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Published online before print August 26, 2005, 10.1148/radiol.2371041430
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(Radiology 2005;237:132-136.)
© RSNA, 2005

Experimental Studies

Heating and Coagulation Volume Obtained with High-Intensity Focused Ultrasound Therapy: Comparison of Perflutren Protein-Type A Microspheres and MRX-133 in Rabbits1

Kenji Takegami, MD, Yukio Kaneko, Toshiaki Watanabe, MD, PhD, Shunsuke Watanabe, Toshiyuki Maruyama, MD, PhD, Yoichiro Matsumoto, PhD and Hirokazu Nagawa, MD, PhD

1 From the Departments of Surgical Oncology (K.T., T.W., H.N.), Mechanical Engineering (Y.K., S.W., Y.M.), and Gastroenterology (T.M.), University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. Received August 19, 2004; revision requested October 27; revision received November 19; accepted December 14. Supported in part by a grant-in-aid from the Ministry of Education, Science, Sports, Culture, and Technology of Japan and in part by grants from the Ministry of Health, Labor, and Welfare of Japan. Address correspondence to K.T. (e-mail: ktakegami-tky{at}umin.ac.jp).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
PURPOSE: To compare the efficiency of different microbubble contrast agents in the heating and coagulation of rabbit liver tissue by using high-intensity focused ultrasound therapy.

MATERIALS AND METHODS: The use of and protocols for Japan white rabbits were approved by the University of Tokyo Committee on Animal Resources. In vitro experiments were conducted in a 1-mL cylindric space of polyacrylamide gel, which contained different microbubble contrast agents (MRX-133 or perflutren protein-type A microspheres). In vivo experiments were performed in six Japan white rabbits (two for the perflutren protein-type A microsphere group, two for the MRX-133 group, and two for the control group). In each rabbit, the liver was directly subjected to high-intensity focused ultrasound after intravenous injection of different microbubble contrast agents. Natural saline was used as a control. High-intensity focused ultrasound was applied for 30 seconds by using a 2.18-MHz transducer, and the temperature increase and volume of coagulation necrosis were evaluated. Statistical analysis was performed by using an analysis of variance test, which was followed by a Student-Newman-Keuls test; a P value of <.05 was considered to indicate a statistically significant difference.

RESULTS: In the MRX-133 group, the mean temperature increase was significantly greater and faster than that in the control group (P < .01) or in the perflutren protein-type A microsphere group (P < .05). In the perflutren protein-type A microsphere group, the mean temperature increase was greater and faster than that of the control group (P < .01) for both in vitro and in vivo experiments. The mean volume of the coagulation necrosis lesion was 117.9 mm3 ± 48.4 (±standard deviation) for the MRX-133 group, 45.4 mm3 ± 24.9 for the perflutren protein-type A microsphere group, and 17.7 mm3 ± 9.0 for the control group. In the MRX-133 group, the mean volume of coagulation necrosis was significantly greater than that of the control or the perflutren protein-type A microsphere group (P < .01), and in the perflutren protein-type A microsphere group, the volume of coagulation necrosis was greater than that of the control group (P < .05).

CONCLUSION: MRX-133 had greater efficiency than perflutren protein-type A microspheres in high-intensity focused ultrasound–induced heating and coagulation of rabbit liver tissue.

© RSNA, 2005


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
A number of minimally invasive treatment options are being investigated to determine a reliable and minimally invasive alternative to open surgery in cancer treatment. The ability to cause cell death in a volume of tissue that is distant from the ultrasound source has made high-intensity focused ultrasound attractive for development as a noninvasive surgical tool. Over the past decade, the use of high-intensity focused ultrasound has been investigated in many clinical settings and is now becoming an accepted treatment therapy in Europe and China (1,2).

There are, however, some limitations of high-intensity focused ultrasound. The energy of an ultrasound beam is attenuated by its passage through tissue, and because of absorption by the tissue, only a small amount of energy can penetrate to the deep tissues. A high-energy ultrasound beam, however, may cause skin burns or destroy normal tissue during its passage to the target area (3). Also, the small coagulation volume produced by the ultrasound beam causes the problem of low treatment throughput (treatment volume divided by treatment time). Thus, treatment times may be longer than desired, and some tissues may not be suitable for high-intensity focused ultrasound treatment (2,4). A number of studies have been performed to solve these problems, that is, to achieve a sufficient energy of ultrasound penetration that will allow coagulation of tissues in situ and to shorten the treatment times of high-intensity focused ultrasound therapy (3,5–8).

There have been a number of studies on ultrasound-induced cavitation. It is well known that, in certain conditions, the presence of microbubble contrast agents enhances cavitation (9–13). Microbubble contrast agents have the potential to act as centers for acoustic cavitation activity, and with stabilized microbubbles acting as cavitation nuclei, the tissue damage threshold is lowered (14). Recently, the infusion of microbubble contrast agents has been shown to increase the tissue volume of coagulation necrosis in the rabbit kidney, thereby improving the therapeutic efficiency of high-intensity focused ultrasound (15).

Microbubble contrast agents are typically used during ultrasonography to enhance the diagnostic capability of this modality. The acoustic properties of four kinds of microbubbles were recently reported in detail (16). To the best of our knowledge, however, the efficiency of different microbubble contrast agents in the heating and coagulation of liver tissue by using high-intensity focused ultrasound has not been evaluated. Comparisons of the various microbubble agents with regard to the volume of tissue that is coagulated by using high-intensity focused ultrasound are now needed. Thus, the purpose of this study was to compare the efficiency of two microbubble contrast agents in the heating and coagulation of rabbit liver tissue by using high-intensity focused ultrasound therapy.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Contrast Agents
Two microbubble contrast agents, perflutren protein-type A microspheres (Optison; Amersham Health, Princeton, NJ) and MRX-133 (ImaRx Pharmaceutical, Tucson, Ariz), were studied. Perflutren protein-type A microspheres are available in a 3.0-mL vial, with about (5.0–8.0) x 108 microspheres per milliliter (17), and consist of octafluoropropane gas encapsulated in a human serum albumin shell; the mean diameter of the microbubbles is 3.0–4.5 mm. MRX-133 is available in a 1.5-mL vial, with about 1.0 x 109 microspheres per milliliter, and consists of microbubbles that have octafluoropropane gas encapsulated in an outer lipid shell; the mean diameter of the microbubbles is about 2.2 mm. Both contrast agents were reconstituted according to each manufacturer's instructions and were then diluted in a plastic test tube to the required concentration by using natural saline. The test tube was then gently inverted to ensure mixing of the agent and diluents.

In Vitro Experiment
A concave piezoelectric ceramic transducer with a natural frequency of 2.18 MHz was constructed as a prototype high-intensity focused ultrasound transducer. Its diameter was 40 mm, and the focal length was 40 mm.

Each vial was diluted to 25 mL before the experiment, and then 1 mL of each contrast agent was put in a 1-mL cylindric space of polyacrylamide gel, as previously described (18–20). Natural saline was used as a control. The temperature increase caused by the exposure of high-intensity focused ultrasound to the microbubble contrast agents was compared by using waves of various frequencies (1.07, 2.18, 3.29, 5.48, 6.49, and 11.10 MHz) in vitro. We found that the highest temperature increase was observed by using a 2.18-MHz wave. The cylindric space was exposed to a continuous 2.18-MHz frequency wave for 30 seconds. A T-type thermocouple (T35052; Sakaguchi-dennestu, Tokyo, Japan) with a diameter of 0.5 mm was placed into the fluid inside the cylindric space, and the temperature increase during high-intensity focused ultrasound exposure was recorded by using a data acquisition system (NR-1000; Keyence, Osaka, Japan). Tests were performed 10 times by one author (K.T.) for each contrast agent (perflutren protein-type A microspheres and MRX-133) and for the control group (natural saline). The temperature increase during high-intensity focused ultrasound exposure was recorded every 0.1 second by two authors (Y.K. and S.W.). A diagram of our in vitro experiment set-up is shown in Figure 1a. The experiment was repeated 10 times for each contrast agent.



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  		Figure 1a. Diagram of experiment setup. (a) Transducer and polyacrylamide gel for in vitro experiment. (b) Transducer and cone-shaped polyacrylamide gel for in vivo experiment.

 
In Vivo Experiment
The use of and protocols for Japan white male rabbits (3.5–4.0 kg body weight) were approved by the University of Tokyo Committee on Animal Resources. A total of six rabbits were used for this study.

Each rabbit was anesthetized with an intramuscular injection of ketamine hydrochloride (Sankyo, Tokyo, Japan) (50 mg per kilogram body weight) combined with xylazine (Bayer, Tokyo, Japan) (2 mg per kilogram body weight) that was administered in the hind limb. Each vial of perflutren protein-type A microspheres and MRX-133 was diluted to 7 mL in volume and injected into the inferior vena cava of each rabbit. We then waited 1 minute for circulation of the bubbles prior to high-intensity focused ultrasound exposure. Two rabbits were given perflutren protein-type A microspheres and were categorized as the perflutren protein-type A microsphere group, two were given MRX-133 and were categorized as the MRX-133 group, and two were given 7 mL of natural saline and were categorized as the control group.

The same transducer that was used for the in vitro experiments was used for the in vivo experiments but with a cone-shaped polyacrylamide gel and a focal length of 5 mm from the end of the gel. The output power from the amplifier was 10 W in all in vivo experiments. The average spatial peak intensity was about 30 W/cm2 in the liver tissue. A thermosensor was placed 2.5 mm from the end of the gel and 3 mm to the side of the focal spot to measure the temperature increase around the focal spot in this experiment (Fig 1b).



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  		Figure 1b. Diagram of experiment setup. (a) Transducer and polyacrylamide gel for in vitro experiment. (b) Transducer and cone-shaped polyacrylamide gel for in vivo experiment.

 
In each rabbit, six or seven separate 30-second exposures to high-intensity focused ultrasound were directly applied to the liver (K.T). During high-intensity focused ultrasound exposure, the temperature in the liver was recorded every 0.1 second with a thermosensor (Y.K. and S.W.). After the experiments were completed, each animal was sacrificed by injecting an overdose of sodium pentobarbital (Dainippon Pharmaceutical, Tokyo, Japan) (4 mL) into the inferior vena cava, and the liver was extracted for measurement of the ablated lesions.

The liver was sectioned, and the tissue volume (V, in cubic millimeters) of coagulation necrosis was calculated by using the formula V = {pi}/6 x L x W x D, where L (in millimeters) is the maximum diameter of the necrotic tissue, D (in millimeters) is the depth of the necrotic tissue (as measured by K.T. and T.M.), and W is the width of the necrotic tissue (2,15).

Statistical Analysis
Results are shown as mean values ± standard deviations. Statistical analysis was performed by using an analysis of variance followed by a Student-Newman-Keuls test (one-tailed), which was used as a post hoc test. A P value of <.05 was considered to indicate a statistically significant difference.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
In Vitro Results
Of the three groups, the MRX-133 group showed the fastest and greatest mean temperature increase during 30-second high-intensity focused ultrasound exposure. The perflutren protein-type A microsphere group showed a mean temperature increase that was faster and greater than that of the control group (Fig 2).



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  		Figure 2. Line graph demonstrates mean temperature increase during 30-second high-intensity focused ultrasound exposure in vitro. MRX-133 group ({diamondsuit}) showed fastest and greatest mean temperature increase during exposure. Mean temperature increase in the perflutren protein-type A microsphere group ({blacktriangleup}) was faster and greater than that of the control group ({blacksquare}). Error bars indicate standard deviations.

 
The mean temperature increase after 30-second high-intensity focused ultrasound exposure was 6.1°C ± 1.8 for the MRX-133 group, 4.9°C ± 0.6 for the perflutren protein-type A microsphere group, and 1.7°C ± 0.8 for the control group. The result of the analysis of variance test was P < .01. Of the three groups, the MRX-133 group showed the greatest mean temperature increase during 30-second high-intensity focused ultrasound exposure, with a significance of P < .01 compared with the control group and P < .05 compared with the perflutren protein-type A microsphere group (Fig 3). The perflutren protein-type A microsphere group showed a mean temperature increase that was greater than that of the control group, with a significance of P < .01.



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  		Figure 3. Bar graph demonstrates mean temperature increase in vitro after 30-second high-intensity focused ultrasound exposure in control group (white bar), perflutren protein-type A microsphere group (gray bar), and MRX-133 group (black bar). P values were calculated by using post hoc test. * = P < .05, ** = P < .01. Error bars indicate standard deviations.

 
In Vivo Results
The mean temperature increase in the rabbit liver during 30-second high-intensity focused ultrasound exposure in each group is shown in Figure 4. The MRX-133 group showed the fastest and greatest temperature increase of the three groups. The perflutren protein-type A microsphere group showed a mean temperature increase that was faster and greater than that of the control group (Fig 4).



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  		Figure 4. Line graph demonstrates mean temperature increase in liver of two rabbits during 30-second high-intensity focused ultrasound exposure. MRX-133 group ({diamondsuit}) showed fastest and greatest temperature increase of the three groups. Mean temperature increase in the perflutren protein-type A microsphere group ({blacktriangleup}) was faster and greater than that of the control group ({blacksquare}). Error bars indicate standard deviations.

 
The mean temperature increase in the rabbits' liver during 30-second high-intensity focused ultrasound exposure was 23.0°C ± 6.5 for the MRX-133 group (n = 14), 15.5°C ± 5.5 for the perflutren protein-type A microsphere group (n = 13), and 9.4°C ± 6.5 for the control group (n = 12). The result of the analysis of variance test was P < .01. Of the three groups, the MRX-133 group showed the greatest mean temperature increase during 30-second high-intensity focused ultrasound exposure, with a significance of P < .01 compared with the control group and the perflutren protein-type A microsphere group (Fig 5). The perflutren protein-type A microsphere group showed a mean temperature increase that was greater than that of the control group, with a significance of P < .01.



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  		Figure 5. Bar graph demonstrates mean temperature increase in rabbit liver after 30-second high-intensity focused ultrasound exposure in control group (white bar), perflutren protein-type A microsphere group (gray bar), and MRX-133 group (black bar). P values were calculated by using post hoc test. ** = P < .01. Error bars indicate standard deviations.

 
The mean volume of the coagulation necrosis lesion was 117.9 mm3 ± 48.4 for the MRX-133 group (n = 14), 45.4 mm3 ± 24.9 for the perflutren protein-type A microsphere group (n = 13), and 17.7 mm3 ± 9.0 for the control group (n = 12). The result of the analysis of variance test was P < .01. In the MRX-133 group, the mean volume of the coagulation necrosis lesion was significantly greater than that of the control group (P < .01) or the perflutren protein-type A microsphere group (P < .01) (Fig 6). The perflutren protein-type A microsphere group showed a volume of coagulation necrosis that was greater than that of the control group, with a significance of P < .05.



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  		Figure 6. Bar graph demonstrates volume of coagulation necrosis after high-intensity focused ultrasound in control group (white bar), perflutren protein-type A microsphere group (gray bar), and MRX-133 group (black bar). P values were calculated by using post hoc test. * = P < .05, ** = P < .01. Error bars indicate standard deviations.

 
The formation of white individual ellipsoid regions of coagulation necrosis was observed, as shown in Figure 7.



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  		Figure 7a. Macroscopic images of coagulated lesion (arrow) obtained after high-intensity focused ultrasound exposure in rabbit liver in (a) control group, (b) perflutren protein-type A microsphere group, and (c) MRX group. Ultrasound beam was directed into liver surface from above. Formation of white individual ellipsoid regions of coagulation necrosis was observed. No macroscopic differences were observed between the three groups. Unit of ruler is centimeters.

 


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  		Figure 7b. Macroscopic images of coagulated lesion (arrow) obtained after high-intensity focused ultrasound exposure in rabbit liver in (a) control group, (b) perflutren protein-type A microsphere group, and (c) MRX group. Ultrasound beam was directed into liver surface from above. Formation of white individual ellipsoid regions of coagulation necrosis was observed. No macroscopic differences were observed between the three groups. Unit of ruler is centimeters.

 


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  		Figure 7c. Macroscopic images of coagulated lesion (arrow) obtained after high-intensity focused ultrasound exposure in rabbit liver in (a) control group, (b) perflutren protein-type A microsphere group, and (c) MRX group. Ultrasound beam was directed into liver surface from above. Formation of white individual ellipsoid regions of coagulation necrosis was observed. No macroscopic differences were observed between the three groups. Unit of ruler is centimeters.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
Microbubble contrast agents have the potential to act as centers for acoustic cavitation activity and lower the tissue damage threshold both in vitro and in vivo, with stabilized microbubbles acting as cavitation nuclei (14). For both in vitro and in vivo experiments, the mean temperature increase during and after 30-second high-intensity focused ultrasound exposure was fastest and greatest in the MRX-133 group and second fastest and second greatest in the perflutren protein-type A microsphere group. The mean volume of coagulation necrosis in the in vivo experiments tended to be the same as that obtained in the thermosensor experiments. From these findings, we believe that heat is created more effectively with MRX-133 than with perflutren protein-type A microspheres. The target tissue is coagulated more effectively when more heat is created by means of cavitation, which is enhanced by using microbubble contrast agents.

The temperature increase in the rabbit liver in this study was lower than the temperature needed to coagulate liver tissues, which is about 60°–80°C. This is because we put the temperature sensors 2.5 mm apart horizontally and 3 mm lateral to the center of the focal spot so that the sensors themselves would not affect the concentration of sound waves. In general, acoustic cavitation is complex and unpredictable. To detect and analyze cavitation, we would need to use a second ultrasound probe at a different angle. The waves from that additional probe, however, could oscillate or destroy the microbubbles, which would influence both the temperature and tissue necrosis. Therefore, we did not try to detect or analyze cavitation in the present study.

Yu et al (15) observed a 3.1–3.4-fold increase in the necrosis volume of the rabbit kidney with high-intensity focused ultrasound and lipid-coated perflupropane microbubble agents combined versus high-intensity focused ultrasound alone. In the current study, MRX-133 was shown to increase the necrosis volume 6.6-fold compared with that of the control group and 2.6-fold compared with that of the perflutren protein-type A microsphere group, and perflutren protein-type A microspheres were shown to increase the necrosis volume 2.6-fold compared with that of the control group. MRX-133 seems to be the most effective microbubble contrast agent in high-intensity focused ultrasound–induced tissue coagulation.

The total heat energy generated by means of cavitation is a complicated phenomenon that is derived through the various interactions between microbubbles, including the oscillation or explosion of microbubbles, the scattering effect from bubbles, the pressure distribution around bubbles, and the pressure and temperature inside each bubble (20,21). It is not yet clear how much heat is actually generated by means of cavitation, and the cavitation activities of different microbubble contrast agents are not fully understood. The gas inside the bubbles, the material of the shell, the diameter of each bubble, the fragility of the bubbles, the adherence of the bubbles to the cavitation nuclei, and the number of actual bubbles are all factors that are thought be important in cavitation and thus create the potential for ultrasound-induced heating and target coagulation.

We selected a 2.18-MHz transducer for our study because the high-intensity focused ultrasound applications that are used in the clinical setting typically use frequencies of about 2 MHz. Bubble resonance is a complex issue. The resonance frequency has a roughly inverse relationship with the bubble diameter for a reasonable range of diameters, and it may be that a 2.2-µm MRX-133 bubble was more resonant at the frequency used in this study.

The two microbubble contrast agents that we used in this study both contained octafluoropropane gas inside, but the shell was made of albumin for perflutren protein-type A microspheres and lipid for MRX-133. The average diameter of the bubbles was approximately 3.9 mm for perflutren protein-type A microspheres and approximately 2.2 mm for MRX-133. The actual number of microbubbles injected into each rabbit was (1.5–2.4) x 109 for the perflutren protein-type A microsphere group and 1.5 x 109 for the MRX-133 group. It is not yet known which factors are more important in producing heat during high-intensity focused ultrasound exposure. The number of microbubbles actually injected into animals, however, seems to be less important than the other specific properties of each microbubble contrast agent. The results of our experiments suggest that the efficiency of creating heat during high-intensity focused ultrasound exposure differs between microbubble agents, and the material of the shell and the diameter of the bubbles are important factors in this phenomenon. We speculate that the difference in coagulation volume and the mean temperature increase between the two microbubble contrast agents used in this study was caused by these specific properties of each microbubble contrast agent.

In this study, our experiments were performed on the normal liver of rabbits and were conducted without detecting cavitation. A passive cavitation detector, hydrophone, or microphone could have been used to detect the inertial cavitation. Further experiments are needed to analyze the heating effects of cavitation in detail and to evaluate the effect of microbubble contrast agents in antitumor high-intensity focused ultrasound therapy.

Practical application: The results of our experiments suggest that coagulation of a larger and deeper volume of tissue in situ may be performed in a relevantly shorter time if an adequate microbubble contrast agent is used in combination with high-intensity focused ultrasound therapy. Further evaluation is needed to investigate the treatment efficiency of different microbubble contrast agents in tissue coagulation by using high-intensity focused ultrasound therapy. We conclude that MRX-133 has greater efficiency than perflutren protein-type A microspheres in high-intensity focused ultrasound-induced heating and target coagulation of rabbit liver tissue.


   FOOTNOTES
 
Authors stated no financial relationship to disclose.

Author contributions: Guarantor of integrity of entire study, K.T.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, K.T., Y.K.; experimental studies, K.T., Y.K., S.W., T.M.; statistical analysis, K.T., S.W., T.M.; and manuscript editing, K.T., Y.K., T.W., Y.M., H.N.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

  1. Kennedy JE, ter Haar GR, Cranston D. High intensity focused ultrasound: surgery of the future? Br J Radiol 2003;76:590–599.[Abstract/Free Full Text]
  2. ter Haar G. Ultrasound focal beam surgery. Ultrasound Med Biol 1995;21:1089–1100.[CrossRef][Medline]
  3. Chauhan S, Lowe MJ, Davies BL. A multiple focused probe approach for high intensity focused ultrasound based surgery. Ultrasonics 2001;39:33–44.[CrossRef][Medline]
  4. Kennedy JE, Wu F, ter Haar GR et al. High-intensity focused ultrasound for the treatment of liver tumours. Ultrasonics 2004;42:931–935.[CrossRef][Medline]
  5. Umemura SI, Kawabata KI, Sasaki K, Sugita N, Azuma T, Yumita N. Therapeutic technology utilizing focused ultrasound [in Japanese]. Igaku Butsuri 2001;21:150–156.[Medline]
  6. Blana A, Walter B, Rogenhofer S, Wieland WF. High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience. Urology 2004;63:297–300.[CrossRef][Medline]
  7. Melodelima D, Prat F, Birer A, Theillere Y, Cathignol D. Comparison of two methods of treatment for intraluminal thermal ablation using an ultrasound cylindrical phased array. Ultrasonics 2004;42:937–942.[CrossRef][Medline]
  8. Hynynen K, Clement GT, McDannold N, et al. 500-element ultrasound phased array system for noninvasive focal surgery of the brain: a preliminary rabbit study with ex vivo human skulls. Magn Reson Med 2004;52:100–107.[CrossRef][Medline]
  9. Miller MW, Battaglia LF. The relevance of cell size on ultrasound-induced hemolysis in mouse and human blood in vitro. Ultrasound Med Biol 2003;29:1479–1485.[CrossRef][Medline]
  10. Miller MW, Brayman AA, Sherman TA, Abramowicz JS, Cox C. Comparative sensitivity of human fetal and adult erythrocytes to hemolysis by pulsed 1 MHz ultrasound. Ultrasound Med Biol 2001;27:419–425.[CrossRef][Medline]
  11. Miller MW, Everbach EC, Cox C, Knapp RR, Brayman AA, Sherman TA. A comparison of the hemolytic potential of Optison and Albunex in whole human blood in vitro: acoustic pressure, ultrasound frequency, donor and passive cavitation detection considerations. Ultrasound Med Biol 2001;27:709–721.[CrossRef][Medline]
  12. Miller MW, Luque AE, Battaglia LF, Mazza S, Everbach EC. Biological and environmental factors affecting ultrasound-induced hemolysis in vitro. I. HIV macrocytosis (cell size). Ultrasound Med Biol 2003;29:77–91.
  13. Abramowicz JS, Miller MW, Battaglia LF, Mazza S. Comparative hemolytic effectiveness of 1 MHz ultrasound on human and rabbit blood in vitro. Ultrasound Med Biol 2003;29:867–873.[CrossRef][Medline]
  14. Tran BC, Seo J, Hall TL, Fowlkes JB, Cain CA. Microbubble-enhanced cavitation for noninvasive ultrasound surgery. IEEE Trans Ultrason Ferroelectr Freq Control 2003;50:1296–1304.[CrossRef][Medline]
  15. Yu T, Wang G, Hu K, Ma P, Bai J, Wang Z. A microbubble agent improves the therapeutic efficiency of high intensity focused ultrasound: a rabbit kidney study. Urol Res 2004;32:14–19.[CrossRef][Medline]
  16. Moran CM, Watson RJ, Fox KA, McDicken WN. In vitro acoustic characterisation of four intravenous ultrasonic contrast agents at 30 MHz. Ultrasound Med Biol 2002;28:785–791.[CrossRef][Medline]
  17. Optison [package insert]. Princeton, NJ: Amersham Health, 2003.
  18. Takegami K, Kaneko Y, Watanabe T, Maruyama T, Matsumoto Y, Nagawa H. Polyacrylamide gel containing egg white as new model for irradiation experiments using focused ultrasound. Ultrasound Med Biol 2004;30:1419–1422.[CrossRef][Medline]
  19. Prokop AF, Vaezy S, Noble ML, Kaczkowski PJ, Martin RW, Crum LA. Polyacrylamide gel as an acoustic coupling medium for focused ultrasound therapy. Ultrasound Med Biol 2003;29:1351–1358.[CrossRef][Medline]
  20. Matsumoto Y, Allen JS, Yoshizawa S, Ikeda T, Kaneko Y. Medical ultrasound with microbubbles. Exp Therm Fluid Sci (in press).
  21. ter Haar G, Rivens I, Chen L, Riddler S. High intensity focused ultrasound for the treatment of rat tumours. Phys Med Biol 1991;36:1495–1501.[CrossRef][Medline]



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