Effect of Thrombin and Incubation Time on Porcine Whole Blood Clot Elasticity and Recombinant Tissue Plasminogen Activator Susceptibility.

Deep vein thrombosis is a major source of morbidity and mortality worldwide. Catheter-directed thrombolytics are the frontline approach for vessel recanalization, though fibrinolytic efficacy is limited for stiff, chronic thrombi. Although thrombin has been used in preclinical models to induce thrombosis, the effect on lytic susceptibility and clot stiffness is unknown. The goal of this study was to explore the effect of bovine thrombin concentration and incubation time on lytic susceptibility and stiffness of porcine whole blood clots in vitro. Porcine whole blood was allowed to coagulate at 37°C in glass pipets primed with 2.5 or 15 U/mL thrombin for 15 to 120 min. Lytic susceptibility to recombinant tissue plasminogen activator (rt-PA, alteplase) over a range of concentrations (3.15-107.00 µg/mL) was evaluated using percentage clot mass loss. The Young's moduli and degrees of retraction of the clots were estimated using ultrasound-based single-track-location shear wave elasticity and B-mode imaging, respectively. Percentage mass loss decreased and clot stiffness increased with the incubation period. Clots formed with 15 U/mL and incubated for 2 h exhibited properties similar to those of highly retracted clots: Young's modulus of 2.39 ± 0.36 kPa and percentage mass loss of 8.69 ± 2.72% when exposed to 3.15 µg/mL rt-PA. The histological differences between thrombin-induced porcine whole blood clots in vitro and thrombi in vivo are described.

Accelerated sonothrombolysis with Definity in a xenographic porcine cerebral thromboembolism model.

Adjuvant ultrasound at 2 MHz with or without an ultrasound contrast agent improves the rate of thrombus resolution by recombinant tissue plasminogen activator (rt-PA) in laboratory and clinical studies. A sub-megahertz approach can further expand this therapy to a subset of patients with an insufficient temporal bone window, improving efficacy in unselected patient populations. The aim of this study was to determine if a clinical ultrasound contrast agent (UCA), Definity, and 220 kHz pulsed ultrasound accelerated rt-PA thrombolysis in a preclinical animal model of vascular occlusion. The effect of Definity and ultrasound on thrombus clearance was first investigated in vitro and subsequently tested in a xenographic porcine cerebral thromboembolism model in vivo. Two different microcatheter designs (end-hole, multi-side-hole) were used to infuse rt-PA and Definity at the proximal edge or directly into clots, respectively. Sonothrombolysis with Definity increased clot mass loss relative to saline or rt-PA alone in vitro, only when rt-PA was administered directly into clots via a multi-side-hole microcatheter. Combined treatment with rt-PA, Definity, and ultrasound in vivo increased the rate of reperfusion up to 45 min faster than clots treated with rt-PA or saline. In this porcine cerebral thromboembolism model employing retracted human clots, 220 kHz ultrasound, in conjunction with Definity increased the probability of early successful reperfusion with rt-PA.

Magnetic Resonance-Guided Nasogastric Feeding Tube Placement for Neonates: A Preclinical Study.

BACKGROUND: Establishing postnatal nutrition delivery is challenging in neonates with immature sucking and swallowing ability. Enteral feeding is the gold standard for such patients, but their small size and fragility present challenges in nasogastric (NG) feeding tube placement. Feeding tubes are typically placed with x-ray guidance, which provides minimal soft tissue contrast and exposes the baby to ionizing radiation. This research investigates magnetic resonance (MR) guidance of NG feeding tube placement in neonates to provide improved soft tissue visualization without ionizing radiation. MATERIALS AND METHODS: A novel feeding tube incorporating 3 solenoid coils for real-time tracking and guidance in the MR environment was developed. The feeding tube was placed 5 times in a rabbit with conventional x-ray guidance to assess mechanical stability and function. After x-ray procedures, the rabbit was transferred to a neonatal MR system, and the tube was placed 5 more times. RESULTS: In procedures guided by x-ray and MR, the feeding tube provided sufficient mechanical strength and functionality to access the esophagus and stomach of the rabbit. MR imaging provided significantly improved soft tissue contrast versus x-ray, which aided in proper tube guidance. Moreover, MR guidance allowed for real-time placement of the tube without the use of ionizing radiation. CONCLUSIONS: The feasibility and benefits offered by an MR-guided approach to NG feeding tube placement were demonstrated. The ability to acquire high-quality MR images of soft tissue without ionizing radiation and a contrast agent, coupled with accurate 3-dimensional device tracking, promises to have a powerful impact on future neonatal feeding tube placements.

Effect of real-time radiation dose feedback on pediatric interventional radiology staff radiation exposure.

PURPOSE: To measure and compare individual staff radiation dose levels during interventional radiologic (IR) procedures with and without real-time feedback to evaluate whether it has any impact on staff radiation dose. MATERIALS AND METHODS: A prospective trial was performed in which individuals filling five different staff roles wore radiation dosimeters during all IR procedures during two phases: a 12-week "closed" phase (measurements recorded but display was off, so no feedback was provided) and a 17-week "open" phase (display was on and provided real-time feedback). Radiation dose rates were recorded and compared by Mann-Whitney U test. RESULTS: There was no significant difference in median procedure time, fluoroscopy time, or patient dose (dose-area product normalized to fluoroscopy time) between the two phases. Overall, the median staff dose was lower in the open phase (0.56 µSv/min of fluoroscopy time) than in the closed phase (3.01 µSv/min; P < .05). The IR attending physician dose decreased significantly for procedures for which the physicians were close to the patient, but not for ones for which they were far away. CONCLUSIONS: A radiation dose monitoring system that provides real-time feedback to the interventional staff can significantly reduce radiation exposure to the primary operator, most likely by increasing staff compliance with use of radiation protection equipment and dose reduction techniques.