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Quantitative Magnetic Resonance Imaging of the Brain: Applications for Tissue Segmentation and Multiple Sclerosis
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.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Magnetic resonance imaging (MRI) is a sensitive technique for assessing white matter (WM) lesions in multiple sclerosis (MS), but there is a low correlation between MRI findings and clinical disability. Because of this, other pathological changes are of interest, including changes in normal appearing white matter (NAWM) and diffusely abnormal white matter (DAWM). Even so, the mechanisms leading to permanent disability in MS remain unclear.

In contrast to conventional MRI, quantitative MRI (qMRI) is aimed at the direct measurement of the physical tissue properties, such as the relaxation times, T1 and T2, as well as the proton density (PD). QMRI is promising for characterising and quantifying changes in MS and for brain tissue segmentation.

The present work describes a novel method of qMRI for the human brain (QMAP), and a segmentation method based on this. The developed methods were validated in control subjects and MR phantoms. Furthermore, an application in diseased human brain was demonstrated in MS patients. In all, 50 healthy controls and 35 MS patients were scanned with qMRI in a total of 225 acquisitions.

One major finding of this work was that qMRI was able to detect and quantify changes in the MS disease that were not visible using conventional MRI. In particular, it was found that DAWM appears to constitute an intermediate between focal white matter (WM) lesions and NAWM. These changes may be caused by pathological processes that are not entirely attributable to Wallerian degeneration.

This study showed that the QMAP method had high accuracy and relatively high precision, within a clinically acceptable time. This work also demonstrated that qMRI could be used for brain tissue segmentation and volume estimation of the whole brain, using pre-defined tissue characteristics. The results showed that brain tissue segmentation had high repeatability, which was somewhat lower when different geometries were acquired or different field strengths used. In particular, small differences were found between 1.5 T and 3.0 T in deep brain structures, the cerebellum and the brain stem.

This work leads the way for early clinical applications of qMRI, and the challenge for the years to come is to understand the connection between qMRI properties of the brain and underlying biology.

Abstract [sv]

Bildtagning med magnetresonanstomografi (MRT) är en teknik som kan användas för att upptäcka lesioner i vit substans hos patienter med multipel skleros (MS), men sambandet mellan lesioner och klinisk funktionsnedsättning är svagt. På grund av detta har intresset för andra patologiska processer i hjärnan ökat. Exempel är förändringar i vit substans som ser normal ut vid MRT (NAWM) och även så kallad diffus vit vävnad (DAWM). Det är emellertid fortfarande oklart vilka mekanismer i MS som leder till klinisk funktionsnedsättning.

Med kvantitativ MRT (qMRT) kan fysiologiska egenskaper i vävnaden, som till exempel relaxationstiderna (T1 och T2) samt protontäthet (PD), mätas. QMRT kan användas för att mäta förändringar i hjärnan hos MS patienter och dessutom för segmentering av hjärnvävnad vid neurodegenerativa sjukdomar.

I detta arbete beskrivs en ny metod för qMRT applicerat på den mänskliga hjärnan (QMAP) och en segmenteringsmetod som baserades på denna. Metoderna validerades både i friska kontroller och i MR fantom. Slutligen användes qMRT för att undersöka hjärnan hos MS patienter. I studierna inkluderades 50 friska kontroller och 35 MS patienter, där totalt 225 bildtagningar med QMAP utfördes.

Ett viktigt resultat var att qMRT kunde användas för att upptäcka och mäta förändringar i hjärnan hos MS patienter som inte var synliga vid konventionell MRT. DAWM utgjorde en intermediär mellan NAWM och lesioner i vit vävnad. Resultaten pekade mot att dessa förändringar inte endast orsakades av Wallerisk degeneration.

QMAP metoden hade hög noggrannhet och relativt hög precision samt kunde användas med en kliniskt relevant tid för bildtagningen. Genom att använda förhandsdefinierade vävnadsegenskaper kunde qMRT tekniken även användas för segmentering av hjärnvävnad och för att beräkna volymer. Segmenteringen hade hög repeterbarhet men den minskade något när olika geometrier eller fältstyrkor användes. Små skillnader mellan 1.5 T och 3.0 T detekterades framför allt i djupa hjärnstrukturer, lillhjärnan och hjärnstammen.

I detta arbete demonstrerades två applikationer av qMRT för hjärnan. Den största utmaningen för kommande år blir att förstå och förklara sambanden mellan qMRT och underliggande biologiska egenskaper.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2014. , 101 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1384
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:liu:diva-103043DOI: 10.3384/diss.diva-103043ISBN: 978-91-7519-472-1 (print)OAI: oai:DiVA.org:liu-103043DiVA: diva2:686108
Public defence
2014-02-14, Eken, ingång 65 (HU) plan 9, Campus US, Linkööpings universitet, Linköping, 13:02 (Swedish)
Opponent
Supervisors
Available from: 2014-01-10 Created: 2014-01-10 Last updated: 2014-10-02Bibliographically approved
List of papers
1. 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: 2017-12-13Bibliographically approved
2. Novel whole brain segmentation and volume estimation using quantitative MRI
Open this publication in new window or tab >>Novel whole brain segmentation and volume estimation using quantitative MRI
2012 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 22, no 5, 998-1007 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES:

Brain segmentation and volume estimation of grey matter (GM), white matter (WM) and cerebro-spinal fluid (CSF) are important for many neurological applications. Volumetric changes are observed in multiple sclerosis (MS), Alzheimer's disease and dementia, and in normal aging. A novel method is presented to segment brain tissue based on quantitative magnetic resonance imaging (qMRI) of the longitudinal relaxation rate R(1), the transverse relaxation rate R(2) and the proton density, PD.

METHODS:

Previously reported qMRI values for WM, GM and CSF were used to define tissues and a Bloch simulation performed to investigate R(1), R(2) and PD for tissue mixtures in the presence of noise. Based on the simulations a lookup grid was constructed to relate tissue partial volume to the R(1)-R(2)-PD space. The method was validated in 10 healthy subjects. MRI data were acquired using six resolutions and three geometries.

RESULTS:

Repeatability for different resolutions was 3.2% for WM, 3.2% for GM, 1.0% for CSF and 2.2% for total brain volume. Repeatability for different geometries was 8.5% for WM, 9.4% for GM, 2.4% for CSF and 2.4% for total brain volume.

CONCLUSION:

We propose a new robust qMRI-based approach which we demonstrate in a patient with MS. KEY POINTS : • A method for segmenting the brain and estimating tissue volume is presented • This method measures white matter, grey matter, cerebrospinal fluid and remaining tissue • The method calculates tissue fractions in voxel, thus accounting for partial volume • Repeatability was 2.2% for total brain volume with imaging resolution <2.0 mm.

Place, publisher, year, edition, pages
Springer, 2012
Keyword
Brain segmentation – Tissue classification – Quantitative MRI – Brain volume estimation – Partial volume
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-73625 (URN)10.1007/s00330-011-2336-7 (DOI)000303875900007 ()22113264 (PubMedID)
Note
funding agencies|CMIV||Research Council of South-East Sweden (FORSS)||National Research Council (VR/NT)||Knowledge Foundation (KK)||University Hospital Research Funds||Available from: 2012-01-10 Created: 2012-01-10 Last updated: 2017-12-08
3. Application of Quantitative MRI for Brain Tissue Segmentation at 1.5 T and 3.0 T Field Strengths
Open this publication in new window or tab >>Application of Quantitative MRI for Brain Tissue Segmentation at 1.5 T and 3.0 T Field Strengths
Show others...
2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 9Article in journal (Refereed) Published
Abstract [en]

Background

Brain tissue segmentation of white matter (WM), grey matter (GM), and cerebrospinal fluid (CSF) are important in neuroradiological applications. Quantitative Mri (qMRI) allows segmentation based on physical tissue properties, and the dependencies on MR scanner settings are removed. Brain tissue groups into clusters in the three dimensional space formed by the qMRI parameters R1, R2 and PD, and partial volume voxels are intermediate in this space. The qMRI parameters, however, depend on the main magnetic field strength. Therefore, longitudinal studies can be seriously limited by system upgrades. The aim of this work was to apply one recently described brain tissue segmentation method, based on qMRI, at both 1.5 T and 3.0 T field strengths, and to investigate similarities and differences.

Methods

In vivo qMRI measurements were performed on 10 healthy subjects using both 1.5 T and 3.0 T MR scanners. The brain tissue segmentation method was applied for both 1.5 T and 3.0 T and volumes of WM, GM, CSF and brain parenchymal fraction (BPF) were calculated on both field strengths. Repeatability was calculated for each scanner and a General Linear Model was used to examine the effect of field strength. Voxel-wise t-tests were also performed to evaluate regional differences.

Results

Statistically significant differences were found between 1.5 T and 3.0 T for WM, GM, CSF and BPF (p<0.001). Analyses of main effects showed that WM was underestimated, while GM and CSF were overestimated on 1.5 T compared to 3.0 T. The mean differences between 1.5 T and 3.0 T were -66 mL WM, 40 mL GM, 29 mL CSF and -1.99% BPF. Voxel-wise t-tests revealed regional differences of WM and GM in deep brain structures, cerebellum and brain stem.

Conclusions

Most of the brain was identically classified at the two field strengths, although some regional differences were observed.

Place, publisher, year, edition, pages
United States: Public Library of Science, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-97960 (URN)10.1371/journal.pone.0074795 (DOI)000324494000135 ()
Available from: 2013-09-23 Created: 2013-09-23 Last updated: 2017-12-06
4. Normal Appearing and Diffusely Abnormal White Matter in Patients with Multiple Sclerosis, Assessed with Quantitative MR: Optimization for clinical usage
Open this publication in new window or tab >>Normal Appearing and Diffusely Abnormal White Matter in Patients with Multiple Sclerosis, Assessed with Quantitative MR: Optimization for clinical usage
Show others...
2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 4, e95161- p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Public Library of Science, 2014
Keyword
Multiple Sclerosis, Quantitative MRI, Quantitative MRS, QMRI, MRS
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-103041 (URN)10.1371/journal.pone.0095161 (DOI)000335226500062 ()
Available from: 2014-01-10 Created: 2014-01-10 Last updated: 2017-12-06Bibliographically approved

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