Perihematomal brain tissue iron concentration measurement by MRI in patients with intracerebral hemorrhage

Abstract

Aims: Over the past two decades, animal intracerebral hemorrhage (ICH) model studies have indicated that iron, released after hemoglobin degradation, is neurotoxic. Iron phantom and animal experiments have shown that magnetic resonance imaging (MRI) relaxivity maps correlate with iron concentration. This study expands this into patients.

Methods: Eighteen human subjects with ICH underwent MRI at 3, 14, and 30 days. R2* relaxivity maps were used to calculate perihematomal iron concentrations and T2 imaging to determine hematoma and edema volumes.

Results: Perihematomal iron concentrations were increased at all three time points and decreased with distance from the hematoma. While perihematomal iron concentrations did not vary with hematoma size, the total iron overload (increased iron concentration x volume of affected tissue) did. Total iron overload correlated with edema volume.

Conclusions: These results demonstrate the feasibility of measuring perihematomal iron in ICH patients which may be important for monitoring treatment strategies and assessing efficacy noninvasively.

Keywords: brain edema; intracerebral hemorrhage; iron; magnetic resonance imaging; relaxivity maps.

Conflict of interest statement

The authors declare no conflict of interest.

© 2020 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

Figures

FIGURE 1

Representative examples of MRIs used to determine perihematomal iron concentrations at 3, 14, and 30 d after ICH. Three concentric rings (green, yellow, and orange) were drawn around the hematoma and iron concentrations determined in each ring as well as contralateral basal ganglia, cortex, and white matter. The graph shows the median perihematomal iron concentration in each ring with time along with contralateral concentrations. Values are median, n = 18, *P < .05 vs contralateral basal ganglia, #P < .001 vs contralateral basal ganglia

FIGURE 2

Representative T2‐weighted MRI used to calculate hematoma volume. The hematoma is delineated in yellow (2nd image). The graph shows the relationship between hematoma volume and both perihematomal iron overload and iron concentration at days 3, 14, and 30. There was a significant correlation between hematoma volume and overall iron overload at all three time points (day 3: r2 = .6014, P = .0004; day 14: r2 = .4682, P = .0141; day 30: r2 = .6980, P = .0026) but not with perihematomal iron concentration at any time points (day 3: r2 = .0759, P = .3017; day 14: r2 = .1115, P = .2888; day 30: Spearman R: −.2121, P = .5603)

FIGURE 3

Representative MRI T2‐weighted image showing perihematomal edema which is delineated in green in the second image. The graph plots edema volume against perihematomal iron overload (IO) in individual patients at days 3 and 14. There was a close correlation at days 3 (Spearman R: .6607; P = .0089) and 14 (r2 = .5174; P = .0084)