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Imaging Neurodegeneration: What Can Magnetic Resonance Spectroscopy Contribute?

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Book cover Magnetic Resonance Spectroscopy of Degenerative Brain Diseases

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

Abstract

With increased prevalence of neurodegenerative diseases with age and an aging society, neuroimaging for diagnosis, prognosis, and therapy monitoring in these diseases has become more important than ever. There is particularly a great need for robust biomarkers and surrogate markers of cerebral pathology that can facilitate development of effective treatments in these conditions. Many radionuclide and MRI modalities are currently used in clinical research, with some already accepted among diagnostic criteria for neurodegenerative diseases. Others are being evaluated for their potential to monitor the pathogenic events during neurodegeneration at multiple levels from the global network level down to the subcellular and molecular levels. This chapter places magnetic resonance spectroscopy (MRS) within the context of other imaging modalities for evaluating neurodegeneration and summarizes its unique role in simultaneously assessing multiple relevant pathophysiological events, including neuronal loss/dysfunction, gliosis, demyelination, impaired energetics, increased membrane turnover, demyelination, synaptic dysfunction, and oxidative stress. Finally, the steps that still need to be taken to facilitate wider utility of advanced MRS methodology are outlined.

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References

  1. Vincent GK, Velkoff VA (2010) The next four decades: the older population in the United States: 2010 to 2050. Current Population Reports. US Census Bureau

    Google Scholar 

  2. Andre R, Scahill RI, Haider S, Tabrizi SJ (2014) Biomarker development for Huntington’s disease. Drug Discov Today 19(7):972–979

    CAS  PubMed  Google Scholar 

  3. Dorsey ER, Holloway RG, Ravina BM (2006) Biomarkers in Parkinson’s disease. Expert Rev Neurother 6(6):823–831

    CAS  PubMed  Google Scholar 

  4. Turner MR, Grosskreutz J, Kassubek J, Abrahams S, Agosta F, Benatar M, Filippi M, Goldstein LH, van den Heuvel M, Kalra S, Lule D, Mohammadi B (2011) Towards a neuroimaging biomarker for amyotrophic lateral sclerosis. Lancet Neurol 10(5):400–403

    PubMed  Google Scholar 

  5. Mueller SG, Schuff N, Weiner MW (2006) Evaluation of treatment effects in Alzheimer’s and other neurodegenerative diseases by MRI and MRS. NMR Biomed 19(6):655–668

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Bossy-Wetzel E, Schwarzenbacher R, Lipton SA (2004) Molecular pathways to neurodegeneration. Nat Med 10(Suppl):S2–S9

    PubMed  Google Scholar 

  7. Jellinger KA (2009) Recent advances in our understanding of neurodegeneration. J Neural Transm 116(9):1111–1162

    CAS  PubMed  Google Scholar 

  8. Ramanan VK, Saykin AJ (2013) Pathways to neurodegeneration: mechanistic insights from GWAS in Alzheimer’s disease, Parkinson’s disease, and related disorders. Am J Neurodegener Dis 2(3):145–175

    PubMed  PubMed Central  Google Scholar 

  9. Zlokovic BV (2011) Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci 12(12):723–738

    CAS  PubMed  PubMed Central  Google Scholar 

  10. DeKosky ST, Marek K (2003) Looking backward to move forward: early detection of neurodegenerative disorders. Science 302(5646):830–834

    CAS  PubMed  Google Scholar 

  11. Zhu XH, Du F, Zhang N, Zhang Y, Lei H, Zhang X, Qiao H, Ugurbil K, Chen W (2009) Advanced in vivo heteronuclear MRS approaches for studying brain bioenergetics driven by mitochondria. Methods Mol Biol 489:317–357

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Blüml S, Moreno A, Hwang JH, Ross BD (2001) 1-13C glucose magnetic resonance spectroscopy of pediatric and adult brain disorders. NMR Biomed 14(1):19–32

    PubMed  Google Scholar 

  13. Gruetter R, Adriany G, Choi IY, Henry PG, Lei H, Öz G (2003) Localized in vivo 13C NMR spectroscopy of the brain. NMR Biomed 16(6–7):313–338

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Jack CR Jr, Holtzman DM (2013) Biomarker modeling of Alzheimer’s disease. Neuron 80(6):1347–1358

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Kantarci K, Jack CR Jr (2003) Neuroimaging in Alzheimer disease: an evidence-based review. Neuroimaging Clin N Am 13(2):197–209

    PubMed  Google Scholar 

  16. Goveas J, O’Dwyer L, Mascalchi M, Cosottini M, Diciotti S, De Santis S, Passamonti L, Tessa C, Toschi N, Giannelli M (2015) Diffusion-MRI in neurodegenerative disorders. Magn Reson Imaging 33(7):853–876

    PubMed  Google Scholar 

  17. Barkhof F, Haller S, Rombouts SA (2014) Resting-state functional MR imaging: a new window to the brain. Radiology 272(1):29–49

    PubMed  Google Scholar 

  18. Pievani M, Filippini N, van den Heuvel MP, Cappa SF, Frisoni GB (2014) Brain connectivity in neurodegenerative diseases—from phenotype to proteinopathy. Nat Rev Neurol 10(11):620–633

    PubMed  Google Scholar 

  19. Iturria-Medina Y, Evans AC (2015) On the central role of brain connectivity in neurodegenerative disease progression. Front Aging Neurosci 7:90

    PubMed  PubMed Central  Google Scholar 

  20. Jack CR Jr, Barrio JR, Kepe V (2013) Cerebral amyloid PET imaging in Alzheimer’s disease. Acta Neuropathol 126(5):643–657

    CAS  PubMed  Google Scholar 

  21. Perani D (2014) FDG-PET and amyloid-PET imaging: the diverging paths. Curr Opin Neurol 27(4):405–413

    CAS  PubMed  Google Scholar 

  22. Stoessl AJ, Lehericy S, Strafella AP (2014) Imaging insights into basal ganglia function, Parkinson’s disease, and dystonia. Lancet 384(9942):532–544

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Zimmer ER, Leuzy A, Benedet AL, Breitner J, Gauthier S, Rosa-Neto P (2014) Tracking neuroinflammation in Alzheimer’s disease: the role of positron emission tomography imaging. J Neuroinflammation 11:120

    PubMed  PubMed Central  Google Scholar 

  24. Jack CR Jr (2012) Alzheimer disease: new concepts on its neurobiology and the clinical role imaging will play. Radiology 263(2):344–361

    PubMed  PubMed Central  Google Scholar 

  25. Filippi M, Rocca MA (2007) Magnetization transfer magnetic resonance imaging of the brain, spinal cord, and optic nerve. Neurotherapeutics 4(3):401–413

    PubMed  PubMed Central  Google Scholar 

  26. Silva AC, Bock NA (2008) Manganese-enhanced MRI: an exceptional tool in translational neuroimaging. Schizophr Bull 34(4):595–604

    PubMed  PubMed Central  Google Scholar 

  27. Dusek P, Dezortova M, Wuerfel J (2013) Imaging of iron. Int Rev Neurobiol 110:195–239

    CAS  PubMed  Google Scholar 

  28. Lehericy S, Sharman MA, Dos Santos CL, Paquin R, Gallea C (2012) Magnetic resonance imaging of the substantia nigra in Parkinson’s disease. Mov Disord 27(7):822–830

    PubMed  Google Scholar 

  29. Brooks DJ (2000) Morphological and functional imaging studies on the diagnosis and progression of Parkinson’s disease. J Neurol 247(Suppl 2):II11–II18

    PubMed  Google Scholar 

  30. Foerster BR, Welsh RC, Feldman EL (2013) 25 years of neuroimaging in amyotrophic lateral sclerosis. Nat Rev Neurol 9(9):513–524

    PubMed  PubMed Central  Google Scholar 

  31. Godbolt AK, Waldman AD, MacManus DG, Schott JM, Frost C, Cipolotti L, Fox NC, Rossor MN (2006) MRS shows abnormalities before symptoms in familial Alzheimer disease. Neurology 66(5):718–722

    CAS  PubMed  Google Scholar 

  32. Öz G, Nelson CD, Koski DM, Henry PG, Marjanska M, Deelchand DK, Shanley R, Eberly LE, Orr HT, Clark HB (2010) Noninvasive detection of presymptomatic and progressive neurodegeneration in a mouse model of spinocerebellar ataxia type 1. J Neurosci 30(10):3831–3838

    PubMed  PubMed Central  Google Scholar 

  33. Kantarci K, Boeve BF, Wszolek ZK, Rademakers R, Whitwell JL, Baker MC, Senjem ML, Samikoglu AR, Knopman DS, Petersen RC, Jack CR Jr (2010) MRS in presymptomatic MAPT mutation carriers: a potential biomarker for tau-mediated pathology. Neurology 75(9):771–778

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Öz G, Alger JR, Barker PB, Bartha R, Bizzi A, Boesch C, Bolan PJ, Brindle KM, Cudalbu C, Dincer A, Dydak U, Emir UE, Frahm J, González RG, Gruber S, Gruetter R, Gupta RK, Heerschap A, Henning A, Hetherington HP, Howe FA, Hüppi PS, Hurd RE, Kantarci K, Klomp DW, Kreis R, Kruiskamp MJ, Leach MO, Lin AP, Luijten PR, Marjańska M, Maudsley AA, Meyerhoff DJ, Mountford CE, Nelson SJ, Pamir MN, Pan JW, Peet AC, Poptani H, Posse S, Pouwels PJ, Ratai EM, Ross BD, Scheenen TW, Schuster C, Smith IC, Soher BJ, Tkáč I, Vigneron DB, Kauppinen RA, The MRS Consensus Group (2014) Clinical proton MR spectroscopy in central nervous system disorders. Radiology 270(3):658–679

    PubMed  Google Scholar 

  35. Duarte JM, Lei H, Mlynárik V, Gruetter R (2012) The neurochemical profile quantified by in vivo 1H NMR spectroscopy. Neuroimage 61(2):342–362

    CAS  PubMed  Google Scholar 

  36. Jenkins BG, Kraft E (1999) Magnetic resonance spectroscopy in toxic encephalopathy and neurodegeneration. Curr Opin Neurol 12(6):753–760

    CAS  PubMed  Google Scholar 

  37. Viau M, Marchand L, Bard C, Boulanger Y (2005) 1H magnetic resonance spectroscopy of autosomal ataxias. Brain Res 1049(2):191–202

    CAS  PubMed  Google Scholar 

  38. Schuff N, Meyerhoff DJ, Mueller S, Chao L, Sacrey DT, Laxer K, Weiner MW (2006) N-acetylaspartate as a marker of neuronal injury in neurodegenerative disease. Adv Exp Med Biol 576:241–262, discussion 361–363

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Marjańska M, Curran GL, Wengenack TM, Henry PG, Bliss RL, Poduslo JF, Jack CR Jr, Ugurbil K, Garwood M (2005) Monitoring disease progression in transgenic mouse models of Alzheimer’s disease with proton magnetic resonance spectroscopy. Proc Natl Acad Sci U S A 102(33):11906–11910

    PubMed  PubMed Central  Google Scholar 

  40. Tkáč I, Dubinsky JM, Keene CD, Gruetter R, Low WC (2007) Neurochemical changes in Huntington R6/2 mouse striatum detected by in vivo 1H NMR spectroscopy. J Neurochem 100(5):1397–1406

    PubMed  PubMed Central  Google Scholar 

  41. Mohamed MA, Barker PB, Skolasky RL, Selnes OA, Moxley RT, Pomper MG, Sacktor NC (2010) Brain metabolism and cognitive impairment in HIV infection: a 3-T magnetic resonance spectroscopy study. Magn Reson Imaging 28(9):1251–1257

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Öz G, Hutter D, Tkáč I, Clark HB, Gross MD, Jiang H, Eberly LE, Bushara KO, Gomez CM (2010) Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status. Mov Disord 25(9):1253–1261

    PubMed  PubMed Central  Google Scholar 

  43. Öz G, Iltis I, Hutter D, Thomas W, Bushara KO, Gomez CM (2011) Distinct neurochemical profiles of spinocerebellar ataxias 1, 2, 6, and cerebellar multiple system atrophy. Cerebellum 10(2):208–217

    PubMed  PubMed Central  Google Scholar 

  44. Öz G, Tkáč I, Charnas LR, Choi IY, Bjoraker KJ, Shapiro EG, Gruetter R (2005) Assessment of adrenoleukodystrophy lesions by high field MRS in non-sedated pediatric patients. Neurology 64(3):434–441

    PubMed  Google Scholar 

  45. Ratai E, Kok T, Wiggins C, Wiggins G, Grant E, Gagoski B, O’Neill G, Adalsteinsson E, Eichler F (2008) Seven-Tesla proton magnetic resonance spectroscopic imaging in adult X-linked adrenoleukodystrophy. Arch Neurol 65(11):1488–1494

    PubMed  PubMed Central  Google Scholar 

  46. Kantarci K, Petersen RC, Boeve BF, Knopman DS, Tang-Wai DF, O’Brien PC, Weigand SD, Edland SD, Smith GE, Ivnik RJ, Ferman TJ, Tangalos EG, Jack CR Jr (2004) 1H MR spectroscopy in common dementias. Neurology 63(8):1393–1398

    CAS  PubMed  Google Scholar 

  47. Zimmerman ME, Pan JW, Hetherington HP, Katz MJ, Verghese J, Buschke H, Derby CA, Lipton RB (2008) Hippocampal neurochemistry, neuromorphometry, and verbal memory in nondemented older adults. Neurology 70(18):1594–1600

    CAS  PubMed  Google Scholar 

  48. Deelchand DK, Adanyeguh IM, Emir UE, Nguyen TM, Valabregue R, Henry PG, Mochel F, Öz G (2015) Two-site reproducibility of cerebellar and brainstem neurochemical profiles with short-echo, single voxel MRS at 3 T. Magn Reson Med 73(5):1718–1725

    PubMed  Google Scholar 

  49. Deelchand DK, Kantarci K, Eberly LE, Öz G (2015) Towards translation of advanced MRS methodology to clinical setting. In: Proc Intl Soc Mag Reson Med, Toronto, Canada. p 4660

    Google Scholar 

  50. Hancu I, Blezek DJ, Dumoulin MC (2005) Automatic repositioning of single voxels in longitudinal 1H MRS studies. NMR Biomed 18(6):352–361

    CAS  PubMed  Google Scholar 

  51. Dou W, Speck O, Benner T, Kaufmann J, Li M, Walter M (2015) Automatic voxel positioning for MRS at 7 T. MAGMA 28:259–270

    PubMed  Google Scholar 

  52. van de Bank BL, Emir UE, Boer VO, van Asten JJ, Maas MC, Wijnen JP, Kan HE, Öz G, Klomp DW, Scheenen TW (2015) Multi-center reproducibility of neurochemical profiles in the human brain at 7 T. NMR Biomed 28(3):306–316

    PubMed  PubMed Central  Google Scholar 

  53. Poste G (2011) Bring on the biomarkers. Nature 469(7329):156–157

    CAS  PubMed  Google Scholar 

  54. European Society of Radiology (ESR) (2010) White paper on imaging biomarkers. Insights Imaging 1(2):42–45

    Google Scholar 

  55. Lin A, Ross BD, Harris K, Wong W (2005) Efficacy of proton magnetic resonance spectroscopy in neurological diagnosis and neurotherapeutic decision making. NeuroRx 2(2):197–214

    PubMed  PubMed Central  Google Scholar 

  56. Lin AP, Tran TT, Ross BD (2006) Impact of evidence-based medicine on magnetic resonance spectroscopy. NMR Biomed 19(4):476–483

    CAS  PubMed  Google Scholar 

  57. Öz G, Tkáč I (2011) Short-echo, single-shot, full-intensity proton magnetic resonance spectroscopy for neurochemical profiling at 4 T: validation in the cerebellum and brainstem. Magn Reson Med 65(4):901–910

    PubMed  Google Scholar 

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Acknowledgments

The preparation of this chapter was in part supported by the National Institute of Neurological Disorders and Stroke (NINDS) grant R01 NS070815. The Center for MR Research is supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) grant P41 EB015894 and the Institutional Center Cores for Advanced Neuroimaging award P30 NS076408. The author acknowledges valuable feedback from Drs. Christophe Lenglet, Pierre-Gilles Henry, and David A. Okar and thanks Drs. Dinesh Deelchand, James Joers, Pierre-Gilles Henry, Fanny Mochel, and Petr Bednařík for providing images and spectra for the figure.

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  1. Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota, 2021 6th St. S.E., Minneapolis, MN, 55455, USA

    Gülin Öz Ph.D.

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  1. Gülin Öz Ph.D.
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Correspondence to Gülin Öz Ph.D. .

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

    Gülin Öz

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Öz, G. (2016). Imaging Neurodegeneration: What Can Magnetic Resonance Spectroscopy Contribute?. 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_1

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