Seven-Tesla proton magnetic resonance spectroscopic imaging in adult X-linked adrenoleukodystrophy
Open accessAbstract
BACKGROUND: Adults with X-linked adrenoleukodystrophy (X-ALD) remain at risk for progressive neurological deterioration. Phenotypes vary in their pathology, ranging from axonal degeneration to inflammatory demyelination. The severity of symptoms is poorly explained by conventional imaging. OBJECTIVE: To test the hypothesis that neurochemistry in normal-appearing brains differs in adult phenotypes of X-ALD and that neurochemical changes correlate with the severity of symptoms. PATIENTS AND METHODS: Using a 7-Tesla scanner, we performed structural and proton magnetic resonance spectroscopic imaging in 13 adult patients with X-ALD: 4 patients with adult cerebral ALD, 5 patients with adrenomyeloneuropathy (AMN), and 4 female heterozygotes. Nine healthy controls were included. RESULTS: Among adult X-ALD phenotypes, the myo-inositol to creatine ratio was 46% higher and the choline to creatine ratio was 21% higher in normal-appearing white matter of those with adult cerebral ALD compared with those with AMN (P < .05). Both N-acetylaspartate to creatine (P = .03) and glutamate to creatine (P = .04) ratios were lower in AMN patients than in controls. There were no significant differences between patients with AMN and female heterozygotes. In the cortex, patients with adult cerebral ALD had lower N-acetylaspartate to creatine ratios compared with female heterozygotes and controls (P = .02). The global myo-inositol to creatine ratio demonstrated a significant association with Expanded Disability Status Scale score (Spearman rho = 0.66, P = .04). CONCLUSIONS: Seven-Tesla proton magnetic resonance spectroscopic imaging reveals differences in the neurochemistry of adult cerebral ALD but cannot distinguish AMN patients from female heterozygotes. Myo-inositol to creatine ratio correlates with the severity of the symptoms and may be a meaningful biomarker in adult X-ALD.
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Cites
Automatic quantitation of localized in vivo1H spectra with LCModel
Provencher, S. W. (2001) · NMR in Biomedicine · doi:10.1002/nbm.698 · Cited by 1,640 · see citing works
Birken, D. L., & Oldendorf, W. H. (1989) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(89)80048-x · Cited by 783 · see citing works
Moser, H. W., Mahmood, A., & Raymond, G. V. (2007) · Nature Clinical Practice Neurology · doi:10.1038/ncpneuro0421 · Cited by 663 · see citing works
Adrenoleukodystrophy: A Clinical and Pathological Study of 17 Cases
Schaumburg, H. H. (1975) · Archives of Neurology · doi:10.1001/archneur.1975.00490510033001 · Cited by 475 · see citing works
Axonal loss and neuroinflammation caused by peroxisome-deficient oligodendrocytes
Kassmann, C. M., Lappe-Siefke, C., Baes, M., Brügger, B., Mildner, A., Werner, H. B., Natt, O., Michaelis, T., Prinz, M., Frahm, J., et al. (2007) · Nature Genetics · doi:10.1038/ng2070 · Cited by 357 · see citing works
Moser, H. W., Loes, D. J., Melhem, E. R., Raymond, G. V., Bezman, L., Cox, C. S., & Lu, S.-E. (2000) · Neuropediatrics · doi:10.1055/s-2000-9236 · Cited by 210 · see citing works
Volumetric spectroscopic imaging with spiral‐based k‐space trajectories
Elfar Adalsteinsson, A., Pablo Irarrázaval, M., Topp, S., Meyer, C. H., Macovski, A., & Spielman, D. M. (1998) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910390606 · Cited by 202 · see citing works
Quantitative proton spectroscopy of canine brain: in Vivo and in Vitro correlations
Barker, P. B., Breiter, S. N., Soher, B. J., Chatham, J. C., Forder, J. R., Samphilipo, M. A., Magee, C. A., & Anderson, J. H. (1994) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910320202 · Cited by 187 · see citing works
van Geel, B. M., Assies, J., Haverkort, E. B., Koelman, J. H. T. M., Verbeeten, B., Wanders, R. J. A., & Barth, P. G. (1999) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.67.3.290 · Cited by 131 · see citing works
Antuono, P. G., Jones, J. L., Wang, Y., & Li, S.-J. (2001) · Neurology · doi:10.1212/wnl.56.6.737 · Cited by 119 · see citing works
Expression of the adrenoleukodystrophy protein in the human and mouse central nervous system
Fouquet, F., Zhou, J. M., Ralston, E., Murray, K., Troalen, F., Magal, E., Robain, O., Dubois-Dalcq, M., & Aubourg, P. (1997) · Neurobiology of Disease · doi:10.1006/nbdi.1997.0127 · Cited by 115 · see citing works
Proton MR spectroscopic study at 3 Tesla on glutamate/glutamine in Alzheimer’s disease
Hattori, N., Abe, K., Sakoda, S., & Sawada, T. (2002) · Neuroreport · doi:10.1097/00001756-200201210-00041 · Cited by 112 · see citing works
Eight‐channel phased array coil and detunable TEM volume coil for 7 T brain imaging
Wiggins, G. C., Potthast, A., Triantafyllou, C., Wiggins, C. J., & Wald, L. L. (2005) · Magnetic Resonance in Medicine · doi:10.1002/mrm.20547 · Cited by 94 · see citing works
Self-citationIN VIVO MR SPECTROSCOPY OF HUMAN DEMENTIA
Ross, B. D., Blüml, S., Cowan, R. P., Danielsen, E. R., Farrow, N. A., & Tan, J. (1998) · Neuroimaging Clinics of North America · doi:10.1016/s1052-5149(25)00541-6 · Cited by 90 · see citing works
Quantitative Proton Magnetic Resonance Spectroscopy of Childhood Adrenoleukodystrophy
Pouwels, P. J. W., Kruse, B., Korenke, G. C., Mao, X., Hanefeld, F. A., & Frahm, J. (1998) · Neuropediatrics · doi:10.1055/s-2007-973571 · Cited by 90 · see citing works
Childhood adrenoleukodystrophy: assessment with proton MR spectroscopy.
Tzika, A. A., Ball, W. S., Vigneron, D. B., Dunn, R. S., Nelson, S. J., & Kirks, D. R. (1993) · Radiology · doi:10.1148/radiology.189.2.8210375 · Cited by 83 · see citing works
The neuropsychiatry of adult-onset adrenoleukodystrophy
Rosebush, P. I., Garside, S., Levinson, A. J., & Mazurek, M. F. (1999) · The Journal of Neuropsychiatry and Clinical Neurosciences · doi:10.1176/jnp.11.3.315 · Cited by 72 · see citing works
MRI and proton MRSI in women heterozygous for X-linked adrenoleukodystrophy
Fatemi, A. S., Barker, P. B., Uluğ, A. M., Nagae‐Poetscher, L. M., Beauchamp, N. J., Moser, A. B., Raymond, G. V., Moser, H. W., & Naidu, S. (2003) · Neurology · doi:10.1212/01.wnl.0000059546.15529.cb · Cited by 71 · see citing works
Eichler, F., Mahmood, A., Loes, D. J., Bezman, L., Lin, D., Moser, H. W., & Raymond, G. V. (2007) · Archives of Neurology · doi:10.1001/archneur.64.5.659 · Cited by 60 · see citing works
Self-citationLate-onset adrenoleukodystrophy associated with long-standing psychiatric symptoms
Garside, S., Rosebush, P. I., Levinson, A. J., & Mazurek, M. F. (1999) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v60n0708 · Cited by 51 · see citing works
Spectroscopic evidence of cerebral axonopathy in patients with “pure” adrenomyeloneuropathy
Dubey, P., Fatemi, A. S., Barker, P. B., Degaonkar, M. N., Tröger, M., Zackowski, K. M., Bastian, A. J., Smith, S. A., Pomper, M. G., Moser, H. W., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000149514.13580.84 · Cited by 45 · see citing works
Broom, K. A., Anthony, D. C., Lowe, J. P., Griffin, J. L., Scott, H., Blamire, A. M., Styles, P., Perry, V. H., & Sibson, N. R. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.04.001 · Cited by 34 · see citing works
Spiral readout gradients for the reduction of motion artifacts in chemical shift imaging
Kim, D., Adalsteinsson, E., & Spielman, D. M. (2004) · Magnetic Resonance in Medicine · doi:10.1002/mrm.20004 · Cited by 32 · see citing works
Self-citationAubourg, P. R. (2007) · Nature Genetics · doi:10.1038/ng0807-936 · Cited by 18 · see citing works
Role for peroxisome proliferator-activated receptor-gamma in Alzheimer's disease.
van Geel (2001) · Open Repository and Bibliography (University of Luxembourg) · doi:10.1002/1531-8249(20010201)49:2 · Cited by 7 · see citing works
Increased activity of surviving locus ceruleus neurons in Alzheimer's disease
Moser (1999) · Pure Amsterdam UMC · doi:10.1002/1531-8249(199901)45:1
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Kemp, S., Berger, J., & Aubourg, P. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.03.012 · Cited by 283 · see citing works
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Trattnig, S., Springer, E., Bogner, W., Hangel, G. J., Strasser, B., Dymerska, B., Cardoso, P. L., & Robinson, S. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.11.031 · Cited by 183 · see citing works
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Ferrer, I., Aubourg, P., & Pujol, A. (2010) · Brain Pathology · doi:10.1111/j.1750-3639.2010.00390.x · Cited by 139 · see citing works
Henning, A. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.07.017 · Cited by 107 · see citing works
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Maguire, C. A., Ramirez, S. H., Merkel, S. F., Sena‐Esteves, M., & Breakefield, X. O. (2014) · Neurotherapeutics · doi:10.1007/s13311-014-0299-5 · Cited by 96 · see citing works
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Hangel, G. J., Strasser, B., Považan, M., Niess, E., Hingerl, L., Boubela, R. N., Gruber, S., Trattnig, S., & Bogner, W. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.10.043 · Cited by 89 · see citing works
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Dale, B. M., Brown, M. A., & Semelka, R. C. (2015) · doi:10.1002/9781119013068.ch13 · Cited by 78 · see citing works
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Jangouk, P., Zackowski, K. M., Naidu, S., & Raymond, G. V. (2012) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2011.11.001 · Cited by 63 · see citing works
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Köhler, W. (2010) · Current Opinion in Neurology · doi:10.1097/wco.0b013e328338313a · Cited by 54 · see citing works
Lee, C. A. A., Seo, H. S., Armien, A. G., Bates, F. S., Tolar, J., & Azarin, S. M. (2018) · Fluids and Barriers of the CNS · doi:10.1186/s12987-018-0094-5 · Cited by 52 · see citing works
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Lauer, A., Da, X., Hansen, M. B., Boulouis, G., Ou, Y., Cai, X., Liberato Celso Pedrotti, A., Kalpathy-Cramer, J., Caruso, P., Hayden, D. L., et al. (2017) · Brain · doi:10.1093/brain/awx262 · Cited by 48 · see citing works
Self-citationHangel, G. J., Strasser, B., Považan, M., Gruber, S., Chmelík, M., Gajdošík, M., Trattnig, S., & Bogner, W. (2015) · NMR in Biomedicine · doi:10.1002/nbm.3386 · Cited by 48 · see citing works
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Cheong, I., Marjańska, M., Deelchand, D. K., Eberly, L. E., Walk, D., & Öz, G. (2017) · Neurochemical Research · doi:10.1007/s11064-017-2248-2 · Cited by 48 · see citing works
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- Authors
- Ratai, E., Kok, T., Wiggins, C., Wiggins, G., Grant, E., Gagoski, B., O’Neill, G., Adalsteinsson, E., & Eichler, F.
- Affiliations
- Massachusetts General Hospital (US)
- Massachusetts Institute of Technology (US)
- Harvard University (US)
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2008-11-10
- Volume
- 65
- Issue
- 11
- Pages
- 1488
- ISSN
- 0003-9942 (ISSN-L)
- PMC
- PMC2829763
- OpenAlex
- W1986041974
- Cited by
- 37
- References
- 26
- Citations by year
- 2021: 4 · 2018: 1 · 2017: 3 · 2016: 7 · 2015: 4 · 2014: 2 · 2013: 2 · 2012: 4
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (K08NS052550, R01NS050041, R21NS059331)
- National Center for Research Resources (P41RR014075)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- X-linked adrenoleukodystrophy, adrenomyeloneuropathy, proton magnetic resonance spectroscopic imaging, 7T MRI, choline/creatine ratio, normal-appearing white matter, neurochemical markers, Expanded Disability Status Scale, disease severity, female heterozygotes, demyelination
- MeSH terms
- Adrenoleukodystrophy, Adult, Aged, Brain, Choline, Creatine, Disability Evaluation, Fatty Acids, Female, Heterozygote, Humans, Inositol, Male, Middle Aged, Magnetic Resonance Spectroscopy, Periaqueductal Gray, Phenotype, Severity of Illness Index, Sex Factors, Young Adult
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