Percutaneous image-guided ablative therapies using thermal energy sources such as radiofrequency, microwave, high intensity focused ultrasound, and laser have received much recent attention as minimally-invasive strategies for the treatment of focal malignant disease. Potential benefits of these techniques include the ability to ablate tumor in non- surgical candidates, reduced morbidity as compared to surgery, and the potential to perform the procedure on an outpatient basis. This manuscript proposes a unified framework using the `Bioheat equation' for discussing aspects of thermal ablation therapies as they relate to the treatment of focal malignancies. Briefly, these include an understanding of under which conditions heat induces cellular damage, the types of energy sources which can supply this heat, and tissue properties such as perfusion mediated cooling which modify tissue response to the heat deposited. Additionally, the various facets of diagnostic imaging which are required to direct thermal ablation therapy are discussed. These include modalities which can be used for targeting of the lesion to be treated, determination of an optimal treatment plan, and assessment of results at long term follow-up.

Thermal treatment to avoid a surgical procedure involves a variety of energy sources. In several sites, radiofrequency energy is used as a source of thermal treatment. In the course of controlling lesion volume and shape during therapy, a number of sizes and shapes of applicators can be used as well as cooling or power pulsing to control or increase lesion size. Multiple sources are also used with monopolar or sesquipolar radiofrequency power delivery to enlarge the treatment volume. Following extensive in-vitro and in-vivo testing to optimize lesion size with time, power, and device, a simulation was set up to correlate theoretical predictions with experimental results with and without blood flow. A finite element model was applied to simulate the electric field and by using the bioheat equation, a thermal profile over time was established for various device parameters used in the experiments. The damage integral was used to estimate lesion size of irreversible damage. These results were compared to experimental results to verify the model's accuracy in predicting lesion size of both in-vitro and in-vivo experiments.

The purpose of this study was to investigate performance characteristics of a catheter-based ultrasound applicator intended for circumferential ablation of cardiac tissue. The catheter design integrates a cylindrical ultrasound transducer within a distendable water filled balloon in order to produce circumferential lesions at sites in the atria (i.e., pulmonary vein ostia), intended for treatment of certain atrial arrhythmias. Biothermal simulations were used to investigate thermal lesion depths corresponding to variations in applied power, duration, balloon diameter, and acoustic efficiency. Prototype applicators of varying frequency (7 - 12 MHz) and balloon diameter were constructed and characterized using measurements of acoustic efficiency and rotational beam plots. In vitro studies were performed in freshly excised beef hearts to characterize the radial penetration, axial length, and angular uniformity of thermal lesions produced by these applicators. Selected applicators were tested in vivo within pulmonary veins, coronary sinus, and atrial appendage of canine and porcine hearts. These preliminary efforts have indicated that circumferential ablation of cardiac tissue using ultrasound balloon catheters is feasible, and devices between 7 - 12 MHz with balloon diameters of 1.5 - 2.0 cm are capable of producing uniform lesions between 1 - 5 mm depth or greater for treatment durations of 120 seconds or less.

The use of internally-cooled, direct-coupled interstitial ultrasound applicators as a means of providing controlled and directed thermal therapy was investigated. Applicators were constructed using tubular ultrasound sources (1.5 - 2.5 mm OD) with active acoustic zones of 90 degree(s), 200 degree(s), 270 degree(s), and 360 degree(s) (single and multiple transducers). Cooling of the inner transducer surface was accomplished by the flow of chilled air or an integrated water mechanism. Thermal performance of the applicators was characterized through high temperature heating trials in vivo (porcine thigh muscle and liver) and in vitro (bovine liver). Both air-cooled and water-cooled applicators produced well- defined angular directional heating, with coagulated zones corresponding to the active sector of the transducer. Axial collimation and control of heating along the length of the applicator was also demonstrated using multiple transducer elements. Thermal penetration and extent of coagulation was reproducible and controlled with sonication time and power, extending radially 12 - 22 mm for 1 - 5 minutes. Directly of lesion shapes (both angular and axial) was found to remain characteristically similar at different heating times. This enhanced thermal penetration and improved control of directional heating with internal cooling shows great potential for treatment of localized tumors in prostate, brain, and liver.

This research represents an experimental investigation of the use of interstitial catheter-cooled ultrasound applicators in various treatment strategies for the management of localized prostate cancer and benign prostatic hyperplasia. The anticipated clinical approaches under consideration were: (1) Ultrasound Interstitial Thermal therapy (USITT) alone for treatment of the whole gland, (2) high dose rate (HDR) brachytherapy with USITT to treat local recurrences or extracapsular extensions of the disease, and (3) sequence HDR brachytherapy and hyperthermia. Directional multielement catheter-cooled ultrasound applicators were fabricated using cylindrical piezoceramic transducers which can be inserted into 13 or 14 gage catheters. The applicators were characterized through measurements of acoustic power output, and beam profile distributions in degassed water. Thermal lesion formation studies were performed in an in vitro setup using fresh beef muscle. Various implant strategies were evaluated for the ability to control the temperature distribution within a pre-determined volume of tissue. Lesions extending more than 15 mm from the applicator surface were generated within 5 minutes of heating. Preliminary results from this study demonstrate the versatility of catheter-cooled interstitial ultrasound applicators, and their potential to provide controlled thermal therapy in the prostate.

A pair of microwave applicators was developed to produce controlled elevation of temperature in the prostate. One applicator was designed for placement in the urethra; it has a diameter of 6 mm and is flexible. This applicator incorporates a choked, resonant microwave dipole with an omnidirectional heating pattern and an air cooling system to control the temperature of the urothelium. The second applicator was designed for placement in the rectum; it has a diameter of 18 mm and is rigid. It incorporates an eccentric, choked, resonant microwave dipole that radiates toward the prostate with a front-to-back power ratio of about twenty. An air cooling system controls the temperature of the rectal mucosa. The applicators are driven at 915 MHz with a phase difference chosen to produce the maximum temperature in the central prostate. We heated the prostates of eight canine subjects with the transurethral and transrectal applicators. After one or two months of followup in four subjects, the prostates and surrounding tissues were evaluated histologically. We present experimental measurements of the power deposition patterns of the applicators and the 3D temperature distributions in vivo, and we correlate the thermal dose with histopathological observations.

The authors have been studying thin coaxial-slot antennas for minimally invasive microwave thermal therapy, particularly, microwave interstitial hyperthermia and microwave coagulation therapy (MCT). In hyperthermia treatment, it is important to keep tumor temperature between 42 and 45 degree(s)C without overheating the surrounding normal tissue. Two different feeding ways to antenna elements are presented as practical and effective heating techniques. One is proper combination of coherent and incoherent feedings. The other is on-off power control. In the MCT treatment, however, tumors have to be heated up to at least 60 degree(s)C to coagulate cancer cells but less than 100 degree(s)C to avoid evaporation. The temperature rise in the tumor is so large that the temperature dependence of electrical properties of the tissue should be taken into account. The electrical properties of liver tissue were measured for various temperatures. Temperature distributions around the antenna inserted into the liver are simulated by using the FDTD method and the FDM (Finite Difference Method) where the temperature dependence of electrical properties of the tissue is considered.

Qualitative and quantitative pathologic techniques can be used for (1) mapping of thermal injury, (2) comparisons lesion sizes and configurations for different instruments or heating sources and (3) comparisons of treatment effects. Concentric zones of thermal damage form around a single volume heat source. The boundaries between some of these zones are distinct and measurable. Depending on the energy deposition, heating times and tissue type, the zones can include the following beginning at the hotter center and progressing to the cooler periphery: (1) tissue ablation, (2) carbonization, (3) tissue water vaporization, (4) structural protein denaturation (thermal coagulation), (5) vital enzyme protein denaturation, (6) cell membrane disruption, (7) hemorrhage, hemostasis and hyperhemia, (8) tissue necrosis and (9) wound organization and healing.

Optoacoustic monitoring of thermally-induced damage in tissues in real time is proposed as a mean for controlling the extent of tissue coagulation in human organs, such as liver, prostate, myocardium, breast, and brain. This technique can potentially provide fast and accurate feedback information during tumor thermal coagulation by interstitial delivery of laser, ultrasonic, radiofrequency, and microwave radiation or conductive and convective heating. Amplitude and temporal characteristics of optoacoustic signals are dependent on optical and thermophysical properties of tissues. Changes in tissue optical properties during coagulation can be detected by measuring and analyzing the amplitude and temporal characteristics of the optoacoustic signals. We performed studies on optoacoustic monitoring of coagulation by CW Nd:YAG laser interstitial irradiation and conductive heating. Q-switched Nd:YAG laser pulses were used as a probing radiation to obtain optoacoustic pressure profiles and images. Our preliminary studies suggest that the laser optoacoustic technique is capable of detecting thermally-induced changes in optical properties of liver, myocardium, and prostate. The major merits of the laser optoacoustic monitoring of tissue coagulation include high contrast provided by changes in tissue optical properties, capability to perform real-time measurements, and high spatial resolution.

Accurate detection of the full extent of lethal thermal injury during and immediately after heating in interstitial thermal therapy is necessary to control the treatment volume while conserving surrounding tissues. A red zone of thermal injury forms in most tissues within thirty seconds as a result of physiologic response to heat in vivo. The red zone is formed by accumulation of blood due to hemostasis, hemorrhage and hyperhemia. The distinct outer boundary of this zone has been found to correspond to the outer boundary of tissue necrosis in rat livers examined 3 days after thermal coagulation. We have developed a minimally invasive fiberoptic probe that can detect this boundary using changes in white light absorption spectra of hemoglobin compared to native tissue. Decreased reflected light intensity marks the development of the outer boundary of the red thermal damage zone that is a hallmark of the full extent of lethal thermal damage.

This report describes preliminary work on the use of signal processing of backscattered ultrasound data for characterizing tissue regions undergoing thermal therapy. The long term objective is to test the hypothesis that pulse-echo ultrasound date from treated tissue, with appropriate signal processing, can provide useful parameters for assessment of tissue state during and after undergoing thermal coagulative therapy. One very promising tissue parameter is tissue attenuation which is known to change drastically in tissues subject to coagulative necrosis. This report presents experimental in-vitro data that strongly support the above hypothesis. Statistical methods for characterization of reversible and irreversible changes in tissue state appear to hold the most promise for providing a solution to this problem.

Magnetic resonance imaging (MRI) can be used to noninvasively detect temperature changes in tissue. Several MR measurable parameters have been shown to have temperature coefficients with sufficient sensitivity to be useful for application in thermal therapy (Parker 1983, LeBihan 1989, Ishihara 1995). Consequently, there have been several reports of the use of MRI to guide, monitor or assess thermal therapeutic procedures (Hynynen 1996, Carter 1998). Most of these applications have been associated with thermal ablation which involves high tissue temperature (< 6OC) and small volumes. In these procedures, a highly localized energy distribution is induced in the target volume for a period of several seconds. Rapid imaging techniques can localize the energy distribution and track the treatment volume. These energy distributions are produced using focused ultrasound (US), lasers, or radiofrequency (RF) electrodes. Other applications are geared to produce elevated temperatures (< 50') for longer time periods in larger volumes of tissue in an effort to sensitize tissue to other cytotoxic agents such as ionizing radiation and drugs. These procedures require tissues at elevated temperatures for times on the order of tens of minutes to hours (Carter 1998). For these procedures, microwave (MW) RF and US sources can be used. This paper concerns this latter application and is specific to malignant target sites that are located in the lower extremity of the body (Leopold 1989, Carter 1998). The heating technique used in combination with MRI is described

The low frequency (<EQ 10 MHz) electrical impedance of a volume of tissue is sensitive to its temperature and its response to heating and other stresses. Major tissue changes, such as those accompanying higher hyperthermic temperatures or prolonged ischemia, and not necessarily reversible unless detected in time to alleviate the stress. Thus, it is imperative to assess the temperature and/or tissue changes in real-time if adequate monitoring of thermal treatments is to be accomplished. To this end, we focus on the use of electrical impedance measurements of a volume of tissue at temperatures in the hyperthermia region (<EQ 47 degree(s)C) where tissue responses occur at a rate which is controllable. First, using well controlled freshly excised tissue data, we examine the prototypical impedance changes associated with the early and later stages of necrosis within a tissue subjected to heating and ischemia. Then, impedance measurements made non-invasively, in vivo, in HT29 tumors are used to demonstrate the differences caused by different thermal treatments and from differences in the ischemic condition of the tissues. The electrical impedance signature of the tumors were indicative of certain cellular-level changes occurring within the tumors. The histological findings corroborate the ability of the electrical impedance to report these cellular changes. The changes are consistent with the cells proceeding along the path of necrosis. Initial cell swelling appears to be largely due to ischemia, and the cell lysing and tumor response to the defined period of heating.

Hyperthermia therapy of superficial skin disease has proven clinically useful, but current heating equipment is clumsy and technically inadequate for many patients. The present effort describes a dual purpose multielement conformal array microwave applicator that is fabricated from flexible printed circuit board (PCB) material to facilitate heating of large surface areas overlying contoured anatomy. Preliminary studies document the feasibility of combining concentric spiral microstrip antennas within multilayer PCB material in order to achieve tissue heating simultaneously with non-invasive thermometry by radiometric sensing of blackbody radiation from the target tissue under the applicator. Results demonstrate that superficial tissue regions may be heated uniformly above 50% of SAR_max out to the periphery of 915 MHz conformal array applicators made from arrays of Dual Concentric Conductor apertures. Finally the data clearly demonstrate that separate complimentary antenna structures may be combined together in thin and lightweight conformal arrays to provide heating simultaneously with microwave radiometry based temperature monitoring of superficial tissue.

The use of diagnostic ultrasound as a tool for 2D noninvasive temperature imaging is described. The mathematical and physical properties behind this new approach are given. It is shown that temperature changes on the order of 0.1 degree(s)C can be detected with a spatial resolution on the order of 1 mm. It is further shown that temperature variations can be tracked up to nearly 20 degree(s)C from baseline for relatively long durations. The advantages and limitations of this new temperature imaging method are discussed. Its application to guidance and control of thermal surgery is discussed and illustrated with examples.

An ultrasonic system capable of Lateral Power Conformability, Penetration Depth Control (PDC), and the ability to deliver hyperthermia concomitantly with external beam radiation is being developed. PDC is achieved by simultaneously insonating with beams of low (1 MHz) and high (5 MHz) frequency. This paper presents a sono-thermal numerical evaluation of the impact of PDC on thermal dose in the treatment of chest wall volumes. The main goal is to assess the potential advantages of impedance-mismatched interface depth-mapping, using therapy transducers in A-scan mode, to select optimal relative output intensities of the beams as a function of bone and lung depths. Simulation results for a representative chest wall anatomy showed that there exists a strong relationship between optimal relative output intensities and bone/lung depth for maximum thermal dose and minimum muscle-bone interface temperature. Consequently, interface depth-mapping prior to a dual- frequency ultrasound hyperthermia treatment would provide patient-specific data useful for selecting PDC parameters that maximize thermal dose and minimize bone heating.

Advantages of MR imaging for guidance of minimally invasive procedures include exceptional soft tissue contrast, intrinsic multiplanar imaging capability, and absence of exposure to ionizing radiation. Specialized imaging sequences are available and under development which can further enhance diagnosis and therapy. Flow-sensitive imaging techniques can be used to identify vascular structures. Temperature-sensitive imaging is possible which can provide interactive feedback prior to, during, and following the delivery of thermal energy. Functional MR imaging and dynamic contrast-enhanced MRI sequences can provide additional information for guidance in neurosurgical applications. Functional MR allows mapping of eloquent areas in the brain, so that these areas may be avoided during therapy. Dynamic contrast enhancement techniques can be useful for distinguishing active tumor from tumor necrosis caused by previous radiation therapy. An open-configuration 0.5T MRI system (GE Signa SP) developed at Brigham and Women's Hospital in collaboration with General Electric Medical Systems is described. Interactive navigation systems have been integrated into the MRI system. The imaging system is sited in an operating room environment, and used for image guided neurosurgical procedures (biopsies and tumor excision), as well as minimally invasive thermal therapies. Examples of MR imaging guidance, navigational techniques, and clinical applications are presented.

This study investigates the feasibility of using MR to monitor tissue thermal coagulation and necrosis during ultrasound interstitial thermal therapy (USITT). Recent studies have demonstrated significant advantages of these multi-transducer ultrasound applicators, most notably the capability to dynamically tailor the longitudinal and angular heating distribution which are important for conformable treatments and preserving critical non-targeted tissue. In this effort we consider the use of MRI-based monitoring as a means of on-line treatment control and verification of USITT with these applicators. Applicator design strategies were devised which have improved MR compatibility and reduced image degradation. For this initial feasibility study, one MR thermal imaging approach was investigated: fast spoiled gradient echo sequence with temperature elevation dependent on differential phase maps. Thermal lesions were produced using interstitial ultrasound applicators in vitro and monitored in real time using the MR technique. MR-based temperature and lesion maps were correlated to physical examination of thermal lesions and temperature measurements. The temperature sensitivity and contrast of lesion determination as applied to USITT are discussed, and specific recommendations on applicator fabrication and implementation of MR imaging sequences are given.

Magnetic resonance (MR) imaging was used to guide and monitor the thermal tissue coagulation of in vivo porcine tissue using a 256 element ultrasonic phased array. The array could coagulate tissue volumes greater than 2 cm³ in liver and 0.5 cm³ in kidney using a single 20 second sonication. This sonication used multiple focus fields which were temporally cycled to heat large tissue volumes simultaneously. Estimates of the coagulated tissue using a thermal dose threshold compare well with T2-weighted images of post sonication lesions. The overlapping large focal volumes could aid in the treatment of large tumor volumes which require multiple overlapping sonications. The ability of MR to detect the presence and undesirable thermal increases at acoustic obstacle such as cartilaginous and bony ribs is demonstrated. This could have a significant impact on the ability to monitor thermal treatments of the liver and other organs which are acoustically blocked.

Cooled LITT applicator systems are known to induce complex temperature patterns. Typical for such devices, the temperature maxima are often shifted away from the applicator into the tissue. Therefore, an adequate temperature monitoring is essential. This, however, has not yet been realized for many of the latest MRI systems. We have implemented an improved MR thermometry system using a gradient echo pulse sequence (5 mm slice, FOV 230 mm, TR/TE equals 80/26 ms, matrix 192 X 256) on a 1.5 T scanner (Magnetron Vision, Siemens, Erlangen, Germany). The recorded temperature expansion during laser irradiation of bovine liver was used as a model setup for LITT. A commercially available water-cooled applicator system (Microdome light guide, Huettinger, Umkirch, Germany, in combination with the Power Catheter, Somatex, Berlin, Germany) was used for the delivery of the Nd:YAG laser radiation ((lambda) equals 1064 nm, cw, 15.5 W, Dornier 4060N, Germering, Germany) and tissue cooling, respectively. MR phase images were recorded every 30 seconds alternating in axial and radial orientation. The temperature distributions were calculated using the proton resonance frequency method. A sensitivity factor of 0.0097 ppm/ degree(s)C has been determined independently by a comparison with fluorooptic temperature measurements. The temperature accuracy of a single pixel (0.9 mm square) during 10 min laser irradiation of bovine liver tissue was found to be (-1.7 +/- 1.4) degree(s)C. The final lesion size diameters after 6 min laser irradiation (15 mm X 26 mm) were found to be in good agreement with the dimensions of the 60 degree(s)C isotherm of the respective 2D temperature map. This indicates that the implemented MR thermometry might be an essential tool for therapy control of interstitial laser treatment with cooled applicator systems.

Laser-induced interstitial thermal therapy (LITT) is a minimally invasive technique for tumor therapy. Light is transmitted to targeted tissue via a percutaneously placed optical fiber; heat generated by the absorption of the light produces a region of cell kill about the fiber's tip. Adequate monitoring of the spatial and temporal profile of the tissue temperature has always been considered key to suitable control of the process, since direct visualization is not possible. Magnetic resonance imaging (MRI) provides an unparalleled solution to the problem of monitoring LITT. Recently developed `open' interventional MRI (iMRI) units provide additional key characteristics (patient access; interactive scan plane control) which make the clinical testing of MRI-guided LITT feasible. An iMRI procedure room has been outfitted for Nd:YAG LITT procedures. Relevant technical highlights of treatments performed to date will be shared including room-layout, output calibration, limitations of the current system and considerations for the future. Clinical LITT has been of long-standing interest, possessing medical, engineering and physical problems to be solved. As it provides suitable monitoring capabilities, iMRI opens the field for earnest pursuit by experts not only for improved monitoring, but in establishing the clinical indications and effectiveness of the therapy.

During surgery, selective resection of soft and hard tissue is obtained using devices based on ultrasound induced cavitation bubbles. Building upon the experience of an earlier study, real-time high speed and thermal imaging techniques were applied to expand the understanding of the mechanism of action in relation to irrigation and aspiration and driving frequency. The Cavitational Ultrasonic Surgical Aspirator (CUSA, Valleylab, Boulder, CO) and the Selector (NMT Neurosciences, UK) equipped with a 2.3 mm hollow titanium needle (frequencies 24 and 35 kHz) were investigated. Close-up photography (1 microsecond(s) ) showed a ring of imploding cavitation bubbles around the rim of the tip which fragmented tissue within a well defined radius. Using Schlieren techniques (10 ns resolution), multiple shock waves generated by imploding cavitation bubbles were observed up to 5 mm inside the transparent tissue without leaving damage. The combined irrigation and aspiration is essential for effective tissue removal. The irrigation provides cooling of the tip and enables cavitation formation. The aspiration draws soft tissue into the area of fragmentation and removes debris. Without irrigation, friction and thermal conduction will result in undesired thermal damage and inefficient tissue removal. The impact of the shock waves and difference in driving frequency are expected to be minimal.

The use of intraoperative MR image guidance has the potential to improve the precision, extent and safety of transsphenoidal pituitary resections. At Brigham and Women's Hospital, an open-bore configuration 0.5T MR system (SIGNA SP, GE Medical Systems, Milwaukee, WI) has been used to provide image guidance for nine transsphenoidal pituitary adenoma resections. The intraoperative MR system allowed the radiologist to direct the surgeon toward the sella turcica successfully while avoiding the cavernous sinus, optic chiasm and other sensitive structures. Imaging performed during the surgery monitored the extent of resection and allowed for removal of tumor beyond the surgeon's view in five cases. Dynamic MR imaging was used to distinguish residual tumor from normal gland and postoperative changes permitting more precise tumor localization. A heme-sensitive long TE gradient echo sequence was used to evaluate for the presence of hemorrhagic debris. All patients tolerated the procedure well without significant complications.