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Neuroimage Clin. 2014 Aug 23;6:93-9. doi: 10.1016/j.nicl.2014.08.018. eCollection 2014.

Cerebellar pathology in Friedreich's ataxia: atrophied dentate nuclei with normal iron content.

Author information

1
Department of Neurology, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.
2
Erwin L. Hahn Institute for Magnetic Resonance Imaging, University Duisburg-Essen, Arendahls Wiese 199, Essen 45141, Germany.
3
Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich 52425, Germany ; Department of Neurology, University Hospital Bonn, Sigmund-Freud-straße 25, Bonn 53127, Germany.
4
Department of Computer Sciences, University of Düsseldorf, Universitätsstraße 1, Düsseldorf 40225, Germany.
5
Department of Neurology, Eberhard Karls-University, Geschwister-Scholl-platz, Tübingen, Tübingen 72074, Germany ; Hertie Institute for Clinical Brain Research, Eberhard Karls-University Tübingen, Hoppe-Seyler-straße 3, Tübingen 72076, Germany ; German Research Center for Neurodegenerative Diseases (DZNE), Otfried-Müller-straße 27, Tübingen 72076, Germany.
6
Institute of Diagnostic and Interventional Radiology and Neuroradiology, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.
7
Erwin L. Hahn Institute for Magnetic Resonance Imaging, University Duisburg-Essen, Arendahls Wiese 199, Essen 45141, Germany ; Institute of Diagnostic and Interventional Radiology and Neuroradiology, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.

Abstract

BACKGROUND:

In Friedreich's ataxia (FA) the genetically decreased expression of the mitochondrial protein frataxin leads to disturbance of the mitochondrial iron metabolism. Within the cerebellum the dentate nuclei (DN) are primarily affected. Histopathological studies show atrophy and accumulation of mitochondrial iron in DN. Dentate iron content has been suggested as a biomarker to measure the effects of siderophores/antioxidant treatment of FA. We assessed the iron content and the volume of DN in FA patients and controls based on ultra-high-field MRI (7 Tesla) images.

METHODS:

Fourteen FA patients (mean age 38.1 yrs) and 14 age- and gender-matched controls participated. Multi-echo gradient echo and susceptibility weighted imaging (SWI) sequences were acquired on a 7 T whole-body scanner. For comparison SWI images were acquired on a 1.5 T MR scanner. Volumes of the DN and cerebellum were assessed at 7 and 1.5 T, respectively. Parametric maps of T2 and T2* sequences were created and proton transverse relaxation rates were estimated as a measure of iron content.

RESULTS:

In FA, the DN and the cerebellum were significantly smaller compared to controls. However, proton transverse relaxation rates of the DN were not significantly different between both groups.

CONCLUSIONS:

Applying in vivo MRI methods we could demonstrate significant atrophy of the DN in the presence of normal iron content. The findings suggest that relaxation rates are not reliable biomarkers in clinical trials evaluating the potential effect of FA therapy.

KEYWORDS:

Dentate iron content; Dentate nuclei; Friedreich's ataxia; Relaxometry; Ultra-high-field MRI; Volumetry

PMID:
25379420
PMCID:
PMC4215469
DOI:
10.1016/j.nicl.2014.08.018
[Indexed for MEDLINE]
Free PMC Article

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