Patent Grant
9770605
Technical Field
The technology disclosed herein relates to methods and apparatus for the treatment of internal body tissues and in particular to the treatment of internal body tissues with high intensity focused ultrasound (HIFU).
Description of the Related Art
There are numerous techniques that are currently used for the treatment of internal body tissues. For example, internal cancerous and non-cancerous tumors can be treated with a variety of techniques such as surgery, radiation and chemotherapy. Each of these techniques offers advantages and disadvantages. One promising non-invasive technology for treating internal body tissues is high intensity focused ultrasound (HIFU). With HIFU, high intensity ultrasound energy is focused at a desired treatment volume. The energy causes tissue destruction via both thermal and mechanical mechanisms.
One of the drawbacks of using HIFU to treat internal body tissues is the time required to treat a given volume of tissue. Currently proposed HIFU procedures may take up to 3 hours to treat a single tumor, which has contributed to poor acceptance of these procedures by both physicians and patients. In addition, the amount of energy required to completely ablate a large volume of tissue results in substantial thermal conduction outward from the ablation volume, which can raise the risk of thermal damage to surrounding healthy tissue.
Given these problems, there is a need for a method of treating internal body tissues in a manner that reduces treatment time, while improving safety, effectiveness and ease of use, and reducing total required energy deposition.
To address the problems discussed above, the technology disclosed herein relates to a system for treating uterine fibroids or other tissue that is compact enough to be used in a physician's office. The system treats the tissue with energy from an energy source, which may include high intensity focused ultrasound (HIFU). Such energy sources could also include radiofrequency, radiation, microwave, cryotherapy, laser, etc. However the preferred embodiment is HIFU, due to its unique ability to be non-invasively focused deep inside body tissues without the need for punctures or incisions.
In one embodiment, a desired target volume of tissue is treated with HIFU by ablating a number of adjacent elemental treatment volumes to form “building blocks” used to treat the full target volume of tissue. Each elemental treatment volume is created by directing the focal zone of a HIFU transducer to ablate a sub-volume that is larger than the focal zone itself but smaller than the overall desired treatment volume. Each elemental treatment volume is created by repeatedly directing the focal zone of the HIFU transducer over the perimeter of the elemental treatment volume as treatment energy is being applied. Treatment signals from the HIFU transducer can be applied to the tissue without using temperature data or feedback control even in the presence of bubbles such that the treatment time is significantly decreased.
In one embodiment, a mechanical or electronic steering apparatus directs the focal zone of a HIFU beam around the perimeter of the elemental treatment volume until the tissue encompassed by the perimeter is ablated. In one embodiment, a center region of the elemental treatment volume is not directly ablated but is treated by thermal conduction as the perimeter is ablated.
In one embodiment, the disclosed technology includes a HIFU transducer that is configured to deliver treatment energy to a focal zone and a computer controlled beam steerer for repeatedly positioning the focal zone over a perimeter of an elemental treatment volume as treatment energy is applied.
In one embodiment, a pattern of elemental treatment volumes is created to form a shell of ablated tissue surrounding the treatment volume (similar to the geometry of an eggshell surrounding an egg). Treating a desired tissue volume using this type of shell ablation has two primary utilities in HIFU therapy: (1) In one embodiment, the ablated shell interrupts the supply of blood to the interior of the treatment volume, causing the otherwise untreated tissue located within the shell to ischemically necrose in situ. In this manner, the ischemic damage to the center of the volume results in the destruction of the entire volume over time, even though only the outer boundary is directly treated with HIFU. (2) In another embodiment, the elemental treatment volumes comprising the shell pattern are deposited in such a way that heat conduction toward the interior of the volume results in immediate thermal destruction of the inner tissue, even though only the outer boundary is directly ablated with HIFU energy. Both of these utilities provided by shell ablation serve to significantly improve the efficiency of HIFU therapy because they result in an effective tissue treatment volume that is larger than the volume directly ablated with HIFU energy. Leveraging either or both of these shell ablation advantages increases the throughput achieved by a given HIFU procedure.
In another embodiment, a number of elemental treatment volumes are created to fill or partially fill the target treatment volume. With this technique, a greater percentage of tissue within the treatment volume is directly necrosed by exposure to the ablating energy than is the case when only the outer boundary is ablated.
In another embodiment, a HIFU treatment device directs a focal zone of a HIFU transducer to move in a path to surround or envelop a tissue volume. The pattern in which the focal zone of the HIFU transducer is moved results in creating a series of ablated tissue toroids of varying diameter that are stacked to surround and envelop the tissue volume. In yet another embodiment, the focal zone is moved to create a spiral shell of ablated tissue to envelop the treatment volume.
In order to minimize treatment time and required user skill, one embodiment employs a computer-controlled mechanism to automatically move the HIFU focal zone and apply HIFU energy in such a manner to create the desired elemental treatment volume and/or geometric shell while the user simply holds the applicator stationary.
This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This summary is not intended to identify key features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.
The foregoing aspects and many of the attendant advantages of this technology will become more readily appreciated by reference to the following detailed description, when taken in conjunction with the accompanying drawings, wherein:
As indicated above, the technology disclosed herein relates to a method of treating internal body tissues such as uterine fibroids, benign or malignant tumors, or the like. Although the following description is directed to the use of the technology to treat uterine fibroids, it will be appreciated by those of skill in the art that the technology can be used to treat a volume of any internal body tissue. In one embodiment, the desired treatment volume is treated by creating a pattern of one or more elemental treatment volumes in the tissue. Though the technology disclosed herein describes several possible geometries for these elemental treatment volumes, each type of elemental volume shares the common feature that it is comprised of a volume of ablated tissue that is greater than the volume of the HIFU focal zone due to controlled motion of that focal zone around or along the elemental volume in a prescribed manner. The acoustic focal zone referenced herein is commonly defined as the volume encompassed by the −6 dB pressure contour of the acoustic waveform as measured from its spatial maximum. Those skilled in the art will recognize that the dimensions of this −6 dB pressure contour are also referred to as the full-width half-maximum, or FWHM, dimensions. A typical focal zone as implemented in the embodiments described herein is ovoid in shape, with FWHM dimensions of approximately 10 mm. in length along the beam axis and 2 mm. in width perpendicular to the beam axis.
In accordance with an embodiment of the disclosed technology, a desired volume of tissue to be treated is exposed to energy that ablates the tissue in a shell-like pattern, which completely or partially surrounds the tissue volume while only directly ablating the outer boundary. The tissue encompassed by the shell then remains in the body and necroses in situ due to effects other than direct ablation. These other effects causing in situ necrosis may include some combination of:
1. ischemic necrosis, resulting from partial or complete isolation of an encapsulated region from a surrounding blood supply;
2. indirect thermal necrosis, resulting from inward thermal conduction occurring during the creation of the ablated shell; and/or
3. secondary injury due to normal healing processes (inflammation, apoptosis, etc.).
The necrosed tissue located inside the ablated shell of the treated volume is subsequently resorbed and/or healed by normal body mechanisms.
In one embodiment, an ablated shell 30 is created by exposing the tissue situated in the shell to HIFU energy for a sufficient time or at sufficient power so as to cause direct tissue necrosis. It should be noted that throughout this description, the concepts of applied HIFU power and energy are used to generally describe the amplitude or “strength” of the HIFU signal transmitted into tissue. In this sense, the terms “HIFU power” and “HIFU energy” can generally be used interchangeably, except in those instances where one or the other of these particular quantities is implied by the context in which it is used. This is to be distinguished from secondary ischemic necrosis that occurs in the tissue inside the shell as a result of it being cut off from its blood supply or as a result of other effects listed above. Because the volume of tissue ablated to create the shell is smaller than the overall volume of tissue to be treated, the time required to treat the combined mass of tissue (i.e. shell plus encapsulated volume) is reduced below that which would be required if the entire volume were to be directly ablated. As used herein, the term “ablation” refers to the direct necrosis of tissue resulting from the immediate thermal and/or mechanical effects caused by exposure of the tissue to the energy source. Also as used herein, the term “shell” refers to an ablated surface which reduces or eliminates blood flow across that surface. The geometry of this surface may be such that it entirely encapsulates a volume (e.g., a sphere) or non-closed such that it only partially encapsulates the volume (e.g., a concave disk). The term “encapsulate” refers to creation of such surfaces.
In
In another embodiment, one or more partial shells are created which do not entirely encapsulate the tissue site, but reduce or eliminate blood flow to or from its interior across those partial shell(s). This leads to necrosis of at least part of the tissue volume.
In another embodiment, the target volume may be larger than the ultrasound image available. Another possibility that may be encountered is that the range of movement of the therapy beam does not allow the entire target to be treated. In the first case, multiple ultrasound 2D images or 3D volumes may be stitched together to visualize the full extent of the target by manually moving the applicator. This image data may be stored for future reference. Next, the algorithm may automatically plan treatment on the stitched images and recommend where the treatment should start. The physician may also plan treatment from the stitched image data. After the treatment has been planned, the physician may move the transducer to a region that enables the therapy transducer to create the initial elemental treatment volumes within the target. Spatial image correlation techniques may be used to assist the physician in appropriate applicator placement with respect to the target. In this case, current ultrasound images are compared to images already acquired and stored during pre-treatment surveys. Device position sensors (e.g. magnetic sensors) may also be used assist with applicator placement. The device position sensors may also be combined with the image correlation techniques for even better accuracy. After the device has exhausted its ability to create elemental treatment volumes with the current applicator position, the applicator may be manually moved such that image correlation techniques and/or position sensors are used to assist the physician in applicator placement for the next treatment site. By continuing the process, the full extent of the target may be treated. In the second case, manual movement of the applicator to acquire images to visualize the entire target is not necessary. The data set to see the entire target may be acquired in one applicator position; however, the applicator will have to be moved as previously described due to the movement limitations of the therapy device inside the applicator.
As shown in
Although the elemental treatment volume 80 shown in
The size of the elemental treatment volumes can be varied as a function of a variety of factors including the geometry of the devices that will apply the treatment energy. In the embodiment shown in
In each of the examples shown in
In one embodiment described in further detail below, the focal zone 81 of the HIFU beam 83 is steered over the perimeter of the cylindrical elemental treatment volume 80 with a mechanical wobbler at a rate that acts to largely confine the heat within the center 79 of the treatment volume as the elemental treatment volume is being created. The focal zone of the HIFU signal is directed around the perimeter of the elemental treatment volume in such a manner that the interior of the treatment volume is ablated by inward thermal conduction, but the energy deposited beyond its exterior boundary remains below the threshold required for inciting thermal or mechanical damage. Alternatively, the focal zone 81 of the HIFU beam 83 can be steered around the perimeter of the elemental treatment volume with electronic beam steering which, in one embodiment, may be performed by depositing energy at a set of discrete points around the perimeter rather than via continuous sweeping of the focal zone.
To create the elemental treatment volumes described herein, a substantially non-linear pulsed waveform of HIFU energy, such as the waveform 230 shown in
In one particular experimental construct, the most preferred peak acoustic powers used to attain the desired level of nonlinearity in the HIFU focal zone range from 600-3100 watts, depending upon the depth of the particular elemental tissue volume with respect to the body surface, the design of the HIFU transducer, and its power handling capability. These acoustic powers are delivered to the elemental volume in a pulsed fashion, where the most preferred pulses consist of 15-45 cycles at a nominal operating frequency of 1 MHz and are delivered at pulse repetition frequencies (PRFs) of 2-8 kHz. These pulses are then delivered in a series of successive bursts, the total number of which determines the overall treatment time.
While the HIFU transmitter is applying energy of these specifications, a cylindrical elemental treatment volume is created by mechanically wobbling the HIFU focus, which is approximately 10 mm. in length and 2 mm. in width in FWHM dimensions in one embodiment, around a trajectory with a most-preferred diameter of 8-12 mm at a rate of nominally 2 Hz. In this case, the diameter around which the HIFU focus rotates is approximately equal to the HIFU focal zone length and five-fold greater than the HIFU focal zone width. The mechanical wobbling and HIFU treatment continue in this fashion for a total treatment duration of 10-50 seconds per elemental volume, in the most-preferred embodiment. The treatment duration per unit volume depends on the tissue depth at which the particular elementary volume is created, as well as the overall treatment volume desired. For example, larger overall treatment volumes typically require less treatment time per unit volume, due to the advantages of cooperative heating among many neighboring unit volumes. Similarly, unit volumes created in shallow layers that abut previously-treated deeper layers typically require less time to ablate, owing to modest “pre-heating” of the shallow layers that occurs while the deeper layers are being treated. Arbitrarily large treatment volumes can then be achieved by successive “stacking” of layers composed of some number of these elemental treatment volumes, with a most-preferred axial separation between adjacent layers of 8-12 mm. The following table summarizes the preferred ranges of focal motion parameters for use in conjunction with the acoustic waveforms and powers described above.
Although the currently preferred embodiment uses a pulsed waveform which is non-linear at the focal zone, it will be appreciated that a continuous-wave (CW) or linear HIFU signal such as the waveform 232 shown in
Though this previous example specifies the use of a 2 Hz mechanical rotation rate around the perimeter of the elemental volume, both lower and higher rates could be used to ablate these types of elemental volumes. However, if too low a rate is used, the heat developed to ablate the perimeter of the elemental treatment volume may not be sufficiently contained within the interior of the elemental volume and may result in adverse effects in collateral tissues. Higher rotation rates may require the use of an electronic beam former instead of mechanical rotation and may also affect the HIFU treatment power necessary. If electronically steered, the beam may, in one embodiment, be focused at a set of discrete points around the perimeter, rather than continuously swept. As indicated in the above table, in one embodiment, the mechanical rotation rate of the HIFU focus about the unit volume diameter is at least 0.25 Hz. In another more preferred embodiment, this rotation rate is at least 1 Hz, while in the most preferred embodiment this rate is nominally 2 Hz. Regardless of the rotation rate used, it is preferable to apply energy over a number of passes (e.g. two or more) around the perimeter using a multiple-pass approach at a rate and power level that allows the entire elemental treatment volume to be ablated in unison, in order to achieve symmetric geometry in the shape of the ablated elemental volume. Otherwise, with a single-pass approach in which the focal zone is scanned relatively slowly to achieve ablation without having to revisit a particular point, the excess heating produced may cause large focal or pre-focal bubbles to form that can cause shielding and distortion, preventing the production of an evenly ablated tissue site, as illustrated in
As will be appreciated, the size of the elemental treatment volume is preferably selected so that a center region 79 can be indirectly treated while not unduly increasing the treatment time required to treat a desired volume of tissue. If the size of the elemental treatment volume is too large, the center region 79 will not be ablated by effective conduction of heat into the interior of the volume. Conversely, if the size of the elemental treatment volume is too small, then the time required to treat the desired treatment volume must be adjusted to avoid over-dosing the elemental volume and potentially causing damage to collateral tissues. In addition, the time to create each elemental treatment volume may decrease as the focal zone is moved proximally toward the surface of the body, due to the residual heat persisting in the treatment volume from ablation of the more distal elemental volumes.
In a currently preferred embodiment, the method of creating the elemental treatment volumes takes advantage of several features of HIFU therapy resulting from the synergistic effects of highly-nonlinear acoustic waveforms and the mechanical or electronic motion of the HIFU focus about the perimeter of the unit volume. These combined effects comprise a set of operating points that result in the enhanced safety and efficacy observed when using this treatment method. This set of operating points includes a combination of the following: (1) The elemental treatment volume is ablated in such a way that the interior region is primarily destroyed through inward conduction of heat, not direct ablation by HIFU. This feature enlarges the size of the elemental volume without increasing the HIFU dose that has to be delivered to the tissue to do so. (2) The motion of the HIFU focal zone about the elemental treatment volume perimeter is accomplished by making multiple passes around the perimeter using a specified rotation rate, as opposed to making one a single pass around the circumference of the unit volume to achieve ablation. This feature allows the tissue within the elemental treatment volume to be ablated with uniform, smooth boundaries and equal length at substantially all points around the perimeter. (3) The elemental treatment volume is subjected to highly concentrated acoustic energy only in the focal region of the HIFU beam by virtue of the use of a highly nonlinear acoustic waveform that dramatically enhances the heating rate in the focal zone. (4) The fundamental acoustic frequency of the HIFU applicator is kept low enough to ensure safe propagation through untargeted collateral tissues. As a result of the system's ability to create substantially uniform elemental treatment volumes despite changes in tissue characteristics or the presence of bubbles in the focal zone, the treatment system can operate without reliance on temperature feedback monitoring, thereby resulting in faster treatment and reduced system complexity and cost. The combination of all these attendant benefits ensures adequate efficacy of the treatment, obviating the need for thermometric techniques to determine the temperature within the treatment volume to verify that temperature levels required for thermal necrosis are being achieved. Additionally, the combination of the feature set described above takes advantage of synergistic effects that allow each unit volume to be ablated with precise boundaries and minimal thermal invasiveness to collateral tissues outside the treatment volume. By amassing the full treatment volume from “building blocks” of elemental treatment volumes, arbitrarily-sized volumes can be ablated with the same inherent spatial precision and heat confinement afforded to each constituent unit volume.
Although the shell 87 illustrated in
The shell 87 is shown in
As will be appreciated, other patterns besides shells of elemental treatment volumes can be used to treat the desired tissue volume. For example, layers of horizontally spaced adjacent elemental treatment volumes can be created in the desired tissue volume. The distance between elemental treatment volumes in a layer can be closely spaced or more spread apart.
Although the shape of the ablated shells is shown as being generally spherical in
Those skilled in the art will readily appreciate that other advantages of the shell ablation approach are (1) increased treatment rate, since energy is applied to only a sub-volume of the tissue ultimately treated, (2) a larger treatment size for a given allotment of treatment time, (3) and less energy required, compared to that which would be used if the entire volume including its interior were directly ablated. Automating a HIFU system to ablate a symmetrical (e.g., spherical) shell will reduce demands on a user with regard to imaging, targeting and probe manipulation. If shell is symmetrical, the user can easily visualize its projected relationship to tumor boundaries as visualized with an imaging mechanism such as an ultrasound imager, MRI, x-ray, etc. The user need only manipulate the HIFU system so as to center an overlay of the projected shell within the image of the target tissue, expand the diameter of the shell to desired dimensions (e.g., just inside periphery of the tumor), and then hold the system stationary relative to the target tissue while the system automatically ablates the specified shell pattern.
The treatment device 150 is coupleable to other components of the treatment system including an image processor and display required to operate the imaging transducer 152 and produce images of the tissue volume. A signal source required to drive the HIFU transducer and a computer to orient the focal zone of the HIFU transducer in a pattern to create the elemental treatment volumes in a desired pattern such as a shell around the tissue volume are also included.
To adjust the depth of the focal zone where the HIFU signals are delivered to the patient, a linear actuator 160 or motor raises or lowers the HIFU transducer 154 within a housing of the treatment device 150 via a threaded rod or other mechanism. By adjusting the height of the transducer 154 within the housing, the depth where the HIFU signals are delivered within the body can be controlled.
In addition, the treatment device 150 includes an offset bearing 170 that, when rotated by a motor 168, wobbles an end of a shaft 172 around the center of the offset bearing 170. The HIFU transducer 154 is coupled to the other end of the shaft 172 through a slidable bearing. A linear actuator 164 or motor positions a spherical bearing 174 that surrounds the shaft 172 towards or away from the offset bearing 170. The position of the spherical bearing 174 on the shaft 172 controls the angular orientation of the focal zone of the HIFU transducer 154.
As shown in
If the motors 164 and 168 are simultaneous rotated back and forth through a desired angle with signals that are approximately 90 degrees out of phase, the focal zone of the HIFU transducer will trace out a substantially circular pattern off a central axis of the treatment device 150, thereby allowing the creation of an elemental treatment volume at a desired location in the body as shown in
In one embodiment, to treat a desired tissue volume, a physician obtains an image of the tissue volume with the imaging transducer 152 and adjusts the radius of a marker ring on the image or interacts with some other graphical user interface or keyboard to define the boundaries of the desired shell. Based on the radius of the marker ring, a computer calculates the volume or shape of the ablated shell to be created in the body. The HIFU transducer and motors within the treatment device 150 are then activated such that a pattern of elemental treatment volumes is ablated to form the shell that surrounds or encapsulates the tissue volume or some other desired pattern of elemental treatment volumes. When creating elemental treatment volumes, the focal zone of the HIFU transducer may be continually moved until a treatment volume is ablated or the focal zone may be moved to discrete positions around the perimeter of the elemental treatment volumes and a HIFU signal applied to create the elemental treatment volumes.
In another embodiment, the linear actuator 160 that adjusts the focal zone depth, the linear actuator 164 that adjusts the angle of the HIFU transducer, and the motor 168 that rotates the shaft 172 are simultaneously operated to create a spiral shell ablation pattern of the type shown in
Following treatment, the patient may be injected with a contrast agent to allow the physician to confirm that blood perfusion has been appropriately reduced or eliminated within the targeted tissue volume. Non-perfusion would provide a strong indication that the treated tissue volume will undergo (or has undergone) ischemic necrosis. Such contrast agents are well known in the art for use with various different imaging modalities including ultrasound, MRI, x-ray, CT, etc.
As will be appreciated, other mechanisms are possible to selectively position the focal zone of a HIFU transducer to create the elemental treatment volumes and treat the desired tissue volume.
In one embodiment, the operating power level is selected by transmitting a number of test signals at different power levels and analyzing the echo signals created in response to the transmitted test signals. The operating power level for HIFU treatment is selected when a desired characteristic of an echo signal is observed, such as when a certain distribution of power at different fundamental and harmonic frequency components is detected within the echo signal. This particular embodiment for selecting the operating power level based on a pre-treatment acoustic assessment the spectral power distribution will be described in more detail subsequently. Further detail of possible methods of selecting and controlling the HIFU power can be found in U.S. patent application Ser. No. 12/537,217 filed Aug. 6, 2009 (U.S. Patent Publication No. 2010/0036292) and which is herein incorporated by reference.
The imaging transducer 152 is controlled by an imaging ultrasound controller 204 that includes conventional ultrasound components such as a transmit/receive switch, beam former, RF amplifiers and signal processors. The output of the ultrasound controller 204 is fed to an ultrasound signal processor 210 that operates to produce ultrasound imaging signals for display on a video monitor 212 or other display. The image signals can also be stored on a computer readable media (DVD, video tape, etc.), printed by a printer or otherwise stored for later diagnosis or analysis.
A computer controlled steerer 205 (or position control) is controlled by the system controller 200 to create a number of elemental treatment volumes to treat a desired volume of tissue. In one embodiment, the computer controlled steerer 205 mechanically adjusts the angular orientation or x,y position of the HIFU transducer 154 and the depth of the focal zone to direct the HIFU energy at a desired location. In another embodiment, the computer controlled steerer 205 electronically adjusts the angular orientation or x,y position of the focal zone of the HIFU transducer 154 and the depth of the focal zone of the HIFU transducer 154 to create the elemental treatment volumes.
A footswitch 214 allows a physician or their assistant to selectively deliver HIFU energy to the patient in order to treat a tissue site. In addition, the physician can manually change the size and shape of the treatment volume and other functions of the system using one or more controls on a control panel 216.
In some embodiments, the system may include an image position control 220 that changes the orientation of the imaging transducer 152 so that the physician can view the desired target tissue volume to be treated at different angles or in different planes. The image position control be either mechanical or electronic and is controlled by the system controller 200.
The system shown in
As indicated above, it has been determined that significant benefits can be obtained both in terms of a reduction in the time required to create a lesion and their uniformity if HIFU treatment signals are delivered at power levels where the treatment signal becomes non-linear in the tissue. In one embodiment mentioned above, a power level used to treat the tissue is selected based on the detected energy in one or more harmonics of the fundamental frequency. Another way of detecting the same effect is to measure the conversion of energy from the fundamental frequency of the treatment signal to the harmonics of the fundamental with changes in applied power and to use the measured conversion as a way to select a power level for the treatment signals.
In one embodiment, the FER curve 300 is computed by applying a number of test signals at different power levels to the treatment site, detecting received backscatter signals and determining how the frequency distribution of the energy in the backscatter signals differs from what the distribution would look like if the tissue were operating like a linear system. For example, for the linear system model, if a test signal of 500 watts of electrical power produces X energy at the fundamental frequency in the received backscatter signal, then 1000 watts of applied electrical power should produce 2× of energy at the fundamental frequency. Any variation from 2× deviates from a linear system and is therefore related to how much energy is being converted into energy at the harmonic frequencies.
In the FER curve 300, those points on the curve in a region 302 are associated with a signal to noise (S/N) ratio that may make their data unreliable. Similarly, those points on the curve in a region 306 are produced at power levels where cavitation is likely in the tissue. Because the tissue is changing state with cavitation, the backscatter signals received at this power level may also not be reliable to determine how much power is being converted to harmonics of the fundamental of the treatment signals.
In order to determine the amount of power that should be applied to the patient to treat the tissue site, it may be necessary to determine how much of the applied power is actually delivered to the focal zone. However, in some cases, identifying the power level associated with the required FER value may be sufficient to determine the appropriate applied power. In cases where additional information is required, an estimation of the power actually delivered to the focal zone can be obtained by measuring the attenuation of the treatment signal between the HIFU transducer and the focal zone.
In one embodiment, the curve 370 is used to select the treatment power of the HIFU signals. For example, empirically determined data obtained from animal trials or from other sources, may be used to select a desired power that should be delivered to the tissue at harmonics of the fundamental frequency. In trials on in-vivo porcine thighs, a level of 100-200 watts of harmonic power at the focal zone has been found to produce uniformly necrosed elemental treatment volumes with little collateral tissue damage, when used in conjunction with the acoustic waveform timing and motion profile parameters described herein. The curve 370 is used to determine what the input electrical power of the treatment signals should be in order to produce 100-200 watts of harmonic power. In the example curve shown, input power levels between 1000 and 1700 watts will produce between 100 and 200 watts of harmonic power. Therefore, by knowing the FER and attenuation curves for the tissue to be treated and what desired level of harmonic power should be delivered to the tissue, a determination can be made of what treatment power should be applied.
Several methodologies for determining the FER and attenuation curves are now described.
At 410, the RF backscatter signals from a number of test signals transmitted at different power levels are detected, digitized and stored in a memory or other computer readable media. At 412, a depth range to interrogate is selected that includes an area around the focal zone of the HIFU transducer. At 414, the RF backscatter signals are filtered to determine the energy at the fundamental frequency of the transmit signals.
At 416, the minimum transmit power needed to obtain backscatter signals with a good signal-to-noise (S/N) ratio at the fundamental frequency is determined. Such determination may be made by nearest neighbor correlation or by determining where the power detected in the window appears to be linear with changes in excitation power. A calculation is made at 418 to determine a transmit power level where cavitation in the tissue begins. Such a power level can be determined using, for example, a template method, nearest neighbor correlation or a noise floor calculation. Each of these techniques is considered known to those of ordinary skill in the art of ultrasound signal processing.
At 420, the energy at the fundamental frequency in a sliding window is determined for various transmit powers. The window size, which is typically determined by transmit pulse attributes, may be selected in response to user input, recalled from memory, or dynamically calculated. The energy in the window at the fundamental frequency is determined and the window is then moved to the next set of data points. The result is a surface plot 424 of the energy at the fundamental frequency at various depths in the tissue versus changes in transmit power.
At 426, the amount of fundamental energy retained (FER) in the backscatter signal for each depth in the depth range is determined. In one embodiment, the energy at the fundamental contained in the backscatter signal for a particular depth is compared with the energy that would be expected if the tissue were operating as a linear system. The expected energy Eexp may be determined by multiplying the energy E0 at the fundamental detected at a lower power PL that is sufficient to produce signals with a good signal to noise ratio by the quotient of the transmit power in question PH divided by PL. The differences between the energy actually detected at the fundamental and the expected energy Eexp is used to produce a surface plot 428 of the local FER values versus depth and applied power.
The process described above, may be repeated for different interrogation angles or positions around the focal zone at 430.
At 432, the results obtained for the local FER values are compounded (such as by averaging the value) for each angle interrogated (if any). The compounded results are fit to a polynomial (which may be first order such as a line) or other mathematically defined function. In one embodiment, the FER curve is normalized to one, such that all values in the FER curve are less than one for depths and power levels where energy is being converted from the fundamental to the harmonics of the fundamental.
As will be appreciated, there are other techniques for producing the FER curve. For example, the filtering at 414 can be done with a digital FIR (finite impulse response) filter and an FFT (fast Fourier transform) can be performed at 420 to determine the amount of energy in the received backscatter signals at the fundamental frequency. Similarly, the signal processing can be performed at baseband by multiplying the backscatter signal by the carrier signal and applying a low pass filter such that the amplitude of the remaining signal is indicative of the energy contained at the fundamental.
To select the treatment power in accordance with this embodiment, it is also necessary to know how much power applied at the tissue surface is actually delivered at the focal zone. To determine this, a computer, such as the system controller 200, is programmed to make an estimation of what the attenuation is in the tissue path from the transducer to the tissue site to be treated. Attenuation values can be recalled from a memory that stores values based on prior experiments or from literature studies for well-known tissue types. However because each patient's physiology is different, the attenuation can also be estimated based on the response of the tissue to one or more test signals.
In the embodiment shown in
In response to a number of test signals being transmitted at different power levels, a number of RF backscatter signals are detected at 504. In one embodiment, such signals are detected with a wide bandwidth receiver (e.g. the imaging transducer 152) that can detect signals at for example, the 2nd-4th harmonics of the transmit signal (other harmonics may be used if available).
At 512, a depth range is selected for which the attenuation is to be measured. The depth range will typically include the focal zone of the transducer. At 514, a window of data in each of the backscatter signals is selected that includes the selected depth range. At 516, the system controller 200 or other computer performs an FFT or some other frequency analysis to determine how much energy is present in each of the 2nd-4th or higher harmonics in the backscatter signals. The energy in the harmonics is then corrected for the response of the detection system due to, for example, roll-off in the pre-amplifiers or the frequency response of the detecting transducer. At 520 the delivered power for which the RF backscatter signals have a good signal-to-noise (S/N) ratio at the harmonics is determined. This power will likely be greater than that required to produce signals with a good S/N ratio at the fundamental frequency. At 518, the power level at which cavitation begins is also determined in the manner described above. A surface plot of the energy at different frequencies versus changes in applied electrical power is calculated at 524. The energy at each harmonic versus applied electrical power is calculated at 526. The steps 510-526 can be repeated for different interrogation points at 528. In one embodiment, measurements are made at 10 points surrounding the desired treatment site.
Once the energy of the harmonics versus changes in applied electrical power have been determined for each of the interrogation points, the results are compounded such as by averaging at 530.
In one embodiment of the disclosed technology, an assumption is made that harmonics are emanating from the vicinity of the focal zone of the HIFU transducer and are created predominantly as result of the nonlinear propagation of the applied HIFU signal. Therefore it is also assumed that signals at the harmonic frequencies are only attenuated on a one-way path from the focal zone back to the detection transducer. In general it is known that signal amplitudes for harmonics generated in tissue should experience a roll-off. For example, if the amount of harmonics has saturated, the roll-off follows a 1/n behavior (where n indicates the nth harmonic). This roll-off should be corrected for and can be determined by the FER value. Because the detected energies of the harmonics have already been corrected for the frequency response of the receiving electronics and detecting transducer, once the harmonic levels have been corrected for the roll off present, any difference in amplitude between the harmonic peaks may be attributed to attenuation. At 532, the energy level of each harmonic at a particular input power level is determined and fitted with a polynomial (or a line). The slope of the polynomial divided by the total length of the tissue path at the point where the signal is measured gives the attenuation of the HIFU signals in units of dB/MHz-cm. This calculation is performed for other applied input powers between the minimum required for good signal-to-noise ratio and the power level at which cavitation begins. The result is an attenuation curve that plots attenuation versus applied input power.
In some situations, it may be desirable to determine a local attenuation value such as in a fibroid itself. As shown in steps 544, the HIFU transducer may be moved with respect to the tissue or its focal zone changed and the new attenuation curve determined in the manner described above. The local attenuation at any given input power is therefore equal to the difference of the attenuation values at each depth, multiplied by their respective depths, divided by the difference in depths.
Once the FER curve and the attenuation curve of the tissue are known, an appropriate input power for treatment is determined by multiplying the input power by the attenuation curve 350 at a number of power levels between the minimum needed for a good S/N ratio and the power level where cavitation begins. As shown in
As will be appreciated, the power of the treatment signals used to treat the tissue can also be predetermined and recalled from stored memory based on a measured characteristic of the tissue in question. If the local attenuation of the tissue is known, a FER curve based on previously performed studies can be used to predict how much energy should be applied to achieve a desired harmonic power at the treatment site. Alternatively, if the FER curve is determined for the tissue in question, a treatment power can be selected based on previously performed studies. Another option relying on predetermined empirical treatment set points is to measure the height of any part of the tissue path that is effectively non-attenuative (e.g., urine contained within the bladder) and reduce the empirically-determined power value known for that tissue depth by the appropriate amount to account for the non-attenuative portion. For example, if the tissue path for a 10 cm treatment depth contains a 2-cm segment composed of urine in the bladder, then the empirically-determined power value for a 8-cm treatment depth can be applied instead as a first-order approximation of the appropriate HIFU output level.
With the foregoing description, various embodiments of the disclosure may be implemented, including but not limited to the following examples.
In at least one example, a system for treating uterine fibroids or other uterine tissue may comprise a hand-held or hand-guided HIFU applicator with a movable transducer focal zone that is configured to deliver HIFU treatment signals to a treatment site in a uterine fibroid or other uterine tissue; an imaging transducer that produces imaging signals representative of the uterine fibroids or other uterine tissue; and a processor programmed to determine a pattern in which to apply HIFU around the periphery of a fibroid or other targeted volume of uterine tissue and to control the position of the focal zone of the HIFU transducer to apply HIFU energy in this pattern.
In various embodiments, the pattern in which HIFU is applied consists of a number of elemental treatment volumes created around the periphery of the fibroid or other targeted volume of uterine tissue. Each elemental treatment volume may have a size selected such that an interior region is treated by indirect heating as the treatment energy is repeatedly applied to a perimeter of the elemental treatment volume. Furthermore, the processor may be programmed to control the position the focal zone of the HIFU transducer in a pattern to create a number of elemental treatment volumes within an interior of the uterine fibroid or the targeted volume of uterine tissue.
In various embodiments, the HIFU treatment signals are transmitted at a power sufficient to convert a substantial portion of the power at a fundamental frequency of the therapeutic HIFU signals to power in the harmonics of the fundamental frequency at the treatment site. The processor may be programmed to determine a power level for the HIFU treatment signals such that a substantial portion of the power at a fundamental frequency of the therapeutic HIFU signals is converted to power in the harmonics of the fundamental frequency at the treatment site based on a number of test signals transmitted at different power levels. The elemental treatment volume may be cylindrical and have a diameter approximately equal to a length of the focal zone. The processor may be programmed to: control a mechanical linkage that adjusts the position of the HIFU transducer to move the focal zone; control an electronic beam steerer to move the focal zone; automatically detect the boundaries of the uterine fibroid or other volume of uterine tissue to be treated; and/or receive input from a user that is indicative of the boundaries of the uterine fibroid or other volume of uterine tissue to be treated.
In another example, a system for thermally necrosing a uterine fibroid or other uterine tissue with high intensity focused ultrasound (HIFU) may comprise a hand-held or hand-guided HIFU applicator with a movable transducer focal zone that is configured to deliver therapeutic HIFU signals having a fundamental frequency to the treatment site; a transmit controller configured to supply driving signals to the HIFU transducer such the transducer produces therapeutic HIFU signals at a power sufficient to convert a substantial portion of the power at a fundamental frequency of the therapeutic HIFU signals to power in the harmonics of the fundamental frequency at the treatment site; and a position controller that is configured to position the focal zone of the HIFU transducer in the uterine fibroid or other uterine tissue to create one or more elemental treatment volumes without temperature feedback.
In various embodiments, each elemental treatment volume may be a cylinder having a diameter substantially equal to a length of the focal zone. The power of the HIFU treatment signals is selected that the HIFU treatment signals reach or exceed the onset of shock at the treatment site.
In yet another example, a system for thermally necrosing tissue at a treatment site with high intensity focused ultrasound (HIFU) may comprise a HIFU transducer with a movable focal zone that is configured to deliver therapeutic HIFU signals having a fundamental frequency to the tissue at the treatment site; a transmit controller configured to supply driving signals to the HIFU transducer such that the transducer produces therapeutic HIFU signals at a power sufficient to convert a substantial portion of the power at a fundamental frequency of the therapeutic HIFU signals to power in the harmonics of the fundamental frequency at the treatment site; and a position controller that is configured to position the focal zone of the HIFU transducer in the tissue to create one or more elemental treatment volumes in the presence of bubbles.
In still another example, a system for treating uterine fibroids or other uterine tissue may comprising a hand-held or hand-guided HIFU applicator with a movable transducer focal zone that is configured to deliver HIFU treatment signals to a treatment site in a uterine fibroid or other uterine tissue; an imaging transducer that produces imaging signals representative of the treatment site; a processor programmed to determine a pattern in which to apply HIFU to a fibroid or other targeted volume of uterine tissue; and a position controller that selectively controls the position of the focal zone of the HIFU transducer to apply HIFU energy in the determined pattern such that a fibroid or other volume of uterine tissue up to 5 cm in diameter can be effectively treated in under 10 minutes.
While illustrative embodiments have been illustrated and described, it will be appreciated that various changes can be made therein without departing from the scope of the invention. For example, although the energy source used to create the ablated shell is HIFU in the disclosed embodiments, other energy sources could be used such as radiation, lasers, RF, microwaves, cryoablation, etc. Some of these energy sources are minimally invasive such that they must be delivered to the tissue volume with a catheter, endoscope, or the like. Applying energy from these energy sources ablates the perimeter of the tissue volume to create an ablated shell. In another embodiment, the HIFU transducer may be insertable in to the body such as transvaginally or rectally. If the tissue volumes to be treated can be seen from the location of the HIFU transducer, then images of the tissue can be obtained with image sensors other than ultrasound image sensors. In some embodiments, the imaging of the desired treatment volume may be done with another type of imaging modality such as MRI, x-ray, infrared, or the like in a manner that allows a physician to confirm that the HIFU is being delivered to the area of desired target tissue volume. Therefore, the scope of the invention is to be determined from the following claims and equivalents thereof.
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