MRI Techniques To Monitor MS Evolution: The Present And The Future
Filippi M, Grossman RI
Neurology 2002 Apr 23;58(8):1147-53
Scientific Institute and University Ospedale San Raffaele, NeuroImaging Research Unit, Department of NeuroScience, Milan, Italy
PMID# 11971079; UI# 21966380
Conventional MRI (cMRI) is limited in its ability to provide specific information about pathology in MS.
Measures commonly derived from cMRI include T2 lesions, T1-enhanced lesions, Atrophy, and possibly T1-HypoIntense lesions, which have been extensively investigated in many clinical trials.
Better MRI measures are needed to advance our understanding of MS and design ideal clinical trials.
This article reviews the strengths and weaknesses of the major MRI-based methods used to monitor MS evolution and submits that:
- Metrics derived from Magnetization Transfer MRI, Diffusion-weighted MRI, and Proton MRS should be implemented to achieve reliable specific in vivo quantification of MS pathology
- Targeted multiparametric MRI protocols rather than generic application of cMRI should be used in all possible clinical circumstances and trials
- Reproducible quantitative MR measures should ideally be used for the assessment of patients but are essential for clinical trials
Serial 1H-MRS in Relapsing/Remitting Multiple Sclerosis: Effects Of Interferon-ß Therapy On Absolute Metabolite Concentrations
Schubert F, Seifert F, Elster C, Link A, Walzel M, Mientus S, Haas J, Rinneberg H
MAGMA 2002 Jun;14(3):213-22
Physikalisch-Technische Bundesanstalt, Department of Medical Physics and Metrological Information Technology, Abbestrasse 2-12, D-10587, Berlin, Germany
To assess the applicability of Magnetic Resonance Spectroscopy (Spectroscopy) for long-term follow-up of Neurological Diseases.
A longitudinal 1H-MRS study at 3 T was carried out on ten patients having Relapsing/Remitting Multiple Sclerosis (MS) who, after baseline examination, received Interferon-beta (IFN-ß-1b).
At 8-20 examinations within up to 34 months absolute concentrations of N-AcetylAspartate (NAA), total Creatine (tG), and Choline-containing compounds (tCho) were determined in a large non-enhancing lesion and ContraLateral Normal Appearing White Matter (NAWM).
MR Spectra were analyzed using a novel time domain-frequency domain method including non-parametric background characterization.
For comparison at baseline, ten healthy controls were examined. The concentrations of tCho and tCr were found to be higher in MS Brain than in control Brain.
Besides a non-significantly lower NAA concentration in lesions there were no concentration differences between lesions and NAWM. Over the follow-up period the measured metabolite concentrations exhibited a high variability.
Most concentrations remained within this scatter, and statistical tests revealed significant fluctuations in the levels of metabolites in one case only.
This stability of the metabolite concentrations over time might result from IFN therapy as for the spontaneous course of Relapsing/Remitting MS decreasing metabolite (NAA/tCr) ratios have been reported.
The results further suggest that future treatment trials intending to use metabolite concentrations as a secondary outcome indicator use even longer observation periods.
And, besides group analysis of large cohorts, investigate the time behavior of selected single cases. The biochemical abnormalities found in NAWM emphasize the importance of analyzing both lesion and NAWM.
Rovaris M, Filippi M
J Rehabil Res Dev 2002 Mar-Apr;39(2):243-59
Scientific Institute and University Ospedale San Raffaele, Department of NeurosScience, Milan, Italy
In Relapsing/Remitting (RR) Multiple Sclerosis (MS), conventional Magnetic Resonance Imaging (MRI) has proved to be a valuable tool to assess the lesion burden and activity over time.
However, conventional MRI cannot characterize and quantify the tissue damage within and outside such lesions and only can provide some gross measures reflecting the presence of irreversible tissue damage, such as the load of T1 "Black Holes" and the severity of Brain or Cord Atrophy.
Other MR-based techniques, including Cell-Specific imaging, Magnetization Transfer (MT) MRI (MT-MRI), Diffusion-Weighted (DW) MRI (DWI-MRI), Proton Magnetic Resonance Spectroscopy (1H-MRS), and Functional MRI (fMRI), have the potential to overcome this limitation.
And, consequently, to provide additional information about the nature and the extent of MS tissue damage, which would inevitably remain undetected when only a conventional MRI is obtained.
Cell-Specific imaging should result in a better definition of the cellular mechanisms associated with MS inflammation.
Metrics derived from MT- and DW-MRI can quantify the structural changes occurring within and outside lesions visible on conventional MRI scans.
1H-MRS could add information on the biochemical nature of such changes.
fMRI is a promising technique to assess the mechanisms of Cortical reorganization, which may limit the consequences of an MS-related injury.
The application of these MR techniques to the study of RRMS is likely to provide useful insights into the PathoPhysiology of this disease and to improve our ability to assess the efficacy of experimental treatments.
Assessment of Normal-Appearing White And Gray Matter In Primary/Progressive Multiple Sclerosis: A Diffusion-Tensor Magnetic Resonance Imaging Study
Rovaris M, Bozzali M, Iannucci G, Ghezzi A, Caputo D, Montanari E, Bertolotto A, Bergamaschi R, Capra R, Mancardi GL, Martinelli V, Comi G, Filippi M
Arch Neurol 2002 Sep;59(9):1406-12
Scientific Institute and University Ospedale San Raffaele, NeuroImaging Research Unit, Department of NeuroScience, Via Olgettina 60, 20132 Milan, Italy
Diffusion-Tensor Magnetic Resonance Imaging is sensitive to the more destructive aspects of Multiple Sclerosis (MS) evolution occurring outside and within T2-visible lesions.
And, as a consequence, holds promise for providing a more complete picture of Primary/Progressive (PP) MS-related tissue damage than conventional Magnetic Resonance Imaging.
To improve our understanding of PPMS by assessing the extent of occult pathological features in the Normal-Appearing White and Gray Matter of the Brain using Diffusion-Tensor Magnetic Resonance Imaging.
Ninety-six patients with PPMS, 47 patients with Secondary/Progressive (SP) MS, and 44 healthy control subjects were studied.
T2-HyperIntense and T1-HypoIntense lesion volumes were calculated, and the volume of the Whole Brain Tissue was measured.
Diffusion-Tensor Magnetic Resonance Imaging scans were postprocessed and analyzed to obtain the Mean Diffusivity and Fractional Anisotropy Histograms from the Brain and from the Normal-Appearing White and Gray Matter in isolation.
The mean T2-HyperIntense and T1-HypoIntense lesion volumes were lower in patients with PPMS than in patients with SPMS, while the mean absolute Brain Volumes were similar in the 2 groups.
The average lesion Diffusivity was significantly higher in patients with SPMS than in patients with PPMS (P < .001).
Histogram-derived metrics of the Brain tissue and Normal-Appearing White and Gray Matter were significantly different between patients with PPMS and healthy subjects (range, P =.004 to < .001).
Average Diffusivity values were significantly higher in patients with SPMS than in patients with PPMS for all the tissues studied (range, P =.001 to < .001).
Fractional Anisotropy Histogram-derived quantities did not significantly differ between the 2 patient groups (range, P =.94 to.03).
This study confirms that, in patients with PPMS, Normal-Appearing White (NAWM) and Gray Matter (NAGM) are not spared by disease-related pathological processes, although they are affected to a lesser degree than in patients with SPMS.