Limited Contribution of T₁ Relaxation to GluCEST MRI Signal Differences Across Four Rat Models with Distinct...

To determine whether measured longitudinal relaxation time (T₁) differences explain glutamate-weighted CEST (GluCEST) group differences across four rat disease models associated with glutamatergic alterations.

GluCEST imaging and quantitative T₁ mapping were performed at 7T in four rat models (insomnia, depression, demyelination, and sepsis). Group differences were assessed using Welch's t-test and standardized effect sizes. The influence of T₁ on GluCEST was examined using disease-specific and pooled analyses of covariance (ANCOVA), as well as correlation analyses.

Across all models, T₁ values did not significantly differ between control and disease groups (all p ≥ 0.53), whereas GluCEST showed significant group differences in each condition (all p < 0.01) with large effect sizes (Cohen's d = 1.75-7.02). In ANCOVA models, group effects remained significant after adjustment for T₁, and T₁ was not a significant predictor of GluCEST in disease-specific or pooled analyses. No consistent correlation between T₁ and GluCEST was observed.

Under the present experimental conditions, between-group T₁ differences were limited and did not significantly explain GluCEST group separation across the four rat models examined. These findings suggest that the T₁ contribution to GluCEST group comparisons should be interpreted in relation to the biological model, the magnitude of between-group T₁ differences, and the acquisition conditions.