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Published on: July 19, 2019
Histopathological correlates of magnetic resonance imaging-defined chronic perinatal white matter injury
Art Riddle1, Justin Dean, Joshua R Buser
1Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239-3098, USA.
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 ~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.
Insights
High-field MRI can identify specific patterns of brain injury in preterm infants, linking white matter injury (WMI) to oligodendrocyte (OL) maturation arrest. This imaging technique shows promise for early detection of WMI in vulnerable newborns.
Area of Science:
- Neuroimaging
- Pathology
- Neonatal Neurology
Background:
- Magnetic resonance imaging (MRI) is crucial for defining cerebral white-matter injury (WMI) in preterm infants.
- Histopathological features of chronic WMI detected by MRI are not well understood.
- Chronic WMI may involve delayed oligodendrocyte (OL) cell death and impaired preoligodendrocyte (preOL) maturation.
Purpose of the Study:
- To investigate the relationship between MRI findings and histopathological characteristics of chronic WMI.
- To determine if ex vivo MRI can differentiate specific microglial and astroglial responses in WMI.
- To assess the correlation between WMI progression and arrested preOL differentiation.
Main Methods:
- Utilized a preterm fetal sheep model of global cerebral ischemia.
- Induced acute WMI leading to selective preOL degeneration.
- Developed algorithms to register histopathology with high-field ex vivo MRI (contrast-weighted and diffusion-weighted).
Main Results:
- Premyelinating OLs were significantly reduced post-ischemia, despite preOL density recovery.
- WMI evolved into gliotic lesions, with arrested preOL differentiation proportional to astrogliosis.
- High-field MRI identified novel signal abnormalities correlating with necrosis and astrogliosis.
Conclusions:
- High-field MRI shows potential for early detection of microscopic necrosis and gliosis in preterm WMI.
- Arrested preOL maturation is a common feature of WMI in preterm survivors.
- MRI can distinguish distinct glial responses associated with different injury types.
