Abstract

BACKGROUND AND PURPOSE: The H63D-HFE single nucleotide polymorphism (SNP) has been associated with brain iron dysregulation; however, the emergent role of this missense variant in brain structure and function has yet to be determined. Previous work has demonstrated that HFE SNP carriers have reduced white matter magnetic resonance imaging (MRI) proton relaxation rates. The mechanism by which white matter alterations perturb MRI relaxation is unknown as is how these metrics are related to myelin integrity. METHODS: Fifteen subjects heterozygous for the HFE-H63D SNP and 25 controls with wild-type HFE had diffusion-weighted, anatomical MRIs taken, and underwent cognitive assessment. Fractional anisotropy (FA), mean diffusion (MD), and mode of anisotropy (MO) were calculated from the diffusion dataset to investigate the relationship between the H63D-HFE SNP and myelin integrity. RESULTS: A decrease in FA, an increase in MD, and an increase in MO are demonstrated in multiple H63D-HFE polymorphism carrier white matter tracts. Regions with altered diffusion metrics are notably located in heavily myelinated white matter association fibers, such as the anterior corona radiata and longitudinal fasciculi. CONCLUSIONS: The MRI data presented here demonstrate that H63D-HFE polymorphism carriers have diffusivity changes in white matter compared to wild-type subjects. The reduced integrity white matter tracts in H63D-HFE carriers are hypothesized to be related to increased susceptibility of these late-myelinating regions to cellular stress induced by oligodendrocyte iron dyshomeostasis.

Original languageEnglish (US)
Pages (from-to)126-133
Number of pages8
JournalJournal of Neuroimaging
Volume28
Issue number1
DOIs
StatePublished - Jan 1 2018

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Single Nucleotide Polymorphism
Anisotropy
Magnetic Resonance Imaging
Myelin Sheath
Iron
Diffusion Magnetic Resonance Imaging
Oligodendroglia
Brain
White Matter
Protons

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging
  • Clinical Neurology

Cite this

@article{d660fdb32ebf48a1917d6ed90199ac44,
title = "Reduced Cerebral White Matter Integrity Assessed by DTI in Cognitively Normal H63D-HFE Polymorphism Carriers",
abstract = "BACKGROUND AND PURPOSE: The H63D-HFE single nucleotide polymorphism (SNP) has been associated with brain iron dysregulation; however, the emergent role of this missense variant in brain structure and function has yet to be determined. Previous work has demonstrated that HFE SNP carriers have reduced white matter magnetic resonance imaging (MRI) proton relaxation rates. The mechanism by which white matter alterations perturb MRI relaxation is unknown as is how these metrics are related to myelin integrity. METHODS: Fifteen subjects heterozygous for the HFE-H63D SNP and 25 controls with wild-type HFE had diffusion-weighted, anatomical MRIs taken, and underwent cognitive assessment. Fractional anisotropy (FA), mean diffusion (MD), and mode of anisotropy (MO) were calculated from the diffusion dataset to investigate the relationship between the H63D-HFE SNP and myelin integrity. RESULTS: A decrease in FA, an increase in MD, and an increase in MO are demonstrated in multiple H63D-HFE polymorphism carrier white matter tracts. Regions with altered diffusion metrics are notably located in heavily myelinated white matter association fibers, such as the anterior corona radiata and longitudinal fasciculi. CONCLUSIONS: The MRI data presented here demonstrate that H63D-HFE polymorphism carriers have diffusivity changes in white matter compared to wild-type subjects. The reduced integrity white matter tracts in H63D-HFE carriers are hypothesized to be related to increased susceptibility of these late-myelinating regions to cellular stress induced by oligodendrocyte iron dyshomeostasis.",
author = "Meadowcroft, {Mark D.} and Jianli Wang and Purnell, {Carson J.} and Eslinger, {Paul J.} and Neely, {Elizabeth B.} and Yang, {Qing X.} and Connor, {James R.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1111/jon.12461",
language = "English (US)",
volume = "28",
pages = "126--133",
journal = "Journal of Neuroimaging",
issn = "1051-2284",
publisher = "Wiley-Blackwell",
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}

Reduced Cerebral White Matter Integrity Assessed by DTI in Cognitively Normal H63D-HFE Polymorphism Carriers. / Meadowcroft, Mark D.; Wang, Jianli; Purnell, Carson J.; Eslinger, Paul J.; Neely, Elizabeth B.; Yang, Qing X.; Connor, James R.

In: Journal of Neuroimaging, Vol. 28, No. 1, 01.01.2018, p. 126-133.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Reduced Cerebral White Matter Integrity Assessed by DTI in Cognitively Normal H63D-HFE Polymorphism Carriers

AU - Meadowcroft, Mark D.

AU - Wang, Jianli

AU - Purnell, Carson J.

AU - Eslinger, Paul J.

AU - Neely, Elizabeth B.

AU - Yang, Qing X.

AU - Connor, James R.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - BACKGROUND AND PURPOSE: The H63D-HFE single nucleotide polymorphism (SNP) has been associated with brain iron dysregulation; however, the emergent role of this missense variant in brain structure and function has yet to be determined. Previous work has demonstrated that HFE SNP carriers have reduced white matter magnetic resonance imaging (MRI) proton relaxation rates. The mechanism by which white matter alterations perturb MRI relaxation is unknown as is how these metrics are related to myelin integrity. METHODS: Fifteen subjects heterozygous for the HFE-H63D SNP and 25 controls with wild-type HFE had diffusion-weighted, anatomical MRIs taken, and underwent cognitive assessment. Fractional anisotropy (FA), mean diffusion (MD), and mode of anisotropy (MO) were calculated from the diffusion dataset to investigate the relationship between the H63D-HFE SNP and myelin integrity. RESULTS: A decrease in FA, an increase in MD, and an increase in MO are demonstrated in multiple H63D-HFE polymorphism carrier white matter tracts. Regions with altered diffusion metrics are notably located in heavily myelinated white matter association fibers, such as the anterior corona radiata and longitudinal fasciculi. CONCLUSIONS: The MRI data presented here demonstrate that H63D-HFE polymorphism carriers have diffusivity changes in white matter compared to wild-type subjects. The reduced integrity white matter tracts in H63D-HFE carriers are hypothesized to be related to increased susceptibility of these late-myelinating regions to cellular stress induced by oligodendrocyte iron dyshomeostasis.

AB - BACKGROUND AND PURPOSE: The H63D-HFE single nucleotide polymorphism (SNP) has been associated with brain iron dysregulation; however, the emergent role of this missense variant in brain structure and function has yet to be determined. Previous work has demonstrated that HFE SNP carriers have reduced white matter magnetic resonance imaging (MRI) proton relaxation rates. The mechanism by which white matter alterations perturb MRI relaxation is unknown as is how these metrics are related to myelin integrity. METHODS: Fifteen subjects heterozygous for the HFE-H63D SNP and 25 controls with wild-type HFE had diffusion-weighted, anatomical MRIs taken, and underwent cognitive assessment. Fractional anisotropy (FA), mean diffusion (MD), and mode of anisotropy (MO) were calculated from the diffusion dataset to investigate the relationship between the H63D-HFE SNP and myelin integrity. RESULTS: A decrease in FA, an increase in MD, and an increase in MO are demonstrated in multiple H63D-HFE polymorphism carrier white matter tracts. Regions with altered diffusion metrics are notably located in heavily myelinated white matter association fibers, such as the anterior corona radiata and longitudinal fasciculi. CONCLUSIONS: The MRI data presented here demonstrate that H63D-HFE polymorphism carriers have diffusivity changes in white matter compared to wild-type subjects. The reduced integrity white matter tracts in H63D-HFE carriers are hypothesized to be related to increased susceptibility of these late-myelinating regions to cellular stress induced by oligodendrocyte iron dyshomeostasis.

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U2 - 10.1111/jon.12461

DO - 10.1111/jon.12461

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AN - SCOPUS:85026634557

VL - 28

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JO - Journal of Neuroimaging

JF - Journal of Neuroimaging

SN - 1051-2284

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