U.S. patent application number 11/158657 was filed with the patent office on 2007-01-18 for controlled, non-linear focused ultrasound treatment.
This patent application is currently assigned to InSightec-Image Guided Treatment Ltd.. Invention is credited to David Freundlich, Shuki Vitek, Kobi Vortman.
Application Number | 20070016039 11/158657 |
Document ID | / |
Family ID | 36950284 |
Filed Date | 2007-01-18 |
United States Patent
Application |
20070016039 |
Kind Code |
A1 |
Vortman; Kobi ; et
al. |
January 18, 2007 |
Controlled, non-linear focused ultrasound treatment
Abstract
A system for treating tissue within a body is configured to
deliver a first level of ultrasound energy to a target tissue
region for a first duration resulting in the generation of
microbubbles in the target tissue region, determine one or more
characteristics of the target tissue region in the presence of the
microbubbles, and deliver a second level of ultrasound energy to
the target tissue region for a second duration, wherein one or both
of the second energy level and the second duration are based, at
least in part, on the determined one or more characteristics of the
target tissue region.
Inventors: |
Vortman; Kobi; (Haifa,
IL) ; Vitek; Shuki; (Haifa, IL) ; Freundlich;
David; (Haifa, IL) |
Correspondence
Address: |
VISTA IP LAW GROUP LLP
12930 Saratoga Avenue
Suite D-2
Saratoga
CA
95070
US
|
Assignee: |
InSightec-Image Guided Treatment
Ltd.
|
Family ID: |
36950284 |
Appl. No.: |
11/158657 |
Filed: |
June 21, 2005 |
Current U.S.
Class: |
600/439 ;
601/2 |
Current CPC
Class: |
A61B 8/481 20130101;
A61B 90/37 20160201; A61B 2090/376 20160201; A61B 2090/378
20160201; A61B 2090/374 20160201; A61N 7/02 20130101; A61B
2017/22008 20130101; A61B 8/467 20130101 |
Class at
Publication: |
600/439 ;
601/002 |
International
Class: |
A61B 8/00 20060101
A61B008/00 |
Claims
1. A method of treating tissue within a body, comprising:
delivering a first level of ultrasound energy to a target tissue
region for a first duration resulting in the generation of
microbubbles in the target tissue region; determining one or more
characteristics of the target tissue region in the presence of the
microbubbles; and delivering a second level of ultrasound energy to
the target tissue region for a second duration, wherein one or both
of the second energy level and the second duration are based, at
least in part, on the determined one or more characteristics of the
target tissue region.
2. The method of claim 1, wherein each of the first duration and
second duration are between 0.05 to 3 seconds.
3. The method of claim 1, wherein the second energy level is
determined by adjusting one or more of a frequency, a phase, and an
amplitude of a drive signal used to generate the first energy level
in order to achieve a maximum coagulation volume while controlling
a coagulation location.
4. The method of claim 1, wherein the second level of ultrasound
energy is delivered to a different focal location in the target
tissue region than the first level.
5. The method of claim 1, wherein the second level of ultrasound
energy is based, at least in part, on maintaining a temperature of
the target tissue region above a prescribed threshold
temperature.
6. The method of claim 1, wherein the second level of ultrasound
energy is based, at least in part, on maintaining a temperature of
the target tissue region below a prescribed threshold
temperature.
7. The method of claim 1, wherein the one or more characteristics
of the target tissue region are determined, at least in part, by
obtaining a temperature sensitive image of the target tissue
region.
8. The method of claim 1, wherein the one or more characteristics
of the target tissue region are determined, at least in part, by
obtaining an actual thermal dose distribution associated with the
target tissue region, and comparing the obtained actual thermal
dose distribution with a predicted thermal dose distribution.
9. The method of claim 1, wherein the second ultrasound energy
level is different from the first ultrasound energy level.
10. The method of claim 1, further comprising repeating the steps
of determining one or more characteristics of the target tissue
region in the presence of microbubbles in the target tissue region,
and delivering the second level of ultrasound energy to the target
tissue region, until a desired effect on the target tissue region
is achieved.
11. A system for treating tissue within a body, comprising: means
for delivering a first level of ultrasound energy to a target
tissue region for a first duration resulting in the generation of
microbubbles in the target tissue region; means for determining one
or more characteristics of the target tissue region in the presence
of the microbubbles; and means for delivering a second level of
ultrasound energy to the target tissue region for a second
duration, wherein one or both of the second energy level and second
duration are based, at least in part, on the determined one or more
characteristics of the target tissue region.
12. A controller for a focused ultrasound system, the focused
ultrasound system having a plurality of transducer elements for
delivering ultrasound energy to a target tissue region in a
patient's body, the controller configured to: cause the delivery of
a first level of ultrasound energy to the target tissue region for
a first duration resulting in the generation of microbubbles in the
target tissue region; determine one or more characteristics of the
target tissue region in the presence of the microbubbles; and cause
the delivery of a second level of ultrasound energy to the target
tissue region for a second duration, wherein one or both of the
second ultrasound energy level and the second duration are based,
at least in part, on the determined one or more characteristics of
the target tissue region.
13. The system of claim 12, wherein each of the first duration and
second duration are between 0.05 to 3 seconds.
14. The system of claim 12, wherein the second energy level is
determined by adjusting one or more of a frequency, a phase, and an
amplitude of a drive signal used to generate the first energy level
in order to achieve a maximum coagulation volume while controlling
a coagulation location.
15. The system of claim 12, wherein the second level of ultrasound
energy is delivered to a different focal location in the target
tissue region than the first level.
16. The system of claim 12, wherein the second level of ultrasound
energy is based, at least in part, on maintaining a temperature of
the target tissue region above a prescribed threshold
temperature.
17. The system of claim 12, wherein the second level of ultrasound
energy is based, at least in part, on maintaining a temperature of
the target tissue region below a prescribed threshold
temperature.
18. The system of claim 12, wherein the one or more characteristics
of the target tissue region are determined, at least in part, by
obtaining a temperature sensitive image of the target tissue
region.
19. The system of claim 12, wherein the one or more characteristics
of the target tissue region are determined, at least in part, by
obtaining an actual thermal dose distribution associated with the
target tissue region, and comparing the obtained actual thermal
dose distribution with a predicted thermal dose distribution.
20. The system of claim 12, wherein the second ultrasound energy
level is different from the first ultrasound energy level.
21. The system of claim 12, wherein the controller is configured to
repeat the processes of determining one or more characteristics of
the target tissue region in the presence of microbubbles in the
target tissue region, and delivering the second level of ultrasound
energy to the target tissue region, until a desired effect on the
target tissue region is achieved.
Description
FIELD OF INVENTION
[0001] The present invention relates generally to apparatus and
methods for delivering focused ultrasound energy to targeted tissue
regions in a patient's body.
BACKGROUND
[0002] High intensity focused ultrasonic energy (i.e., having a
frequency greater than about 20 kilohertz), may be used
therapeutically to treat internal tissue regions within a patient.
For example, ultrasonic waves may be used to induce coagulation
and/or necrosis in a target tissue region, such as a tumor. In this
process, the ultrasonic energy is "absorbed" by the tissue, causing
the generation of heat. The absorbed energy heats the tissue cells
in the target region to temperatures that exceed protein
denaturation thresholds, usually above 60.degree. C., resulting in
coagulation and/or necrosis of the tissue in the target region.
[0003] During a focused ultrasound procedure, small gas bubbles, or
"microbubbles," may be generated in the liquid contained in the
tissue, e.g., due to the stress resulting from negative pressure
produced by the propagating ultrasonic waves and/or from when the
heated liquid ruptures and is filled with gas/vapor. On the one
hand, the microbubbles have the positive treatment effect by
generating higher harmonic frequencies of the original wave energy,
thereby greatly increasing the absorption of energy in the tissue,
and by multiple reflection that extends the acoustic pass in the
target region. On the other hand, the reaction of tissue containing
a higher relative percentage of microbubbles to the continued
application of the ultrasound energy is non-linear and difficult to
predict. For example, the microbubbles may collapse due to the
applied stress from an acoustic field. This mechanism, called
"cavitation," may cause extensive tissue damage beyond that
targeted, and may be difficult to control.
SUMMARY OF THE INVENTION
[0004] In accordance with one embodiment of the invention, a method
of treating tissue within a body includes delivering a first level
of ultrasound energy to a target tissue region for a first duration
resulting in the generation of microbubbles in the target tissue
region, determining one or more characteristics of the target
tissue region in the presence of the microbubbles, and delivering a
second level of ultrasound energy to the target tissue region for a
second duration, wherein one or both of the second energy level and
the second duration are based, at least in part, on the determined
one or more characteristics of the target tissue region.
[0005] In accordance with another embodiment of the invention, a
system for treating tissue within a body includes means for
delivering a first level of ultrasound energy to a target tissue
region for a first duration resulting in the generation of
microbubbles in the target tissue region, means for determining one
or more characteristics of the target tissue region in the presence
of the microbubbles, and means for delivering a second level of
ultrasound energy to the target tissue region for a second
duration, wherein one or both of the second energy level and second
duration are based, at least in part, on the determined one or more
characteristics of the target tissue region.
[0006] In accordance with still another embodiment of the
invention, a controller for a focused ultrasound system, the
focused ultrasound system having a plurality of transducer elements
for delivering ultrasound energy to a target tissue region in a
patient's body, the controller configured to cause the delivery of
a first level of ultrasound energy to the target tissue region for
a first duration resulting in the generation of microbubbles in the
target tissue region, determine one or more characteristics of the
target tissue region in the presence of the microbubbles, and cause
the delivery of a second level of ultrasound energy to the target
tissue region for a second duration, wherein one or both of the
second ultrasound energy level and the second duration are based,
at least in part, on the determined one or more characteristics of
the target tissue region.
[0007] Other aspects and features of the invention will be evident
from reading the following detailed description of the illustrated
embodiments.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] Various embodiments of the invention are described
hereinafter with reference to the accompanying figures. It should
be noted that the figures are not drawn to scale and elements of
similar structures or functions are represented by like reference
numerals throughout the figures. It should also be noted that the
figures are only intended to facilitate the description of the
illustrated embodiments, and are not intended as an exhaustive
illustration or description thereof.
[0009] FIG. 1A illustrates an exemplary focused ultrasound system,
including an ultrasound transducer for focusing ultrasonic energy
at a target tissue region within a patient.
[0010] FIG. 1B is a cross-sectional detail of the ultrasonic
transducer and target tissue region of FIG. 1A, illustrating
microbubbles generated in tissue located in a focal zone of the
transducer.
[0011] FIG. 2 is a cross-sectional view of a target tissue mass,
illustrating a series of planned sonication areas.
[0012] FIG. 3 illustrates a method for constructing a treatment
plan using the system of FIG. 1A, in accordance with some
embodiments of the invention.
[0013] FIG. 4 illustrates a method for treating tissue using
microbubbles to enhance heating of the target tissue region, in
accordance with some embodiments of the invention.
[0014] FIGS. 5A and 5B are two-dimensional representations of a
target sonication area, illustrating instances in which the actual
thermal ablation is either greater than (FIG. 5A), or less than
(FIG. 5B), a predicted amount.
[0015] FIG. 6 illustrates an exemplary comparison of actual versus
predicted thermal doses for a target tissue region.
[0016] FIG. 7 illustrates a method of controlling thermal dosing in
accordance with some embodiments of the invention.
[0017] FIG. 8 illustrates a method for updating a treatment plan in
accordance with some embodiments of the invention.
DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS
[0018] FIG. 1A illustrates a focused ultrasound system 10 in
accordance with some embodiments. The system 10 includes an
ultrasound transducer 14, drive circuitry (driver) 16 coupled to
the transducer 14, a controller 18 coupled to the driver 16, an
imaging device 20, and a processor 22 coupled to the imaging device
20 and the controller 18. The transducer 14 may direct acoustic
energy represented by beam 15 towards a target 42, typically a
tumor or other tissue region, within a patient 40. The beam 15 may
be used to coagulate, generate mechanical damage, necrose, heat, or
otherwise treat the target 42, which may be a benign or malignant
tumor within an organ or other tissue structure (not shown). The
system 10 also includes a user interface (UI) 23, such as a screen,
keyboard, a mouse, a button, a touch pad, and the like, for
allowing a user to input data, such as treatment parameters, to the
processor 22. The user interface 23 is shown as a separate
component from the processor 22. Alternatively, the user interface
23 can be integrated with the processor 22.
[0019] The transducer 14 includes multiple piezoelectric elements
24 together providing a transducer array. Alternatively, the
transducer 14 may include a single piezoelectric transducer
element. In some embodiments, the transducer 14 may have a concave
or bowl shape, such as a "spherical cap" shape, i.e., having a
substantially constant radius of curvature such that the transducer
14 has an inside surface defining a portion of a sphere.
Alternatively, the transducer 14 may have a substantially flat
configuration (not shown), and/or may include an outer perimeter
that is generally, but not necessarily, circular. The transducer 14
may be divided into any desired number of elements (not shown).
[0020] In alternative embodiments, the transducer 14 may include
one or more transducer elements 24 having a variety of geometric
shapes, such as hexagons, triangles, squares, and the like, and may
be disposed about a central axis, preferably but not necessarily,
in a substantially uniform or symmetrical configuration. In the
illustrated embodiments, each of the transducer elements 24 may be
a one-piece piezoceramic part, or alternatively, be composed of a
mosaic arrangement of a plurality of small piezoceramic elements
(e.g., phased array). The piezoceramic parts or the piezoceramic
elements may have a variety of geometric shapes, such as hexagons,
triangles, squares, and the like. Alternatively the transducer
could be built from other materials that are capable to produce
high power acoustic wave. The transducer elements 24 can be
time-delayed or phase-delayed driven. Delay elements (not shown),
well known in the art, may be coupled to respective transducer
elements 24 for providing delay times for the respective transducer
elements 24 such that the delivered acoustic waves by the
transducer elements 24 focuses onto the zone 38. If the transducer
elements 24 include a plurality of elements, each element may be
coupled to a respective delay element. The delay elements may be
implemented as a part of the ultrasound transducer device 14, the
driver 16, or the controller 18.
[0021] In some embodiments, the transducer elements 24 can be
movably secured to a structure (not shown) such that the position
and/or shape of the focal zone 38 can be varied during use. In such
cases, the transducer device 14 includes a positioner for moving
the transducer elements 24. The positioner may be configured to
move the transducer 14 in one or more directions, and preferably in
any of three orthogonal directions. The positioner can, for
examples, include a motor, such as an electric motor or a
piezoelectric motor, a hydraulic, or a gimbal system. In some
embodiments, the structure can include a plurality of movable
sections to which one or more of the transducer elements 24 are
secured. In such cases, the movable sections are installed on
respective gimbals, and the transducer elements 24 are movable by
operation of the gimbals. The transducer elements 24 can be
configured to move in one degree of freedom, or in multiple degree
of freedoms (e.g., two to six degree of freedoms). A focal distance
(a distance from the transducer 14 to a focal zone 38 of the
acoustic energy emitted by the transducer 14) may be adjusted
electronically, mechanically, or using a combination of mechanical
and electronic positioning, as is known in the art.
[0022] The actual configuration of the transducer 14, however, is
not important for purposes of understanding the embodiments of the
present invention, and any of a variety of ultrasound transducers
may be used, such as flat circular arrays, linear arrays, and the
like.
[0023] The transducer 14 may be mounted within a casing or chamber
(not shown) filled with degassed water or acoustically transmitting
fluid. The chamber may be located within a table (not shown) upon
which a patient 40 may be positioned, or within a fluid-filled bag
mounted on a movable arm that may be placed against a patient's
body. The contact surface of the chamber, generally includes a
flexible membrane (not shown) that is substantially transparent to
ultrasound. For examples, the flexible member may be constructed
from mylar, polyvinyl chloride (PVC), or other suitable plastic
material. A fluid-filled bay (not shown) may be provided on the
membrane that may conform easily to the contours of the patient 40
positioned on the table, thereby acoustically coupling the patient
40 to the transducer 14 within the chamber. In addition or
alternatively, acoustic gel, water, or other fluid may be provided
between the patient 40 and the membrane to facilitate further
acoustic coupling between the transducer 14 and the patient 40.
[0024] In the illustrated embodiments, the transducer elements 24
are coupled to the driver 16 and/or controller 18 for generating
and/or controlling the acoustic energy emitted by the transducer
elements 24. For example, the driver 16 may generate one or more
electronic drive signals, which may be controlled by the controller
18. The transducer elements 24 convert the drive signals into
acoustic energy 15, which may be focused using conventional
methods. The controller 18 and/or driver 16 may be separate or
integral components. It will be appreciated by one skilled in the
art that the operations performed by the controller 18 and/or
driver 16 may be performed by one or more controllers, processors,
and/or other electronic components, including software and/or
hardware components. The terms controller and control circuitry may
be used herein interchangeably, and the terms driver and drive
circuitry may be used herein interchangeably.
[0025] The driver 16, which may be an electrical oscillator, may
generate drive signals in the ultrasound frequency spectrum, e.g.,
as low as fifty kilohertz (20 KHz), or as high as ten megahertz (10
MHz), and more preferably, between 0.1 to 10 MHz. Preferably, the
driver 16 provides drive signals to the transducer elements 24 at
radio frequencies (RF), for example, between about a hundred
Kiloherz to ten Megahertz (0.1-10 MHz), and more preferably between
200 Kilohertz and three Megahertz (0.20 and 3.0 MHz). However, in
other embodiments, the driver 16 can also be configured to operate
in other ranges of frequencies. When the drive signals are provided
to the transducer elements 24, the transducer elements 24 emit
acoustic energy 15 from their respective exposed surfaces, as is
well known to those skilled in the art.
[0026] The controller 18 may control a phase component of the drive
signals to respective elements 24 of the transducer 14, e.g., to
control a shape of a focal zone 38 generated by the transducer 14
and/or to move the focal zone 38 to a desired location. For
example, the controller 18 may control the phase shift of the drive
signals based upon a radial position of respective transducer
elements 24 of the transducer 14, e.g., to adjust a focal distance,
or to adjust phases to control the focus lateral position. In
addition or alternatively, the controller 18 may control the
positioning system to move the transducer 14, and consequently, the
location of the focal zone 38 of the transducer 14, to a desired
location (e.g., within the target tissue region 42). In some
embodiments, the controller 18 may also control a frequency of the
drive signals.
[0027] The controller 18 may control amplitude (and/or other
aspects) of the drive signals, and therefore, the intensity or
power of the acoustic waves transmitted by the transducer elements
24. For example, the controller 18 may cause the drive circuitry 16
to provide drive signals to the transducer 14 above a threshold
such that the acoustic energy emitted by the transducer 14 may
generate microbubbles in fluid within tissue in the focal zone 38.
Subsequently, the controller 18 may lower the intensity below a
threshold to a level at which the generation of microbubbles is
minimized in the tissue within the focal zone 38, yet may still
necrose, coagulate, or otherwise heat tissue, as explained below.
For example, the controller 18 may subsequently lower the intensity
to approximately 0 to thereby prevent further formation of
microbubbles at the focal zone 38 during a treatment process.
[0028] In some embodiments, the controller 18 is also used to
control respective transducer elements 24 to protect a tissue
region (e.g., healthy tissue that is adjacent the target tissue 42,
at the far field relative to the target tissue 42, or at the near
field relative to the target tissue 42), while treating the target
tissue. Particularly, the controller 18 is configured to control an
amplitude, a phase, a frequency, or a combination thereof, of
respective transducer elements 14, such that an energy intensity at
the target tissue 42 is above a prescribed threshold (treatment
threshold) level sufficient to treat the target tissue 42, while an
energy intensity at tissue (sensitive tissue) desired to be
protected is below a prescribed threshold (safety threshold) level
for protection of the sensitive tissue. For examples, the
controller 18 can generate a drive signal to reduce an energy
delivered to the sensitive tissue by one of the transducer elements
24, or not activate one of the transducer elements 24, thereby
creating a zone of relatively lower energy at the sensitive tissue.
As used herein, the term, "sensitive tissue", refers to tissue that
is desired to be protected, and should not be limited to tissue
have a certain sensitivity.
[0029] In the illustrated embodiments, the imaging device 20 is
configured for obtaining image data of at least a portion of the
target region 42 before or while treating the patient 40. For
example, the imaging device 20 may be a magnetic resonance imaging
(MRI) device, such as that disclosed in U.S. Pat. Nos. 5,247,935,
5,291,890, 5,368,031, 5,368,032, 5,443,068 issued to Cline et al.,
and U.S. Pat. Nos. 5,307,812, 5,323,779, 5,327,884 issued to Hardy
et al., the disclosures of which are expressly incorporated by
reference herein. In other embodiments, the imaging device 20 can
be another type of device capable of performing an imaging of
tissue, such as, a x-ray device, a fluoroscope, an ultrasound
imaging device, or a computed tomography machine. Although the
imaging device 20 is shown separated from the transducer device 14,
in alternative embodiments, the imaging device 20 can be a
component of, or integrated with, the transducer device 14. For
example, the imaging device 20 can be secured to a center of the
transducer device 14 in some embodiments. Also, the term "image" as
used herein is intended to include image data that may be stored in
a circuitry or a computer-readable medium, and is not limited to
image data that is displayed to be visually perceived.
[0030] During use of the system 10, image data obtained from the
imaging device 20 are transmitted to processor 22 for processing.
In some embodiments, the processor 22 can be a computer, or a
component of a computer. As used herein, the term, "computer" is
not limited to desktop computers and laptops, and include any
device capable of performing the functions described herein. For
example, the processor 22 can be a general purpose processor, or an
application specific processor (e.g., an ASIC processor, DSP,
etc.). In further embodiments, the processor 22 can be a software
(an example of a computer product), or a combination of a software
and a hardware. In FIG. 1A, the processor 22 is shown as a separate
component from the driver 16 and the controller 18. Alternatively,
the processor 22 can be a component of the driver 16, and/or a
component of the controller 18.
[0031] After receiving image data from the imager 20, the processor
22 may use the image data to construct a treatment plan, in which
case, the processor 22 functions as a planner. When functioning as
a planner, the processor 22 automatically constructs a treatment
plan, which consists of a series of treatment site represented by
thermal dose properties. The purpose of the treatment plan is to
ensure complete ablation of target mass 42 by planning a series of
sonications that will apply a series of thermal doses at various
points within target mass 42, resulting in a composite thermal dose
sufficient to ablate the entire mass 42.
[0032] For example, the plan will include the location, frequency,
duration, and power of the sonication and the position and mode of
the focal spot for each treatment site in series of treatment
sites. The mode of the focal spot refers to the fact that the focal
spot can be of varying dimensions. Typically, there will be a range
of focal modes from small to large with several intermediate modes
in between. The actual size of the focal spot will vary, however,
as a function of the focal distance (l), the frequency, and focal
spot dispersion mode that could be generated by spatial dithering
of the focus or by shaping of the focus acoustically. While
planning, the processor 22 may take the tissue data in the pass
zone, types of tissues, frequency, mode and focal spot size
variation into account when planning the position of the focal spot
for a treatment site, the required power level and energy level.
The treatment plan is then passed to the controller 18 in the
relevant format to allow the controller 18 to perform its
tasks.
[0033] In order to construct the treatment plan, the processor 22
uses input from the user interface 23 and the imager 20. For
example, in one implementation, a user specifies the target volume,
the clinical application protocol, i.e., breast, pelvis, eye,
prostate, etc., via the user interface 23. Selection of the
clinical application protocol may control at least some of the
default thermal dose prediction properties such as thermal dose
threshold, thermal dose prediction algorithm, maximum allowed
energy density, thermal dose for different treatment site, cooling
time between thermal doses, etc.
[0034] In other implementations, some or all of these properties
are input through the user interface 23 as user specified thermal
dose prediction properties. Other properties that may be input as
user specified thermal dose prediction properties are the
sonication grid density (how much the sonications should overlap)
and the physical parameters of transducer 14. The latter two
properties may also be defined as default parameters in certain
implementations. Additionally, a user may edit any of the default
parameters via the user interface 23. In one implementation, user
interface 23 comprises a Graphical User Interface (GUI): A user
employs a mouse or touch screen to navigate through menus or
choices as displayed on a display device in order to make the
appropriate selections and supply the required information.
[0035] To further aid the processor 22 in constructing the
treatment plan, the imager 20 supplies image data of the target
mass 42 that can be used to determine volume, position, and
distance from a skin surface 25 (FIG. 1B). In one implementation,
the imager 20 is a MRI device and the images provided are
three-dimensional images of the target mass 42. Once the processor
22 receives the input from the user interface 23 and the image data
from the imager 20, the processor 22 automatically constructs the
treatment plan.
[0036] As illustrated in FIG. 2, the goal of the treatment plan is
to completely cover a target tissue mass 42, and a predefined
margin around it if so desired, by delivering a series of
sonications to treat a plurality of portions 80 of the target
tissue mass 42, so that the entire target mass 42 is fully ablated.
In one implementation, once the treatment plan is constructed, a
user may, if required, edit the plan by using the user interface
23. In one implementation, the processor 22 will also produce a
predicted thermal dose distribution. This distribution is similar
to the distribution illustrated in FIG. 2, wherein the predicted
thermal doses are mapped onto images of target mass 42 provided by
the imager 20. In one implementation, the distribution is a
three-dimensional distribution. In some embodiments, an algorithm
is included in the processor 22 that limits the peak temperature of
the focal zone 38. The algorithm is referred to as the dose
predictor.
[0037] In one implementation, the treatment plan is a
three-dimensional treatment plan. FIG. 3 illustrates one preferred
process flow diagram for constructing a three-dimensional treatment
plan, using three-dimensional images of the target mass 42 and a
three-dimensional predicted thermal dose distribution. The ability
of focusing at different focal lengths (l) leads to variable focal
spots and variable lesion sizes in the target mass 42 as a function
of (y), the transducer axis (FIG. 1B). Therefore, as a result of
the process illustrated in FIG. 3, the processor 22 finds a minimum
number of overlapping cross-sectional treatment layers required to
ablate a portion of the target mass 42 extending from y.sub.near to
y.sub.far. The processor 22 may also predict the lesion size in the
cross-sectional layer and will provide the maximal allowed energy
in each layer, taking into account the maximum allowed temperature
rise. The energy or power will be normalized among different
layers, such that the maximal temperature at the focus remains
approximately constant throughout the treatment zone.
[0038] Constructing the three-dimensional treatment plan begins in
step 102 with obtaining diagnostic quality images of the target
mass 42. For example, the diagnostic quality images may be the
preliminary images supplied by an imager such as the imager 20. In
step 104, the processor 22 uses the diagnostic images to define the
treatment region, or the user may define it through the user
interface 23. Then, in step 106, a line y[y.sub.near:y.sub.far] is
defined such that (y) cuts through target zone perpendicular to the
transducer 14 along the transducer axis from the nearest point
within the target mass 42 (y.sub.near) to the furthest point
(y.sub.far). Line (y) will be the axis along which the treatment
layers will be defined.
[0039] Once (y) is defined, the processor 22 will perform a dose
prediction in step 108 using the maximal power required for small
and large spot sizes at (y.sub.far) In step 110, the processor 22
determines if the resulting maximal temperature exceeds the allowed
limit. It should be noted that properties such as the maximal power
and the maximal temperature limit may be supplied as default
thermal dose prediction properties or may be supplied as user
supplied thermal dose prediction properties. If the resulting
maximal temperature does exceed the allowable limit, the power is
scaled down linearly in step 112 until the temperature elevation is
within the allowable limit, or until some other predefined
threshold is crossed.
[0040] The small and large focal modes may correspond to modes 0
and 4, respectively, with additional modes 1, 2 and 3 falling
between modes 0 and 4. Therefore, in step 114, the processor 22
predicts the maximal power for the intermediate modes 1, 2 and 3,
from the scaled max powers at modes 0 and 4. Thus, in step 116, if
there are further modes, the processor 22 reverts to step 108 and
predicts the maximal power for these modes. If it is the last mode
for (y.sub.far) then the processor 22 uses the same scaled max
power, as in step 118, to find the corresponding maximal powers for
each focal mode at (y.sub.near). Then in step 120, the processor 22
finds the maximal temperature elevation and lesion size for the
appropriate mode and the required maximal power at a point
(y.sub.1), such that y.sub.near<y.sub.1<y.sub.far.
Preferably, (y.sub.1) is close to (y.sub.near). For example, in one
implementation, y.sub.1=y.sub.near+25 mm. If the temperature
elevation at (y.sub.1) exceeds the allowable limit as determined in
step 122, then in step 124 the power is scaled down until the
temperature elevation is within the limit, and then the processor
22 determines the resulting lesion size at (y.sub.1).
[0041] Using an overlap criterion with respect to the (y.sub.near)
boundary, which may be provided via a sonication grid density, the
first treatment is placed (step 126). Of course, the treatment will
actually be a three-dimensional volume. Then, in step 128, using an
inter-layer overlap criterion, an auxiliary treatment slice is
placed on top of the previous treatment layer using the same height
for the second slice as for the first slice. In step 130, the
processor 22 determines if more layers are needed to reach
(y.sub.far). If more layers are needed, then the process reverts to
step 118, and (y.sub.1) replaces (y.sub.near) (step 132) in the
algorithm.
[0042] Once the last treatment layer is reached, the processor 22
will determine if the layer extends beyond the target limit
(y.sub.far). If the layer does extend too far, then the overlap
criterion should be used with the outer limit (y.sub.far) as a
boundary instead of the previous layer. Using (y.sub.far) in the
overlap criterion may cause overdose but will not damage healthy
tissue outside target mass 42. In one implementation, the thermal
dose properties are automatically optimized using physiological
parameters as the optimization criterion. For example, mechanical
tissue parameters like compressibility, stiffness, and scatter, may
be used.
[0043] It should be noted that the method of determining a
treatment plan should not be limited by the above example, and that
other techniques known in the art may also be used to determine a
treatment plan as an example non-layer based planning. Also, in
other embodiments, the processor 22 does not construct the
treatment plan. Instead, the processor 22 is configured to receive
a pre-determined treatment plan via an input (e.g., a disk drive, a
cable port, a USB port, a phone port, a memory slot, etc.).
[0044] After a treatment plan has been obtained, the system 10 can
then be used to treat the patient 40. During use, the patient 40
may be positioned on the table with water, acoustically conductive
gel, and the like applied between the patient 40 and the bag or
membrane, thereby acoustically coupling the patient 40 to the
transducer 14. The transducer 14 may be focused towards a target
tissue region 38 within a tissue 42, which may, for example, be a
cancerous or benign tumor. The transducer 14 may be activated by
supplying a set of drive signals at one or more frequencies to the
transducer 14 to focus acoustic energy at the target tissue 42,
represented by energy beam 15. As the acoustic energy 15 passes
through the patient's body, a fraction of the acoustic energy 15 is
converted to heat, which may raise the temperature of the target
tissue 42. The acoustic energy 15 may be focused on the target
tissue 42 to raise the temperature of the target tissue 42
sufficiently to coagulate and/or necrose the tissue 42, while
minimizing damage to surrounding healthy tissue.
[0045] In order to optimize a therapeutic procedure, the system 10
may be operated to achieve a maximal coagulation rate (coagulated
tissue volume/time/energy) in the target tissue 42, while
minimizing heating in the surrounding tissue, particularly within
the near field region 52, as well as in the far field. The
coagulation rate may be optimized by achieving preferential
absorption of the ultrasonic waves, where the absorption by the
tissue within the focal zone 38 is higher than the tissue outside
the focal zone 38. The presence of microbubbles 56 in tissue within
the focal zone 38 (shown in FIG. 1B) may achieve this goal, because
tissue including microbubbles 56 therein may have a higher energy
absorption coefficient than then surrounding tissue without
microbubbles.
[0046] FIG. 4 illustrates an overview of a method 200 for heating
tissue within a target region, e.g., to induce tissue coagulation
and/or necrosis during a sonication that includes a series of
acoustic energy transmissions at different intensities. Initially,
a target tissue 42, e.g., a benign or malignant tumor within an
organ, such as a liver, kidney, uterus, breast, brain, and the
like, may be selected for treatment. At step 202, ultrasonic waves
above a certain threshold intensity may be directed towards the
target tissue structure 42 to generate microbubbles 56 within focal
zone 38. Although this threshold intensity may differ with each
patient and/or tissue structure, appropriate threshold intensities
may be readily determined by those skilled in the art, e.g.,
through the use of a monitoring mechanism sensitive to the
generation of micro-bubbles.
[0047] Transmission of acoustic energy at the intensity above the
threshold level may be relatively brief, e.g., having a duration of
about three seconds or less, and preferably having a duration of
not more than about 0.1-0.5 second, yet sufficiently long to
generate microbubbles within the focal zone 38 without
substantially generating microbubbles in tissue outside the focal
zone 38, e.g., in the near field 52 (shown in FIG. 1B). The
generated microbubbles in the focal zone 38 oscillates at the
frequency of the delivered acoustic wave, and assists in extending
the acoustic pass in the focus area by multiple reflections and/or,
acting as non linear multipliers receiving energy at a lower
frequency and transmitting it back at a higher frequencies and/or
generating some limited local cavitation hence enhancing absorption
of the energy at the focal volume, thereby allowing tissue within
the focal zone 38 to be heated faster and more efficiently.
[0048] At step 204, the intensity of the beam 15 may be lowered
below the threshold level and, maintained at a lower intensity
while the beam 15 remains focused substantially at the focal zone
38 so as to heat the tissue within the focal zone 38 without
collapsing the microbubbles 56 within the focal zone 38 or the
following transmission could be spaced in time and be with short
enough duration to allow partial bubbles dissipation and minimize
collapse the bubbles collapse as a result of the acoustic beam or
eventually dissipate back into the tissue. By way of one example,
this lower intensity level may be reduced below the intensity used
to generate the microbubbles 56 by a factor of about two to three.
The transmission at this lower intensity may have a substantially
longer duration as compared to the transmission at the higher
intensity used to generate the microbubbles 56. By way of another
example, the acoustic energy may be transmitted for at least about
two or three seconds (2-3 s.), and preferably about eight to ten
seconds (8-10 s.). By way of further example, microbubbles 56
generated within tissue may be present for as little as eight to
ten seconds (8-10 s.), e.g., due to natural perfusion of the
tissue. Thus, the acoustic energy may be maintained for as long as
sufficient supply of microbubbles are present. Because of the
microbubbles 56, acoustic energy absorption by the tissue within
the focal zone 38 may be substantially enhanced, as explained
above.
[0049] At step 206, the controller 18 may determine whether the
sonication has been sufficiently long to heat the tissue within the
focal zone 38 to a desired level, e.g., to coagulate or otherwise
necrose the tissue within the focal zone 38. If not, additional
microbubbles may be generated in the target tissue region, e.g., by
repeating step 202, and then the intensity may be reduced to heat
the tissue while avoiding causing collapse of microbubbles, e.g.,
by repeating step 164 or by using temporally spaced short high
power transmissions. Steps 202 and 204 may be repeated
periodically, e.g., one or more times, during the sonication until
sufficient time has passed to substantially ablate or otherwise
treat the tissue within the focal zone 38.
[0050] Thus, a single sonication, which may last between one and
twenty seconds (1-20 s.), and preferably, about ten seconds (10 s.)
or more, may include multiple transmissions above and below the
threshold necessary to generate microbubbles. For example, after
perfusion has at least partially dispersed the microbubbles from
the tissue within the focal zone 38, transmission at an intensity
above the threshold level may be repeated in order to maintain a
level of microbubble density sufficient to create preferential
absorption of the tissue within the focal zone. Transmission of
acoustic energy at an intensity below the threshold level may then
be repeated to cause heating of the tissue within the focal zone
without causing bubble collapse. The intensity levels of the
acoustic energy may be set to switch between an increment above and
an increment below the threshold intensity, or to switch between on
and off periods. Alternatively, the intensities may be varied
during the course of the sonication. This alternating sequence of
acoustic transmissions may be localized and timed in such a way as
to create and maintain a microbubble "cloud" in the target tissue
42 to optimize the coagulation process.
[0051] This alternating sequence during a single sonication may
provide several advantages as compared to conventional focused
ultrasound ("FUS") ablation without microbubbles. For example, if
an intensity level is utilized in the heating, while minimizing the
bubble collapse step (step 204) that is comparable to conventional
FUS ablation, a substantially larger focal zone 38 may created. For
example, due to the enhanced energy absorption, the resulting focal
zone 38 may be about two to three times larger than conventional
FUS ablation utilizing the same energy, thereby necrosing or
otherwise heating a larger volume of tissue within the target
tissue 42. This increased ablation volume may result in requiring
fewer sonications to ablate an entire target tissue 42.
[0052] Alternatively, a lower intensity level may be used as
compared to conventional FUS, thereby generating a comparably sized
focal zone while using substantially less energy. This may reduce
energy consumption by the system 10 and/or may result in
substantially less energy being absorbed by surrounding tissue,
particularly in the near field 52. With less energy absorbed,
cooling times between sonications may be substantially reduced. For
example, where conventional FUS may require ninety seconds or more
of cooling time between sonications, systems and methods in
accordance with embodiments described herein may allow cooling
times of about forty seconds or less.
[0053] Thus, in either case, an overall treatment time to ablate or
otherwise treat a target tissue structure may be substantially
reduced as compared to conventional FUS without microbubbles.
[0054] Upon completing the sonication, the transducer 14 may be
deactivated, e.g., for sufficient time to allow heat absorbed by
the patient's tissue to dissipate. The transducer 14 may then be
focused on another portion of the target tissue region 42, e.g.,
adjacent the previously treated tissue, and the process 200 is
repeated for another portion of the target tissue region 42.
Alternatively, the acoustic beam 15 may be steered continuously or
discretely without any cooling time, e.g., using a mechanical
positioner or electronic steering.
[0055] Sometimes, the actual thermal dose delivered with a
particular sonication may not be the same as the thermal dose
predicted by the processor 22. For example, absorption coefficient,
blood flow, uneven heat conduction, different rates of conduction
for different tissue masses, tissue induced beam aberration, and
variances in system tolerances, may make it difficult to accurately
predict thermal dosages. Moreover, the actual focal spot dimensions
are variable as a function of focal distance (l) and of focal spot
dispersion, making accurate thermal dosing predictions even more
difficult.
[0056] As illustrated in FIGS. 5A-B, two situations can occur.
First, as illustrated by comparison 302 in FIG. 5A, actual thermal
dose 306 may be larger than predicted thermal dose 308. In this
case there will be an excess 310 of ablated tissue. The second
situation is illustrated by comparison 304 in FIG. 5B. In this
case, actual thermal dose 306 is smaller than predicted thermal
dose 308. Therefore, there is an area 312 of non-ablated tissue
remaining after sonication.
[0057] In some embodiments, the processor 22 can use the image data
from the imager 20 to monitor at least a portion of the target
region 42 during a treatment process. For example, the imager 20
may provide real-time temperature sensitive magnetic resonance
images of target mass 42 after some or all of the sonications. The
processor 22 then uses the images from the imager 20 to construct
an actual thermal dose distribution 400 comparing the actual
composite thermal dose to the predicted composite thermal dose as
illustrated in FIG. 6. In particular, thermal dose distribution 400
illustrates a comparison of the actual versus predicted thermal
dose for each or some of the sonications. As can be seen, excess
areas 310 and non-ablated areas 312 will result in over- or
under-dosing as the thermal doses are applied to different
treatment sites 414 within the target tissue 42.
[0058] In one implementation, the image data provided by the imager
20 and the updated thermal dose distributions 400 represent
three-dimensional data. The processor 22 uses thermal dose
distribution 400 to automatically adjust the treatment plan in
real-time after each sonication, or uses the thermal dose
distribution 400 in some of the points to adjust for the
neighboring points. The processor 22 can adjust the treatment plan
by adding treatment sites, removing treatment sites, or continuing
to the next treatment site. Additionally, the thermal dose
properties of some or all remaining treatment sites may
automatically be adjusted by the processor 22 based on real-time
feedback from the imager 20.
[0059] In some embodiments, the processor 22 may reformulate the
treatment plan automatically after each thermal dose or after some
of the sonications, thus ensuring that the target tissue 42 is
completely ablated in an efficient and effective manner. In
addition, the feedback provided by the imager 20 might be used to
manually adjust the treatment plan or to override the changes made
by the processor 22.
[0060] A method 500 of treating tissue that involves controlling
thermal dosing is illustrated in FIG. 7. Initially, a user selects
an appropriate clinical application protocol in step 502. For
example, a user may use an interface such as the user interface 23
to select the clinical application protocol. In some embodiments,
selecting the clinical application protocol controls a set of
default thermal dose prediction parameters. After the clinical
application is selected, relevant magnetic resonant images of a
target mass (e.g., the target tissue 42) are retrieved in step 504.
For example, the images may be retrieved by the imager 20. In step
506, the images are used to define a target region such as a
treatment slice.
[0061] In some embodiments, defining the target region involves
manually or automatically tracing the target mass onto the images
retrieved in step 504. In one implementation, the target mass is
traced in three dimensions onto three-dimensional images for
three-dimensional treatment planning. In other embodiments that
uses ultrasound, an operator is allowed to account for obstacles
such as bones, gas, or other sensitive tissue, and plan accordingly
to ensure that the ultrasound beam 15 will not pass through these
obstacles. Based on this planning, a patient may be repositioned or
the transducer 14 may be repositioned and/or tilted in order to
avoid the obstacles.
[0062] In step 508, the user may enter additional thermal dose
prediction properties or modify any default thermal dose prediction
properties already selected. For example, these additional
properties may be entered via the user interface 23. Then in step
510, a treatment plan is automatically constructed based on the
properties obtained in the previous steps. The purpose of the
treatment plan is to ensure a proper composite thermal dose
sufficient to ablate the target mass by applying a series of
thermal doses to a series of treatment sites, automatically
accounting for variations in the focal spot sizes and in the
thermal dose actually delivered to the treatment site.
[0063] The treatment plan may, for example, be automatically
constructed by the processor 22. For example, in some embodiments,
the processor 22 may be configured to perform the method of FIG. 3
to create the treatment plan. In some embodiment, automatically
constructing the treatment plan includes constructing an expected
thermal dose distribution showing the predicted thermal dose at
each treatment site within the target tissue 42. This thermal dose
distribution may represent a three-dimensional distribution.
[0064] In step 512, the treatment plan may be edited by manual
input. For example, the user interface 23 may be used to edit the
treatment plan. In one embodiment, editing the plan may include
adding treatment sites, deleting treatment sites, changing the
location of some or all of the treatment sites, changing other
thermal dose properties for some or all treatment sites, or
reconstructing the entire plan. As illustrated by step 520, if the
plan is edited, then the process reverts to step 508 and continues
from there. Once the plan is set, then verification step 514 is
performed. Particularly, verification is performed to ensure that
the system 100 is properly registered with regard to the position
of the focal spot relative to the patient 40 and the target tissue
42.
[0065] In some embodiments, verification comprises performing a low
energy thermal dose at a predefined spot within the target tissue
42 in order to verify proper registration. In a following step, the
verification could be repeated at full energy level to calibrate
the dosing parameters. As illustrated by step 522, re-verification
may be required depending on the result of step 514. In this case,
the process reverts back to step 514 and verification is performed
again. On the other hand, mechanical properties, such as position,
relating to transducer 14 may need to be changed (step 520) and,
therefore, the process may revert to step 508. In other
embodiments, the method 500 does not include steps 512 and 514.
[0066] Once the verification is complete, the treatment plan is
implemented in step 516. For example, the treatment plan may be
implemented by performing the method 200 of FIG. 4 to treat one or
more portions of the target tissue 42. In some embodiments, this
step also comprises capturing temperature sensitive image sequences
of the target tissue 42 as each step of the plan is being
implemented. These images will illustrate the actual thermal dose
distribution resulting from each successive thermal dose. The
imager 20 may, for example, provide the temperature sensitive
images that are used to construct the actual thermal dose
distribution.
[0067] For example, the imaging device 20 can be used to acquire
images taken along a two-dimensional image plane (or slice) passing
through a portion of the focal zone 38. The acquired images are
processed by the processor 22 to monitor a change in temperature of
this portion of the target region 42. The tissue temperature
changes measured from images acquired in one or more imaging planes
are used to derive a three-dimensional thermal evolution of the
entire focal zone 38. The thermal evolution is used to verify that
a sufficient thermal dose for tissue destruction is reached in the
focal zone 38, as well as to track which portions of the target
region 42 have been destroyed. This information, in turn, is used
by the ultrasound controller 18 for positioning (e.g., mechanically
or electronically) the ultrasound energy beam 15 and focal zone 38
for successive sonications of the target region 42. Thus, it is
critical that the thermal evolution of the three-dimensional focal
zone 38 be accurate.
[0068] In step 518, the actual thermal dose distribution is
compared with the predicted thermal dose distribution in order to
determine how closely the actual treatments are tracking the
treatment plan. Then in step 524, it is determined if the treatment
can proceed to the next step (e.g., repeat step 516 to treat other
portion(s) of the target tissue 42), or if changes must be made to
the treatment plan (step 520). The changes may be accomplished
manually or automatically, and may comprise adding treatment sites,
deleting treatment sites, repeating treatment sites, or modifying
specific thermal dose properties for some or all of the treatment
sites.
[0069] One of a variety of methods may be used to change or update
the treatment plan. For example, at the end of each thermal dose,
there may be regions within the target layer that are not covered
by accumulated dose contours. These untreated areas are separated
into individual regions. Each of these regions is then sent through
the process, beginning with step 506, resulting in an updated
treatment plan constructed to treat the remaining regions. The
process will repeat until there are no more untreated regions. By
way of more specific background information relating to this
process, relevant methods and systems for changing and updating a
treatment are described in U.S. Pat. No. 6,618,620, the entire
disclosure of which is incorporated by reference herein.
[0070] FIG. 8 illustrates an alternative method for updating the
treatment plan does not include steps 510, 512, and 514 in FIG. 7.
Instead, the system 10 accepts the target mass 42 to be treated.
First, it is determined if there is an untreated region 614 (step
602). This may be performed after step 506 or 508. If there is,
then treatment site 616 is selected in step 604, and thermal dose
properties are estimated so as to deliver the appropriate thermal
dose the treatment site 616. Then, in step 606, the thermal dose is
applied to treatment site 616 resulting in a treated region 618. In
step 608, the size of treated region is calculated and stored as a
linked-list so that in step 610 the treated region can be
subtracted from the untreated region 620 in order to determine the
remaining untreated region. The process then reverts to step 602,
and a new treatment site is selected. Once the entire target mass
614 is treated, there will not be any untreated regions and the
process will exit.
[0071] Referring back to FIG. 7, after the treatment is complete,
it is determined in step 526 whether to restart a treatment or to
exit. Additionally, if there is insufficient information or a fatal
error occurs in any of steps 504-516, the process will
automatically go to step 526, where it can be decided to proceed
with a new treatment plan or to terminate a treatment process.
[0072] As illustrated in the above embodiments, the imager 20 and
the processor 22 provide feedback control to thereby allow the
target tissue 42 to be treated efficiently and accurately using
microbubbles, while protecting adjacent tissue desired to be
protected. By using the imager 20 and the processor 22 to provide
data on treatment location and damage volume, the system 10 or a
user can control an ultrasound treatment that uses microbubbles, to
thereby prevent, or at least reduce the risk of, irreversible
tissue damage in non-targeted tissue.
[0073] Although particular embodiments have been shown and
described, it should be understood that the above discussion is not
intended to limit the present invention, and it will be obvious and
apparent to those skilled in the art that various changes and
modifications may be made to the illustrated embodiments without
departing from the scope of the invention set forth in the
following claims. Further, an aspect or an advantage described in
conjunction with a particular embodiment is not necessarily limited
to that embodiment and can be practiced in any other embodiments
even if not so illustrated.
* * * * *