MR-guided focused ultrasound.

The joining of high-intensity focused ultrasound with high-resolution MR guidance has created a system that can produce tissue destruction deep within solid organs without any invasion. Accurate targeting and thermal mapping are provided by MRI and allow very accurate deposition of energy in tissues that can be altered in response to near real-time thermal imaging produced by MR so that the variation in tissue response that is otherwise observed can be overcome. Current areas of successful application of MR-guided focused ultrasound are described in the treatment of uterine fibroids and other areas of emerging applications in additional solid organs are also discussed.

Thermal ablation of tissues is a relatively new modality of therapy that is now performed with increasing frequency in the treatment of many conditions [1]. It is a minimally invasive, local technique used to treat local disease in solid viscera. This type of therapy involves the destruction of tissue using either heat or, occasionally, cold to destroy cells. There are many individual technologies that can be used to achieve this effect in tissue and radiofrequency probes, interstitial laser fibers and microwave probes can all be utilized commonly in a percutaneous approach to deliver this effect. This type of work is carried out via percutaneous puncture into the targeted area using some form of image guidance, which may be MR, CT or ultrasound, which is crucial to the success of the procedure. Once the target is reached, heating is performed to destroy the lesion. Neither ultrasound nor CT guidance are sufficient to correctly indicate the level of heating achieved within the tissues during the heating process [2]. MR, with its thermal abilities, visualizes heated areas almost in real time [3]. Thermal ablative therapy has been very successful in broadening the treatment options available in many conditions that are otherwise difficult to treat using purely conventional modalities. Liver metastases and hepatocellular carcinoma are good examples and the best results in these areas using thermal ablation are quite comparable to surgery, which is commonly carried out in more select groups, particularly for hepatic secondaries [4]. The success of these approaches to the treatment of local tissue has led practitioners in this field to assess whether there are any other methods in which heat can be delivered into deep body structures that may be less invasive. All of the techniques described above are minimally invasive but still require significant percutaneous punctures into potentially vascular organs and vascular tumors with obvious potential complications that could ensue from this. In particular, when patients with diseased livers are treated, such as with hepatocellular carcinomas, this becomes an area of particular concern.
Therefore, if one were to speculate on the most desirable method of applying this thermal therapy, an immediate desire would be to minimize the size of the percutaneous puncture to a minimal size and yet to produce the maximum lesion in a highly controlled manner within the body. Under current normal circumstances this combination is usually mutually exclusive.
Focused ultrasound (FUS) surgery is a method of depositing heat into tissues without any form of physical agent, such as needles or other probes, passing through the skin. In this situation, only very high-intensity FUS beams pass through the skin and are focused very tightly into a small area in which tissue can be heated only at the focus. The potential, therefore, is that FUS may approach some of the above hypothetical goals for thermal ablation. A very substantial amount of work remains to develop this technology completely but the potential is such that within a decade it may change many of our current methods of work [5].

What is focused ultrasound?
Described very crudely, FUS utilizes acoustic energies between 5000-and 100,000-times greater than those of conventional diagnostic ultrasound, focused to very small points within solid tissue [6]. At the focus, the molecules are rapidly agitated causing localized heating. When the temperature of the localized heating exceeds 56°C for 1 s, it causes protein precipitation and denaturation, which leads to cell necrosis [7]. The tissues anterior to the focus may heat slightly but it is only at the focal spot that full heating is generated leading to cellular destruction. No ischemic infarction is produced by this technique. Cooling intervals are placed between each sonication so that the tissue anterior and, to a lesser extent, posterior to the focal spot cool between sonications allowing further sonications to be placed closer to the first one without any damage to the intervening tissues [8]. The passage of the FUS beam through the tissues depends on the same physical factors as conventional diagnostic ultrasound. In other words, gas will reflect the FUS beam and may cause areas of high heat build-up at tissue-gas interfaces that must be avoided. Bone and calcifications will absorb FUS energy very avidly, potentially shielding structures immediately behind them from heating but may also cause heat build up at the bone-soft tissue interface. Fluid allows unimpeded rapid conduction of ultrasound.
Taking these factors into account, it is clear that by utilizing this technology it is possible to deposit destructive lesions in solid tissues if there is an appropriate acoustic window from the outside without any form of intervention, such as needles, fibers and probes, passing through the intervening tissues. This process, therefore, allows the creation of a destructive lesion deep within the body without any form of invasion.
The possibility of using ultrasound to carry out destructive surgery of this nature was described as early as 1942 by Lynn and colleagues [9]. These early concepts, although insightful, suffered greatly from the relatively undeveloped technological environment of the time and it is only in the last 20 years that we have had the ability to apply this form of therapy in a safe and controlled manner.

MR-guided FUS
No single universally adhered method of utilizing FUS has yet emerged. Many of the earlier utilizations of this technique use conventional diagnostic ultrasound transducers combined with FUS surgery transducers so that the targeting of the highenergy therapeutic ultrasound is carried out with diagnostic ultrasound [10]. This allows a reasonable amount of flexibility in the targeting, but it does have several substantial drawbacks.
The first of these is that the lower spatial resolution of diagnostic ultrasound makes it less accurate as a targeting technique than MRI or CT. In addition, when there is bowel and air in the vicinity, it may be hard to visualize the details of adjacent structures around these gas-containing portions, as well as behind them, so that targeting may be limited. Similarly, the resolution of the target and the extent of disease that is being aimed at is significantly more difficult to assess with ultrasound than with the excellent soft tissue contrast that is obtainable with MR [11].
MR has become the modality of choice for the precise staging of tumors in many instances because it offers excellent visualization of the full extent of tumor within its tissue structure and depicts the boundary with normal tissues very clearly. It is precisely this ability that is so useful in the targeting of FUS and where diagnostic ultrasound guidance alone is most problematic. In addition, thermal mapping is difficult with ultrasound. While there are a variety of techniques becoming available gradually that may improve the thermal resolution of ultrasound, these techniques remain quite cumbersome and experimental only, with many problems still remaining. MR, in comparison, has the very best possible thermal resolution available of any modality and real-time thermal scans can be obtained in approximately 1-2 s with high spatial resolution [5]. Therefore, thermal maps are rapidly and easily acquired with MR and are accurate to ±2°C using conventional phase shift imaging [5].
Despite these relative drawbacks, ultrasound-guided highintensity FUS has been utilized to treat many patients, particularly in the Far East, in a variety of applications and shows substantial promise in these areas [12,13].
Developing FUS machinery that works in the extremely hostile environment of an MR scanner is a substantial technical achievement [14][15][16]. No ferromagnetic material may be used and radiofrequency leakage from electrical components will cause substantial imaging degradation. Simple motion of the transducer has to be accomplished by MR compatible means, such as the utilization of piezoelectric motors rather than conventional electric motors. Substantial filtering of radiofrequency leakage together with shielding of electric connections must be utilized to limit interference with imaging. Once these problems are overcome, it becomes perfectly possible to move machinery within the MR environment and to carry out procedures in an effective and safe manner (FIGURE 1).
Only one commercially available MR-compatible machine is currently available (ExAblate ® 2000, Insigtec, Haifa, Israel), although several other prototypes are currently being tested and most of the major medical equipment manufacturers are investigating this technology in detail. The ExAblate 2000 system consists of four components, which all work in synergy. These are an MR scanner, the FUS table containing the transducer and water bath, the electronic components driving the system and the FUS workstation, which links to the MR workstation and allows user interaction in a versatile manner. To date, this system works only on the General Electric (WI, USA) MRI scanner platform. The FUS  table is identical to the conventional MR  table, with the addition of a built-in transducer and water bath, and electronic connections. The current machinery contains a 211 phased array element within a water bath. The transducer may be moved by its robotic system to any position in the water bath plus pitch and roll angulations of up to 25° can be set and the depth of focus can be varied electronically to allow great flexibility of positioning. The transducer frequency is variable, ranging from 0.9 to 1.4 MHz.

Description of the procedure
At the beginning of each procedure, a full MRI scan of the targeted volume is carried out in coronal, axial and sagittal planes using the most appropriate sequences that will demonstrate the target. These images are transferred to the FUS workstation and the target volume is selected carefully by the operator drawing around the area in question in all planes. During the same procedure, areas of tissue that must be avoided are also outlined. A simple example of this is the margins of adjacent bones and bowel that must not be crossed. These coordinates are incorporated into the planning sequence so that all subsequent potential sonications have these positions imbedded in them preventing inadvertent or deliberate sonication through these areas. Similarly, distances of skin to focal site and focal spot to distal structures, such as nerves and bones, may also be outlined so that a calculation of power deposition can be updated continuously with each sonication, allowing early warning of undesirable potential thermal accumulation in these structures.
A grid of sonications to be carried out is projected onto the target volume, which may be altered in an appropriate manner for the type of tissue being treated. For instance, benign fibroids do not need overlapping sonications with a substantial margin around the target zone to produce a significant symptomatic effect, whereas in the treatment of a small liver malignancy, overlapping sonications with margins around the visible tumor would be applied. The machinery is flexible enough to allow multiple variations in this context. Initial sonications are produced at subtherapeutic doses to confirm the alignment of MR scanning and FUS and to make any simple corrections for tissue aberration. Once these corrections are made sequential sonications are performed, slowly covering the target area. The result of each sonication is measured with a phase-shift MR thermal map, which can be calibrated to indicate areas in the target, where the temperature has exceeded tissue necrotic levels. This is then displayed on the cumulative dose thermal map so that, over a period of sonications, the thermal dose map is built up overlaying the target area and it is immediately apparent which areas have been treated, which portion of tissue may have not responded or received adequate therapeutic doses and where adjustments can be made to ensure that the whole area is covered with a uniform treatment. The thermal maps are produced within seconds of the deposition of the thermal dose and allow the operator to interact with the system in multiple ways to optimize the thermal dose response that is observed within the targeted tissues. The ability to interact with the system to produce consistent effective tissue doses is of great benefit during the procedure. Our experience in treating many hundreds of patients with this technique is that there is a huge variation in the acoustic powers required between patients and even within the same tumor, which would not be appreciated without this type of monitoring [15]. Thermal imaging is largely independent of tissue type but lesions with large fatty components do cause problems for conventional phase-shift imaging. The result of this type of thermal monitoring is that we can produce an accurate, very safe and reproducible treatment with minimal disruption to adjacent normal tissues. Without this, the procedure necessarily involves a much greater element of guess work and hope.
Complications observed with MR-guided FUS (MRgFUS) are similar to those of FUS applied in any other manner. Burns to the skin are produced occasionally, particularly if gas bubbles are trapped at the interface of skin and water bath. Neural damage is possible if energy deposition in sensitive areas, such as the sacrum, is high or impinges directly on a nerve. Current machine software incorporates safety mechanisms to minimize these possibilities and seems to be effective, and patient feedback is extremely useful during the procedure in reducing these complications.
At the end of the procedure, a post-MR contrast volume scan is usually carried out to try and assess the extent of tissue damage that has been produced in a volumetric manner, by looking at the amount of tissue that has lost its normal vascular enhancement thereby accurately depicting the total treated volume (FIGURES 2-4).

Areas of clinical application of MR-guided FUS
The largest clinical area of application to date using this type of technology has been in the treatment of uterine fibroids. Overall, approximately 2500 patients have been treated with this approach worldwide. Initial studies using this technology to treat uterine fibroids, were limited to fibroids of a maximum 10-cm diameter since this was part of an early US FDAsanctioned study [17,18]. Patients were enrolled who had fibroids that could be easily accessed via a suitable acoustic window through the anterior abdominal wall. Clearly, uteruses with fibroids that had a substantial amount of bowel interposed between the uterus and the abdominal wall could not be treated. This interposition of bowel between uterus and abdominal wall remains an absolute contraindication. In some instances, bladder filling may provide an acoustic window but this is not always the case. Similarly, it has become evident that scars in the pathway of the FUS beam are problematic. It appears that the dense collagenous, fibrous, avascular nature of the scar absorbs ultrasound avidly, and causes local heating and possibly even burning of the skin and disrupts the FUS beam so that the focal spot is lost. Therefore, we try and avoid applying FUS treatment through surgical scars. Many of the patients who wish to have treatment for fibroids have had previous cesarean sections and myomectomies, and this may be problematic. If the scar is a low transverse one it may be quite easy to avoid by simply treating above this area (FIGURE 3) and many procedures can be carried out with great success with these types of provisos. Vertical scars running right through the middle of the potential FUS acoustic window are much more problematic and usually prevent proper procedures being carried out. Initial studies that treated only fibroids measuring a maximum of 10 cm in diameter have shown an excellent improvement in symptoms measured by dedicated uterine fibroid symptom severity scores. Between 70 and 80% of patients show a significant improvement in these symptomatic scores at both 3 and 6 months post treatment [19]. In patients that could be followed to 12 months these figures were usually maintained, but initial studies were only designed to measure patients for up to 6 months and successful follow-up has been difficult and is still emerging.
Many fibroids are much larger than 10 cm in diameter and these are often associated with much greater symptoms. A modified approach has been developed for fibroids measuring between 10 and 20 cm. In these circumstances, we now pretreat these patients with gonadotropin-releasing hormone (GnRH) agonists for 3 months, causing a medical hypo-estrogenic state, which usually results in a significant degree of fibroid shrinkage [20]. At the end of the 3 months, patients are treated with conventional FUS in the manner described above. This process allows treatment of a large fibroid when it is smaller since there is, on average, 40% shrinkage of fibroids using this medical therapy over the 3-month period. In addition, it seems that the effects of each FUS sonication is potentiated by the GnRH agonist pretreatment [21]. This is thought to be due to a reduction in vascularity of fibroids induced by the GnRH and allows a greater amount of treatment per joule applied, which is also advantageous in this situation. A study examining 50 patients with fibroids all greater than 10 cm (10-20 cm) indicated that patients treated in this manner had a symptomatic response equal to that of the previous study when only fibroids smaller than 10 cm were treated [20]. This type of adjuvant therapy applied to this FUS technique has greatly increased the range of fibroids that can be treated in this way. Overall, therefore, it is now possible to treat fibroids up to 20 cm in diameter with the expectancy of excellent symptomatic success plus significant volume reductions at 6 and 12 months. We are at a relatively early stage in the evolution of this treatment for fibroids and results are still being acquired at 24 and 36 months post treatment. Initial groups of patients that were treated were only those who had completed their family. Despite this, some patients in the treatment groups have become pregnant, with several going on to deliver healthy babies without any complications to the pregnancy [22]. Dedicated studies are being developed to assess whether FUS can improve fertility in patients with fibroids and, although this will be a long-term undertaking, it does appear that FUS may not produce any adverse problems for pregnancy and delivery.

Other applications of FUS
MRgFUS is now slowly being applied to a variety of other areas. The following are very brief descriptions of these early applications.

Breast cancer
The intention of using FUS in the treatment of breast cancer is to try to replace conventional surgery with a completely noninvasive procedure. This would allow patients to have an outpatient treatment with no associated surgical scars and to replace procedures, such as lumpectomy and wide local excision. The overall treatment for breast cancer would otherwise be as normal in terms of radiotherapy, drug treatments and sentinel node biopsy, but breast surgery would be avoided. Studies are at an early stage but, in a recent study, 30 patients in Japan were treated with FUS followed by a lumpectomy of the treated area [23]. These samples were then examined carefully histologically and an average of 97% of malignant cells in the treated area were destroyed by this procedure [24]. This high percentage is extremely promising and far exceeds the percentage of cells considered to be removed by conventional lumpectomy in a wide local excision [25]. Studies continue in this area but these early results appear promising and currently expanded versions of this study are ongoing. Development of similar protocols where patients receive FUS without subsequent surgery and the patient is followed over a period of time using detailed imaging criteria to measure the response are also now underway.

Liver & abdominal MR-guided FUS
There is a wealth of experience in the literature describing the use of percutaneous thermal destructive devices, such as laser, radiofrequency or microwave probes, in the treatment of local liver disease due to primary or secondary hepatic tumors [26]. Success rates in these areas are highly promising and have led to worldwide interest in this form of technology as a method of treating local disease within the liver, with very low morbidity and reduced in-patient stay in comparison with conventional hepatic surgery [27].
FUS, in this field, has the potential of completely removing the invasiveness from this procedure and allowing localized destruction of areas of the liver to be achieved entirely as an outpatient without the requirement of any percutaneous needles and probes being pushed through the liver with their attendant complications, particularly when underlying liver disease is present, as is so often the case with patients who have hepatocellular carcinoma.
The difficulties with using MRgFUS with current equipment are as follows. The majority of the liver is covered by the ribcage and the footprint of the FUS beam from the current transducer is relatively wide. The ribs absorb the FUS, preventing a focused target being achieved in the liver and there is also substantial rib heating produced causing not only damage to the underlying bone, but also potential heating and burning of the overlying skin. Respiratory motion of the liver, under normal circumstances, would prevent consistent repeated application of an ultrasound spot to successive areas in a target zone in an accurate fashion because respiration may move the liver in an unpredictable manner between sonications.
Using general anesthesia in conjunction with FUS application has solved this latter problem. To achieve this, a MRcompatible ventilator is used, which is coupled to the FUS machine and always returns the patient's diaphragm to the same position prior to sonication being allowed [28]. This recaptures These images have been obtained immediately after focused ultrasound therapy. Intravenous contrast was given and the bright areas show a normally enhancing myometrium. The low signal areas are multiple fibroids, which have been treated and now show no perfusion (thick arrows). The thin arrow points to an area on the skin where there was a transverse scar, which we have accentuated by painting it with a solution containing very dilute ferromagnetic compounds, making it easier to identify the scar at the time of the procedure. Without the full bladder, the uterus would have been much lower and it would have been difficult to achieve an acoustic window without traversing the scar but in this situation the uterus is elevated and we were easily able to reach the multiple fibroids present without going through the scar. These images were obtained on the focused ultrasound bed so that the area immediately in front of the skin line is a gel pad sitting in the water bath of the transducer within the modified table.
the exact 3D spatial control of the studies that is lost with voluntary respiration and allows spots to be placed in a consistent, controlled manner one after the other, so that a targeted area can be covered easily.
The problem of the ribs is much harder to overcome currentlyt and, to date, only areas of the liver that are either below the right rib line or in the mid line and not covered by the ribs can be treated. It is anticipated that within 12 months further technological upgrades will allow treatment in between the ribs using modified transducers, overcoming the problem of rib shielding.
Early procedures have, however, been carried out using the above techniques in suitable patients. The early results suggest that the coupling of the MRgFUS machinery to a ventilator does indeed allow effective control of lesion positioning in the liver and that FUS can easily produce thermal destructive areas within the liver, covering areas of abnormality to produce effective thermal lesions. Only a few procedures have been performed so far due to the restrictions imposed by the above factors but the potential of this approach is immense. Similar concerns and restrictions apply in the treatment of the kidney and, again, further technology upgrades are required to completely reach the kidney and overcome the problems of overlying ribs and respiratory motion as above.

MR-guided FUS of bone
Radiotherapy is the most common conventionally used treatment in patients with painful bone primaries or secondaries. Despite this, a proportion of patients continue to have pain despite the additional use of other conventional therapies, such as hormonal manipulation and chemotherapy. Several groups have attempted to use percutaneous thermal ablation techniques similar to those in the liver and other areas of the body to try and treat these conditions. Callstrom and colleagues describe 62 patients treated with this form of percutaneous thermal therapy using radiofrequency ablation techniques with very effective improvement in pain scores following just one single treatment [29]. It is known that bone absorbs FUS very avidly and this property can be utilized to heat large areas of periosteum quite rapidly. The percutaneous techniques described previously have produced the interesting finding that palliation of pain was much more effective when the periphery of the target lesion was treated rather than its center and, indeed, these authors have suggested that if the center was treated alone, palliation was poor. It is postulated, therefore, that the periosteum is the primary site of pain induction in these conditions. To this end, as described above, FUS may be easily applied to wide areas of the periosteum utilizing a broader portion of the beam rather than just the small focal spot [30]. This type of modified application allows treatment to encompass relatively large areas of the periosteum with each sonication. A total of 35 patients have been treated worldwide in early studies using this technique and early experience suggests that palliation is a very effective technique, similar to percutaneous techniques, and good results can be achieved very rapidly under these conditions. Therefore, FUS in bone may provide a noninvasive one-stop outpatient treatment of painful bone lesions with highly effective pain control, without the need for longer courses and multiple attendances, as is usually required for radiotherapy. Similarly, radiotherapy failures may also be treated with this type of approach in an effective manner. Hopefully, this type of therapy application will provide a further option for pain palliation in these difficult cases.

MR-guided FUS of the brain
Early work is evolving at two sites in the world indicating that FUS can be deposited within the brain through the closed skull. This requires complex computational calculation of calvarial thickness and curvature along the potential lines of sonication but it is becoming clear that destructive energy can be focused through the closed skull into target areas within the brain to destroy tissues [31]. If this early promise is maintained, the prospect of achieving surgical destruction of abnormal lesions through a closed skull is very exciting for the future. This area, however, is intensely complex, with many problems still to be solved, however, the promise of this early work remains.

Conclusion
Most of the discussion above has related to the direct thermal ablation capabilities of MRgFUS. This is clearly the most immediately accessible and understandable method of applying this type of energy in a controlled manner. There are, however, several other methods of utilizing heat therapeutically in the body, which are becoming apparent as this technology progresses. The ability to activate a variety of drugs at discreet sites within the body may become a very powerful tool when combined with FUS [32]. This will allow us to administer potentially toxic drugs in a form that is nonreactive to the majority of body structures but when discreet areas of the body, where the treatment is required are heated, the drugs become activated in those areas. This type of combination therapy may prove to be as important as the more direct physical effects of FUS. Similar exciting capabilities are coming to light with the combined use of FUS with clot dissolving agents, such as tissue plasminogen activators and early work again is promising using a combination of these therapies where it seems that FUS, by virtue of its direct mechanical effects on clot, may potentiate clot destruction.
The coupling of FUS with other powerful modalities of image guidance, particularly MR, offers a complete method for applying this destructive technology safely within the body to a variety of areas. The hope is that utilizing this more expensive technology will be highly cost effective since it will replace many open operations and similar procedures with a simple noninvasive outpatient procedure, thus saving much patient morbidity and freeing up a large amount of expensive hospital inpatient utilization. It is likely that numerous other areas of application will evolve over the ensuing years as this technology diffuses more rapidly.

Expert commentary
FUS can produce destructive thermal lesions at depth within the body in an entirely noninvasive manner. The coupling of this technology with MR guidance and monitoring allows this destructive energy to be utilized in a highly accurate and safe manner producing reliable lesions in a controlled effective manner so that as little damage as possible is produced to adjacent normal tissue, while treating the maximum amount of the abnormal tissue within the target field. MR guidance provides the best possible targeting of the lesion and the MR thermal mapping that is achieved in almost real time allows the operator to interact with the procedure to overcome the substantial inherent tissue variability that is observed.
The technology required to carry out MRgFUS is expanding rapidly and it is anticipated that further advances in transducer development will allow us to easily apply this type of therapy to most solid organs in the body so that hepatic and renal tumors may be treated in the future with this technology as easily as we can treat fibroids currently. The hope is that many surgical procedures that are currently utilized will be replaced by a noninvasive outpatient FUS procedure. Although the initial capital investment to acquire this equipment is substantial, the potential cost savings from improvements in patient morbidity and quality of life plus the decreased requirement for in-patient care will more than offset the initial costs.

Five-year view
Within 5 years, we anticipate that MRgFUS will be a well established method for the treatment of lesions in many solid organs within the body. Fibroid treatment with MRgFUS, which is already gaining worldwide acceptance, will be established as the primary modality for treatment in this field, greatly reducing the need for conventional hysterectomy. Effective therapies will be available with new transducer development for the treatment of hepatic lesions, renal lesions, prostate malignancies and breast tumors. FUS with MR guidance will become a mainstream oncological therapy providing substantial further options for tumor treatment and lead to a substantial reduction in surgical procedures in many areas. Further development of transducer technology will allow procedures to be carried out much more quickly and we anticipate the development of multiple dedicated MR machines that carry out only FUS treatment. Continuing development of the drug activation aspects will occur so that stroke patients may well be treated with clot destruction and FUS as a primary modality after admission. Disclosure W Gedroyc acts as an occasional consultant to Insight Tec., for which he is paid.

Key issues
• Focused ultrasound (FUS) is a method that allows the deposition of a high amount of ultrasound energy at selected sites in solid organs deep within the body without any intervention passing through the skin allowing noninvasive thermal ablation to be carried out.
• The use of MR guidance in association with FUS allows highly accurate targeting of the delivery of the FUS to the correct location and does not involve adjacent tissue, and the thermal mapping that is produced easily and rapidly by MRI allows great control of the procedure so that these two techniques combined produce an accurate, safe and reliable method for the deposition of this destructive energy into deep tissues with very few safety issues.
• MR-guided FUS can be carried out as an entirely noninvasive outpatient procedure and has the potential to replace many surgical and other more invasive processes. In 2004, the US FDA approved the treatment of uterine fibroids and multiple other areas of application are evolving that utilize this technology.