Quantification of iron in the non-human primate brain with diffusion-weighted magnetic resonance imaging

Abstract

Pathological iron deposits in the brain, especially within basal ganglia, are linked to severe neurodegenerative disorders like Parkinson's disease. As iron induces local changes in magnetic susceptibility, its presence can be visualized with magnetic resonance imaging (MRI). The usual approach, based on iron induced changes in magnetic relaxation (T2/T2'), is often prone, however, to confounding artifacts and lacks specificity. Here, we propose a new method to quantify and map iron deposits using water diffusion MRI. This method is based on the differential sensitivity of two image acquisition schemes to the local magnetic field gradients induced by iron deposits and their cross-term with gradient pulses used for diffusion encoding. Iron concentration could be imaged and estimated with high accuracy in the brain cortex, the thalamus, the substantia nigra and the globus pallidus of macaques, showing iron distributions in agreement with literature. Additionally, iron maps could clearly show a dramatic increase in iron content upon injection of an UltraSmall Particle Iron Oxide (USPIO) contrast agent, notably in the cortex and the thalamus, reflecting regional differences in blood volume. The method will benefit clinical investigations on the effect of iron deposits in the brain or other organs, as iron deposits are increasingly seen as a biomarker for a wide range of diseases, notably, neurodegenerative diseases in the pre-symptomatic stage. It also has the potential for quantifying variations in blood volume induced by brain activation in fMRI studies using USPIOs.

Thalamic white matter in multiple sclerosis: A combined diffusion‐tensor imaging and quantitative susceptibility mapping study

“…Fifth, given the relatively small sample size, we did not investigate whether there were differences between the different MS phenotypes. Finally, investigations with phantom and in vivo data have suggested that iron can influence DTI measurements as a result of a decreased signal to noise ratio, (Rulseh, et al, 2013; Zhang, et al, 2013) or cross-term effects with the diffusion gradients (Fujiwara, et al, 2014), resulting in artificially lowered MD and increased FA values. As a consequence, greater iron content in HCs may result in an overestimation of diffusivity differences between the HC and MS groups.…”

Diffusion tensor imaging in hemorrhagic stroke

“…In parallel our understanding of the pathomechanisms of neuronal damage in hemorrhagic stroke is also increasing. A very good example is the depiction of iron mediated neuronal injury that has come across through several studies on this topic especially in the non-human primate and non-primate animal models (39, 89). The authors of this review firmly believe large human population studies are needed to explore correlation of parenchymal tissue iron levels and damage to white matter tracts detected by DTI and further connection of these biomarkers with motor function outcome.…”

Characterization of age-related microstructural changes in locus coeruleus and substantia nigra pars compacta

“…Furthermore, as SNpc experiences age-related iron deposition in addition to neuronal loss 13 , SNpc diffusion metrics might be influenced by age-related iron accumulations in SNpc. Specifically, iron reduces diffusivity values 14 in diffusion-weighted acquisitions using monopolar diffusion encoding gradients 15 .…”