Abstract
A recent MRI method, fast macromolecular proton fraction (MPF) mapping, was used to quantify demyelination in the transient middle cerebral artery occlusion (MCAO) rat stroke model. MPF and other quantitative MRI parameters (T1, T2, proton density, and apparent diffusion coefficient) were compared with histological and immunohistochemical markers of demyelination (Luxol Fast Blue stain, (LFB)), neuronal loss (NeuN immunofluorescence), axonal loss (Bielschowsky stain), and inflammation (Iba1 immunofluorescence) in three animal groups (n = 5 per group) on the 1st, 3rd, and 10th day after MCAO. MPF and LFB optical density (OD) were significantly reduced in the ischemic lesion on all days after MCAO relative to the symmetrical regions of the contralateral hemisphere. Percentage changes in MPF and LFB OD in the ischemic lesion relative to the contralateral hemisphere significantly differed on the first day only. Percentage changes in LFB OD and MPF were strongly correlated (R = 0.81, P < 0.001) and did not correlate with other MRI parameters. MPF also did not correlate with other histological variables. Addition of T2 into multivariate regression further improved agreement between MPF and LFB OD (R = 0.89, P < 0.001) due to correction of the edema effect. This study provides histological validation of MPF as an imaging biomarker of demyelination in ischemic stroke.
| Original language | English |
|---|---|
| Pages (from-to) | 919-931 |
| Number of pages | 13 |
| Journal | Journal of Cerebral Blood Flow and Metabolism |
| Volume | 38 |
| Issue number | 5 |
| DOIs | |
| Publication status | Accepted/In press - 1 Jan 2018 |
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Keywords
- histology
- Macromolecular proton fraction
- magnetic resonance imaging
- middle cerebral artery occlusion
- myelin
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
- Cardiology and Cardiovascular Medicine
Cite this
Quantitative assessment of demyelination in ischemic stroke in vivo using macromolecular proton fraction mapping. / Khodanovich, Marina Y.; Kisel, Alena A.; Akulov, Andrey E.; Atochin, Dmitriy N.; Kudabaeva, Marina S.; Glazacheva, Valentina Y.; Svetlik, Michael V.; Medvednikova, Yana A.; Mustafina, Lilia R.; Yarnykh, Vasily L.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 38, No. 5, 01.01.2018, p. 919-931.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Quantitative assessment of demyelination in ischemic stroke in vivo using macromolecular proton fraction mapping
AU - Khodanovich, Marina Y.
AU - Kisel, Alena A.
AU - Akulov, Andrey E.
AU - Atochin, Dmitriy N.
AU - Kudabaeva, Marina S.
AU - Glazacheva, Valentina Y.
AU - Svetlik, Michael V.
AU - Medvednikova, Yana A.
AU - Mustafina, Lilia R.
AU - Yarnykh, Vasily L.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - A recent MRI method, fast macromolecular proton fraction (MPF) mapping, was used to quantify demyelination in the transient middle cerebral artery occlusion (MCAO) rat stroke model. MPF and other quantitative MRI parameters (T1, T2, proton density, and apparent diffusion coefficient) were compared with histological and immunohistochemical markers of demyelination (Luxol Fast Blue stain, (LFB)), neuronal loss (NeuN immunofluorescence), axonal loss (Bielschowsky stain), and inflammation (Iba1 immunofluorescence) in three animal groups (n = 5 per group) on the 1st, 3rd, and 10th day after MCAO. MPF and LFB optical density (OD) were significantly reduced in the ischemic lesion on all days after MCAO relative to the symmetrical regions of the contralateral hemisphere. Percentage changes in MPF and LFB OD in the ischemic lesion relative to the contralateral hemisphere significantly differed on the first day only. Percentage changes in LFB OD and MPF were strongly correlated (R = 0.81, P < 0.001) and did not correlate with other MRI parameters. MPF also did not correlate with other histological variables. Addition of T2 into multivariate regression further improved agreement between MPF and LFB OD (R = 0.89, P < 0.001) due to correction of the edema effect. This study provides histological validation of MPF as an imaging biomarker of demyelination in ischemic stroke.
AB - A recent MRI method, fast macromolecular proton fraction (MPF) mapping, was used to quantify demyelination in the transient middle cerebral artery occlusion (MCAO) rat stroke model. MPF and other quantitative MRI parameters (T1, T2, proton density, and apparent diffusion coefficient) were compared with histological and immunohistochemical markers of demyelination (Luxol Fast Blue stain, (LFB)), neuronal loss (NeuN immunofluorescence), axonal loss (Bielschowsky stain), and inflammation (Iba1 immunofluorescence) in three animal groups (n = 5 per group) on the 1st, 3rd, and 10th day after MCAO. MPF and LFB optical density (OD) were significantly reduced in the ischemic lesion on all days after MCAO relative to the symmetrical regions of the contralateral hemisphere. Percentage changes in MPF and LFB OD in the ischemic lesion relative to the contralateral hemisphere significantly differed on the first day only. Percentage changes in LFB OD and MPF were strongly correlated (R = 0.81, P < 0.001) and did not correlate with other MRI parameters. MPF also did not correlate with other histological variables. Addition of T2 into multivariate regression further improved agreement between MPF and LFB OD (R = 0.89, P < 0.001) due to correction of the edema effect. This study provides histological validation of MPF as an imaging biomarker of demyelination in ischemic stroke.
KW - histology
KW - Macromolecular proton fraction
KW - magnetic resonance imaging
KW - middle cerebral artery occlusion
KW - myelin
UR - http://www.scopus.com/inward/record.url?scp=85045035995&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045035995&partnerID=8YFLogxK
U2 - 10.1177/0271678X18755203
DO - 10.1177/0271678X18755203
M3 - Article
VL - 38
SP - 919
EP - 931
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 5
ER -