The hypothesis surrounding this project is that application of ultrasound contrast agents can improve efficacy of HIFU hemostasis of injured solid organs, while maintaining treatment safety.

Specific Aim 1: Determination of efficacy and safety of HIFU hemostasis in the presence of ultrasound contrast agents (UCA).

• Aim 1a: Mechanisms of HIFU hemostasis in the presence of commercially available UCA Optison.
• Aim 1b: Efficacy and safety of HIFU hemostasis in the presence of Optison.

Specific Aim 2: Development and testing of autologous UCA for HIFU hemostasis.

• Aim 2a: Development of autologous UCA.
• Aim 2b: Determination of the efficacy of HIFU hemostasis in the presence of autologous UCA.

Key Findings
Thermal measurements showed similar temperatures of the coagulum formed at the injury site treated with HIFU, with or without UCA administration. Inertial cavitation activity, a signature of mechanical effects, was higher during HIFU application in the presence of UCA. The presence of Optison in the blood stream during HIFU hemostasis of liver injuries resulted in 37 percent faster times (p<0.05) needed to achieve complete hemostasis as compared to control treatments (with no UCA present).

The presence of in-house UCA in the blood stream also resulted in faster hemostasis times for the sealing of liver injuries (46 percent faster as compared to control treatments, p<0.05). Coagulum formation at the injury site was faster as the concentration of administered UCA increased. Hemostatic seal over injury sites achieved with HIFU or HIFU+UCA was more robust as compared to the seal achieved with electrocautery.

UCA (both Optison and in-house UCA) increased the rate of successful bleeding detection and localization of hidden solid organ injuries (in rabbit kidneys and liver) and vessel injuries (in rabbit and porcine arteries). With regular ultrasound imaging methods (B-mode and Color Doppler), injuries with slow bleeding could not be detected unless UCA were present in the blood stream.

The levels of systemic blood hemolysis during HIFU therapy increased if UCA were administered before the therapy. Light microscopy observations showed no histological difference between the liver tissue treated with HIFU only or HIFU in the presence of UCA. The presence of in-house UCA resulted in 35 percent reduction of the lesion depth (i.e., resulted in the production of shallow lesions localized at the injury site), and prevented the formation of HIFU lesions beyond the focus. The presence of bubbles at the HIFU focus prevented the temperature increase at the tissue-air interface in the post-focal region.

Impact of Findings
Both in-house UCA and commercially available UCA Optison can be used to achieve faster hemostasis times of liver injuries and faster coagulum formation at the injury site. Our findings showed that faster coagulum formation and hemorrhage control was due to the mechanical effects of HIFU application in the presence of UCA. Bleeding detection experiments showed that UCA (both Optison and in-house UCA) can be used to improve the detection and localization of bleeding sites, which could be of significant importance during HIFU treatment of hidden bleedings and for eventual extracorporeal HIFU application.

Earth-based Applications of Research Project:
On Earth, bleeding due to blunt trauma is one of the primary causes of death within an hour after the injury if adequate care is not provided. Rapid achievement of hemostasis is necessary to prevent hemorrhagic shock following intra-abdominal injury. However, hemostasis is not an easy task in trauma patients due to the usual presence of coagulopathy, resulting from hypothermia, acidosis and dilution of clotting factors.

Difficulties associated with treating battlefield and civilian trauma hemorrhage are in being able to detect and localize the hemorrhage site and to stop the bleeding noninvasively, all within a very short time (of several minutes) after the trauma has occurred. Our group demonstrated the potential of ultrasound-guided HIFU to both detect a bleeding site and deliver energy to produce hemostasis. Specifically, this project addressed HIFU-induced hemorrhage control from solid organs in the presence of ultrasound contrast agents (UCA). The administration of UCA may facilitate detection and localization of bleeding sites and allow faster hemorrhage control. Our eventual goal is to develop a portable automatic HIFU device that can be used at the site of accident to localize and stop the bleeding by a non-skilled operator, similar to current usage of defibrillators.

Project Description
NASA Task Book Entry