Evaluation of Brain Impairment Using Proton Exchange Rate MRI in a Kainic Acid-Induced Rat Model of Epilepsy

Purpose: Proton exchange rate (K_ex) is a valuable biophysical metric. K_ex MRI may augment conventional structural MRI by revealing brain impairments at the molecular level. This study aimed to investigate the feasibility of K_ex MRI in evaluating brain injuries at multiple epilepsy stages.

Procedures: Six adult rats with epilepsy induced by intra-amygdalae administration of kainic acid (KA) underwent MRI experiment at 11.7 T. Two MRI scans, including T₁ mapping and CEST imaging under three B₁ amplitudes of 0.75, 1.0, and 1.5 μT, were conducted before and 2, 7, and 28 days after KA injection. Quasi-steady-state analysis was performed to reconstruct equilibrium Z spectra. Direct saturation was resolved using a multi-pool Lorentzian model and removed from Z spectra. The residual spectral signal (ΔZ) was used to construct the omega plot of (1-ΔZ)/ΔZ as a linear function of 1/ ${\omega }_1^2$ , from which K_ex was quantified from the X-axis intercept. One-way ANOVA or two-tailed paired student's t-test was employed with P < 0.05 as statistically significant.

Results: All animals exhibited repetitive status epilepticus with IV to V seizure stages after KA injection. At day 28, K_ex values in the hippocampus and cerebral cortex at the surgical hemisphere with KA injection were significantly higher than that at the time points of control and/or day 2 in the same regions (P < 0.01). Moreover, the values were significantly higher than that in respective contralateral regions at day 28 (P < 0.02). No substantial changes of K_ex were seen in bilateral thalamus or contralateral hemisphere among time points (all P > 0.05).

Conclusions: K_ex increase significantly in the cerebral cortex and hippocampus at the surgical hemisphere, especially at day 28, likely due to substantial alterations at chronic epilepsy stage. K_ex MRI is promising to evaluate brain impairment, facilitating the diagnosis and evaluation of neurological disorders.