Abstract Body: Introduction
Intracerebral hemorrhage (ICH) is commonly associated with poor neurologic outcomes. Early intervention has been shown to improve patient prognosis, highlighting the necessity of sensitive biomarkers. In this study, we aim to explore the potential of magnetic resonance imaging (MRI)-based physiological parameters for detecting microvascular dysfunction in an acute ICH mouse model.
Methods
Young (5 months old, N=2) and aged (22 months old, N=2) C57BL/6 male mice were utilized. ICH was induced via a stereotaxic intra-striatal injection of collagenase. These mice were scanned before and 1 day after surgery longitudinally. We employed a range of non-invasive MRI techniques at 11.7T to characterize microvascular dysfunctions. These techniques included: (a) spin echo MRI for brain volume, (b) T₂-relaxation-under-spin-tagging (TRUST) and phase contrast MRI for cerebral metabolic rate of oxygen (CMRO₂), (c) arterial spin labeling MRI for regional cerebral perfusion, and (d) water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST) MRI for blood-brain-barrier (BBB) permeability.
Results
Brain volume demonstrated a significant age effect (linear mixed effect [LME] model: P=0.044), but was not significantly influenced by ICH, indicating negligible brain dwelling at the examined timepoints. TRUST imaging reveals distinct patterns of change from baseline to ICH between young and aged mice (Fig. 1A). A significant ICH-by-age interaction effect (LME: P=0.004) suggests that the impact of ICH on brain metabolism varies between young and aged mice. ICH-affected brain regions were identifiable in the perfusion maps for both age groups with hemorrhagic areas showing associated hypoperfusion, as indicated by the arrows (Fig. 2). In terms of BBB function, there was a notable reduction in the WEPCAST signal observed around the great vein of Galen (arrows in Fig. 3A). The significant ICH-by-age effect on the permeability-by-area-product (PS) (P=0.006, Fig. 3B) of LME analysis indicates that aged mice are more vulnerable to the BBB disruption following ICH.
Conclusion
Our study highlights the potential of physiological imaging biomarkers for detecting early microvascular dysfunctions in ICH. Specifically, functional parameters (i.e., CMRO₂ and BBB permeability) show promise as sensitive indicators for the early detection of ICH. These biomarkers could facilitate timely interventions, potentially improving outcomes for stroke patients.