation after surgery.

There was a profound postural dysfunction in the patients with many falls, especially in test situations intended to measure vestibular function. This implies that there is a central vestibular disturbance. The discrete improvement in postural function postoperatively was lower than previously reported.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. 90 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1333
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-84243 (URN)978-91-7519-781-4 (ISBN)
Public defence
2012-10-26, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2012-10-03 Created: 2012-10-02 Last updated: 2012-10-04Bibliographically approved
2. The Non-Invasive Brain Biopsy: Implementation and Application of Quantitative Magnetic Resonance Spectroscopy on Healthy and Diseased Human Brain
Open this publication in new window or tab >>The Non-Invasive Brain Biopsy: Implementation and Application of Quantitative Magnetic Resonance Spectroscopy on Healthy and Diseased Human Brain
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction: In this thesis, one of the major objectives was to implement a method for (absolute) quantitative magnetic resonance spectroscopy (qMRS) of the human brain, intended for clinical use. The implemented method was based on standard spatially selective MRS sequences. The tissue water was used as an internal reference, which was calibrated using whole brain quantitative magnetic resonance imaging (qMRI). The second objective was to apply the method in clinical neuroimaging investigation, of different disease processes in the human brain.

Materials and Methods: In total, 158 subjects were included and 507 MRS measurements (330 in white matter and 177 in the thalamus) were acquired.

In a cross-sectional study of multiple sclerosis (MS), 35 ‘clinically definite MS’ (CDMS) patients were included, of which 15 were atypical CDMS patients with a very low number of white matter lesions (two or fewer), and 20 were typical CDMS patients with white matter lesions (three or more) were included. The metabolite concentrations in normal appearing white matter (NAWM) and the thalamus were assessed using the qMRS method developed in this thesis, and the brain parenchymal fraction (BPF) was calculated from the qMRI data. A cohort of 27 CDMS patients were then treated with Natalizumab and examined both at baseline, and after one year of treatment. Both qMRS and CSF samples for the purpose of assessing intrathecal inflammation were obtained. In addition, the frontal deep white matter (FDWM) and the thalamus were investigated in 20 idiopathic normal pressure hydrocephalus (iNPH) patients using qMRS. Finally, the left thalamus of 14 Kleine-Levin Syndrome (KLS) patients were examined using both qMRS and functional MRI (fMRI) of neurological activation of the left thalamus during a working memory test. Moreover, 63 healthy subjects were included as controls for this work.

Results: A quantitative MRS method based on water referencing was successfully developed, implemented, and evaluated at 1.5 T. Both healthy subjects and MS patients showed a positive correlation between the concentrations of total Creatine (tCr) and myo Inositol (mIns) and age, and also a negative correlation with BPF were observed. Glutamate and Glutamine (Glx) levels were elevated for all MS patient groups compared to healthy controls. In contrast, lower concentrations of total N-acetyl aspartate and N-acetyl aspartate glutamate (tNA) and higher mIns concentrations in NAWM were only observed in MS patients that had developed white matter lesions. Moreover, the change in concentrations of tCr and total Choline (tCho) in MS patients during Natalizumab-treatment were positively correlated with markers of intrathecal inflammation. The iNPH patients had lower tNA and N-acetyl aspartate (NAA) concentrations in the thalamus compared to the controls. In addition, the NAA concentrations in the left thalamus were inversely correlated to the fMRI activation in the left thalamus during the working memory test in KLS patients.

Discussion: The calculated calibration factors were in good agreement with the results found in the literature, indicating that the calibration factors were accurate.

The observed elevated Glx concentration in MS could be due to increased concentrations of glutamate (Glu), which is neurotoxic at high concentrations, thus the elevated Glx could be linked to the clinically observed neurodegeneration in MS both in patients that have developed lesions and in atypical patients that do not develop any (or extremely few) lesions.

Both tCr and mIns can be used as glia markers, thus the correlations of tCr and mIns concentrations with both age and BPF indicates that the local glia cell density, or tissue fraction, increases with age and atrophy. Moreover, the higher mIns concentrations in the NAWM of MS patients with a substantial white matter lesion load indicate that the glia tissue amount in NAWM is increased in MS patients that develop lesions. NAA is neuronal-specific, thus the lower tNA concentrations indicate that the neurone concentration is lower in the NAWM of MS patients that develop MS lesions. The lack of correlation between tNA with age and BPF in combination with the presence of correlation between tCr and mIns with both age and BPF, might be explained using a model for neurodegeneration. In which, there is a higher neurone loss compared to the glia loss. However, the lost tissue is compensated by compression of the tissue, which keeps the density of neurones more or less constant and the density of glia increased.

The low concentration levels of the neuronal marker NAA in the thalamus of the iNPH patients indicates that the basal ganglia-thalamic-subcortical frontal circuits are damage or at least strongly modulated in the thalamus.

The correlation between strong activation in left thalamus during a working memory test with the neuronal marker NAA indicate that the KLS patients that have low neuronal concentration also needed to utilise the working memory circuitry more heavily in order to perform the task as healthy subjects.

Conclusion: It is possible to use qMRI for accurate and robust determination of qMRS in clinical practice, even at 1.5 T field strength. The tGlx concentration may be an important marker for pathology in the nonlesional white matter of MS-patients. The increased glia and loss of neurones in the NAWM are associated with the formation of white matter lesions.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. 69 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1328
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85929 (URN)978-91-7519-795-1 (ISBN)
Public defence
2012-12-21, Elsa Brändströmsalen, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2012-12-03 Created: 2012-12-03 Last updated: 2014-10-02Bibliographically approved

Open Access in DiVA

fulltext(732 kB)385 downloads
File information
File name FULLTEXT01.pdfFile size 732 kBChecksum SHA-512
371206cc1b70ebb24c7b2df9a5c0468cbfa8e3062ec9e3b007f312f6229bad07eb7d03dcde03dde5290719b442cc9aaf3fb678f284865f11cf4e9f96e46423fd
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Authority records BETA

Lundin, FredrikTisell, AndersDahlqvist Leinhard, OlofLundberg, PeterLeijon, Göran

Search in DiVA

By author/editor
Lundin, FredrikTisell, AndersDahlqvist Leinhard, OlofLundberg, PeterLeijon, Göran
By organisation
NeurologyFaculty of Health SciencesDepartment of NeurologyRadiation PhysicsDepartment of Radiation PhysicsCenter for Medical Image Science and Visualization (CMIV)RadiologyDepartment of Radiology in Linköping
In the same journal
Journal of Neurology, Neurosurgery and Psychiatry
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 385 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 305 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf