Neuroimaging in amyotrophic lateral sclerosis

Biomarkers in Medicine

Volumn 6, Issue 3, 2012, Pages 319-337

  Turner, Martin R ^a   Agosta, Federica ^b   Bede, Peter ^c   Govind, Varan ^d   Lulé, Dorothée ^e   Verstraete, Esther ^f  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

^c TRINITY COLLEGE DUBLIN   (Ireland)

^d UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF ULM   (Germany)

^f UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

diffusion tensor imaging; functional imaging; magnetic resonance spectroscopy; morphometry; motor neuron disease; MRI; PET; resting state

Indexed keywords

11C WAY 100635; 4 AMINOBUTYRIC ACID A RECEPTOR; 6 FLUORODOPA F 18; BENZODIAZEPINE RECEPTOR; BIOLOGICAL MARKER; CHOLINE; CREATINE; FLUMAZENIL C 11; FLUORODEOXYGLUCOSE F 18; GLUTAMIC ACID; GLUTAMINE; HEXAMETHYLPROPYLENE AMINE OXIME TECHNETIUM TC 99M; INOSITOL; IOFETAMINE I 123; N [2 [4 (2 METHOXYPHENYL) 1 PIPERAZINYL]ETHYL] N (2 PYRIDYL)CYCLOHEXANECARBOXAMIDE C 11; N ACETYLASPARTIC ACID; N SEC BUTYL 1 (2 CHLOROPHENYL) N METHYL 3 ISOQUINOLINECARBOXAMIDE C 11; RADIOPHARMACEUTICAL AGENT; UNCLASSIFIED DRUG;

AMYOTROPHIC LATERAL SCLEROSIS; BOLD SIGNAL; BRAIN ATROPHY; BRAIN BLOOD FLOW; BRAIN FUNCTION; CORPUS CALLOSUM; DEMENTIA; DIFFUSION TENSOR IMAGING; FUNCTIONAL MAGNETIC RESONANCE IMAGING; HUMAN; IMAGE DISPLAY; MORPHOMETRICS; MOTOR SYSTEM; NEUROIMAGING; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PHENOTYPE; POSITRON EMISSION TOMOGRAPHY; PYRAMIDAL TRACT; REVIEW; SENSITIVITY ANALYSIS; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY; SPINAL CORD; SURFACE BASED MORPHOMETRY; VOXEL BASED MORPHOMETRY;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; BRAIN; HUMANS; MAGNETIC RESONANCE IMAGING; NEUROIMAGING;

EID: 84862889813     PISSN: 17520363     EISSN: 17520371     Source Type: Journal    
DOI: 10.2217/bmm.12.26     Document Type: Review

References (211)

1. Kiernan MC, Vucic S, Cheah BC et al. Amyotrophic lateral sclerosis. Lancet 377(9769), 942-955 (2011).
2. Smith MC. Nerve fiber degeneration in the brain in amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry 23, 269-282 (1960).
3. Phukan J, Pender NP, Hardiman O. Cognitive impairment in amyotrophic lateral sclerosis. Lancet Neurol. 6(11), 994-1003 (2007).
4. Neumann M, Sampathu DM, Kwong LK et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science, 314(5796), 130-133 (2006).
5. Renton AE, Majounie E, Waite A et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72(2), 257-268 (2011).
6. DeJesus-Hernandez M, Mackenzie IR, Boeve BF et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72(2), 245-256 (2011).
7. Giordana MT, Ferrero P, Grifoni S, Pellerino A, Naldi A, Montuschi A. Dementia and cognitive impairment in amyotrophic lateral sclerosis: a review. Neurol. Sci. 32(1), 9-16 (2011).
8. Ince PG, Evans J, Knopp M et al. Corticospinal tract degeneration in the progressive muscular atrophy variant of ALS. Neurology 60(8), 1252-1258 (2003).
9. Turner MR, Kiernan MC, Leigh PN, Talbot K. Biomarkers in amyotrophic lateral sclerosis. Lancet Neurol. 8(1), 94-109 (2009).
10. Filippi M, Agosta F, Abrahams S et al. EFNS guidelines on the use of neuroimaging in the management of motor neuron diseases. Eur. J. Neurol. 17(4), 526-533 (2010).
11. Turner MR. MRI as a frontrunner in the search for amyotrophic lateral sclerosis biomarkers? Biomark. Med. 5(1), 79-81 (2011).
12. Ludolph AC, Elger CE, Bottger IW, Kuttig AG, Lottes G, Brune GG. N-isopropyl-p-123I-amphetamine single photon emission computer tomography in motor neuron disease. Eur. Neurol. 29(5), 255-260 (1989).
13. Neary D, Snowden JS, Mann DM, Northen B, Goulding PJ, Macdermott N. Frontal lobe dementia and motor neuron disease. J. Neurol. Neurosurg. Psychiatry 53(1), 23-32 (1990).
14. Talbot PR, Goulding PJ, Lloyd JJ, Snowden JS, Neary D, Testa HJ. Inter-relation between classic motor neuron disease and frontotemporal dementia: neuropsychological and single photon emission computed tomography study. J. Neurol. Neurosurg. Psychiatry 58(5), 541-547 (1995).
15. Dalakas MC, Hatazawa J, Brooks RA, Di Chiro G. Lowered cerebral glucose utilization in amyotrophic lateral sclerosis. Ann. Neurol. 22(5), 580-586 (1987).
16. Ludolph AC, Langen KJ, Regard M et al. Frontal lobe function in amyotrophic lateral sclerosis: a neuropsychologic and positron emission tomography study. Acta Neurol. Scand. 85(2), 81-89 (1992).
17. Tanaka M, Kondo S, Hirai S, Sun X, Yamagishi T, Okamoto K. Cerebral blood flow and oxygen metabolism in progressive dementia associated with amyotrophic lateral sclerosis. J. Neurol. Sci. 120(1), 22-28 (1993).
18. Kew JJ, Goldstein LH, Leigh PN et al. The relationship between abnormalities of cognitive function and cerebral activation in amyotrophic lateral sclerosis. A neuropsychological and positron emission tomography study. Brain 116(6), 1399-1423 (1993).
19. Kew JJ, Leigh PN, Playford ED et al. Cortical function in amyotrophic lateral sclerosis. A positron emission tomography study. Brain 116(Pt 3), 655-680 (1993).
20. Takahashi H, Snow BJ, Bhatt MH, Peppard R, Eisen A, Calne DB. Evidence for a dopaminergic deficit in sporadic amyotrophic lateral sclerosis on positron emission scanning. Lancet 342(8878), 1016-1018 (1993).
21. Lloyd CM, Richardson MP, Brooks DJ, Al Chalabi A, Leigh PN. Extramotor involvement in ALS: PET studies with the GABA(A) ligand [(11)C]flumazenil. Brain 123(Pt 11), 2289-2296 (2000).
22. Turner MR, Kiernan MC. Does interneuronal dysfunction contribute to neurodegneration in amytrophic lateral sclerosis? Amyotroph. Lateral Scler. 13(3), 245-250 (2012).
23. Turner MR, Hammers A, Al Chalabi A et al. Distinct cerebral lesions in sporadic and 'D90A' SOD1 ALS: studies with [11C]flumazenil PET. Brain 128(6), 1323-1329 (2005).
24. Philips T, Robberecht W. Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol. 10(3), 253-263 (2011).
25. Turner MR, Cagnin A, Turkheimer FE et al. Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [(11)C](R)-PK11195 positron emission tomography study. Neurobiol. Dis. 15(3), 601-609 (2004).
26. Turner MR, Gerhard A, Al-Chalabi A et al. Mills' and other isolated upper motor neuron syndromes: in vivo study with [11C]-PK11195 PET. J. Neurol. Neurosurg. Psychiatry 76(6), 871-874 (2005).
27. Turner MR, Rabiner EA, Hammers A et al. [11C]-WAY100635 PET demonstrates marked 5-HT1A receptor changes in sporadic ALS. Brain 128(Pt 4), 896-905 (2005).
28. Lanctôt KL, Herrmann N, Ganjavi H et al. Serotonin-1A receptors in frontotemporal dementia compared with controls. Psychiatry Res. 156(3), 247-250 (2007).
29. Bowen DM, Procter AW, Mann DM et al. Imbalance of a serotonergic system in frontotemporal dementia: implication for pharmacotherapy. Psychopharmacology (Berl.) 196(4), 603-610 (2008).
30. DeFelipe J, Arellano JI, Gomez A, Azmitia EC, Munoz A. Pyramidal cell axons show a local specialization for GABA and 5-HT inputs in monkey and human cerebral cortex. J. Comp. Neurol. 433(1), 148-155 (2001).
31. Sandyk R. Serotonergic mechanisms in amyotrophic lateral sclerosis. Int. J Neurosci. 116(7), 775-826 (2006).
32. Talbot PR, Snowden JS, Lloyd JJ, Neary D, Testa HJ. The contribution of single photon emission tomography to the clinical differentiation of degenerative cortical brain disorders. J. Neurol. 242(9), 579-586 (1995).
33. Ashburner J, Friston KJ. Voxel-based morphometry - the methods. Neuroimage. 11(6 Pt 1), 805-821 (2000).
34. Fischl B, Dale AM. Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc. Natl Acad. Sci. USA 97(20), 11050-11055 (2000).
35. Pereira JB, Ibarretxe-Bilbao N, Marti MJ et al. Assessment of cortical degeneration in patients with parkinson's disease by voxel-based morphometry, cortical folding, and cortical thickness. Hum. Brain Mapp. doi:10.1002/hbm.21378 (2011) (Epub ahead of print).
36. Kassubek J, Unrath A, Huppertz HJ et al. Global brain atrophy and corticospinal tract alterations in ALS, as investigated by voxel-based morphometry of 3-D MRI. Amyotroph. Lateral Scler. 6(4), 213-220 (2005).
37. Filippini N, Douaud G, Mackay CE, Knight S, Talbot K, Turner MR. Corpus callosum involvement is a consistent feature of amyotrophic lateral sclerosis. Neurology 75(18), 1645-1652 (2010).
38. Senda J, Kato S, Kaga T et al. Progressive and widespread brain damage in ALS: MRI voxel-based morphometry and diffusion tensor imaging study. Amyotroph. Lateral Scler. 12(1), 59-69 (2011).
39. Ellis CM, Suckling J, Amaro E Jr et al. Volumetric analysis reveals corticospinal tract degeneration and extramotor involvement in ALS. Neurology 57(9), 1571-1578 (2001).
40. Mezzapesa DM, Ceccarelli A, Dicuonzo F et al. Whole-brain and regional brain atrophy in amyotrophic lateral sclerosis. Am. J. Neuroradiol. 28(2), 255-259 (2007).
41. Tsujimoto M, Senda J, Ishihara T et al. Behavioral changes in early ALS correlate with voxel-based morphometry and diffusion tensor imaging. J. Neurol. Sci. 307(1-2), 34-40 (2011).
42. Abrahams S, Goldstein LH, Suckling J et al. Frontotemporal white matter changes in amyotrophic lateral sclerosis. J. Neurol. 252(3), 321-331 (2005).
43. Chen Z, Ma L. Grey matter volume changes over the whole brain in amyotrophic lateral sclerosis: a voxel-wise meta-analysis of voxel based morphometry studies. Amyotroph. Lateral Scler. 11(6), 549-554 (2010).
44. Raaphorst J, de Visser M, Linssen WH, de Haan RJ, Schmand B. The cognitive profile of amyotrophic lateral sclerosis: a meta-analysis. Amyotroph. Lateral Scler. 11(1-2), 27-37 (2011).
45. Grossman M, Anderson C, Khan A, Avants B, Elman L, McCluskey L. Impaired action knowledge in amyotrophic lateral sclerosis. Neurology 71(18), 1396-1401 (2008).
46. Chang JL, Lomen-Hoerth C, Murphy J et al. A voxel-based morphometry study of patterns of brain atrophy in ALS and ALS/FTLD. Neurology 65(1), 75-80 (2005).
47. Agosta F, Gorno-Tempini ML, Pagani E et al. Longitudinal assessment of grey matter contraction in amyotrophic lateral sclerosis: a tensor based morphometry study. Amyotroph. Lateral Scler. 10(3), 168-174 (2009).
48. Elamin M, Phukan J, Bede P et al. Executive dysfunction is a negative prognostic indicator in patients with ALS without dementia. Neurology 76(14), 1263-1269 (2011).
49. Roccatagliata L, Bonzano L, Mancardi G, Canepa C, Caponnetto C. Detection of motor cortex thinning and corticospinal tract involvement by quantitative MRI in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 10(1), 47-52 (2009).
50. Verstraete E, van den Heuvel MP, Veldink JH et al. Motor network degeneration in amyotrophic lateral sclerosis: a structural and functional connectivity study. PLoS ONE 5(10), e13664 (2010).
51. Verstraete E, Veldink JH, Hendrikse J, Schelhaas HJ, van den Heuvel MP, van den Berg LH. Structural MRI reveals cortical thinning in amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry 83(4), 383-388 (2012).
52. Basser PJ, Mattiello J, LeBihan D. Estimation of the effective self-diffusion tensor from the NMR spin echo. J. Magn. Reson. B 103(3), 247-254 (1994).
53. Pierpaoli C, Jezzard P, Basser PJ, Barnett A, Di Chiro G. Diffusion tensor MR imaging of the human brain. Radiology 201(3), 637-648 (1996).
54. Beaulieu C. The basis of anisotropic water diffusion in the nervous system - A technical review. NMR Biomed. 15(7-8), 435-455 (2002).
55. Pierpaoli C, Barnett A, Pajevic S et al. Water diffusion changes in Wallerian degeneration and their dependence on white matter architecture. Neuroimage 13(6 Pt 1), 1174-1185 (2001).
56. Abe O, Yamada H, Masutani Y et al. Amyotrophic lateral sclerosis: diffusion tensor tractography and voxel-based analysis. NMR Biomed. 17(6), 411-416 (2004).
57. Agosta F, Pagani E, Petrolini M et al. Assessment of white matter tract damage in patients with amyotrophic lateral sclerosis: a diffusion tensor MR imaging tractography study. Am. J. Neuroradiol. 31(8), 1457-1461 (2010).
58. Ciccarelli O, Behrens TE, Altmann DR et al. Probabilistic diffusion tractography: a potential tool to assess the rate of disease progression in amyotrophic lateral sclerosis. Brain 129(Pt 7), 1859-1871 (2006).
59. Cosottini M, Giannelli M, Siciliano G et al. Diffusion-tensor MR imaging of corticospinal tract in amyotrophic lateral sclerosis and progressive muscular atrophy. Radiology 237(1), 258-264 (2005).
60. Ellis CM, Simmons A, Jones DK et al. Diffusion tensor MRI assesses corticospinal tract damage in ALS. Neurology 53(5), 1051-1058 (1999).
61. Graham JM, Papadakis N, Evans J et al. Diffusion tensor imaging for the assessment of upper motor neuron integrity in ALS. Neurology 63(11), 2111-2119 (2004).
62. Iwata NK, Aoki S, Okabe S et al. Evaluation of corticospinal tracts in ALS with diffusion tensor MRI and brainstem stimulation. Neurology 70(7), 528-532 (2008).
63. Sach M, Winkler G, Glauche V et al. Diffusion tensor MRI of early upper motor neuron involvement in amyotrophic lateral sclerosis. Brain 127(Pt 2), 340-350 (2004).
64. Sage CA, Peeters RR, Gorner A, Robberecht W, Sunaert S. Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis. Neuroimage 34(2), 486-499 (2007).
65. Schimrigk SK, Bellenberg B, Schluter M et al. Diffusion tensor imaging-based fractional anisotropy quantification in the corticospinal tract of patients with amyotrophic lateral sclerosis using a probabilistic mixture model. Am. J. Neuroradiol. 28(4), 724-730 (2007).
66. Senda J, Ito M, Watanabe H et al. Correlation between pyramidal tract degeneration and widespread white matter involvement in amyotrophic lateral sclerosis: a study with tractography and diffusion-tensor imaging. Amyotroph. Lateral Scler. 10(5-6), 288-294 (2009).
67. Basser PJ, Mattiello J, LeBihan D. Estimation of the effective self-diffusion tensor from the NMR spin echo. J. Magn. Reson. B 103(3), 247-254 (1994).
68. Pierpaoli C, Jezzard P, Basser PJ, Barnett A, Di Chiro G. Diffusion tensor MR imaging of the human brain. Radiology 201(3), 637-648 (1996).
69. Beaulieu C. The basis of anisotropic water diffusion in the nervous system - a technical review. NMR Biomed. 15(7-8), 435-455 (2002).
70. Pierpaoli C, Barnett A, Pajevic S et al. Water diffusion changes in Wallerian degeneration and their dependence on white matter architecture. Neuroimage 13(6 Pt 1), 1174-1185 (2001).
71. Abe O, Yamada H, Masutani Y et al. Amyotrophic lateral sclerosis: diffusion tensor tractography and voxel-based analysis. NMR Biomed. 17(6), 411-416 (2004).
72. Agosta F, Pagani E, Petrolini M et al. Assessment of white matter tract damage in patients with amyotrophic lateral sclerosis: a diffusion tensor MR imaging tractography study. Am. J. Neuroradiol. 31(8), 1457-1461 (2010).
73. Ciccarelli O, Behrens TE, Altmann DR et al. Probabilistic diffusion tractography: a potential tool to assess the rate of disease progression in amyotrophic lateral sclerosis. Brain 129(Pt 7), 1859-1871 (2006).
74. Cosottini M, Giannelli M, Siciliano G et al. Diffusion-tensor MR imaging of corticospinal tract in amyotrophic lateral sclerosis and progressive muscular atrophy. Radiology 237(1), 258-264 (2005).
75. Ellis CM, Simmons A, Jones DK et al. Diffusion tensor MRI assesses corticospinal tract damage in ALS. Neurology 53(5), 1051-1058 (1999).
76. Graham JM, Papadakis N, Evans J et al. Diffusion tensor imaging for the assessment of upper motor neuron integrity in ALS. Neurology 63(11), 2111-2119 (2004).
77. Iwata NK, Aoki S, Okabe S et al. Evaluation of corticospinal tracts in ALS with diffusion tensor MRI and brainstem stimulation. Neurology 70(7), 528-532 (2008).
78. Sach M, Winkler G, Glauche V et al. Diffusion tensor MRI of early upper motor neuron involvement in amyotrophic lateral sclerosis. Brain 127(Pt 2), 340-350 (2004).
79. Sage CA, Peeters RR, Gorner A, Robberecht W, Sunaert S. Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis. Neuroimage 34(2), 486-499 (2007).
80. Schimrigk SK, Bellenberg B, Schluter M et al. Diffusion tensor imaging-based fractional anisotropy quantification in the corticospinal tract of patients with amyotrophic lateral sclerosis using a probabilistic mixture model. Am. J. Neuroradiol. 28(4), 724-730 (2007).
81. Senda J, Ito M, Watanabe H et al. Correlation between pyramidal tract degeneration and widespread white matter involvement in amyotrophic lateral sclerosis: a study with tractography and diffusion-tensor imaging. Amyotroph. Lateral Scler. 10(5-6), 288-294 (2009).
82. Wang S, Poptani H, Bilello M et al. Diffusion tensor imaging in amyotrophic lateral sclerosis: volumetric analysis of the corticospinal tract. Am. J. Neuroradiol. 27(6), 1234-1238 (2006).
83. Sage CA, Van Hecke W, Peeters R et al. Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis: revisited. Hum. Brain Mapp. 30(11), 3657-3675 (2009).
84. Sach M, Winkler G, Glauche V et al. Diffusion tensor MRI of early upper motor neuron involvement in amyotrophic lateral sclerosis. Brain 127(Pt 2), 340-350 (2004).
85. Iwata NK, Kwan JY, Danielian LE et al. White matter alterations differ in primary lateral sclerosis and amyotrophic lateral sclerosis. Brain 134(Pt 9), 2642-2655 (2011).
86. Agosta F, Pagani E, Petrolini M et al. MRI predictors of long-term evolution in amyotrophic lateral sclerosis. Eur. J. Neurosci. 32(9), 1490-1496 (2010).
87. Agosta F, Pagani E, Rocca MA et al. Voxel-based morphometry study of brain volumetry and diffusivity in amyotrophic lateral sclerosis patients with mild disability. Hum. Brain Mapp. 28(12), 1430-1438 (2007).
88. Ciccarelli O, Behrens TE, Johansen-Berg H et al. Investigation of white matter pathology in ALS and PLS using tract-based spatial statistics. Hum. Brain Mapp. 30(2), 615-624 (2009).
89. Zhang Y, Schuff N, Woolley SC et al. Progression of white matter degeneration in amyotrophic lateral sclerosis: a diffusion tensor imaging study. Amyotroph. Lateral Scler. 12(6), 421-429 (2011).
90. Rose S, Pannek K, Bell C et al. Direct evidence of intra- and interhemispheric corticomotor network degeneration in amyotrophic lateral sclerosis: an automated MRI structural connectivity study. Neuroimage 59(3), 2661-2669 (2012).
91. Probst M. Zur Kenntnis der amyotrophischen Lateralsklerose. S-B. Akad. Wiss. Wien. 112(3), 683-824 (1903).
92. Bartels C, Mertens N, Hofer S et al. Callosal dysfunction in amyotrophic lateral sclerosis correlates with diffusion tensor imaging of the central motor system. Neuromuscul. Disord. 18(5), 398-407 (2008).
93. Eisen A. Amyotrophic lateral sclerosis -evolutionary and other perspectives. Muscle Nerve 40(2), 297-304 (2009).
94. Muller HP, Unrath A, Huppertz HJ, Ludolph AC, Kassubek J. Neuroanatomical patterns of cerebral white matter involvement in different motor neuron diseases as studied by diffusion tensor imaging analysis. 13 3 254-264 Amyotroph. Lateral Scler. 2012
95. Canu E, Agosta F, Riva N et al. The topography of brain microstructural damage in amyotrophic lateral sclerosis assessed using diffusion tensor MR imaging. Am. J. Neuroradiol. 32(7), 1307-1314 (2011).
96. Mackenzie IR, Feldman HH. Ubiquitin immunohistochemistry suggests classic motor neuron disease, motor neuron disease with dementia, and frontotemporal dementia of the motor neuron disease type represent a clinicopathologic spectrum. J. Neuropathol. Exp. Neurol. 64(8), 730-739 (2005).
97. Sato K, Aoki S, Iwata NK et al. Diffusion tensor tract-specific analysis of the uncinate fasciculus in patients with amyotrophic lateral sclerosis. Neuroradiology 52(8), 729-733 (2010).
98. Sarro L, Agosta F, Canu E et al. Cognitive functions and white matter tract damage in amyotrophic lateral sclerosis: a diffusion tensor tractography study. AJNR Am. J. Neuroradiol. 32(10), 1866-1872 (2011).
99. Aoki S, Iwata NK, Masutani Y et al. Quantitative evaluation of the pyramidal tract segmented by diffusion tensor tractography: feasibility study in patients with amyotrophic lateral sclerosis. Radiat. Med. 23(3), 195-199 (2005).
100. van der Graaff MM, Sage CA, Caan MW et al. Upper and extra-motoneuron involvement in early motoneuron disease: a diffusion tensor imaging study. Brain 134(Pt 4), 1211-1228 (2011).
101. Unrath A, Muller HP, Riecker A, Ludolph AC, Sperfeld AD, Kassubek J. Whole brain-based analysis of regional white matter tract alterations in rare motor neuron diseases by diffusion tensor imaging. Hum. Brain Mapp. 31(11), 1727-1740 (2010).
102. Stanton BR, Shinhmar D, Turner MR et al. Diffusion tensor imaging in sporadic and familial (D90A SOD1) forms of amyotrophic lateral sclerosis. Arch. Neurol. 66(1), 109-115 (2009).
103. Blain CR, Brunton S, Williams VC et al. Differential corticospinal tract degeneration in homozygous 'D90A' SOD-1 ALS and sporadic ALS. J. Neurol. Neurosurg. Psychiatry, 82(8), 843-849 (2011).
104. Agosta F, Rocca MA, Valsasina P et al. A longitudinal diffusion tensor MRI study of the cervical cord and brain in amyotrophic lateral sclerosis patients. J. Neurol. Neurosurg. Psychiatry 80(1), 53-55 (2009).
105. Blain CR, Williams VC, Johnston C et al. A longitudinal study of diffusion tensor MRI in ALS. Amyotroph. Lateral Scler. 8(6), 348-355 (2007).
106. Mitsumoto H, Ulug AM, Pullman SL et al. Quantitative objective markers for upper and lower motor neuron dysfunction in ALS. Neurology 68(17), 1402-1410 (2007).
107. Miller R, Bradley W, Cudkowicz M et al. Phase II/III randomized trial of TCH346 in patients with ALS. Neurology 69(8), 776-784 (2007).
108. Cosottini M, Giannelli M, Vannozzi F et al. Evaluation of corticospinal tract impairment in the brain of patients with amyotrophic lateral sclerosis by using diffusion tensor imaging acquisition schemes with different numbers of diffusion-weighting directions. J. Comput. Assist. Tomogr. 34(5), 746-750 (2010).
109. Konrad C, Henningsen H, Bremer J et al. Pattern of cortical reorganization in amyotrophic lateral sclerosis: a functional magnetic resonance imaging study. Exp. Brain Res. 143(1), 51-56 (2002).
110. Han J, Ma L. Functional magnetic resonance imaging study of the brain in patients with amyotrophic lateral sclerosis. Chin. Med. Sci. J. 21(4), 228-233 (2006).
111. Stanton BR, Williams VC, Leigh PN et al. Altered cortical activation during a motor task in ALS. Evidence for involvement of central pathways. J. Neurol. 254(9), 1260-1267 (2007).
112. Lule D, Diekmann V, Kassubek J et al. Cortical plasticity in amyotrophic lateral sclerosis: motor imagery and function. Neurorehabil. Neural Repair 21(6), 518-526 (2007).
113. Cosottini M, Pesaresi I, Piazza S et al. Structural and functional evaluation of cortical motor areas in amyotrophic lateral sclerosis. Exp. Neurol. 234(1), 169-180 (2011).
114. Schoenfeld MA, Tempelmann C, Gaul C et al. Functional motor compensation in amyotrophic lateral sclerosis. J. Neurol. 252(8), 944-952 (2005).
115. Konrad C, Jansen A, Henningsen H et al. Subcortical reorganization in amyotrophic lateral sclerosis. Exp. Brain Res. 172(3), 361-369 (2006).
116. Mohammadi B, Kollewe K, Samii A, Dengler R, Munte TF. Functional neuroimaging at different disease stages reveals distinct phases of neuroplastic changes in amyotrophic lateral sclerosis. Hum. Brain Mapp. 32(5), 750-758 (2011).
117. Weiller C, May A, Sach M, Buhmann C, Rijntjes M. Role of functional imaging in neurological disorders. J. Magn. Reson. Imaging 23(6), 840-850 (2006).
118. Tessitore A, Esposito F, Monsurro MR et al. Subcortical motor plasticity in patients with sporadic ALS: an fMRI study. Brain Res. Bull. 69(5), 489-494 (2006).
119. Kollewe K, Munte TF, Samii A, Dengler R, Petri S, Mohammadi B. Patterns of cortical activity differ in ALS patients with limb and/or bulbar involvement depending on motor tasks. J. Neurol. 258(5), 804-810 (2011).
120. Li S, Chen Q, Yu B et al. Structural and functional changes mapped in the brains of amyotrophic lateral sclerosis patients with/without dysphagia: a pilot study. Amyotroph. Lateral Scler. 10(5-6), 280-287 (2009).
121. Mohammadi B, Kollewe K, Samii A, Krampfl K, Dengler R, Munte TF. Decreased brain activation to tongue movements in amyotrophic lateral sclerosis with bulbar involvement but not Kennedy syndrome. J. Neurol. 256(8), 1263-1269 (2009).
122. Stanton BR, Williams VC, Leigh PN et al. Cortical activation during motor imagery is reduced in amyotrophic lateral sclerosis. Brain Res. 1172, 145-151 (2007).
123. Abrahams S, Goldstein LH, Simmons A et al. Word retrieval in amyotrophic lateral sclerosis: a functional magnetic resonance imaging study. Brain 127(Pt 7), 1507-1517 (2004).
124. Goldstein LH, Newsom-Davis IC, Bryant V, Brammer M, Leigh PN, Simmons A. Altered patterns of cortical activation in ALS patients during attention and cognitive response inhibition tasks. J. Neurol. 258(12), 2186-2198 (2011).
125. Lule D, Diekmann V, Anders S et al. Brain responses to emotional stimuli in patients with amyotrophic lateral sclerosis (ALS). J. Neurol. 254(4), 519-527 (2007).
126. Palmieri A, Naccarato M, Abrahams S et al. Right hemisphere dysfunction and emotional processing in ALS: an fMRI study. J. Neurol. 257(12), 1970-1978 (2010).
127. Lule D, Diekmann V, Muller HP, Kassubek J, Ludolph AC, Birbaumer N. Neuroimaging of multimodal sensory stimulation in amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry 81(8), 899-906 (2010).
128. Smith SM, Fox PT, Miller KL et al. Correspondence of the brain's functional architecture during activation and rest. Proc. Natl Acad. Sci. USA 106(31), 13040-13045 (2009).
129. Greicius M. Resting-state functional connectivity in neuropsychiatric disorders. Curr. Opin Neuro. 21(4), 424-430 (2008).
130. van den Heuvel MP, Hulshoff Pol HE. Exploring the brain network: a review on resting-state fMRI functional connectivity. Eur. Neuropsychopharmacol. 20(8), 519-534 (2010).
131. Mohammadi B, Kollewe K, Samii A, Krampfl K, Dengler R, Munte TF. Changes of resting state brain networks in amyotrophic lateral sclerosis. Exp. Neurol. 217(1), 147-153 (2009).
132. Jelsone-Swain LM, Fling BW, Seidler RD, Hovatter R, Gruis K, Welsh RC. Reduced interhemispheric functional connectivity in the motor cortex during rest in limb-onset amyotrophic lateral sclerosis. Front Syst. Neurosci. 4, 158 (2010).
133. Agosta F, Valsasina P, Absinta M et al. Sensorimotor functional connectivity changes in amyotrophic lateral sclerosis. Cereb. Cortex 21(10), 2291-2298 (2011).
134. Douaud G, Filippini N, Knight S, Talbot K, Turner MR. Integration of structural and functional magnetic resonance imaging in amyotrophic lateral sclerosis. Brain 134(Pt 12), 3470-3479 (2011).
135. Govindaraju V, Young K, Maudsley AA. Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed. 13(3), 129-153 (2000).
136. Jones AP, Gunawardena WJ, Coutinho CM, Gatt JA, Shaw IC, Mitchell JD. Preliminary results of proton magnetic resonance spectroscopy in motor neurone disease (amyotrophic lateral sclerosis). J. Neurol. Sci. 129(Suppl.), 85-89 (1995).
137. Giroud M, Walker P, Bernard D et al. Reduced brain N-acetyl-aspartate in frontal lobes suggests neuronal loss in patients with amyotrophic lateral sclerosis. Neurol. Res. 18(3), 241-243 (1996).
138. Han J, Ma L. Study of the features of proton MR spectroscopy ((1)H-MRS) on amyotrophic lateral sclerosis. J. Magn. Reson. Imaging 31(2), 305-308 (2010).
139. Usman U, Choi C, Camicioli R et al. Mesial prefrontal cortex degeneration in amyotrophic lateral sclerosis: a high-field proton MR spectroscopy study. Am. J. Neuroradiol. 32(9), 1677-1680 (2011).
140. Pioro EP, Antel JP, Cashman NR, Arnold DL. Detection of cortical neuron loss in motor neuron disease by proton magnetic resonance spectroscopic imaging in vivo. Neurology 44(10), 1933-1938 (1994).
141. Rooney WD, Miller RG, Gelinas D, Schuff N, Maudsley AA, Weiner MW. Decreased N-acetylaspartate in motor cortex and corticospinal tract in ALS. Neurology 50(6), 1800-1805 (1998).
142. Gredal O, Rosenbaum S, Topp S, Karlsborg M, Strange P, Werdelin L. Quantification of brain metabolites in amyotrophic lateral sclerosis by localized proton magnetic resonance spectroscopy. Neurology 48(4), 878-881 (1997).
143. Bradley WG, Bowen BC, Pattany PM, Rotta F. 1H-magnetic resonance spectroscopy in amyotrophic lateral sclerosis. J. Neurol. Sci. 169(1-2), 84-86 (1999).
144. Pohl C, Block W, Karitzky J et al. Proton magnetic resonance spectroscopy of the motor cortex in 70 patients with amyotrophic lateral sclerosis. Arch. Neurol. 58(5), 729-735 (2001).
145. Sarchielli P, Pelliccioli GP, Tarducci R et al. Magnetic resonance imaging and 1H-magnetic resonance spectroscopy in amyotrophic lateral sclerosis. Neuroradiology 43(3), 189-197 (2001).
146. Schuff N, Rooney WD, Miller R et al. Reanalysis of multislice (1)H MRSI in amyotrophic lateral sclerosis. Magn. Reson. Med. 45(3), 513-516 (2001).
147. Block W, Traber F, Flacke S, Jessen F, Pohl C, Schild H. In-vivo proton MR-spectroscopy of the human brain: assessment of N-acetylaspartate (NAA) reduction as a marker for neurodegeneration. Amino Acids 23(1-3), 317-323 (2002).
148. Suhy J, Miller RG, Rule R et al. Early detection and longitudinal changes in amyotrophic lateral sclerosis by (1)H MRSI. Neurology 58(5), 773-779 (2002).
149. Block W, Karitzky J, Traber F et al. Proton magnetic resonance spectroscopy of the primary motor cortex in patients with motor neuron disease: subgroup analysis and follow-up measurements. Arch. Neurol. 55(7), 931-936 (1998).
150. Abe K, Takanashi M, Watanabe Y et al. Decrease in N-acetylaspartate/ creatine ratio in the motor area and the frontal lobe in amyotrophic lateral sclerosis. Neuroradiology 43(7), 537-541 (2001).
151. Rule RR, Suhy J, Schuff N, Gelinas DF, Miller RG, Weiner MW. Reduced NAA in motor and non-motor brain regions in amyotrophic lateral sclerosis: a cross-sectional and longitudinal study. Amyotroph. Lateral Scler. 5(3), 141-149 (2004).
152. Yin H, Lim CC, Ma L et al. Combined MR spectroscopic imaging and diffusion tensor MRI visualizes corticospinal tract degeneration in amyotrophic lateral sclerosis. J. Neurol. 251(10), 1249-1254 (2004).
153. Kalra S, Hanstock CC, Martin WR, Allen PS, Johnston WS. Detection of cerebral degeneration in amyotrophic lateral sclerosis using high-field magnetic resonance spectroscopy. Arch. Neurol. 63(8), 1144-1148 (2006).
154. Kalra S, Tai P, Genge A, Arnold DL. Rapid improvement in cortical neuronal integrity in amyotrophic lateral sclerosis detected by proton magnetic resonance spectroscopic imaging. J. Neurol. 253(8), 1060-1063 (2006).
155. Charil A, Corbo M, Filippi M et al. Structural and metabolic changes in the brain of patients with upper motor neuron disorders: a multiparametric MRI study. Amyotroph. Lateral Scler. 10(5-6), 269-279 (2009).
156. Lombardo F, Frijia F, Bongioanni P et al. Diffusion tensor MRI and MR spectroscopy in long lasting upper motor neuron involvement in amyotrophic lateral sclerosis. Arch. Ital. Biol. 147(3), 69-82 (2009).
157. Pyra T, Hui B, Hanstock C et al. Combined structural and neurochemical evaluation of the corticospinal tract in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 11(1-2), 157-165 (2010).
158. Sivak S, Bittsansky M, Kurca E et al. Proton magnetic resonance spectroscopy in patients with early stages of amyotrophic lateral sclerosis. Neuroradiology 52(12), 1079-1085 (2010).
159. Bowen BC, Pattany PM, Bradley WG et al. MR imaging and localized proton spectroscopy of the precentral gyrus in amyotrophic lateral sclerosis. Am. J. Neuroradiol. 21(4), 647-658 (2000).
160. Wang S, Poptani H, Woo JH et al. Amyotrophic lateral sclerosis: diffusion-tensor and chemical shift MR imaging at 3.0 T. Radiology 239(3), 831-838 (2006).
161. Ellis CM, Simmons A, Andrews C, Dawson JM, Williams SC, Leigh PN. A proton magnetic resonance spectroscopic study in ALS: correlation with clinical findings. Neurology 51(4), 1104-1109 (1998).
162. Cwik VA, Hanstock CC, Allen PS, Martin WR. Estimation of brainstem neuronal loss in amyotrophic lateral sclerosis with in vivo proton magnetic resonance spectroscopy. Neurology 50(1), 72-77 (1998).
163. Pioro EP, Majors AW, Mitsumoto H, Nelson DR, Ng TC. 1H-MRS evidence of neurodegeneration and excess glutamate + glutamine in ALS medulla. Neurology 53(1), 71-79 (1999).
164. Hanstock CC, Cwik VA, Martin WR. Reduction in metabolite transverse relaxation times in amyotrophic lateral sclerosis. J. Neurol. Sci. 198(1-2), 37-41 (2002).
165. Rothstein JD. Current hypotheses for the underlying biology of amyotrophic lateral sclerosis. Ann. Neurol. 65(Suppl. 1), S3-S9 (2009).
166. Sharma KR, Saigal G, Maudsley AA, Govind V. 1H MRS of basal ganglia and thalamus in amyotrophic lateral sclerosis. NMR Biomed. 24(10), 1270-1276 (2011).
167. Sudharshan N, Hanstock C, Hui B, Pyra T, Johnston W, Kalra S. Degeneration of the mid-cingulate cortex in amyotrophic lateral sclerosis detected in vivo with MR spectroscopy. Am. J. Neuroradiol. 32(2), 403-407 (2011).
168. Unrath A, Ludolph AC, Kassubek J. Brain metabolites in definite amyotrophic lateral sclerosis. A longitudinal proton magnetic resonance spectroscopy study. J. Neurol. 254(8), 1099-1106 (2007).
169. Kalra S, Cashman NR, Genge A, Arnold DL. Recovery of N-acetylaspartate in corticomotor neurons of patients with ALS after riluzole therapy. Neuroreport. 9(8), 1757-1761 (1998).
170. Atassi N, Ratai EM, Greenblatt DJ et al. A Phase I, pharmacokinetic, dosage escalation study of creatine monohydrate in subjects with amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 11(6), 508-513 (2010).
171. Pohl C, Block W, Traber F et al. Proton magnetic resonance spectroscopy and transcranial magnetic stimulation for the detection of upper motor neuron degeneration in ALS patients. J. Neurol. Sci. 190(1-2), 21-27 (2001).
172. Kaufmann P, Pullman SL, Shungu DC et al. Objective tests for upper motor neuron involvement in amyotrophic lateral sclerosis (ALS). Neurology 62(10), 1753-1757 (2004).
173. Dadon-Nachum M, Melamed E, Offen D. The dying-back phenomenon of motor neurons in ALS. J. Mol. Neurosci. 43(3), 470-477 (2010).
174. Nair G, Carew JD, Usher S, Lu D, Hu XP, Benatar M. Diffusion tensor imaging reveals regional differences in the cervical spinal cord in amyotrophic lateral sclerosis. Neuroimage 53(2), 576-583 (2010).
175. Ravits JM, La Spada AR. ALS motor phenotype heterogeneity, focality, and spread: deconstructing motor neuron degeneration. Neurology 73(10), 805-811 (2009).
176. Brooks JC, Beckmann CF, Miller KL et al. Physiological noise modelling for spinal functional magnetic resonance imaging studies. Neuroimage 39(2), 680-692 (2008).
177. Figley CR, Stroman PW. Development and validation of retrospective spinal cord motion time-course estimates (RESPITE) for spin-echo spinal fMRI: improved sensitivity and specificity by means of a motion-compensating general linear model analysis. Neuroimage 44(2), 421-427 (2009).
178. Terao S, Sobue G, Yasuda T, Kachi T, Takahashi M, Mitsuma T. Magnetic resonance imaging of the corticospinal tracts in amyotrophic lateral sclerosis. J. Neurol. Sci. 133(1-2), 66-72 (1995).
179. Waragai M, Shinotoh H, Hayashi M, Hattori T. High signal intensity on T1 weighted MRI of the anterolateral column of the spinal cord in amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry 62(1), 88-91 (1997).
180. Sperfeld AD, Bretschneider V, Flaith L et al. MR-pathologic comparison of the upper spinal cord in different motor neuron diseases. Eur. Neurol. 53(2), 74-77 (2005).
181. Freund PA, Dalton C, Wheeler-Kingshott CA et al. Method for simultaneous voxel-based morphometry of the brain and cervical spinal cord area measurements using 3D-MDEFT. J. Magn. Reson. Imaging 32(5), 1242-1247 (2010).
182. Valsasina P, Agosta F, Benedetti B et al. Diffusion anisotropy of the cervical cord is strictly associated with disability in amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry 78(5), 480-484 (2007).
183. Carew JD, Nair G, Pineda-Alonso N, Usher S, Hu X, Benatar M. Magnetic resonance spectroscopy of the cervical cord in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 12(3), 185-191 (2011).
184. Carew JD, Nair G, Andersen PM et al. Presymptomatic spinal cord neurometabolic findings in SOD1-positive people at risk for familial ALS. Neurology 77(14), 1370-1375 (2011).
185. Evans MC, Modo M, Talbot K, Sibson N, Turner MR. Magnetic resonance imaging of pathological processes in rodent models of amyotrophic lateral sclerosis. 13(3), 288-301 Amyotroph. Lateral Scler. (2011).
186. Underwood CK, Kurniawan ND, Butler TJ, Cowin GJ, Wallace RH. Non-invasive diffusion tensor imaging detects white matter degeneration in the spinal cord of a mouse model of amyotrophic lateral sclerosis. Neuroimage 55(2), 455-461 (2011).
187. Choi JK, Kustermann E, Dedeoglu A, Jenkins BG. Magnetic resonance spectroscopy of regional brain metabolite markers in FALS mice and the effects of dietary creatine supplementation. Eur. J. Neurosci. 30(11), 2143-2150 (2009).
188. Wilson JM, Petrik MS, Grant SC, Blackband SJ, Lai J, Shaw CA. Quantitative measurement of neurodegeneration in an ALS-PDC model using MR microscopy. Neuroimage 23(1), 336-343 (2004).
189. Choi JK, Dedeoglu A, Jenkins BG. Longitudinal monitoring of motor neuron circuitry in FALS rats using in-vivo phMRI. Neuroreport 21(3), 157-162 (2010).
190. Bouwman CJ, Wilmink JT, Mess WH, Backes WH. Spinal cord functional MRI at 3 T: gradient echo echo-planar imaging versus turbo spin echo. Neuroimage 43(2), 288-296 (2008).
191. Kornelsen J, Stroman PW. fMRI of the lumbar spinal cord during a lower limb motor task. Magn. Reson. Med. 52(2), 411-414 (2004).
192. Cohen-Adad J, Descoteaux M, Rossignol S, Hoge RD, Deriche R, Benali H. Detection of multiple pathways in the spinal cord using q-ball imaging. Neuroimage 42(2), 739-749 (2008).
193. Sigmund EE, Suero GA, Hu C et al. High-resolution human cervical spinal cord imaging at 7 T. NMR Biomed. doi:10.1002/nbm.1809 (2011) (Epub ahead of print).
194. Ding XQ, Kollewe K, Blum K et al. Value of quantitative analysis of routine clinical MRI sequences in ALS. Amyotroph. Lateral Scler. 12(6), 406-413 (2011).
195. Minnerop M, Specht K, Ruhlmann J, Grothe C, Wullner U, Klockgether T. In vivo voxel-based relaxometry in amyotrophic lateral sclerosis. J. Neurol. 256(1), 28-34 (2009).
196. Langkammer C, Enzinger C, Quasthoff S et al. Mapping of iron deposition in conjunction with assessment of nerve fiber tract integrity in amyotrophic lateral sclerosis. J. Magn. Reson. Imaging. 31(6), 1339-1345 (2010).
197. da Rocha AJ, Maia AC Jr, Nogueira RG, Lederman HM. Magnetic resonance findings in amyotrophic lateral sclerosis using a spin echo magnetization transfer sequence. Preliminary report. Arq. Neuropsiquiatr. 57(4), 912-915 (1999).
198. Kato Y, Matsumura K, Kinosada Y, Narita Y, Kuzuhara S, Nakagawa T. Detection of pyramidal tract lesions in amyotrophic lateral sclerosis with magnetization-transfer measurements. Am. J. Neuroradiol. 18(8), 1541-1547 (1997).
199. Tanabe JL, Vermathen M, Miller R, Gelinas D, Weiner MW, Rooney WD. Reduced MTR in the corticospinal tract and normal T2 in amyotrophic lateral sclerosis. Magn. Reson. Imaging 16(10), 1163-1169 (1998).
200. Carrara G, Carapelli C, Venturi F et al. A distinct MR imaging phenotype in amyotrophic lateral sclerosis: correlation between T1 magnetization transfer contrast hyperintensity along the corticospinal tract and diffusion tensor imaging analysis. Am. J. Neuroradiol. 33(4), 733-739 (2012).
201. Rule RR, Schuff N, Miller RG, Weiner MW. Gray matter perfusion correlates with disease severity in ALS. Neurology 74(10), 821-827 (2010).
202. Skotland T. Molecular imaging: challenges of bringing imaging of intracellular targets into common clinical use. Contrast Media Mol. Imaging 7(1), 1-6 (2012).
203. Sporns O. The human connectome: a complex network. Ann. NY Acad. Sci. 1224, 109-125 (2011).
204. Achard S, Salvador R, Whitcher B, Suckling J, Bullmore E. A resilient, low-frequency, small-world human brain functional network with highly connected association cortical hubs. J. Neurosci. 26(1), 63-72 (2006).
205. Hagmann P, Kurant M, Gigandet X et al. Mapping human whole-brain structural networks with diffusion MRI. PLoS ONE, 2(7), e597 (2007).
206. Chen ZJ, He Y, Rosa-Neto P, Germann J, Evans AC. Revealing modular architecture of human brain structural networks by using cortical thickness from MRI. Cereb. Cortex 18(10), 2374-2381 (2008).
207. Stam CJ. Functional connectivity patterns of human magnetoencephalographic recordings: a 'small-world' network? Neurosci. Lett. 355(1-2), 25-28 (2004).
208. van den Heuvel MP, Stam CJ, Boersma M, Hulshoff Pol HE. Small-world and scale-free organization of voxel-based resting-state functional connectivity in the human brain. Neuroimage 43(3), 528-539 (2008).
209. van den Heuvel MP, Sporns O. Rich-club organization of the human connectome. J. Neurosci. 31(44), 15775-15786 (2011).
210. Turner MR, Grosskreutz J, Kassubek J et al. Towards a neuroimaging biomarker for amyotrophic lateral sclerosis. Lancet Neurol. 10(5), 400-403 (2011).
211. Charcot JM. Lectures on the Diseases of the Nervous System. The New Sydenham Society, London, UK, 163-204 (1881).