The primary goal of treatments for acute ischemic stroke (AIS) is to restore cerebral blood flow in occluded vessels through thrombolysis, either in conjunction with thrombectomy or as a standalone procedure. However, even after successful recanalization, downstream microcirculation may still be obstructed by microvascular thrombosis leading to compromised brain reperfusion and cognitive decline. Regrettably, identifying these microthrombi through non-invasive methods remains challenging. For this specific purpose, we developed the PHySIOMIC (Polydopamine Hybridized Self-assembled Iron Oxide Mussel Inspired Clusters), an innovative MRI-based contrast agent which unmasks microthrombi in vivo. In a mouse model of thromboembolic ischemic stroke, our findings demonstrate that PHySIOMIC generate a distinct hypointense signal on T2*-weighted MRI in the presence of microthrombi, as confirmed by histological analysis. The extent of hypointense signal at the onset of stroke displayed a correlation with the lesion sizes observed 24 hours post-stroke. Mice treated with thrombolytic agents exhibited a disappearance of the hypointense signal, validating effective thrombolysis of microthrombi. Our microfluidic studies revealed the role of fibrinogen present in the protein corona composition for the targeting of PHySIOMIC to microthrombi. Furthermore, we established the degradation patterns of these particles within the liver and spleen over time. The PHySIOMIC particles offer an innovative and valuable tool for non-invasive in vivo diagnosis and monitoring of microthrombi, using MRI during AIS.