Neurotherapeutics

, Volume 4, Issue 3, pp 330–345

Recent advances in magnetic resonance neurospectroscopy

Article

Summary

Over the past two decades, proton magnetic resonance spectroscopy (proton MRS) of the brain has made the transition from research tool to a clinically useful modality. In this review, we first describe the localization methods currently used in MRS studies of the brain and discuss the technical and practical factors that determine the applicability of the methods to particular clinical studies. We also describe each of the resonances detected by localized solvent-suppressed proton MRS of the brain and discuss the metabolic and biochemical information that can be derived from an analysis of their concentrations. We discuss spectral quantitation and summarize the reproducibility of both single-voxel and multivoxel methods at 1.5 and 3–4 T. We have selected three clinical neurologic applications in which there has been a consensus as to the diagnostic value of MRS and summarize the information relevant to clinical applications. Finally, we speculate about some of the potential technical developments, either in progress or in the future, that may lead to improvements in the performance of proton MRS.

Key Words

Metabolism MR spectroscopy Alzheimer’s disease epilepsy brain tumors reproducibility 

References

  1. 1.
    Burt CT, Cohen SM, Barany M. Analysis of intact tissue with 31P MR. Annu Rev Biophys Bioeng 1979;8: 1–25.PubMedCrossRefGoogle Scholar
  2. 2.
    Burt CT, Wyrwicz AM. Phosphorus-31 nuclear magnetic-resonance observations in biological-systems I. Intact tissue. Trends Biochem Sci 1979;4: 244–246.CrossRefGoogle Scholar
  3. 3.
    Kuchel PW. Nuclear magnetic-resonance of biological samples. CRC Crit Rev Anal Chem 1981;12: 155–231.Google Scholar
  4. 4.
    Roberts JKM, Jardetzky O. Monitoring of cellular-metabolism by NMR. Biochim Biophys Acta 1981;639: 53–76.PubMedGoogle Scholar
  5. 5.
    Gadian DG, Radda GK. NMR studies of tissue metabolism. Annu Rev Biochem 1981;50: 69–83.PubMedCrossRefGoogle Scholar
  6. 6.
    Iles RA, Stevens AN, Griffiths JR. NMR studies of metabolites in living tissue. Prog NMR Spectrosc 1982;15: 49–200.CrossRefGoogle Scholar
  7. 7.
    Bernard M, Canioni P, Cozzone PJ. Study of in vivo cellular metabolism by phosphorus 31 nuclear magnetic resonance [In French]. Biochimie 1983;65: 449–470.PubMedCrossRefGoogle Scholar
  8. 8.
    Radda GK, Taylor DJ. Applications of nuclear magnetic-resonance spectroscopy in pathology. Int Rev Exp Pathol 1985;27: 1–58.PubMedGoogle Scholar
  9. 9.
    Avison MJ, Hetherington HP, Shulman RG. Applications of NMR to studies of tissue metabolism. Annu Rev Biophys Biophys Chem 1986;15: 377–402.PubMedCrossRefGoogle Scholar
  10. 10.
    Bottomley PA. Human in vivo NMR spectroscopy in diagnostic medicine: clinical tool or research probe? Radiology 1989;170: 1–15.PubMedGoogle Scholar
  11. 11.
    Cerdan S, Seelig J. NMR studies of metabolism. Annu Rev Biophys Biophys Chem 1990;19: 43–67.PubMedCrossRefGoogle Scholar
  12. 12.
    Allen PS. In vivo nuclear magnetic resonance spectroscopy applied to medicine. Can Assoc Radiol J 1990;41: 39–44.PubMedGoogle Scholar
  13. 13.
    Ruizcabello J, Cohen JS. NMR and the study of pathological state in cells and tissues. Int Rev Cytol 1993;145: 1–63.CrossRefGoogle Scholar
  14. 14.
    Bottomley PA, Edelstein WA, Foster TH, Adams WA. In vivo solvent-suppressed localized hydrogen nuclear magnetic resonance spectroscopy: a window to metabolism? Proc Natl Acad Sci U S A 1985;82: 2148–2152.PubMedCrossRefGoogle Scholar
  15. 15.
    Frahm J, Bruhn H, Gyngell ML, Merboldt KD, Hanicke W, Sauter R. Localized proton NMR spectroscopy in different regions of the human brain in vivo: relaxation times and concentrations of cerebral metabolites. Magn Reson Med 1989;11: 47–63.PubMedCrossRefGoogle Scholar
  16. 16.
    Frahm J, Michaelis T, Merboldt KD, et al. Localized NMR spectroscopy in vivo: progress and problems. NMR Biomed 1989;2: 188–195.PubMedCrossRefGoogle Scholar
  17. 17.
    Behar KL, den Hollander JA, Stromski ME, et al. High-resolution 1H nuclear magnetic resonance study of cerebral hypoxia in vivo. Proc Natl Acad Sci U S A 1983;80: 4945–4948.PubMedCrossRefGoogle Scholar
  18. 18.
    Luyten PR, den Hollander JA. Observation of metabolites in the human brain by MR spectroscopy. Radiology 1986;161: 795–798.PubMedGoogle Scholar
  19. 19.
    Hanstock CC, Rothman DL, Richard JW, Jue T, Shulman RG. Spatially localized 1H NMR spectra of metabolites in the human brain. Proc Natl Acad Sci U S A 1988;85: 1821–1825.PubMedCrossRefGoogle Scholar
  20. 20.
    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.PubMedCrossRefGoogle Scholar
  21. 21.
    Bolinger L, Lenkinski RE. Localization in clinical NMR spectroscopy. In Berliner LJ, Reuben J, editors. Biological magnetic resonance. New York: Plenum Press, 1992: 1–53.Google Scholar
  22. 22.
    Aue WP. Localization methods for in vivo nuclear magnetic resonance spectroscopy. Rev Magn Reson Med 1986;1: 21–72.Google Scholar
  23. 23.
    Narayana PA, DeLayre JL. Localization methods in NMR. In: Partain CL, Price RR, Patton JA, Kulkami MV, James AE, editors. Magnetic resonance imaging. 2nd ed, Vol 11. Physical principles and instrumentation. Philadelphia: W.B. Saunders, 1988: 1609–1630.Google Scholar
  24. 24.
    Keevil SF. Spatial localization in nuclear magnetic resonance spectroscopy. Phys Med Biol 2006;51: R579-R636.PubMedCrossRefGoogle Scholar
  25. 25.
    Gillard JH, Waldman AD, Barker PB, editors. Clinical neuroimaging: diffusion, perfusion and spectroscopy. New York: Cambridge University Press, 2005.Google Scholar
  26. 26.
    Barker PB, Lin DDM. In vivo proton MR spectroscopy of the human brain. Prog NMR Spectrosc 2006;49: 99–128.CrossRefGoogle Scholar
  27. 27.
    Lentz MR, Taylor JL, Feldman DA, Cheng LL. Current clinical applications of in vivo magnetic resonance spectroscopy and spectroscopic imaging. Curr Med Imaging Rev 2005;1: 271–301.CrossRefGoogle Scholar
  28. 28.
    Ross BD, Coletti P, Lin A. Magnetic resonance spectroscopy of the brain: neurospectroscopy. In Edelman RR, Hesselink JR, Zlatkin MB, Crues JV, editors. Clinical magnetic resonance imaging, 3rd ed. Philadelphia: Saunders, 2006: 1840–1901.Google Scholar
  29. 29.
    Moonen CT, von Kienlin M, van Zijl PC, et al. Comparison of single-shot localization methods (STEAM and PRESS) for in vivo proton NMR spectroscopy. NMR Biomed 1989;2: 201–208.PubMedCrossRefGoogle Scholar
  30. 30.
    Yongbi NM, Payne GS, Collins DJ, Leach MO. Quantification of signal selection efficiency, extra volume suppression and contamination for ISIS, STEAM and PRESS localized 1H NMR spectroscopy using an EEC localization test object. Phys Med Biol 1995;40: 1293–1303.PubMedCrossRefGoogle Scholar
  31. 31.
    Shinnar M, Leigh JS. The application of spinors to pulse synthesis and analysis. Magn Reson Med 1989;12: 93–98.PubMedCrossRefGoogle Scholar
  32. 32.
    Shinnar M, Bolinger L, Leigh JS. The synthesis of soft pulses with a specified frequency response. Magn Reson Med 1989;12: 88–92.PubMedCrossRefGoogle Scholar
  33. 33.
    Shinnar M, Bolinger L, Leigh JS. The use of finite impulse response filters in pulse design. Magn Reson Med 1989; 12: 81–87.PubMedCrossRefGoogle Scholar
  34. 34.
    Shinnar M, Eleff S, Subramanian H, Leigh JS. The synthesis of pulse sequences yielding arbitrary magnetization vectors. Magn Reson Med 1989;12: 74–80.PubMedCrossRefGoogle Scholar
  35. 35.
    Spielman D, Pauly J, Macovski A, Enzmann D. Spectroscopic imaging with multidimensional pulses for excitation: SIMPLE. Magn Reson Med 1991;19: 67–84.PubMedCrossRefGoogle Scholar
  36. 36.
    Pauly J, Leroux P, Nishimura D, Macovski A. Parameter relations for the Shinnar-Leroux selective excitation pulse design algorithm. IEEE Trans Med Imaging 1991;10: 53–65.PubMedCrossRefGoogle Scholar
  37. 37.
    Chan F, Pauly J, Macovski A. Effects of RF amplifier distortion on selective excitation and their correction by prewarping. Magn Reson Med 1992;23: 224–238.PubMedCrossRefGoogle Scholar
  38. 38.
    Conolly S, Pauly J, Nishimura D, Macovski A. Two-dimensional selective adiabatic pulses. Magn Reson Med 1992;24: 302–313.PubMedCrossRefGoogle Scholar
  39. 39.
    Shinnar M. Reduced power selective excitation radio frequency pulses. Magn Reson Med 1994;32: 658–660.PubMedCrossRefGoogle Scholar
  40. 40.
    Tran TKC, Vigneron DB, Sailasuta N, et al. Very selective suppression pulses for clinical MRSI studies of brain and prostate cancer. Magn Reson Med 2000;43: 23–33.PubMedCrossRefGoogle Scholar
  41. 41.
    Gonen O, Murdoch JB, Stoyanova R, Goelman G. 3D multivoxel proton spectroscopy of human brain using a hybrid of 8th-order Hadamard encoding with 2D chemical shift imaging. Magn Reson Med 1998;39: 34–40.PubMedCrossRefGoogle Scholar
  42. 42.
    Gonen O, Catalaa I, Babb JS, et al. Total brain N-acetylaspartate: a new measure of disease load in MS. Neurology 2000;54: 15–19.PubMedGoogle Scholar
  43. 43.
    Pohmann R, von Kienlin M, Haase A. Theoretical evaluation and comparison of fast chemical shift imaging methods. J Magn Reson 1997;129: 145–160.PubMedCrossRefGoogle Scholar
  44. 44.
    Brown MA. Time-domain combination of MR spectroscopy data acquired using phased-array coils. Magn Reson Med 2004;52: 1207–1213.PubMedCrossRefGoogle Scholar
  45. 45.
    Maril N, Lenkinski RE. An automated algorithm for combining multivoxel MRS data acquired with phased-array coils. J Magn Reson Imaging 2005;21: 317–322.PubMedCrossRefGoogle Scholar
  46. 46.
    Roemer PB, Edelstein WA, Hayes CE, Souza SP, Mueller OM. The NMR phased array. Magn Reson Med 1990;16: 192–225.PubMedCrossRefGoogle Scholar
  47. 47.
    Ross B, Bluml S. Magnetic resonance spectroscopy of the human brain. Anat Rec 2001;265: 54–84.PubMedCrossRefGoogle Scholar
  48. 48.
    Lopez Villegas D, Lenkinski RE, Wehrli SL, Ho WZ, Douglas SD. Lactate production by human monocytes macrophages determined by proton MR spectroscopy. Magn Reson Med 1995; 34: 32–38.PubMedCrossRefGoogle Scholar
  49. 49.
    Tallan HH, Moore S, Stein WH. N-Acetyl-l-aspartic acid in brain. J Biol Chem 1956;219: 257–264.PubMedGoogle Scholar
  50. 50.
    Birken DL, Oldendorf WH. N-Acetyl-l-aspartic acid: a literature-review of a compound prominent in 1H-NMR spectroscopic studies of brain. Neurosci Biobehav Rev 1989;13: 23–31.PubMedCrossRefGoogle Scholar
  51. 51.
    Simmons ML, Frondoza CG, Coyle JT. Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 1991;45: 37–45.PubMedCrossRefGoogle Scholar
  52. 52.
    Martin E, Capone A, Schneider J, Hennig J, Thiel T. Absence of N-acetylaspartate in the human brain: impact on neurospectroscopy? Ann Neurol 2001;49: 518–521.PubMedCrossRefGoogle Scholar
  53. 53.
    Sullivan EV, Adalsteinsson E, Spielman DM, Hurd RE, Pfefferbaum A. N-Acetylaspartate: a marker of neuronal integrity. Ann Neurol 2001;50: 823–823.PubMedCrossRefGoogle Scholar
  54. 54.
    Barker PB. N-Acetyl aspartate: a neuronal marker? Ann Neurol 2001;49: 423–424.PubMedCrossRefGoogle Scholar
  55. 55.
    Martin E, Thiel T, Capone A, Henning J, Schneider J. N-Acetylaspartate: usefulness as an indicator of viable neuronal tissue—Reply. Ann Neurol 2001;50: 824–825.CrossRefGoogle Scholar
  56. 56.
    Baslow MH. Brain N-acetylaspartate as a molecular water pump and its role in the etiology of Canavan disease: a mechanistic explanation. Mol Neurosci 2003;21: 185–189.CrossRefGoogle Scholar
  57. 57.
    Baslow MH. N-Acetylaspartate in the vertebrate brain: metabolism and function. Neurochem Res 2003;28: 941–953.PubMedCrossRefGoogle Scholar
  58. 58.
    Baslow MH. 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 2002;40: 295–300.PubMedCrossRefGoogle Scholar
  59. 59.
    Bluml S, McComb JG, Ross BD. Differentiation between cortical atrophy and hydrocephalus using 1H MRS. Magn Reson Med 1997;37: 395–403.PubMedCrossRefGoogle Scholar
  60. 60.
    Mason GF, Pan JW, Ponder SL, Twieg DB, Pohost GM, Hetherington HP. Detection of brain glutamate and glutamine in spectroscopic images at 4.1 T. Magn Reson Med 1994;32: 142–145.PubMedCrossRefGoogle Scholar
  61. 61.
    JW, Pan, Mason GF, Pohost GM, Hetherington HP. Spectroscopic imaging of human brain glutamate by water-suppressed J-refocused coherence transfer at 4.1 T. Magn Reson Med 1996;36: 7–12.PubMedCrossRefGoogle Scholar
  62. 62.
    Ugurbil K, Adriany G, Andersen P, et al. Ultrahigh field magnetic resonance imaging and spectroscopy. Magn Reson Imaging 2003; 21: 1263–1281.PubMedCrossRefGoogle Scholar
  63. 63.
    Tkac I, Rao R, Georgieff MK, Gruetter R. Developmental and regional changes in the neurochemical profile of the rat brain determined by in vivo 1H NMR spectroscopy. Magn Reson Med 2003;50: 24–32.PubMedCrossRefGoogle Scholar
  64. 64.
    Srinivasan R, Cunningham C, Chen A, et al. TE-averaged two-dimensional proton spectroscopic imaging of glutamate at 3 T. Neuroimage 2006;30: 1171–1178.PubMedCrossRefGoogle Scholar
  65. 65.
    Sibson NR, Dhankhar A, Mason GF, Rothman DL, Behar KL, Shulman RG. Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity. Proc Natl Acad Sci U S A 1998;95: 316–321.PubMedCrossRefGoogle Scholar
  66. 66.
    Magistretti PJ, Pellerin L, Rothman DL, Shulman RG. Energy on demand. Science 1999;283: 496–497.PubMedCrossRefGoogle Scholar
  67. 67.
    Srinivasan R, Sailasuta N, Hurd R, Nelson S, Pelletier D. Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T. Brain 2005;128: 1016–1025.PubMedCrossRefGoogle Scholar
  68. 68.
    Ross BD, Jacobson S, Villamil F, et al. Subclinical hepatic encephalopathy: proton MR spectroscopic abnormalities. Radiology 1994;193: 457–463.PubMedGoogle Scholar
  69. 69.
    Shawcross DL, Balata S, Damink S, et al. Low myo-inositol and high glutamine levels in brain are associated with neuropsychological deterioration after induced hyperammonemia. Am J Physiol Gastrointest Liver Physiol 2004;287: G503-G509.PubMedCrossRefGoogle Scholar
  70. 70.
    Mechtcheriakov S, Schocke M, Kugener A, et al. Chemical shift magnetic resonance spectroscopy of cingulate grey matter in patients with minimal hepatic encephalopathy. Neuroradiology 2005;47: 27–34.PubMedCrossRefGoogle Scholar
  71. 71.
    Kreis R, Pfenninger J, Herschkowitz N, Boesch C. In vivo proton magnetic resonance spectroscopy in a case of Reye’s syndrome. Intensive Care Med 1995;21: 266–269.PubMedCrossRefGoogle Scholar
  72. 72.
    Moore CM, Wardrop M, Frederick BD, Renshaw PF. Topiramate raises anterior cingulate cortex glutamine levels in healthy men; a 4.0 T magnetic resonance spectroscopy study. Psychopharmacology 2006;188: 236–243.PubMedCrossRefGoogle Scholar
  73. 73.
    Keltner JR, Wald LL, Christensen JD, et al. A technique for detecting GABA in the human brain with PRESS localization and optimized refocusing spectral editing radiofrequency pulses. Magn Reson Med 1996;36: 458–461.PubMedCrossRefGoogle Scholar
  74. 74.
    Keltner JR, Wald LL, Frederick BD, Renshaw PF. In vivo detection of GABA in human brain using a localized double-quantum filter technique. Magn Reson Med 1997;37: 366–371.PubMedCrossRefGoogle Scholar
  75. 75.
    Hetherington HP, Newcomer BR, Pan JW. Measurements of human cerebral GABA at 4.1 T using numerically optimized editing pulses. Magn Reson Med 1998;39: 6–10.PubMedCrossRefGoogle Scholar
  76. 76.
    Kuzniecky R, Hetherington H, Ho S, et al. Topiramate increases cerebral GABA in healthy humans. Neurology 1998;51: 627–629.PubMedGoogle Scholar
  77. 77.
    Ke Y, Cohen BM, Bang JY, Yang MQ, Renshaw PF. Assessment of GABA concentration in human brain using two-dimensional proton magnetic resonance spectroscopy. Psychiatry Res 2000; 100: 169–178.PubMedCrossRefGoogle Scholar
  78. 78.
    Kuzniecky R, Ho S, Pan J, et al. Modulation of cerebral GABA by topiramate, lamotrigine, and gabapentin in healthy adults. Neurology 2002;58: 368–372.PubMedGoogle Scholar
  79. 79.
    Ke Y, Streeter CC, Nassar LE, et al. Frontal lobe GABA levels in cocaine dependence: a two-dimensional, J-resolved magnetic resonance spectroscopy study. Psychiatry Res 2004; 130: 283–293.PubMedCrossRefGoogle Scholar
  80. 80.
    Jensen JE, Frederick BD, Renshaw PF. Grey and white matter GABA level differences in the human brain using two-dimensional, J-resolved spectroscopic imaging. NMR Biomed 2005;18: 570–576.PubMedCrossRefGoogle Scholar
  81. 81.
    Jensen JE, Frederick BD, Wang LQ, Brown J, Renshaw PF. Two-dimensional, J-resolved spectroscopic imaging of GABA at 4 tesla in the human brain. Magn Reson Med 2005;54: 783–788.PubMedCrossRefGoogle Scholar
  82. 82.
    Streeter CC, Hennen J, Ke Y, et al. Prefrontal GABA levels in cocaine-dependent subjects increase with pramipexole and venlafaxine treatment. Psychopharmacology 2005;182: 516–526.PubMedCrossRefGoogle Scholar
  83. 83.
    Ross BD, Bluml S. New aspects of brain physiology. NMR Biomed 1996;9: 279–296.PubMedCrossRefGoogle Scholar
  84. 84.
    Hanefeld F, Holzbach U, Kruse B, Wilichowski E, Christen HJ, Frahm J. Diffuse white matter disease in three children: an encephalopathy with unique features on magnetic resonance imaging and proton magnetic resonance spectroscopy. Neuropediatrics 1993;24: 244–248.PubMedCrossRefGoogle Scholar
  85. 85.
    Miller BL. A review of chemical issues in 1H NMR spectroscopy: N-acetyl-l-aspartate, creatine and choline. NMR Biomed 1991;4: 47–52.PubMedCrossRefGoogle Scholar
  86. 86.
    Gill SS, Small RK, Thomas DG, et al. Brain metabolites as 1H NMR markers of neuronal and glial disorders. NMR Biomed 1989;2: 196–200.PubMedCrossRefGoogle Scholar
  87. 87.
    Gill SS, Thomas DG, Van Bruggen N, et al. Proton MR spectroscopy of intracranial tumours: in vivo and in vitro studies. J Comput Assist Tomogr 1990;14: 497–504.PubMedCrossRefGoogle Scholar
  88. 88.
    Kotitschke K, Jung H, Nekolla S, Haase A, Bauer A, Bogdahn U. High-resolution one- and two-dimensional 1H MRS of human brain tumor and normal glial cells. NMR Biomed 1994;7: 111–120.PubMedCrossRefGoogle Scholar
  89. 89.
    Matthews PM, Francis G, Antel J, Arnold DL. Proton magnetic resonance spectroscopy for metabolic characterization of plaques in multiple sclerosis. Neurology 1991;41: 1251–1256.PubMedGoogle Scholar
  90. 90.
    Venkatesh SK, Gupta RK, Pal L, Husain N, Husain M. Spectroscopic increase in choline signal is a nonspecific marker for differentiation of infective/inflammatory from neoplastic lesions of the brain. J Magn Reson Imaging 2001;14: 8–15.PubMedCrossRefGoogle Scholar
  91. 91.
    Brenner RE, Munro PM, Williams SC, et al. The proton NMR spectrum in acute EAE: the significance of the change in the Cho:Cr ratio. Magn Reson Med 1993;29: 737–745.PubMedCrossRefGoogle Scholar
  92. 92.
    Butteriss DJA, Ismail A, Ellison DW, Birchall D. Use of serial proton magnetic resonance spectroscopy to differentiate low grade glioma from tumefactive plaque in a patient with multiple sclerosis. Br J Radiol 2003;76: 662–665.PubMedCrossRefGoogle Scholar
  93. 93.
    Law M, Meltzer DE, Cha S. Spectroscopic magnetic resonance imaging of a tumefactive demyelinating lesion. Neuroradiology 2002;44: 986–989.PubMedCrossRefGoogle Scholar
  94. 94.
    Saindane AM, Cha S, Law M, Xue X, Knopp EA, Zagzag D. Proton MR Spectroscopy of tumefactive demyelinating lesions. Am J Neuroradiol 2002;23: 1378–1386.PubMedGoogle Scholar
  95. 95.
    Ernst T, Chang L, Walot I, Huff K. Physiologic MRI of a tumefactive multiple sclerosis lesion. Neurology 1998;51: 1486–1488.PubMedGoogle Scholar
  96. 96.
    Negendank W. Studies of human tumors by MRS: a review. NMR Biomed 1992;5: 303–324.PubMedCrossRefGoogle Scholar
  97. 97.
    Aboagye EO, Bhujwalla ZM. Malignant transformation alters membrane choline phospholipid metabolism of human mammary epithelial cells. Cancer Res 1999;59: 80–84.PubMedGoogle Scholar
  98. 98.
    Podo F. Tumour phospholipid metabolism. NMR Biomed 1999; 12: 413–439.PubMedCrossRefGoogle Scholar
  99. 99.
    Kwock L, Smith JK, Castillo M, et al. Clinical applications of proton MR spectroscopy in oncology. Technol Cancer Res Treat 2002;1: 17–28.PubMedGoogle Scholar
  100. 100.
    Smith JK, Castillo M, Kwock L. MR spectroscopy of brain tumors. Magn Reson Imaging Clin N Am 2003;11: 415–429, v-vi.PubMedCrossRefGoogle Scholar
  101. 101.
    Nelson SJ. Magnetic resonance spectroscopic imaging. Evaluating responses to therapy for gliomas. IEEE Eng Med Biol Mag 2004;23: 30–39.PubMedCrossRefGoogle Scholar
  102. 102.
    Alger JR. MR Spectroscopy of brain tumors in adults. In Gillard JH, Waldman AD, Barker PB, editors. Clinical MR neuroimaging: diffusion, perfusion and spectroscopy. New York: Cambridge University Press, 2005: 288–311.Google Scholar
  103. 103.
    Kwock L, Smith JK, Castillo M, et al. Clinical role of proton magnetic resonance spectroscopy in oncology: brain, breast, and prostate cancer. Lancet Oncol 2006;7: 859–868.PubMedCrossRefGoogle Scholar
  104. 104.
    Font C, García-Campos M, Hansen AJ, Siemkowicz E, Gjedde A. Simultaneous diffusion of inositol and mannitol in the rat brain [In Spanish]. Rev Esp Fisiol 1982;38: 317–319.PubMedGoogle Scholar
  105. 105.
    Brand A, Richter-Landsberg C, Leibfritz D. Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci 1993;15: 289–298.PubMedCrossRefGoogle Scholar
  106. 106.
    Strange K, Emma F, Paredes A, Morrison R. Osmoregulatory changes in myo-inositol content and Na+/myo-inositol cotransport in rat cortical astrocytes. Glia 1994;12: 35–43.PubMedCrossRefGoogle Scholar
  107. 107.
    Kruse B, Hanefeld F, Christen HJ, et al. Alterations of brain metabolites in metachromatic leukodystrophy as detected by localized proton magnetic resonance spectroscopy in vivo. J Neurol 1993;241: 68–74.PubMedCrossRefGoogle Scholar
  108. 108.
    Jansen JF, Backes WH, Nicolay K, Kooi ME. 1H MR spectroscopy of the brain: absolute quantification of metabolites. Radiology 2006;240: 318–332.PubMedCrossRefGoogle Scholar
  109. 109.
    Hennig J, Pfister H, Ernst T, Ott D. Direct absolute quantification of metabolites in the human brain with invivolLocalized proton spectroscopy. NMR Biomed 1992;5: 193–199.PubMedCrossRefGoogle Scholar
  110. 110.
    Kreis R, Ernst T, Ross BD. Absolute quantitation of water and metabolites in the human brain. 2. Metabolite concentrations. J Cardiovasc Magn Reson Ser B 1993;102: 9–19.CrossRefGoogle Scholar
  111. 111.
    Ernst T, Kreis R, Ross BD. Absolute quantitation of water and metabolites in the human brain. 1. Compartments and water. J Cardiovasc Magn Reson Ser B 1993;102: 1–8.CrossRefGoogle Scholar
  112. 112.
    Kreis R, Emst T, Ross BD. Development of the human brain: in vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy. Magn Reson Med 1993;30: 424–437.PubMedCrossRefGoogle Scholar
  113. 113.
    Helms G. A precise and user-independent quantification technique for regional comparison of single volume proton MR spectroscopy of the human brain. NMR Biomed 2000;13: 398–406.PubMedCrossRefGoogle Scholar
  114. 114.
    Helms G. Volume collection for edema in single-volume proton MR spectroscopy of contrast-enhancing multiple sclerosis lesions. Magn Reson Med 2001;46: 256–263.PubMedCrossRefGoogle Scholar
  115. 115.
    Knight-Scott J, Haley AP, Rossmiller SR, et al. Molality as a unit of measure for expressing 1H MRS brain metabolite concentrations in vivo. Magn Reson Imaging 2003;21: 787–797.PubMedCrossRefGoogle Scholar
  116. 116.
    Horska A, Calhoun VD, Bradshaw DH, Barker PB. Rapid method for collection of CSF partial volume in quantitative proton MR spectroscopic imaging. Magn Reson Med 2002;48: 555–558.PubMedCrossRefGoogle Scholar
  117. 117.
    Zandt H, van der Graaf M, Heerschap A. Common processing of in vivo MR spectra. NMR Biomed 2001;14: 224–232.CrossRefGoogle Scholar
  118. 118.
    Vanhamme L, Sundin T, Van Hecke P, Van Huffel S. MR spectroscopy quantitation: a review of time-domain methods. NMR Biomed 2001;14: 233–246.PubMedCrossRefGoogle Scholar
  119. 119.
    Mierisova S, Ala-Korpela M. MR spectroscopy quantitation: a review of frequency domain methods. NMR Biomed 2001;14: 247–259.PubMedCrossRefGoogle Scholar
  120. 120.
    Provencher SW. Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed 2001;14: 260–264.PubMedCrossRefGoogle Scholar
  121. 121.
    McLean MA, Woermann FG, Simister RJ, Barker GJ, Duncan JS. In vivo short echo time 1H-magnetic resonance spectroscopic imaging (MRSI) of the temporal lobes. Neuroimage 2001;14: 501–509.PubMedCrossRefGoogle Scholar
  122. 122.
    McLean MA, Woermann FG, Barker GJ, Duncan JS. Quantitative analysis of short echo time 1H-MRSI of cerebral gray and white matter. Magn Reson Med 2000;44: 401–411.PubMedCrossRefGoogle Scholar
  123. 123.
    Webb PG, Sailasuta N, Kohler SJ, Raidy T, Moats RA, Hurd RE. Automated single-voxel proton MRS: technical development and multisite verification. Magn Reson Med 1994;31: 365–373.PubMedCrossRefGoogle Scholar
  124. 124.
    Venkatraman TN, Hamer RM, Perkins DO, Song AW, Lieberman JA, Steen RG. Single-voxel 1H PRESS at 4.0 T: precision and variability of measurements in anterior cingulate and hippocampus. NMR Biomed 2006;19: 484–491.PubMedCrossRefGoogle Scholar
  125. 125.
    Macri MA, Garreffa G, Giove F, et al. In vivo quantitative 1H MRS of cerebellum and evaluation of quantitation reproducibility by simulation of different levels of noise and spectral resolution. Magn Reson Imaging 2004;22: 1385–1393.PubMedCrossRefGoogle Scholar
  126. 126.
    Kubo H, Harada M, Sakama M, Nishitani H. Reproducibility of metabolite concentration evaluated by intraclass correlation coefficient using clinical MR apparatus. J Comput Assist Tomogr 2003;27: 449–453.PubMedCrossRefGoogle Scholar
  127. 127.
    Hsu YY, Chen MC, Lim KE, Chang C. Reproducibility of hippocampal single-voxel proton MR spectroscopy and chemical shift imaging. AJR Am J Roentgenol 2001;176: 529–536.PubMedGoogle Scholar
  128. 128.
    Bartha R, Drost DJ, Menon RS, Williamson PC. Comparison of the quantification precision of human short echo time H1 spectroscopy at 1.5 and 4.0 tesla. Magn Reson Med 2000;44: 185–192.PubMedCrossRefGoogle Scholar
  129. 129.
    Schirmer T, Auer DP. On the reliability of quantitative clinical magnetic resonance spectroscopy of the human brain. NMR Biomed 2000;13: 28–36.PubMedCrossRefGoogle Scholar
  130. 130.
    Simmons A, Smail M, Moore E, Williams SCR. Serial precision of metabolite peak area ratios and water referenced metabolite peak areas in proton MR spectroscopy of the human brain. Magn Reson Imaging 1998;16: 319–330.PubMedCrossRefGoogle Scholar
  131. 131.
    Stanley JA, Drost DJ, Williamson PC, Thompson RT. The use of a priori knowledge to quantify short echo in vivo 1H MR spectra. Magn Reson Med 1995;34: 17–24.PubMedCrossRefGoogle Scholar
  132. 132.
    Provencher SW. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 1993; 30: 672–679.PubMedCrossRefGoogle Scholar
  133. 133.
    Narayana PA, Johnston D, Flamig DP. In vivo proton magnetic resonance spectroscopy studies of human brain. Magn Reson Imaging 1991;9: 303–308.PubMedCrossRefGoogle Scholar
  134. 134.
    Christiansen P, Henriksen O, Stubgaard M, Gideon P, Larsson HB. In vivo quantification of brain metabolites by 1H-MRS using water as an internal standard. Magn Reson Imaging 1993;11: 107–118.PubMedCrossRefGoogle Scholar
  135. 135.
    Michaelis T, Merboldt KD, Bruhn H, Hanicke W, Frahm J. Absolute concentrations of metabolites in the adult human brain in vivo: quantification of localized proton MR spectra. Radiology 1993;187: 219–227.PubMedGoogle Scholar
  136. 136.
    Danielsen ER, Henriksen O. Absolute quantitative proton NMR spectroscopy based on the amplitude of the local water suppression pulse: quantification of brain water and metabolites. NMR Biomed 1994;7: 311–318.PubMedCrossRefGoogle Scholar
  137. 137.
    Marshall I, Wardlaw J, Cannon J, Slattery J, Sellar RJ. Reproducibility of metabolite peak areas in 1H MRS of brain. Magn Reson Med 1996;14: 281–292.Google Scholar
  138. 138.
    Brooks WM, Friedman SD, Stidley CA. Reproducibility of 1H-MRS in vivo. Magn Reson Med 1999;41: 193–197.PubMedCrossRefGoogle Scholar
  139. 139.
    Choi CG, Frahm J. Localized proton MRS of the human hippocampus: metabolite concentrations and relaxation times. Magn Reson Med 1999;41: 204–207.PubMedCrossRefGoogle Scholar
  140. 140.
    Helms G. Analysis of 1.5 tesla proton MR spectra of human brain using LCModel and an imported basis set. Magn Reson Imaging 1999;17: 1211–1218.PubMedCrossRefGoogle Scholar
  141. 141.
    Mullins PG, Rowland L, Bustillo J, Bedrick EJ, Lauriello J, Brooks WM. Reproducibility of 1H-MRS measurements in schizophrenic patients. Magn Reson Med 2003;50: 704–707.PubMedCrossRefGoogle Scholar
  142. 142.
    Sigmundsson T, Maier M, Toone BK, et al. Frontal lobe N-acetylaspartate correlates with psychopathology in schizophrenia: a proton magnetic resonance spectroscopy study. Schizophr Res 2003;64: 63–71.PubMedCrossRefGoogle Scholar
  143. 143.
    Geurts JJG, Barkhof F, Castelijns JA, Uitdehaag BMJ, Polman CH, Pouwels PJW. Quantitative 1H-MRS of healthy human cortex, hippocampus, and thalamus: metabolite concentrations, quantification precision, and reproducibility. J Magn Reson Imaging 2004;20: 366–371.PubMedCrossRefGoogle Scholar
  144. 144.
    Komoroski RA, Kotrla KJ, Lernen L, Lindquist D, Diaz P, Foundas A. Brain metabolite concentration ratios in vivo: multisite reproducibility by single-voxel 1H MR spectroscopy. Magn Reson Imaging 2004;22: 721–725.PubMedCrossRefGoogle Scholar
  145. 145.
    Steen RG, Hamer RM, Lieberman JA. Measurement of brain metabolites by 1H magnetic resonance spectroscopy in patients with schizophrenia: a systematic review and meta-analysis. Neuropsychopharmacology 2005;30: 1949–1962.PubMedCrossRefGoogle Scholar
  146. 146.
    Michael N, Gosling M, Reutemann M, et al. Metabolic changes after repetitive transcranial magnetic stimulation (rTMS) of the left prefrontal cortex: a sham-controlled proton magnetic resonance spectroscopy (1H MRS) study of healthy brain. Eur J Neurosci 2003;17: 2462–2468.PubMedCrossRefGoogle Scholar
  147. 147.
    Hammen T, Stadlbauer A, Tomandl B, et al. Short TE single-voxel 1H-MR spectroscopy of hippocampal structures in healthy adults at 1.5 tesla: how reproducible are the results? NMR Biomed 2005;18: 195–201.PubMedCrossRefGoogle Scholar
  148. 148.
    Wellard RM, Briellmann RS, Jennings C, Jackson GD. Physiologic variability of single-voxel proton MR spectroscopic measurements at 3T. AJNR Am J Neuroradiol 2005;26: 585–590.PubMedGoogle Scholar
  149. 149.
    Soreni N, Noseworthy MD, Cormier T, Oakden WK, Bells S, Schachar R. Intraindividual variability of striatal (1)H-MRS brain metabolite measurements at 3 T. Magn Reson Imaging 2006;24: 187–194.PubMedCrossRefGoogle Scholar
  150. 150.
    Jayasundar R, Raghunathan P. Evidence for left-right asymmetries in the proton MRS of brain in normal volunteers. Magn Reson Imaging 1997;15: 223–234.PubMedCrossRefGoogle Scholar
  151. 151.
    Ricci PE, Pitt A, Keller PJ, Coons SW, Heiserman JE. Effect of voxel position on single-voxel MR spectroscopy findings. AJNR Am J Neuroradiol 2000;21: 367–374.PubMedGoogle Scholar
  152. 152.
    Jayasundar R. Human brain: biochemical lateralization in normal subjects. Neurol India 2002;50: 267–271.PubMedGoogle Scholar
  153. 153.
    Inglese M, Spindler M, Babb JS, Sunenshine P, Law M, Gonen O. Field, coil, and echo-time influence on sensitivity and reproducibility of brain proton MR spectroscopy. AJNR Am J Neuroradiol 2006;27: 684–688.PubMedGoogle Scholar
  154. 154.
    Srinivasan R, Vigneron D, Sailasuta N, Hurd R, Nelson S. A comparative study of myo-inositol quantification using LCmodel at 1.5 T and 3.0 T with 3 D 1H proton spectroscopic imaging of the human brain. Magn Reson Imaging 2004;22: 523–528.PubMedCrossRefGoogle Scholar
  155. 155.
    Marshall I, Wardlaw J, Graham C, Murray L, Blane A. Repeatability of long and short echo-time in vivo proton chemical-shift imaging. Neuroradiology 2002;44: 973–980.PubMedCrossRefGoogle Scholar
  156. 156.
    Chard DT, McLean MA, Parker GJM, MacManus DG, Miller DH. Reproducibility of in vivo metabolite quantification with proton magnetic resonance spectroscopic imaging. J Magn Reson Imaging 2002;15: 219–225.PubMedCrossRefGoogle Scholar
  157. 157.
    Li BSY, Babb JS, Soher BJ, Maudsley AA, Gonen O. Reproducibility of 3D proton spectroscopy in the human brain. Magn Reson Med 2002;47: 439–446.PubMedCrossRefGoogle Scholar
  158. 158.
    Wiedermann D, Schuff N, Matson GB, et al. Short echo time multislice proton magnetic resonance spectroscopic imaging in human brain: metabolite distributions and reliability. Magn Reson Imaging 2001;19: 1073–1080.PubMedCrossRefGoogle Scholar
  159. 159.
    Maton B, Londono A, Sawrie S, Knowlton R, denHollander J, Kuzniecky R. Reproducibility of proton magnetic resonance spectroscopy imaging measurements of normal human hippocampus at 1.5 T: clinical implications. J Neuroimaging 2001;11: 194–201.PubMedCrossRefGoogle Scholar
  160. 160.
    Narayana PA, Doyle TJ, Lai DJ, Wolinsky JS. Serial proton magnetic resonance spectroscopic imaging, contrast-enhanced magnetic resonance imaging, and quantitative lesion volumetry in multiple sclerosis. Ann Neurol 1998;43: 56–71.PubMedCrossRefGoogle Scholar
  161. 161.
    Tedeschi G, Bertolino A, Campbell G, et al. Reproducibility of proton MR spectroscopic imaging findings. AJNR Am J Neuroradiol 1996;17: 1871–1879.PubMedGoogle Scholar
  162. 162.
    Charles HC, Lazeyras F, Tupler LA, Krishnan KRR. Reproducibility of high spatial resolution proton magnetic resonance spectroscopic imaging in the human brains. Magn Reson Med 1996; 35: 606–610.PubMedCrossRefGoogle Scholar
  163. 163.
    Bertolino A, Callicott JH, Nawroz S, et al. Reproducibility of proton magnetic resonance spectroscopic imaging in patients with schizophrenia. Neuropsychopharmacology 1998;18: 1–9.PubMedCrossRefGoogle Scholar
  164. 164.
    Jackson EF, Doyle TJ, Wolinsky JS, Narayana PA. Short TE hydrogen-1 spectroscopic MR imaging of normal human brain: reproducibility studies. J Magn Reson Imaging 1994;4: 545–551.PubMedCrossRefGoogle Scholar
  165. 165.
    Lenkinski RE. High-field magnetic resonance imaging. In: Edelman RR, Hesselink JR, Zlatkin MB, Crues JV 3rd, editors. Clinical magnetic resonance imaging. Philadelphia: Saunders Elsevier, 2006: 493–511.Google Scholar
  166. 166.
    Tkac I, Andersen P, Adriany G, Merkle H, Ugurbil K, Gruetter R. In vivo 1H NMR spectroscopy of the human brain at 7 T. Magn Reson Med 2001;46: 451–456.PubMedCrossRefGoogle Scholar
  167. 167.
    Barker PB, Hearshen DO, Boska MD. Single-voxel proton MRS of the human brain at 1.5T and 3.0T. Magn Reson Med 2001;45: 765–769.PubMedCrossRefGoogle Scholar
  168. 168.
    Gonen O, Gruber S, Li BSY, Mlynarik V, Moser E. Multivoxel 3D proton spectroscopy in the brain at 1.5 versus 3.0 T: signal-to-noise ratio and resolution comparison. AJNR Am J Neuroradiol 2001;22: 1727–1731.PubMedGoogle Scholar
  169. 169.
    Li BSY, Regal J, Gonen O. SNR versus resolution in 3D 1H MRS of the human brain at high magnetic fields. Magn Reson Med 2001;46: 1049–1053.PubMedCrossRefGoogle Scholar
  170. 170.
    Lenkinski RE. MR spectroscopy. In Filippi M, De Stefano N, Dousset V, McGowan JC, editors. MR imaging in white matter diseases of the brain and spinal cord. New York: Springer, 2005: 288–311.Google Scholar
  171. 171.
    Mandai PK. Magnetic resonance spectroscopy (MRS) and its application in Alzheimer disease, concepts in magnetic resonance Part A 2007;30A: 40–64.Google Scholar
  172. 172.
    Soher BJ, Doraiswamy PM, Charles HC. A review of 1H MR spectroscopy findings in Alzheimer’s disease. Neuroimaging Clin N Am 2005; 15: 847–852.PubMedCrossRefGoogle Scholar
  173. 173.
    Miller BL, Moats RA, Shonk T, Ernst T, Woolley S, Ross BD. Alzheimer disease: depiction of increased cerebral myo-inositol with proton MR spectroscopy. Radiology 1993;187: 433–437.PubMedGoogle Scholar
  174. 174.
    Kantarci K, Petersen RC, Boeve BF, et al. 1H MR spectroscopy in common dementias. Neurology 2004;63: 1393–1398.PubMedGoogle Scholar
  175. 175.
    den Heijer T, Sijens PE, Prins ND, et al. MR spectroscopy of brain white matter in the prediction of dementia. Neurology 2006; 66: 540–544.CrossRefGoogle Scholar
  176. 176.
    Metastasio A, Rinaldi P, Tarducci R, et al. Conversion of MCI to dementia: role of proton magnetic resonance spectroscopy. Neurobiol Aging 2006;27: 926–932.PubMedCrossRefGoogle Scholar
  177. 177.
    Kantarci K, Smith GE, Ivnik RJ, et al. 1H Magnetic resonance spectroscopy, cognitive function, and apolipoprotein E genotype in normal aging, mild cognitive impairment and Alzheimer’s disease. J Int Neuropsychol Soc 2002;8: 934–942.PubMedCrossRefGoogle Scholar
  178. 178.
    Doraiswamy PM, Charles HC, Krishnan KRR. Prediction of cognitive decline in early Alzheimer’s disease. Lancet 1998;352: 1678–1678.PubMedCrossRefGoogle Scholar
  179. 179.
    Ross AJ, Sachdev PS. Magnetic resonance spectroscopy in cognitive research. Brain Res Rev 2004;44: 83–102.PubMedCrossRefGoogle Scholar
  180. 180.
    Briellmann RS, Wellard RM, Jackson GD. MR Spectroscopy in seizure disorders. In: Gillard JH, Waldman AD, Barker PB, editors. Clinical MR neuroimaging: diffusion, perfusion and spectroscopy. New York: Cambridge University Press, 2005: 488–508.Google Scholar
  181. 181.
    Connelly A, Jackson GD, Duncan JS, King MD, Gadian DG. Magnetic resonance spectroscopy in temporal lobe epilepsy. Neurology 1994;44: 1411–1417.PubMedGoogle Scholar
  182. 182.
    Wellard RM, Briellmann RS, Prichard JW, Syngeniotis A, Jackson GD. Myoinositol abnormalities in temporal lobe epilepsy. Epilepsia 2003;44: 815–821.PubMedCrossRefGoogle Scholar
  183. 183.
    Hammen T, Schwarz M, Doelken M, et al. 1H-MR spectroscopy indicates severity markers in temporal lobe epilepsy: correlations between metabolic alterations, seizures, and epileptic discharges in EEG. Epilepsia 2007;48: 263–269.PubMedCrossRefGoogle Scholar
  184. 184.
    Garcia PA, Laxer KD, van der Grond J, Hugg JW, Matson GB, Weiner MW. Correlation of seizure frequency with N-acetyl-aspartate levels determined by 1H magnetic resonance spectroscopic imaging. Magn Reson Imaging 1997;15: 475–478.PubMedCrossRefGoogle Scholar
  185. 185.
    Series W, Li LM, Caramanos Z, Arnold DL, Gotman J. Relation of interictal spike frequency to 1H-MRSI-measured NAA/Cr. Epilepsia 1999;40: 1821–1827.CrossRefGoogle Scholar
  186. 186.
    Park SA, Kim GS, Lee SK, et al. Interictal epileptiform discharges relate to 1H-MRS-detected metabolic abnormalities in mesial temporal lobe epilepsy. Epilepsia 2002;43: 1385–1389.PubMedCrossRefGoogle Scholar
  187. 187.
    Willmann O, Wennberg R, May T, Woermann FG, Pohlmann-Eden B. The role of 1H magnetic resonance spectroscopy in pre-operative evaluation for epilepsy surgery: a meta-analysis. Epilepsy Res 2006;71: 149–158.PubMedCrossRefGoogle Scholar
  188. 188.
    Hammen T, Kerling F, Schwarz M, et al. Identifying the affected hemisphere by 1H-MR spectroscopy in patients with temporal lobe epilepsy and no pathological findings in high resolution MRI. Eur J Neurol 2006;13: 482–490.PubMedCrossRefGoogle Scholar
  189. 189.
    Hollingworth W, Medina LS, Lenkinski RE, et al. A systematic literature review of magnetic resonance spectroscopy for the characterization of brain tumors. AJNR Am J Neuroradiol 2006;27: 1404–1411.PubMedGoogle Scholar
  190. 190.
    Moller-Hartmann W, Herminghaus S, Krings T, et al. Clinical application of proton magnetic resonance spectroscopy in the diagnosis of intracranial mass lesions. Neuroradiology 2002;44: 371–381.PubMedCrossRefGoogle Scholar
  191. 191.
    Posse S, DeCarli C, Le Bihan D. Three-dimensional echo-planar MR spectroscopic imaging at short echo times in the human brain. Radiology 1994;192: 733–738.PubMedGoogle Scholar
  192. 192.
    Posse S, Tedeschi G, Risinger R, Ogg R, Le Bihan D. High speed 1H spectroscopic imaging in human brain by echo planar spatial-spectral encoding. Magn Reson Med 1995;33: 34–40.PubMedCrossRefGoogle Scholar
  193. 193.
    Adalsteinsson E, Irarrazabal P, Spielman DM, Macovski A. Three-dimensional spectroscopic imaging with time-varying gradients. Magn Reson Med 1995;33: 461–466.PubMedCrossRefGoogle Scholar
  194. 194.
    Thomas MA, Binesh N, Yue K, DeBruhl N. Volume-localized two-dimensional correlated magnetic resonance spectroscopy of human breast cancer. J Magn Reson Imaging 2001;14: 181–186.PubMedCrossRefGoogle Scholar
  195. 195.
    Thomas MA, Ryner LN, Mehta MP, Turski PA, Sorenson JA. Localized 2D J-resolved 1H MR spectroscopy of human brain tumors in vivo. J Magn Reson Imaging 1996;6: 453–459.PubMedCrossRefGoogle Scholar
  196. 196.
    Thomas MA, Yue K, Binesh N, et al. Localized two-dimensional shift correlated MR spectroscopy of human brain. Magn Reson Med 2001;46: 58–67.PubMedCrossRefGoogle Scholar
  197. 197.
    Frydman L, Lupulescu A, Scherf T. Principles and features of single-scan two-dimensional NMR spectroscopy. J Am Chem Soc 2003;125: 9204–9217.PubMedCrossRefGoogle Scholar
  198. 198.
    Mishkovsky M, Frydman L. Interlaced Fourier transformation of ultrafast 2D NMR data. J Magn Reson 2005;173: 344–350.PubMedCrossRefGoogle Scholar
  199. 199.
    Sela N, Degani H, Frydman L. Ultrafast 2D NMR spectroscopy using sinusoidal gradients: principles and ex vivo brain investigations. Magn Reson Med 2004;52: 893–897.PubMedCrossRefGoogle Scholar
  200. 200.
    Shapira B, Frydman L. Spatially encoded pulse sequences for the acquisition of high resolution NMR spectra in inhomogeneous fields. J Magn Reson 2006;182: 12–21.PubMedCrossRefGoogle Scholar
  201. 201.
    Shrot Y, Frydman L. Single-scan NMR spectroscopy at arbitrary dimensions. J Am Chem Soc 2003;125: 11385–11396.PubMedCrossRefGoogle Scholar
  202. 202.
    Shrot Y, Shapira B, Frydman L. Ultrafast 2D NMR spectroscopy using a continuous spatial encoding of the spin interactions. J Magn Reson 2004;171: 163–170.PubMedCrossRefGoogle Scholar
  203. 203.
    Ardenkjaer-Larsen JH, Fridlund B, Gram A, et al. Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR. Proc Natl Acad Sci U S A 2003;100: 10158–10163.PubMedCrossRefGoogle Scholar
  204. 204.
    Golman K, Ardenkjaer-Larsen JH, Petersson JS, Mansson S, Leunbach I. Molecular imaging with endogenous substances. Proc Natl Acad Sci U S A 2003;100: 10435–10439.PubMedCrossRefGoogle Scholar
  205. 205.
    Golman K, Zandt RI, Thaning M. Real-time metabolic imaging. Proc Natl Acad Sci U S A 2006;103: 11270–11275.PubMedCrossRefGoogle Scholar
  206. 206.
    Golman K, Olsson LE, Axelsson O, Mansson S, Karlsson M, Petersson JS. Molecular imaging using hyperpolarized 13C. Br J Radiol 2003;76 Spec No 2: S118–127.Google Scholar
  207. 207.
    Golman K, Petersson JS. Metabolic imaging and other applications of hyperpolarized 13C. Acad Radiol 2006;13: 932–942.PubMedCrossRefGoogle Scholar
  208. 208.
    Golman K, Zandt RI, Lerche M, Pehrson R, Ardenkjaer-Larsen JH. Metabolic imaging by hyperpolarized 13C magnetic resonance imaging for in vivo tumor diagnosis. Cancer Res 2006;66: 10855–10860.PubMedCrossRefGoogle Scholar
  209. 209.
    Mansson S, Johansson E, Magnusson P, et al. 13C imaging: a new diagnostic platform. Eur Radiol 2006;16: 57–67.PubMedCrossRefGoogle Scholar

Copyright information

© Springer New York 2007

Authors and Affiliations

  1. 1.Department of Radiology, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBoston

Personalised recommendations