FOCUSED ULTRASOUND SYSTEM WITH FAR FIELD TAIL SUPPRESSION

FIELD OF INVENTION

The invention relates generally to thermal treatment systems, and more particularly to image-guided, focused ultrasound systems for controllably delivering thermal energy for treating internal body tissue.

BACKGROUND

It is well-known to use high intensity, focused acoustic wave energy, such as ultrasonic waves (i.e., acoustic waves having a frequency greater than about 20 kilohertz) to generate thermal ablation energy for treating internal body tissue, such as tumors. It is also well-known to employ a tissue imaging system (e.g., MRI) in order to guide the delivery of such high intensity ultrasound energy, and to provide realtime feedback. One such image-guided focused ultrasound system is the Exablate® system manufactured and distributed by InSightec Ltd, located in Haifa, Israel. (www.insightec.com).

By way of illustration, FIG 1 is a simplified schematic representation of an image-guided, focused ultrasound system 100 used to deliver thermal energy to a target tissue mass 104 in a patient 1 10. The system 100 employs an ultrasound transducer 102 to deliver an acoustic energy beam 1 12 generated by a large number of individual piezoelectric transducer elements 1 16 mounted on a distal (outward) facing surface 1 18 (shown in FIG. 2) of the transducer 102. The transducer 102 is geometrically shaped and positioned in order to focus the acoustic energy beam 1 12 at a three-dimensional focal zone located within the target tissue mass 104. While the illustrated transducer 102 has a spherical cap configuration, there are a variety of other geometric transducer designs that may be employed.

In particular, ultrasound is vibrational energy propagated as a mechanical wave through a target medium (e.g., body tissue). In the illustrated system 100, the individual transducer elements 1 16 collectively generate the mechanical wave by converting respective electronic drive signals received from a system controller 106 into mechanical motion. Wave energy transmitted from the individual elements collectively forms the acoustic energy beam 1 12 as it converges on the target tissue

mass 104. Within the focal zone, the wave energy of the beam 1 12 is absorbed (attenuated) by the tissue, thereby generating heat and raising the temperature of the target tissue mass to a point where the tissue cells are killed ("ablated"). An imaging system (e.g., an MRI system) 1 14 is used to acquire images of the target tissue region 104 both before, during and after the wave energy is delivered. For example, the images may be thermally sensitive, so that the actual thermal dosing boundaries (i.e., the geometric boundaries and thermal gradients) of the target tissue region may be monitored.

The transducer 102 may be focused at different locations within the target tissue region 104 by mechanical movement, including orientation of the transducer. -. Electronic "beam steering" may additionally or alternatively be used to change location of the focal zone by making corresponding changes in the attributes (e.g., phase, amplitude, frequency) and the individual transducer element drive signals. In a typical tumor ablation procedure, the transducer 102 delivers a series of discrete pulses of high intensity acoustic wave energy, each for a sufficient duration to generate tissue-destroying heat in a given focal zone. The energy pulses are sequentially focused at a number of differing focal zones located in close proximity to one another, until complete destruction ("ablation") of the target tissue region 104 is achieved. Further information regarding image-guided focused ultrasound systems and their use for performing non-invasive tissue (e.g., tumor) ablation procedures may be found, for example, in U.S. Patent Nos. 6,618,620, 6,582,381, and 6,506,154. FIG. 3 is an MRI image of the heat intensity distribution 125 caused by a nominal "sonication" (delivery of acoustic energy) of a target tissue area using a spherical cap transducer (such as transducer 102 in system 100 of FIGS. 1 and 2). The heat intensity distribution 125 is shaped by the interaction of the acoustic beam with the tissue, as well as the frequency, duration, and power (i.e., mechanical pressure) of the beam. More particularly, the wave energy converges as it propagates (from left to right in FIG. 3) through a "near field" region 119 to a focal zone 120, which tends to have an elongate, cylindrical shape. The conversation of wave energy to heat is most intense in the focal zone 120, due to the convergence (and collisions) of the individual waves, and can be generally equated with the tissue destruction, or "ablation" volume. Notably, some of the wave energy is absorbed in the near field region 1 19, especially in the area adjacent to the focal zone 120. A further portion of

the wave energy passes through the focal zone and is absorbed in a "far-field" region 122, which refers generally to the tissue region located distally of the focal zone relative to the transducer. Although the waves that pass through (or are reflected from) the focal zone 120 tend to diverge in the far field region 122, to the extent any such far field energy absorption occurs in a concentrated area, it can result in undesirable and potentially harmful (and painful) heating and necrosis of otherwise healthy tissue.

As described in PCT publication WO 2003/097162, it is possible to increase the effectiveness of thermal dosing of a target tissue region by delivering one or more relatively high pressure, short duration acoustic energy pulses to generate air bubbles in tissue located in the intended focal zone just prior to delivering a regular "ablation energy" wave pulse. The presence of the bubbles serves to increase the mechanical- to-thermal energy conversion in the tissue, which, along with the added reflection and scattering of the main acoustic beam, has the positive effect of reducing the overall amount of potentially detrimental far-field energy absorption. However, as shown in FIGS. 4 and 5, while the overall amount of far-field energy is decreased by the presence of the bubbles at the focal zone center, a far greater concentration of the remaining far field energy is concentrated along a central beam propagation axis 124, extending distally from a center focal plane 126 of the "enhanced ablation" focal zone 128. This thermal energy concentration has the appearance of a thermal "tail" 130 that tapers into a highly undesirable stick portion 132 (best seen in FIG. 5), thereby elongating the effective tissue ablation region 134, and resulting in an even higher temperature in a close-in portion of the far field region 136 than occurs during a non- bubble enhanced sonication.

SUMMARY OF THE INVENTION

In one embodiment, a system for treating internal body tissue using acoustic energy includes a transducer configured for delivering acoustic energy to internal body tissue, an imaging system configured for acquiring image data of the internal body tissue, and a controller configured to identify a three-dimensional target tissue ablation zone in a patient's internal body tissue based on acquired image data and/or operator input provided through a user interface, cause delivery of a relatively short

duration pulse of acoustic energy from the transducer to generate bubbles in tissue located in a distal portion (relative to the transducer) of the target ablation zone, and in the presence of the bubbles, cause delivery of a substantially longer duration pulse of acoustic energy from the transducer to a more proximally located focal center of the target ablation zone for causing tissue ablation. In particular, the bubbles generated in the distal portion of the focal zone by the short duration pulse form a "bubble mask" which inhibits formation of a far-field thermal ablation tail that would otherwise form if the bubbles had been generated at the focal center. Because the bubbles will rapidly dissipate, the system may cause delivery of one or more additional bubble formation pulses by the transducer in between relatively longer "ablation energy" pulses, in order to re-establish and/or maintain the bubble mask in the distal portion of the target tissue ablation zone.

By way of illustration, in a procedure carried out using a focused ultrasound system constructed and programmed according to one embodiment of the invention, a short duration (e.g., 0.1 second) bubble formation pulse is delivered to a distal portion of the target ablation zone, e.g., approximately 10 mm distal of the focal center relative to the transducer. The bubble formation pulse is immediately followed by a relatively longer duration (e.g., 0.5 second) ablation energy pulse delivered to the focal center of the target ablation zone. After a delay of approximately 2.0 seconds to allow for bubbles generated in the focal center by the ablation energy pulse to dissipate, the system controller repeats the cycle by delivering another a short duration (e.g., 0.1 second) bubble formation pulse to the distal portion of the target ablation zone, another longer duration (e.g., 0.5 second) ablation energy pulse delivered to the focal center, and another (e.g., 2.0 second) delay ("off) period. The series of "bubble-masked" sonications is repeated by the system, until ablation of the entire the target tissue zone is achieved. In a variation of this procedure, bubbles generated by an ablation energy pulse are used as a bubble mask for an ensuing ablation energy pulse focused proximally (relative to the transducer) of the immediately preceding pulse. In another embodiment, a system for treating internal body tissue using acoustic energy includes a transducer configured for delivering acoustic energy to internal body tissue, an imaging system configured for acquiring image data of the internal body tissue, and a controller configured to identify a three-dimensional target

tissue ablation zone in a patient's internal body tissue based on acquired image data and/or operator input provided through a user interface, and cause delivery of respective ablation energy pulses to focal locations distributed about a focal center of the identified target ablation zone. By way of non-limiting example, the system may cause a series of three to five ablation energy pulses to be delivered, each pulse lasting for approximately 0.5 seconds followed by an approximate 2.0 second delay, to respective focal locations distributed in a substantially symmetrical pattern about the focal center of the target ablation zone. The sequence of distributed ablation energy pulses may be repeated by the controller, whether in a same or a differing pattern, until ablation of the entire the target tissue zone is achieved.

In yet another embodiment in which features of the previously-described embodiments are combined, a system for treating internal body tissue using acoustic energy includes a transducer configured for delivering acoustic energy to internal body tissue, an imaging system configured for acquiring image data of the internal body tissue, and a controller configured to identify a three-dimensional target tissue ablation zone in a patient's internal body tissue based on acquired image data and/or operator input provided through a user interface, and cause delivery of respective pairs of bubble formation and ablation energy pulses in a substantially symmetrical pattern distributed about a focal center of the target ablation zone.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is simplified schematic diagram of a focused ultrasound treatment system for providing thermal energy dosing of a target tissue region in a patient.

FIG. 2 is a cut-away schematic side view of the transducer in the system of FIG. 1, illustrating the concentrated transmission of focused ultrasonic energy to a targeted internal body tissue structure.

FIG. 3 is an image obtained by a magnetic resonance imaging (MRI) system of a heating phantom in a target tissue region during delivery of converging (low power) acoustic energy from a transducer (not shown), illustrating formation of a heat-intensity focal zone.

FIG. 4 is an MRI thermal profile image of a cross-section of an area of tissue being heated in a conventional, bubble-enhanced sonication, including illustrating a heat-intensity focal zone at its highest temperature point.

FIG. 5 illustrates a tissue ablation zone resulting from a conventional, bubble- enhanced sonication, such as that illustrated in FIG. 4.

FIGS. 6 and 7 are a cut-away schematic side views illustrating delivery of respective bubble-formation and ablation energy pulses to a target focal zone using a tissue treatment system constructed and programmed in accordance with one embodiment of the invention.

FIG. 8 is an MRI thermal profile image of tissue heated during the sonication illustrated in FIGS. 6 and 7, illustrating a heat-intensity focal zone at its highest temperature point. FIG. 9 illustrates a tissue ablation zone resulting from the sonication illustrated in FIGS. 6 and 7.

FIGS. lOA-C are a cut-away schematic side views illustrating delivery of respective bubble-formation and ablation energy pulses to successive target focal zones located along a propagation axis of a transducer of a tissue treatment system constructed and programmed in accordance with another embodiment of the invention.

FIG. 1 1 is a cut-away schematic view of a focal plane of a target tissue ablation zone, illustrating the distribution of a plurality of tissue ablation pulses dithered about the focal center during a tissue sonication procedure carried out using a system constructed and programmed in accordance with yet another embodiment of the invention.

FIG. 12 is a schematic illustration of a three-dimensional coordinate system having an x-y plane at a focal plane of a target tissue ablation zone, with the z-axis extending in a distal direction from the focal plane, illustrating the focal centers of respective bubble-generating and tissue ablation pulses delivered during the sonication illustrated in FIGS. 6 and 7.

FIG. 13 is a schematic illustration of a three-dimensional coordinate system having an x-y plane at a focal plane of a target tissue ablation zone, with the z-axis extending in a distal direction from the focal plane, illustrating the focal centers of a series of pairs of respective bubble-generating and tissue ablation pulses delivered during a tissue sonication procedure carried out using a system constructed and programmed in accordance with still another embodiment of the invention.

DETAILED DESCRIPTION

It will be appreciated that embodiments of the invention may be software and/or hardware implemented in a controller or control system of an acoustic energy tissue treatment system, such as an image-guided focused ultrasound system (e.g., in controller 106 of system 100 of FIG. 1). Such embodiments of the invention are used to deliver acoustic wave energy to a selected three-dimensional focal zone in a target tissue region for providing controlled thermal dosing of body tissue, and may manually controlled, or may be partially or fully automated. In particular, embodiments of the invention may be implemented in systems for providing and controlling a series of acoustic energy sonications for ablating a target tissue region, and may involve one or both of user input and control (e.g., operational commands entered through a user interface), and automated functions performed by a system controller (e.g., a programmable computer). In accordance with this general understanding, the following detailed description refers to a "controller" of a focused ultrasound system which may be readily implemented based on the disclosure provided herein, since the particular control aspects and features of a system controller configured for performing and/or assisting in the performance of the illustrated and described embodiments will be apparent from the herein-described functional descriptions.

Referring to FIG. 6, in one embodiment, a system for treating tissue using acoustic energy is configured to deliver a first, relatively short duration, high power (i.e., wave pressure) pulse of acoustic wave energy 148 from a transducer 150 along a transducer propagation axis 152 to generate tissue bubbles 154 in a distal region 156, relative to the transducer 150, of a target tissue ablation focal zone 160 identified based on one or both of acquired image data and operator input provided through a user interface. This initial bubble-formation pulse 148 does not necessarily make a significant contribution to the overall tissue ablation, and preferably has a relatively short duration so as to not form its own far-field thermal tail. By way of non-limiting examples, the duration of the bubble-formation pulse 148 may be in a range from 0.05 to 0.15 seconds, and in one embodiment is approximately 0.1 seconds. In various embodiments, the bubble-formation pulse 148 is focused along the propagation axis 152 in a range of 5 mm to 15 mm distal of a focal plane 162 lying normal to the

propagation axis 152 and including the focal center 158. In one such embodiment, propagation axis is also the focal axis of the focal zone 160, and the bubble-formation pulse 148 is focused along the propagation axis 152 approximately 10 mm distal of the focal plane 162 including the focal center 158. Referring to Fig. 7, immediately following delivery of the bubble-formation pulse 148, and in the presence of the bubbles 154 the system delivers a further, substantially longer duration pulse of acoustic wave energy 168 from the transducer 150 along the transducer propagation axis 152 to apply thermal ablation energy 170 to the target focal zone 160. The ablation energy pulse 168 is focused at the focal center 158 and is in a range of between approximately 0.2 to 1.0 seconds in duration, e.g., approximately 0.5 seconds in one embodiment. Notably, the relative positioning/focusing of the transducer 150, and the delivery of respective bubble formation and ablation energy pulses 148 and 168 are under the control of the system controller (not shown). The respective target focal zone 160 may be identified by the controller based, at least in part, on images of the body tissue acquired by an associatedimaging system and operator input provided through a user interface (not shown). A respective time duration and power level of the bubble-formation and ablation energy pulses 148 and 168 may be selected by user input, or may be automatically determined by the controller based, at least in part, on characteristics of the tissue located in or near the focal zone 160. The focal center 156 of the bubble- formation pulse 148 may also be selected by user input or automatically determined by the controller, and may be a predetermined distance from the focal center 158 along the transducer propagation axis 152, e.g., 10 mm distal of the focal center 158 in one embodiment. As seen in FIGS. 8 and 9, it has been observed by the inventors that by configuring the system (e.g., using programmable software) to focus the bubble formation pulse 148 of the enhanced ablation procedure in a distal region 156 of the target focal zone 160, the bubbles 154 act as a "bubble mask" (indicated by arrows 172 in FIG. 7) that suppresses formation of a far-field thermal tail in the resulting ablation 174. Although some of the acoustic energy from the ablation pulse 168 will pass through the focal zone 160 into the far field region 176, the bubble mask 154 inhibits this remaining energy portion from forming a potentially harmful thermal tail. Because the bubble mask 154 generated by the bubble formation pulse 148 will

rapidly dissipate, the controller may cause delivery of an additional bubble formation pulses to the distal region in between relatively longer duration ablation energy pulses 168, in order to re-establish and/or maintain the bubble mask 154 in the distal portion 156 of the target tissue focal zone 160. By way of example, in a procedure carried out using one embodiment, the bubble formation pulse 148 is approximately 0.1 seconds in duration, and is delivered approximately 10 mm distal of the focal center 158 along the transducer propagation axis 152 (see FIG. 12). Because of its relative short duration, in some embodiments the controller may cause delivery of the bubble formation pulse 148 at a higher power than the ablation pulse, although it is not a requirement of the invention.

The bubble formation pulse 148 is immediately followed by an approximately 0.5 second ablation energy pulse delivered to the focal center 158. The transducer is then left off for an approximately 2.0 second delay in order for the bubbles generated in the focal center 158 by the ablation energy pulse to dissipate, and the same cycle is repeated by delivering another 0.1 second bubble formation pulse to the distal region 156, followed by another 0.5 second ablation energy pulse delivered to the focal center 158, and another 2.0 second off period. This series of bubble-masked ablation pulses may be repeated by the system until ablation of the entire the target tissue zone is achieved, which may be verified, e.g., using MRI thermal images. By way of illustration, a system constructed and configured (e.g., programmed) according to one embodiment may be used to ablate an entire target tissue structure, e.g., a tumor, by performing successive sonications delivered to respective target focal zones that collectively cover the tissue region, each sonication comprising delivery of an initial bubble-formation pulse to a relatively distal region of the respective focal zone, immediately followed by delivery of a more proximally- focused ablation energy pulse. For each of the respective focal zones, the system causes delivery of a distal bubble mask pulse, followed by a central ablation pulse, which pulses may be repeated until the respective focal zone is completely ablated. In a variation of the foregoing, bubbles generated by respective ablation energy pulse may be used by the system as a bubble mask for an ensuing ablation energy pulse delivered to a focal location proximal of the focal location of the present ablation energy pulse. Depending on the size and dimensions of the tissue region to be ablated, following an initial bubble-formation pulse in a distal region of a target

focal zone tissue region, two or more sequential ablation energy pulses maybe delivered by the system to locations successively proximal of each immediately preceding pulse, with the tissue bubbles generated from the immediately preceding pulse acting as a respective bubble mask to suppress formation of a far-field energy tail during each present pulse.

By way of illustration, with reference to FIG. 1OA, a bubble-formation pulse of acoustic wave energy 178 is delivered using a system configured according to one embodiment of the invention for approximately 0.1 seconds from a transducer 180 along a transducer propagation axis 182. The bubble formation pulse 178 generates tissue bubbles 187 in a distal region 186 (relative to the transducer 180) of a first target ablation focal zone having a focal center 189. As shown in FIG. 1OB, the initial bubble-formation pulse 178 is immediately followed by a delivery of a first (approximately 0.5 second) ablation energy pulse 188 to the focal center 189 of the first target focal zone. As described above, the bubbles generated by the bubble- formation pulse 178 suppress formation of a thermal tail by the ablation energy pulse 188. Also, the ablation energy pulse itself generates bubbles 190 in a central focal region 196 of the first target ablation zone, and is immediately followed (as shown in FIG. 10C) by a further ablation energy pulse 198 delivered to a focal center 209 of a second target ablation zone located proximately (relative to the transducer 180) of the first target ablation zone along the propagation axis 182. In this manner, the bubbles 190 in region 196 form a bubble mask to inhibit formation of a far-field tail that would otherwise result during ablation pulse 198.

In accordance with yet another embodiment, a system for treating tissue using acoustic energy is configured to identify a three-dimensional target tissue ablation zone e.g., based on acquired image data and /or operator input provided through a user interface, and then deliver respective ablation energy pulses to focal points distributed about a focal center of the target ablation zone. FIG. 1 1 depicts illustrates a procedure being carried out using such system embodiment, in which a plurality of successive ablation energy pulses 202A-D are delivered to respective focal locations lying in or proximate to a focal plane 204 of a target tissue ablation zone. In particular, the focal plane 204 lies substantially orthogonal to a main focal axis, which passes through (i.e., coming out of or into the figure) a focal center 200 lying in the plane 204. The ablation energy pulses 202A-D are distributed by the system in a

symmetrical pattern, each located a respective 1 mm in the x direction and 1 mm in the y direction (i.e., for an absolute distance of approximately 1.4 mm) from the focal center 200. The pulses 202A-D are preferably delivered sequentially by the system, for example, each for a duration of between approximately 0.2 second and 1.0 second, with a delay, e.g., of approximately 1.0 to 3.0 seconds interposed between transmission of each successive ablation energy pulse. In one system implementation, the pulses are delivered for approximately 0.5 second each, with an "off-period" delay of approximately 2.0 seconds between successive pulses.

The sequence of ablation energy pulses 202A-D may be repeated by the system, as necessary, until ablation of the entire target tissue focal zone is complete. Alternatively, following delivery of a first sequence of pulses 202A-D, a different sequence may be delivered by the system, e.g., by rotating the focal location of each of the pulses 202A-D by 45°. It has been observed by the inventors that by configuring the system to dither the focal locations of the ablation energy pulses about the focal center, formation of a thermal tail along the main focal axis is inhibited. The particular number, duration, and pattern of the respective ablation pulses in a given sequence may vary, and need not be perfectly symmetrical.

In accordance with still another system embodiment, in which features of the previously-described system embodiments are combined, a system for treating tissue using acoustic energy is configured to identify a three-dimensional target tissue ablation zone based on acquired image data and/or operator input provided through a user interface, and then deliver respective bubble-masked ablation energy pulses in a pattern distributed about a focal center of the target ablation zone. By way of example, with reference to FIG. 13, a first (e.g., 0.1 second) bubble formation pulse is delivered by the system along a first axis that is approximately parallel to, but off- center (e.g., 1-2 mm) from, a focal axis of a target ablation zone to a first distal focal location 212A that is (e.g., 10 mm) beyond a focal plane 214 of the target ablation zone. The first bubble pulse is immediately followed by a (e.g., 0.5 second duration) ablation energy pulse delivered by the system along the same first axis to a focal location 210A lying in or proximate the focal plane 214. Following an (e.g., approximately 2.0 second) off-period, the respective bubble formation, ablation pulse and off-period steps are repeated along three further respective axes, each

approximately parallel to, but off-center from, the focal axis of the target ablation zone, for a total of four, bubble-masked ablation pulses 21 OA-D.

The respective distal bubble pulses 212A-D and ablation pulses 21 OA-D may be distributed in a similar pattern about the focal center of the target ablation zone (not shown) as pulses 202A-D in FIG. 1 1. The sequence of respective bubble formation and ablation energy pulses 212A-D and 21 OA-D in the embodiment of FIG. 13 may be repeated by the system, as necessary, until ablation of the entire target tissue focal zone is complete. Alternatively, following delivery of a first sequence of bubble mask-ablation pulses (212A-D and 21 OA-D), a different sequence of bubble- masked pulses may be delivered by the system, e.g., by rotating the focal locations of the respective pulse pairs 212A-210A, 212B-210B, 212C-210C, and 212D-210D by 45°. The particular number, duration, and pattern of the respective bubble-masked ablation pulses in a given sequence may vary, and need not be perfectly symmetrical.