Nikolas M. Ivancevich

ULTRASOUND-ENHANCED rt-PA THROMBOLYSIS IN AN EX VIVO PORCINE CAROTID ARTERY MODEL

Ultrasound is known to enhance recombinant tissue plasminogen activator (rt-PA) thrombolysis. In this study, occlusive porcine whole blood clots were placed in flowing plasma within living porcine carotid arteries. Ultrasonically induced stable cavitation was investigated as an adjuvant to rt-PA thrombolysis. Aged, retracted clots were exposed to plasma alone, plasma containing rt-PA (7.1 ± 3.8 μg/mL) or plasma with rt-PA and Definity® ultrasound contrast agent (0.79 ± 0.47 μL/mL) with and without 120-kHz continuous wave ultrasound at a peak-to-peak pressure amplitude of 0.44 MPa. An insonation scheme was formulated to promote and maximize stable cavitation activity by incorporating ultrasound quiescent periods that allowed for the inflow of Definity®-rich plasma. Cavitation was measured with a passive acoustic detector throughout thrombolytic treatment. Thrombolytic efficacy was measured by comparing clot mass before and after treatment. Average mass loss for clots exposed to rt-PA and Definity® without ultrasound (n = 7) was 34%, and with ultrasound (n = 6) was 83%, which constituted a significant difference (p < 0.0001). Without Definity® there was no thrombolytic enhancement by ultrasound exposure alone at this pressure amplitude (n = 5, p < 0.0001). In the low-oxygen environment of the ischemic artery, significant loss of endothelium occurred but no correlation was observed between arterial tissue damage and treatment type. Acoustic stable cavitation nucleated by an infusion of Definity® enhances rt-PA thrombolysis without apparent treatment-related damage in this ex vivo porcine carotid artery model.

RSNA/QIBA: Shear wave speed as a biomarker for liver fibrosis staging

An interlaboratory study of shear wave speed (SWS) estimation was performed. Commercial shear wave elastography systems from Fibroscan, Philips, Siemens and Supersonic Imagine, as well as several custom laboratory systems, were involved. Fifteen sites were included in the study. CIRS manufactured and donated 11 pairs of custom phantoms designed for the purposes of this investigation. Dynamic mechanical tests of equivalent phantom materials were also performed. The results of this study demonstrate that there is very good agreement among SWS estimation systems, but there are several sources of bias and variance that can be addressed to improve consistency of measurement results.

Assessing thrombolytic efficacy in vitro: Clot mass loss versus fibrinogen protein fragment concentration

Ultrasound (US) acts synergistically with recombinant tissue plasminogen activator (rt-PA) to accelerate thrombolysis. A correlation between clot mass loss and production of the fibrin degradation product D-dimer was investigated using an in vitro clot thrombolysis model. Fully retracted clots formed from 1.5-ml human whole blood were suspended in plasma at 37°C and treated with rt-PA, or rt-PA, Definity®, and pulsed 120-kHz US for 30 min. Clots in plasma alone served as controls. Thrombolytic efficacy was assessed as percent clot mass loss. Samples from plasma surrounding the clot and from macerated clots were analyzed for D-dimer using an enzyme linked immunosorbent serologic assay. A statistically significant enhancement in clot mass loss was observed for clots exposed to rt-PA, Definity®, and US compared to rt-PA alone. Clots treated with rt-PA exhibited a higher concentration of D-dimer both in the clots and plasma. However, clots treated with rt-PA, Definity®, and US did not exhibit an enhanced leve...

Ultrasound‐enhanced thrombolysis in an ex vivo porcine carotid artery model.

Ultrasound enhances recombinant tissue plasminogen activator (rt‐PA) thrombolysis via a cavitational mechanism. An ex vivo porcine carotid arterial model incorporating physiologic flow and pressure was developed and stable cavitation promoted for thrombolysis. Aged, retracted whole blood clots were exposed to plasma alone, plasma containing rt‐PA (3.15 μg/ml), or plasma with rt‐PA and the Definity ultrasound contrast agent (0.31 μl/ml), with and without 120‐kHz continuous wave ultrasound at a peak‐to‐peak pressure amplitude of 0.44 MPa. An insonation scheme was formulated to promote and maximize stable cavitation activity by incorporating ultrasound quiescent periods that allowed for the inflow of Definity‐rich plasma. Cavitation was measured with a passive acoustic detector throughout thrombolytic treatment. Thrombolytic efficacy was measured by comparing clot mass before and after treatment. Average mass loss for clots exposed to rt‐PA and Definity without ultrasound was 34%, and with ultrasound was 83%...

Determination of optimal ultrasound parameters for ex vivo sonothrombolysis.

Stable cavitation is correlated with thrombolytic efficacy for recombinant tissue plasminogen activator (rt‐PA) mediated thrombolysis. An infusion of Definity® nucleated, promoted, and sustained stable cavitation in an ex vivo porcine carotid model exposed to 120‐kHz continuous wave ultrasound. The optimal ultrasound pressure amplitude and the durations of active and quiescent periods were determined to maximize stable cavitation. Oxygenated porcine plasma with Definity® (0.31 μL/mL) and rt‐PA (3.15 μL/mL) flowed through excised carotids loaded with whole‐blood clots exposed to 120‐kHz ultrasound and monitored with a 2.25‐MHz passive cavitation detector. Using ultraharmonic and broadband emissions to quantify stable and inertial cavitation, respectively, intraluminal ultrasound‐induced bubble activity was monitored in three vessels at four acoustic pressures. Thirty‐minute treatment trials were simulated to determine the optimal acoustic pressure amplitude (0.44 MPa peak‐to‐peak) and ultrasound duration (...