Magnetic resonance imaging of microvascular leakage induced by myocardial contrast echocardiography in rats

The extent and magnitude of microvascular leakage induced by myocardial contrast echocardiography (MCE) were characterized with contrast-aided magnetic resonance imaging (MRI). Evans blue dye, Definity ultrasound contrast agent and Omniscan magnetic resonance contrast agent were injected intravenously in anesthetized rats suspended in a water bath. Diagnostic ultrasound B mode scans with 1:4 end-systolic triggering were performed at 1.5 MHz using a cardiac phased array scanhead to provide a short axis view of the left ventricle. The in situ peak rarefactional pressure amplitude (PRPA) was 2.0 MPa. Microvascular leakage was characterized by extraction of the dye from tissue samples and by imaging the distribution and concentration of Omniscan within the myocardium. The extracted Evans blue was 2.3 times greater than in shams (P<.05) for heart samples perfused with heparin saline, and 1.6 times greater than shams (not significant) for unperfused samples. The MRI showed the penetration of the ultrasound-induced capillary leakage throughout much of the scan plane. The overall gadolinium content measured by MR showed the same trends as the extracted Evans blue, but was more variable. For pooled data (perfused and unperfused), the exposed samples were significantly increased (P<.05) relative to the sham samples for both Evans blue and gadolinium content. Omniscan leakage was also discernable in two of four MRIs from intact rats (after sacrifice). These results demonstrate a potential for MR mapping of capillary leakage induced by contrast-aided ultrasound, with a possible application to spatial characterization of local drug delivery.