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2029
P90
Ultrasound in Medicine and Biology
amine nephron injury induced by GBCA activation with diagnostic ultrasound. Methods: Anesthetized hairless rats were scanned in a water bath using a diagnostic ultrasound system with 1.5 MHz probe. The probe was clamped to image the right kidney 4 cm away with a tissue mimicking phantom inserted between the probe and the rat. A dose of 10 L/kg of GBCA was diluted in saline and injected via tail vein. Ten single imaging frames were then triggered every 10 s at a measured MI of 1.6 (after the phantom). Results: When the kidney was removed within 5 minutes, a band of blood-filled nephrons was visible on the surface of the kidney. Histological examination revealed blood-filled glomerulus and proximal convoluted tubules. Proteinuria, hematuria and detached podocytes were detected in urine samples collected four hours after imaging. In 24 hr kidney samples, some tubules remained packed with blood cells and the epithelial lining of the tubules appeared to be injured. Similar results were obtained using a single imaging frame. Conclusions: GBCA activated by diagnostic ultrasound in rats caused potentially irreversible injury to entire nephrons under conditions simulating clinical use. 2029 Standardization of medical ultrasound instrumentation applying high-intensity ultrasound energy—the cavitation index and cavitation biosafety index Topaz M, Meyerstein N, Meyerstein D, Gedanken A, Department of Chemistry, Bar Ilan University; the Kreitman School of Advanced Graduate Studies; Plastic Surgery Unit, Hillel Yaffe Medical Center, Israel; Experimental Hematology Laboratory, Ben Gurion University of the Negev, Israel; Department of Chemistry, Ben Gurion University of the Negev; the College of Judea and Samaria, Israel; Department of Chemistry, Bar Ilan University, Israel Objectives: Mechanical and thermal indices for standardization of diagnostic ultrasound instrumentation have been defined and clinically applied; however, reported damage by the authors associated with application of high-intensity ultrasound energy (HIUE) in ultrasound-assisted lipoplasty (UAL) and in phacoemulsification cataract surgery necessitated the implementation of safety parameters for instrumentation and surgical procedures clinically applying HIUE. The purpose of this study was to define safety standards for clinical surgical applications of HIUE. Methods: In vitro generation of sonoluminescence and free radicals in simulated clinical applications of HIUE were evaluated by sensitive PMT and EPR spectroscopy, respectively. The extent of in vivo damage induced by HIUE to retinal endothelial cells was evaluated by specular microscopy in the rabbit eye model. Results: We found a linear correlation between the generation of free radicals by HIUE in the in vitro setup and the extent of damage to the retinal endothelial cells in vivo. Conclusions: We propose the standardization of clinically applied HIUE by assessing the direct effectors of acoustic cavitation—sonoluminescence and free radicals. We introduced the cavitation index (CI) and cavitation biosafety index (CBI) as direct indices for acoustic cavitation. CI and CBI provide a direct, accurate indication of US exposure-related collateral damage and adverse biological effects.
Volume 32, Number 5S, 2006 Methods: Patch clamp technique is used in sonoporation conditions to measure the variations in membrane potential of a single cell which directly indicates the modulation of ion exchange through the membrane and thus its conductance. Mammary cancer cells MDA-MB-231 were used with SonoVue excited with 1 MHz 200kPa 20 cycles every 100 us during 20 sec. Results: A marked hyperpolarization of the cell membrane potential occurs (⫺30 mV) during US excitation, indicating the triggering of specific ion channels while the cell and the bubble remain viable. The mechanism revealed that only cells in direct contact with the bubbles undergo hyperpolarization. Smaller acoustic amplitudes induced only mild hyperpolarization (⬎20 mV) while shutting off US brings the potential to its resting value. US alone does not affect the cell membrane potential. A similar hyperpolarization of 17 mV was observed when a stress is applied mechanically to the cell using a glass rod. The hyperpolarizations was inhibited by iberiotoxin, a specific inhibitor of potassium (BKCa) channels. Conclusions: The results demonstrate that microbubbles oscillations trigger ionic transports through the cell membrane. We propose that one mechanism for enhanced permeability of cell membrane is the increased of BKCa conductance. 2031 The protective effects of antioxidants in phacoemulsification cataract surgery Topaz M, Nemet A, Assia EI, Meyerstein N, Meyerstin D, Gedanken A, Department of Chemistry, Bar Ilan University; the Kreitman School of Advanced Graduate Studies; Plastic Surgery Unit, Hillel Yaffe Medical Center, Israel; Department of Ophthalmology, Meir Hospital, Israel; Physiology Department, Ben Gurion University of the Negev, Israel; Department of Chemistry, Ben Gurion University of the Negev, Israel; Department of Chemistry, Bar Ilan University, Israel Objectives: To determine the optimal antioxidant formula that would reduce damage induced by free radicals generated by high-intensity ultrasound energy (HIUE) during phacoemulsification cataract surgery, and thereby promote the safety of this most commonly used procedure. Methods: Rabbit corneal endothelial cells were exposed to HIUE in vivo by simulating clinical phacoemulsification. Cell loss was determined by specular microscopy. Various antioxidants in differing concentrations were applied to the irrigating solution. Endothelial cell loss was determined for each group. The animals were then sacrificed and the corneas were examined histologically. Results: Endothelial cell damage correlated inversely to the concentration of antioxidants in the irrigating solutions. The application of water-soluble antioxidants in the irrigating solution reduced the level of radicals in the medium and increased endothelial cell survival. The differences in the various groups were found to be statistically significant. Conclusions: Our findings further established the extent of damage induced by HIUE in various clinical applications. The optimal concentrations of free radical scavengers for clinical use in irrigating solutions were determined; damage correlated linearly to previous in vitro findings. Application of antioxidants in effective concentrations to the irrigating solution should be clinically tested and utilized to reduce adverse effects and improve safety. 2032
On the mechanisms of cell membrane permeabilization with ultrasound and microbubbles Bouakaz A, Tran TA, Roger S, Leguennec JY, Tranquart F, Inserm U619, France; Inserm E0211, France
Do air boundaries in soft tissue increase the expected ultrasound induced temperature rise? Duck F, Vella G, Barnett S, Medical Physics Department, Royal United Hospital Bath, United Kingdom of Great Britain and Northern Ireland; School of Biomedical Sciences, University of Sydney, Australia
Objectives: We explore the mechanisms by which microbubbles and ultrasound (US) modulate cell membrane permeability.
Objectives: To measure the temperature rise at the interface of soft tissue mimicking material in contact with air and a material
2030
Ultrasound in Medicine and Biology
amine nephron injury induced by GBCA activation with diagnostic ultrasound. Methods: Anesthetized hairless rats were scanned in a water bath using a diagnostic ultrasound system with 1.5 MHz probe. The probe was clamped to image the right kidney 4 cm away with a tissue mimicking phantom inserted between the probe and the rat. A dose of 10 L/kg of GBCA was diluted in saline and injected via tail vein. Ten single imaging frames were then triggered every 10 s at a measured MI of 1.6 (after the phantom). Results: When the kidney was removed within 5 minutes, a band of blood-filled nephrons was visible on the surface of the kidney. Histological examination revealed blood-filled glomerulus and proximal convoluted tubules. Proteinuria, hematuria and detached podocytes were detected in urine samples collected four hours after imaging. In 24 hr kidney samples, some tubules remained packed with blood cells and the epithelial lining of the tubules appeared to be injured. Similar results were obtained using a single imaging frame. Conclusions: GBCA activated by diagnostic ultrasound in rats caused potentially irreversible injury to entire nephrons under conditions simulating clinical use. 2029 Standardization of medical ultrasound instrumentation applying high-intensity ultrasound energy—the cavitation index and cavitation biosafety index Topaz M, Meyerstein N, Meyerstein D, Gedanken A, Department of Chemistry, Bar Ilan University; the Kreitman School of Advanced Graduate Studies; Plastic Surgery Unit, Hillel Yaffe Medical Center, Israel; Experimental Hematology Laboratory, Ben Gurion University of the Negev, Israel; Department of Chemistry, Ben Gurion University of the Negev; the College of Judea and Samaria, Israel; Department of Chemistry, Bar Ilan University, Israel Objectives: Mechanical and thermal indices for standardization of diagnostic ultrasound instrumentation have been defined and clinically applied; however, reported damage by the authors associated with application of high-intensity ultrasound energy (HIUE) in ultrasound-assisted lipoplasty (UAL) and in phacoemulsification cataract surgery necessitated the implementation of safety parameters for instrumentation and surgical procedures clinically applying HIUE. The purpose of this study was to define safety standards for clinical surgical applications of HIUE. Methods: In vitro generation of sonoluminescence and free radicals in simulated clinical applications of HIUE were evaluated by sensitive PMT and EPR spectroscopy, respectively. The extent of in vivo damage induced by HIUE to retinal endothelial cells was evaluated by specular microscopy in the rabbit eye model. Results: We found a linear correlation between the generation of free radicals by HIUE in the in vitro setup and the extent of damage to the retinal endothelial cells in vivo. Conclusions: We propose the standardization of clinically applied HIUE by assessing the direct effectors of acoustic cavitation—sonoluminescence and free radicals. We introduced the cavitation index (CI) and cavitation biosafety index (CBI) as direct indices for acoustic cavitation. CI and CBI provide a direct, accurate indication of US exposure-related collateral damage and adverse biological effects.
Volume 32, Number 5S, 2006 Methods: Patch clamp technique is used in sonoporation conditions to measure the variations in membrane potential of a single cell which directly indicates the modulation of ion exchange through the membrane and thus its conductance. Mammary cancer cells MDA-MB-231 were used with SonoVue excited with 1 MHz 200kPa 20 cycles every 100 us during 20 sec. Results: A marked hyperpolarization of the cell membrane potential occurs (⫺30 mV) during US excitation, indicating the triggering of specific ion channels while the cell and the bubble remain viable. The mechanism revealed that only cells in direct contact with the bubbles undergo hyperpolarization. Smaller acoustic amplitudes induced only mild hyperpolarization (⬎20 mV) while shutting off US brings the potential to its resting value. US alone does not affect the cell membrane potential. A similar hyperpolarization of 17 mV was observed when a stress is applied mechanically to the cell using a glass rod. The hyperpolarizations was inhibited by iberiotoxin, a specific inhibitor of potassium (BKCa) channels. Conclusions: The results demonstrate that microbubbles oscillations trigger ionic transports through the cell membrane. We propose that one mechanism for enhanced permeability of cell membrane is the increased of BKCa conductance. 2031 The protective effects of antioxidants in phacoemulsification cataract surgery Topaz M, Nemet A, Assia EI, Meyerstein N, Meyerstin D, Gedanken A, Department of Chemistry, Bar Ilan University; the Kreitman School of Advanced Graduate Studies; Plastic Surgery Unit, Hillel Yaffe Medical Center, Israel; Department of Ophthalmology, Meir Hospital, Israel; Physiology Department, Ben Gurion University of the Negev, Israel; Department of Chemistry, Ben Gurion University of the Negev, Israel; Department of Chemistry, Bar Ilan University, Israel Objectives: To determine the optimal antioxidant formula that would reduce damage induced by free radicals generated by high-intensity ultrasound energy (HIUE) during phacoemulsification cataract surgery, and thereby promote the safety of this most commonly used procedure. Methods: Rabbit corneal endothelial cells were exposed to HIUE in vivo by simulating clinical phacoemulsification. Cell loss was determined by specular microscopy. Various antioxidants in differing concentrations were applied to the irrigating solution. Endothelial cell loss was determined for each group. The animals were then sacrificed and the corneas were examined histologically. Results: Endothelial cell damage correlated inversely to the concentration of antioxidants in the irrigating solutions. The application of water-soluble antioxidants in the irrigating solution reduced the level of radicals in the medium and increased endothelial cell survival. The differences in the various groups were found to be statistically significant. Conclusions: Our findings further established the extent of damage induced by HIUE in various clinical applications. The optimal concentrations of free radical scavengers for clinical use in irrigating solutions were determined; damage correlated linearly to previous in vitro findings. Application of antioxidants in effective concentrations to the irrigating solution should be clinically tested and utilized to reduce adverse effects and improve safety. 2032
On the mechanisms of cell membrane permeabilization with ultrasound and microbubbles Bouakaz A, Tran TA, Roger S, Leguennec JY, Tranquart F, Inserm U619, France; Inserm E0211, France
Do air boundaries in soft tissue increase the expected ultrasound induced temperature rise? Duck F, Vella G, Barnett S, Medical Physics Department, Royal United Hospital Bath, United Kingdom of Great Britain and Northern Ireland; School of Biomedical Sciences, University of Sydney, Australia
Objectives: We explore the mechanisms by which microbubbles and ultrasound (US) modulate cell membrane permeability.
Objectives: To measure the temperature rise at the interface of soft tissue mimicking material in contact with air and a material
2030