Mechanical compaction alters microstructural and magnetic resonance imaging properties of acute ischemic stroke clots

Thrombolytic recanalization rates in acute ischemic stroke (AIS) patients remain low. Magnetic resonance susceptibility vessel sign has been correlated with reduced thrombolytic susceptibility. However, the driving mechanisms have not been clarified. In the present study, high-field magnetic resonance imaging is used to quantify relaxation rates and compaction of embolus analogs undergoing simulated AIS with varying pressures. Microscopy and perfusion tests are used to study the effect of compaction on clot microstructure and permeability, respectively. The results show that pressure dependent compaction alters clot microstructural characteristics and increases the R2 relaxation rate. Following compaction, the R2 in red blood cell (RBC) rich clots increases up to 224%, corresponding to a twofold increase in RBC volume fraction and polyhedrocyte formation. RBC and fibrin dominant clot permeabilities decrease by 78% and 97%, respectively, when compaction pressure increases 50 mmHg. Compacted RBC rich clots are the most likely to present with susceptibility vessel sign and have the lowest permeability. Our results suggest that increased clot constituent density due to compaction can lead to susceptibility vessel sign and elevated thrombolytic resistance by limiting thrombolytic perfusion. This is the first study to evaluate the clinical relevance of clot compaction during AIS using multiple imaging techniques.