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Assessment of lesion pathology in multiple sclerosis using quantitative MRI morphometry and magnetic resonance
P M Matthews1, E Pioro, S Narayanan
1Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Abstract:
Quantitative measurement of MRI-defined brain lesions can provide an index of the extent and activity of disease in multiple sclerosis patients. However, the relationships between these indices and clinical features are not well-understood. Heterogeneity of the pathological changes underlying MRI lesions may be an important factor determining the correlation between MRI lesion volumes and clinical measures. Recent studies have suggested that with magnetic resonance spectroscopy (MRS), it may be possible to define chemical changes that better reflect the pathological changes in multiple sclerosis. Here we report results of combined quantitative brain T2-weighted MRI lesion volume and proton MRS examinations that demonstrate heterogeneity of the chemical pathology underlying brain lesions in patients selected on the basis of similar clinical disability but differing with respect to the presence or absence of clinical relapses. We examined 29 patients with disease characterized by either clear relapses with at least partial remissions (RR) or secondary, chronic progression after an earlier history of a more relapsing and remitting course (SP). Total hemispheric lesion volume was greater (P < 0.04) in the RR (32.5 +/- 20.9 cm3) than in the SP (16.2 +/- 9.0 cm3) patients, despite the longer duration of disease in the latter group. Central brain N-acetyl aspartate: creatine (NAA:Cr) ratios were reduced relative to normal controls (4.0 +/- 0.3, n = 19) by similar amounts in the two patients groups (RR, 3.1 +/- 0.5; SP, 3.2 +/- 0.4; P < 0.0001). The ratio lesion volume:(NAA:Cr) was greater for the RR group (11.7 +/- 9.3 cm3) than for the SP group (5.4 +/- 3.3 cm3, P < 0.05), implying a greater average degree of axonal loss per unit lesion volume defined by MRI for subjects in the SP group or, alternatively, a greater proportion of lesions without axonal damage or loss in the RR group. Our results emphasize a limitation of using T2-weighted MRI lesion volume alone and suggest that combined analysis of MR-based chemical and imaging data might allow improved non-invasive assessment of lesion pathology in order to better understand its relationship to clinical features of multiple sclerosis.
Insights
Magnetic resonance imaging (MRI) lesion volume alone is insufficient for understanding multiple sclerosis (MS) pathology. Combining MRI with magnetic resonance spectroscopy (MRS) reveals chemical differences in brain lesions, offering a more comprehensive assessment of MS disease activity.
Area of Science:
- Neurology
- Neuroimaging
- Biochemistry
Background:
- Quantitative MRI lesion volume is a key metric in multiple sclerosis (MS) but its correlation with clinical features is unclear.
- Pathological heterogeneity within MRI-defined lesions may explain the weak relationship between lesion volume and clinical outcomes.
- Magnetic resonance spectroscopy (MRS) shows promise in detecting chemical changes indicative of MS pathology.
Purpose of the Study:
- To investigate the heterogeneity of chemical pathology in MS brain lesions using combined quantitative MRI and proton MRS.
- To compare lesion characteristics between relapsing-remitting (RR) and secondary progressive (SP) MS subtypes with similar clinical disability.
- To explore the relationship between MRI lesion volume, chemical changes (NAA:Cr ratio), and axonal damage in MS.
Main Methods:
- Quantitative T2-weighted MRI and proton MRS were performed on 29 MS patients (RR and SP subtypes).
- Patients were selected for similar clinical disability but differing relapse history.
- Brain lesion volumes and N-acetyl aspartate to creatine (NAA:Cr) ratios were measured and compared between groups and with healthy controls.
Main Results:
- Total hemispheric lesion volume was significantly greater in RR patients compared to SP patients (P < 0.04), despite shorter disease duration in RR.
- Central brain NAA:Cr ratios were similarly reduced in both RR and SP groups compared to controls (P < 0.0001).
- The ratio of lesion volume to NAA:Cr was higher in RR patients than SP patients (P < 0.05), suggesting less axonal loss per unit lesion volume in RR MS.
Conclusions:
- T2-weighted MRI lesion volume alone provides an incomplete picture of MS pathology.
- Combined MRI and MRS analysis reveals distinct chemical pathologies underlying lesions in different MS subtypes.
- Integrated MR-based chemical and imaging data may improve non-invasive assessment of MS lesion pathology and its clinical correlations.