Assessing early erythrolysis and the relationship to perihematomal iron overload and white matter survival in human intracerebral hemorrhage

Nemanja Novakovic, Zachary M Wilseck, Thomas L Chenevert, Guohua Xi, Richard F Keep, Aditya S Pandey, Neeraj Chaudhary, Nemanja Novakovic, Zachary M Wilseck, Thomas L Chenevert, Guohua Xi, Richard F Keep, Aditya S Pandey, Neeraj Chaudhary

Abstract

Aims: Iron released from lysed red blood cells within the hematoma plays a role in intracerebral hemorrhage (ICH)-related neurotoxicity. This study utilizes magnetic resonance imaging (MRI) to examine the time course, extent of erythrolysis, and its correlation with perihematomal iron accumulation and white matter loss.

Methods: The feasibility of assessing proportional erythrolysis using T2* MRI was examined using pig blood phantoms with specified degrees of erythrolysis. Fifteen prospectively enrolled ICH patients had MRIs (3-Tesla) at days 1-3, 14, and 30 (termed early, subacute, and late periods, respectively). Measurement was performed on T2*, 1/T2*, and fractional anisotropy (FA) maps.

Results: Pig blood phantoms showed a linear relationship between 1/T2* signal and percent erythrolysis. MRI on patients showed an increase in erythrolysis within the hematoma between the early and subacute phases after ICH, almost completing by day 14. Although perihematomal iron overload (IO) correlated with the erythrolysis extent and hematoma volume at days 14 and 30, perihematomal white matter (WM) loss significantly correlated with both, only at day 14.

Conclusion: MRI may reliably assess the portion of the hematoma that lyses over time after ICH. Perihematomal IO and WM loss correlate with both the erythrolysis extent and hematoma volume in the early and subacute periods following ICH.

Keywords: erythrolysis; hematoma; intracerebral hemorrhage; iron overload; magnetic resonance imaging; white matter loss.

Conflict of interest statement

The authors declare that they have no conflict of interest.

© 2021 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Porcine blood phantom vials containing different percentages of lysed red blood cells (RBCs) and one vial with purified water were evaluated using T2* MRI. T2* maps were created, and 1/T2* = R2* (Hz) values determined. A, An example of such analysis, with color‐coded image for 1/T2*. The percentage of cell lysis is shown against each vial. B, A plot of 1/T2* against the percentage of lysed RBCs shows a linear relationship (p = 0.0013, R2 = 0.979). Values are represented as means ± standard deviation, n = 6
FIGURE 2
FIGURE 2
Sixty‐seven‐year‐old male patient presenting with 25‐mL right putaminal ICH. Axial T2* imaging was performed at days 3 (A) and 14 (B). These show the difference in the extent of T2* non‐hypointense signal within the hematoma with time. Non‐hypointense regions of ICH (depicting erythrolysis volume), shown by the shaded regions at days 3 (C; green) and 14 (D; red), demonstrate increased erythrolysis volume with time post‐ICH presentation. E, The non‐hypointense T2* volume was divided by hematoma volume to calculate percentage erythrolysis in individual patients examined at days 1–3 and 14. The percentage erythrolysis increased markedly between those time points (Mann‐Whitney p = 0.0006; n = 10–13). F, Almost all patients examined at both days ≤3 and 14 showed a marked increase in percent erythrolysis with time (Wilcoxon p = 0.0156; n = 7)
FIGURE 3
FIGURE 3
Relationship between erythrolysis and hematoma volume at days (A) ≤3 and (B) 14. There was a highly significant correlation between erythrolysis volume and hematoma volume at day 14 (p < 0.0001, R2 = 0.985), but not for day ≤3 (p = 0.4109, R2 = 0.053)
FIGURE 4
FIGURE 4
Relationship between perihematomal iron overload and erythrolysis volume at days 3, 14, and 30 is shown in the top graphs (A‐C). There was a significant relationship at days 14 (p = 0.0347, R2 = 0.447) and 30 (p = 0.0061, R2 = 0.631), but not at day 3 (p = 0.3168, R2 = 0.1110). Bottom graphs (D‐F) show the relationship between iron overload and hematoma volume. There was a significant relationship at days 14 (p = 0.0268, R2 = 0.527) and 30 (p = 0.0029, R2 = 0.690), but not at day 3 (p = 0.0886, R2 = 0.288)
FIGURE 5
FIGURE 5
Relationship between perilesional white matter loss and either erythrolysis volume (A) or hematoma volume (B) at day 14. There was a significant correlation with perilesional white matter loss at day 14 with both erythrolysis volume (p = 0.0006, R2 = 0.836) and hematoma volume (p = 0.0006, R2 = 0.834)

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