Deep gray matter involvement on brain MRI scans is associated with clinical progression in multiple sclerosis
Open accessAbstract
BACKGROUND: Conventional brain MRI lesion measures have unreliable associations with clinical progression in multiple sclerosis (MS). Gray matter imaging may improve clinical-MRI correlations. METHODS: We tested if gray matter MRI measures and conventional measures of lesions/atrophy predicted clinical progression in a 4-year longitudinal study of 97 patients with MS. Baseline and follow-up brain MRI were analyzed for basal ganglia and thalamic normalized T2 signal intensity, whole brain T2-hyperintense lesion volume, and whole brain atrophy. Logistic regression tested the ability of baseline or on-study change in MRI to predict disability progression, as reported by area under the receiver operator characteristics curve (AUC). RESULTS: Lower caudate T2-intensity at baseline (P= .04; AUC = .69) and on-study decreasing T2-intensity in the putamen (P= .03; AUC = .70) and thalamus (P= .01; AUC = .71) were the MRI variables associated with clinical progression when regression modeling was adjusted for length of follow-up interval, baseline EDSS, disease duration, age, and sex. CONCLUSIONS: Gray matter T2-hypointensity, suggestive of excessive iron deposition is associated with worsening disability in patients with MS. Gray matter MRI assessment may be able to capture neurodegenerative aspects of the disease, with more clinical relevance than derived from conventional MRI measures. J Neuroimaging 2009;19:3-8.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Iron concentrations increase in many deep grey matter structures as multiple sclerosis progresses.
“Iron concentrations increase in many deep grey matter structures as multiple sclerosis progresses.156,157”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [156]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS)
Kurtzke, J. F. (1983) · Neurology · doi:10.1212/wnl.33.11.1444 · Cited by 15,011 · see citing works
Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”
Polman, C. H., Reingold, S. C., Edan, G., Filippi, M., Hartung, H., Kappos, L., Lublin, F. D., Metz, L. M., McFarland, H. F., O'Connor, P. W., et al. (2005) · Annals of Neurology · doi:10.1002/ana.20703 · Cited by 5,017 · see citing works
A longitudinal study of abnormalities on MRI and disability from multiple sclerosis
Brex, P. A., Ciccarelli, O., O'Riordan, J. I., Sailer, M., Thompson, A. J., & Miller, D. H. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa011341 · Cited by 861 · see citing works
Progressive cerebral atrophy in multiple sclerosis A serial MRI study
Losseff, N. A., Wang, L., Lai, H. M., Yoo, D. S., Gawne-Cain, M. L., McDonald, W. I., Miller, D., & Thompson, A. J. (1996) · Brain · doi:10.1093/brain/119.6.2009 · Cited by 472 · see citing works
The measurement and clinical relevance of brain atrophy in multiple sclerosis.
Bermel, R., & Bakshi, R. (2006) · Lancet Neurology · doi:10.1016/s1474-4422(06)70349-0 · Cited by 454 · see citing works
Self-citationEight-year follow-up study of brain atrophy in patients with MS
Fisher, E., Rudick, R. A., Simon, J. H., Cutter, G., Baier, M. L., Lee, J., Miller, D., Weinstock‐Guttman, B., Mass, M. K., Dougherty, D. S., et al. (2002) · Neurology · doi:10.1212/01.wnl.0000036271.49066.06 · Cited by 373 · see citing works
Gray matter involvement in multiple sclerosis
Pirko, I., Lucchinetti, C., Sriram, S., & Bakshi, R. (2007) · Neurology · doi:10.1212/01.wnl.0000250267.85698.7a · Cited by 354 · see citing works
Self-citationMRI in multiple sclerosis: current status and future prospects
Bakshi, R., Thompson, A. J., Rocca, M. A., Pelletier, D., Dousset, V., Barkhof, F., Inglese, M., Guttmann, C. R., Horsfield, M. A., & Filippi, M. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70137-6 · Cited by 348 · see citing works
Self-citationIron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications
Stankiewicz, J. M., Panter, S. S., Neema, M., Arora, A., Batt, C. E., & Bakshi, R. (2007) · Neurotherapeutics · doi:10.1016/j.nurt.2007.05.006 · Cited by 301 · see citing works
Self-citationHammond, K. E., Metcalf, M., Carvajal, L. E., Okuda, D. T., Srinivasan, R., Vigneron, D. B., Nelson, S. J., & Pelletier, D. (2008) · Annals of Neurology · doi:10.1002/ana.21582 · Cited by 281 · see citing works
T2 Hypointensity in the Deep Gray Matter of Patients With Multiple Sclerosis
Bakshi, R., Benedict, R. H. B., Bermel, R. A., Caruthers, S. D., Puli, S. R., Tjoa, C. W., Fabiano, A. J., & Jacobs, L. R. (2002) · Archives of Neurology · doi:10.1001/archneur.59.1.62 · Cited by 231 · see citing works
Self-citationIron deposits surrounding multiple sclerosis plaques.
Craelius, W., Mw, M., Luessenhop, C. P., Sugar, A. W., & Mihalakis, I. (1982) · PubMed · Cited by 197 · see citing works
Levine, S. M., & Chakrabarty, A. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1306.021 · Cited by 183 · see citing works
Brass, S. D., Benedict, R. H. B., Weinstock‐Guttman, B., Munschauer, F., & Bakshi, R. (2006) · Multiple Sclerosis Journal · doi:10.1191/135248506ms1301oa · Cited by 158 · see citing works
Self-citationGauthier, S. A., Glanz, B. I., Mandel, M., & Weiner, H. L. (2006) · Autoimmunity Reviews · doi:10.1016/j.autrev.2006.02.012 · Cited by 152 · see citing works
Self-citationGe, Y., Jensen, J. H., Lu, H., Helpern, J. A., Miles, L., Inglese, M., Babb, J. S., Herbert, J., & Grossman, R. I. (2007) · American Journal of Neuroradiology · doi:10.3174/ajnr.a0646 · Cited by 142 · see citing works
Clinical–Magnetic Resonance Imaging Correlations in Multiple Sclerosis
Zivadinov, R., & Leist, T. P. (2005) · Journal of Neuroimaging · doi:10.1177/1051228405283291 · Cited by 134 · see citing works
Neema, M., Stankiewicz, J., Arora, A., Dandamudi, V. S. R., Batt, C. E., Guss, Z. D., AL-Sabbagh, A., & Bakshi, R. (2007) · Journal of Neuroimaging · doi:10.1111/j.1552-6569.2007.00131.x · Cited by 123 · see citing works
Self-citationWei, X., Warfield, S. K., Zou, K. H., Wu, Y. G., Li, X., Guimond, A., Mugler, J. P., Benson, R. R., WOLFSON, L. I., Weiner, H. L., et al. (2002) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.10053 · Cited by 122 · see citing works
Self-citationHeme Oxygenase‐1: Transducer of Pathological Brain Iron Sequestration under Oxidative Stress
Schipper, H. M. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1306.007 · Cited by 117 · see citing works
Bakshi, R., Dmochowski, J., Shaikh, Z. A., & Jacobs, L. (2001) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(01)00477-4 · Cited by 107 · see citing works
Self-citationTjoa, C. W., Benedict, R. H. B., Weinstock‐Guttman, B., Fabiano, A. J., & Bakshi, R. (2005) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2005.02.009 · Cited by 103 · see citing works
Self-citationBermel, R. A., Puli, S. R., Rudick, R. A., Weinstock‐Guttman, B., Fisher, E., Munschauer, F. E., & Bakshi, R. (2005) · Archives of Neurology · doi:10.1001/archneur.62.9.1371 · Cited by 99 · see citing works
Self-citationMRI in Multiple Sclerosis: What’s Inside the Toolbox?
Neema, M., Stankiewicz, J., Arora, A., Guss, Z. D., & Bakshi, R. (2007) · Neurotherapeutics · doi:10.1016/j.nurt.2007.08.001 · Cited by 91 · see citing works
Self-citationMeasurement of Whole-Brain Atrophy in Multiple Sclerosis
Pelletier, D., Garrison, K. A., & Henry, R. G. (2004) · Journal of Neuroimaging · doi:10.1177/1051228404266264 · Cited by 81 · see citing works
Desferrioxamine suppresses experimental allergic encephalomyelitis induced by MBP in SJL mice
Pedchenko, T. V., & LeVine, S. M. (1998) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(97)00256-7 · Cited by 78 · see citing works
Iron-deficient mice fail to develop autoimmune encephalomyelitis
Grant, S. M., Wiesinger, J. A., Beard, J. L., & Cantorna, M. T. (2003) · The Journal of Nutrition · doi:10.1093/jn/133.8.2635 · Cited by 78 · see citing works
Iron deposits in the central nervous system of SJL mice with experimental allergic encephalomyelitis
Forge, J. K., Pedchenko, T. V., & Vine, S. M. L. (1998) · Life Sciences · doi:10.1016/s0024-3205(98)00512-8 · Cited by 55 · see citing works
Zhang, Y., Zabad, R., Wei, X., Metz, L., Hill, M. D., & Mitchell, J. (2007) · Multiple Sclerosis Journal · doi:10.1177/1352458507076411 · Cited by 52 · see citing works
Mitchell, K. M., Dotson, A. L., Cool, K. M., Chakrabarty, A., Benedict, S. H., & LeVine, S. M. (2007) · Multiple Sclerosis Journal · doi:10.1177/1352458507078916 · Cited by 51 · see citing works
Predicting short-term disability in multiple sclerosis
Gauthier, S. A., Mandel, M., Guttmann, C. R. G., Glanz, B. I., Khoury, S. J., Betensky, R. A., & Weiner, H. L. (2007) · Neurology · doi:10.1212/01.wnl.0000264890.97479.b1 · Cited by 50 · see citing works
Self-citationMeasurement of Whole‐Brain Atrophy in Multiple Sclerosis
Pelletier, D., Garrison, K. A., & Henry, R. G. (2004) · Journal of Neuroimaging · doi:10.1111/j.1552-6569.2004.tb00274.x · Cited by 50 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [4]Zivadinov R Leist TP Clinical–MRI correlations in multiple sclerosis J Neuroimaging 2005 15 10S 21S 16385015
- [12]Hammond KE Metcalf M Okuda DT In vivo high resolution MR imaging at 7T of multiple sclerosis with sensitivity to iron Neurology 2008 70 A8 19107998
Cited by
Sorted by citations
The role of iron in brain ageing and neurodegenerative disorders
Ward, R. J., Zucca, F. A., Duyn, J. H., Crichton, R. R., & Zecca, L. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70117-6 · Cited by 1,819 · see citing works
Kell, D. B. (2010) · Archives of Toxicology · doi:10.1007/s00204-010-0577-x · Cited by 361 · see citing works
MRI assessment of iron deposition in multiple sclerosis
Ropele, S., de Graaf, W., Khalil, M., Wattjes, M. P., Langkammer, C., Rocca, M. A., Rovira, A., Palace, J., Barkhof, F., Filippi, M., et al. (2011) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.22590 · Cited by 103 · see citing works
Iron chelation and multiple sclerosis
Weigel, K. J., Lynch, S. G., & LeVine, S. M. (2014) · ASN NEURO · doi:10.1042/an20130037 · Cited by 63 · see citing works
- Authors
- Neema, M., Arora, A., Healy, B. C., Guss, Z. D., Brass, S. D., Duan, Y., Buckle, G. J., Glanz, B. I., Stazzone, L., Khoury, S. J., Weiner, H. L., Guttmann, C. R. G., & Bakshi, R.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Bakshi, Rohit
- ORCID
- Venue
- Journal of Neuroimaging
- Publisher
- Wiley
- Published
- 2009-01
- Volume
- 19
- Issue
- 1
- Pages
- 3-8
- ISSN
- 1051-2284 (ISSN-L)
- 1552-6569
- PMC
- PMC2762230
- OpenAlex
- W2054346790
- Cited by
- 128
- References
- 32
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 6 · 2019: 3 · 2018: 9 · 2017: 5 · 2016: 14 · 2015: 10 · 2014: 13 · 2013: 11 · 2012: 11
- FWCI
- 8.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuroimaging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (K23 NS42379-01, K23NS042379, R01NS055083)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
- Keywords
- multiple sclerosis, clinical progression, disability progression, basal ganglia, thalamus, caudate nucleus, putamen, T2 hypointensity, iron accumulation, neurodegeneration, brain atrophy, T2 hyperintensity, predictive biomarkers
- MeSH terms
- Adult, Brain, Female, Humans, Iron, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Retrospective Studies, Chi-Square Distribution, Logistic Models, Disease Progression, Area Under Curve
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
