Differences in iron and manganese concentration may confound the measurement of myelin from R1 and R2 relaxation rates in studies of dysmyelination

NMR in Biomedicine

Volumn 29, Issue 7, 2016, Pages 985-998

  Desmond, Kimberly L ^a,b   Al Ebraheem, Alia ^a   Janik, Rafal ^b,c   Oakden, Wendy ^b,c   Kwiecien, Jacek M ^a,d   Dabrowski, Wojciech ^d   Rola, Radoslaw ^d   Geraki, Kalotina ^e   Farquharson, Michael J ^a   Stanisz, Greg J ^b,c,d   Bock, Nicholas A ^a  

^a MCMASTER UNIVERSITY   (Canada)

^b Institute of Clinical Evaluative Sciences   (Canada)

^c UNIVERSITY OF TORONTO   (Canada)

^d MEDICAL UNIVERSITY OF LUBLIN   (Poland)

^e DIAMOND LIGHT SOURCE LTD   (United Kingdom)

Author keywords

cerebellum; iron; les; manganese; micro synchrotron radiation X ray fluorescence ( SRSRF); myelin; relaxometry; Shaker

Indexed keywords

BRAIN; COPYRIGHTS; FLUORESCENCE; IRON; MANGANESE; PARAMAGNETISM; SYNCHROTRON RADIATION; SYNCHROTRONS; TISSUE; TISSUE ENGINEERING; X RAYS;

CEREBELLUM; MYELIN; RELAXOMETRY; SHAKER; SYNCHROTRON RADIATION X-RAY FLUORESCENCE;

RATE CONSTANTS;

IRON; MANGANESE; MYELIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN LEVEL; CONTROLLED STUDY; IN VIVO STUDY; MALE; MYELIN DEFICIENCY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; NUCLEAR MAGNETIC RESONANCE SCANNER; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; RAT; SYNCHROTRON RADIATION; WHITE MATTER; X RAY FLUORESCENCE;

EID: 84974799112     PISSN: 09523480     EISSN: 10991492     Source Type: Journal    
DOI: 10.1002/nbm.3549     Document Type: Article

References (118)

1. Koenig SH. Cholesterol of myelin is the determinant of gray–white contrast in MRI of brain. Magn. Reson. Med. 1991; 20(2): 285–291.
2. Kucharczyk W, Macdonald P, Stanisz G, Henkelman RM. Relaxivity and magnetization transfer of white matter lipids at MR imaging: importance of cerebrosides and pH. Radiology 1994; 192(2): 521–529.
3. Koenig S, Brown R, Spiller M, Lundbom N. Relaxometry of brain: why white matter appears bright in MRI. Magn. Reson. Med. 1990; 14(3): 482–495.
4. Paus T, Collins D, Evans A, Leonard G, Pike B, Zijdenbos A. Maturation of white matter in the human brain: a review of magnetic resonance studies. Brain Res. Bull. 2001; 54(3): 255–266.
5. Barkovich AJ. Concepts of myelin and myelination in neuroradiology. Am. J. Neuroradiol. 2000; 21(6): 1099–1109.
6. Samsonov A, Alexander AL, Mossahebi P, Wu Y-C, Duncan ID, Field AS. Quantitative MR imaging of two-pool magnetization transfer model parameters in myelin mutant shaking pup. Neuroimage 2012; 62(3): 1390–1398.
7. Holland BA, Haas DK, Norman D, Brant-Zawadzki M, Newton TH. MRI of normal brain maturation. Am. J. Neuroradiol. 1986; 7(2): 201–208.
8. Laule C, Leung E, Li DK, Traboulsee A, Paty D, MacKay A, Moore GR. Myelin water imaging in multiple sclerosis: quantitative correlations with histopathology. Mult. Scler. 2006; 12(6): 747–753.
9. Flynn S, Lang D, Mackay A, Goghari V, Vavasour I, Whittall K, Smith G, Arango V, Mann J, Dwork A. Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte proteins. Mol. Psychiatry 2003; 8(9): 811–820.
10. Miot-Noirault E, Barantin L, Akoka S, le Pape A. T2 relaxation time as a marker of brain myelination: experimental MR study in two neonatal animal models. J. Neurosci. Methods 1997; 72(1): 5–14.
11. Stanisz G, Kecojevic A, Bronskill M, Henkelman R. Characterizing white matter with magnetization transfer and T2. Magn. Reson. Med. 1999; 42(6): 1128–1136.
12. Kwiecien J, O'connor L, Goetz B, Delaney K. Morphological and morphometric studies of the dysmyelinating mutant, the Long Evans shaker rat. J. Neurocytol. 1998; 27(8): 581–591.
13. Kwiecien JM. Cellular compensatory mechanisms in the CNS of dysmyelinated rats. Comp. Med. 2010; 60(3): 205.
14. Chernoff GF. Shiverer: an autosomal recessive mutant mouse with myelin deficiency. J. Hered. 1981; 72(2): 128.
15. O'Connor JPB, Jackson A, Asselin MC, Buckley DL, Parker GJM, Jayson GC. Quantitative imaging biomarkers in the clinical development of targeted therapeutics: current and future perspectives. Lancet Oncol. 2008; 9(8): 766–776.
16. Rosenbluth J. Peripheral myelin in the mouse mutant Shiverer. J. Comp. Neurol. 1980; 193(3): 729–739.
17. Yangho K. Neuroimaging in manganism. Neurotoxicology 2006; 27(3): 369–372.
18. Hasan KM, Walimuni IS, Kramer LA, Narayana PA. Human brain iron mapping using atlas-based T2 relaxometry. Magn. Reson. Med. 2012; 67(3): 731–739.
19. Moldovan N, Al-Ebraheem A, Lobo L, Park R, Farquharson MJ, Bock NA. Altered transition metal homeostasis in the cuprizone model of demyelination. Neurotoxicology 2015; 48: 1–8.
20. Aspli KT, Flaten TP, Roos PM, Holmøy T, Skogholt JH, Aaseth J. Iron and copper in progressive demyelination–new lessons from Skogholt's disease. J. Trace Elem. Med. Biol. 2015; 31: 183–187.
21. Prodan C, Holland N, Wisdom P, Burstein S, Bottomley S. CNS demyelination associated with copper deficiency and hyperzincemia. Neurology 2002; 59(9): 1453–1456.
22. Popescu G, Florin B, Nichol H. Mapping brain metals to evaluate therapies for neurodegenerative disease. CNS Neurosci. Ther. 2011; 17(4): 256–268.
23. Merkler D, Boretius S, Stadelmann C, Ernsting T, Michaelis T, Frahm J, Brück W. Multicontrast MRI of remyelination in the central nervous system. NMR Biomed. 2005; 18(6): 395–403.
24. Barkhof F, Brück W, de Groot CJ, Bergers E, Hulshof S, Geurts J, Polman CH, van der Valk P. Remyelinated lesions in multiple sclerosis: magnetic resonance image appearance. Arch. Neurol. 2003; 60(8): 1073–1081.
25. LeVine SM. Iron deposits in multiple sclerosis and Alzheimer's disease brains. Brain Res. 1997; 760(1): 298–303.
26. Khalil M, Enzinger C, Langkammer C, Tscherner M, Wallner-Blazek M, Jehna M, Ropele S, Fuchs S, Fazekas F. Quantitative assessment of brain iron by R2* relaxometry in patients with clinically isolated syndrome and relapsing–remitting multiple sclerosis. Mult. Scler. 2009; 15(9): 1048–1054.
27. Melø TM, Larsen C, White LR, Aasly J, Sjøbakk TE, Flaten TP, Sonnewald U, Syversen T. Manganese, copper, and zinc in cerebrospinal fluid from patients with multiple sclerosis. Biol. Trace Elem. Res. 2003; 93(1–3): 1–8.
28. Gouw A, Seewann A, Vrenken H, van der Flier W, Rozemuller J, Barkhof F, Scheltens P, Geurts J. Heterogeneity of white matter hyperintensities in Alzheimer's disease: post-mortem quantitative MRI and neuropathology. Brain 2008; 131(12): 3286–3298.
29. Adlard PA, Bush AI. Metals and Alzheimer's disease. J. Alzheimers Dis. 2006; 10(2, 3): 145–163.
30. Braak H, Ghebremedhin E, Rüb U, Bratzke H, del Tredici K. Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res. 2004; 318(1): 121–134.
31. Dexter D, Wells F, Lee A, Agid F, Agid Y, Jenner P, Marsden C. Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson's disease. J. Neurochem. 1989; 52(6): 1830–1836.
32. Rosas HD, Lee SY, Bender AC, Zaleta AK, Vangel M, Yu P, Fischl B, Pappu V, Onorato C, Cha J-H. Altered white matter microstructure in the corpus callosum in Huntington's disease: implications for cortical “disconnection”. Neuroimage 2010; 49(4): 2995–3004.
33. Stoffers D, Sheldon S, Kuperman J, Goldstein J, Corey-Bloom J, Aron A. Contrasting gray and white matter changes in preclinical Huntington disease. An MRI study. Neurology 2010; 74(15): 1208–1216.
34. Rosas HD, Chen YI, Doros G, Salat DH, Chen N-k, Kwong KK, Bush A, Fox J, Hersch SM. Alterations in brain transition metals in Huntington disease: an evolving and intricate story. Arch. Neurol. 2012; 69(7): 887–893.
35. Bartzokis G, Lu PH, Tishler TA, Fong SM, Oluwadara B, Finn JP, Huang D, Bordelon Y, Mintz J, Perlman S. Myelin breakdown and iron changes in Huntington's disease: pathogenesis and treatment implications. Neurochem. Res. 2007; 32(10): 1655–1664.
36. Bloch F. Nuclear induction. Phys. Rev. 1946; 70(7–8): 460–474.
37. Gelman N, Ewing JR, Gorell JM, Spickler EM, Solomon EG. Interregional variation of longitudinal relaxation rates in human brain at 3.0 T: relation to estimated iron and water contents. Magn. Reson. Med. 2001; 45(1): 71–79.
38. 2O relaxation in vivo. Magn. Reson. Med. 2007; 57(2): 308–318.
39. Vymazal J, Righini A, Brooks RA, Canesi M, Mariani C, Leonardi M, Pezzoli G. T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: relation to iron content 1. Radiology 1999; 211(2): 489–495.
40. Whittall KP, Mackay AL, Graeb DA, Nugent RA, Li DK, Paty DW. In vivo measurement of T2 distributions and water contents in normal human brain. Magn. Reson. Med. 1997; 37(1): 34–43.
41. Bakker C, Vriend J. Multi-exponential water proton spin–lattice relaxation in biological tissues and its implications for quantitative NMR imaging. Phys. Med. Biol. 1984; 29(5): 509.
42. Does MD, Beaulieu C, Allen PS, Snyder RE. Multi-component T1 relaxation and magnetisation transfer in peripheral nerve. Magn. Reson. Imaging 1998; 16(9): 1033–1041.
43. Deichmann R, Adolf H, Kuchenbrod E, Nöth U, Schwarzbauer C, Haase A. Compensation of diffusion effects in T2 measurements. Magn. Reson. Med. 1995; 33(1): 113–115.
44. Oakden W, Stanisz GJ. Effects of diffusion on high-resolution quantitative T2 MRI. NMR Biomed. 2014; 27(6): 672–680.
45. Bailey C, Giles A, Czarnota GJ, Stanisz GJ. Detection of apoptotic cell death in vitro in the presence of Gd-DTPA-BMA. Magn. Reson. Med. 2009; 62(1): 46–55.
46. Landis CS, Li X, Telang FW, Molina PE, Palyka I, Vetek G, Springer CS. Equilibrium transcytolemmal water-exchange kinetics in skeletal muscle in vivo. Magn. Reson. Med. 1999; 42(3): 467–478.
47. Morrison C, Stanisz G, Henkelman RM. Modeling magnetization transfer for biological-like systems using a semi-solid pool with a super-Lorentzian lineshape and dipolar reservoir. J. Magn. Reson. B 1995; 108(2): 103–113.
48. Kwiecien JM, Blanco M, Fox JG, Delaney KH, Fletch AL. Neuropathology of bouncer Long Evans, a novel dysmyelinated rat. Comp. Med. 2000; 50(5): 503–510.
49. Karlsen OT, Verhagen R, Bovée WMMJ. Parameter estimation from Rician-distributed data sets using a maximum likelihood estimator: application to T1 and perfusion measurements. Magn. Reson. Med. 1999; 41(3): 614–623.
50. Vidarsson L, Conolly SM, Lim KO, Gold GE, Pauly JM. Echo time optimization for linear combination myelin imaging. Magn. Reson. Med. 2005; 53(2): 398–407.
51. Mackay A, Whittall K, Adler J, Li D, Paty D, Graeb D. In vivo visualization of myelin water in brain by magnetic resonance. Magn. Reson. Med. 1994; 31(6): 673–677.
52. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. Academic Press: Boston, MA, 2007.
53. Solé V, Papillon E, Cotte M, Walter P, Susini J. A multiplatform code for the analysis of energy-dispersive X-ray fluorescence spectra. Spectrochim. Acta, Part B: Atom. Spectrosc. 2007; 62(1): 63–68.
54. Falzon G, Pearson S, Murison R, Hall C, Siu K, Round A, Schültke E, Kaye A, Lewis R. Myelin structure is a key difference in the x-ray scattering signature between meningioma, schwannoma and glioblastoma multiforme. Phys. Med. Biol. 2007; 52(21): 6543.
55. Al-Ebraheem A, Miller L, Geraki K, Desmond KL, Bock NA, Farquharson MJ. Transition metal distribution in the brain and spinal cord of a rat model of myelin loss. In Procedings of the 23rd International Congress on X-ray Optics and Microanalysis (ICXOM23). Long Island: New York, 2015.
56. Minty EP, Bjarnason TA, Laule C, MacKay AL. Myelin water measurement in the spinal cord. Magn. Reson. Med. 2009; 61(4): 883–892.
57. House MJ, St Pierre TG, McLean C. 1.4 T study of proton magnetic relaxation rates, iron concentrations, and plaque burden in Alzheimer's disease and control postmortem brain tissue. Magn. Reson. Med. 2008; 60(1): 41–52.
58. Bock NA, Paiva FF, Nascimento GC, Newman JD, Silva AC. Cerebrospinal fluid to brain transport of manganese in a non-human primate revealed by MRI. Brain Res. 2008; 1198: 160–170.
59. Zhang N, Fitsanakis VA, Erikson KM, Aschner M, Avison MJ, Gore JC. A model for the analysis of competitive relaxation effects of manganese and iron in vivo. NMR Biomed. 2009; 22(4): 391–404.
60. Delaney KH, Kwiecien JM, Wegiel J, Wisniewski HM, Percy DH, Fletch AL. Familial dysmyelination in a Long Evans rat mutant. Lab. Anim. Sci. 1995; 45(5): 547–553.
61. Biddle F, March E, Miller JH. Research news. Mouse News Lett. 1971; 48: 24.
62. Venturini G. Enzymic activities and sodium, potassium and copper concentrations in mouse brain and liver after cuprizone treatment in vivo. J. Neurochem. 1973; 21(5): 1147–1151.
63. Zatta P, Raso M, Zambenedetti P, Wittkowski W, Messori L, Piccioli F, Mauri P, Beltramini M. Copper and zinc dismetabolism in the mouse brain upon chronic cuprizone treatment. Cell. Mol. Life Sci. 2005; 62(13): 1502–1513.
64. Tezuka T, Tamura M, Kondo MA, Sakaue M, Okada K, Takemoto K, Fukunari A, Miwa K, Ohzeki H. Kano S-i. Cuprizone short-term exposure: astrocytic IL-6 activation and behavioral changes relevant to psychosis. Neurobiol. Dis. 2013; 59: 63–68.
65. Gerber MR, Connor JR. Do oligodendrocytes mediate iron regulation in the human brain? Ann. Neurol. 1989; 26(1): 95–98.
66. Connor J, Menzies S, St Martin S, Mufson E. Cellular distribution of transferrin, ferritin, and iron in normal and aged human brains. J. Neurosci. Res. 1990; 27(4): 595–611.
67. Wedler FC, Denman RB. Glutamine synthetase: the major Mn(II) enzyme in mammalian brain. Curr. Top. Cell. Regul. 1983; 24: 153–169.
68. Tholey G, Ledig M, Mandel P, Sargentini L, Frivold A, Leroy M, Grippo A, Wedler F. Concentrations of physiologically important metal ions in glial cells cultured from chick cerebral cortex. Neurochem. Res. 1988; 13(1): 45–50.
69. Norenberg MD, Martinez-Hernandez A. Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res. 1979; 161(2): 303–310.
70. Cammer W. Glutamine synthetase in the central nervous system is not confined to astrocytes. J. Neuroimmunol. 1990; 26(2): 173–178.
71. Smith CM, Cooksey E, Duncan ID. Myelin loss does not lead to axonal degeneration in a long-lived model of chronic demyelination. J. Neurosci. 2013; 33(6): 2718–2727.
72. Bourre J, Cloez I, Galliot M, Buisine A, Dumont O, Piciotti M, Prouillet F, Bourdon R. Occurrence of manganese, copper and zinc in myelin. Alterations in the peripheral nervous system of dysmyelinating trembler mutant are at variance with brain mutants (quaking and shiverer). Neurochem. Int. 1987; 10(3): 281–286.
73. Smeyers-Verbeke J, Michotte Y, Pelsmaeckers J, Lowenthal A, Massart D, Dekegel D, Karcher D. The chemical composition of idiopathic nonarteriosclerotic cerebral calcifications. Neurology 1975; 25(1): 48–57.
74. Dean KM, Qin Y, Palmer AE. Visualizing metal ions in cells: an overview of analytical techniques, approaches, and probes. Biochim. Biophys. Acta (BBA) Molec. Cell Res. 2012; 1823(9): 1406–1415.
75. Villafranca JJ, Wedler FC. Nuclear magnetic resonance study of the complexes of manganese(II) and fully adenylylated glutamine synthetase (Escherichia coli W). Frequency, temperature, and substrate dependence of water proton relaxation rates. Biochemistry (Moscow) 1974; 13(16): 3286–3291.
76. Wood JC, Fassler JD, Meade T. Mimicking liver iron overload using liposomal ferritin preparations. Magn. Reson. Med. 2004; 51(3): 607–611.
77. Cohen B, Dafni H, Meir G, Harmelin A, Neeman M. Ferritin as an endogenous MRI reporter for noninvasive imaging of gene expression in C6 glioma tumors. Neoplasia 2005; 7(2): 109–117.
78. Bock NA, Paiva FF, Silva AC. Fractionated manganese-enhanced MRI. NMR Biomed. 2008; 21(5): 473–478.
79. Clark PR, Chua-anusorn W, St Pierre TG. Proton transverse relaxation rate (R2) images of iron-loaded liver tissue: mapping local tissue iron concentrations with MRI. Magn. Reson. Med. 2003; 49(3): 572–575.
80. Ghugre NR, Coates TD, Nelson MD, Wood JC. Mechanisms of tissue–iron relaxivity: nuclear magnetic resonance studies of human liver biopsy specimens. Magn. Reson. Med. 2005; 54(5): 1185–1193.
81. Stüber C, Morawski M, Schäfer A, Labadie C, Wähnert M, Leuze C, Streicher M, Barapatre N, Reimann K, Geyer S, Spemann D, Turner R. Myelin and iron concentration in the human brain: a quantitative study of MRI contrast. Neuroimage 2014; 93: 95–106.
82. Vymazal J, Brooks RA, Baumgarner C, Tran V, Katz D, Bulte JW, Bauminger ER, Chiro GD. The relation between brain iron and NMR relaxation times: an in vitro study. Magn. Reson. Med. 1996; 35(1): 56–61.
83. Caravan P, Farrar CT, Frullano L, Uppal R. Influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium- and manganese-based T1 contrast agents. Contrast Media Mol. Imaging 2009; 4(2): 89–100.
84. Barazany D, Basser PJ, Assaf Y. In vivo measurement of axon diameter distribution in the corpus callosum of rat brain. Brain 2009; 132(5): 1210–1220.
85. Harkins KD, Xu J, Dula AN, Li K, Valentine WM, Gochberg DF, Gore JC, Does MD. The microstructural correlates of t1 in white matter. Magn. Reson. Med. 2016; 75(3): 1341–1345.
86. Lee J, Shmueli K, Fukunaga M, van Gelderen P, Merkle H, Silva AC, Duyn JH. Sensitivity of MRI resonance frequency to the orientation of brain tissue microstructure. Proc. Natl. Acad. Sci. 2010; 107(11): 5130–5135.
87. Lee J, van Gelderen P, Kuo L-W, Merkle H, Silva AC, Duyn JH. T2*-based fiber orientation mapping. Neuroimage 2011; 57(1): 225–234.
88. Lee J, Shmueli K, Kang B-T, Yao B, Fukunaga M, van Gelderen P, Palumbo S, Bosetti F, Silva AC, Duyn JH. The contribution of myelin to magnetic susceptibility-weighted contrasts in high-field MRI of the brain. Neuroimage 2012; 59(4): 3967–3975.
89. Sati P, van Gelderen P, Silva AC, Reich DS, Merkle H, de Zwart JA, Duyn JH. Micro-compartment specific T2* relaxation in the brain. Neuroimage 2013; 77: 268–278.
90. Uddin MN, Lebel RM, Wilman AH. Value of transverse relaxometry difference methods for iron in human brain. Magn. Reson. Imaging 2016; 34(1): 51–59.
91. Knight MJ, Wood B, Couthard E, Kauppinen R. Anisotropy of spin-echo T2 relaxation by magnetic resonance imaging in the human brain in vivo. Biomed. Spectrosc. Imaging 2015; 4(3): 299–310.
92. Sati P, Silva AC, van Gelderen P, Gaitan MI, Wohler JE, Jacobson S, Duyn JH, Reich DS. In vivo quantification of T2* anisotropy in white matter fibers in marmoset monkeys. Neuroimage 2012; 59(2): 979–985.
93. Anaby D, Duncan ID, Smith CM, Cohen Y. White matter maturation in the brains of Long Evans shaker myelin mutant rats by ex.-vivo QSI and DTI. Magn. Reson. Imaging 2013; 31(7): 1097–1104.
94. Bird T, Farrell D, Sumi S. Brain lipid composition of the shiverer mouse: (genetic defect in myelin development). J. Neurochem. 1978; 31(1): 387–391.
95. Harris JJ, Attwell D. The energetics of CNS white matter. J. Neurosci. 2012; 32(1): 356–371.
96. Lin A-L, Fox PT, Hardies J, Duong TQ, Gao J-H. Nonlinear coupling between cerebral blood flow, oxygen consumption, and ATP production in human visual cortex. Proc. Natl. Acad. Sci. 2010; 107(18): 8446–8451.
97. Bergers E, Bot J, de Groot C, Polman C. à Nijeholt GL, Castelijns J, Van Der Valk P, Barkhof F. Axonal damage in the spinal cord of MS patients occurs largely independent of T2 MRI lesions. Neurology 2002; 59(11): 1766–1771.
98. Cohen-Adad J, el Mendili M, Lehéricy S, Pradat P, Blancho S, Rossignol S, Benali H. Demyelination and degeneration in the injured human spinal cord detected with diffusion and magnetization transfer MRI. Neuroimage 2011; 55(3): 1024–1033.
99. Bagnato F, Hametner S, Yao B, van Gelderen P, Merkle H, Cantor FK, Lassmann H, Duyn JH. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla. Brain 2011; 134(12): 3602–3615.
100. Schwarz J, Weis S, Kraft E, Tatsch K, Bandmann O, Mehraein P, Vogl T, Oertel W. Signal changes on MRI and increases in reactive microgliosis, astrogliosis, and iron in the putamen of two patients with multiple system atrophy. J. Neurol. Neurosurg. Psychiatry 1996; 60(1): 98–101.
101. Bermel RA, Puli SR, Rudick RA, Weinstock-Guttman B, Fisher E, Munschauer FE, III, Bakshi R. Gray matter MRI T2 hypointensity predicts longitudinal brain atrophy in multiple sclerosis. Arch. Neurol. 2005; 62(9): 1371.
102. Chen JC, Hardy P, Kucharczyk W, Clauberg M, Joshi J, Vourlas A, Dhar M, Henkelman R. MR of human postmortem brain tissue: correlative study between T2 and assays of iron and ferritin in Parkinson and Huntington disease. Am. J. Neuroradiol. 1993; 14(2): 275–281.
103. Laule C, Vavasour IM, Whittall KP, Oger J, Paty DW, Li DKB, MacKay AL, Arnold DL. Evolution of focal and diffuse magnetisation transfer abnormalities in multiple sclerosis. J. Neurol. 2003; 250(8): 924–931.
104. MacKay A, Laule C, Vavasour I, Bjarnason T, Kolind S, Madler B. Insights into brain microstructure from the T-2 distribution. Magn. Reson. Imaging 2006; 24(4): 515–525.
105. Sirrs SM, Laule C, Madler B, Brief EE, Tahir SA, Bishop C, MacKay AL. Normal-appearing white matter in patients with phenylketonuria: water content, myelin water fraction, and metabolite concentrations. Radiology 2007; 242(1): 236–243.
106. Webb S, Munro C, Midha R, Stanisz G. Is multicomponent T-2 a good measure of myelin content in peripheral nerve? Magn. Reson. Med. 2003; 49: 638–645.
107. Labadie C, Lee J-H, Rooney WD, Jarchow S, Aubert-Frecon M, Springer CS, Jr, Moeller HE. Myelin water mapping by spatially regularized longitudinal relaxographic imaging at high magnetic fields. Magn. Reson. Med. 2014; 71(1): 375–387.
108. van Gelderen P, Jiang X, Duyn JH. Effects of magnetization transfer on T1 contrast in human brain white matter. Neuroimage 2016; 128: 85–95.
109. Zimmerman J, Brittin WE. Nuclear magnetic resonance studies in multiple phase systems: lifetime of a water molecule in an adsorbing phase on silica gel. J. Phys. Chem. 1957; 61(10): 1328–1333.
110. Vavasour IM, Whittall KP, MacKay AL, Li DKB, Vorobeychik G, Paty DW. A comparison between magnetization transfer ratios and myelin water percentages in normals and multiple sclerosis patients. Magn. Reson. Med. 1998; 40: 763–768.
111. Whittall KP, MacKay AL. Quantitative interpretation of NMR relaxation data. J. Magn. Reson. 1989; 95: 134.
112. Whittall KP, MacKay AL, Li DKB, Vavasour IM, Jones CK, Paty DW. Normal-appearing white matter in multiple sclerosis has heterogeneous, diffusely prolonged T-2. Magn. Reson. Med. 2002; 47: 403–408.
113. Bjarnason TA, McCreary CR, Dunn JF, Mitchell JR. Quantitative T(2) analysis: the effects of noise, regularization, and multivoxel approaches. Magn. Reson. Med. 2010; 63(1): 212–217.
114. Portnoy S, Stanisz G. Modeling pulsed magnetization transfer. Magn. Res. Med. 2007; 58(1): 144–155.
115. Stanisz G, Odrobina E, Pun J, Graham S, Bronskill M, Henkelman R. T1, T2 relaxation and magnetization transfer at 3 T. Magn. Res. Med. 2005; 54(3): 507–512.
116. Diakova G, Korb J-P, Bryant RG. The magnetic field dependence of water T1 in tissues. Magn. Reson. Med. 2012; 68(1): 272–277.
117. Bottomley PA, Foster TH, Argersinger RE, Pfeifer LM. A review of normal tissue hydrogen NMR relaxation-times and relaxation mechanisms from 1–100 MHz – dependence on tissue-type, NMR frequency, temperature, species, excision, and age. Med. Phys. 1984; 11(4): 425–448.
118. Oakden W, Kwiecien JM, O'Reilly MA, Dabrowski W, Whyne C, Finkelstein J, Hynynen K, Stanisz GJ. Quantitative MRI in a non-surgical model of cervical spinal cord injury. NMR Biomed. 2015; 28(8): 925–936.