Abstract
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, qMRI and qMRS were 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 1.5 T Philips MR-scanner. 35 patients with clinically definite MS and 20 healthy controls were included. Twenty of the patients fulfilled the ‘Barkhof-Tintoré criteria’ for MS, (‘MRIpos’), whereas 15 showed radiologically atypical findings with few WM lesions (‘MRIneg’). QMRI properties were determined in ROIs of NAWM, DAWM and 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 MS groups. N-acetyl aspartate correlated negatively with R1 and R2 in MRIneg. R2 of DAWM was associated with BPF. Conclusions: Changes in NAWM and DAWM are independent pathological entities in the disease. The correlation between qMRI and clinical status may shed new light on the clinicoradiological paradox.
Highlights
Magnetic Resonance Imaging is a sensitive technique for detecting white matter (WM) Multiple Sclerosis (MS) lesions, but the relation with clinical disability is low
Vrenken et al showed that T1 times in diffusely abnormal white matter’ (DAWM) differed between primaryprogressive (PP) and secondary-progressive (SP) MS patients [18] and that quantitative magnetic resonance imaging (qMRI) characteristics of normal appearing white matter (NAWM) changed with distance to focal WM lesions [32]. These findings suggest that the sensitivity of qMRI may be higher than conventional imaging, and of value for describing diffuse pathology
Subjects A total of 35 clinically definite (CDMS) patients and 20 healthy subjects were included in the investigations. (i) Fifteen MS patients with two or fewer T2-hyperintense WM lesions, on a previous clinical examination, were prospectively included in the low-lesion MS group (‘MRIneg’), (ii) 20 MS patients fulfilling the ‘BarkhofTintorecriteria’ as defined in [13] were included in the MS group with typical WM lesions (‘MRIpos’), and (iii) 20 healthy control subjects were included in the control group
Summary
Magnetic Resonance Imaging is a sensitive technique for detecting white matter (WM) MS lesions, but the relation with clinical disability is low. QMRI properties were determined in ROIs of NAWM, DAWM and lesions in the MS groups and of NWM in controls. The correlation between focal white matter (WM) lesions and clinical disability is only modest, a phenomenon which has persisted for many years and is referred to as the clinicoradiological paradox [2]. Interest in other pathological tissue changes, beside WM lesions, has been of interest in recent years These include changes in cortical grey matter [6,7], deep grey matter structures [8], and changes in normal appearing white matter (NAWM) [9,10,11,12]. Mechanisms leading to persistent disability in MS remain unclear
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