Magnetization transfer and diffusion imaging of acute axonal damage in the cerebral peduncle following hypoxia–ischemia in neonatal rats

Abstract

Background: Magnetic resonance imaging (MRI) of axonal degenerative changes in the cerebral peduncle of the corticospinal tract following cerebral hypoxic-ischemic damage might distinguish infants most appropriate for receiving prompt treatment. The optimal MRI sequence for very early diagnosis of axonal degenerative changes is unknown. We hypothesized that magnetization transfer ratio (MTR) imaging would be more sensitive than traditional MRI, e.g., T 2 or diffusion weighted imaging. Methods: Transient unilateral cerebral hypoxia-ischemia was produced in the neonatal rat followed by MRI of changes in T 2 , the apparent diffusion coefficient (aDc) of water, and MTR, with a focus on the parietal cortex (an ischemic damaged region) and the cerebral peduncle (remote within the corticospinal tract). Rats were imaged at 2 h, 1 d, or 1 wk postinsult. results: In the cerebral peduncle, MTR and T 2 responded similarly, with alterations occurring ipsilaterally at 1 d postinsult. aDc was most sensitive for detecting changes as early as 2 h postinsult, and this corresponded to a reduced staining of axonal filaments ipsilaterally. conclusion: MTR and T 2 imaging have comparable sensitivity for distinguishing early axonal damage in the cerebral peduncle. aDc imaging is highly sensitive for detecting early disruption of corticospinal axons, supporting its potential hyperacute diagnostic use clinically.

Cellular correlates of longitudinal diffusion tensor imaging of axonal degeneration following hypoxic–ischemic cerebral infarction in neonatal rats

“…Acutely following cerebral hypoxia–ischemia, T 2 MR images presented with areas of hyperintensity within the territory typically supplied by the middle cerebral artery, as described previously (Lama et al, 2011; Tuor et al, 2013). Very bright cystic areas developed in regions of infarction such as the parietal cortex by 1 or 4 w post-insult.…”

“…Experiments followed the Canadian Council on Animal Care guidelines and were approved by a University of Calgary Animal Care Committee. A moderate unilateral ischemic lesion with hypoxia (Vannucci and Vannucci, 2005) was produced as described previously (Lama et al, 2011; Qiao et al, 2009; Tuor et al, 2013). Briefly, pups ( n  = 38) on their 7th day of life had their right common carotid artery ligated under isoflurane anesthesia followed by a 60 minute exposure to hypoxia in a chamber containing 8% O 2 and 92% N 2 at 35.5 °C.…”

“…Detecting secondary axonal or Wallerian degeneration is also possible with standard MR sequences. We recently demonstrated that following neonatal hypoxia with unilateral transient ischemia there is evidence for early Wallerian degeneration visible as either decreases in the apparent diffusion coefficient (ADC) and magnetization transfer ratio or increases in DW or T2 (Lama et al, 2011; Tuor et al, 2013) which pseudonormalize transiently. In these studies, the early corticospinal axonal changes (e.g.…”

“…Differences are expected considering the different cellular compositions, for example neuronal rich cerebral cortex compared to axonal bundles within the descending corticospinal tract. A differential timing of DTI alterations is also expected considering direct ischemic injury is thought to be followed by a delayed Wallerian degeneration (Lama et al, 2011; Tuor et al, 2013). In order to better understand the unique cellular and DTI imaging alterations associated with secondary Wallerian degeneration relative to the onset and progression of direct ischemically damaged brain, it is necessary to compare their progression directly at multiple time points.…”

Sex differences in brain MRI abnormalities and neurodevelopmental outcomes in a rat model of neonatal hypoxia-ischemia

“…Cliff aversion reflex at P14 coefficient imaging able to identify axonal changes within 2 hours of the ischemic insult [35]. Moreover, MRI carried out within hours of ischemic injury is predictive of histological changes at 48 hours [36].…”