Sensitivity of quantitative (1)H magnetic resonance spectroscopy of the brain in detecting early neuronal damage in systemic lupus erythematosus.

OBJECTIVE To quantify N-acetylaspartate (NAA), total creatines (tCr), total cholines (tCho), and myo-inositol (mI) levels in normal and abnormal appearing white matter of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) in order to determine the specific changes in metabolite concentrations. METHODS Axial proton density and T(2) weighted magnetic resonance images, and short echo time (TE 30 ms) (1)H spectra were acquired with a GE SIGNA 1.5 T magnetic resonance system. Concentrations of NAA, tCr, tCho, and mI were determined, using brain tissue water as a reference, from nine patients (seven female, mean age 40.3 years, range 16-65) with NPSLE and eight healthy women (mean age 43 years, range 31-65). RESULTS A significant rise of tCho (12.4%, p<0.05) and mI (31.4%, p<0.005) and a significant reduction in NAA (-12%, p<0.05) was found in normal appearing white matter compared with controls. Analysis according to severity of the clinical NPSLE features (subgrouped as major or minor) showed that SLE major had reduced NAA compared with SLE minor (-18.4%, p<0.05) and controls (-20%, p<0.005). The SLE major group showed a significant rise of mI (32%, p<0.01) and the SLE minor group a significant increase in tCho (18.6%, p<0.05) compared with controls. Longitudinal analysis of brain metabolites in normal appearing white matter showed consistent abnormalities in NAA, tCho, and mI in a patient with stable clinical features and a constant rise of tCho, but transient rise of mI was seen during a flare of disease in another patient. CONCLUSION Quantitative (1)H magnetic resonance spectroscopy (MRS) suggests a particular course of neurometabolite changes that precedes irreversible reductions in NAA and permanent neuronal loss. Initially, in patients with SLE minor, there is a significant rise in tCho and a trend (reversible) for mI also to be raised. In patients with SLE major the NAA is significantly and permanently reduced and mI is significantly raised, whereas the tCho levels are near normal. Further investigations are needed to determine how specific MRS is as a clinical marker for brain disturbance in SLE.

[1]  J R Griffiths,et al.  Aging of the adult human brain: In vivo quantitation of metabolite content with proton magnetic resonance spectroscopy , 1999, Journal of magnetic resonance imaging : JMRI.

[2]  W. Brooks,et al.  Neurometabolite markers of cerebral injury in the antiphospholipid antibody syndrome of systemic lupus erythematosus. , 1998, Stroke.

[3]  B. Hart,et al.  Brain injury and neurometabolic abnormalities in systemic lupus erythematosus. , 1998, Radiology.

[4]  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.

[5]  P. V. van Zijl,et al.  Neurochemistry of brain lesions determined by spectroscopic imaging in systemic lupus erythematosus. , 1997, The Journal of rheumatology.

[6]  R. Lenkinski,et al.  Biochemical changes in the frontal lobe of HIV-infected individuals detected by magnetic resonance spectroscopy. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[7]  W M Brooks,et al.  Neurometabolism of active neuropsychiatric lupus determined with proton MR spectroscopy. , 1997, AJNR. American journal of neuroradiology.

[8]  T Ernst,et al.  Frontotemporal dementia and early Alzheimer disease: differentiation with frontal lobe H-1 MR spectroscopy. , 1997, Radiology.

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

[10]  S. West,et al.  Neuropsychiatric lupus erythematosus: a 10-year prospective study on the value of diagnostic tests. , 1995, The American journal of medicine.

[11]  P. Williamson,et al.  The use of a priori knowledge to quantify short echo in vivo 1h mr spectra , 1995, Magnetic resonance in medicine.

[12]  M. McLean,et al.  Continuing ischemic damage after acute middle cerebral artery infarction in humans demonstrated by short-echo proton spectroscopy. , 1995, Stroke.

[13]  T. Shonk,et al.  Role of Increased Cerebral myo‐Inositol in the Dementia of Down Syndrome , 1995, Magnetic resonance in medicine.

[14]  B D Ross,et al.  Human cerebral osmolytes during chronic hyponatremia. A proton magnetic resonance spectroscopy study. , 1995, The Journal of clinical investigation.

[15]  S. West,et al.  Magnetic resonance imaging in systemic lupus erythematosus patients without a history of neuropsychiatric lupus erythematosus. , 1994, Arthritis and rheumatism.

[16]  J Hennig,et al.  Proton magnetic resonance spectroscopy studies on human brain myo-inositol in hypo-osmolarity and hepatic encephalopathy. , 1994, Gastroenterology.

[17]  B. Ross,et al.  Brief report: organic osmolytes in the brain of an infant with hypernatremia. , 1994, The New England journal of medicine.

[18]  R. Griffey,et al.  Analysis of cerebral structural changes in systemic lupus erythematosus by proton MR spectroscopy. , 1994, AJNR. American journal of neuroradiology.

[19]  P G Webb,et al.  Automated single‐voxel proton MRS: Technical development and multisite verification , 1994, Magnetic resonance in medicine.

[20]  J. Denburg,et al.  Lymphocyte antigens in neuropsychiatric systemic lupus erythematosus. Relationship of lymphocyte antibody specificities to clinical disease. , 1994, Arthritis and rheumatism.

[21]  Roland Kreis,et al.  Development of the human brain: In vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy , 1993, Magnetic resonance in medicine.

[22]  G J Barker,et al.  The proton NMR spectrum in acute EAE: The significance of the change in the Cho:Cr ratio , 1993, Magnetic resonance in medicine.

[23]  B. Bourke Central nervous system involvement in systemic lupus erythematosus. Are we any further forward? , 1993, British Journal of Rheumatology.

[24]  F. Quismorio,et al.  Magnetic resonance imaging of the brain in neuropsychiatric systemic lupus erythematosus. , 1993, Seminars in arthritis and rheumatism.

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

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

[27]  R. Kreis,et al.  Cerebral metabolic disturbances in patients with subacute and chronic diabetes mellitus: detection with proton MR spectroscopy. , 1992, Radiology.

[28]  Y. Sidi,et al.  Lupus anticoagulant: correlation with magnetic resonance imaging of brain lesions. , 1992, The Journal of rheumatology.

[29]  J. Fisk,et al.  Cognitive impairment in patients with systemic lupus erythematosus. , 1992, The Journal of rheumatology.

[30]  D. van Ormondt,et al.  SVD-based quantification of magnetic resonance signals , 1992 .

[31]  U. Klose In vivo proton spectroscopy in presence of eddy currents , 1990, Magnetic Resonance in Medicine.

[32]  P. Luyten,et al.  Accurate quantification of in vivo 31P NMR signals using the variable projection method and prior knowledge , 1988, Magnetic resonance in medicine.

[33]  J F Fries,et al.  The 1982 revised criteria for the classification of systemic lupus erythematosus. , 1982, Arthritis and rheumatism.

[34]  W M Brooks,et al.  Relationship between neurometabolite derangement and neurocognitive dysfunction in systemic lupus erythematosus. , 1999, The Journal of rheumatology.

[35]  I. Wilkinson,et al.  Magnetic resonance imaging of the brain and cerebral proton spectroscopy in patients with systemic lupus erythematosus. , 1997, Arthritis and rheumatism.

[36]  B J Soher,et al.  Quantitation of proton NMR spectra of the human brain using tissue water as an internal concentration reference , 1993, NMR in biomedicine.