Skip to main content
SpringerLink
Log in

MRS in Motor Neuron Diseases

  • Chapter
  • First Online:
Magnetic Resonance Spectroscopy of Degenerative Brain Diseases

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

  • 856 Accesses

Abstract

Upper motor neurons (UMN) in the motor cortex and/or lower motor neurons (LMN) in the brainstem and spinal cord are affected in a heterogeneous group of related or pathologically similar adult-onset diseases, collectively termed as motor neuron diseases (MND). Amyotrophic lateral sclerosis (ALS) is the most predominant (85 %) among MND in which both UMN and LMN progressively degenerate. The etiology of ALS is not known in approximately 90 % of patients; however, inheritance of genetic mutations underlies in about 10 % of them. To date, neither conventional neuroimaging techniques nor laboratory tests of body fluids or biopsy samples yielded definitive biomarkers for ALS. Furthermore, molecular and cellular mechanisms involved in this disease remain poorly understood. Proton MRS is well suited to quantify metabolite alterations in the brain, and it has been used on patients with ALS in an effort to gain insight into the pathophysiology of ALS. A brief description on MND and their subtypes, limitations of clinical neuroimaging methods to diagnose ALS, a number of brain metabolites that can be quantified by in vivo MRS and their relevance to MND, and MRS techniques and their limitations are provided. Use of a whole-brain MRSI approach to fully characterize changes within the brain due to disease is described with a sample dataset obtained in a patient with ALS. Changes in the concentration or ratio of brain metabolites in patients with ALS and their pathophysiological significances are described. Finally, the use of MRS methods for longitudinal and therapeutic evaluation studies and future perspectives are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Pringle CE, Hudson AJ, Munoz DG, Kiernan JA, Brown WF, Ebers GC (1992) Primary lateral sclerosis. Clinical features, neuropathology and diagnostic criteria. Brain 115(Pt 2):495–520

    PubMed  Google Scholar 

  2. Brooks BR, Miller RG, Swash M, Munsat TL (2000) El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1(5):293–299

    CAS  PubMed  Google Scholar 

  3. Traynor BJ, Codd MB, Corr B, Forde C, Frost E, Hardiman OM (2000) Clinical features of amyotrophic lateral sclerosis according to the El Escorial and Airlie House diagnostic criteria: A population-based study. Arch Neurol 57(8):1171–1176

    CAS  PubMed  Google Scholar 

  4. Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, Burrell JR, Zoing MC (2011) Amyotrophic lateral sclerosis. Lancet 377(9769):942–955

    CAS  PubMed  Google Scholar 

  5. Tandan R, Bradley WG (1985) Amyotrophic lateral sclerosis: Part 1. Clinical features, pathology, and ethical issues in management. Ann Neurol 18(3):271–280

    CAS  PubMed  Google Scholar 

  6. Turner MR, Talbot K (2013) Mimics and chameleons in motor neurone disease. Pract Neurol 13(3):153–164

    PubMed  PubMed Central  Google Scholar 

  7. Cui F, Liu M, Chen Y, Huang X, Cui L, Fan D, Pu C, Lu J, Zhou D, Zhang C, Yan C, Li C, Ding X, Liu Y, Li X, Jiang Y, Zhang J, Shang H, Yao X, Ding Y, Niu Q, Wang L (2014) Epidemiological characteristics of motor neuron disease in Chinese patients. Acta Neurol Scand 130(2):111–117

    CAS  PubMed  Google Scholar 

  8. Brownell B, Oppenheimer DR, Hughes JT (1970) The central nervous system in motor neurone disease. J Neurol Neurosurg Psychiatry 33(3):338–357

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Chio A, Calvo A, Moglia C, Mazzini L, Mora G, group Ps (2011) Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study. J Neurol Neurosurg Psychiatry 82(7):740–746

    Google Scholar 

  10. Ikemoto A, Hirano A, Akiguchi I (2000) Neuropathology of amyotrophic lateral sclerosis with extra-motor system degeneration: characteristics and differences in the molecular pathology between ALS with dementia and Guamanian ALS. Amyotroph Lateral Scler Other Motor Neuron Disord 1(2):97–104

    CAS  PubMed  Google Scholar 

  11. Abrahams S, Goldstein LH, Suckling J, Ng V, Simmons A, Chitnis X, Atkins L, Williams SC, Leigh PN (2005) Frontotemporal white matter changes in amyotrophic lateral sclerosis. J Neurol 252(3):321–331

    PubMed  Google Scholar 

  12. Sage CA, Peeters RR, Gorner A, Robberecht W, Sunaert S (2007) Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis. Neuroimage 34(2):486–499

    PubMed  Google Scholar 

  13. Witgert M, Salamone AR, Strutt AM, Jawaid A, Massman PJ, Bradshaw M, Mosnik D, Appel SH, Schulz PE (2010) Frontal-lobe mediated behavioral dysfunction in amyotrophic lateral sclerosis. Eur J Neurol 17(1):103–110

    CAS  PubMed  Google Scholar 

  14. Agosta F, Valsasina P, Riva N, Copetti M, Messina MJ, Prelle A, Comi G, Filippi M (2012) The cortical signature of amyotrophic lateral sclerosis. PLoS One 7(8), e42816

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Goldstein LH, Abrahams S (2013) Changes in cognition and behaviour in amyotrophic lateral sclerosis: nature of impairment and implications for assessment. Lancet Neurol 12(4):368–380

    PubMed  Google Scholar 

  16. Kasper E, Schuster C, Machts J, Kaufmann J, Bittner D, Vielhaber S, Benecke R, Teipel S, Prudlo J (2014) Microstructural white matter changes underlying cognitive and behavioural impairment in ALS--an in vivo study using DTI. PLoS One 9(12), e114543

    PubMed  PubMed Central  Google Scholar 

  17. Lomen-Hoerth C, Murphy J, Langmore S, Kramer JH, Olney RK, Miller B (2003) Are amyotrophic lateral sclerosis patients cognitively normal? Neurology 60(7):1094–1097

    CAS  PubMed  Google Scholar 

  18. Phukan J, Pender NP, Hardiman O (2007) Cognitive impairment in amyotrophic lateral sclerosis. Lancet Neurol 6(11):994–1003

    CAS  PubMed  Google Scholar 

  19. Giordana MT, Ferrero P, Grifoni S, Pellerino A, Naldi A, Montuschi A (2011) Dementia and cognitive impairment in amyotrophic lateral sclerosis: a review. Neurol Sci 32(1):9–16

    PubMed  Google Scholar 

  20. Lomen-Hoerth C, Anderson T, Miller B (2002) The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 59(7):1077–1079

    PubMed  Google Scholar 

  21. Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314(5796):130–133

    CAS  PubMed  Google Scholar 

  22. Lillo P, Hodges JR (2009) Frontotemporal dementia and motor neurone disease: overlapping clinic-pathological disorders. J Clin Neurosci 16(9):1131–1135

    PubMed  Google Scholar 

  23. Renton AE, Majounie E, Waite A, Simon-Sanchez J, Rollinson S, Gibbs JR, Schymick JC, Laaksovirta H, van Swieten JC, Myllykangas L, Kalimo H, Paetau A, Abramzon Y, Remes AM, Kaganovich A, Scholz SW, Duckworth J, Ding J, Harmer DW, Hernandez DG, Johnson JO, Mok K, Ryten M, Trabzuni D, Guerreiro RJ, Orrell RW, Neal J, Murray A, Pearson J, Jansen IE, Sondervan D, Seelaar H, Blake D, Young K, Halliwell N, Callister JB, Toulson G, Richardson A, Gerhard A, Snowden J, Mann D, Neary D, Nalls MA, Peuralinna T, Jansson L, Isoviita VM, Kaivorinne AL, Holtta-Vuori M, Ikonen E, Sulkava R, Benatar M, Wuu J, Chio A, Restagno G, Borghero G, Sabatelli M, Consortium I, Heckerman D, Rogaeva E, Zinman L, Rothstein JD, Sendtner M, Drepper C, Eichler EE, Alkan C, Abdullaev Z, Pack SD, Dutra A, Pak E, Hardy J, Singleton A, Williams NM, Heutink P, Pickering-Brown S, Morris HR, Tienari PJ, Traynor BJ (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72(2):257–268

    CAS  PubMed  PubMed Central  Google Scholar 

  24. DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, Nicholson AM, Finch NA, Flynn H, Adamson J, Kouri N, Wojtas A, Sengdy P, Hsiung GY, Karydas A, Seeley WW, Josephs KA, Coppola G, Geschwind DH, Wszolek ZK, Feldman H, Knopman DS, Petersen RC, Miller BL, Dickson DW, Boylan KB, Graff-Radford NR, Rademakers R (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72(2):245–256

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Swinnen B, Robberecht W (2014) The phenotypic variability of amyotrophic lateral sclerosis. Nat Rev Neurol 10(11):661–670

    PubMed  Google Scholar 

  26. Rowland LP, Shneider NA (2001) Amyotrophic lateral sclerosis. N Engl J Med 344(22):1688–1700

    CAS  PubMed  Google Scholar 

  27. Renton AE, Chio A, Traynor BJ (2014) State of play in amyotrophic lateral sclerosis genetics. Nat Neurosci 17(1):17–23

    CAS  PubMed  Google Scholar 

  28. Strong MJ (2001) Progress in clinical neurosciences: the evidence for ALS as a multisystems disorder of limited phenotypic expression. Can J Neurol Sci 28(4):283–298

    CAS  PubMed  Google Scholar 

  29. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O'Regan JP, Deng HX et al (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362(6415):59–62

    CAS  PubMed  Google Scholar 

  30. Bains JS, Shaw CA (1997) Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res Brain Res Rev 25(3):335–358

    CAS  PubMed  Google Scholar 

  31. Hirano A, Donnenfeld H, Sasaki S, Nakano I (1984) Fine structural observations of neurofilamentous changes in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 43(5):461–470

    CAS  PubMed  Google Scholar 

  32. Strong MJ, Kesavapany S, Pant HC (2005) The pathobiology of amyotrophic lateral sclerosis: a proteinopathy? J Neuropathol Exp Neurol 64(8):649–664

    CAS  PubMed  Google Scholar 

  33. Van Den Bosch L, Van Damme P, Bogaert E, Robberecht W (2006) The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis. Biochim Biophys Acta 1762(11-12):1068–1082

    PubMed  Google Scholar 

  34. Bruijn LI, Houseweart MK, Kato S, Anderson KL, Anderson SD, Ohama E, Reaume AG, Scott RW, Cleveland DW (1998) Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science (New York, NY) 281(5384):1851–1854

    CAS  Google Scholar 

  35. Wu CH, Fallini C, Ticozzi N, Keagle PJ, Sapp PC, Piotrowska K, Lowe P, Koppers M, McKenna-Yasek D, Baron DM, Kost JE, Gonzalez-Perez P, Fox AD, Adams J, Taroni F, Tiloca C, Leclerc AL, Chafe SC, Mangroo D, Moore MJ, Zitzewitz JA, Xu ZS, van den Berg LH, Glass JD, Siciliano G, Cirulli ET, Goldstein DB, Salachas F, Meininger V, Rossoll W, Ratti A, Gellera C, Bosco DA, Bassell GJ, Silani V, Drory VE, Brown RH Jr, Landers JE (2012) Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 488(7412):499–503

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Vance C, Rogelj B, Hortobagyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P, Ganesalingam J, Williams KL, Tripathi V, Al-Saraj S, Al-Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gallo JM, Miller CC, Shaw CE (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323(5918):1208–1211

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, Ackerley S, Durnall JC, Williams KL, Buratti E, Baralle F, de Belleroche J, Mitchell JD, Leigh PN, Al-Chalabi A, Miller CC, Nicholson G, Shaw CE (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319(5870):1668–1672

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Sasaki S, Iwata M (2007) Mitochondrial alterations in the spinal cord of patients with sporadic amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 66(1):10–16

    PubMed  Google Scholar 

  39. Bruijn LI, Miller TM, Cleveland DW (2004) Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu Rev Neurosci 27:723–749

    CAS  PubMed  Google Scholar 

  40. Eisen A, Weber M (2001) The motor cortex and amyotrophic lateral sclerosis. Muscle Nerve 24(4):564–573

    CAS  PubMed  Google Scholar 

  41. Takahashi T, Yagishita S, Amano N, Yamaoka K, Kamei T (1997) Amyotrophic lateral sclerosis with numerous axonal spheroids in the corticospinal tract and massive degeneration of the cortex. Acta Neuropathol 94(3):294–299

    CAS  PubMed  Google Scholar 

  42. Fischer LR, Culver DG, Tennant P, Davis AA, Wang M, Castellano-Sanchez A, Khan J, Polak MA, Glass JD (2004) Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man. Exp Neurol 185(2):232–240

    PubMed  Google Scholar 

  43. Frey D, Schneider C, Xu L, Borg J, Spooren W, Caroni P (2000) Early and selective loss of neuromuscular synapse subtypes with low sprouting competence in motoneuron diseases. J Neurosci 20(7):2534–2542

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Kennel PF, Finiels F, Revah F, Mallet J (1996) Neuromuscular function impairment is not caused by motor neurone loss in FALS mice: an electromyographic study. Neuroreport 7(8):1427–1431

    CAS  PubMed  Google Scholar 

  45. Chiu AY, Zhai P, Dal Canto MC, Peters TM, Kwon YW, Prattis SM, Gurney ME (1995) Age-dependent penetrance of disease in a transgenic mouse model of familial amyotrophic lateral sclerosis. Mol Cell Neurosci 6(4):349–362

    CAS  PubMed  Google Scholar 

  46. Bensimon G, Lacomblez L, Meininger V (1994) A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med 330(9):585–591

    CAS  PubMed  Google Scholar 

  47. Lacomblez L, Bensimon G, Leigh PN, Guillet P, Meininger V (1996) Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet 347(9013):1425–1431

    CAS  PubMed  Google Scholar 

  48. Erminio F, Buchthal F, Rosenfalck P (1959) Motor unit territory and muscle fiber concentration in paresis due to peripheral nerve injury and anterior horn cell involvement. Neurology 9:657–671

    CAS  PubMed  Google Scholar 

  49. Carvalho MD, Swash M (2009) Awaji diagnostic algorithm increases sensitivity of El Escorial criteria for ALS diagnosis. Amyotroph Lateral Scler 10(1):53–57

    PubMed  Google Scholar 

  50. Douglass CP, Kandler RH, Shaw PJ, McDermott CJ (2010) An evaluation of neurophysiological criteria used in the diagnosis of motor neuron disease. J Neurol Neurosurg Psychiatry 81(6):646–649

    CAS  PubMed  Google Scholar 

  51. Piao YS, Wakabayashi K, Kakita A, Yamada M, Hayashi S, Morita T, Ikuta F, Oyanagi K, Takahashi H (2003) Neuropathology with clinical correlations of sporadic amyotrophic lateral sclerosis: 102 autopsy cases examined between 1962 and 2000. Brain Pathol 13(1):10–22

    PubMed  Google Scholar 

  52. Goodin DS, Rowley HA, Olney RK (1988) Magnetic resonance imaging in amyotrophic lateral sclerosis. Ann Neurol 23(4):418–420

    CAS  PubMed  Google Scholar 

  53. Hofmann E, Ochs G, Pelzl A, Warmuth-Metz M (1998) The corticospinal tract in amyotrophic lateral sclerosis: an MRI study. Neuroradiology 40(2):71–75

    CAS  PubMed  Google Scholar 

  54. Peretti-Viton P, Azulay JP, Trefouret S, Brunel H, Daniel C, Viton JM, Flori A, Salazard B, Pouget J, Serratrice G, Salamon G (1999) MRI of the intracranial corticospinal tracts in amyotrophic and primary lateral sclerosis. Neuroradiology 41(10):744–749

    CAS  PubMed  Google Scholar 

  55. Bowen BC, Pattany PM, Bradley WG, Murdoch JB, Rotta F, Younis AA, Duncan RC, Quencer RM (2000) MR imaging and localized proton spectroscopy of the precentral gyrus in amyotrophic lateral sclerosis. AJNR Am J Neuroradiol 21(4):647–658

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Zhang L, Ulug AM, Zimmerman RD, Lin MT, Rubin M, Beal MF (2003) The diagnostic utility of FLAIR imaging in clinically verified amyotrophic lateral sclerosis. J Magn Reson Imaging 17(5):521–527

    PubMed  Google Scholar 

  57. Agosta F, Chio A, Cosottini M, De Stefano N, Falini A, Mascalchi M, Rocca MA, Silani V, Tedeschi G, Filippi M (2010) The present and the future of neuroimaging in amyotrophic lateral sclerosis. AJNR Am J Neuroradiol 31(10):1769–1777

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Chan S, Shungu DC, Douglas-Akinwande A, Lange DJ, Rowland LP (1999) Motor neuron diseases: comparison of single-voxel proton MR spectroscopy of the motor cortex with MR imaging of the brain. Radiology 212(3):763–769

    CAS  PubMed  Google Scholar 

  59. Sarchielli P, Pelliccioli GP, Tarducci R, Chiarini P, Presciutti O, Gobbi G, Gallai V (2001) Magnetic resonance imaging and 1H-magnetic resonance spectroscopy in amyotrophic lateral sclerosis. Neuroradiology 43(3):189–197

    CAS  PubMed  Google Scholar 

  60. Abe K, Fujimura H, Kobayashi Y, Fujita N, Yanagihara T (1997) Degeneration of the pyramidal tracts in patients with amyotrophic lateral sclerosis. A premortem and postmortem magnetic resonance imaging study. J Neuroimaging 7(4):208–212

    CAS  PubMed  Google Scholar 

  61. Osei-Lah AD, Mills KR (2004) Optimising the detection of upper motor neuron function dysfunction in amyotrophic lateral sclerosis--a transcranial magnetic stimulation study. J Neurol 251(11):1364–1369

    PubMed  Google Scholar 

  62. Kaufmann P, Pullman SL, Shungu DC, Chan S, Hays AP, Del Bene ML, Dover MA, Vukic M, Rowland LP, Mitsumoto H (2004) Objective tests for upper motor neuron involvement in amyotrophic lateral sclerosis (ALS). Neurology 62(10):1753–1757

    CAS  PubMed  Google Scholar 

  63. Takahashi H, Snow BJ, Bhatt MH, Peppard R, Eisen A, Calne DB (1993) Evidence for a dopaminergic deficit in sporadic amyotrophic lateral sclerosis on positron emission scanning. Lancet 342(8878):1016–1018

    CAS  PubMed  Google Scholar 

  64. Turner MR, Leigh PN (2000) Positron emission tomography (PET)--its potential to provide surrogate markers in ALS. Amyotroph Lateral Scler Other Motor Neuron Disord 1(Suppl 2):S17–S22

    PubMed  Google Scholar 

  65. Turner MR, Agosta F, Bede P, Govind V, Lule D, Verstraete E (2012) Neuroimaging in amyotrophic lateral sclerosis. Biomark Med 6(3):319–337

    CAS  PubMed  Google Scholar 

  66. Govindaraju V, Young K, Maudsley AA (2000) Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed 13(3):129–153

    CAS  PubMed  Google Scholar 

  67. Bottomley PA (1987) Spatial localization in NMR spectroscopy in vivo. Ann N Y Acad Sci 508:333–348

    CAS  PubMed  Google Scholar 

  68. Smith SA, Levante TO, Meier BH, Ernst RR (1994) Computer simulations in magnetic resonance. An object oriented programming approach. J Magn Reson, Series A 106(1):75–105

    CAS  Google Scholar 

  69. van der Graaff MM, de Jong JM, Baas F, de Visser M (2009) Upper motor neuron and extra-motor neuron involvement in amyotrophic lateral sclerosis: a clinical and brain imaging review. Neuromuscul Disord 19(1):53–58

    PubMed  Google Scholar 

  70. Sudharshan N, Hanstock C, Hui B, Pyra T, Johnston W, Kalra S (2011) Degeneration of the mid-cingulate cortex in amyotrophic lateral sclerosis detected in vivo with MR spectroscopy. AJNR Am J Neuroradiol 32(2):403–407

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Harris AD, Puts NA, Barker PB, Edden RA (2014) Spectral-editing measurements of GABA in the human brain with and without macromolecule suppression. Magn Reson Med. doi:10.1002/mrm.25549

    Article  PubMed  PubMed Central  Google Scholar 

  72. Maudsley AA, Domenig C, Govind V, Darkazanli A, Studholme C, Arheart K, Bloomer C (2009) Mapping of brain metabolite distributions by volumetric proton MR spectroscopic imaging (MRSI). Magn Reson Med 61(3):548–559

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Ding XQ, Maudsley AA, Sabati M, Sheriff S, Dellani PR, Lanfermann H (2014) Reproducibility and reliability of short-TE whole-brain MR spectroscopic imaging of human brain at 3T. Magn Reson Med 73(3):921–928

    PubMed  PubMed Central  Google Scholar 

  74. Bogner W, Gagoski B, Hess AT, Bhat H, Tisdall MD, van der Kouwe AJ, Strasser B, Marjanska M, Trattnig S, Grant E, Rosen B, Andronesi OC (2014) 3D GABA imaging with real-time motion correction, shim update and reacquisition of adiabatic spiral MRSI. Neuroimage 103C:290–302

    Google Scholar 

  75. Gurney ME (1997) Transgenic animal models of familial amyotrophic lateral sclerosis. J Neurol 244(Suppl 2):S15–S20

    PubMed  Google Scholar 

  76. Howland DS, Liu J, She Y, Goad B, Maragakis NJ, Kim B, Erickson J, Kulik J, DeVito L, Psaltis G, DeGennaro LJ, Cleveland DW, Rothstein JD (2002) Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proc Natl Acad Sci U S A 99(3):1604–1609

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Yang C, Wang H, Qiao T, Yang B, Aliaga L, Qiu L, Tan W, Salameh J, McKenna-Yasek DM, Smith T, Peng L, Moore MJ, Brown RH Jr, Cai H, Xu Z (2014) Partial loss of TDP-43 function causes phenotypes of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 111(12):E1121–E1129

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Huang C, Zhou H, Tong J, Chen H, Liu YJ, Wang D, Wei X, Xia XG (2011) FUS transgenic rats develop the phenotypes of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. PLoS Genet 7(3), e1002011

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Mitchell JC, McGoldrick P, Vance C, Hortobagyi T, Sreedharan J, Rogelj B, Tudor EL, Smith BN, Klasen C, Miller CC, Cooper JD, Greensmith L, Shaw CE (2013) Overexpression of human wild-type FUS causes progressive motor neuron degeneration in an age- and dose-dependent fashion. Acta Neuropathol 125(2):273–288

    CAS  PubMed  Google Scholar 

  80. Suzuki N, Maroof AM, Merkle FT, Koszka K, Intoh A, Armstrong I, Moccia R, Davis-Dusenbery BN, Eggan K (2013) The mouse C9ORF72 ortholog is enriched in neurons known to degenerate in ALS and FTD. Nat Neurosci 16(12):1725–1727

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Duchen LW, Strich SJ (1968) An hereditary motor neurone disease with progressive denervation of muscle in the mouse: the mutant 'wobbler'. J Neurol Neurosurg Psychiatry 31(6):535–542

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Panda SK, Wefers B, Ortiz O, Floss T, Schmid B, Haass C, Wurst W, Kuhn R (2013) Highly efficient targeted mutagenesis in mice using TALENs. Genetics 195(3):703–713

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Laferriere F, Polymenidou M (2015) Advances and challenges in understanding the multifaceted pathogenesis of amyotrophic lateral sclerosis. Swiss Med Wkly 145:w14054

    PubMed  Google Scholar 

  84. Moser JM, Bigini P, Schmitt-John T (2013) The wobbler mouse, an ALS animal model. Mol Genet Genomics 288(5-6):207–229

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Turner MR, Hardiman O, Benatar M, Brooks BR, Chio A, de Carvalho M, Ince PG, Lin C, Miller RG, Mitsumoto H, Nicholson G, Ravits J, Shaw PJ, Swash M, Talbot K, Traynor BJ, Van den Berg LH, Veldink JH, Vucic S, Kiernan MC (2013) Controversies and priorities in amyotrophic lateral sclerosis. Lancet Neurol 12(3):310–322

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H, Mann D, Tsuchiya K, Yoshida M, Hashizume Y, Oda T (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 351(3):602–611

    CAS  PubMed  Google Scholar 

  87. Kwiatkowski TJ Jr, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, Davis A, Gilchrist J, Kasarskis EJ, Munsat T, Valdmanis P, Rouleau GA, Hosler BA, Cortelli P, de Jong PJ, Yoshinaga Y, Haines JL, Pericak-Vance MA, Yan J, Ticozzi N, Siddique T, McKenna-Yasek D, Sapp PC, Horvitz HR, Landers JE, Brown RH Jr (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323(5918):1205–1208

    CAS  PubMed  Google Scholar 

  88. Turner BJ, Talbot K (2008) Transgenics, toxicity and therapeutics in rodent models of mutant SOD1-mediated familial ALS. Prog Neurobiol 85(1):94–134

    CAS  PubMed  Google Scholar 

  89. Pioro EP, Wang Y, Moore JK, Ng TC, Trapp BD, Klinkosz B, Mitsumoto H (1998) Neuronal pathology in the wobbler mouse brain revealed by in vivo proton magnetic resonance spectroscopy and immunocytochemistry. Neuroreport 9(13):3041–3046

    CAS  PubMed  Google Scholar 

  90. Choi JK, Kustermann E, Dedeoglu A, Jenkins BG (2009) Magnetic resonance spectroscopy of regional brain metabolite markers in FALS mice and the effects of dietary creatine supplementation. Eur J Neurosci 30(11):2143–2150

    PubMed  PubMed Central  Google Scholar 

  91. Andreassen OA, Jenkins BG, Dedeoglu A, Ferrante KL, Bogdanov MB, Kaddurah-Daouk R, Beal MF (2001) Increases in cortical glutamate concentrations in transgenic amyotrophic lateral sclerosis mice are attenuated by creatine supplementation. J Neurochem 77(2):383–390

    CAS  PubMed  Google Scholar 

  92. Ghoddoussi F, Galloway MP, Jambekar A, Bame M, Needleman R, Brusilow WS (2010) Methionine sulfoximine, an inhibitor of glutamine synthetase, lowers brain glutamine and glutamate in a mouse model of ALS. J Neurol Sci 290(1-2):41–47

    CAS  PubMed  Google Scholar 

  93. Niessen HG, Debska-Vielhaber G, Sander K, Angenstein F, Ludolph AC, Hilfert L, Willker W, Leibfritz D, Heinze HJ, Kunz WS, Vielhaber S (2007) Metabolic progression markers of neurodegeneration in the transgenic G93A-SOD1 mouse model of amyotrophic lateral sclerosis. Eur J Neurosci 25(6):1669–1677

    PubMed  Google Scholar 

  94. Block W, Karitzky J, Traber F, Pohl C, Keller E, Mundegar RR, Lamerichs R, Rink H, Ries F, Schild HH, Jerusalem F (1998) Proton magnetic resonance spectroscopy of the primary motor cortex in patients with motor neuron disease: subgroup analysis and follow-up measurements. Arch Neurol 55(7):931–936

    CAS  PubMed  Google Scholar 

  95. Kalra S, Arnold DL (2006) Magnetic resonance spectroscopy for monitoring neuronal integrity in amyotrophic lateral sclerosis. Adv Exp Med Biol 576:275–282, discussion 361-273

    CAS  PubMed  Google Scholar 

  96. Ludolph AC (2006) Matrix metalloproteinases--a conceptional alternative for disease-modifying strategies in ALS/MND? Exp Neurol 201(2):277–280

    CAS  PubMed  Google Scholar 

  97. Benatar M (2007) Lost in translation: treatment trials in the SOD1 mouse and in human ALS. Neurobiol Dis 26(1):1–13

    CAS  PubMed  Google Scholar 

  98. Scott S, Kranz JE, Cole J, Lincecum JM, Thompson K, Kelly N, Bostrom A, Theodoss J, Al-Nakhala BM, Vieira FG, Ramasubbu J, Heywood JA (2008) Design, power, and interpretation of studies in the standard murine model of ALS. Amyotroph Lateral Scler 9(1):4–15

    CAS  PubMed  Google Scholar 

  99. Pioro EP, Antel JP, Cashman NR, Arnold DL (1994) Detection of cortical neuron loss in motor neuron disease by proton magnetic resonance spectroscopic imaging in vivo. Neurology 44(10):1933–1938

    CAS  PubMed  Google Scholar 

  100. Gredal O, Rosenbaum S, Topp S, Karlsborg M, Strange P, Werdelin L (1997) Quantification of brain metabolites in amyotrophic lateral sclerosis by localized proton magnetic resonance spectroscopy. Neurology 48(4):878–881

    CAS  PubMed  Google Scholar 

  101. Bradley WG, Bowen BC, Pattany PM, Rotta F (1999) 1H-magnetic resonance spectroscopy in amyotrophic lateral sclerosis. J Neurol Sci 169(1-2):84–86

    CAS  PubMed  Google Scholar 

  102. Schuff N, Rooney WD, Miller R, Gelinas DF, Amend DL, Maudsley AA, Weiner MW (2001) Reanalysis of multislice 1H MRSI in amyotrophic lateral sclerosis. Magn Reson Med 45(3):513–516

    CAS  PubMed  Google Scholar 

  103. Pohl C, Block W, Karitzky J, Traber F, Schmidt S, Grothe C, Lamerichs R, Schild H, Klockgether T (2001) Proton magnetic resonance spectroscopy of the motor cortex in 70 patients with amyotrophic lateral sclerosis. Arch Neurol 58(5):729–735

    CAS  PubMed  Google Scholar 

  104. Block W, Traber F, Flacke S, Jessen F, Pohl C, Schild H (2002) In-vivo proton MR-spectroscopy of the human brain: assessment of N-acetylaspartate (NAA) reduction as a marker for neurodegeneration. Amino Acids 23(1-3):317–323

    CAS  PubMed  Google Scholar 

  105. Suhy J, Miller RG, Rule R, Schuff N, Licht J, Dronsky V, Gelinas D, Maudsley AA, Weiner MW (2002) Early detection and longitudinal changes in amyotrophic lateral sclerosis by 1H MRSI. Neurology 58(5):773–779

    CAS  PubMed  Google Scholar 

  106. Mitsumoto H, Ulug AM, Pullman SL, Gooch CL, Chan S, Tang MX, Mao X, Hays AP, Floyd AG, Battista V, Montes J, Hayes S, Dashnaw S, Kaufmann P, Gordon PH, Hirsch J, Levin B, Rowland LP, Shungu DC (2007) Quantitative objective markers for upper and lower motor neuron dysfunction in ALS. Neurology 68(17):1402–1410

    CAS  PubMed  Google Scholar 

  107. Abe K, Takanashi M, Watanabe Y, Tanaka H, Fujita N, Hirabuki N, Yanagihara T (2001) Decrease in N-acetylaspartate/creatine ratio in the motor area and the frontal lobe in amyotrophic lateral sclerosis. Neuroradiology 43(7):537–541

    CAS  PubMed  Google Scholar 

  108. Yin H, Lim CC, Ma L, Gao Y, Cai Y, Li D, Liang Y, Guo X (2004) Combined MR spectroscopic imaging and diffusion tensor MRI visualizes corticospinal tract degeneration in amyotrophic lateral sclerosis. J Neurol 251(10):1249–1254

    PubMed  Google Scholar 

  109. Rule RR, Suhy J, Schuff N, Gelinas DF, Miller RG, Weiner MW (2004) Reduced NAA in motor and non-motor brain regions in amyotrophic lateral sclerosis: a cross-sectional and longitudinal study. Amyotroph Lateral Scler Other Motor Neuron Disord 5(3):141–149

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Kalra S, Hanstock CC, Martin WR, Allen PS, Johnston WS (2006) Detection of cerebral degeneration in amyotrophic lateral sclerosis using high-field magnetic resonance spectroscopy. Arch Neurol 63(8):1144–1148

    PubMed  Google Scholar 

  111. Kalra S, Tai P, Genge A, Arnold DL (2006) Rapid improvement in cortical neuronal integrity in amyotrophic lateral sclerosis detected by proton magnetic resonance spectroscopic imaging. J Neurol 253(8):1060–1063

    CAS  PubMed  Google Scholar 

  112. Lombardo F, Frijia F, Bongioanni P, Canapicchi R, Minichilli F, Bianchi F, Hlavata H, Rossi B, Montanaro D (2009) Diffusion tensor MRI and MR spectroscopy in long lasting upper motor neuron involvement in amyotrophic lateral sclerosis. Arch Ital Biol 147(3):69–82

    CAS  PubMed  Google Scholar 

  113. Charil A, Corbo M, Filippi M, Kesavadas C, Agosta F, Munerati E, Gambini A, Comi G, Scotti G, Falini A (2009) Structural and metabolic changes in the brain of patients with upper motor neuron disorders: a multiparametric MRI study. Amyotroph Lateral Scler 10(5-6):269–279

    CAS  PubMed  Google Scholar 

  114. Sivak S, Bittsansky M, Kurca E, Turcanova-Koprusakova M, Grofik M, Nosal V, Polacek H, Dobrota D (2010) Proton magnetic resonance spectroscopy in patients with early stages of amyotrophic lateral sclerosis. Neuroradiology 52(12):1079–1085

    PubMed  Google Scholar 

  115. Pyra T, Hui B, Hanstock C, Concha L, Wong JC, Beaulieu C, Johnston W, Kalra S (2010) Combined structural and neurochemical evaluation of the corticospinal tract in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 11(1-2):157–165

    CAS  PubMed  Google Scholar 

  116. Han J, Ma L (2010) Study of the features of proton MR spectroscopy (1H-MRS) on amyotrophic lateral sclerosis. J Magn Reson Imaging 31(2):305–308

    PubMed  Google Scholar 

  117. Jones AP, Gunawardena WJ, Coutinho CM, Gatt JA, Shaw IC, Mitchell JD (1995) Preliminary results of proton magnetic resonance spectroscopy in motor neurone disease (amyotrophic lateral sclerosis). J Neurol Sci 129(Suppl):85–89

    PubMed  Google Scholar 

  118. Giroud M, Walker P, Bernard D, Lemesle M, Martin D, Baudouin N, Brunotte F, Dumas R (1996) Reduced brain N-acetyl-aspartate in frontal lobes suggests neuronal loss in patients with amyotrophic lateral sclerosis. Neurol Res 18(3):241–243

    CAS  PubMed  Google Scholar 

  119. Rooney WD, Miller RG, Gelinas D, Schuff N, Maudsley AA, Weiner MW (1998) Decreased N-acetylaspartate in motor cortex and corticospinal tract in ALS. Neurology 50(6):1800–1805

    CAS  PubMed  Google Scholar 

  120. Govind V, Sharma KR, Maudsley AA, Arheart KL, Saigal G, Sheriff S (2012) Comprehensive evaluation of corticospinal tract metabolites in amyotrophic lateral sclerosis using whole-brain 1H MR spectroscopy. PLoS One 7(4), e35607

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Brooks BR (1994) El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial “Clinical limits of amyotrophic lateral sclerosis” workshop contributors. J Neurol Sci 124:96–107

    PubMed  Google Scholar 

  122. Wang S, Poptani H, Woo JH, Desiderio LM, Elman LB, McCluskey LF, Krejza J, Melhem ER (2006) Amyotrophic lateral sclerosis: diffusion-tensor and chemical shift MR imaging at 3.0 T. Radiology 239(3):831–838

    PubMed  Google Scholar 

  123. Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B, Nakanishi A (1999) The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci 169(1-2):13–21

    CAS  PubMed  Google Scholar 

  124. Verma G, Woo JH, Chawla S, Wang S, Sheriff S, Elman LB, McCluskey LF, Grossman M, Melhem ER, Maudsley AA, Poptani H (2013) Whole-brain analysis of amyotrophic lateral sclerosis by using echo-planar spectroscopic imaging. Radiology 267(3):851–857

    PubMed  PubMed Central  Google Scholar 

  125. Stagg CJ, Knight S, Talbot K, Jenkinson M, Maudsley AA, Turner MR (2013) Whole-brain magnetic resonance spectroscopic imaging measures are related to disability in ALS. Neurology 80(7):610–615

    PubMed  PubMed Central  Google Scholar 

  126. Hurd R, Sailasuta N, Srinivasan R, Vigneron DB, Pelletier D, Nelson SJ (2004) Measurement of brain glutamate using TE-averaged PRESS at 3T. Magn Reson Med 51(3):435–440

    CAS  PubMed  Google Scholar 

  127. Frahm J, Bruhn H, Gyngell ML, Merboldt KD, Hanicke W, Sauter R (1989) Localized high-resolution proton NMR spectroscopy using stimulated echoes: initial applications to human brain in vivo. Magn Reson Med 9(1):79–93

    CAS  PubMed  Google Scholar 

  128. Foerster BR, Callaghan BC, Petrou M, Edden RA, Chenevert TL, Feldman EL (2012) Decreased motor cortex gamma-aminobutyric acid in amyotrophic lateral sclerosis. Neurology 78(20):1596–1600

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Foerster BR, Pomper MG, Callaghan BC, Petrou M, Edden RA, Mohamed MA, Welsh RC, Carlos RC, Barker PB, Feldman EL (2013) An imbalance between excitatory and inhibitory neurotransmitters in amyotrophic lateral sclerosis revealed by use of 3-T proton magnetic resonance spectroscopy. JAMA Neurol 70(8):1009–1016

    PubMed  PubMed Central  Google Scholar 

  130. Mescher M, Merkle H, Kirsch J, Garwood M, Gruetter R (1998) Simultaneous in vivo spectral editing and water suppression. NMR Biomed 11(6):266–272

    CAS  PubMed  Google Scholar 

  131. Chi L, Ke Y, Luo C, Gozal D, Liu R (2007) Depletion of reduced glutathione enhances motor neuron degeneration in vitro and in vivo. Neuroscience 144(3):991–1003

    CAS  PubMed  Google Scholar 

  132. Li Y, Maher P, Schubert D (1997) A role for 12-lipoxygenase in nerve cell death caused by glutathione depletion. Neuron 19(2):453–463

    CAS  PubMed  Google Scholar 

  133. Weiduschat N, Mao X, Hupf J, Armstrong N, Kang G, Lange DJ, Mitsumoto H, Shungu DC (2014) Motor cortex glutathione deficit in ALS measured in vivo with the J-editing technique. Neurosci Lett 570:102–107

    CAS  PubMed  Google Scholar 

  134. Terpstra M, Henry PG, Gruetter R (2003) Measurement of reduced glutathione (GSH) in human brain using LCModel analysis of difference-edited spectra. Magn Reson Med 50(1):19–23

    CAS  PubMed  Google Scholar 

  135. Sharma KR, Saigal G, Maudsley AA, Govind V (2011) 1H MRS of basal ganglia and thalamus in amyotrophic lateral sclerosis. NMR Biomed 24(10):1270–1276

    PubMed  PubMed Central  Google Scholar 

  136. Smith MC (1960) Nerve Fibre Degeneration in the Brain in Amyotrophic Lateral Sclerosis. J Neurol Neurosurg Psychiatry 23(4):269–282

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Usman U, Choi C, Camicioli R, Seres P, Lynch M, Sekhon R, Johnston W, Kalra S (2011) Mesial prefrontal cortex degeneration in amyotrophic lateral sclerosis: a high-field proton MR spectroscopy study. AJNR Am J Neuroradiol 32(9):1677–1680

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Lawyer T Jr, Netsky MG (1953) Amyotrophic lateral sclerosis. AMA Arch Neurol Psych 69(2):171–192

    Google Scholar 

  139. Cwik VA, Hanstock CC, Allen PS, Martin WR (1998) Estimation of brainstem neuronal loss in amyotrophic lateral sclerosis with in vivo proton magnetic resonance spectroscopy. Neurology 50(1):72–77

    CAS  PubMed  Google Scholar 

  140. Hanstock CC, Cwik VA, Martin WR (2002) Reduction in metabolite transverse relaxation times in amyotrophic lateral sclerosis. J Neurol Sci 198(1-2):37–41

    CAS  PubMed  Google Scholar 

  141. Pioro EP, Majors AW, Mitsumoto H, Nelson DR, Ng TC (1999) 1H-MRS evidence of neurodegeneration and excess glutamate + glutamine in ALS medulla. Neurology 53(1):71–79

    CAS  PubMed  Google Scholar 

  142. Carew JD, Nair G, Pineda-Alonso N, Usher S, Hu X, Benatar M (2011) Magnetic resonance spectroscopy of the cervical cord in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 12(3):185–191

    CAS  PubMed  Google Scholar 

  143. Ikeda K, Murata K, Kawase Y, Kawabe K, Kano O, Yoshii Y, Takazawa T, Hirayama T, Iwasaki Y (2013) Relationship between cervical cord 1H-magnetic resonance spectroscopy and clinoco-electromyographic profile in amyotrophic lateral sclerosis. Muscle Nerve 47(1):61–67

    CAS  PubMed  Google Scholar 

  144. Carew JD, Nair G, Andersen PM, Wuu J, Gronka S, Hu X, Benatar M (2011) Presymptomatic spinal cord neurometabolic findings in SOD1-positive people at risk for familial ALS. Neurology 77(14):1370–1375

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Unrath A, Ludolph AC, Kassubek J (2007) Brain metabolites in definite amyotrophic lateral sclerosis. A longitudinal proton magnetic resonance spectroscopy study. J Neurol 254(8):1099–1106

    CAS  PubMed  Google Scholar 

  146. Kalra S, Cashman NR, Genge A, Arnold DL (1998) Recovery of N-acetylaspartate in corticomotor neurons of patients with ALS after riluzole therapy. Neuroreport 9(8):1757–1761

    CAS  PubMed  Google Scholar 

  147. Khiat A, D'Amour M, Souchon F, Boulanger Y (2010) MRS study of the effects of minocycline on markers of neuronal and microglial integrity in ALS. Magn Reson Imaging 28(10):1456–1460

    CAS  PubMed  Google Scholar 

  148. Atassi N, Ratai EM, Greenblatt DJ, Pulley D, Zhao Y, Bombardier J, Wallace S, Eckenrode J, Cudkowicz M, Dibernardo A (2010) A phase I, pharmacokinetic, dosage escalation study of creatine monohydrate in subjects with amyotrophic lateral sclerosis. Amyotroph Lateral Scler 11(6):508–513

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Kalra S, Cashman NR, Caramanos Z, Genge A, Arnold DL (2003) Gabapentin therapy for amyotrophic lateral sclerosis: lack of improvement in neuronal integrity shown by MR spectroscopy. AJNR Am J Neuroradiol 24(3):476–480

    PubMed  PubMed Central  Google Scholar 

  150. Kalra S, Genge A, Arnold DL (2003) A prospective, randomized, placebo-controlled evaluation of corticoneuronal response to intrathecal BDNF therapy in ALS using magnetic resonance spectroscopy: feasibility and results. Amyotroph Lateral Scler Other Motor Neuron Disord 4(1):22–26

    CAS  PubMed  Google Scholar 

  151. Maudsley AA, Darkazanli A, Alger JR, Hall LO, Schuff N, Studholme C, Yu Y, Ebel A, Frew A, Goldgof D, Gu Y, Pagare R, Rousseau F, Sivasankaran K, Soher BJ, Weber P, Young K, Zhu X (2006) Comprehensive processing, display and analysis for in vivo MR spectroscopic imaging. NMR Biomed 19(4):492–503

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Cai K, Haris M, Singh A, Kogan F, Greenberg JH, Hariharan H, Detre JA, Reddy R (2012) Magnetic resonance imaging of glutamate. Nat Med 18(2):302–306

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Chatnuntawech I, Gagoski B, Bilgic B, Cauley SF, Setsompop K, Adalsteinsson E (2014) Accelerated H MRSI using randomly undersampled spiral-based k-space trajectories. Magn Reson Med. doi:10.1002/mrm.25394

    Article  PubMed  Google Scholar 

  154. Cao P, Wu EX (2015) Accelerating phase-encoded proton MR spectroscopic imaging by compressed sensing. J Magn Reson Imaging 41(2):487–495

    PubMed  Google Scholar 

  155. Wilson NE, Iqbal Z, Burns BL, Keller M, Thomas MA (2015) Accelerated five-dimensional echo planar J-resolved spectroscopic imaging: Implementation and pilot validation in human brain. Magn Reson Med. doi:10.1002/mrm.25605

    Article  PubMed  PubMed Central  Google Scholar 

  156. Sabati M, Sheriff S, Gu M, Wei J, Zhu H, Barker PB, Spielman DM, Alger JR, Maudsley AA (2014) Multivendor implementation and comparison of volumetric whole-brain echo-planar MR spectroscopic imaging. Magn Reson Med. doi:10.1002/mrm.25510

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was funded by a grant from the National Institutes of Health (R01 NS060874), USA. The author gratefully acknowledges Drs. Maudsley and Sharma for their collaboration in this project. Mr. Sulaiman Sheriff is thanked for his help to make a figure included in this chapter.

Author information

Authors and Affiliations

  1. Department of Radiology, University of Miami School of Medicine, Miami, FL, USA

    Varan Govind Ph.D.

Authors
  1. Varan Govind Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Varan Govind Ph.D. .

Editor information

Editors and Affiliations

  1. University of Minnesota Medical School, Center Magnetic Resonance Research University of Minnesota Medical School, Minneapolis, MN, USA

    Gülin Öz

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Govind, V. (2016). MRS in Motor Neuron Diseases. In: Öz, G. (eds) Magnetic Resonance Spectroscopy of Degenerative Brain Diseases. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-319-33555-1_7

Download citation

Publish with us

Policies and ethics

Search

Navigation