Abstract
Background: Thrombolysis using ultrasound (US) induced destruction of systemically injected microbubbles (MBs) is a potential targeted treatment for acute myocardial infarction or ischemic stroke. The physical mechanisms underlying MB mediated clot lysis are incompletely elucidated, partly due to limitations in methods to characterize morphologic and volumetric changes in a thrombus resulting from MB destruction. Here, we explore possibilities for 3D quantitative assessment of sonothrombolysis using optical coherence tomography (OCT), a high resolution imaging modality. Methods: Thrombi were formed in polyethylene tubing (1.67 mm i.d.) from recalcified porcine blood using silk suture as a nidus for thrombosis. Lipid shell MBs suspended in saline and tissue plasminogen activator (rt-PA, 3 μ g/ml) were perfused through the tube (22 μ l/min, 2x107 MBs/ml) using a syringe pump while US pulses (1 MHz, 1.0 MPa, 100 cycles) were delivered over 30 min to the clot from a single element transducer every 5 sec to ensure MB replenishment between destructive pulses. 3D OCT images of clots were obtained before and after US treatment, rt-PA alone, or saline alone (n=3/condition). Clot volume was measured using clot boundary determination by thresholding pixel intensity of each cross-sectional OCT image. Results: Thrombi treated with US + MBs + rt-PA decreased in volume by 55.7% (0.02 mm3; p=0.02). rt-PA alone resulted in a 25.6% (0.009 mm3; p=0.39) decrease in volume and treatment with saline alone did not change clot volume (0.003 mm3; p=0.94). OCT images qualitatively showed greatest change in clot shape and volume in regions closest to the source of US (Fig 1). Conclusion: 3D OCT can quantify thrombolysis. As expected, the addition of US and MBs enhanced the lytic effect of rt-PA. OCT imaging may reveal the physical effects of contrast US on thrombus structure, thereby yielding insights into mechanisms of sonothrombolysis that can be used to optimize treatment regimens.
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