IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 25, NO. 6, JUNE 2006 723 MRI-Guided Focused Ultrasound: Methodology and Applications Steffen L. Hokland* , Michael Pedersen, Rares Salomir, Bruno Quesson, Hans Stødkilde-Jørgensen, and Chrit T. W. Moonen Abstract—Focused ultrasound is very well suited for inducing noninvasive local hyperthermia. Since magnetic resonance imaging (MRI) may be employed to obtain real-time temperature maps noninvasively the combination of these two technologies offers great advantages specifically aimed toward oncological studies. Real-time identification of the target region and accurate control of the temperature evolution during the treatment has now become possible. Thermal ablation of pathological tissue, local drug delivery using thermosensitive micro-carriers and controlled transgene expression using thermosensitive promoters have recently been demonstrated with this unique technology. Based on these experiments combined focused ultrasound and MRI thermometry holds promise for future oncological diagnos- tics and treatment. In this paper, we review some of the recent methodological developments as well as experimental and first clinical studies using this approach. Index Terms—Automatic temperature control, focused ultra- sound, high-intensity focused ultrasound, hyperthermia, MRI thermometry, thermal ablation, thermotherapy. I. INTRODUCTION U LTRASOUND (US) may propagate safely through biolog- ical tissue even at high-intensity levels. However, if the beam is tightly focused, energy may be deposited in a small focal region, making focused ultrasound (FUS) an attractive method for minimally invasive surgery. Hence, application of FUS surgery has been studied for more than half a century (ac- counts of the historical development of therapeutic ultrasound are found in [1] and [2]). In 1942, Lynn et al. [3] reported focal lesions in mammalian brain tissue, showing, however, only modest success. Improving this methodology—primarily by removing the piece of skull in- tersecting the US beam path—Fry et al. [4], [5] and Lele [6], [7] performed an extensive research on neurological applications of high-intensity FUS (HIFU). The proposition by Burov in 1956 [8] to utilize HIFU as a modality for cancer treatment spurged Manuscript received October 14, 2005; revised February 23, 2006. The work of S. L. Hokland was supported in pat by the Helga og Peter Kornings Fond and the Danish Medical Research Council. This work was supported in part by the Danish Medical Research Council under Grant 22-05-0519 BMP-MP. Asterisk indicates corresponding author. *S. L. Hokland is with the MR-Research Centre, Institute of Clinical Medicine, Aarhus University Hospital, Skejby, DK-8200 Aarhus N, Denmark (e-mail: hokland@mr.au.dk). M. Pedersen and H. Stødkilde-Jørgensen are with the MR-Research Centre, Institute of Clinical Medicine, Aarhus University Hospital, Skejby, DK-8200 Aarhus N, Denmark. R. Salomir is with the INSERM Unit 556, 69424 Lyon Cedex 03, France. B. Quesson and C. T. W. Moonen are with the Imagerie Moléculaire et Fonc- tionelle: de la Physiologie á la Thérapie, ERT CNRS/University Victor Saignat, University of Bordeaux 2, F-33076 Bordeaux, France. Digital Object Identifier 10.1109/TMI.2006.873296 a series of investigations into this new area. These initial efforts suffered, however, greatly from the lack of reliable treatment monitoring and guidance. The advent of modalities capable of guidance of FUS such as magnetic resonance imaging (MRI) and US, has opened a new avenue of FUS-research. However, despite the substantial amount of published work as well as clin- ical trials reported between 1958 [9] and today, FUS is yet to be implemented in daily clinical practice. II. METHODS The purpose of this paper is to review recent methodological developments, pioneering in vivo feasibility studies and clinical trials performed up to date. There is a large number of oncolog- ical applications using FUS, and in the present review we have chosen to concentrate on FUS guided by MRI. Consequently, we will not review the extensive work performed with HIFU without MRI-guidance. For a comprehensive review of methodology and advances within this field, see [10] and references therein. The methodological development section in this review focuses on the real-time feed-back control of the temperature, based on MRI-derived thermometry. Coupling of FUS and MRI-guidance has currently been employed for three main applications in vivo. • Thermal ablation in tissue, using thermal doses which in- duce widespread coagulative necrosis. • Localized gene expression control based on heat-activated promoters using nondestructive thermal doses, and. • Local drug delivery, also using nondestructive thermal doses. A. Nomenclature and Abreviations No common nomenclature and abbreviations have yet been established in this field. 1 Hence, considering the lack of a com- monly accepted set of abbreviations, the authors suggest the ab- breviations presented in Table I. In the following, Thermotherapy will refer to the entire field of research employing elevated temperatures as a means of pro- moting a therapeutic effect. Hyperthermia will refer to appli- cation of “moderate” thermal doses, which when applied ex- clusively may be considered to be nonlethal. Thermal ablation will refer to application of lethal thermal doses resulting in wide spread coagulative necrosis in the affected area. B. Selection of Cases In this review, one study—considered to be the most rele- vant in terms of treatment efficacy and clinical potential, or 1 For example, “FUS” is employed in literature to refer to both “focused ul- trasound” (e.g., [11]) as well as “focused ultrasound surgery” (e.g., [10]). 0278-0062/$20.00 © 2006 IEEE