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Treatment of Deeply Located Acute Intravascular Thrombi With Therapeutic Ultrasound Guided by Diagnostic Ultrasound and Intravenous Microbubbles

Department of Internal Medicine, Section of Cardiology (J.M.T., F.X., J.L., B.C., T.R.P.), and Department of Surgery (J.J.), University of Nebraska Medical Center, Omaha, Nebraska USA; Siemens Medical Solutions USA, Inc, Mountain View, California USA (A.H., L.T.); and ImaRx Therapeutics, Inc, Tucson, Arizona USA (T.M., E.U.).

Address correspondence to Thomas R. Porter, MD, University of Nebraska Medical Center, 981165 Nebraska Medical Center, Omaha NE 68198-1165 USA. E-mail: trporter{at}unmc.edu

Objective. We sought to determine the added value of simultaneous imaging of intravenously infused microbubbles that are being used to dissolve an intravascular thrombus with therapeutic ultrasound (TUS). Methods. In a chronic canine arteriovenous graft occluded by a thrombus, TUS (1 MHz) was applied through a 6-cm-thick tissue-mimicking phantom (measured mean ± SD peak negative pressure through the phantom, 958 ± 104 kPa) during an intravenous infusion of either saline (n = 6 occlusions) or lipid-encapsulated microbubbles (ImaRx Therapeutics, Inc, Tucson, AZ). Therapeutic ultrasound was intermittently applied during the microbubble infusion either at set time intervals (n = 6 occlusions) or when simultaneous diagnostic ultrasound (DUS) indicated a sustained presence of microbubbles (n = 12 occlusions). Success was defined as return of rapid flow within the graft (grade 3 flow). Results. Diagnostic ultrasound showed microbubbles moving through small channels within the thrombus before angiographic evidence of flow in the graft. This guided the timing of TUS application better than using set time intervals. Angiographic clearance of the thrombus and restoration of grade 3 flow at 45 minutes of treatment were seen in 33% of deeply located thrombosed grafts treated with TUS at set time intervals and 92% of grafts treated with TUS guided by DUS (P < .001 compared with set time intervals). Conclusions. The use of TUS with intravenous microbubbles has a high success rate in recanalizing deeply located thrombosed arteriovenous grafts when performed with DUS guidance.

Key Words: microbubbles • therapeutic ultrasound • thrombolysis

Abbreviations: CPS, contrast pulse sequencing • DUS, diagnostic ultrasound • LEMB, lipid-encapsulated microbubble • TUS, therapeutic ultrasound

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