Quantification of brain age using high-resolution 7 tesla MR imaging and implications for patients with epilepsy

Purpose: Epilepsy patients exhibit morphological differences on neuroimaging compared to age-matched healthy controls, including cortical and sub-cortical volume loss and altered gray-white matter ratios. The objective was to develop a model of normal aging using the 7T MRIs of healthy controls. This model can then be used to determine if the changes in epilepsy patients resemble the changes seen in aging, and potentially give a marker for the severity of those changes. Methods: Sixty-nine healthy controls (24F/45M, mean age 36.5 ± 10.5 years) and forty-four epilepsy patients (24F/20M, 33.2 ± 9.9 years) non-lesional at 3T were scanned with volumetric T1-MPRAGE at 7T. These images were segmented and quantified using FreeSurfer. A linear regression-based model trained on healthy controls was developed to predict ages using derived imaging features among the epilepsy patient cohort. The model used 114 features with significant linear correlation with age. Results: The regression-based model estimated brain age with mean absolute error (MAE) of 6.6 years among controls. Comparable prediction accuracy of 6.9 years MAE was seen epilepsy patients. T-test of mean absolute error showed no difference in the prediction accuracy with controls and epilepsy patients (p = 0.68). However, average signed error showed elevated (+5.0 years, p = 0.0007) predicted age differences (PAD; brain-PAD=, predicted minus biological age) among epilepsy patients. Morphological metrics in the medial temporal lobe were major contributors to PAD. Additionally, patients with seizure frequency greater than once a week showed significantly elevated brain-PAD (+8.2 ± 5.3 years, n = 13) compared to patients with lower seizure frequency (3.7 ± 6.5 years, n = 31, p = 0.033). Major conclusions: Morphological patterns suggestive of premature aging were observed in non-lesional epilepsy patients vs. controls and in high seizure frequency patients vs. low frequency patients. Modeling brain age with 7T MRI may provide a sensitive imaging marker to assess the differential effects of the aging process in diseases such as epilepsy.