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Fiscal Year: FY 2007  Task Last Updated:  01/31/2008 
PI Name: Zderic, Vesna  
Project Title: Contrast Agents for High-Intensity Focused Ultrasound Hemostasis 
   
Division Name: Human Research 
Program/Discipline: NSBRI Teams 
Element/Subdiscipline: Smart Medical Systems Team 
Joint Agency Name:  
Human Research Program Elements: None
Human Research Program Risks:: None
Human Research Program Gaps: None
PI Email: zderic@gwu.edu  Fax:   
PI Organization Type: UNIVERSITY  Phone: 206-818-0960  
Organization Name: University of Washington 
PI Address 1: 1705 NE Pacific Street 
PI Address 2:  
PI Web Page:  
City: Seattle  State: WA 
Zip Code: 98195  Congressional District: 
Comments:  
Project Type: GROUND  Solicitation:  2004 NSBRI-RFP-04-01 Postdoctoral Fellowships 
Start Date: 11/01/2004  End Date:  10/31/2006 
No. of Post Docs: No. of PhD Degrees: 
No. of PhD Candidates: No. of Master' Degrees: 
No. of Master's Candidates: No. of Bachelor's Degrees: 
No. of Bachelor's Candidates: Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment:

 

Key Personnel Changes/Previous PI:  
COI Name (Institution): Crum, Lawrence  ( University of Washington ) 
Grant/Contract No.: NCC 9-58-PF00505 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: POSTDOCTORAL FELLOWSHIP

(1) the original aims:

The hypothesis 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.

(2) the 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% 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 sealing of liver injuries (46% 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 the injury site 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% 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.

(3) the impact of these 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.

 

Research Impact/Earth Benefits: 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 non-invasively, all within a very short time (of several minutes) after the trauma has occurred. Our group demonstrated potential of ultrasound-guided HIFU to both detect a bleeding site and deliver energy to produce hemostasis. Specifically, this NSBRI-funded 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.

 

Task Progress: Specific tasks accomplished in the Project year 2 are described below:

1. Development of in-house ultrasound contrast agents (UCA) for High Intensity Focused Ultrasound (HIFU) therapy. The size of UCA had to be optimized to be less than 10 µm to allow passage through lungs. A variety of UCA manufacturing methods were explored. Our current in-house UCA solution consists of 5% albumin and 10% dextrose in saline. This solution is sonicated in the presence of perfuoropropane gas for 90 s using 20 kHz sonicator (at ~40 W/cm^2) to produce microbubbles of appropriate size. These in-house UCA have concentration of 3x10^8 bubbles/ml with the bubble size of 1-8 µm (mean size of 3 µm).

2. Bleeding detection in the presence of in-house UCA. Scalpel cuts (3 cm in length and 0.5 cm deep) were produced in the posterior surface of rabbit livers and kidneys; or puncture injuries were produced transcutaneously in the rabbit femoral arteries. The in-house UCA made of albumin, dextrose and perfluoropropane gas improved detection and localization of slow bleeding from solid organ injuries and punctured vessels. This bleeding is otherwise not detected using standard ultrasound methods.

3. Determination of the efficiency of HIFU treatment in the presence of in-house UCA. HIFU treatments (at the frequency of 5.5 MHz, in-situ intensity of 6,800 W/cm^2) of liver lacerations were performed in rabbit in-vivo, with or without the presence of in-house UCA (0.8 ml, 1:2 saline dilution) in the blood stream. The average hemostasis times normalized with the bleeding rate were 39 s/ml*min for HIFU only treatments and 21 s/ml*min for HIFU+UCA treatments. The presence of home-made UCA in the blood stream resulted in 44% percent reduction in the times to the first formation of the blood coagulum at the HIFU treatment site, and 46% reduction (p<0.05) in HIFU hemostasis times.

4. Determination of the size and shape of HIFU lesions in the rabbit liver in-vivo, which were produced immediately after the injection of in-house UCA or without the presence of UCA. The objective of this study was to see whether it would be possible to customize the shape of HIFU lesions such that the lesion is localized at the site of interest (i.e., organ surface injury), without causing damage in the healthy deep tissue regions. The presence of in-house UCA resulted in 35% reduction of the lesion depth (i.e., resulted in the production of more shallow lesions). The maximal diameter of the lesions increased by 30% in the presence of in-house UCA, as compared to control lesions. It appeared that the presence of in-house microbubbles in the liver tissue caused the shielding of the postfocal region from the HIFU exposure.

 

Bibliography Type: Description: (Last Updated: 04/10/2008) Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Burgess S, Zderic V, Vaezy S. "Image-guided acoustic hemostasis for hemorrhage in the posterior liver." Ultrasound Med Biol. 2007 Jan;33(1):113-9. PMID: 17189053 , Jan-2007
Articles in Peer-reviewed Journals Greaby R, Zderic V, Vaezy S. "Pulsatile flow phantom for ultrasound image-guided HIFU treatment of vascular injuries." Ultrasound Med Biol. 2007 Aug;33(8):1269-76. Epub 2007 Apr 27. PMID: 17466441 , Aug-2007
Articles in Peer-reviewed Journals Held RT, Zderic V, Nguyen TN, Vaezy S. "Annular phased-array high-intensity focused ultrasound device for image-guided therapy of uterine fibroids." IEEE Trans Ultrason Ferroelectr Freq Control. 2006 Feb;53(2):335-48. PMID: 16529108 , Feb-2006
Articles in Peer-reviewed Journals Lafon C, Zderic V, Noble ML, Yuen JC, Kaczkowski PJ, Sapozhnikov OA, Chavrier F, Crum LA, Vaezy S. "Gel phantom for use in high-intensity focused ultrasound dosimetry." Ultrasound Med Biol. 2005 Oct;31(10):1383-9. PMID: 16223642 , Oct-2005
Articles in Peer-reviewed Journals Luo W, Zderic V, Carter S, Crum L, Vaezy S. "Detection of bleeding in injured femoral arteries with contrast-enhanced sonography." J Ultrasound Med. 2006 Sep;25(9):1169-77. PMID: 16929018 , Sep-2006
Articles in Peer-reviewed Journals Luo W, Zderic V, Vaezy S. "Detection of bleeding from puncture wounds in the femoral artery using color and pulsed doppler methods." Ultrasound Med Biol. Submitted, 2006. , Oct-2006
Articles in Peer-reviewed Journals Rabkin BA, Zderic V, Crum LA, Vaezy S. "Biological and physical mechanisms of HIFU-induced hyperecho in ultrasound images." Ultrasound Med Biol. 2006 Nov;32(11):1721-9. PMID: 17112958 , Nov-2006
Articles in Peer-reviewed Journals Vaezy S, Zderic V, Karmy-Jones R, Jurkovich GJ, Cornejo C, Martin RW. "Hemostasis and sealing of air leaks in lung using high-intensity focused ultrasound." J Trauma. 2007 Jun;62(6):1390-5. PMID: 17563654 , Jun-2007
Articles in Peer-reviewed Journals Vaezy S, Zderic V. "Hemorrhage control using high intensity focused ultrasound." Int J Hyperthermia. 2007 Mar;23(2):203-11. Review. PMID: 17578344 , Mar-2007
Articles in Peer-reviewed Journals Zderic V, Brayman AA, Sharar SR, Crum LA, Vaezy S. "Microbubble-enhanced hemorrhage control using high intensity focused ultrasound." Ultrasonics. 2006 Dec;45(1-4):113-20. PMID: 16949630 , Dec-2006
Articles in Peer-reviewed Journals Zderic V, O' Keefe GE, Foley JL, Vaezy S. "Resection of abdominal solid organs using high-intensity focused ultrasound." Ultrasound Med Biol. 2007 Aug;33(8):1251-8. Epub 2007 May 11. PMID: 17498864 , Aug-2007
Articles in Peer-reviewed Journals Zderic V, Keshavarzi A, Noble ML, Paun M, Sharar SR, Crum LA, Martin RW, Vaezy S. "Hemorrhage control in arteries using high-intensity focused ultrasound: a survival study." Ultrasonics. 2006 Jan;44(1):46-53. PMID: 16176829 , Jan-2006
Articles in Peer-reviewed Journals Zderic V, Vaezy S, Foley J, Luo W, Lebedev A. "Bubbles at the HIFU focus for prevention of thermal damage at soft tissue-air interfaces in the post-focal region." Ultrasound Med Biol. Submitted, 2006. , Oct-2006
Awards Zderic V. "Gold Prize for Young Investigator Award at the 11th Congress of the World Federation for Ultrasound in Medicine and Biology, Seoul, Korea, June 2006." Jun-2006
Awards Zderic V. "Reviewer for Journal of Ultrasound in Medicine and Biology, 2006." Oct-2006
Patents PCT/US05/33585. Patent September 2005. Sep-2005 Vaezy S, Held RT, Zderic V, Managuli R, Sikdar S. "Interference-Free Ultrasound Imaging During HIFU Therapy, Using Software Tools."
Patents PCT/US2005/033587. Patent September 2005. Sep-2005 Vaezy S, Nguyen TN, Zderic V, Foley JL. "Acoustic Coupling using an Independent Water Pillow with Circulation for Cooling the Transducer."
Patents PCT/US2006/036106. Patent September 2006. Sep-2006 Vaezy S, Zderic V. "Thin-Profile Transducers for Intraoperative Hemostasis."
Patents 60/825,610. Patent September 2006. Sep-2006 Vaezy S, Yu J, Zderic V. "Ultrasound Transducer Design for Customized Beam Forming."
 
Fiscal Year: FY 2006  Task Last Updated:  11/09/2005 
PI Name: Zderic, Vesna  
Project Title: Contrast Agents for High-Intensity Focused Ultrasound Hemostasis 
   
Division Name: Human Research 
Program/Discipline: NSBRI Teams 
Element/Subdiscipline: Smart Medical Systems Team 
Joint Agency Name:  
Human Research Program Elements: None
Human Research Program Risks:: None
Human Research Program Gaps: None
PI Email: zderic@gwu.edu  Fax:   
PI Organization Type: UNIVERSITY  Phone: 206-818-0960  
Organization Name: University of Washington 
PI Address 1: 1705 NE Pacific Street 
PI Address 2:  
PI Web Page:  
City: Seattle  State: WA 
Zip Code: 98195  Congressional District: 
Comments:  
Project Type: GROUND  Solicitation:  2004 NSBRI-RFP-04-01 Postdoctoral Fellowships 
Start Date: 11/01/2004  End Date:  10/31/2006 
No. of Post Docs: No. of PhD Degrees: 
No. of PhD Candidates: No. of Master' Degrees: 
No. of Master's Candidates: No. of Bachelor's Degrees: 
No. of Bachelor's Candidates: Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment:

 

Key Personnel Changes/Previous PI:  
COI Name (Institution): Crum, Lawrence  ( University of Washington ) 
Grant/Contract No.: NCC 9-58-PF00505  
Performance Goal No.:  
Performance Goal Text:

 

Task Description: POSTDOCTORAL FELLOWSHIP

(1) the original aims The hypothesis is that the application of ultrasound contrast agents will improve efficacy of HIFU hemostasis of injured solid organs, while maintaining the treatment safety. Specific Aim 1: Determination of efficacy and safety of HIFU hemostasis in the presence of ultrasound contrast agents. Aim 1a: Mechanisms of HIFU hemostasis in the presence of commercially available UCA Optison. Thermal, mechanical and biological mechanisms of hemostasis in the presence of Optison will be investigated for the treatment optimization. Aim 1b: Efficacy and safety of HIFU hemostasis in the presence of Optison. Hemostasis efficacy will be determined, as well as healing of hemostatic liver incisions in rabbits for up to 60 days after the treatment. Specific Aim 2: Development and testing of autologous UCA for HIFU hemostasis. Aim 2a: Development of autologous UCA. UCA consisting of blood, saline and air will be produced, characterized, and optimized for hemostasis application. Aim 2b: Determination of the efficacy of HIFU hemostasis in the presence of autologous UCA. HIFU treatment of liver incisions will be performed in the presence of autologous UCA to determine the treatment efficacy in producing hemostasis. (2) the 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 coagulum formation was faster as the concentration of administered Optison increased. - Hemostatic seal over injury site achieved with HIFU or HIFU+UCA was more robust as compared to the seal achieved with electrocautery. - Our results showed that UCA can increase the rate of successful bleeding detection. - The levels of systemic blood hemolysis during HIFU therapy increased if UCA were administered before the therapy. - Light microscopy observations showed no difference between the liver tissue treated with HIFU only or HIFU in the presence of UCA. - We developed a method for occlusion of large blood vessels of up to 1 cm in diameter. - Ultrasound-guided phased array was used for occlusion of blood vessels at different depths inside a liver. - We showed the feasibility of ultrasound-guided HIFU treatment of occult injuries located in the posterior surface of the liver. - The presence of bubbles at the HIFU focus prevented the temperature increase at the tissue-air interface in the post-focal region. - Color Doppler HIFU can be used for transcutaneous detection and sealing of puncture wounds in the femoral arteries in a porcine model. (3) the impact of these findings Our findings showed that faster coagulum formation and hemorrhage control of liver incisions was due to the mechanical effects of HIFU application in the presence of UCA. Initial safety experiments showed a potentially higher blood hemolysis after the administration of UCA. The safety of our method will be explored in more detail during long-term survival studies proposed for the next funding year of this project. Bleeding detection experiments showed that UCA can be used to improve the detection and localization of bleeding sites, which would be of significant importance during HIFU treatment of hidden bleedings and eventual extracorporeal HIFU application. (4) the proposed research plan for the coming year: Specific Aim 1b: Efficacy and safety of Optison-enhanced HIFU hemostasis (Months 13-18). A survival study will be performed to observe healing of liver lacerations for up to 60 days after the treatment. A total of 35 adult New Zealand White rabbits will be divided into 2 groups: Optison treatment (n = 21) and control treatment (HIFU only) (n = 14). Ultrasound images, blood and histological samples will be collected immediately (day 0) and on days 1, 3, 7, 14, 28, and 60 after the treatment. Specific Aim 2a: Investigations for development of in-house UCA for HIFU therapy (Months 13-18). The shelf life of Optison of 2 years may be too short for longer space flights, for example to Mars. Therefore, we will pursue the development of contrast agents that could be made in Space. These could potentially consist of blood or blood components, saline, and air or other biologically compatible gases. This work will provide valuable guidelines on eventual development of fully-autologous contrast agents that can be made on site during flight missions. The properties of the developed UCA such as bubble size, concentrations, life time, and echogenicity, will be studied specifically for therapy applications. Specific Aim 2b: Determination of the efficiency of HIFU treatment in the presence of in-house UCA (Months 19-24). HIFU treatment of liver lacerations in rabbit in-vivo will be performed in the presence of in-house UCA. The application of in-house UCA, optimized in Specific Aim 2a, is expected to provide similar values of the hemostasis time reduction as the application of Optison. Specific Aim 2c: Determination of the utility of in-house UCA for improving the bleeding detection using ultrasound imaging (Months 19-24). The in-house UCA will be administered at the distal site after induction of injury in the posterior surface of solid organs in rabbits. Conventional B-mode, Color Doppler, Pulsed Doppler, Harmonic Imaging, and Pulse Inversion Harmonic Imaging (PIHI) will be used to visualize and potentially locate the bleeding site. We expect that our in-house contrast agents will show similar enhancement of bleeding detection as Optison during the first phases of interrogation by ultrasound.

 

Research Impact/Earth Benefits: 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 (Sauaia et al. 1995, Franklin et al. 2000). Rapid achievement of hemostasis is necessary to prevent hemorrhagic shock following intra-abdominal injury (Feliciano et al. 2000). 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 (Bellamy 1984). The 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 non-invasively, all within a very short time (of several minutes) after the trauma has occurred. Our group has demonstrated a potential of ultrasound-guided HIFU to both detect a bleeding site and deliver energy to produce hemostasis. Our current NSBRI-funded project addresses the HIFU 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.

 

Task Progress: We accomplished research tasks proposed to be performed in the Year 1, and described in Specific Aim 1a (Mechanisms of HIFU-induced hemostasis in the presence of Optison). Methods: A HIFU applicator was scanned over the incision in the liver until hemostasis was achieved. Optison solution (0.8, 1.2, or 1.8 ml) was injected into a mesenteric vein, 20 s before the start of HIFU application. Temperature was measured using infrared thermal camera and a thermocouple connected to LabView acquisition system. Broadband noise, an indication of inertial cavitation, was measured using passive cavitation detection. The tension strength was determined as the applied force at which the hemostatic incision started to bleed. For bleeding detection, triangular incisions were made in the posterior surface of liver and kidneys in heparinized rabbits. The transcutaneous punctures in the femoral arteries were also observed. Bleeding detection was performed using Color Doppler ultrasound and harmonic imaging, before and after injection of Optison (~0.1 ml/Kg). Results: Thermal Measurements. The coagulum temperature was independent of Optison concentration: 75.1 +/- 5.2, 78.9 +/- 5.2, 76.7 +/- 4.2, and 72.7 +/- 9.3 deg C at Optison concentrations of 0, 0.8, 1.2 and 1.8 ml, respectively (n=6-24). Cavitation Detection. The broadband noise measured during HIFU sealing of liver incisions was 1.7 +/- 1.0 (relative units) (n=17) without Optison, and 2.9 +/- 2.3 (n=24) with Optison administration. Coagulum Formation. The coagulum formation times were 9, 7, 5 and 4 s at Optison concentrations of 0, 0.8, 1.2 and 1.8 ml, respectively (n=6-24). The statistical significance (p<0.05) between control and Optison treatments was achieved. Live Microscopy. No difference was observed in the appearance of coagulum formed with and without Optison administration. Tension strength. The tension strength at which the hemostatic liver incisions started to bleed was 1.2 +/- 0.7 N, 1.2 +/- 0.5 N and 0.8 +/- 0.3 N for HIFU, Optison+HIFU, and electrocautery treatments, respectively (n=6-11). The incisions sealed with HIFU were 35% stronger (p<0.05). Histological Analysis. Histological observations showed similar appearance of HIFU and HIFU+UCA lesions. Hemolysis. The concentration of free hemoglobin in blood (indication of blood hemolysis) was on average 12 ml/dL after HIFU treatment, and 51 ml/dL after HIFU+Optison treatment (n=6-9). Bleeding Detection. The administration of Optison increased the rate of successful detection (by ~60%) of occult bleedings from solid organ injuries and vessel punctures. Conclusion. The enhancement of HIFU-induced hemostasis in the presence of Optison appeared to be due to mechanical mechanisms. The presence of UCA resulted in both better visualization of bleeding sites and faster formation of the coagulum over the liver incisions during acoustic hemostasis.

 

Bibliography Type: Description: (Last Updated: 04/10/2008) Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Held RT, Zderic V, Nguyen TN, Vaezy S "Annular Phased Array High Intensity Focused Ultrasound Device for Image-guided Therapy" N/A , Jan-2004
Articles in Peer-reviewed Journals Lafon C, Zderic V, Noble ML, Yuen JC, Kaczkowski PJ, Sapozhnikov OA, Chavrier F, Crum LA, Vaezy S "Gel Phantom for Use in High-Intensity Focused Ultrasound Dosimetry" N/A , Jan-2004
Articles in Peer-reviewed Journals Paek B, Foley J, Zderic V, Starr F, Shields LE, Vaezy S "Selective Reduction of Multifetal Pregnancy using High-Intensity Focused Ultrasound in the Rabbit Model" N/A , Sep-2005
Articles in Peer-reviewed Journals Vaezy S, Zderic V, Jurkovich GJ, Crum LA, Martin RW. "Hemostasis and Sealing of Air Leaks in Lung using High-Intensity Focused Ultrasound" N/A , Jan-2004
Articles in Peer-reviewed Journals Zderic V, Brayman AA, Sharar SR, O Keefe GE, Crum LA, Vaezy S. "Microbubble-Enhanced Hemorrhage Control with High Intensity Focused Ultrasound" N/A , Jan-2004
Articles in Peer-reviewed Journals Zderic V, Keshavarzi A, Noble ML, Paun M, Sharar SR, Crum LA, Martin RW, Vaezy S "Hemorrhage Control in Arteries using High-Intensity Focused Ultrasound: A Survival Study" N/A , Jan-2004
Awards N/A "Asked to be a reviewer for Cell and Mol Biol, J Pharm Pharmacol, Pharmacol Res, and Medical Science Monitor International Reviewers Panel" Jan-2004
Awards N/A "Award: 5% salary increase" Jan-2004
Awards N/A "Chaired a session on Therapy Monitoring at IEEE International Ultrasonics Symposium, September 2005 Rotterdam" Jan-2004
Books/Book Chapters Vaezy S, Zderic V, Fujimoto V "Uterine Fibroids: Pathogenesis & Management. Treatment of Uterine Fibroids: New Non-Invasive Developments High Intensity Focused Ultrasound" Ed. Brosens I Taylor&Francis Group, Nov-2005
NASA Technical Documents Zderic, V. "Acoustic Hemostasis in the Presence of Ultrasound Contrast Agents" N/A

Jul-2005

Patents 60/610,456 is converting Patent Jan-2006 Vaezy S, Held RT, Zderic V "Interference-Free Ultrasound Imaging During HIFU Therapy, Using Software Tools"
Patents 20050038340 Patent Jan-2006 Vaezy S, Martin RW, Carter SJ, Crum LA "Use of Contrast Agents to increase the Effectiveness of High Intensity Focused Ultrasound Therapy"
Patents 60/610,451 is converting Patent Jan-2006 Vaezy S, Nguyen TN, Zderic V, Foley JL "Acoustic Coupling using an Independent Water Pillow with Circulation for Cooling the Transducer"
Presentation Zderic V, Vaezy S, Crum LA "HIFU Hemostasis of Liver Injuries Enhanced by Ultrasound Contrast Agents" N/A

Jan-2005

Presentation Zderic, V. "Acoustic Hemostasis" N/A

Jul-2005

Presentation Zderic, V. "Ultrasound-Mediated Gene and Drug Delivery" N/A

May-2005

Presentation Burgess S, Zderic V, Vaezy S "Image-guided Acoustic Hemostasis" N/A

May-2005

Presentation Luo W, Zderic V, Starr F, Paun M, Vaezy S "Contrast-enhanced Detection of Arterial Bleeding" N/A

May-2005

Presentation Vaezy S, Zderic V, Foley J, Luo W, Starr F, Lebedev A "Thermal Effects of HIFU at Soft Tissue-Air Interface in the Post-Focal Region: A Safety Concern, and a Potential Solution using Cavitation" N/A

Sep-2005

Presentation Zderic V, Burgess S, Vaezy S "Thin-Profile HIFU Applicators for Intraoperative Hemostasis" N/A

Sep-2005

Presentation Zderic V, Crum L, Vaezy S "Selective Liver Vessel Occlusion with an Ultrasound-Guided HIFU Phased Array" N/A

Sep-2005

Presentation Zderic V, Crum L, Vaezy S "Ultrasound Contrast Agents for Bleeding Detection and Acoustic Hemostasis" N/A

Sep-2005

Presentation Zderic V, Crum LA, Vaezy S "Remote Acoustic Hemostasis (RAH) - Preclinical Studies" N/A

Jun-2005

Presentation Zderic V, Foley J, Burgess S, Vaezy S "High Throughput High Intensity Focused Ultrasound (HIFU) Treatment for Tissue Necrosis" N/A

May-2005

Presentation Zderic V, Foley J, O Keefe G, Crum L, Vaezy S "High-Throughput HIFU Treatment for Intraoperative Resection of Solid Organs" N/A

Sep-2005

Presentation Zderic V, Held R, Nguyen T, Vaezy S "Image-guided High Intensity Focused Ultrasound Annular Array for Hemostasis and Tumor Treatment" N/A

May-2005

Presentation Zderic V, Luo W, Brayman A, Crum L, Vaezy S "Ultrasound Contrast Agents for Bleeding Detection and Acoustic Hemostasis" N/A

May-2005

Presentation Zderic V, Rabkin B, Crum L, Vaezy S "Color-Doppler guided High Intensity Focused Ultrasound for Hemorrhage Control" N/A

May-2005

 
Fiscal Year: FY 2005  Task Last Updated:  12/12/2006 
PI Name: Zderic, Vesna  
Project Title: Contrast Agents for High-Intensity Focused Ultrasound Hemostasis 
   
Division Name: Human Research 
Program/Discipline: NSBRI Teams 
Element/Subdiscipline: Smart Medical Systems Team 
Joint Agency Name:  
Human Research Program Elements: None
Human Research Program Risks:: None
Human Research Program Gaps: None
PI Email: zderic@gwu.edu  Fax:   
PI Organization Type: UNIVERSITY  Phone: 206-818-0960  
Organization Name: University of Washington 
PI Address 1: 1705 NE Pacific Street 
PI Address 2:  
PI Web Page:  
City: Seattle  State: WA 
Zip Code: 98195  Congressional District: 
Comments:  
Project Type: GROUND  Solicitation:  2004 NSBRI-RFP-04-01 Postdoctoral Fellowships 
Start Date: 11/01/2004  End Date:  10/31/2006 
No. of Post Docs:   No. of PhD Degrees:   
No. of PhD Candidates:   No. of Master' Degrees:   
No. of Master's Candidates:   No. of Bachelor's Degrees:   
No. of Bachelor's Candidates:   Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment:

 

Key Personnel Changes/Previous PI:  
COI Name (Institution): Crum, Lawrence  ( University of Washington ) 
Grant/Contract No.: NCC 9-58-PF00505 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: POSTDOCTORAL FELLOWSHIP

(1) Original aims. The hypothesis is that the application of ultrasound contrast agents will improve efficacy of HIFU hemostasis of injured solid organs, while maintaining the treatment safety.

Specific Aim 1: Determination of efficacy and safety of HIFU hemostasis in the presence of ultrasound contrast agents. Aim 1a: Mechanisms of HIFU hemostasis in the presence of commercially available UCA Optison. Thermal, mechanical and biological mechanisms of hemostasis in the presence of Optison will be investigated for the treatment optimization. Aim 1b: Efficacy and safety of HIFU hemostasis in the presence of Optison. Hemostasis efficacy will be determined, as well as healing of hemostatic liver incisions in rabbits for up to 60 days after the treatment.

Specific Aim 2: Development and testing of autologous UCA for HIFU hemostasis. Aim 2a: Development of autologous UCA. UCA consisting of blood, saline and air will be produced, characterized, and optimized for hemostasis application. Aim 2b: Determination of the efficacy of HIFU hemostasis in the presence of autologous UCA. HIFU treatment of liver incisions will be performed in the presence of autologous UCA to determine the treatment efficacy in producing hemostasis.

 

Research Impact/Earth Benefits: 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 (Sauaia et al. 1995, Franklin et al. 2000). Rapid achievement of hemostasis is necessary to prevent hemorrhagic shock following intra-abdominal injury (Feliciano et al. 2000). 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 (Bellamy 1984). The 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 non-invasively, all within a very short time (of several minutes) after the trauma has occurred. Our group has demonstrated a potential of ultrasound-guided HIFU to both detect a bleeding site and deliver energy to produce hemostasis. Our current NSBRI-funded project addresses the HIFU 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.

 

Task Progress: New project for FY2005; no progress this reporting period.

 

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