In-vivo characterization of magnetic inclusions in the subcortex from non-exponential transverse relaxation decay

Abstract

According to theoretical studies, the MRI signal decay due to transverse relaxation, in brain tissue with magnetic inclusions (e.g. blood vessels, myelin, iron-rich cells), exhibits a transition from a Gaussian behaviour at short echo times to exponential at long echo times. Combined, the Gaussian and exponential decay parameters carry information about the inclusions (e.g., size, volume fraction) and provide a unique insight into brain tissue microstructure. However, gradient echo decays obtained experimentally typically only capture the long-time exponential behaviour. Here, we provide experimental evidence of non-exponential transverse relaxation signal decay at short times in human subcortical grey matter, from MRI data acquired in vivo at 3T. The detection of the non-exponential behaviour of the signal decay allows the subsequent characterization of the magnetic inclusions in the subcortex. The gradient-echo data was collected with short inter-echo spacings, a minimal echo time of 1.25 ms and novel acquisition strategies tailored to mitigate the effect of motion and cardiac pulsation. The data was fitted using both a standard exponential model and non-exponential theoretical models describing the impact of magnetic inclusions on the MRI signal. The non-exponential models provided superior fits to the data, indicative of a better representation of the observed signal. The strongest deviations from exponential behaviour were detected in the substantia nigra and globus pallidus. Numerical simulations of the signal decay, conducted from histological maps of iron concentration in the substantia nigra, closely replicated the experimental data - highlighting that non-heme iron can be at the source of the non-exponential signal decay. To investigate the potential of the non-exponential signal decay as a tool to characterize brain microstructure, we attempted to estimate the properties of the inclusions at the source of this decay behaviour using two available analytical models of transverse relaxation. Under the assumption of the static dephasing regime, the magnetic susceptibility and volume fractions of the inclusions was estimated to range from 1.8 to 4 ppm and from 0.02 to 0.04 respectively. Alternatively, under the assumption of the diffusion narrowing regime, the typical inclusion size was estimated to be [~]2.4 m. Both simulations and experimental data point towards an intermediate regime with a non-negligible effect of water diffusion to signal decay. Non-exponential transverse relaxation decay provides new means to characterize the spatial distribution of magnetic material within subcortical grey matter tissue with increased specificity, with potential applications to Parkinsons disease and other pathologies.