40 - Assessment of cerebral perfusion and metabolism following neonatal seizures in a preclinical model

Seizures induce significant changes in cerebral metabolism and perfusion.  MR imaging and proton MR spectroscopy (¹H MRS) are standard MR tools to assess neonatal seizures. Phosphorus (³¹P) MRS and arterial spin labelling (ASL) MRI are other techniques for the assessment of cerebral metabolism and perfusion respectively.


Objective:

To assess the effect of seizures on brain perfusion and metabolism using pre and post ictally acquired MR imaging, ¹H MRS, ³¹P MRS and ASL MRI, in a preclinical model of a healthy newborn brain.


Design/Methods:

Ten healthy male newborn piglets had seizure induction with bicuculine 4mg/kg IV over two time periods 3h apart. Piglets were sedated and anaesthetised throughout the experiment and underwent aEEG/EEG and systemic physiological monitoring. All imaging data were acquired in a 3T Philips Achieva scanner using a Lammers Medical MR Conditional transport incubator, Lammers 8ch custom-made proton coil and Philips phosphorous flex coil. Each animal had a scan at the start of the study (pre-ictal) and a repeat scan 5h p seizure (post-ictal).

ASL was performed using pseudo-continuous labelling (pCASL) with 1.8s labelling duration and 2s post-labelling delay and a 3D GRASE readout (TE/TR=13 ms/4187 ms, voxel size 2.5*2.5*5 (mm), 26 slices).  Cerebral blood flow [ml/100g/min] maps were computed and mean CBF[ml/100g/min] within regions were quantified using an automated atlas segmentation approach. Chemical shift imaging (CSI) was acquired with an 8 × 8 matrix, a voxel size of 7.5 × 7.5 mm2 and slab thickness of 10 mm (TE/TR= repetition time was 288 ms / 2 s. CSI data was processed using TARQUIN yielding signal amplitudes. ³¹P MRS was acquired with Image-Selected In vivo Spectroscopy (ISIS) voxel size of 40x55x70 mm (adapted to include the whole brain) (FID, TR=10000ms). ISIS data was processed using JMRUI.


Results:

Generalised tonic clonic seizures with electrographic changes noted immediately after bicuculine administration. Significant differences noted between the pre-ictal and post-ictal period in the whole brain (P=0.007) and cortical (P=0.004) blood flow (CBF) (figure 1A, 1B). In the post-ictal period, there was a trend to an increase in Intracellular pH (pHi) as a result of postepileptic intracellular alkalosis (fig 1E), (7.13±0.07 vs 7.18±0.08) and reduction in brain energy metabolism high energy phosphate state (NTP/epp) (figure 1D). Lac/NAA on ¹H MRS did not differ between the two scans.


Conclusion(s):

Increased whole brain and cortical perfusion measured on ASL-MRI persisted following seizures 5h after the seizure induction in a preclinical seizure model.