AJR AJR-based Continuing Ed for Technologists
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow CME
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dubinsky, T. J.
Right arrow Articles by Hwang, J. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dubinsky, T. J.
Right arrow Articles by Hwang, J. H.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Hotlight (NEW!)
Right arrow
What's Hotlight?
DOI:10.2214/AJR.07.2671
AJR 2008; 190:191-199
© American Roentgen Ray Society

Review

High-Intensity Focused Ultrasound: Current Potential and Oncologic Applications

Theodore J. Dubinsky1, Carlos Cuevas, Manjiri K. Dighe, Orpheus Kolokythas and Joo Ha Hwang

1 All authors: Department of Radiology, University of Washington, Box 359728, 325 Ninth Ave., Seattle, WA 98104.

Received December 7, 2006; accepted after revision July 27, 2007.

 
Address correspondence to T. J. Dubinsky (tdub{at}u.washington.edu).

CME This article is available for CME credit. See www.arrs.org. for more information.

FOR YOUR INFORMATION

This article is available for CME credit. See www.arrs.org for more information.


Abstract
Top
 Abstract
Introduction
 Clinical History of HIFU
 HIFU Overview
 Limitations of HIFU
 Imaging Guidance and Monitoring...
 Current Clinical Applications
 HIFU Technology
 References
 
OBJECTIVE. The objective of this article is to introduce the reader to the principles and applications of high-intensity focused ultrasound (HIFU).

CONCLUSION. Although a great deal about HIFU physics is understood, its clinical applications are currently limited, and multiple trials are underway worldwide to determine its efficacy.

Keywords: apoptosis • coagulation necrosis • hemostasis • high-intensity focused ultrasound • tumor ablation


Introduction
Top
 Abstract
 Introduction
Clinical History of HIFU
 HIFU Overview
 Limitations of HIFU
 Imaging Guidance and Monitoring...
 Current Clinical Applications
 HIFU Technology
 References
 
The use of ultrasound in clinical practice is no longer limited to diagnostic imaging or to simple needle guidance in the performance of percutaneous procedures such as amniocentesis or tumor biopsy. Ultrasound technology now allows the use of focused ultrasound energy for therapeutic purposes such as tissue ablation and hemostasis. High-intensity focused ultrasound (HIFU) is being promoted as a noninvasive method to treat certain primary solid tumors and metastatic disease, to ablate foci of ectopic electrical activity in the heart, and to achieve hemostasis in acute traumatic injuries to the extremities and visceral organs.

The field of medicine is evolving toward greater use of noninvasive and minimally invasive therapies such as HIFU. Unlike radiofrequency or cryoablation, which are also used to ablate tumors, ultrasound is completely noninvasive and can be used to reach areas of hemorrhage or tumors that are deep within the body, provided there is an acoustic window to allow the transmission of ultrasound energy. Preliminary reports suggest that there is reduced toxicity with HIFU ablation compared with other ablation techniques because of the noninvasive nature of the procedure.

This article presents a review of HIFU, including its mechanisms of action, current clinical applications, and future requirements to expand the clinical applications of this technique.


Clinical History of HIFU
Top
 Abstract
 Introduction
 Clinical History of HIFU
HIFU Overview
 Limitations of HIFU
 Imaging Guidance and Monitoring...
 Current Clinical Applications
 HIFU Technology
 References
 
As early as 1954, Lindstrom [1] and Fry et al. [2] investigated the possibility of using high-intensity ultrasound for treating neurologic disorders in humans. Fry and colleagues are credited with the first application of HIFU in humans by producing elevated acoustic intensities in vivo by focusing ultrasound energy in a manner analogous to the way a magnifying glass can be used to focus light. In the 1970s, ultrasound was again investigated, but at lower intensities and for treating tumors [3]. The concept was to induce hyperthermia (elevation of tissue temperature to {approx} 43°C) in the entire tumor volume and then maintain the tumor at that temperature for an extended time ({approx} 1 hour). Unfortunately, this strategy did not work out, with difficulties including the lack of a noninvasive temperature-measuring method to use in feedback control of the delivered acoustic power to the tumor. This inability resulted in the lack of uniform heating and maintenance of the entire tumor volume at a temperature greater than 43°C.

The next innovation arose in the 1980s with the development of extracorporeal shockwave lithotripsy (ESWL) [4]. The use of ESWL as a method for treating kidney stones was approved in 1984 by the U.S. Food and Drug Administration. It was the first clinical application of high-(pulse-averaged) intensity ultrasound. A rediscovery of HIFU for the treatment of tumors occurred in the 1990s with the refinement of modern technology, in particular, advanced imaging methods such as MR thermometry. Furthermore, the realization that HIFU can produce almost instantaneous cell death by coagulation necrosis to selected regions of tissue has made it a candidate for direct and rapid treatment of tumors [5-14]. Finally, not only has tumor treatment been targeted, but HIFU can also be used to achieve hemostasis, as shown in animal experiments [15-21].


Figure 1
View larger version (84K):
[in this window]
[in a new window]
[as a PowerPoint slide]
  		Fig. 1 —High-intensity focused ultrasound lesion formation in polyacrylamide hydrogel containing bovine serum albumin that becomes optically opaque when denatured. Treatment site is roughly 9 mm long by 3 mm wide.

 


Figure 2
View larger version (35K):
[in this window]
[in a new window]
[as a PowerPoint slide]
  		Fig. 2 —Illustration depicts extracorporeal high-intensity focused ultrasound therapy of intraabdominal tumor.

 

HIFU Overview
Top
 Abstract
 Introduction
 Clinical History of HIFU
 HIFU Overview
Limitations of HIFU
 Imaging Guidance and Monitoring...
 Current Clinical Applications
 HIFU Technology
 References
 
In comparing the differences in intensities of HIFU and diagnostic ultrasound, HIFU has significantly higher time-averaged intensities in the focal region of the ultrasound transducer. Typical diagnostic ultrasound transducers deliver ultrasound with time-averaged intensities of approximately 0.1-100 mW/cm2 or compression and rarefaction pressures of 0.001-0.003 MPa, depending on the mode of imaging (B-mode, pulsed Doppler sonography, or continuous wave Doppler sonography). In contrast, HIFU transducers deliver ultrasound with intensities in the range of 100-10,000 W/cm2 to the focal region, with peak compression pressures of up to 30 MPa and peak rarefaction pressures up to 10 MPa.

Thermal Effects of HIFU
The major effect of high acoustic intensities in tissue is heat generation due to absorption of the acoustic energy. The heat raises the temperature rapidly to 60°C or higher in the tissue, causing coagulation necrosis within a few seconds. Focusing results in high intensities at a specific location and over only a small volume (e.g., 1-mm diameter and 9-mm length). This focusing minimizes the potential for thermal damage to tissue located between the transducer and the focal point because the intensities are much lower outside the focal region (Figs. 1 and 2).

Mechanical Effects of HIFU
Mechanical phenomena, in addition to thermal effects, are associated at high intensities but are not present at lower intensities. Mechanical phenomena include cavitation, microstreaming, and radiation forces.

Cavitation—Cavitation can be defined as the creation or motion of a gas cavity in an acoustic field [22, 23]; for example, the oscillatory movement of a gas-filled bubble in a liquid medium exposed to an acoustic field. Cavitation occurs due to alternating compression and expansion of tissue as an ultrasound field propagates through it. If the tissue expansion or rarefaction pressure is of sufficient magnitude, gas can be extracted from the tissue, resulting in bubble formation. This bubble can then further interact with the ultrasound field. There are two forms of cavitation to consider. The first is stable cavitation, in which a bubble is exposed to a low-pressure acoustic field, resulting in stable oscillation of the size of the bubble. The other is inertial cavitation, in which the exposure of the bubble to the acoustic field results in violent oscillations of the bubble and rapid growth of the bubble during the rarefaction phase, eventually leading to the violent collapse and destruction of the bubble. An interesting phenomenon has been observed when inertial cavitation occurs against a solid surface. The asymmetric collapse of a bubble near such a surface can create high-velocity liquid jets that impinge on the surface with a force sufficient to damage metal surfaces and disrupt cell membranes [24-27]. If inertial cavitation occurs near a cell membrane, one may anticipate mechanical, rather than thermal, damage to the cell.

Microstreaming—Stable cavitation may lead to a phenomenon called "microstreaming" (rapid movement of fluid near the bubble due to its oscillating motion). Microstreaming can produce high shear forces close to the bubble that can disrupt cell membranes and may play a role in ultrasound-enhanced drug or gene delivery when damage to the cell membrane is transient [26].

Radiation forces—Radiation forces are developed when a wave is either absorbed or reflected. Complete reflection produces twice the force that complete absorption does. These forces are constant if the amplitude of a wave is steady and the absorption or reflection is constant. If the reflecting or absorbing medium is tissue or other solid material, the force presses against the medium, producing a pressure termed "radiation pressure." If the medium is liquid and can move under pressure, then streaming results [16].

Biologic Effects and Thermal Mechanisms
Diagnostic ultrasound has an excellent safety profile, with no clinically significant deleterious biologic effects having been reported using current diagnostic equipment. However, at high intensities, ultrasound can result in tissue heating and necrosis, cell apoptosis, and cell lysis (Fig. 3A and 3B). Mechanisms involved in HIFU-induced biologic effects are primarily caused by thermal and cavitation mechanisms, as discussed previously [22, 23].


Figure 3
View larger version (100K):
[in this window]
[in a new window]
[as a PowerPoint slide]
  		Fig. 3A —Ex vivo porcine liver treated with high-intensity focused ultrasound (HIFU). Transducer is above liver and energy is propagated down. Thermocouple is placed in focal region to measure temperature during HIFU exposure (arrow).

 

Figure 4
View larger version (109K):
[in this window]
[in a new window]
[as a PowerPoint slide]
  		Fig. 3B —Ex vivo porcine liver treated with high-intensity focused ultrasound (HIFU). B-mode sonogram corresponding to sample in A. Hyperechoic area (arrow) corresponds to damaged tissue. Hyperecho is due to gas bubble formation from tissue boiling in targeted region.

 
Coagulation Necrosis
Coagulation necrosis occurs in tissue exposed to high-intensity ultrasound when the temperature of the tissue is elevated to a certain level for a certain time [28]. The temperature required to induce coagulation necrosis is time-dependent. Tissue temperature elevated to more than 60°C for 1 second will generally lead to instantaneous cell death via coagulation necrosis in most tissues, which is the primary mechanism for tumor cell destruction in HIFU therapy. Figures 3C and 3D show a lesion with coagulation necrosis after a single treatment with HIFU in ex vivo porcine liver. In a study performed by Wu et al. [28], pathologic changes were reported in human malignant tumors that were initially treated with HIFU and then resected 1-14 days after HIFU therapy. Tissue evaluated 1-7 days after HIFU therapy showed homogeneous areas of coagulation necrosis with no evidence of residual viable tumor cells. Seven to 14 days after HIFU therapy, granulation tissue began to replace the necrotic tissue, and the boundary area between treated and untreated tissue was replaced by fibrous tissue.


Figure 5
View larger version (152K):
[in this window]
[in a new window]
[as a PowerPoint slide]
  		Fig. 3C —Ex vivo porcine liver treated with high-intensity focused ultrasound (HIFU). Histology from ex vivo porcine liver treated with HIFU (cross-section of single HIFU lesion) shows central region of coagulation necrosis. (H and E).

 

Figure 6
View larger version (178K):
[in this window]
[in a new window]
[as a PowerPoint slide]
  		Fig. 3D —Ex vivo porcine liver treated with high-intensity focused ultrasound (HIFU). Corresponding viability stain shows central region of nonviable cells with margin of tissue that has some viable cells. Scale bar = 1 mm.

 

Apoptosis
Although most initial cell death in tissues exposed to HIFU fields is caused by cell necrosis from thermal injury, HIFU can also induce apoptosis. In apoptotic cells, the nucleus of the cell self-destructs, with rapid degradation of DNA by endonucleases. The primary mechanism of cell death by hyperthermia is apoptosis [29]. Apoptosis has also been shown in leukemic cells exposed to low-intensity ultrasound [30] and in leukemic cells exposed to ultrasound-induced cavitation [31]. Apoptosis may be an important delayed bioeffect in tissue exposed to low-energy HIFU, especially in cell types that regenerate poorly, such as neurons. Hence, there may be a more extensive area of cellular death than just the target area of the HIFU, and this mechanism might be a potential limitation of the technique because cell death due to apoptosis occurs at a lower level of energy deposition than occurs during HIFU, and tissue adjacent to the target may be at risk from this effect [32, 33].

Nonlinear Effects of HIFU
Finally, nonlinear effects are observed at high acoustic intensities. As a high-intensity acoustic wave propagates through water or tissue, the wave can become distorted so that a sinusoidal wave initially generated by an ultrasound transducer can become sawtooth-shaped due to conversion of energy carried in the fundamental frequency to higher harmonics, which are more rapidly absorbed. This process results in more rapid attenuation of the ultrasound energy and more rapid tissue heating. This can also have the effect of distorting the distribution of heat production that would be predicted if nonlinear effects did not occur. A better understanding of nonlinear effects in biologic systems will be critical for advancing clinical HIFU.

To date, the contribution of each of these effects remains poorly understood. Tissue specimens obtained after HIFU ablation of prostate gland, for example, show incomplete destruction of tissue by coagulation necrosis [34]; and to our knowledge no follow-up studies exist at this time to determine the ultimate extent of tissue destruction by apoptosis. Dose delivery to targeted tissues depends on the transducer array, the energy input, and the tissue attenuation that occurs between the transducer and the target. With more research, it may be possible to control which type of effect is being induced in the targeted tissues, but for now the ablative effect of HIFU is a combination of all of them.


Limitations of HIFU
Top
 Abstract
 Introduction
 Clinical History of HIFU
 HIFU Overview
 Limitations of HIFU
Imaging Guidance and Monitoring...
 Current Clinical Applications
 HIFU Technology
 References
 
Although it offers tremendous potential for noninvasive therapy of malignancies, particularly those that are widespread or inoperable, the usefulness of HIFU has limitations, and risk is associated with its use that could result in adverse outcomes. Because HIFU is essentially ultrasound, any artifacts related to ultrasound would apply to HIFU as well, such as acoustic shadowing, reverberation, and refraction. Hence, lesions that are deep in relation to bones, such as a liver lesion adjacent to a rib, will be difficult to treat. Gas in bowel cannot be penetrated by HIFU just as it cannot be with diagnostic sonography, and these sound waves are reflected back toward the transducer. With diagnostic sonography, these reflected sound waves are of such low energy that there is no adverse effect from them. However, with HIFU, these reflected waves are very high energy, and they can produce burns in the tissues that lie between the transducer and the target. In our experience, even small amounts of gas in the gastrointestinal tract can produce burns in the wall of the bowel anterior to the gas and in the abdominal wall musculature overlying the gas. Refraction artifacts can result in energy deposition in the soft tissues adjacent to the target area, and energy deposition can occur superficially to the target if the ultrasound beam is not carefully focused into a small point.

The amount of energy absorbed by the tissues is essentially estimated by making the assumption that the attenuation of the sound waves in the soft tissues between the transducer and the target is linear. This assumption may not always be true; and fibrotic, fatty, and highly vascularized tissues attenuate sound energy differently. Excessive energy absorption can lead to unpredictable distributions of cell death [19]. Hence, targeting is of extreme importance, which is why MRI guidance for HIFU has initially become more rapidly accepted clinically than sonographically guided HIFU [35]. One potential complication of HIFU is the dissemination of malignant cells from the shear forces generated by the procedure, but this potential complication has not been substantiated either in vitro or in vivo [36, 37]. Great care will be necessary in treating patients with HIFU to ensure that complications do not occur.


Imaging Guidance and Monitoring of Therapy
Top
 Abstract
 Introduction
 Clinical History of HIFU
 HIFU Overview
 Limitations of HIFU
 Imaging Guidance and Monitoring...
Current Clinical Applications
 HIFU Technology
 References
 
Guidance and monitoring of acoustic therapy is most important to ensure that the desired region is treated and to minimize damage to adjacent structures. Monitoring using real-time imaging, such as with sonography, ensures that the targeting of the HIFU beam is maintained on the correct area throughout the procedure. Currently, MRI and sonography are being used for guidance and monitoring of HIFU therapy. Both methods have their advantages and disadvantages. MRI has the advantage of providing temperature data within seconds after HIFU exposure. However, MRI guidance is expensive, labor-intensive, and of lower spatial resolution in some cases, although it is superior to sonography in obese patients [35]. Sonographic guidance provides the benefit of imaging using the same form of energy that is being used for therapy. The significance of this is that the acoustic window can be verified with sonography. Therefore, if the target cannot be well visualized with sonography, then it is unlikely that HIFU therapy will be effective in the target region, and it may potentially cause thermal injury to unintended tissue. Temperature monitoring using sonography is not yet available, although sonographic thermometry is being actively investigated and a clinical HIFU device in China has an incorporated sonographic thermometry system [32]. In some instances when tissue contrast is not sufficient to visualize a tumor in the background of normal tissue, elastography may prove helpful [18].

Imaging methods to assess HIFU treatment are similar to those used to assess the response to other methods of ablation such as radiofrequency ablation and include contrastenhanced CT and MRI. In addition, the use of microbubble contrast-enhanced sonography is also being examined as a method to evaluate the treatment effect of HIFU [36]. These methods all examine the change in vascularity of the treated volume. Another method currently being examined in oncologic applications is the use of PET to assess for changes in metabolic activity after HIFU treatment.


Current Clinical Applications
Top
 Abstract
 Introduction
 Clinical History of HIFU
 HIFU Overview
 Limitations of HIFU
 Imaging Guidance and Monitoring...
 Current Clinical Applications
HIFU Technology
 References
 
The investigation and applications of HIFU are growing rapidly. The major application of HIFU clinically is for the treatment of benign and malignant solid tumors [37-39]. Several other potential therapeutic applications of HIFU are being investigated, including thrombolysis [40-44], arterial occlusion for the treatment of tumors and bleeding [45, 46], hemostasis of bleeding vessels and organs [47-49], and drug and gene delivery [50-60].

To date, studies using animals and human subjects have been published for the treatment of hepatocellular carcinoma (HCC), renal cell carcinoma, pancreatic cancer, sarcomas, urinary bladder tumors, and prostate carcinoma. HCC is rapidly becoming the most common malignancy worldwide. Surgery, particularly liver transplantation, offers the only real hope for cure; survival rates are only 25-30% at 5 years. As a result, noninvasive alternatives to surgery, such as radiofrequency ablation, ethanol injection, and HIFU, have generated increasing interest as alternative or adjunct treatments to surgery.

Animal models for the assessment of HIFU devices have been published. Small-animal models [11] have established that HIFU can ablate areas of normal liver, and energy thresholds for liver tissue destruction have been published [17]. Further small-animal experiments have correlated the histology of HIFU [18] with tissue depth intensity levels [12, 19-22, 61-64]. Pig liver specimens have been used to show that the site for ablation can be accurately placed [65-70].

Liver Tumors
Human studies have been performed as well. Studies of the treatment of HCC and secondary liver metastases in human clinical trials have been published [71].

Wu et al. [72] used an extracorporeal HIFU device to treat 68 patients with liver malignancies. In 30 cases in which surgical excision followed HIFU ablation, the tumor was totally ablated. Subsequently, 474 patients with HCC were treated using the same device [73]. HIFU has also been used for palliation in patients with advanced-stage liver cancer [74]. After treatment, 87% of patients reported symptomatic improvement. Another study designed to assess the safety of HIFU in the treatment of metastatic liver cancer showed that in 20 patients morbidity was low when compared with open or minimally invasive techniques [75]. Wu et al. [76] randomized patients between transarterial chemoembolization (TACE) and HIFU. The median patient survival times were 11.3 months in the combined HIFU-TACE group and 4 months in the TACE-only group (p = 0.0042). To date, both animal and human subject investigations show significant promise in the treatment of hepatic malignancies with HIFU.

Renal Tumors
As with hepatic malignancies, the mainstay of treatment for renal tumors remains surgery, with 5-year survival rates greater than 80% after resection [77]. Because most renal lesions are small, a noninvasive approach for their treatment would be attractive. Animal models for renal tumor HIFU ablation exist and have been used to evaluate the use of HIFU to treat these tumors [78-83]. HIFU ablation of renal tumors in humans remains in the early stages of clinical trials. A clinical feasibility study using HIFU to ablate renal tumors has been performed on eight patients who showed histologic evidence of ablation in the treated areas after excision; however, 10% of patients suffered skin burns from the treatment [84, 85]. Other instances of using HIFU to treat renal tumors in humans have been reported [86]. Wu et al. [87] described a series of 13 patients with renal cell carcinoma. Nine of 10 patients treated for palliation reported a reduction in pain. No side effects occurred after ablation using an experimental handheld device [87]. Further investigations continue to study the efficacy of HIFU treatment of renal cell carcinoma for both cure and palliation.

Pancreatic Cancer
More than 32,000 people are diagnosed with pancreatic cancer annually in the United States and as many as 200,000 patients annually worldwide; the 5-year survival rate after diagnosis is less than 5% [88, 89]. Pancreatic adenocarcinoma accounts for 5% of cancer deaths in the United States and is the fourth leading cause of cancer mortality.

HIFU for the palliative treatment of pancreatic cancer may be useful in patients who develop symptoms that would benefit from local tumor control. Results from an open-label study in China in 251 patients with advanced pancreatic cancer (TNM stages II-IV) suggested that HIFU treatment can reduce the size of pancreatic tumors without causing pancreatitis and thus prolong survival [90]. An interesting finding was that 84% of patients with pain due to pancreatic cancer obtained significant relief of their pain after treatment with HIFU. Initial nonrandomized open-label human studies in China have provided additional evidence to suggest that HIFU treatment of pancreatic tumors indeed relieves pancreatic adenocarcinoma-related pain and focally ablates malignant tissue [29, 90-98]. Although HIFU is a noninvasive, nonsurgical treatment that has the potential to eliminate or significantly reduce pain associated with pancreatic cancer, no rigorously conducted prospective randomized controlled trials have been conducted to determine whether treatment of pancreatic tumors with HIFU will result in local tumor response or a clinically beneficial outcome by improving pain, functional status, quality of life, or survival.

Prostate Carcinoma
HIFU has been used to treat prostate carcinoma and prostatic hypertrophy at a few medical centers in Europe and Japan for the past decade. However, nearly 50% of patients with prostatic hypertrophy ultimately needed transurethral prostate resection [99], so HIFU has not been recommended for treatment of this condition. Either the entire prostate is ablated or, using sonographic guidance, a focal ablation of the tumor is performed [100]. Endorectal and transperineal treatment protocols have been evaluated in animals and humans [101]. Such treatments are performed under general or spinal anesthesia, and all patients have a Foley or suprapubic catheter [102, 103] left in place after the procedure. In general, entry criteria to qualify for prostate HIFU are quite specific, including a serum prostate-specific antigen (PSA) level greater than 15 ng/mL [104], a Gleason score of less than 7 [105], local disease either stage T1 or T2 [106], no known lymph node or metastatic disease, a total prostate weight of less than 30-40 g, and a greater than 5-year life expectancy [107]. All series reported in these patients used decreasing PSA values, negative repeat biopsies, an International Prostate Symptom Score [108], or quality of life index to assess outcome. Follow-up intervals reported in these patients have ranged from a few months to 5 years [108, 109]. In some series, HIFU has been performed with some success as a salvage method for incompletely treated tumor from external radiation therapy [110, 111].

Success rates for the treatment of prostate cancer range from 60% [5, 112] to 80% [113] of patients being disease-free at repeat biopsy and show a reduction of serum PSA values to less than 4 ng/mL [114, 115]. Failure is generally defined as positive biopsy or three consecutive increases in PSA with negative biopsy findings [116]. Whole-gland versus focal treatment resulted in a reduced incidence of recurrent tumor of 35% to 17% in one series [113]; in patients not found to be disease-free, reductions in tumor volume greater than 90% have been reported [113]. Treatment success correlates highly with pretreatment staging and PSA levels, with more than 90% of patients disease-free and having PSA levels of 4 ng/mL initially to 57% disease-free with PSA levels greater than 4 ng/mL [117].

Complications from prostate HIFU are reported to occur with a frequency of 0-50% [118]. Reported complications include urinary retention, incontinence, urinary infection, impotence, chronic pain, rectal anal fistulas, and incomplete treatment of disease [118]. Repeat treatment with HIFU is associated with much higher complication rates than single treatments [118]. To mitigate urinary retention associated with prostate HIFU, some investigators perform transurethral resection before treatment [119, 120]; and in these patients, the length of time indwelling catheters remain in the bladder has been reduced from 40 to 7 days [121]. However, long-term follow-up in these patients is still not available, and because of the small numbers of patients who have undergone HIFU for prostate carcinoma, several authors have concluded that there are still not enough data to justify substitution of HIFU for more conventional therapies, although in short-term follow-up of up to 1 year, data look promising [122-125]. Prostate HIFU seems most appropriate in men older than 65 years, those who are not candidates for surgery, and those who are obese [126].


HIFU Technology
Top
 Abstract
 Introduction
 Clinical History of HIFU
 HIFU Overview
 Limitations of HIFU
 Imaging Guidance and Monitoring...
 Current Clinical Applications
 HIFU Technology
References
 
To deposit large amounts of energy deep into the body without causing damage to tissue in the prefocal or postfocal region, it is necessary to use a wide aperture system that delivers acoustic energy with a beam that has a large angle of convergence. Some units have been produced with an aperture as large as 40 cm.

Critical to the performance of HIFU, just as with diagnostic imaging, is the ability to obtain an adequate acoustic window to allow propagation of acoustic energy to the target. An acoustic window is an area through which a sonogram of the structures within can be obtained. There are a limited number of such acoustic windows because bone, air, and gas interfere with the propagation of ultrasound beams into the body, thus obscuring targets beyond these interfaces. For example, the bladder is an excellent acoustic window, and treatment results of urinary bladder tumors with HIFU have been published [127-131].

Three-dimensional sonography may provide information that would be valuable to the performance of HIFU. Three-dimensional sonography is likely to better delineate a volume of tissue to be treated than just a single plane or orthogonal planes, and most commercially available HIFU systems display with 2D sonography systems. Therefore, the application of 3D sonography techniques is an exciting area of future opportunity, especially for HIFU treatment planning and monitoring.

HIFU has the potential to allow completely noninvasive treatment of tumors. The main advantage of HIFU is its ability to deposit high amounts of energy deep inside the body and tissue, with millimeter accuracy and little or no damage to intervening tissue. In some applications, no sedation or anesthesia is used during the delivery of HIFU therapy.

HIFU is being increasingly used for limited applications in Asia and Europe; however, these studies have all been preliminary, and further investigation will be necessary before the widespread use of HIFU can be recommended. With advances in imaging and transducer technology and better understanding of HIFU-related bioeffects, HIFU will likely gain acceptance clinically as a technique for noninvasive ablation of tissue for oncologic applications.


Acknowledgments
 
We thank Marie Moffitt for her help in preparing this article.


References
Top
 Abstract
 Introduction
 Clinical History of HIFU
 HIFU Overview
 Limitations of HIFU
 Imaging Guidance and Monitoring...
 Current Clinical Applications
 HIFU Technology
 References
 

  1. Lindstrom PA. Prefrontal ultrasonic irradiation: a substitute for lobotomy. Arch Neurol Psych 1954;72 : 399-425
  2. Fry W, Barnard J, Fry F, Krumins R, Brennan J. Ultrasonic lesions in the mammalian central nervous system with ultrasound. Science 1955; 122:517 -518[Free Full Text]
  3. Hynynen K, Lulu BA. Hyperthermia in cancer treatment. Invest Radiol 1990;25 : 824-834[CrossRef][Medline]
  4. Sanghvi NT, Foster RS, Bihrle R, et al. Noninvasive surgery of prostate tissue by high intensity focused ultrasound: an updated report. Eur J Ultrasound 1999;9 : 19-29[CrossRef][Medline]
  5. Gelet A, Chapelon JY, Bouvier R, et al. Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer. J Endourol 2000;14 : 519-528[Medline]
  6. Hynynen K, Freund WR, Cline HE, et al. A clinical, noninvasive, MR imaging monitored ultrasound surgery method RadioGraphics 1996;16 : 185-195[Abstract/Free Full Text]
  7. Mencaglia L, Guidetti R, Tonellotto D, Fanfani A. Energy focused ultrasound for the clinical treatment of uterine myoma. Ultrasound Med Biol 2000; 26 [suppl 2]: A207
  8. Visioli AG, Rivens IH, ter Haar GR, et al. Preliminary results of a phase I dose escalation clinical trial using focused ultrasound in the treatment of localised tumours. Eur J Ultrasound1999; 9:11 -18[CrossRef][Medline]
  9. ter Haar G. Biological effects of ultrasound in clinical applications. In: Suslick K, ed. Ultrasound: its chemical, physical, and biological effects. New York, NY: VCH Publishers,1988 : 305-320
  10. Chaussy C, Brendel W, Schmiedt E. Extracorporeally induced destruction of kidney stones by shock waves. Lancet1980; 2:1265 -1268[Medline]
  11. Linke CA, Carstensen EL, Frizzell LA, Elbadawi A, Fridd CW. Localized tissue destruction by high-intensity focused ultrasound. Arch Surg 1973;107 : 887-891[Abstract/Free Full Text]
  12. Sibille A, Prat F, Chapelon JY, et al. Characterization of extracorporeal ablation of normal and tumor-bearing liver tissue by high intensity focused ultrasound. Ultrasound Med Biol1993; 19:803 -813[CrossRef][Medline]
  13. Chapelon JY, Ribault M, Vernier F, Souchon R, Gelet A. Treatment of localized prostate cancer with transrectal high intensity focused ultrasound. Eur J Ultrasound 1999;9 : 31-38[CrossRef][Medline]
  14. Kallel F, Stafford RJ, Price RE, Righetti R, Ophir J, Hazle JD. The feasibility of elastographic visualization of HIFU-induced thermal lesions in soft tissues: image-guided high-intensity focused ultrasound. Ultrasound Med Biol 1999;25 : 641-647[CrossRef][Medline]
  15. Shi X, Martin R, Rouseff D, Vaezy S. Detection of high intensity focused ultrasound liver lesions using dynamic elastometry. Ultrason Imaging 1999;21 : 107-126[Medline]
  16. Vaezy S, Shi X, Martin R, et al. Real-time visualization of high intensity focused ultrasound treatment using ultrasound imaging. Ultrasound Med Biol 2001;27 : 33-42[CrossRef][Medline]
  17. Frizzell LA. Threshold dosages for damage to mammalian liver by high intensity focused ultrasound. IEEE Transactions on Ultrasonics, Ferro-electrics and Frequency Control1988 : 35:578 -581[CrossRef]
  18. ter Haar G, Robertson D. Tissue destruction with focused ultrasound in vivo. Eur Urol 1993:23 [suppl 1]:8 -11[Medline]
  19. Sibille A, Prat F, Chapelon JY, et al. Extracorporeal ablation of liver tissue by high intensity focused ultrasound. Oncology 1993: 50:375 -379[Medline]
  20. Chen L, ter Haar G, Hill CR, et al. Effect of blood perfusion on the ablation of liver parenchyma with high-intensity focused ultrasound. Phys Med Biol 1994:38 : 1661-1673[CrossRef]
  21. Moore WE, Lopez R-M, Mathews DE, et al. Evaluation of high-intensity therapeutic ultrasound irradiation in the treatment of experimental hepatoma. J Pediatr Surg1989; 24: 30-33; discussion 33[CrossRef][Medline]
  22. Yang R, Reilly CR, Rescorla FJ, et al. High-intensity focused ultrasound in the treatment of experimental liver cancer. Arch Surg 1991: 126:1002 -1009[Abstract/Free Full Text]
  23. Chen WS. Investigations on the destruction of ultrasound contrast agents: fragmentation thresholds, inertial cavitation and bioeffects [dissertation]. Seattle, WA: University of Washington,2002
  24. Martin RW, Hwang JH. Therapeutic potential and consideration of high intensity focused ultrasound in gastroenterology. In: Odegaard S, Gilja O, Gregersen H, eds. Basic and new aspects in gastrointestinal ultrasonography. Seattle, WA: World Scientific,2005
  25. Coleman AJ, Saunders JE, Crum LA, Dyson M. Acoustic cavitation generated by an extracorporeal shockwave lithotripter. Ultrasound Med Biol 1987; 13:69 -76[CrossRef][Medline]
  26. Holland CK, Apfel RE. Thresholds for transient cavitation produced by pulsed ultrasound in a controlled nuclei environment. J Acoust Soc Am 1990; 88:2059 -2069[CrossRef][Medline]
  27. Marmottant P, Hilgenfeldt S. Controlled vesicle deformation and lysis by single oscillating bubbles. Nature2003; 423:153 -156[CrossRef][Medline]
  28. Wu F, Chen WZ, Bai J, et al. Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound. Ultrasound Med Biol 2001;27 : 1099-1106[CrossRef][Medline]
  29. Vykhodtseva N, McDannold N, Martin H, Bronson RT, Hynynen K. Apoptosis in ultrasound-produced threshold lesions in the rabbit brain. Ultrasound Med Biol 2001;27 : 111-117[CrossRef][Medline]
  30. Lagneaux L, de Meulenaer EC, Delforge A, et al. Ultrasonic low-energy treatment: a novel approach to induce apoptosis in human leukemic cells. Exp Hematol 2002;30 : 1293-1301[CrossRef][Medline]
  31. Ashush H, Rozenszajn LA, Blass M, et al. Apoptosis induction of human myeloid leukemic cells by ultrasound exposure. Cancer Res 2000; 60:1014 -1020[Abstract/Free Full Text]
  32. Qian ZW, Xiong L, Yu J, Shao D, Zhu H, Wu D. Noninvasive thermometer for HIFU and its scaling. Ultrasonics2006; 44[suppl 1]:e31 -e35; Epub 2006 Jun 30[CrossRef][Medline]
  33. Fujitomi Y, Kashima K, Ueda S, Yamada Y, Mori H, Uchida Y. Histopathological features of liver damage induced by laser ablation in rabbits. Lasers Surg Med 1999;24 : 14-23[CrossRef][Medline]
  34. Van Leenders GJ, Beerlage HP, Ruijter ET, de la Rosette JJ, van de Kaa CA. Histopathological changes associated with high intensity focused ultrasound (HIFU) treatment for localised adenocarcinoma of the prostate. J Clin Pathol 2000;53 : 391-394[Abstract/Free Full Text]
  35. Yagel S. High-intensity focused ultrasound: a revolution in non-invasive ultrasound treatment? Ultrasound Obstet Gynecol 2004; 23:216 -217[CrossRef][Medline]
  36. Kennedy JE, ter Haar GR, Wu F, et al. Contrast-enhanced ultrasound assessment of tissue response to high-intensity focused ultrasound. Ultrasound Med Biol 2004;30 : 851-854[CrossRef][Medline]
  37. Kennedy JE. High-intensity focused ultrasound in the treatment of solid tumours. Nature Reviews: CancerMarch 2005; doi:10.1039/nrc1591
  38. Wu F, Wang Z, Chen W, et al. Extracorporeal focused ultrasound surgery for treatment of human solid carcinomas: early Chinese clinical experience. Ultrasound Med Biol 2004;30 : 245-260[CrossRef][Medline]
  39. Wu F, Wang ZB, Chen WZ, et al. Extracorporeal high intensity focused ultrasound ablation in the treatment of 1038 patients with solid carcinomas in China: an overview. Ultrason Sonochem2004; 11:149 -154[CrossRef][Medline]
  40. Everbach EC, Francis CW. Cavitational mechanisms in ultrasound-accelerated thrombolysis at 1 MHz. Ultrasound Med Biol 2000; 26:1153 -1160[CrossRef][Medline]
  41. Kodama T, Tatsuno M, Sugimoto S, et al. Liquid jets, accelerated thrombolysis: a study for revascularization of cerebral embolism. Ultrasound Med Biol 1999;25 : 977-983[CrossRef][Medline]
  42. Rosenschein U, Furman V, Kerner E, et al. Ultrasound imaging-guided noninvasive ultrasound thrombolysis: preclinical results. Circulation 2000;102 : 238-245[Abstract/Free Full Text]
  43. Rosenschein U, Yakubov SJ, Guberinich D, et al. Shock-wave thrombus ablation, a new method for noninvasive mechanical thrombolysis. Am J Cardiol 1992; 70:1358 -1361[CrossRef][Medline]
  44. Tachibana K, Tachibana S. Albumin microbubble echo contrast material as an enhancer for ultrasound accelerated thrombolysis. Circulation 1995;92 : 1148-1150[Abstract/Free Full Text]
  45. Hynynen K, Colucci V, Chung A, Jolesz F. Noninvasive arterial occlusion using MRI-guided focused ultrasound. Ultrasound Med Biol 1996; 22:1071 -1077[CrossRef][Medline]
  46. Wu F, Chen WZ, Bai J, et al. Tumor vessel destruction resulting from high-intensity focused ultrasound in patients with solid malignancies. Ultrasound Med Biol 2002;28 : 535-542[CrossRef][Medline]
  47. Hwang JH, Vaezy S, Martin RW, et al. High-intensity focused US: a potential new treatment for GI bleeding. Gastrointest Endosc 2003; 58:111 -115[CrossRef][Medline]
  48. Martin RW, Vaezy S, Kaczkowski P, et al. Hemostasis of punctured vessels using Doppler-guided high-intensity ultrasound. Ultrasound Med Biol 1999; 25:985 -990[CrossRef][Medline]
  49. Vaezy S, Martin R, Yaziji H, et al. Hemostasis of punctured blood vessels using high-intensity focused ultrasound. Ultrasound Med Biol 1998; 24:903 -910[CrossRef][Medline]
  50. Lawrie A, Brisken AF, Francis SE, et al. Microbubble-enhanced ultrasound for vascular gene delivery. Gene Ther2000; 7:2023 -2027[CrossRef][Medline]
  51. Miller DL, Pislaru SV, Greenleaf JE. Sonoporation: mechanical DNA delivery by ultrasonic cavitation. Somat Cell Mol Genet 2002; 27:115 -134[CrossRef][Medline]
  52. Ng KY, Liu Y. Therapeutic ultrasound: its application in drug delivery. Med Res Rev 2002;22 : 204-223[CrossRef][Medline]
  53. Porter TR, Xie F. Therapeutic ultrasound for gene delivery. Echocardiography 2001;18 : 349-353[CrossRef][Medline]
  54. Price RJ, Skyba DM, Kaul S, Skalak TC. Delivery of colloidal particles and red blood cells to tissue through microvessel ruptures created by targeted microbubble destruction with ultrasound. Circulation 1998;98 : 1264-1267[Abstract/Free Full Text]
  55. Tachibana K, Tachibana S. The use of ultrasound for drug delivery. Echocardiography 2001;18 : 323-328[CrossRef][Medline]
  56. Taniyma Y, Tachibana K, Hiraoka K, et al. Local delivery of plasmid DNA into rat carotid artery using ultrasound. Circulation 2002;105 : 1233-1239[Abstract/Free Full Text]
  57. Unger EC, Hersh E, Vannan M, Matsunaga TO, McCreery T. Local drug and gene delivery through microbubbles. Prog Cardiovasc Dis 2001; 44:45 -54[CrossRef][Medline]
  58. Unger EC, Matsunaga TO, McCreery T, et al. Therapeutic applications of microbubbles. Eur J Radiol 2002;42 : 160-168[CrossRef][Medline]
  59. Frenkel V, Etherington A, Greene M, et al. Delivery of liposomal doxorubicin (Doxil) in a breast cancer tumor model: investigation of potential enhancement by pulsed-high intensity focused ultrasound exposure. Acad Radiol 2006;13 : 469-479[CrossRef][Medline]
  60. Zderic V, Vaezy S, Martin RW, Clark JI. Ocular drug delivery using 20-kHz ultrasound. Ultrasound Med Biol2002; 28:823 -829[CrossRef][Medline]
  61. Prat F, Centarti M, Sibille A, et al. Extracorporeal high-intensity focused ultrasound for VX2 liver tumors in the rabbit. Hepatology 1995;21 : 832-836[Medline]
  62. Kong F, Wu F, Bai J, et al. Intraoperative high-intensity focused ultrasound in treatment of advanced experimental liver cancer [in Chinese]. Chin J Ultrasonog 1999;8 : 251-254
  63. ter Haar G, Rivens I, Chen L, et al. High intensity focused ultrasound for the treatment of rat tumours. Phys Med Biol 1991; 36:1495 -1501[CrossRef][Medline]
  64. ter Haar G, Clarke RL, Vaughan MG, et al. Trackless surgery using focused ultrasound: technique and case report. Minim Invasive Ther 1991; 1:13 -15
  65. Bush NL, Rivens I, ter Haar GR, et al. Acoustic properties of lesions generated with an ultrasound therapy system. Ultrasound Med Biol 1993; 19:789 -801[CrossRef][Medline]
  66. Vaughan MG, ter Haar GR, Hill CR, et al. Minimally invasive cancer surgery using focused ultrasound: a preclinical, normal tissue study. Br J Radiol 1994;67 : 267-274[Abstract/Free Full Text]
  67. Arefiev A, Prat F, Chapelon JY, et al. Ultrasound-induced tissue ablation: studies on isolated, perfused porcine liver. Ultrasound Med Biol 1998; 24:1033 -1043[CrossRef][Medline]
  68. Wang ZB, Wu F, Wang ZL, et al. Targeted damage effects of high intensity focused ultrasound (HIFU) on liver tissues of Guizhou Province miniswine. Ultrason Sonochem 1997;4 : 181-182[CrossRef][Medline]
  69. Bai J, Wu F, Wang Z-B, et al. Localised lesion to normal miniswine liver with high intensity focused ultrasound and dose-effect relation [in Chinese]. Chin J Ultrasonog 1999;8 : 247-250
  70. Ruan X, Du Y, Kong F. Pathological regression following localised ablation of liver tissue of 28 miniswine with high-intensity focused ultrasound [in Chinese]. Chin J Exp Surg1999; 16:263 -264
  71. Vallancien G, Harouni M, Veillon B, et al. Focused extracorporeal pyrotherapy: feasibility study in man. J Endourol1992; 6:173 -181
  72. Wu F, Chen W, Bai J. Effect of high-intensity focused ultrasound on patients with hepatocellular cancer: preliminary report [in Chinese]. Chin J Ultrasonog 1999:8 : 213-216
  73. Wu F, Wang Z, Chen W, et al. Extracorporeal high-intensity focused ultrasound for treatment of solid carcinomas: four-year Chinese clinical experience. In: Vaezy S, ed. Proceedings of the 2nd International Symposium on Therapeutic Ultrasound. Seattle, WA: University of Washington, 2003: 34-43
  74. Li CX, Xu GL, Jiang ZY, et al. Analysis of clinical effect of high-intensity focused ultrasound on liver cancer. World J Gastroenterol 2004; 10:2201 -2204[Medline]
  75. Illing RO, Kennedy JE, Wu F, et al. The safety and feasibility of extracorporeal high intensity focused ultrasound (HIFU) for the treatment of liver and kidney tumours in a Western population. Br J Cancer 2005; 93:890 -895[CrossRef][Medline]
  76. Wu F, Wang ZB, Chen WZ, et al. Advanced hepatocellular carcinoma: treatment with high-intensity focused ultrasound ablation combined with transcatheter arterial embolization. Radiology2005; 235:659 -667[Abstract/Free Full Text]
  77. Reddan DN, Raj GV, Polascik TJ. Management of small renal tumors: an overview. Am J Med 2001;110 : 558-562[CrossRef][Medline]
  78. Chapelon JY, Margonari J, Theillere Y, et al. Effects of high-energy focused ultrasound on kidney tissue in the rat and the dog. Eur Urol 1992: 22:147 -152[Medline]
  79. Adams JB, Moore RG, Anderson JH., et al. High-intensity focused ultrasound ablation of rabbit kidney tumors. J Endourol 1996; 10:71 -75[Medline]
  80. Frizzell LA, Linke CA, Carstensen EL, et al. Thresholds for focal ultrasonic lesions in rabbit kidney, liver, and testicle. IEEE Transactions in Biomedical Engineering 1977;24 : 393-396[CrossRef]
  81. Tu G, Qiao T-Y, He S, et al. An experimental study on high-intensity focused ultrasound in the treatment of VX2 rabbit and kidney tumours [in Chinese]. Chin J Urol 1999;20 : 456-458
  82. Watkin NA, Morris SB, Rivens IH, et al. High-intensity focused ultrasound ablation of the kidney in a large animal model. J Endourol 1997; 11:191 -196[Medline]
  83. Vallancien G, Chartier-Kastler E, Chopin D, et al. Focussed extracorporeal pyrotherapy: experimental results. Eur Urol 1991; 20;211 -219[Medline]
  84. Roberts WW, Hall TL, Ives K, et al. Pulsed cavitational ultrasound: a noninvasive technology for controlled tissue ablation (histotripsy) in the rabbit kidney. J Urol 2006;175 : 734-738[CrossRef][Medline]
  85. Vallancien G, Chartier-Kastler E, Harouni M, et al. Focused extracorporeal pyrotherapy: experimental study and feasibility in man. Semin Urol 1993;11 : 7-9[Medline]
  86. Marberger M, Schatzl G, Cranston D, et al. Extracorporeal ablation of renal tumors with high intensity focused ultrasound. Br J Urol 2005: 95 [suppl 2]: 52-55
  87. Wu F, Wang ZB, Chen WZ, et al. Preliminary experience using high intensity focused ultrasound for the treatment of patients with advanced stage renal malignancy. J Urol 2003;170 : 2237-2240[CrossRef][Medline]
  88. Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer1993; 54:594 -606[Medline]
  89. Jemal A, Tiwari RC, Murray T, et al. Cancer statistics, 2004. CA Cancer J Clin 2004;54 : 8-29[Abstract/Free Full Text]
  90. He SX, Wang GM. The noninvasive treatment of 251 cases of advanced pancreatic cancer with focused ultrasound surgery. In: Andrew MA, Crum LA, Vaezy S, eds. Proceedings from the 2nd International Symposium on Therapeutic Ultrasound. Seattle, WA: University of Washington,2002 : 51-56
  91. Gu Y, Wang G, Xia H, et al. Application of high intensity focused ultrasound in treating 45 cases of carcinoma of the pancreas [in Chinese]. Fudan Univ J Med Sci 2005;31 : 135-141
  92. Wang RS, Mu QX, Liu LX, Shu YQ. A clinical study of thermotherapy of HIFU in combination with chemotherapy on treating advanced pancreatic cancer [in Chinese]. Acta Nanjing Med Univ2003; 23:460 -463
  93. Wang X, Sun JZ. Preliminary study of high intensity focused ultrasound in treating patients with advanced pancreatic carcinoma [in Chinese]. Chin J Gen Surg 2002;17 : 654-655
  94. Wu F, Wang ZB, Zhu H, et al. Feasibility of US-guided high-intensity focused ultrasound treatment in patients with advanced pancreatic cancer: initial experience. Radiology2005; 236:1034 -1040[Abstract/Free Full Text]
  95. Xie DR, Chen D, Teng H. A multicenter nonrandomized clinical study of high intensity focused ultrasound in treating patients with local advanced pancreatic carcinoma [in Chinese]. Chin J Clin Oncol2003; 30:630 -634
  96. Xiong LL, He CJ, Yao SS, et al. The preliminary clinical results of the treatment for advanced pancreatic carcinoma by high intensity focused ultrasound [in Chinese]. Chin J Gen Surg2005; 16:345 -347
  97. Xu YQ, Wang GM, Gu YZ, Zhang HF. The acesodyne effect of high intensity focused ultrasound on the treatment of advanced pancreatic carcinoma [in Chinese]. Clin Med J China 2003;10 : 322-323
  98. Yuan C, Yang L, Yao C. Observation of high intensity focused ultrasound treating 40 cases of pancreatic cancer [in Chinese]. Chin J Clin Hepatol 2003;19 : 145-146
  99. Madersbacher S, Schatzl G, Djavan B, Stulnig T, Marberger M. Long-term outcome of transrectal high-intensity focused ultrasound therapy for benign prostatic hyperplasia. Eur Urol2000; 37:687 -694[CrossRef][Medline]
  100. Rouvière O, Mège-Lechevallier F, Chapelon JY, et al. Evaluation of color Doppler in guiding prostate biopsy after HIFU ablation. Eur Urol 2006; 50:490 -497[CrossRef][Medline]
  101. Häcker A, Köhrmann KU, Back W, et al. Extracorporeal application of high-intensity focused ultrasound for prostatic tissue ablation. BJU Int 2005;96 : 71-76[CrossRef][Medline]
  102. Chaussy C, Thuroff S. Results and side effects of high-intensity focused ultrasound in localized prostate cancer. J Endourol 2001; 15:437 -440[CrossRef][Medline]
  103. Ficarra V, Antoniolli SZ, Novara G, et al. Short-term outcome after high-intensity focused ultrasound in the treatment of patients with high-risk prostate cancer. BJU Int 2006;98 : 1193-1198[CrossRef][Medline]
  104. Kiel HJ, Wieland WF, Rössler W. Local control of prostate cancer by transrectal HIFU-therapy. Arch Ital Urol Androl 2000; 72:313 -319[Medline]
  105. 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]
  106. Uchida T, Sanghvi NT, Gardner TA, et al. Transrectal high-intensity focused ultrasound for treatment of patients with stage T1b-2N0M0 localized prostate cancer: a preliminary report. Urology2002; 59:394 -398[CrossRef][Medline]
  107. Coulange C. High intensity focused ultrasound in localized prostate cancer [in French]. Cancer Radiother2005; 9:377 -378[Medline]
  108. Uchida T. High-intensity focused ultrasound for localized prostate cancer [in Japanese]. Nippon Rinsho 2005;63 : 345-349[Medline]
  109. Schatzl G, Madersbacher S, Djavan B, Lang T, Marberger M. Two-year results of transurethral resection of the prostate versus four "less invasive" treatment options. Eur Urol2000; 37:695 -701[CrossRef][Medline]
  110. Gelet A, Chapelon JY, Poissonnier L, et al. Local recurrence of prostate cancer after external beam radiotherapy: early experience of salvage therapy using high-intensity focused ultrasonography. Urology 2004; 63:625 -629[CrossRef][Medline]
  111. Lledo Garcia E, Jara Rascon J, Subira Ros D, et al. Scientific evidence on the use of high-intensity focal ultrasound (HIFU) in the treatment of prostatic carcinoma [in Spanish]. Actas Urol Esp2005; 29:131 -137[Medline]
  112. Chaussy C, Thuroff S, Bergsdorf T, et al. Local recurrence of prostate cancer after curative therapy: HIFU(Ablatherm) as a treatment option [in German]. Urologe A 2006;45 : 1271-1275[CrossRef][Medline]
  113. Chaussy C, Thuroff S. High-intensity focused ultrasound in prostate cancer: results after 3 years. Mod Urol2000; 4:179 -182
  114. Thuroff S, Chaussy C. Therapy of local prostatic carcinoma with high intensity focused ultrasound (HIFU): outcome and side effects [in German]. Urologe A 2001;40 : 191-194[CrossRef][Medline]
  115. Uchida T, Ohkusa H, Yamashita H, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Int J Urol2006; 13:228 -233[CrossRef][Medline]
  116. Gelet A, Chapelon JY, Bouvier R, Rouvi re O, Lyonnet D, Dubernard JM. Transrectal high intensity focused ultrasound for the treatment of localized prostate cancer: factors influencing the outcome. Eur Urol 2001; 40:124 -129[CrossRef][Medline]
  117. Poissonnier L, Gelet A, Chapelon JY, et al. Results of transrectal focused ultrasound for the treatment of localized prostate cancer (120 patients with PSA < or + 10 ng/ml) [in French]. Prog Urol 2003; 13:60 -72[Medline]
  118. Blana A, Rogenhofer S, Ganzer R, Wild PJ, Wieland WF, Walter B. Morbidity associated with repeated transrectal high-intensity focused ultrasound treatment of localized prostate cancer. World J Urol 2006; 24:585 -590[CrossRef][Medline]
  119. Lee HM, Hong JH, Choi HY. High-intensity focused ultrasound therapy for clinically localized prostate cancer. Prostate Cancer Dis 2006; 9:439 -443[CrossRef]
  120. Vallancien G, Prapotnich D, Cathelineau X, Baumert H, Rozet F. Transrectal focused ultrasound combined with transurethral resection of the prostate for the treatment of localized prostate cancer: feasibility study. J Urol 2004;171 (6 Pt 1):2265 -2267[CrossRef][Medline]
  121. Chaussy C, Thuroff S. The status of high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer and the impact of a combined resection. Curr Urol Rep2003; 4:248 -252[CrossRef][Medline]
  122. Aus G. Current status of HIFU and cryotherapy in prostate cancer: a review. Eur Urol 2006;50 : 927-934[CrossRef][Medline]
  123. Pickles T, Goldenberg L, Steinhoff G. Technology review: high-intensity focused ultrasound for prostate cancer. Can J Urol 2005; 12:2593 -2597[Medline]
  124. Rébillard X, Davin JL, Soulié M; Comité de Cancérologie de l'Association Fran aise d'Urologie. Treatment by HIFU of prostate cancer: survey of literature and treatment indications [in French]. Prog Urol 2003;13 : 1428-1456[Medline]
  125. Rewcastle JC. High intensity focused ultrasound for prostate cancer: a review of the scientific foundation, technology and clinical outcomes. Technol Cancer Res Treat 2006;5 : 619-625[Medline]
  126. Rebillard X, Gelet A, Darvin JL, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer. J Endourol 2005; 19:693 -701[CrossRef][Medline]
  127. Jemal A, Thomas A, Murray T, et al. Cancer statistics, 2002. CA Cancer J Clin 2002;52 : 23-47[Abstract/Free Full Text]
  128. Whittington R, Neuberg D, Tester WJ, et al. Protracted intravenous fluorouracil infusion with radiation therapy in the management of localized pancreaticobiliary carcinoma: a phase I Eastern Cooperative Oncology Group Trial. J Clin Oncol 1995;13 : 227-232[Abstract/Free Full Text]
  129. Chartier-Kastler E, Chopin D, Vallancien G. The effects of focused extracorporeal pyrotherapy on a human bladder tumor cell line (647 V). J Urol 1993; 149:643 -647[Medline]
  130. Watkin NA, Morris SB, Rivens IH, et al. A feasibility study for the non-invasive treatment of superficial bladder tumours with focused ultrasound. Br J Urol 1996;78 : 715-721[Medline]
  131. Kashcheeva SS, Sapozhnikov OA, Khokhlova VA, Averkiou MA, Crum LA. Nonlinear distortion and attenuation of intense acoustic waves in lossy media obeying a frequency power law. Acoust Physics2000; 46: 170-177 (translated from Russian)[CrossRef]

Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow CME
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dubinsky, T. J.
Right arrow Articles by Hwang, J. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dubinsky, T. J.
Right arrow Articles by Hwang, J. H.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Hotlight (NEW!)
Right arrow
What's Hotlight?

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS