In Vivo Characterization of Magnetic Inclusions in the Subcortex From Nonexponential Transverse Relaxation Decay

According to theoretical studies, MRI signal decay due to transverse relaxation in brain tissue with magnetic inclusions (e.g., blood vessels and iron-rich cells) is expected to follow a transition from Gaussian behaviour at short echo times to exponential behaviour at longer times. The decay parameters carry information about the inclusions (e.g., size and volume fraction) and provide unique insights into brain microstructure. However, gradient-echo decays typically only capture the long-time exponential behaviour. We provide experimental evidence of nonexponential transverse relaxation decay in human subcortical grey matter from in vivo MRI data acquired at 3 T, allowing the subsequent characterization of the magnetic inclusions. Gradient-echo data were collected with short interecho spacings, minimal echo time (1.25 ms) and novel acquisition strategies to mitigate motion and cardiac-induced effects. The data were fitted using exponential and nonexponential models that describe the impact of magnetic inclusions on the MRI signal. Nonexponential models provided superior fits. The strongest deviations from exponential were detected in the substantia nigra and globus pallidus. Numerical simulations of the signal decay from histological maps of iron concentration in the substantia nigra replicated the experimental data, highlighting that non-haem iron can be at the source of the nonexponential decay. To investigate the potential of nonexponential decays to characterize brain microstructure, we estimated the properties of the underlying inclusions using two analytical models. Under the static dephasing regime, the magnetic susceptibility and volume fractions of the inclusions ranged between 1.8-4 and 0.02-0.04 ppm, respectively. Alternatively, under the diffusion narrowing regime, the typical inclusion size was ~2.4 μm. Both simulations and experimental data suggest an intermediate regime with a non-negligible effect of water diffusion. Nonexponential transverse relaxation decay allows to characterize the spatial distribution of magnetic material within subcortical tissue with increased specificity, with potential applications for Parkinson's disease and other pathologies.