Nuclei-specific deposits of iron and calcium in the rat thalamus after status epilepticus revealed with quantitative susceptibility mapping (QSM)

Purpose: To investigate pathological changes in the rat brain after pilocarpine-induced status epilepticus using quantitative susceptibility mapping (QSM). Materials and Methods: 3D multiecho gradient-echo (GRE) data were acquired from ex vivo brains of pilocarpine-injected and age-matched control rats at 11.7T. Maps of R2* and quantitative susceptibility were calculated from the acquired 3D GRE magnitude and phase data, respectively. QSM and R2* maps were compared with Perls' (iron) and Alizarin-red-S (calcium) stainings in the same brains to investigate the pathophysiological basis of susceptibility contrast. Results: Bilaterally symmetric lesions were detected in reproducible thalamic regions of pilocarpine-treated rats, characterized by hyperintensity in R2* maps. In comparison, quantitative susceptibility maps demonstrated heterogeneous contrast within the lesions, with distinct hyperintense (paramagnetic) and hypointense (diamagnetic) areas. Comparison with histological assessment revealed localized deposits of iron- and calcium-positive granules in thalamic nuclei corresponding to paramagnetic and diamagnetic areas delineated in the susceptibility maps, respectively. Pronounced differences were observed in the lesions between background-corrected phase images and reconstructed susceptibility maps, indicating unreliable differentiation of iron and calcium deposits in phase maps. Multiple linear regression showed a significant association between susceptibility values and measured optical densities (ODs) of iron and calcium in the lesions (R² = 0.42, P < 0.001), with a positive dependence on OD of iron and negative dependence on OD of calcium. Conclusion: QSM can detect and differentiate pathological iron and calcium deposits with high sensitivity and improved spatial accuracy compared to R2* or GRE phase images, rendering it a promising technique for diagnosing thalamic lesions after status epilepticus. Level of Evidence: 1. Technical Efficacy: Stage 1. J. Magn. Reson. Imaging 2018;47:554–564.