Objective: To serially quantify changes of iron concentration within hematomas in the intracerebral hemorrhage (ICH) pig model using non-invasive R2* and quantitative susceptibility mapping (QSM) MRI methods.
Introduction: Hemolysis-related release of hemoglobin/heme/free iron after ICH causes cytotoxic injury. An accurate post hemorrhage assessment of iron would be valuable to develop strategies to prevent secondary damage. The T2* relaxation rate (R2* =1/T2*) on MRI depends on the regional oxy- versus deoxyhemoglobin. Post-ICH excess of deoxyhemoglobin has been applied as a quantitative marker to estimate iron in the brain. However, quantitative susceptibility mapping (QSM) is a new MRI technique that can quantify iron concentration within the hematoma by measuring induced magnetic susceptibility. Using R2* mapping and QSM in a large animal ICH model, we measured spatiotemporal changes in iron concentration in the brain.
Methods: Lobar ICH was induced by infusion of 2.5 ml autologous blood in 8 Yorkshire pigs with average age/wt of 4-6wk/12.5±2.5kg. MRI was obtained at days 1 and 7. A 3D anatomical and multi-echo gradient echo images were obtained on a clinical 3.0 T Philips Ingenia MRI system. Parametric R2* and susceptibility maps were generated. Regions of interest were placed within hematoma and contralesional CSF.
Results: R2* measurements in the hematoma at day 1 and day 7 were 41.3 ± 7.3 and 37.7 ± 7.7 s-1, respectively, whereas the corresponding susceptibility measurements were 0.75± 0.3 and 0.70 ± 0.5 ppm. The CSF R2* were 5.53 ± 2.1 and 6.85 ± 2.4 s-1, whereas susceptibility showed 0.06 ± 0.16 and 0.02 ± 0.03 ppm at the two time points. Both R2* and QSM showed no significant change in iron concentration within the hematoma ROI with p-value of 0.18 and 0.72 over a week. Absence of hyperintense regions remote from the hematoma in susceptibility maps suggested lack of diffuse iron deposition. Good correlation was observed between R2* and QSM (correlation coefficient 0.83 and 0.78 within hematoma, and -0.66 and -0.07 within CSF, at day 1 and 7, respectively).
Conclusion: R2* and especially QSM, with their ability to provide quantitative iron content, are valuable tools to test new ICH treatments particularly targeting iron in this large animal model.