Serial proton MR spectroscopy of contrast-enhancing multiple sclerosis plaques: absolute metabolic values over 2 years during a clinical pharmacological study.

BACKGROUND AND PURPOSE The time courses of total creatine (Cr), N-acetylaspartate (NAA), choline (Cho), and myo-inositol have not previously been investigated in the follow-up of contrast-enhancing multiple sclerosis (MS) plaques. Therefore, over a period of 2 years, we compared the absolute concentrations of these metabolites between patients treated with a placebo or 15 +/- deoxyspergualin (DSG) and between clinical groups with relapsing-remitting or secondary-progressive MS. METHODS Sixteen patients, recruited from a pharmacological study of DSG, and 11 healthy control subjects were investigated by a stimulated-echo acquisition mode sequence (TR/TE = 3000/20). The selected volume initially contained a contrast-enhancing plaque, which was followed up for a period of 2 years. RESULTS In contrast-enhancing plaques, Cho was significantly elevated and showed a significant reduction after both 3 and 12 months. The initially normal Cr significantly increased between 3 and 12 months, and was negatively correlated with plaque volume on T1-weighted MR images. NAA initially showed normal values, a significant decrease at 1 month, and a slow recovery over 2 years. Myo-inositol did not show a clear tendency. The placebo group did not differ from the treated group, nor did the relapsing-remitting group differ from the secondary-progressive group. CONCLUSION The contradictory time courses of Cr and NAA show that an absolute quantification in proton MR spectroscopy in MS is necessary to avoid a false interpretation of reduced NAA/Cr ratios. The increase in Cr is probably due to remyelination. The initial dip and later recovery of NAA seem to be related to diminishing edema and remyelination.

[1]  P M Matthews,et al.  Imaging axonal damage of normal-appearing white matter in multiple sclerosis. , 1998, Brain : a journal of neurology.

[2]  P. Dupont,et al.  Positron emission tomography, magnetic resonance imaging and proton NMR spectroscopy of white matter in multiple sclerosis , 1997, Multiple sclerosis.

[3]  J. denBoer,et al.  A study of multiple sclerosis patients with magnetic resonance spectroscopic imaging , 1995, Multiple sclerosis.

[4]  P. Hecke,et al.  Human brain proton localized NMR spectroscopy in multiple sclerosis , 1991, Magnetic resonance in medicine.

[5]  H. Larsson,et al.  The concentration of N-acetyl aspartate, creatine + phosphocreatine, and choline in different parts of the brain in adulthood and senium. , 1993, Magnetic resonance imaging.

[6]  William H. Oldendorf,et al.  N-Acetyl-L-Aspartic acid: A literature review of a compound prominent in 1H-NMR spectroscopic studies of brain , 1989, Neuroscience & Biobehavioral Reviews.

[7]  D. L. Collins,et al.  Statistics for Investigation of Multimodal MR Imaging Data and an Application to Multiple Sclerosis Patients , 1996, NMR in biomedicine.

[8]  G J Barker,et al.  Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions. , 1994, Brain : a journal of neurology.

[9]  W. Roser.  Reproducibility of metabolite peak areas in 1H MRS of the human brain. , 1997, Magnetic resonance imaging.

[10]  P. Matthews,et al.  Use of proton magnetic resonance spectroscopy for monitoring disease progression in multiple sclerosis , 1994, Annals of neurology.

[11]  R E Lenkinski,et al.  Correlation of spectroscopy and magnetization transfer imaging in the evaluation of demyelinating lesions and normal appearing white matter in multiple sclerosis , 1994, Magnetic resonance in medicine.

[12]  J. Kurtzke.  Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[13]  Jullie W Pan,et al.  Evaluation of multiple sclerosis by 1H spectroscopic imaging at 4.1 T , 1996, Magnetic resonance in medicine.

[14]  S. Provencher.  Estimation of metabolite concentrations from localized in vivo proton NMR spectra , 1993, Magnetic resonance in medicine.

[15]  R. Lenkinski,et al.  MR spectroscopy in the evaluation of enhancing lesions in the brain in multiple sclerosis. , 1996, AJNR. American journal of neuroradiology.

[16]  M. Castillo,et al.  Extraneous lipid contamination in single-volume proton MR spectroscopy: phantom and human studies. , 1997, AJNR. American journal of neuroradiology.

[17]  J S Wolinsky,et al.  Serial proton magnetic resonance spectroscopic imaging, contrast‐enhanced magnetic resonance imaging, and quantitative lesion volumetry in multiple sclerosis , 1998, Annals of neurology.

[18]  J. Frahm,et al.  Absolute concentrations of metabolites in the adult human brain in vivo: quantification of localized proton MR spectra. , 1993, Radiology.

[19]  R E Lenkinski,et al.  MR proton spectroscopy in multiple sclerosis. , 1992, AJNR. American journal of neuroradiology.

[20]  B J Soher,et al.  Quantitation of automated single‐voxel proton MRS using cerebral water as an internal reference , 1996, Magnetic resonance in medicine.

[21]  L. Kappos,et al.  Proton MRS of Gadolinium‐enhancing MS Plaques and Metabolic Changes in Normal‐Appearing White Matter , 1995, Magnetic resonance in medicine.

[22]  E. Cho,et al.  Multiple sclerosis: remyelination of nascent lesions. , 1993, Annals of neurology.

[23]  Joseph Granot,et al.  Selected Volume Excitation Using Stimulated Echoes (VEST). Applications to spatially localized spectroscopy and imaging , 1986 .

[24]  E. Cabanis,et al.  In vivo localized NMR proton spectroscopy of normal appearing white matter in patients with multiple sclerosis. , 1996, Journal of neuroradiology. Journal de neuroradiologie.

[25]  N. Herschkowitz,et al.  N-acetyl-L-aspartate is a major source of acetyl groups for lipid synthesis during rat brain development. , 1991, Developmental neuroscience.

[26]  H. Bruhn,et al.  Multiple sclerosis in children: Cerebral metabolic alterations monitored by localized proton magnetic resonance spectroscopy in vivo , 1992, Annals of neurology.

[27]  R. Kimmich,et al.  Volume-selective multipulse spin-echo spectroscopy , 1987 .

[28]  P M Matthews,et al.  Axonal dysfunction and disability in a relapse of multiple sclerosis: Longitudinal study of a patient , 1997, Neurology.

[29]  G. Barker,et al.  1H magnetic resonance spectroscopy of chronic cerebral white matter lesions and normal appearing white matter in multiple sclerosis , 1997, Journal of neurology, neurosurgery, and psychiatry.

[30]  J. Frahm,et al.  Localized proton NMR spectroscopy in different regions of the human brain in vivo. Relaxation times and concentrations of cerebral metabolites , 1989, Magnetic resonance in medicine.

[31]  Anne-Marie Landtblom,et al.  Proton MR Spectroscopy and MR Imaging in Acute and Chronic Multiple Sclerosis — Ringlike Appearances in Acute Plaques , 1996, Acta radiologica.

[32]  O Henriksen,et al.  Absolute quantitative proton NMR spectroscopy based on the amplitude of the local water suppression pulse. Quantification of brain water and metabolites , 1994, NMR in biomedicine.

[33]  G. Fein,et al.  Biochemical alterations in multiple sclerosis lesions and normal‐appearing white matter detected by in vivo 31P and 1H spectroscopic imaging , 1994, Annals of neurology.

[34]  Chrit T. W. Moonen,et al.  Highly Effective Water Suppression for in vivo proton NMR Spectroscopy (DRYSTEAM) , 1990 .

[35]  A. Thompson,et al.  Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss. , 1995, Brain : a journal of neurology.

[36]  R. Tarducci,et al.  1H-MRS in patients with multiple sclerosis undergoing treatment with interferon β-1a: results of a preliminary study , 1998, Journal of neurology, neurosurgery, and psychiatry.

[37]  O Henriksen,et al.  In vivo quantification of brain metabolites by 1H-MRS using water as an internal standard. , 1993, Magnetic resonance imaging.

[38]  D. Paty,et al.  Magnetic resonance spectroscopy of multiple sclerosis: in-vivo detection of myelin breakdown products , 1993, The Lancet.

[39]  J. Hennig,et al.  Direct absolute quantification of metabolites in the human brain with in vivo localized proton spectroscopy , 1992, NMR in biomedicine.

[40]  M W Weiner,et al.  1H MRSI of normal appearing white matter in multiple sclerosis , 1997, Multiple sclerosis.

[41]  P M Matthews,et al.  Assessment of lesion pathology in multiple sclerosis using quantitative MRI morphometry and magnetic resonance spectroscopy. , 1996, Brain : a journal of neurology.

[42]  P. Matthews,et al.  Chemical pathology of acute demyelinating lesions and its correlation with disability , 1995, Annals of neurology.

[43]  Jia Newcombe,et al.  High Resolution Proton NMR Spectroscopy of Multiple Sclerosis Lesions , 1995, Journal of neurochemistry.

[44]  D Origgi,et al.  Benign versus secondary-progressive multiple sclerosis: the potential role of proton MR spectroscopy in defining the nature of disability. , 1998, AJNR. American journal of neuroradiology.

[45]  P M Matthews,et al.  Proton magnetic resonance spectroscopy for metabolic characterization of plaques in multiple sclerosis , 1991, Neurology.

[46]  I. Marshall,et al.  Reproducibility of metabolite peak areas in 1H MRS of brain. , 1996, Magnetic resonance imaging.

[47]  R E Lenkinski,et al.  Proton MR spectroscopy and magnetization transfer ratio in multiple sclerosis: correlative findings of active versus irreversible plaque disease. , 1996, AJNR. American journal of neuroradiology.

[48]  Lublin Fd,et al.  Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. , 1996 .

[49]  E Moore,et al.  Serial precision of metabolite peak area ratios and water referenced metabolite peak areas in proton MR spectroscopy of the human brain. , 1998, Magnetic resonance imaging.

[50]  G. Barker,et al.  Detection of myelin breakdown products by proton magnetic resonance spectroscopy , 1993, The Lancet.

[51]  J. Olesen,et al.  Localized in vivo proton spectroscopy in the brain of patients with multiple sclerosis , 1991, Magnetic resonance in medicine.

[52]  U. Klose.  In vivo proton spectroscopy in presence of eddy currents , 1990, Magnetic resonance in medicine.

[53]  P M Matthews,et al.  Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. , 1998, Brain : a journal of neurology.

[54]  D. Silberberg,et al.  New diagnostic criteria for multiple sclerosis: Guidelines for research protocols , 1983, Annals of neurology.

[55]  J. Frahm,et al.  Inflammatory CNS demyelination: histopathologic correlation with in vivo quantitative proton MR spectroscopy. , 1999, AJNR. American journal of neuroradiology.

[56]  W. Steinbrich,et al.  [Results and consequences of frequent quality control of quantitative clinical 1H-MR-spectroscopy]. , 1997, RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin.