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Low Choline Concentrations in Normal-Appearing White Matter of Patients with Multiple Sclerosis and Normal MR Imaging Brain Scans
Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
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.
Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Care, Radiation Physics. Linköping University, Department of Medicine and Care, Radiology. Linköping University, Department of Medicine and Care, Center for Medical Image Science and Visualization. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0001-8661-2232
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2007 (English)In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 28, no 7, 1306-1312 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND PURPOSE: Spectroscopic studies (1H-MR spectroscopy) of normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS) with MR imaging brain lesions have already been performed, but our intention was to investigate NAWM in MS patients who lack brain lesions to elucidate whether the same pathologic changes could be identified.

MATERIALS AND METHODS: We checked 350 medical files of patients with MS who are registered in our institution. Fourteen patients (11 women and 3 men; mean age, 48.6 years; handicap score, Expanded Disability Status Scale [EDSS] 2.9; range, 1–6.5) with clinically definite MS and a normal MR imaging of the brain were included. 1H-MR spectroscopy was performed in 4 voxels (size approximately 17 × 17 × 17 mm3) using absolute quantification of metabolite concentrations. Fourteen healthy control subjects (11 women and 3 men; mean age, 43.3 years) were analyzed in the same way.

RESULTS: Significant differences in absolute metabolite concentrations were observed, with the patients with MS showing a lower total concentration of N-acetyl compounds (tNA), including N-acetylaspartate and N-acetyl aspartylglutamate (13.5 mmol/L versus 14.6 mmol/L; P = .002) compared with the healthy control subjects. Unexpectedly, patients with MS presented significantly lower choline-containing compounds (Cho) compared with healthy control subjects (2.2 mmol/L versus 2.4 mmol/L; P < .001). The EDSS showed a positive correlation to myo-inositol concentrations (0.14 mmol/L per EDSS; r2 = 0.06) and a negative correlation to tNA concentrations (−0.41 mmol/L per EDSS; r2 = 0.22).

CONCLUSION: The unexpected finding of lower Cho concentrations has not been reported previously. We suggest that patients with MS who lack lesions in the brain constitute a separate entity and may have increased protective or healing abilities.

Place, publisher, year, edition, pages
2007. Vol. 28, no 7, 1306-1312 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-39360DOI: 10.3174/ajnr.A0580ISI: 000249278700021Local ID: 47991OAI: oai:DiVA.org:liu-39360DiVA: diva2:260209
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2014-10-02
In thesis
1. Quantitative Magnetic Resonance in Diffuse Neurological and Liver Disease
Open this publication in new window or tab >>Quantitative Magnetic Resonance in Diffuse Neurological and Liver Disease
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction: Magnetic resonance (MR) imaging is one of the most important diagnostic tools in modern medicine. Compared to other imaging modalities, it provides superior soft tissue contrast of all parts of the body and it is considered to be safe for patients. Today almost all MR is performed in a nonquantitative manner, only comparing neighboring tissue in the search for pathology. It is possible to quantify MR-signals and relate them to their physical entities, but time consuming and complicated calibration procedures have prevented this being used in a practical manner for clinical routines. The aim of this work is to develop and improve quantification methods in MRspectroscopy (MRS) and MR-imaging (MRI). The techniques are intended to be applied to diffuse diseases, where conventional imaging methods are unable to perform accurate staging or to reveal metabolic changes associated with disease development.

Methods: Proton (1H) MRS was used to characterize the white matter in the brain of multiple sclerosis (MS) patients. Phosphorus (31P) MRS was used to evaluate the energy metabolism in patients with diffuse liver disease. A new quantitative MRI (qMRI) method was invented for accurate, rapid and simultaneous quantification of B1, T1, T2, and proton density. A method for automatic assessment of visceral adipose tissue volume based on an in- and out-ofphase imaging protocol was developed. Finally, a method for quantification of the hepatobiliary uptake of liver specific T1 enhancing contrast agents was demonstrated on healthy subjects.

Results: The 1H MRS investigations of white matter in MS-patients revealed a significant correlation between tissue concentrations of Glutamate and Creatine on the one hand and the disease progression rate on the other, as measured using the MSSS. High accuracy, both in vitro and in vivo, of the measured MR-parameters from the qMRI method was observed. 31P MRS showed lower concentrations of phosphodiesters, and a higher metabolic charge in patients with cirrhosis, compared to patients with mild fibrosis and to controls. The adipose tissue quantification method agreed with estimates obtained using manual segmentation, and enabled measurements which were insensitive to partial volume effects. The hepatobiliary uptake of Gd-EOB-DTPA and Gd-BOPTA was significantly correlated in healthy subjects.

Conclusion: In this work, new methods for accurate quantification of MR parameters in diffuse diseases in the liver and the brain were demonstrated. Several applications were shown where quantitative MR improves the interpretation of observed signal changes in MRI and MRS in relation to underlying differences in physiology and pathophysiology.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2010. 127 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1184
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-54728 (URN)978-91-7393-390-2 (ISBN)
Public defence
2010-04-29, Elsa Brändströmsalen, Campus US, Linköpings universitet, Linköping, 13:15 (English)
Opponent
Supervisors
Available from: 2010-04-07 Created: 2010-04-07 Last updated: 2017-01-31Bibliographically approved
2. Quantitative magnetic resonance in diffuse liver and neurological disease
Open this publication in new window or tab >>Quantitative magnetic resonance in diffuse liver and neurological disease
2008 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Magnetic resonance (MR) has become one of the most important diagnostic tools in modern medicine. It provides superior soft tissue contrast compared to other imaging modalities, it is extremely flexible as it can be used to image all parts of the body, and it is considered to be safe for patients.

Today almost all MR is performed in a non-quantitative manner, only by comparing neighbouring tissue in the search for pathology. It is possible to quantify the MR-signals to its physical entities, but time consuming and complicated calibration procedures have prevented this in clinical routine.

In this work two different applications of quantitative MR-spectroscopy in diffuse liver and neurological disease, and a new rapid method for simultaneous quantification of proton density, T1 relaxation and T2* relaxation in MR-imaging are presented.

In Paper I, absolutely quantified phosphorus MR-spectroscopy was tested as a predictive tool in order to determine the degree of fibrosis on patients with diffuse liver disease. One group with steatosis and none to moderate inflammation (n=13), one group with severe fibrosis or cirrhosis (n=16), and one group of healthy volunteers (n=13) were included in the study.

Lower concentrations of PDE (p = 0.025), and a higher metabolic charge (AC) [42] (p < 0.001) were found in the cirrhosis group. A sensitivity and specificity of 81% and 69% respectively, were found for the discrimination between mild and advanced fibrosis using PDE concentrations, and 93% and 54% using AC. The results suggest PDE as a marker of liver fibrosis and AC as a potential clinically useful parameter in discriminating mild from advanced fibrosis.

In Paper II proton MR-spectroscopy was used to investigate if there were differences in the concentrations of the observable metabolites in normal appearing white matter in patients with clinically definite multiple sclerosis (MS), and with normal MR-images compared to healthy volunteers. This 'MRI-negative' group consisted of fourteen patients which were compared with fourteen healthy controls. Absolutely quantified proton MR-spectra were acquired from four different voxels in NAWM.

Significant differences in absolute metabolite concentrations were observed between the two groups. The MS-patients had lower total N-acetyl compounds (tNA) (p=0.002) compared to the healthy controls and lower concentration of choline-containing compounds (Cho) compared to the healthy controls (p<0.001). EDSS showed a slightly positive correlation to myolns concentrations (0.14mM/EDSS,r2 = 0.06) and a slightly negative correlation to tNA concentrations (-0.41 mM/EDSS,r2 = 0.22). The finding of lower Cho concentrations has not been reported previously and was unexpected.

In Paper III a new rapid imaging method was presented for determination of proton density, B1, T2* relaxation and T1 relaxation. The method was based on a modified Look-Locker pulse sequence with two main differences. (1) The exchange of the inversion pulse in the Lock-Looker sequence to a saturation pulse in order to enable detection of the B1 field, and (2) the introduction of a multi-echo read-out to enable the detection of T2*. The signal intensity was then scaled to proton density using the estimated B1, T1, and T2* value.

The method was validated in vitro, using phantoms filled with solution of different T1 and T2* water relaxation values, and by comparing the results of the measurements to reference metcyods. In vivo the method was compared with literature values.

The validation showed that the method was highly accurate, both in vitro and in vivo, and that this method enabled quantitative imaging of MR-parameters within a clinically feasible examination time. Potential applications of the method are, among a great range of possibilities, to rapidly provide all the necessary quantification parameters in MR-spectroscopy, and to simultaneously provide fast quantitative diagnostic imaging.

Place, publisher, year, edition, pages
Linköping: Radiofysik, Linköpings universitet, 2008. 72 p.
Series
Linköping Studies in Health Sciences. Thesis, ISSN 1100-6013 ; 86
Keyword
Mapping--methods, Choline--analysis, Liver diseases--diagnosis, Magnetic resonance imaging--methods, Magnetic resonance spectroscopy--methods, Multiple sclerosis--diagnosis, Multiple sclerosis--metabolism, Nerve fibers, myelinated--metabolism
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-44480 (URN)76794 (Local ID)978-91-7393-858-7 (ISBN)76794 (Archive number)76794 (OAI)
Presentation
(English)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-01-31Bibliographically approved

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Gustafsson, M CDahlqvist Leinhard, OlofJaworski, JLundberg, PeterLandtblom, Anne-Marie

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