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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
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  		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
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  		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
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  		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
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  		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
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  		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
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  		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
 

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