Histopathological correlates of magnetic resonance imaging-defined chronic perinatal white matter injury

Art Riddle, Justin Dean, Joshua R. Buser, Xi Gong, Jennifer Maire, Kevin Chen, Tahir Ahmad, Victor Cai, Thuan Nguyen, Christopher (Chris) Kroenke, Alan (Roger) Hohimer, Stephen Back

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Objective: Although magnetic resonance imaging (MRI) is the optimal imaging modality to define cerebral white-matter injury (WMI) in preterm survivors, the histopathological features of MRI-defined chronic lesions are poorly defined. We hypothesized that chronic WMI is related to a combination of delayed oligodendrocyte (OL) lineage cell death and arrested maturation of preoligodendrocytes (preOLs). We determined whether ex vivo MRI can distinguish distinct microglial and astroglial responses related to WMI progression and arrested preOL differentiation. Methods: We employed a preterm fetal sheep model of global cerebral ischemia in which acute WMI results in selective preOL degeneration. We developed novel algorithms to register histopathologically- defined lesions with contrast-weighted and diffusion-weighted high-field ex vivo MRI data. Results: Despite mild delayed preOL degeneration, preOL density recovered to control levels by 7 days after ischemia and was â2 fold greater at 14 days. However, premyelinating OLs were significantly diminished at 7 and 14 days. WMI evolved to mostly gliotic lesions where arrested preOL differentiation was directly proportional to the magnitude of astrogliosis. A reduction in cerebral WM volume was accompanied by four classes of MRI-defined lesions. Each lesion type displayed unique astroglial and microglial responses that corresponded to distinct forms of necrotic or non-necrotic injury. High-field MRI defined 2 novel hypointense signal abnormalities on T 2-weighted images that coincided with microscopic necrosis or identified astrogliosis with high sensitivity and specificity. Interpretation: These studies support the potential of high-field MRI for early identification of microscopic necrosis and gliosis with preOL maturation arrest, a common form of WMI in preterm survivors.

Original languageEnglish (US)
Pages (from-to)493-507
Number of pages15
JournalAnnals of Neurology
Volume70
Issue number3
DOIs
StatePublished - Sep 2011

Fingerprint

Magnetic Resonance Imaging
Wounds and Injuries
Necrosis
Gliosis
Oligodendroglia
White Matter
Brain Ischemia
Sheep
Cell Death
Ischemia
Sensitivity and Specificity

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Histopathological correlates of magnetic resonance imaging-defined chronic perinatal white matter injury. / Riddle, Art; Dean, Justin; Buser, Joshua R.; Gong, Xi; Maire, Jennifer; Chen, Kevin; Ahmad, Tahir; Cai, Victor; Nguyen, Thuan; Kroenke, Christopher (Chris); Hohimer, Alan (Roger); Back, Stephen.

In: Annals of Neurology, Vol. 70, No. 3, 09.2011, p. 493-507.

Research output: Contribution to journalArticle

Riddle, A, Dean, J, Buser, JR, Gong, X, Maire, J, Chen, K, Ahmad, T, Cai, V, Nguyen, T, Kroenke, CC, Hohimer, AR & Back, S 2011, 'Histopathological correlates of magnetic resonance imaging-defined chronic perinatal white matter injury', Annals of Neurology, vol. 70, no. 3, pp. 493-507. https://doi.org/10.1002/ana.22501
Riddle, Art ; Dean, Justin ; Buser, Joshua R. ; Gong, Xi ; Maire, Jennifer ; Chen, Kevin ; Ahmad, Tahir ; Cai, Victor ; Nguyen, Thuan ; Kroenke, Christopher (Chris) ; Hohimer, Alan (Roger) ; Back, Stephen. / Histopathological correlates of magnetic resonance imaging-defined chronic perinatal white matter injury. In: Annals of Neurology. 2011 ; Vol. 70, No. 3. pp. 493-507.
@article{15f6598b7678415eb71e4ee2f023f051,
title = "Histopathological correlates of magnetic resonance imaging-defined chronic perinatal white matter injury",
abstract = "Objective: Although magnetic resonance imaging (MRI) is the optimal imaging modality to define cerebral white-matter injury (WMI) in preterm survivors, the histopathological features of MRI-defined chronic lesions are poorly defined. We hypothesized that chronic WMI is related to a combination of delayed oligodendrocyte (OL) lineage cell death and arrested maturation of preoligodendrocytes (preOLs). We determined whether ex vivo MRI can distinguish distinct microglial and astroglial responses related to WMI progression and arrested preOL differentiation. Methods: We employed a preterm fetal sheep model of global cerebral ischemia in which acute WMI results in selective preOL degeneration. We developed novel algorithms to register histopathologically- defined lesions with contrast-weighted and diffusion-weighted high-field ex vivo MRI data. Results: Despite mild delayed preOL degeneration, preOL density recovered to control levels by 7 days after ischemia and was {\^a}2 fold greater at 14 days. However, premyelinating OLs were significantly diminished at 7 and 14 days. WMI evolved to mostly gliotic lesions where arrested preOL differentiation was directly proportional to the magnitude of astrogliosis. A reduction in cerebral WM volume was accompanied by four classes of MRI-defined lesions. Each lesion type displayed unique astroglial and microglial responses that corresponded to distinct forms of necrotic or non-necrotic injury. High-field MRI defined 2 novel hypointense signal abnormalities on T 2-weighted images that coincided with microscopic necrosis or identified astrogliosis with high sensitivity and specificity. Interpretation: These studies support the potential of high-field MRI for early identification of microscopic necrosis and gliosis with preOL maturation arrest, a common form of WMI in preterm survivors.",
author = "Art Riddle and Justin Dean and Buser, {Joshua R.} and Xi Gong and Jennifer Maire and Kevin Chen and Tahir Ahmad and Victor Cai and Thuan Nguyen and Kroenke, {Christopher (Chris)} and Hohimer, {Alan (Roger)} and Stephen Back",
year = "2011",
month = "9",
doi = "10.1002/ana.22501",
language = "English (US)",
volume = "70",
pages = "493--507",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

TY - JOUR

T1 - Histopathological correlates of magnetic resonance imaging-defined chronic perinatal white matter injury

AU - Riddle, Art

AU - Dean, Justin

AU - Buser, Joshua R.

AU - Gong, Xi

AU - Maire, Jennifer

AU - Chen, Kevin

AU - Ahmad, Tahir

AU - Cai, Victor

AU - Nguyen, Thuan

AU - Kroenke, Christopher (Chris)

AU - Hohimer, Alan (Roger)

AU - Back, Stephen

PY - 2011/9

Y1 - 2011/9

N2 - Objective: Although magnetic resonance imaging (MRI) is the optimal imaging modality to define cerebral white-matter injury (WMI) in preterm survivors, the histopathological features of MRI-defined chronic lesions are poorly defined. We hypothesized that chronic WMI is related to a combination of delayed oligodendrocyte (OL) lineage cell death and arrested maturation of preoligodendrocytes (preOLs). We determined whether ex vivo MRI can distinguish distinct microglial and astroglial responses related to WMI progression and arrested preOL differentiation. Methods: We employed a preterm fetal sheep model of global cerebral ischemia in which acute WMI results in selective preOL degeneration. We developed novel algorithms to register histopathologically- defined lesions with contrast-weighted and diffusion-weighted high-field ex vivo MRI data. Results: Despite mild delayed preOL degeneration, preOL density recovered to control levels by 7 days after ischemia and was â2 fold greater at 14 days. However, premyelinating OLs were significantly diminished at 7 and 14 days. WMI evolved to mostly gliotic lesions where arrested preOL differentiation was directly proportional to the magnitude of astrogliosis. A reduction in cerebral WM volume was accompanied by four classes of MRI-defined lesions. Each lesion type displayed unique astroglial and microglial responses that corresponded to distinct forms of necrotic or non-necrotic injury. High-field MRI defined 2 novel hypointense signal abnormalities on T 2-weighted images that coincided with microscopic necrosis or identified astrogliosis with high sensitivity and specificity. Interpretation: These studies support the potential of high-field MRI for early identification of microscopic necrosis and gliosis with preOL maturation arrest, a common form of WMI in preterm survivors.

AB - Objective: Although magnetic resonance imaging (MRI) is the optimal imaging modality to define cerebral white-matter injury (WMI) in preterm survivors, the histopathological features of MRI-defined chronic lesions are poorly defined. We hypothesized that chronic WMI is related to a combination of delayed oligodendrocyte (OL) lineage cell death and arrested maturation of preoligodendrocytes (preOLs). We determined whether ex vivo MRI can distinguish distinct microglial and astroglial responses related to WMI progression and arrested preOL differentiation. Methods: We employed a preterm fetal sheep model of global cerebral ischemia in which acute WMI results in selective preOL degeneration. We developed novel algorithms to register histopathologically- defined lesions with contrast-weighted and diffusion-weighted high-field ex vivo MRI data. Results: Despite mild delayed preOL degeneration, preOL density recovered to control levels by 7 days after ischemia and was â2 fold greater at 14 days. However, premyelinating OLs were significantly diminished at 7 and 14 days. WMI evolved to mostly gliotic lesions where arrested preOL differentiation was directly proportional to the magnitude of astrogliosis. A reduction in cerebral WM volume was accompanied by four classes of MRI-defined lesions. Each lesion type displayed unique astroglial and microglial responses that corresponded to distinct forms of necrotic or non-necrotic injury. High-field MRI defined 2 novel hypointense signal abnormalities on T 2-weighted images that coincided with microscopic necrosis or identified astrogliosis with high sensitivity and specificity. Interpretation: These studies support the potential of high-field MRI for early identification of microscopic necrosis and gliosis with preOL maturation arrest, a common form of WMI in preterm survivors.

UR - http://www.scopus.com/inward/record.url?scp=80052556491&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052556491&partnerID=8YFLogxK

U2 - 10.1002/ana.22501

DO - 10.1002/ana.22501

M3 - Article

C2 - 21796666

AN - SCOPUS:80052556491

VL - 70

SP - 493

EP - 507

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 3

ER -