In vivo assessment of age-related brain iron differences by magnetic field correlation imaging

Abstract

Purpose: To assess a recently developed magnetic resonance imaging (MRI) technique called magnetic field correlation (MFC) imaging along with a conventional imaging method, the transverse relaxation rate (R2), for estimating age-related brain iron concentration in adolescents and adults. Brain region measures were compared with nonheme iron concentrations (C(PM) ) based on a prior postmortem study.

Materials and methods: Asymmetric spin echo (ASE) images were acquired at 3T from 26 healthy individuals (16 adolescents, 10 adults). Regions of interest (ROIs) were placed in areas in which age-related iron content was estimated postmortem: globus pallidus (GP), putamen (PUT), caudate nucleus (CN), thalamus (THL), and frontal white matter (FWM). Regression and group analyses were conducted on ROI means.

Results: MFC and R2 displayed significant linear relationships to C(PM) when all regions were combined. Whereas MFC was significantly correlated with C(PM) for every individual region except FWM and detected significantly lower means in adolescents than adults for each region, R2 detected significant correlation and lower means for only PUT and CN.

Conclusion: Our results support the hypothesis that MFC is sensitive to brain iron in GM regions and detects age-related iron increases known to occur from adolescence to adulthood. MFC may be more sensitive than R2 to iron-related changes occurring within specific brain regions.

Fig. 1. Regions of interest

Bilateral regions of interest (ROIs) were manually drawn on the zero shift image (TE = 50 ms) for the globus pallidus (GP), putamen (PUT), caudate nucleus (CN), thalamus (THL) and frontal white matter (FWM). Each ROI was delineated according to anatomical boundaries with the exception of FWM which was sampled with square ROIs. Each region was sampled in every slice where the region was visible except for the two most inferior slices where echo planar imaging (EPI) distortion was prevalent and for the FWM where the last superior slice sampled was the slice prior to the emergence of the corpus callosum body. The ROIs were then applied over the MFC and R2 maps (that had CSF removed) to extract metric means and standard errors.

Fig. 2. Linear regression of putative postmortem iron concentration versus MFC means

A. Global linear regression of all regions. B. Linear regression of frontal white matter (FWM, diamonds). C. Linear regression of thalamus (THL, squares). D. Linear regression of caudate nucleus (CN, upright triangles). E. Linear regression of putamen (PUT, circles). F. Linear regression of globus pallidus (GP, downward triangles). For each subplot: X-axis is the putative postmortem non-heme iron concentration (C_PM), Y-axis is MFC mean, the linear regression equation, Pearson’s correlation coefficient and p-value are reported.

Fig. 3. Linear regression of putative postmortem iron concentration versus R2 means

A. Global linear regression of all regions. B. Linear regression of frontal white matter (FWM, diamonds). C. Linear regression of thalamus (THL, squares). D. Linear regression of caudate nucleus (CN, upright triangles). E. Linear regression of putamen (PUT, circles). F. Linear regression of globus pallidus (GP, downward triangles). For each subplot: X-axis is putative postmortem non-heme iron concentration (C_PM), Y-axis is R2 mean, the linear regression equation, Pearson’s correlation coefficient and p-value are reported.

Fig. 4. MFC and R2 means with age

Left column graphs are MFC means plotted over age for globus pallidus (GP, downward triangles), putamen (PUT, circles), caudate nucleus (CN, upward triangles), thalamus (THL, squares) and frontal white matter (FWM, diamonds) (top to bottom graphs, respectively). Right column graphs are R2 means plotted over age for GP, PUT, CN, THL and FWM (top to bottom graphs, respectively). For all subplots: X-axis is age in years, left Y-axis is the MFC (left column graphs) or R2 (right column graphs) metric means corresponding to the individual points, and right Y-axis is putative postmortem non-heme iron concentration (C_PM) corresponding to the adjusted growth curve from Hallgren and Sourander (6) (solid line).