Purpose Proton exchange rate (Kex) is a valuable biophysical metric. Kex MRI may augment conventional structural MRI by revealing brain impairments at the molecular level. This study aimed to investigate the feasibility of Kex 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/<InlineEquation ID="IEq1"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="11307_2024_1980_Article_IEq1.gif" Format="GIF" Height="20" Rendition="HTML" Resolution="72" Type="Linedraw" Width="19" /> </InlineMediaObject> <EquationSource Format="TEX">${\omega }_{1}^{2}$</EquationSource> <EquationSource Format="MATHML"><math> <msubsup> <mi>ω</mi> <mrow> <mn>1</mn> </mrow> <mn>2</mn> </msubsup> </math></EquationSource> </InlineEquation>, from which Kex 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, Kex 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 Kex were seen in bilateral thalamus or contralateral hemisphere among time points (all P > 0.05). Conclusions Kex 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. Kex MRI is promising to evaluate brain impairment, facilitating the diagnosis and evaluation of neurological disorders.

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

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发表日期：

2025年1月2日

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Huanhuan Yang,
Qiting Wu,
Lin Li,
Yin Wu

摘要

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/ ${\omega }_{1}^{2}$ $ω_{1}^{2}$ , 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.