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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. 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.

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.