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Noninvasive thermal ablation of hepatocellular carcinoma by using magnetic resonance imaging-guided focused ultrasound

2004; Elsevier BV; Volume: 127; Issue: 5 Linguagem: Inglês

10.1053/j.gastro.2004.09.056

1528-0012

Ferenc A. Jólesz, Kullervo Hynynen, Nathan McDannold, David Freundlich, Doron Kopelman,

Photoacoustic and Ultrasonic Imaging

A number of minimally invasive methods have been tested for the thermal ablation of liver tumors as an alternative to surgical resection. The use of focused ultrasound transducers to ablate deep tumors offers the first completely noninvasive alternative to these techniques. By increasing the flexibility of this technology with modern phased-array transducer design and by combining it with magnetic resonance imaging for targeting and online guidance, a powerful tool results with the potential to offer treatment to a larger population of patients, to reduce trauma to the patient, and to reduce the cost of treatment. In this article, we review previous work with focused ultrasound in the liver and recent experimental results with magnetic resonance imaging guidance. A number of minimally invasive methods have been tested for the thermal ablation of liver tumors as an alternative to surgical resection. The use of focused ultrasound transducers to ablate deep tumors offers the first completely noninvasive alternative to these techniques. By increasing the flexibility of this technology with modern phased-array transducer design and by combining it with magnetic resonance imaging for targeting and online guidance, a powerful tool results with the potential to offer treatment to a larger population of patients, to reduce trauma to the patient, and to reduce the cost of treatment. In this article, we review previous work with focused ultrasound in the liver and recent experimental results with magnetic resonance imaging guidance. Although surgical resection is considered the therapy of choice for liver cancer, the relatively low percentage of patients who are good candidates for surgery, the high incidence of new metastases after resection, and the poor success rate after multiple resections have led to the development of several less invasive local ablative therapies for liver tumors. These approaches have included percutaneous ethanol injection; radiofrequency (RT), microwave, and laser ablation; and cryotherapy.1Livraghi T. Lazzaroni S. Meloni F. Torzilli G. Vettori C. Intralesional ethanol in the treatment of unresectable liver cancer.World J Surg. 1995; 19: 801-806Crossref PubMed Scopus (39) Google Scholar, 2McCall J.L. Booth M.W. Morris D.L. Hepatic cryotherapy for metastatic liver tumors.Br J Hosp Med. 1995; 54: 378-381PubMed Google Scholar, 3Yamanaka N. Okamoto E. Tanaka T. Oriyama T. Fujimoto J. Furukawa K. Kawamura E. Laparoscopic microwave coagulonecrotic therapy for hepatocellular carcinoma.Surg Laparosc Endosc. 1995; 5: 444-449PubMed Google Scholar, 4Mack M.G. Straub R. Eichler K. Engelmann K. Zangos S. Roggan A. Woitaschek D. Bottger M. Vogl T.J. Percutaneous MR imaging-guided laser-induced thermotherapy of hepatic metastases.Abdom Imaging. 2001; 26: 369-374Crossref PubMed Scopus (94) Google Scholar, 5Gewiese B. Beuthan J. Fobbe F. Stiller D. Muller G. 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Several studies have shown the effectiveness of these local ablative therapies for the treatment of primary liver cancer.8Ramsey W.H. Wu G.Y. Hepatocellular carcinoma update on diagnosis and treatment.Dig Dis. 1995; 13: 81-91Crossref PubMed Scopus (55) Google Scholar, 9Lin D.Y. Lin S.M. Liaw Y.F. Non-surgical treatment of hepatocellular carcinoma.J Gastroenterol Hepatol. 1997; 12: S319-S328Crossref PubMed Scopus (157) Google Scholar These therapies have also produced survival rates similar to those with surgical resection in the treatment of metastases,7Oshowo A. Gillams A. Harrison E. Lees W.R. Taylor I. Comparison of resection and radiofrequency ablation for treatment of solitary colorectal liver metastases.Br J Surg. 2003; 90: 1240-1243Crossref PubMed Scopus (259) Google Scholar, 10Dodd G.D. Soulen M.C. Kane R.A. Livraghi T. Lees W.R. Yamashita Y. Gillams A.R. Karahan O.I. Rhim H. Minimally invasive treatment of malignant hepatic tumors at the threshold of a major breakthrough.Radiographics. 2000; 20: 9-27Crossref PubMed Scopus (553) Google Scholar, 11Solbiati L. Livraghi T. Goldberg S.N. Ierace T. Meloni F. Dellanoce M. Cova L. Halpern E.F. Gazelle G.S. Percutaneous radio-frequency ablation of hepatic metastases from colorectal cancer long-term results in 117 patients.Radiology. 2001; 221: 159-166Crossref PubMed Scopus (811) Google Scholar, 12Vogl T.J. Straub R. Eichler K. Sollner O. Mack M.G. Colorectal carcinoma metastases in liver laser-induced interstitial thermotherapy—local tumor control rate and survival data.Radiology. 2004; 230: 450-458Crossref PubMed Scopus (227) Google Scholar but a relatively high local recurrence rate has also been reported.11Solbiati L. Livraghi T. Goldberg S.N. Ierace T. Meloni F. Dellanoce M. Cova L. Halpern E.F. Gazelle G.S. Percutaneous radio-frequency ablation of hepatic metastases from colorectal cancer long-term results in 117 patients.Radiology. 2001; 221: 159-166Crossref PubMed Scopus (811) Google Scholar More recent studies have shown that it is possible to improve the local recurrence rate with percutaneous laser ablation under magnetic resonance imaging (MRI) guidance, at least in patients with smaller metastases.4Mack M.G. Straub R. Eichler K. Engelmann K. Zangos S. Roggan A. Woitaschek D. Bottger M. Vogl T.J. Percutaneous MR imaging-guided laser-induced thermotherapy of hepatic metastases.Abdom Imaging. 2001; 26: 369-374Crossref PubMed Scopus (94) Google Scholar, 12Vogl T.J. Straub R. Eichler K. Sollner O. Mack M.G. Colorectal carcinoma metastases in liver laser-induced interstitial thermotherapy—local tumor control rate and survival data.Radiology. 2004; 230: 450-458Crossref PubMed Scopus (227) Google Scholar Thermal ablation methods are poised to become a mainstream treatment option for many patients; approximately 5000 patients were treated with RT ablation in the year 2000 alone.13Rhim H. Dodd G.D. Chintapalli K.N. Wood B.J. Dupuy D.E. Hvizda J.L. Sewell P.E. Goldberg S.N. Radiofrequency thermal ablation of abdominal tumors lessons learned from complications.Radiographics. 2004; 24: 41-52Crossref PubMed Scopus (256) Google Scholar However, randomized studies comparing surgical resection and thermal ablation have yet to be performed. Ultrasound with the therapeutic use of acoustic energy to ablate cancerous lesions offers an exciting and completely noninvasive approach to therapy for primary liver cancer. Focused ultrasound (FUS) beams have been applied as an ablative surgical technique to treat deep tumors for several decades.14Lynn J.G. Zwemer R.L. Chick A.J. Miller A.E. A new method for the generation and use of focused ultrasound in experimental biology.J Gen Physiol. 1942; 26: 179-193Crossref PubMed Scopus (545) Google Scholar, 15Fry W.J. Intense ultrasound in investigations of the central nervous system.Adv Biol Med Phys. 1958; 6: 281-348Crossref PubMed Google Scholar Unlike thermal energy deposition created by RT, lasers, or cryoprobes, the thermal energy produced by FUS sonications lasts for only a few seconds and has a relatively narrow temperature gradient that peaks between 60°C and 80°C. The sharp temperature gradients result in less variable thermal effects in the tissue, and the rapid deposition of thermal energy leads to a peak temperature increase that is mostly independent of cooling by blood flow. These features are especially important for treating tumors in which the vascular pattern is unpredictable. Large tumors can be ablated by targeting sonications at multiple overlapping locations. Without an imaging system that allows for online monitoring of the deposition of ultrasound energy or the creation of induced lesion, it is impossible to predict the precise location of the FUS beam, to monitor the temperature changes, or to control the deposited thermal dose. In the past, these major constraints limited the development of FUS as a noninvasive surgical technique. In recent years, however, integration of FUS with MRI, which allows high-sensitivity tumor detection and the ability to monitor temperature in real time, has increased the interest in FUS ablative therapy and opened the way for several potentially groundbreaking clinical applications.16Jolesz F.A. Hynynen K. Magnetic resonance image-guided focused ultrasound surgery.Cancer J. 2002; 8: S100-S112PubMed Google Scholar The integration of FUS with MRI has resulted in a noninvasive therapy-delivery system that is used for planning, guiding, monitoring, and controlling the therapy for a wide range of applications in the body. Currently, clinical trials have been completed for the treatment of breast fibroadenoma,17Hynynen K. Pomeroy O. Smith D.N. Huber P.E. McDannold N.J. Kettenbach J. Baum J. Singer S. Jolesz F.A. MR imaging-guided focused ultrasound surgery of fibroadenomas in the breast a feasibility study.Radiology. 2001; 219: 176-185Crossref PubMed Scopus (554) Google Scholar breast cancer,18Gianfelice D. Khiat A. Amara M. Belblidia A. Boulanger Y. MR imaging-guided focused US ablation of breast cancer histopathologic assessment of effectiveness—initial experience.Radiology. 2003; 227: 849-855Crossref PubMed Scopus (246) Google Scholar, 19Gianfelice D. Khiat A. Amara M. Belblidia A. Boulanger Y. MR imaging-guided focused ultrasound surgery of breast cancer correlation of dynamic contrast-enhanced MRI with histopathologic findings.Breast Cancer Res Treat. 2003; 82: 93-101Crossref PubMed Scopus (125) Google Scholar, 20Gianfelice D. Khiat A. Boulanger Y. Amara M. Belblidia A. Feasibility of magnetic resonance imaging-guided focused ultrasound surgery as an adjunct to tamoxifen therapy in high-risk surgical patients with breast carcinoma.J Vasc Interv Radiol. 2003; 14: 1275-1282Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar and uterine fibroids.21Tempany C.M. Stewart E.A. McDannold N. Quade B.J. Jolesz F.A. Hynynen K. MR imaging-guided focused ultrasound surgery of uterine leiomyomas a feasibility study.Radiology. 2003; 226: 897-905Crossref PubMed Scopus (536) Google Scholar, 22Stewart E.A. Gedroyc W.M.H. Tempany C.M.C. Quade B.J. Inbar Y. Ehrenstein T. Shushan A. Hindley J.T. Goldin R.D. David M. Sklair M. Rabinovici J. Itzchak Y. McDannold N. Hynynen K. Jolesz F.A. Oestmann J.W. Yagel S. Revel A. Gomori M. Regan L. Focused ultrasound treatment of uterine fibroids safety and feasibility of a noninvasive thermoablative technique.Am J Obstet Gynecol. 2003; 189: 48-54Abstract Full Text Full Text PDF PubMed Scopus (384) Google Scholar These successful applications and the large number of systematic studies with experimental animal tumor models clearly suggest that MRI-guided FUS has significant potential. Among the promising future applications, the noninvasive thermal ablation of hepatocellular carcinoma and other liver tumors is particularly exciting. There have been several experimental and clinical investigations of noninvasive FUS treatment of liver tumors. In animals, both tumor-bearing and normal liver lobes have been treated with high-intensity focused beam ultrasound, and histopathologic evaluation of the ablated lesions has consistently shown sharply demarcated, homogeneous coagulative necrosis with irreversible tumor cell death and severe damage to tumor blood vessels at the level of the microvasculature within the targeted region.23Fry F.J. Johnson L.K. Tumor irradiation with intense ultrasound.Ultrasound Med Biol. 1978; 4: 337-341Abstract Full Text PDF PubMed Scopus (134) Google Scholar, 24Yang R. Reilly C.R. Rescorla F.J. Faught P.R. Sanghvi N.T. Fry F.J. Franklin T.D.J. Lumeng L. Grosfeld J.L. High-intensity focused ultrasound in the treatment of experimental liver cancer.Arch Surg. 1991; 126: 1002-1009Crossref PubMed Scopus (166) Google Scholar, 25Prat F. Centarti M. Sibille A. Abou el Fadil F.A. Henry L. Chapelon J.Y. Cathignol D. Extracorporeal high-intensity focused ultrasound for VX2 liver tumors in the rabbit.Hepatology. 1995; 21: 832-836PubMed Google Scholar, 26Chen L. ter Haar G.R. Robertson D. Bensted J.P. Hill C.R. Histological study of normal and tumor-bearing liver treated with focused ultrasound.Ultrasound Med Biol. 1999; 25: 847-856Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar Clinical trials have also been reported with somewhat encouraging results by using only diagnostic ultrasound targeting without temperature monitoring. The feasibility of FUS surgery in liver was shown by Vallancien et al.,27Vallancien G. Harouni M. Veillon B. Mombet A. Prapotnich D. Bisset J.M. Bougaran J. Focused extracorporeal pyrotherapy feasibility study in man.J Endourol. 1992; 6: 173-180Crossref Scopus (106) Google Scholar who treated 2 patients before surgical resection. Recently, Visioli et al.28Visioli A.G. Rivens I.H. ter Haar G.R. Horwich A. Huddart R.A. Moskovic E. Padhani A. Glees J. Preliminary results of a phase I dose escalation clinical trial using focused ultrasound in the treatment of localised tumours.Eur J Ultrasound. 1999; 9: 11-18Crossref PubMed Scopus (130) Google Scholar reported on FUS treatments of liver tumors in 6 patients and showed that the procedure can be performed on conscious patients with minimal sedation. In those treatments, patients were trained to hold their breath in a repeatable fashion. In these studies, the ultrasound imaging transducer was removed during the therapeutic sonications, so online feedback could not be obtained. The most experience has come from China, where a large number of patients have been treated under general anesthesia and with online ultrasound guidance.29Wu F. Chen W.Z. Bai J. Zou J.Z. Wang Z.L. Zhu H. Wang Z.B. Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound.Ultrasound Med Biol. 2001; 27: 1099-1106Abstract Full Text Full Text PDF PubMed Scopus (333) Google Scholar Handheld FUS probes are also being developed for the intraoperative treatment of liver cancer during open procedures. A way to substantially improve current thermal ablation techniques would be to provide a means for quantitative image guidance for reliable monitoring of the progress of the ablation. Currently, thermal ablation procedures are performed under ultrasound, computerized tomography, or MRI guidance or, in some situations, no guidance at all. Although each imaging method has its relative advantages, MRI offers the most promise as a guidance method because it provides superior soft tissue contrast and an ability to detect the ablated area and to monitor the procedure through temperature-sensitive sequences. The ability to quantify the temperature increase during the procedure with MRI offers perhaps the best level of control, and currently only MRI has been shown to provide reliable temperature monitoring in vivo. A growing number of studies have shown that MRI-based thermometry and thermal dosimetry techniques can accurately predict the threshold for tissue damage and the spatial extent of the ablated volume.30Chung A.H. Jolesz F.A. Hynynen K. Thermal dosimetry of a focused ultrasound beam in vivo by magnetic resonance imaging.Med Phys. 1999; 26: 2017-2026Crossref PubMed Scopus (168) Google Scholar, 31Sherar M.D. Moriarty J.A. Kolios M.C. Chen J.C. Peters R.D. Ang L.C. Hinks R.S. Henkelman R.M. Bronskill M.J. Kucharcyk W. Comparison of thermal damage calculated using magnetic resonance thermometry, with magnetic resonance imaging post-treatment and histology, after interstitial microwave thermal therapy of rabbit brain.Phys Med Biol. 2000; 45: 3563-3576Crossref PubMed Scopus (76) Google Scholar, 32Hazle J.D. Stafford R.J. Price R.E. Magnetic resonance imaging-guided focused ultrasound thermal therapy in experimental animal models correlation of ablation volumes with pathology in rabbit muscle and VX2 tumors.J Magn Reson Imaging. 2002; 15: 185-194Crossref PubMed Scopus (71) Google Scholar, 33McDannold N. Vykhodtseva N. Jolesz F.A. Hynynen K. MRI investigation of the threshold for thermally induced blood-brain barrier disruption and brain tissue damage in the rabbit brain.Magn Reson Med. 2004; 51: 913-923Crossref PubMed Scopus (150) Google Scholar, 34Chen L. Wansapura J.P. Heit G. Butts K. Study of laser ablation in the in vivo rabbit brain with MR thermometry.J Magn Reson Imaging. 2002; 16: 147-152Crossref PubMed Scopus (60) Google Scholar Most tissue parameters that make up the contrast in MRI are temperature sensitive. The T1 relaxation time,35Parker D.L. Smith V. Sheldon P. Crooks L.E. Fussell L. Temperature distribution measurements in two-dimensional NMR imaging.Med Phys. 1983; 10: 321-325Crossref PubMed Scopus (269) Google Scholar the diffusion coefficient,36Le Bihan D. Delannoy J. Levin R.L. Temperature mapping with MR imaging of molecular diffusion application to hyperthermia.Radiology. 1989; 171: 853-857PubMed Google Scholar and the proton resonant frequency shift (PRF)37Ishihara Y. Calderon A. Watanabe H. Okamoto K. Suzuki Y. Kuroda K. A precise and fast temperature mapping using water proton chemical shift.Magn Reson Med. 1995; 34: 814-823Crossref PubMed Scopus (905) Google Scholar have all been tested for monitoring temperature changes during thermal therapy. However, only the PRF-based methods have been shown to be tissue-type independent,38Peters R.D. Hinks R.S. Henkelman R.M. Ex vivo tissue-type independence in proton-resonance frequency shift MR thermometry.Magn Reson Med. 1998; 40: 454-459Crossref PubMed Scopus (302) Google Scholar linear above the tissue coagulation threshold,39Kuroda K. Chung A.H. Hynynen K. Jolesz F.A. Calibration of water proton chemical shift with temperature for noninvasive temperature imaging during focused ultrasound surgery.J Magn Reson Imaging. 1998; 8: 175-181Crossref PubMed Scopus (79) Google Scholar and independent of the thermal history of the tissue.38Peters R.D. Hinks R.S. Henkelman R.M. Ex vivo tissue-type independence in proton-resonance frequency shift MR thermometry.Magn Reson Med. 1998; 40: 454-459Crossref PubMed Scopus (302) Google Scholar These properties, and the superior temperature sensitivity of PRF,40Wlodarczyk W. Hentschel M. Wust P. Noeske R. Hosten N. Rinneberg H. Felix R. Comparison of four magnetic resonance methods for mapping small temperature changes.Phys Med Biol. 1999; 44: 607-624Crossref PubMed Scopus (118) Google Scholar make it the only method that can accurately quantify temperature changes during high-temperature thermal ablation. Currently, PRF can be measured rapidly only by using phase imaging of a gradient echo sequence.37Ishihara Y. Calderon A. Watanabe H. Okamoto K. Suzuki Y. Kuroda K. A precise and fast temperature mapping using water proton chemical shift.Magn Reson Med. 1995; 34: 814-823Crossref PubMed Scopus (905) Google Scholar Unfortunately, because of inhomogeneities in the magnetic field, image subtractions are necessary and make this method sensitive to motion. Nevertheless, several new techniques have been developed to correct for motion, and they should be available soon for clinical testing.41Vigen K.K. Daniel B.L. Pauly J.M. Butts K. Triggered, navigated, multi-baseline method for proton resonance frequency temperature mapping with respiratory motion.Magn Reson Med. 2003; 50: 1003-1010Crossref PubMed Scopus (149) Google Scholar, 42Weidensteiner C. Kerioui N. Quesson B. de Senneville B.D. Trillaud H. Moonen C.T. Stability of real-time MR temperature mapping in healthy and diseased human liver.J Magn Reson Imaging. 2004; 19: 438-446Crossref PubMed Scopus (79) Google Scholar, 43Rieke V. Vigen K.K. Sommer G. Daniel B.L. Pauly J.M. Butts K. Referenceless PRF shift thermometry.Magn Reson Med. 2004; 51: 1223-1231Crossref PubMed Scopus (242) Google Scholar Because of its reduced motion sensitivity and relative simplicity, T1-weighted imaging has been the method of choice for monitoring thermal ablation in the liver.6Vogl T.J. Straub R. Eichler K. Woitaschek D. Mack M.G. Malignant liver tumors treated with MR imaging-guided laser-induced thermotherapy experience with complications in 899 patients (2,520 lesions).Radiology. 2002; 225: 367-377Crossref PubMed Scopus (201) Google Scholar T1-weighted images allow for monitoring the extent of the heating in tissue online, but this has not proven to be predictive of the extent of the thermal damage and is thus of limited usefulness. Novel contrast agents that are temperature activated may also provide a solution both for online delineation of the area that has received a sufficient temperature increase and for tracking this area in a moving organ, such as the liver.44Fossheim S.L. Il'yasov K.A. Hennig J. Bjornerud A. Thermosensitive paramagnetic liposomes for temperature control during MR imaging-guided hyperthermia in vitro feasibility studies.Acad Radiol. 2000; 7: 1107-1115Abstract Full Text PDF PubMed Scopus (90) Google Scholar In vivo animal tests in the liver of this agent have recently been reported, and an example from that work showing an enhanced lesion is shown in Figure 1.45McDannold N. Fossheim S.L. Rasmussen H. Martin H. Vykhodtseva N. Hynynen K. Heat-activated liposomal MR contrast agent initial in vivo results in rabbit liver and kidney.Radiology. 2004; 230: 743-752Crossref PubMed Scopus (70) Google Scholar Phased-array transducers allow for the creation of larger focal spots and rapid control of the position of the focus, and they could even provide the ability to target the beam through the rib cage. These devices consist of an array of many small transducer elements, each driven by a separate RF amplifier. By controlling the relative phase of the driving signals, the position and shape of the focus can be rapidly controlled. Such transducers will likely be critical for the widespread implementation of FUS surgery in liver, because of the large volumes that often need to be ablated and the need to track the moving target. Large-scale MRI-compatible phased arrays have been developed and tested in the liver in animals. By using MRI-based temperature monitoring, a 256-element, continuous-wave large-scale ultrasonic phased array has been used to thermally coagulate deep-seated liver tissue in pigs.46Daum D.R. Smith N.B. King R. Hynynen K. In vivo demonstration of noninvasive thermal surgery of the liver and kidney using an ultrasonic phased array.Ultrasound Med Biol. 1999; 25: 1087-1098Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar The transducer was driven by a MRI-compatible RT amplifier system that could drive up to 512 channels with independent phase and amplitude control.47Daum D.R. Buchanan M.T. Fjield T. Hynynen K. Design and evaluation of a feedback based phased array system for ultrasound surgery.IEEE Trans Ultrason Ferroelectr Freq Contr. 1998; 45: 431-438Crossref PubMed Scopus (69) Google Scholar In this study, focal lesion volumes greater than 0.5 cm3 in kidney and 2 cm3 in liver were formed from a single 20-second sonication. Thermal imaging was performed while breathing was halted, and it was possible to map the temperature increase without major artifacts (Figure 2). A commercially available MRI-compatible large-scale phased-array system (ExAblate 2000; InSightec Ltd., Haifa, Israel) has also been developed. This system is fully integrated with a clinical MRI scanner and provides online control and feedback during FUS surgery. The ability of the system to treat deep targets in soft tissue was first verified in animal experiments at Brigham and Women's Hospital in Boston, and since then it has been used to treat uterine fibroids at sites around the world.21Tempany C.M. Stewart E.A. McDannold N. Quade B.J. Jolesz F.A. Hynynen K. MR imaging-guided focused ultrasound surgery of uterine leiomyomas a feasibility study.Radiology. 2003; 226: 897-905Crossref PubMed Scopus (536) Google Scholar, 22Stewart E.A. Gedroyc W.M.H. Tempany C.M.C. Quade B.J. Inbar Y. Ehrenstein T. Shushan A. Hindley J.T. Goldin R.D. David M. Sklair M. Rabinovici J. Itzchak Y. McDannold N. Hynynen K. Jolesz F.A. Oestmann J.W. Yagel S. Revel A. Gomori M. Regan L. Focused ultrasound treatment of uterine fibroids safety and feasibility of a noninvasive thermoablative technique.Am J Obstet Gynecol. 2003; 189: 48-54Abstract Full Text Full Text PDF PubMed Scopus (384) Google Scholar These treatments of these large tumor volumes have shown that the system can safely target deep targets (up to approximately 10 cm deep) in the clinic under MRI guidance. Recently, a Food and Drug Administration panel recommended approval of this device for uterine fibroid treatments. This system has undergone recent tests for liver ablation. Experimental work on pigs with this system has shown that MRI-guided FUS seems to provide safe thermal ablation in liver.48Inbar Y. Hananel A. Freundlich D. Yagel R. Grunfeld A. Papa M. Kopelman D. Controlled apnea for focused ultrasound ablation of liver tissue—animal model.in: Proceedings of the Twelfth Meeting of the International Society for Magnetic Resonance in Medicine, Kyoto, Japan. ISMRM, Berkeley, CA2004: 2697Google Scholar In those tests, the ablation system was integrated with a respirator so that the liver was still enough to provide accurate thermal imaging with the PRF-based method. Discrete large tissue volumes could be ablated in the liver with the device, with verification both from contrast-enhanced MRI and pathology (Figure 3, Figure 4). These encouraging results will, it is hoped, soon lead to clinical tests with this device. The increased accuracy of treatment with thermal mapping combined with the cost savings of ambulatory treatment may lead to significant changes in the treatment of these common malignant tumors.Figure 4(A) Thermal ablation with FUS in the liver in pigs using the Exablate 2000 device (InSightec, Haifa, Israel). (B) Gross pathology of the thermal lesion. (C) The areas of macroscopic damage show a clear 'zonal' pattern, or 'geographic' pattern of necrosis (original magnification, ×12.5; arrow on border between preserved and necrotic). (D) The border between the preserved and necrotic liver parenchyma is vascularized and shows an isolated residual viable hepatocytes (original magnification, ×100).View Large Image Figure ViewerDownload (PPT) MRI-guided FUS provides targeted destruction in breast tumors and uterine leiomyomas and has an excellent safety profile.17Hynynen K. Pomeroy O. Smith D.N. Huber P.E. McDannold N.J. Kettenbach J. Baum J. Singer S. Jolesz F.A. MR imaging-guided focused ultrasound surgery of fibroadenomas in the breast a feasibility study.Radiology. 2001; 219: 176-185Crossref PubMed Scopus (554) Google Scholar, 18Gianfelice D. Khiat A. Amara M. Belblidia A. Boulanger Y. MR imaging-guided focused US ablation of breast cancer histopathologic assessment of effectiveness—initial experience.Radiology. 2003; 227: 849-855Crossref PubMed Scopus (246) Google Scholar, 19Gianfelice D. Khiat A. Amara M. Belblidia A. Boulanger Y. MR imaging-guided focused ultrasound surgery of breast cancer correlation of dynamic contrast-enhanced MRI with histopathologic findings.Breast Cancer Res Treat. 2003; 82: 93-101Crossref PubMed Scopus (125) Google Scholar, 20Gianfelice D. Khiat A. Boulanger Y. Amara M. Belblidia A. Feasibility of magnetic resonance imaging-guided focused ultrasound surgery as an adjunct to tamoxifen therapy in high-risk surgical patients with breast carcinoma.J Vasc Interv Radiol. 2003; 14: 1275-1282Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar, 21Tempany C.M. Stewart E.A. McDannold N. Quade B.J. Jolesz F.A. Hynynen K. MR imaging-guided focused ultrasound surgery of uterine leiomyomas a feasibility study.Radiology. 2003; 226: 897-905Crossref PubMed Scopus (536) Google Scholar, 22Stewart E.A. Gedroyc W.M.H. Tempany C.M.C. Quade B.J. Inbar Y. Ehrenstein T. Shushan A. Hindley J.T. Goldin R.D. David M. Sklair M. Rabinovici J. Itzchak Y. McDannold N. Hynynen K. Jolesz F.A. Oestmann J.W. Yagel S. Revel A. Gomori M. Regan L. Focused ultrasound treatment of uterine fibroids safety and feasibility of a noninvasive thermoablative technique.Am J Obstet Gynecol. 2003; 189: 48-54Abstract Full Text Full Text PDF PubMed Scopus (384) Google Scholar FUS is potentially the first completely noninvasive surgical therapy for hepatocellular cancer. The prevalence of this cancer and its significant effects on quality of life suggest that the future treatment of liver cancer would be very different if effective noninvasive therapy were possible. The MRI-based thermal mapping not only enhances safety, but also should give enhanced efficacy of thermal ablations. Further studies will be important to document the feasibility and cost-effectiveness of this new therapy modality. Several problems need to be overcome before MRI-guided FUS can be used clinically on a widespread basis. First, the problem of motion needs to be overcome, both for tracking the targeting during the treatment and for allowing the MRI thermal imaging to be performed. Second, the area that can be targeted needs to be increased. Currently, the rib cage blocks much of the liver from the ultrasound beam. Next-generation phased-array transducers and advanced MRI methods are currently being developed for these needs.