Ex vivo diffusion tensor imaging and neuropathological correlation in a murine model of hypoxia-ischemia-induced thrombotic stroke

Ahmed Shereen, Niza Nemkul, Dianer Yang, Faisal Adhami, R. Scott Dunn, Missy L. Hazen, Masato Nakafuku, Gang Ning, Diana M. Lindquist, Chia Yi Kuan

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Diffusion tensor imaging (DTI) is a powerful method to visualize white matter, but its use in patients with acute stroke remains limited because of the lack of corresponding histologic information. In this study, we addressed this issue using a hypoxia-ischemia (HI)-induced thrombotic model of stroke in adult mice. At 6, 15, and 24 hours after injury, animals were divided into three groups for (1) in vivo T2- and diffusion-weighted magnetic resonance imaging, followed by histochemistry, (2) ex vivo DTI and electron microscopy, and (3) additional biochemical or immunochemical assays. The temporal changes of diffusion anisotropy and histopathology were compared in the fimbria, internal capsule, and external capsule. We found that HI caused a rapid reduction of axial and radial diffusivities in all three axonal bundles. A large decrease in fractional anisotropy, but not in axial diffusivity per se, was associated with structural breakdown of axons. Furthermore, the decrease in radial diffusivity correlated with swelling of myelin sheaths and compression of the axoplasma. The gray matter of the hippocampus also exhibited a high level of diffusion anisotropy, and its reduction signified dendritic degeneration. Taken together, these results suggest that cross-evaluation of multiple DTI parameters may provide a fuller picture of axonal and dendritic injury in acute ischemic stroke.

Original languageEnglish (US)
Pages (from-to)1155-1169
Number of pages15
JournalJournal of Cerebral Blood Flow and Metabolism
Volume31
Issue number4
DOIs
StatePublished - Apr 1 2011

Fingerprint

Diffusion Tensor Imaging
Anisotropy
Ischemia
Stroke
Internal Capsule
Diffusion Magnetic Resonance Imaging
Wounds and Injuries
Myelin Sheath
Axons
Hippocampus
Electron Microscopy
Hypoxia

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Shereen, Ahmed ; Nemkul, Niza ; Yang, Dianer ; Adhami, Faisal ; Dunn, R. Scott ; Hazen, Missy L. ; Nakafuku, Masato ; Ning, Gang ; Lindquist, Diana M. ; Kuan, Chia Yi. / Ex vivo diffusion tensor imaging and neuropathological correlation in a murine model of hypoxia-ischemia-induced thrombotic stroke. In: Journal of Cerebral Blood Flow and Metabolism. 2011 ; Vol. 31, No. 4. pp. 1155-1169.
@article{7a278b496ae142578264b13208d57f43,
title = "Ex vivo diffusion tensor imaging and neuropathological correlation in a murine model of hypoxia-ischemia-induced thrombotic stroke",
abstract = "Diffusion tensor imaging (DTI) is a powerful method to visualize white matter, but its use in patients with acute stroke remains limited because of the lack of corresponding histologic information. In this study, we addressed this issue using a hypoxia-ischemia (HI)-induced thrombotic model of stroke in adult mice. At 6, 15, and 24 hours after injury, animals were divided into three groups for (1) in vivo T2- and diffusion-weighted magnetic resonance imaging, followed by histochemistry, (2) ex vivo DTI and electron microscopy, and (3) additional biochemical or immunochemical assays. The temporal changes of diffusion anisotropy and histopathology were compared in the fimbria, internal capsule, and external capsule. We found that HI caused a rapid reduction of axial and radial diffusivities in all three axonal bundles. A large decrease in fractional anisotropy, but not in axial diffusivity per se, was associated with structural breakdown of axons. Furthermore, the decrease in radial diffusivity correlated with swelling of myelin sheaths and compression of the axoplasma. The gray matter of the hippocampus also exhibited a high level of diffusion anisotropy, and its reduction signified dendritic degeneration. Taken together, these results suggest that cross-evaluation of multiple DTI parameters may provide a fuller picture of axonal and dendritic injury in acute ischemic stroke.",
author = "Ahmed Shereen and Niza Nemkul and Dianer Yang and Faisal Adhami and Dunn, {R. Scott} and Hazen, {Missy L.} and Masato Nakafuku and Gang Ning and Lindquist, {Diana M.} and Kuan, {Chia Yi}",
year = "2011",
month = "4",
day = "1",
doi = "10.1038/jcbfm.2010.212",
language = "English (US)",
volume = "31",
pages = "1155--1169",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "4",

}

Ex vivo diffusion tensor imaging and neuropathological correlation in a murine model of hypoxia-ischemia-induced thrombotic stroke. / Shereen, Ahmed; Nemkul, Niza; Yang, Dianer; Adhami, Faisal; Dunn, R. Scott; Hazen, Missy L.; Nakafuku, Masato; Ning, Gang; Lindquist, Diana M.; Kuan, Chia Yi.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 31, No. 4, 01.04.2011, p. 1155-1169.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ex vivo diffusion tensor imaging and neuropathological correlation in a murine model of hypoxia-ischemia-induced thrombotic stroke

AU - Shereen, Ahmed

AU - Nemkul, Niza

AU - Yang, Dianer

AU - Adhami, Faisal

AU - Dunn, R. Scott

AU - Hazen, Missy L.

AU - Nakafuku, Masato

AU - Ning, Gang

AU - Lindquist, Diana M.

AU - Kuan, Chia Yi

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Diffusion tensor imaging (DTI) is a powerful method to visualize white matter, but its use in patients with acute stroke remains limited because of the lack of corresponding histologic information. In this study, we addressed this issue using a hypoxia-ischemia (HI)-induced thrombotic model of stroke in adult mice. At 6, 15, and 24 hours after injury, animals were divided into three groups for (1) in vivo T2- and diffusion-weighted magnetic resonance imaging, followed by histochemistry, (2) ex vivo DTI and electron microscopy, and (3) additional biochemical or immunochemical assays. The temporal changes of diffusion anisotropy and histopathology were compared in the fimbria, internal capsule, and external capsule. We found that HI caused a rapid reduction of axial and radial diffusivities in all three axonal bundles. A large decrease in fractional anisotropy, but not in axial diffusivity per se, was associated with structural breakdown of axons. Furthermore, the decrease in radial diffusivity correlated with swelling of myelin sheaths and compression of the axoplasma. The gray matter of the hippocampus also exhibited a high level of diffusion anisotropy, and its reduction signified dendritic degeneration. Taken together, these results suggest that cross-evaluation of multiple DTI parameters may provide a fuller picture of axonal and dendritic injury in acute ischemic stroke.

AB - Diffusion tensor imaging (DTI) is a powerful method to visualize white matter, but its use in patients with acute stroke remains limited because of the lack of corresponding histologic information. In this study, we addressed this issue using a hypoxia-ischemia (HI)-induced thrombotic model of stroke in adult mice. At 6, 15, and 24 hours after injury, animals were divided into three groups for (1) in vivo T2- and diffusion-weighted magnetic resonance imaging, followed by histochemistry, (2) ex vivo DTI and electron microscopy, and (3) additional biochemical or immunochemical assays. The temporal changes of diffusion anisotropy and histopathology were compared in the fimbria, internal capsule, and external capsule. We found that HI caused a rapid reduction of axial and radial diffusivities in all three axonal bundles. A large decrease in fractional anisotropy, but not in axial diffusivity per se, was associated with structural breakdown of axons. Furthermore, the decrease in radial diffusivity correlated with swelling of myelin sheaths and compression of the axoplasma. The gray matter of the hippocampus also exhibited a high level of diffusion anisotropy, and its reduction signified dendritic degeneration. Taken together, these results suggest that cross-evaluation of multiple DTI parameters may provide a fuller picture of axonal and dendritic injury in acute ischemic stroke.

UR - http://www.scopus.com/inward/record.url?scp=79953270139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953270139&partnerID=8YFLogxK

U2 - 10.1038/jcbfm.2010.212

DO - 10.1038/jcbfm.2010.212

M3 - Article

C2 - 21139628

AN - SCOPUS:79953270139

VL - 31

SP - 1155

EP - 1169

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 4

ER -