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Quantitative Magnetic Resonance in Diffuse Neurological and Liver Disease
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.
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: urn:nbn:se:liu:diva-54728ISBN: 978-91-7393-390-2 (print)OAI: oai:DiVA.org:liu-54728DiVA: diva2:309555
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
List of papers
1. Low Choline Concentrations in Normal-Appearing White Matter of Patients with Multiple Sclerosis and Normal MR Imaging Brain Scans
Open this publication in new window or tab >>Low Choline Concentrations in Normal-Appearing White Matter of Patients with Multiple Sclerosis and Normal MR Imaging Brain Scans
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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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-39360 (URN)10.3174/ajnr.A0580 (DOI)000249278700021 ()47991 (Local ID)47991 (Archive number)47991 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2014-10-02
2. Rapid magnetic resonance quantification on the brain: Optimization for clinical usage
Open this publication in new window or tab >>Rapid magnetic resonance quantification on the brain: Optimization for clinical usage
2008 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 60, no 2, 320-329 p.Article in journal (Refereed) Published
Abstract [en]

A method is presented for rapid simultaneous quantification of the longitudinal T1 relaxation, the transverse T2 relaxation, the proton density (PD), and the amplitude of the local radio frequency B 1 field. All four parameters are measured in one single scan by means of a multislice, multiecho, and multidelay acquisition. It is based on a previously reported method, which was substantially improved for routine clinical usage. The improvements comprise of the use of a multislice spin-echo technique, a background phase correction, and a spin system simulation to compensate for the slice-selective RF pulse profile effects. The aim of the optimization was to achieve the optimal result for the quantification of magnetic resonance parameters within a clinically acceptable time. One benchmark was high-resolution coverage of the brain within 5 min. In this scan time the measured intersubject standard deviation (SD) in a group of volunteers was 2% to 8%, depending on the tissue (voxel size = 0.8 x 0.8 x 5 mm). As an example, the method was applied to a patient with multiple sclerosis in whom the diseased tissue could clearly be distinguished from healthy reference values. Additionally it was shown that, using the approach of synthetic MRI, both accurate conventional contrast images as well as quantification maps can be generated based on the same scan. © 2008 Wiley-Liss, Inc.

Keyword
quantitatie MRI, T1 mapping, T2mapping, PD mapping, B1 mapping, synthetic MRI, neurodegenerative disease
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-42804 (URN)10.1002/mrm.21635 (DOI)000258105800011 ()68904 (Local ID)68904 (Archive number)68904 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2015-10-08Bibliographically approved
3. Is Increased Normal White Matter Glutamate Concentration a Precursor of Gliosis and Disease Progression in Multiple Sclerosis?
Open this publication in new window or tab >>Is Increased Normal White Matter Glutamate Concentration a Precursor of Gliosis and Disease Progression in Multiple Sclerosis?
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(English)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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-54726 (URN)
Available from: 2010-04-07 Created: 2010-04-07 Last updated: 2014-10-02Bibliographically approved
4. Separation of advanced from mild fibrosis in diffuse liver disease using 31P magnetic resonance spectroscopy
Open this publication in new window or tab >>Separation of advanced from mild fibrosis in diffuse liver disease using 31P magnetic resonance spectroscopy
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2008 (English)In: European Journal of Radiology, ISSN 0720-048X, E-ISSN 1872-7727, Vol. 66, no 2, 313-320 p.Article in journal (Refereed) Published
Abstract [en]

31P-MRS using DRESS was used to compare absolute liver metabolite concentrations (PME, Pi, PDE, γATP, αATP, βATP) in two distinct groups of patients with chronic diffuse liver disorders, one group with steatosis (NAFLD) and none to moderate inflammation (n = 13), and one group with severe fibrosis or cirrhosis (n = 16). All patients underwent liver biopsy and extensive biochemical evaluation. A control group (n = 13) was also included. Absolute concentrations and the anabolic charge, AC = {PME}/({PME} + {PDE}), were calculated.

Comparing the control and cirrhosis groups, lower concentrations of PDE (p = 0.025) and a higher AC (p < 0.001) were found in the cirrhosis group. Also compared to the NAFLD group, the cirrhosis group had lower concentrations of PDE (p = 0.01) and a higher AC (p = 0.009). No significant differences were found between the control and NAFLD group. When the MRS findings were related to the fibrosis stage obtained at biopsy, there were significant differences in PDE between stage F0–1 and stage F4 and in AC between stage F0–1 and stage F2–3.

Using a PDE concentration of 10.5 mM as a cut-off value to discriminate between mild, F0–2, and advanced, F3–4, fibrosis the sensitivity and specificity were 81% and 69%, respectively. An AC cut-off value of 0.27 showed a sensitivity of 93% and a specificity of 54%.

In conclusion, the results suggest that PDE is a marker of liver fibrosis, and that AC is a potentially clinically useful parameter in discriminating mild fibrosis from advanced.

Place, publisher, year, edition, pages
Elsevier, 2008
Keyword
Absolute quantification; Phosphorus; MRS; Steatosis; In vivo
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-43125 (URN)10.1016/j.ejrad.2007.06.004 (DOI)000256140900026 ()17646074 (PubMedID)71944 (Local ID)71944 (Archive number)71944 (OAI)
Projects
NILB
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2014-10-02Bibliographically approved
5. Quantitative Abdominal Fat Estimation Using MRI
Open this publication in new window or tab >>Quantitative Abdominal Fat Estimation Using MRI
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2008 (English)In: Proceedings - International Conference on Pattern Recognition, IEEE Computer Society, 2008, 1-4 p.Conference paper, Published paper (Refereed)
Abstract [en]

This paper introduces a new method for automaticquantification of subcutaneous, visceral and nonvisceralinternal fat from MR-images acquired usingthe two point Dixon technique in the abdominal region.The method includes (1) a three dimensionalphase unwrapping to provide water and fat images, (2)an image intensity inhomogeneity correction, and (3) amorphon based registration and segmentation of thetissue. This is followed by an integration of the correctedfat images within the different fat compartmentsthat avoids the partial volume effects associated withtraditional fat segmentation methods. The method wastested on 18 subjects before and after a period of fastfoodhyper-alimentation showing high stability andperformance in all analysis steps.

Place, publisher, year, edition, pages
IEEE Computer Society, 2008
Series
International Conference on Pattern Recognition, ISSN 1051-4651
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:liu:diva-21108 (URN)10.1109/ICPR.2008.4761764 (DOI)000264729001041 ()978-1-4244-2174-9 (ISBN)978-1-4244-2175-6 (ISBN)
Conference
19th International Conference on Pattern Recognition, Tampa FL USA, 8-11 Dec. 2008
Available from: 2009-09-29 Created: 2009-09-29 Last updated: 2015-10-09Bibliographically approved
6. Quantifying differences in hepatic uptake of the liver specific contrast agents Gd-EOB-DTPA and Gd-BOPTA: a pilot study
Open this publication in new window or tab >>Quantifying differences in hepatic uptake of the liver specific contrast agents Gd-EOB-DTPA and Gd-BOPTA: a pilot study
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2012 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 22, no 3, 642-653 p.Article in journal (Refereed) Published
Abstract [en]

Objectives   To develop and evaluate a procedure for quantifying the hepatocyte-specific uptake of Gd-BOPTA and Gd-EOB-DTPA using dynamic contrast-enhanced (DCE) MRI. Methods   Ten healthy volunteers were prospectively recruited and 21 patients with suspected hepatobiliary disease were retrospectively evaluated. All subjects were examined with DCE-MRI using 0.025 mmol/kg of Gd-EOB-DTPA. The healthy volunteers underwent an additional examination using 0.05 mmol/kg of Gd-BOPTA. The signal intensities (SI) of liver and spleen parenchyma were obtained from unenhanced and enhanced acquisitions. Using pharmacokinetic models of the liver and spleen, and an SI rescaling procedure, a hepatic uptake rate, K Hep, estimate was derived. The K Hep values for Gd-EOB-DTPA were then studied in relation to those for Gd-BOPTA and to a clinical classification of the patient’s hepatobiliary dysfunction. Results   K Hep estimated using Gd-EOB-DTPA showed a significant Pearson correlation with K Hep estimated using Gd-BOPTA (r = 0.64; P < 0.05) in healthy subjects. Patients with impaired hepatobiliary function had significantly lower K Hep than patients with normal hepatobiliary function (K Hep = 0.09 ± 0.05 min-1 versus K Hep = 0.24 ± 0.10 min−1; P < 0.01). Conclusions   A new procedure for quantifying the hepatocyte-specific uptake of T 1-enhancing contrast agent was demonstrated and used to show that impaired hepatobiliary function severely influences the hepatic uptake of Gd-EOB-DTPA. Key Points   • The liver uptake of contrast agents may be measured with standard clinical MRI.Calculation of liver contrast agent uptake is improved by considering splenic uptake.Liver function affects the uptake of the liver-specific contrast agent Gd-EOB-DTPA.Hepatic uptake of two contrast agents (Gd-EOB-DTPA, Gd-BOPTA) is correlated in healthy individuals.This method can be useful for determining liver function, e.g. before hepatic surgery

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2012
Keyword
Gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid – Gadobenate Dimeglumine – Dynamic contrast-enhanced MRI – Pharmacokinetics – Liver
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-73624 (URN)10.1007/s00330-011-2302-4 (DOI)000299768000018 ()21984449 (PubMedID)
Funder
Swedish Research Council, VR/M 2007-2884Medical Research Council of Southeast Sweden (FORSS), 12621Linköpings universitet
Note

The previous status of this article was Manuscript and the working titles was Liver Specific Gd-EOB-DTPA vs. Gd-BOPTA Uptake in Healthy Subjects: A Novel and Quantitative MRI Analysis of Hepatic Uptake and Vascular Enhancement and Hepatic Uptake of Gd-EOB-DTPA in Patients with Varying Degree of Hepatobiliary Disease.

Available from: 2012-01-10 Created: 2012-01-10 Last updated: 2017-12-08

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Dahlqvist Leinhard, Olof

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