Quantitative magnetic resonance spectroscopic imaging in Parkinson's disease, progressive supranuclear palsy and multiple system atrophy.
OBJECTIVE
Magnetic resonance spectroscopy (MRS) allows the measurement of a number of brain tissue metabolites in vivo, including N-acetylaspartate (NAA), a putative marker of neuronal integrity. Unlike single voxel MRS, magnetic resonance spectroscopic imaging (MRSI) enables quantification of these metabolites simultaneously from multiple anatomically localized voxels. Both single voxel MRS and MRSI allow the absolute quantification of these metabolites and, when combined with tissue segmentation, can give accurate metabolite concentrations even in the presence of partial volume effects from nearby cerebrospinal fluid.


METHODS
Using MRSI with cubic voxels with a nominal volume of 1.0 cm(3), we tested the hypothesis that concentrations of NAA in the basal ganglia in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) would show differences compared to Parkinson's disease (IPD). NAA values (in mM) from MRSI voxels centred to the putamen, pallidum and thalamus were obtained from 11 patients with IPD, 11 with MSA-P, six with MSA-C, 13 with PSP and 18 controls. The mean concentrations of NAA and its bulk grey and white matter values were also estimated over the whole brain slab.


RESULTS
N-acetylaspartate concentrations in the pallidum, putamen and lentiform nucleus were significantly lower in patients with MSA-P and PSP compared to IPD and controls. The putaminal values were also significantly reduced in PSP compared to MSA-P. There were no significant differences between groups in the thalamus and over the whole brain slab.


CONCLUSIONS
Our findings support the notion that MRSI can potentially quantify basal ganglia cellular pathology in MSA and PSP.
Guevara
C A
CA
Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London.
Blain
C R
CR
Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London.
Stahl
D
D
Department of Biostatistics and Computing, King's College London, Institute of Psychiatry, London, UK.
Lythgoe
D J
DJ
Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London.
Leigh
P N
PN
Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London.
Barker
G J
GJ
Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London.
D000368:Aged; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001480:Basal Ganglia Diseases / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D011237:Predictive Value of Tests; D013494:Supranuclear Palsy, Progressive / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*
D015415:Biomarkers; D001224:Aspartic Acid; C000179:N-acetylaspartate
Fearnley JM, Lees AJ. Striatonigral degeneration. A clinicopathological study. Brain 1990; 113(Pt 6): 1823-1842.
Litvan I, Bhatia KP, Burn DJ, et al. SIC Task Force appraisal of clinical diagnostic criteria for parkinsonian disorders. Mov Disord 2003; 18: 467-486.
Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992; 55: 181-184.
Gilman S, Low PA, Quinn N, et al. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 1999; 163: 94-98.
Bottomley PA. Spatial localization in NMR spectroscopy in vivo. Ann N Y Acad Sci 1987; 508: 333-348.
Haase A, Frahm J, Hanicke W, Matthaei D. 1H NMR chemical shift selective (CHESS) imaging. Phys Med Biol 1985; 30: 341-344.
Ashburner J, Friston KJ. Unified segmentation. Neuroimage 2005; 26: 839-851.
McLean MA, Woermann FG, Barker GJ, Duncan JS. Quantitative analysis of short echo time (1)H-MRSI of cerebral gray and white matter. Magn Reson Med 2000; 44: 401-411.
Provencher SW. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 1993; 30: 672-679.
Brooker HR, Mareci TH, Mao J. Selective fourier transform localization. Magn Reson Med 1987; 5: 417-433.
Pellecchia MT, Barone P, Mollica C, et al. Diffusion-weighted imaging in multiple system atrophy: a comparison between clinical subtypes. Mov Disord 2009; 24: 689-696.
Brenneis C, Seppi K, Schocke MF, et al. Voxel-based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy. Mov Disord 2003; 18: 1132-1138.
Abe K, Terakawa H, Takanashi M, et al. Proton magnetic resonance spectroscopy of patients with parkinsonism. Brain Res Bull 2000; 52: 589-595.
Watanabe H, Fukatsu H, Katsuno M, et al. Multiple regional 1H-MR spectroscopy in multiple system atrophy: NAA/Cr reduction in pontine base as a valuable diagnostic marker. J Neurol Neurosurg Psychiatry 2004; 75: 103-109.
Seppi K, Schocke MFH, Esterhammer R, et al. Diffusion-weighted imaging discriminates progressive supranuclear palsy from PD, but not from the parkinson variant of multiple system atrophy. Neurology 2003; 60: 922-927.
Schocke MFH, Seppi K, Esterhammer R, et al. Trace of diffusion tensor differentiates the Parkinson variant of multiple system atrophy and Parkinson’s disease. Neuroimage 2004; 21: 1443-1451.
Brenneis C, Seppi K, Schocke M, Benke T, Wenning GK, Poewe W. Voxel based morphometry reveals a distinct pattern of frontal atrophy in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 2004; 75: 246-249.
Brenneis C, Egger K, Scherfler C, et al. Progression of brain atrophy in multiple system atrophy. A longitudinal VBM study. J Neurol 2007; 254: 191-196.
Price S, Paviour D, Scahill R, et al. Voxel-based morphometry detects patterns of atrophy that help differentiate progressive supranuclear palsy and Parkinson’s disease. Neuroimage 2004; 23: 663-669.
Paviour DC, Thornton JS, Lees AJ, Jager HR. Diffusion-weighted magnetic resonance imaging differentiates Parkinsonian variant of multiple-system atrophy from progressive supranuclear palsy. Mov Disord 2007; 22: 68-74.
Nicoletti G, Lodi R, Condino F, et al. Apparent diffusion coefficient measurements of the middle cerebellar peduncle differentiate the Parkinson variant of MSA from Parkinson’s disease and progressive supranuclear palsy. Brain 2006; 129: 2679-2687.
Tedeschi G, Litvan I, Bonavita S, et al. Proton magnetic resonance spectroscopic imaging in progressive supranuclear palsy, Parkinson’s disease and corticobasal degeneration. Brain 1997; 120(Pt 9): 1541-1552.
Federico F, Simone IL, Lucivero V, et al. Usefulness of proton magnetic resonance spectroscopy in differentiating parkinsonian syndromes. Ital J Neurol Sci 1999; 20: 223-229.
Clarke CE, Lowry M. Basal ganglia metabolite concentrations in idiopathic Parkinson’s disease and multiple system atrophy measured by proton magnetic resonance spectroscopy. Eur J Neurol 2000; 7: 661-665.
Davie CA, Barker GJ, Machado C, Miller DH, Lees AJ. Proton magnetic resonance spectroscopy in Steele-Richardson-Olszewski syndrome. Mov Disord 1997; 12: 767-771.
Davie CA, Wenning GK, Barker GJ, et al. Differentiation of multiple system atrophy from idiopathic Parkinson’s disease using proton magnetic resonance spectroscopy. Ann Neurol 1995; 37: 204-210.
Baik HM, Choe BY, Lee HK, Suh TS, Son BC, Lee JM. Metabolic alterations in Parkinson’s disease after thalamotomy, as revealed by 1H MR spectroscopy. Korean J Radiol 2002; 3: 180-188.
Axelson D, Bakken IJ, Susann Gribbestad I, Ehrnholm B, Nilsen G, Aasly J. Applications of neural network analyses to in vivo 1H magnetic resonance spectroscopy of Parkinson disease patients. J Magn Reson Imaging 2002; 16: 13-20.
Lucetti C, Del Dotto P, Gambaccini G, et al. Proton magnetic resonance spectroscopy (1H-MRS) of motor cortex and basal ganglia in de novo Parkinson’s disease patients. Neurol Sci 2001; 22: 69-70.
O’Neill J, Schuff N, Marks WJ Jr, Feiwell R, Aminoff MJ, Weiner MW. Quantitative 1H magnetic resonance spectroscopy and MRI of Parkinson’s disease. Mov Disord 2002; 17: 917-927.
Ross BD, Hoang TQ, Bluml S, et al. In vivo magnetic resonance spectroscopy of human fetal neural transplants. NMR Biomed 1999; 12: 221-236.
Taylor-Robinson SD, Turjanski N, Bhattacharya S, et al. A proton magnetic resonance spectroscopy study of the striatum and cerebral cortex in Parkinson’s disease. Metab Brain Dis 1999; 14: 45-55.
Hoang TQ, Bluml S, Dubowitz DJ, et al. Quantitative proton-decoupled 31P MRS and 1H MRS in the evaluation of Huntington’s and Parkinson’s diseases. Neurology 1998; 50: 1033-1040.
Cruz CJ, Aminoff MJ, Meyerhoff DJ, Graham SH, Weiner MW. Proton MR spectroscopic imaging of the striatum in Parkinson’s disease. Magn Reson Imaging 1997; 15: 619-624.
Holshouser BA, Komu M, Moller HE, et al. Localized proton NMR spectroscopy in the striatum of patients with idiopathic Parkinson’s disease: a multicenter pilot study. Magn Reson Med 1995; 33: 589-594.
Clarke CE, Lowry M, Horsman A. Unchanged basal ganglia N-acetylaspartate and glutamate in idiopathic Parkinson’s disease measured by proton magnetic resonance spectroscopy. Mov Disord 1997; 12: 297-301.
Chaudhuri KR, Lemmens G, Williams SC. Proton magnetic resonance spectroscopy of the striatum in Parkinson’s disease patients with motor response fluctuations. Parkinsonism Relat Disord 1996; 2: 63-67.
Ellis CM, Lemmens G, Williams SC, et al. Changes in putamen N-acetylaspartate and choline ratios in untreated and levodopa-treated Parkinson’s disease: a proton magnetic resonance spectroscopy study. Neurology 1997; 49: 438-444.
Clarke CE, Lowry M. Systematic review of proton magnetic resonance spectroscopy of the striatum in parkinsonian syndromes. Eur J Neurol 2001; 8: 573-577.
Mierisova S, Ala-Korpela M. MR spectroscopy quantitation: a review of frequency domain methods. NMR Biomed 2001; 14: 247-259.
Provencher SW. Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed 2001; 14: 260-264.
Frahm J, Bruhn H, Gyngell ML, Merboldt KD, Hanicke W, Sauter R. Localized high-resolution proton NMR spectroscopy using stimulated echoes: initial applications to human brain in vivo. Magn Reson Med 1989; 9: 79-93.
Brief EE, Whittall KP, Li DK, MacKay A. Proton T1 relaxation times of cerebral metabolites differ within and between regions of normal human brain. NMR Biomed 2003; 16: 503-509.