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 T-1 mapping and CEST imaging under three B-1 amplitudes of 0.75, 1.0, and 1.5 mu T, 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 (Delta Z) was used to construct the omega plot of (1-Delta Z)/Delta Z as a linear function of 1/omega(2)(1), 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.