Abstracts

Rationale: Lateral fluid percussion injury (FPI) results in diffuse axonal injury and microhemorrhages along fiber bundles. These alterations co-occur with development of increased seizure susceptibility. We hypothesized that microbleeds are associated with the development of focal hyperexcitability.Methods: Lateral FPI was induced in adult male Spraque-Dawley rats (200-250g, 16 injured, 9 sham-operated). MRI was performed at 9.4T ultra high field. Phase imaging for white matter pathology detection was done at 1 month post-injury. T2* weighted multi slice gradient echo images were assessed under isoflurane with spatial resolution of 66*66*200 m, TE/TR/flip=16ms/1250ms/20 . Phase maps were calculated after high-pass filtering. At 2 months post-TBI fMRI data were acquired by single-shot spin-echo echo-planar imaging, TR/TE=4000/60 ms. fMRI started with a baseline acquisition, then, pentylenetetrazol (PTZ, 30mg/kg) was injected intraperitoneally, and the onset and spread of induced seizure activity were monitored by BOLD. Field potentials were monitored with electrodes implanted in the frontal cortex.Results: All injured animals developed cortical lesions with rostro-caudal extent of 6.0-8.4mm. Large intracortical hematomas (score 3, at a size scale from 1 to 3) were detected at contusion site in 15/16 FPI animals and 1/16 had small (score 1) hematoma. Phase maps revealed that at 1 month post-injury the myelin volume ipsilaterally was decreased by 7% (p<0.05) frontally and 19% (p<0.001) at lesion core level. Blood volume was increased by 135% (p<0.001) frontally and 199% (p<0.001) at lesion level due to hemorrhages within the white matter ROI (Fig.1). Contralaterally there were no differences between the groups even though 15/16 rats with lateral FPI had small microbleed(s), visible in phase map, in the contralateral white matter. Phase contrast also highlighted thalamic calsifications in 14/16 trauma animals. The temporal evolution of BOLD signal showed that after PTZ administration, the seizure related BOLD activation initiated exclusively in the ipsilateral cortex in 3/13 injured rats whereas in 10/13 FPIs and in all sham animals it began bilaterally. The BOLD activation was seen to spread into the ipsilateral thalamus in 10/13 and into the contralateral thalamus in 12/13 injured animals, and it varied in magnitude.Conclusions: Our data provide proof-of-principle evidence that diffuse axonal injury related pathologies can be quantified non-invasively using phase contrast. Comparison of phase contrast findings to the BOLD activation spread pattern shows that the ipsilaterally more pronounced hemosiderin load does not co-locate with the induced-seizure focus, except in a subgroup of FPI animals. The role of the demyelination ipsilaterally in regards to the seizure spread pattern yearns holistic analysis incorporating thalamic damage and activation.