TY - JOUR
T1 - Quantitative susceptibility mapping suggests altered brain iron in premanifest Huntington disease
AU - Van Bergen, Jiri M.G.
AU - Hua, J.
AU - Unschuld, P. G.
AU - Lim, Issel Anne L.
AU - Jones, Craig K.
AU - Margolis, Russell L.
AU - Ross, Christopher A.
AU - Van Zijl, Peter C.M.
AU - Li, Xu
N1 - Funding Information:
This project was supported by the National Center for Research Resources and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health through resource grant P41 EB015909, with educational funding from a National Institutes of Health Training Grant for Interdisciplinary Training in Psychiatry and Neuroscience T32 MH015330. In addition, a grant from the Huntington's Disease Society of America-Centers of Excellence and a grant from the David Mahoney Neuroimaging Program from the Dana Foundation supported this work. Dr Peter van Zijl is a paid lecturer for Philips Healthcare and is the inventor of technology that is licensed to Philips Healthcare. Dr Xu Li's salary is supported, in part, by a grant from Philips Healthcare. This arrangement has been approved by Johns Hopkins University in accordance with its conflict of interest policies. Issel Anne Lim-RELATED: Grant: National Institutes of Health Training Grant for Interdisciplinary Training in Psychiatry and Neuroscience (T32 MH015330).∗ Craig Jones-RELATED: Grant: Philips Healthcare,∗ Comments:My salary was paid, in part, by a grant to the Kennedy Krieger Institute from Philips Healthcare. Russell Margolis-RELATED: Grant: National Institutes of Health ∗; UNRELATED: Grants/Grants Pending: National Institutes of Health, Prana, Auspex, Teva, Child Health and Development Institute, Comments: treatment trials and pathogenic studies of HD. Christopher Ross-RELATED: Grant: Huntington's Disease Society of America-Centers of Excellence.∗ Peter van Zijl-RELATED: Grant: Philips Healthcare (technical development grant)∗; Support for Travel to Meetings for the Study or Other Purposes: Philips Healthcare (supported travel to conferences); UNRELATED: Payment for Lectures (including service on Speakers Bureaus): Philips Healthcare, Comments: In the past, they have provided honoraria for lectures; Patents (planned, pending or issued): Philips Healthcare,∗ Comments: provided funds for patent licensing to the institution and also got income from such patent licenses; Travel/Accommodations/Meeting Expenses Unrelated to Activities Listed: Philips Healthcare, Comments: supported travel to conferences; OTHER: Dr Peter van Zijl is a paid lecturer for Philips Healthcare and is the inventor of technology that is licensed to Philips Healthcare. Xu Li-RELATED: Grant: Philips Healthcare, Comments: Dr Xu Li's salary is supported, in part, by a grant from Philips Healthcare. This arrangement has been approved by Johns Hopkins University in accordance with its conflict of interest policies. ∗Money paid to the institution.
PY - 2016/5
Y1 - 2016/5
N2 - BACKGROUND AND PURPOSE: In patients with premanifest (nonsymptomatic) and advanced Huntington disease, changes in brain iron levels in the basal ganglia have been previously reported, especially in the striatum. Quantitative susceptibility mapping by using MR phase imaging allows in vivo measurements of tissue magnetic susceptibility, which has been shown to correlate well with iron levels in brain gray matter and is believed to be more specific than other imaging-based iron measures. The purpose of this study was to investigate the use of magnetic susceptibility as a biomarker of disease progression. MATERIALS AND METHODS: Fifteen subjects with premanifest Huntington disease and 16 age-matched healthy controls were scanned at 7T. Magnetic susceptibility, effective relaxation, and tissue volume in deep gray matter structures were quantified and compared with genetic and clinical measures. RESULTS: Subjects with premanifest Huntington disease showed significantly higher susceptibility values in the caudate nucleus, putamen, and globus pallidus, indicating increased iron levels in these structures. Significant decreases in magnetic susceptibility were found in the substantia nigra and hippocampus. In addition, significant volume loss (atrophy) and an increase effective relaxation were observed in the caudate nucleus and putamen. Susceptibility values in the caudate nucleus and putamen were found to be inversely correlated with structure volumes and directly correlated with the genetic burdens, represented by cytosine-adenine-guanine repeat age-product-scaled scores. CONCLUSIONS: The significant magnetic susceptibility differences between subjects with premanifest Huntington disease and controls and their correlation with genetic burden scores indicate the potential use of magnetic susceptibility as a biomarker of disease progression in premanifest Huntington disease.
AB - BACKGROUND AND PURPOSE: In patients with premanifest (nonsymptomatic) and advanced Huntington disease, changes in brain iron levels in the basal ganglia have been previously reported, especially in the striatum. Quantitative susceptibility mapping by using MR phase imaging allows in vivo measurements of tissue magnetic susceptibility, which has been shown to correlate well with iron levels in brain gray matter and is believed to be more specific than other imaging-based iron measures. The purpose of this study was to investigate the use of magnetic susceptibility as a biomarker of disease progression. MATERIALS AND METHODS: Fifteen subjects with premanifest Huntington disease and 16 age-matched healthy controls were scanned at 7T. Magnetic susceptibility, effective relaxation, and tissue volume in deep gray matter structures were quantified and compared with genetic and clinical measures. RESULTS: Subjects with premanifest Huntington disease showed significantly higher susceptibility values in the caudate nucleus, putamen, and globus pallidus, indicating increased iron levels in these structures. Significant decreases in magnetic susceptibility were found in the substantia nigra and hippocampus. In addition, significant volume loss (atrophy) and an increase effective relaxation were observed in the caudate nucleus and putamen. Susceptibility values in the caudate nucleus and putamen were found to be inversely correlated with structure volumes and directly correlated with the genetic burdens, represented by cytosine-adenine-guanine repeat age-product-scaled scores. CONCLUSIONS: The significant magnetic susceptibility differences between subjects with premanifest Huntington disease and controls and their correlation with genetic burden scores indicate the potential use of magnetic susceptibility as a biomarker of disease progression in premanifest Huntington disease.
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U2 - 10.3174/ajnr.A4617
DO - 10.3174/ajnr.A4617
M3 - Article
C2 - 26680466
AN - SCOPUS:84969849443
SN - 0195-6108
VL - 37
SP - 789
EP - 796
JO - American Journal of Neuroradiology
JF - American Journal of Neuroradiology
IS - 5
ER -