Skip to main content Accessibility help
Hostname: page-component-684899dbb8-pcn4s Total loading time: 1.046 Render date: 2022-05-23T23:35:21.621Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "useNewApi": true }

21 - Magnetic resonance spectroscopy of neurodegenerative illness

from Part II - Neuroimaging in neurodegeneration

Published online by Cambridge University Press:  04 August 2010

M. Flint Beal
Cornell University, New York
Anthony E. Lang
University of Toronto
Albert C. Ludolph
Universität Ulm, Germany
Bruce G. Jenkins
Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School
Ji-Kyung Choi
Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School
Get access



Since its introduction for human study in the early 1980s, magnetic resonance (MR) has proven itself an extremely versatile technique for evaluation of many different parameters of anatomic, physiologic, and metabolic interest. The number of phenomena amenable to analysis using magnetic resonance (MR) techniques is increasing every year. This versatility arises from the many different sources of magnetic contrast that can be generated using either endogenous or exogenous contrast, from the versatility of the techniques for manipulation of the nuclear spins that generate the observed signals, and from the extremely safe nature of MR that lends itself well to longitudinal studies and large patient populations.

MR techniques can now evaluate tissue parameters relevant to TCA cycle metabolism, anaerobic glycolysis, ATP levels, blood–brain barrier permeability, macrophage infiltration, cytotoxic edema, spreading depression, cerebral blood flow and volume, and neurotransmitter function. The paramagnetic nature of certain oxidation states of iron leads to the ability to map out brain function using deoxyhemoglobin as an endogenous contrast agent, and also allows for mapping of local tissue iron concentrations. In addition to these metabolic parameters, the number of ways to generate anatomic contrast using MR is also expanding, and in addition to conventional anatomic scans, mapping of axonal fiber tracts can also be performed using the anisotropy of water diffusion. A selective, non-exhaustive, summary of the various parameters of relevance to neurodegeneration (ND) that can be measured using MR techniques is presented in Table 21.1.

Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
, pp. 301 - 326
Publisher: Cambridge University Press
Print publication year: 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


Andreassen, O. A., Jenkins, B. G., Dedeoglu, al. (2001a). Increases in cortical glutamate concentrations in transgenic amyotrophic lateral sclerosis mice are attenuated by creatine supplementation. J. Neurochem., 77, 383–90CrossRefGoogle Scholar
Andreassen, O. A., Dedeoglu, A., Ferrante, R. al. (2001b). Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease. Neurobiol. Dis., 8, 479–91CrossRefGoogle Scholar
Argov, Z. (1998). Functional evaluation techniques in mitochondrial disorders. Eur. Neurol., 39, 65–71CrossRefGoogle ScholarPubMed
Argov, Z. & Bank, W. J. (1991). Phosphorus magnetic resonance spectroscopy (31P MRS) in neuromuscular disorders. Ann. Neurol., 30, 90–7CrossRefGoogle Scholar
Badar-Goffer, R. S., Bachelard, H. S. & Morris, P. G. (1990). Cerebral metabolism of acetate and glucose studied by 13C-n.m.r. spectroscopy. A technique for investigating metabolic compartmentation in the brain. Biochem. J., 266, 133–9CrossRefGoogle Scholar
Barbiroli, B., Montagna, P., Martinelli, al. (1993). Defective brain energy metabolism shown by in vivo 31P MR spectroscopy in 28 patients with mitochondrial cytopathies. J. Cereb. Blood Flow Metab., 13, 469–74CrossRefGoogle ScholarPubMed
Barbiroli, B., Frassineti, C., Martinelli, al. (1997). Coenzyme Q10 improves mitochondrial respiration in patients with mitochondrial cytopathies. An in vivo study on brain and skeletal muscle by phosphorous magnetic resonance spectroscopy. Cell. Mol. Biol., 43, 741–9Google Scholar
Barbiroli, B., Iotti, S. & Lodi, R. (1998). Aspects of human bioenergetics as studied in vivo by magnetic resonance spectroscopy. Biochimie, 80, 847–53CrossRefGoogle ScholarPubMed
Bartha, R., Drost, D. J. & Williamson, P. C. (1999). Factors affecting the quantification of short echo in-vivo 1H MR spectra: prior knowledge, peak elimination, and filtering. NMR Biomed., 12, 205–163.0.CO;2-1>CrossRefGoogle ScholarPubMed
Baslow, M. H. (2002). Evidence supporting a role for N-acetyl-L-aspartate as a molecular water pump in myelinated neurons in the central nervous system. An analytical review. Neurochem. Int., 40, 295–300CrossRefGoogle Scholar
Baslow, M. H. (2003). Brain N-acetylaspartate as a molecular water pump and its role in the etiology of Canavan disease: a mechanistic explanation. J. Mol. Neurosci., 21, 185–90CrossRefGoogle ScholarPubMed
Beal, M. F., Brouillet, E., Jenkins, B. al. (1993). Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J. Neurosci., 13, 4181–92CrossRefGoogle ScholarPubMed
Beal, M. F., Henshaw, D. R., Jenkins, B. G., Rosen, B. R. & Schulz, J. B. (1994). Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate. Ann. Neurol., 36, 882–8CrossRefGoogle ScholarPubMed
Bendahan, D., Desnuelle, C., Vanuxem, al. (1992). 31P NMR spectroscopy and ergometer exercise test as evidence for muscle oxidative performance improvement with coenzyme Q in mitochondrial myopathies. Neurology, 42, 1203–8CrossRefGoogle ScholarPubMed
Birken, D. L. & Oldendorf, W. H. (1989). N-acetyl-L-aspartic acid: a literature review of a compound prominent in 1H-NMR spectroscopic studies of brain. Neurosci. Biobehav. Rev., 13, 23–31CrossRefGoogle ScholarPubMed
Blass, J. P., Sheu, R. K. & Cedarbaum, J. M. (1988). Energy metabolism in disorders of the nervous system. Rev. Neurol., 144, 543–63Google ScholarPubMed
Bluml, S., Moreno, A., Hwang, J. H. & Ross, B. D. (2001). 1-(13)C glucose magnetic resonance spectroscopy of pediatric and adult brain disorders. NMR Biomed., 14, 19–32CrossRefGoogle ScholarPubMed
Bluml, S., Moreno-Torres, A., Shic, F., Nguy, C. H. & Ross, B. D. (2002). Tricarboxylic acid cycle of glia in the in vivo human brain. NMR Biomed., 15, 1–5CrossRefGoogle ScholarPubMed
Bottomley, P. (1987). Spatial localization in NMR spectroscopy in vivo. Ann. NY Acad. Sci., 508, 333–8CrossRefGoogle ScholarPubMed
Brand, A., Richter-Landsberg, C. & Leibfritz, D. (1993). Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev. Neurosci., 15, 289–98CrossRefGoogle ScholarPubMed
Bristol, L. A. & Rothstein, J. D. (1996). Glutamate transporter gene expression in amyotrophic lateral sclerosis motor cortex. Ann. Neurol., 39, 676–9CrossRefGoogle ScholarPubMed
Brownell, A. L., Jenkins, B. G., Elmaleh, D. R., Deacon, T. W., Spealman, R. D. & Isacson, O. (1998). Combined PET/MRS brain studies show dynamic and long-term physiological changes in a primate model of Parkinson disease. Nat. Med., 4, 1308–12CrossRefGoogle Scholar
Chance, B., Leigh, J. S., Smith, D. S., Nioka, S. & Clark, B. J. (1986). Phosphorus magnetic resonance spectroscopy studies of the role of mitochondria in the disease process. Ann. NY Acad. Sci., 488, 140–53CrossRefGoogle ScholarPubMed
Choe, B. Y., Park, J. W., Lee, K. al. (1998). Neuronal laterality in Parkinson's disease with unilateral symptom by in vivo 1H magnetic resonance spectroscopy. Invest. Radiol., 33, 450–5CrossRefGoogle ScholarPubMed
Choi J.-K., Kuestermann, E., Andreassen, O. A., Beal, M. F. & Jenkins, B. G. (2003). A tale of two mice: impaired glial-neuronal cycling in mouse models of Huntington's disease and amyotrophic lateral sclerosis. In International Society of Magnetic Resonance in Medicine, p. 437. Toronto, Canada
Cruz, C. J., Aminoff, M. J., Meyerhoff, D. J., Graham, S. H. & Weiner, M. W. (1997). Proton MR spectroscopic imaging of the striatum in Parkinson's disease. Magn. Reson. Imagin., 15, 619–24CrossRefGoogle ScholarPubMed
Dager, S. R., Strauss, W. L., Marro, K. I., Richards, T. L., Metzger, G. D. & Artru, A. A. (1995). Proton magnetic resonance spectroscopy investigation of hyperventilation in subjects with panic disorder and comparison subjects. Am. J. Psychiatr., 152, 666–72Google ScholarPubMed
Davie, C. A., Hawkins, C. P., Barker, G. al. (1994). Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions. Brain, 117, 49–58CrossRefGoogle ScholarPubMed
Stefano, N., Matthews, P. M. & Arnold, D. L. (1995a). Reversible decreases in N-acetylaspartate after acute brain injury. Magn. Reson. Med., 34, 721–7CrossRefGoogle Scholar
Stefano, N., Matthews, P. M., Ford, B., Genge, A., Karpati, G. & Arnold, D. L. (1995b). Short-term dichloroacetate treatment improves indices of cerebral metabolism in patients with mitochondrial disorders. Neurology, 45, 1193–8CrossRefGoogle Scholar
Stefano, N., Matthews, P. M., Narayanan, S., Francis, G. S., Antel, J. P. & Arnold, D. L. (1997). Axonal dysfunction and disability in a relapse of multiple sclerosis: longitudinal study of a patient. Neurology, 49, 1138–41CrossRefGoogle Scholar
Dijkhuizen, R. M., Lookeren Campagne, M., Niendorf, al. (1996). Status of the neonatal rat brain after NMDA-induced excitotoxic injury as measured by MRI, MRS and metabolic imaging. NMR Biomed., 9, 84–923.0.CO;2-B>CrossRefGoogle ScholarPubMed
Dimlich, R. V. & Nielsen, M. M. (1992). Facilitating postischemic reduction of cerebral lactate in rats. Stroke, 23, 1145–52; discussion 1152–63CrossRefGoogle ScholarPubMed
Dunlop, D. S., McHale, D. M. & Lajtha, A. (1992). Decreased brain N-acetylaspartate in Huntington's disease. Brain Res., 580, 44–8CrossRefGoogle ScholarPubMed
Ellis, C. M., Lemmens, G., Williams, S. al. (1997). Changes in putamen N-acetylaspartate and choline ratios in untreated and levodopa-treated Parkinson's disease: a proton magnetic resonance spectroscopy study. Neurology, 49, 438–44CrossRefGoogle ScholarPubMed
Endres, M., Namura, S., Shimizu-Sasamata, al. (1998). Attenuation of delayed neuronal death after mild focal ischemia in mice by inhibition of the caspase family. J. Cereb. Blood Flow Metab., 18, 238–47CrossRefGoogle ScholarPubMed
Fenstermacher, M. J. & Narayana, P. A. (1990). Serial proton magnetic resonance spectroscopy of ischemic brain injury in humans. Invest. Radiol., 25, 1034–9CrossRefGoogle ScholarPubMed
Ferrante, R. J., Andreassen, O. A., Jenkins, B. al. (2000). Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J. Neurosci., 20, 4389–97CrossRefGoogle Scholar
Fisher, M. (1995). Potentially effective therapies for acute ischemic stroke. Eur. Neurol., 35, 3–7CrossRefGoogle ScholarPubMed
Frahm, J., Merboldt, K. D. & Hanicke, W. (1987). Localized proton spectroscopy using stimulated echoes. J. Magn. Reson., 72, 502–8Google Scholar
Frahm, J., Bruhn, H., Gyngell, M. L., Merboldt, K. D., Hanicke, W. & Sauter, R. (1989). Localized proton NMR spectroscopy in different regions of the human brain in vivo. Relaxation times and concentrations of cerebral metabolites. Magn. Reson. Med., 11, 47–63CrossRefGoogle ScholarPubMed
Gadian, D. G. & Radda, G. K. (1981). NMR studies of tissue metabolism. Annu. Rev. Biochem., 50, 69–83CrossRefGoogle ScholarPubMed
Granot, J. (1986). Selected volume spectroscopy using stimulated echoes (VEST). Application to spatially localized spectroscopy and imaging. J. Magn. Reson., 70Google Scholar
Gruetter, R., Novotny, E. J., Boulware, S. al. (1994). Localized 13C NMR spectroscopy in the human brain of amino acid labeling from D-[1-13C]glucose. J. Neurochem., 63, 1377–85CrossRefGoogle Scholar
Hahn, E. (1950). Spin echoes. Phys. Rev., 80, 580–94CrossRefGoogle Scholar
Harada, M., Tanouchi, M., Arai, K., Nishitani, H., Miyoshi, H. & Hashimoto, T. (1996). Therapeutic efficacy of a case of pyruvate dehydrogenase complex deficiency monitored by localized proton magnetic resonance spectroscopy. Magn. Reson. Imagin., 14, 129–33CrossRefGoogle ScholarPubMed
Hassel, B., Sonnewald, U. & Fonnum, F. (1995). Glial-neuronal interactions as studied by cerebral metabolism of [2–13C]acetate and [1-13C]glucose: an ex vivo 13C NMR spectroscopic study. J. Neurochem., 64, 2773–82CrossRefGoogle ScholarPubMed
Henshaw, R., Jenkins, B. G., Schulz, J. al. (1994). Malonate produces striatal lesions by indirect NMDA receptor activation. Brain Res., 647, 161–6CrossRefGoogle ScholarPubMed
Hetherington, H. P., Pan, J. W., Mason, G. al. (1996). Quantitative 1H spectroscopic imaging of human brain at 4.1 T using image segmentation. Magn. Reson. Med., 36, 21–9CrossRefGoogle Scholar
Higuchi, T., Fernandez, E. J., Maudsley, A. A., Shimizu, H., Weiner, M. W. & Weinstein, P. R. (1996). Mapping of lactate and N-acetyl-L-aspartate predicts infarction during acute focal ischemia: in vivo 1H magnetic resonance spectroscopy in rats. Neurosurgery, 38, 121–9; discussion 129–30CrossRefGoogle ScholarPubMed
Hilal, S. K., Maudsley, A. A., Simon, H. al. (1983). In vivo NMR imaging of tissue sodium in the intact cat before and after acute cerebral stroke. AJNR Am. J. Neuroradiol., 4, 245–9Google ScholarPubMed
Hoang, T. Q., Bluml, S., Dubowitz, D. al. (1998). Quantitative proton-decoupled 31P MRS and 1H MRS in the evaluation of Huntington's and Parkinson's diseases. Neurology, 50, 1033–40CrossRefGoogle ScholarPubMed
Holshouser, B. A., Komu, M., Moller, H. al. (1995). Localized proton NMR spectroscopy in the striatum of patients with idiopathic Parkinson's disease: a multicenter pilot study. Magn. Reson. Med., 33, 589–94CrossRefGoogle ScholarPubMed
Hossmann, K. A. (1994). Glutamate-mediated injury in focal cerebral ischemia: the excitotoxin hypothesis revised. Brain Pathol., 4, 23–36CrossRefGoogle ScholarPubMed
Hwang, J. H., Graham, G. D., Behar, K. L., Alger, J. R., Prichard, J. W. & Rothman, D. L. (1996). Short echo time proton magnetic resonance spectroscopic imaging of macromolecule and metabolite signal intensities in the human brain. Magn. Reson. Med., 35, 633–9CrossRefGoogle ScholarPubMed
Isaacks, R. E., Bender, A. S., Kim, C. Y., Shi, Y. F. & Norenberg, M. D. (1999). Effect of ammonia and methionine sulfoximine on myo-inositol transport in cultured astrocytes. Neurochem. Res., 24, 51–9CrossRefGoogle ScholarPubMed
Jenkins, B., Brouillet, E., Chen, al. (1996). Non-invasive neurochemical analysis of focal excitotoxic lesions in models of neurodegenerative illness using spectroscopic imaging. J. Cereb. Blood Flow Metab., 16, 450–61CrossRefGoogle ScholarPubMed
Jenkins B., Chen, Y. & Rosen, B. eds. (1997). Investigating the Neurochemistry and Etiology of Neurodegenrative Disorders using Magnetic Resonance Spectroscopy. New York, NY: Wiley-Liss
Jenkins, B. G. & Kraft, E. (1999). Magnetic resonance spectroscopy in toxic encephalopathy and neurodegeneration. Curr. Opin. Neurol., 12, 753–60CrossRefGoogle ScholarPubMed
Jenkins, B. G., Koroshetz, W. J., Beal, M. F. & Rosen, B. R. (1993). Evidence for impairment of energy metabolism in vivo in Huntington's disease using localized 1H NMR spectroscopy. Neurology, 43, 2689–95CrossRefGoogle ScholarPubMed
Jenkins, B. G., Burns, L., Pakzaban, P. et al. (1994). Spectroscopic studies of neurochemical changes in a primate model of neurodegeneration and neural transplantation. In: Society of Magnetic Resonance, p 1423. San Francisco
Jenkins, B. G., Rosas, H. D., Chen, Y. al. (1998). 1H NMR spectroscopy studies of Huntington's disease: correlations with CAG repeat numbers. Neurology, 50, 1357–65CrossRefGoogle ScholarPubMed
Jenkins, B. G., Klivenyi, P., Kustermann, al. (2000). Nonlinear decrease over time in N-acetyl aspartate levels in the absence of neuronal loss and increases in glutamine and glucose in transgenic Huntington's disease mice. J. Neurochem., 74, 2108–19CrossRefGoogle ScholarPubMed
Kalra, S., Cashman, N. R., Genge, A. & Arnold, D. L. (1998). Recovery of N-acetylaspartate in corticomotor neurons of patients with ALS after riluzole therapy. Neuroreport, 9, 1757–61CrossRefGoogle ScholarPubMed
Kalra, S., Arnold, D. L. & Cashman, N. R. (1999). Biological markers in the diagnosis and treatment of ALS. J. Neurol. Sci., 165 Suppl. 1, S27–32CrossRefGoogle ScholarPubMed
Kalyanapuram, R., Seshan, V. & Bansal, N. (1998). Three-dimensional triple-quantum-filtered 23Na imaging of the dog head in vivo. J. Magn. Reson. Imagin., 8, 1182–9CrossRefGoogle ScholarPubMed
Keller, J. N., Kindy, M. S., Holtsberg, F. al. (1998). Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction. J. Neurosci., 18, 687–97CrossRefGoogle ScholarPubMed
Kirschner, P. B., Jenkins, B. G., Schulz, J. al. (1996). NGF, BDNF and NT-5, but not NT-3 protect against MPP+ toxicity and oxidative stress in neonatal animals. Brain Res., 713, 178–85CrossRefGoogle Scholar
Klunk, W. E., Xu, C., Panchalingam, K., McClure, R. J. & Pettegrew, J. W. (1996). Quantitative 1H and. 31P MRS of PCA extracts of postmortem Alzheimer's disease brain. Neurobiol. Agin., 17, 349–57CrossRefGoogle ScholarPubMed
Kogure, T. & Kogure, K. (1997). Molecular and biochemical events within the brain subjected to cerebral ischemia (targets for therapeutical intervention). Clin. Neurosci., 4, 179–83Google Scholar
Kopito, R. R. (2000). Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol., 10, 524–30CrossRefGoogle ScholarPubMed
Koroshetz, W. J., Jenkins, B. G., Rosen, B. R. & Beal, M. F. (1997). Energy metabolism defects in Huntington's disease and effects of coenzyme Q10. Ann. Neurol., 41, 160–5CrossRefGoogle ScholarPubMed
Kuzniecky, R., Palmer, C., Hugg, al. (2001). Magnetic resonance spectroscopic imaging in temporal lobe epilepsy: neuronal dysfunction or cell loss?Arch. Neurol., 58, 2048–53CrossRefGoogle ScholarPubMed
Lebon, V., Petersen, K. F., Cline, G. al. (2002). Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism. J. Neurosci., 22, 1523–31CrossRefGoogle ScholarPubMed
Lee, W. T., Shen, Y. Z. & Chang, C. (2000). Neuroprotective effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid: evaluation by magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy. Neuroscience, 95, 89–95CrossRefGoogle ScholarPubMed
Lin, A. P., Shic, F., Enriquez, C. & Ross, B. D. (2003). Reduced glutamate neurotransmission in patients with Alzheimer's disease – an in vivo (13)C magnetic resonance spectroscopy study. Magma, 16, 29–42CrossRefGoogle Scholar
Lin, S. P., Song, S. K., Miller, J. P., Ackerman, J. J. & Neil, J. J. (2001). Direct, longitudinal comparison of (1)H and (23)Na MRI after transient focal cerebral ischemia. Stroke, 32, 925–32CrossRefGoogle ScholarPubMed
Lodi, R., Schapira, A. H., Manners, al. (2000). Abnormal in vivo skeletal muscle energy metabolism in Huntington's disease and dentatorubropallidoluysian atrophy. Ann. Neurol., 48, 72–63.0.CO;2-I>CrossRefGoogle ScholarPubMed
Magistretti, P. J. & Pellerin, L. (1997). Metabolic coupling during activation. A cellular view. Adv. Exp. Med. Biol., 413, 161–6CrossRefGoogle ScholarPubMed
Mason, G. F., Behar, K. L., Rothman, D. L. & Shulman, R. G. (1992). NMR determination of intracerebral glucose concentration and transport kinetics in rat brain. J. Cereb. Blood Flow Metab., 12, 448–55CrossRefGoogle ScholarPubMed
Mason, G. F., Pan, J. W., Ponder, S. L., Twieg, D. B., Pohost, G. M. & Hetherington, H. P. (1994). Detection of brain glutamate and glutamine in spectroscopic images at 4.1 T. Magn. Reson. Med., 32, 142–5CrossRefGoogle ScholarPubMed
Mason, G. F., Gruetter, R., Rothman, D. L., Behar, K. L., Shulman, R. G. & Novotny, E. J. (1995). Simultaneous determination of the rates of the TCA cycle, glucose utilization, alpha-ketoglutarate/glutamate exchange, and glutamine synthesis in human brain by NMR. J. Cereb. Blood Flow Metab., 15, 12–25CrossRefGoogle Scholar
Matthews, P. M., Ford, B., Dandurand, R. al. (1993). Coenzyme Q10 with multiple vitamins is generally ineffective in treatment of mitochondrial disease. Neurology, 43, 884–90CrossRefGoogle ScholarPubMed
Matthews, R. T., Yang, L., Jenkins, B. al. (1998). Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington's disease. J. Neurosci., 18, 156–63CrossRefGoogle ScholarPubMed
Pavlakis, S. G., Kingsley, P. B., Kaplan, G. P., Stacpoole, P. W., O'Shea, M. & Lustbader, D. (1998). Magnetic resonance spectroscopy: use in monitoring MELAS treatment. Arch. Neurol., 55, 849–52CrossRefGoogle ScholarPubMed
Penn, A. M., Roberts, T., Hodder, J., Allen, P. S., Zhu, G. & Martin, W. R. (1995). Generalized mitochondrial dysfunction in Parkinson's disease detected by magnetic resonance spectroscopy of muscle. Neurology, 45, 2097–9CrossRefGoogle ScholarPubMed
Petroff, O. A., Graham, G. D., Blamire, A. al. (1992). Spectroscopic imaging of stroke in humans: histopathology correlates of spectral changes. Neurology, 42, 1349–54CrossRefGoogle ScholarPubMed
Petroff, O. A., Pleban, L. A. & Spencer, D. D. (1995). Symbiosis between in vivo and in vitro NMR spectroscopy: the creatine, N-acetylaspartate, glutamate, and GABA content of the epileptic human brain. Magn. Reson. Imagin., 13, 1197–211CrossRefGoogle ScholarPubMed
Petroff, O. A., Errante, L. D., Rothman, D. L., Kim, J. H. & Spencer, D. D. (2002). Neuronal and glial metabolite content of the epileptogenic human hippocampus. Ann. Neurol., 52, 635–42CrossRefGoogle ScholarPubMed
Pettegrew, J. W., Klunk, W. E., Panchalingam, K., McClure, R. J. & Stanley, J. A. (1997). Magnetic resonance spectroscopic changes in Alzheimer's disease. Ann. NY Acad. Sci., 826, 282–306CrossRefGoogle ScholarPubMed
Pfeuffer, J., Tkac, I., Provencher, S. W. & Gruetter, R. (1999). Toward an in vivo neurochemical profile: quantification of 18 metabolites in short-echo-time (1)H NMR spectra of the rat brain. J. Magn. Reson., 141, 104–20CrossRefGoogle Scholar
Pioro, E. P., Majors, A. W., Mitsumoto, H., Nelson, D. R. & Ng, T. C. (1999). 1H-MRS evidence of neurodegeneration and excess glutamate + glutamine in ALS medulla. Neurology, 53, 71–9CrossRefGoogle ScholarPubMed
Podo, F. (1999). Tumour phospholipid metabolism. NMR Biomed., 12, 413–393.0.CO;2-U>CrossRefGoogle ScholarPubMed
Prichard, J., Rothman, D., Novotny, al. (1991). Lactate rise detected by 1H NMR in human visual cortex during physiologic stimulation. Proc. Natl Acad. Sci., USA, 88, 5829–31CrossRefGoogle ScholarPubMed
Provencher, S. W. (1993). Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn. Reson. Med., 30, 672–9CrossRefGoogle ScholarPubMed
Radda, G. K. (1992). Control, bioenergetics, and adaptation in health and disease: noninvasive biochemistry from nuclear magnetic resonance. FASEB J., 6, 3032–8CrossRefGoogle ScholarPubMed
Ross, B. D., Hoang, T. Q., Bluml, al. (1999). In vivo magnetic resonance spectroscopy of human fetal neural transplants. NMR Biomed., 12, 221–363.0.CO;2-Q>CrossRefGoogle ScholarPubMed
Rothstein, J. D., Kammen, M., Levey, A. I., Martin, L. J. & Kuncl, R. W. (1995). Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann. Neurol., 38, 73–84CrossRefGoogle ScholarPubMed
Rubio-Gozalbo, M. E., Heerschap, A., Trijbels, J. M., Meirleir, L. D., Thijssen, H. O. & Smeitink, J. A. (1999). Proton MR spectroscopy in a child with pyruvate dehydrogenase complex deficiency. Magn. Reson. Imagin., 17, 939–44CrossRefGoogle Scholar
Saunders, D. E. (2000). MR spectroscopy in stroke. Br. Med. Bull., 56, 334–45CrossRefGoogle ScholarPubMed
Schulz, J. B. & Dichgans, J. (1999). Molecular pathogenesis of movement disorders: are protein aggregates a common link in neuronal degeneration?Curr. Opin. Neurol., 12, 433–9CrossRefGoogle ScholarPubMed
Schulz, J. B., Matthews, R. T., Jenkins, B. G., Brar, P. & Beal, M. F. (1995a). Improved therapeutic window for treatment of histotoxic hypoxia with a free radical spin trap. J. Cereb. Blood Flow Metab., 15, 948–52CrossRefGoogle Scholar
Schulz, J. B., Henshaw, D. R., Siwek, al. (1995b). Involvement of free radicals in excitotoxicity in vivo. J. Neurochem., 64, 2239–47CrossRefGoogle Scholar
Schurr, A., West, C. A. & Rigor, B. M. (1988). Lactate-supported synaptic function in the rat hippocampal slice preparation. Science, 240, 1326–8CrossRefGoogle ScholarPubMed
Serles, W., Li, L. M., Antel, S. al. (2001). Time course of postoperative recovery of N-acetyl-aspartate in temporal lobe epilepsy. Epilepsia., 42, 190–7Google ScholarPubMed
Shonk, T. K., Moats, R. A., Gifford, al. (1995). Probable Alzheimer disease: diagnosis with proton MR spectroscopy [see comments]. Radiology, 195, 65–72CrossRefGoogle Scholar
Sibson, N. R., Dhankhar, A., Mason, G. F., Behar, K. L., Rothman, D. L. & Shulman, R. G. (1997). In vivo 13C NMR measurements of cerebral glutamine synthesis as evidence for glutamate-glutamine cycling. Proc. Natl Acad. Sci., USA, 94, 2699–704CrossRefGoogle ScholarPubMed
Siesjo, B. K. (1992). Pathophysiology and treatment of focal cerebral ischemia. Part II: Mechanisms of damage and treatment. J. Neurosurg., 77, 337–54CrossRefGoogle ScholarPubMed
Signoretti, S., Marmarou, A., Fatouros, al. (2002). Application of chemical shift imaging for measurement of NAA in head injured patients. Acta. Neurochir. Suppl., 81, 373–5Google ScholarPubMed
Simmons, M., Frandoza, C. & Coyle, J. (1991). Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience, 45, 37–45CrossRefGoogle ScholarPubMed
Smith, J. K., Castillo, M. & Kwock, L. (2003). MR spectroscopy of brain tumors. Magn. Reson. Imaging Clin. N. Am., 11, 415–29, v–viCrossRefGoogle ScholarPubMed
Sotak, C. H. & Alger, J. R. (1991). A pitfall associated with lactate detection using stimulated-echo proton spectroscopy. Magn. Reson. Med., 17, 533–8CrossRefGoogle ScholarPubMed
Storey, E., Hyman, B., Jenkins, al. (1992). MPP+ produces excitotoxic lesions in rat striatum due to impairment of oxidative metabolism. J. Neurochem., 58, 1271–8CrossRefGoogle ScholarPubMed
Tanabe, J. L., Vermathen, M., Miller, R., Gelinas, D., Weiner, M. W. & Rooney, W. D. (1998). Reduced MTR in the corticospinal tract and normal T2 in amyotrophic lateral sclerosis. Magn. Reson. Imagin., 16, 1163–9CrossRefGoogle ScholarPubMed
Taylor, D. L., Davies, S. E., Obrenovitch, T. al. (1995). Investigation into the role of N-acetylaspartate in cerebral osmoregulation. J. Neurochem., 65, 275–81CrossRefGoogle ScholarPubMed
Terao, S., Sobue, G., Yasuda, T., Kachi, T., Takahashi, M. & Mitsuma, T. (1995). Magnetic resonance imaging of the corticospinal tracts in amyotrophic lateral sclerosis. J. Neurol. Sci., 133, 66–72CrossRefGoogle ScholarPubMed
Thulborn, K. R., Gindin, T. S., Davis, D. & Erb, P. (1999). Comprehensive MR imaging protocol for stroke management: tissue sodium concentration as a measure of tissue viability in nonhuman primate studies and in clinical studies. Radiology, 213, 156–66CrossRefGoogle ScholarPubMed
Thurston, J. H., Sherman, W. R., Hauhart, R. E. & Kloepper, R. F. (1989). Myo-inositol: a newly identified nonnitrogenous osmoregulatory molecule in mammalian brain. Pediatr. Res., 26, 482–5CrossRefGoogle ScholarPubMed
Tkac, I., Andersen, P., Adriany, G., Merkle, H., Ugurbil, K. & Gruetter, R. (2001). In vivo 1H NMR spectroscopy of the human brain at 7 T. Magn. Reson. Med., 46, 451–6CrossRefGoogle Scholar
Urenjak, J., Williams, S. R., Gadian, D. G. & Noble, M. (1992). Specific expression of N-acetylaspartate in neurons, oligodendrocyte-type-2 astrocyte progenitors, and immature oligodendrocytes in vitro. J. Neurochem., 59, 55–61CrossRefGoogle ScholarPubMed
Urenjak, J., Williams, S. R., Gadian, D. G. & Noble, M. (1993). Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J. Neurosci., 13, 981–9CrossRefGoogle ScholarPubMed
Zijl, P. C., Davis, D., Eleff, S. M., Moonen, C. T., Parker, R. J. & Strong, J. M. (1997). Determination of cerebral glucose transport and metabolic kinetics by dynamic MR spectroscopy. Am. J. Physiol., 273, E1216–27Google ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the or variations. ‘’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats