U.S. patent application number 15/012319 was filed with the patent office on 2018-03-15 for optimization and feedback control of hifu power deposition through the analysis of detected signal characteristics.
The applicant listed for this patent is Mirabilis Medica, Inc.. Invention is credited to Gregory P. Darlington, Charles D. Emery, Barry Friemel, Justin A. Reed.
Application Number | 20180071552 15/012319 |
Document ID | / |
Family ID | 41653589 |
Filed Date | 2018-03-15 |
United States Patent
Application |
20180071552 |
Kind Code |
A9 |
Darlington; Gregory P. ; et
al. |
March 15, 2018 |
OPTIMIZATION AND FEEDBACK CONTROL OF HIFU POWER DEPOSITION THROUGH
THE ANALYSIS OF DETECTED SIGNAL CHARACTERISTICS
Abstract
A system and method for adjusting or selecting the treatment
parameters for HIFU signals to treat a target treatment site,
and/or to aid in visualizing the likely degree and location of HIFU
effects on patient tissue. The system transmits one or more test
signals into patient tissue and receives signals created in
response to the test signals. The signals are analyzed to determine
a response curve of how a characteristic of the signal varies with
the one or more test signals. The response curve of the detected
signals is used to select a treatment parameter.
Inventors: |
Darlington; Gregory P.;
(Snohomish, WA) ; Emery; Charles D.; (Issaquah,
WA) ; Reed; Justin A.; (Seattle, WA) ;
Friemel; Barry; (Redmond, WA) |
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Applicant: |
Name |
City |
State |
Country |
Type |
Mirabilis Medica, Inc. |
Bothell |
WA |
US |
|
|
Prior
Publication: |
|
Document Identifier |
Publication Date |
|
US 20160287910 A1 |
October 6, 2016 |
|
|
Family ID: |
41653589 |
Appl. No.: |
15/012319 |
Filed: |
February 1, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12537217 |
Aug 6, 2009 |
9248318 |
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15012319 |
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12187318 |
Aug 6, 2008 |
8216161 |
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12537217 |
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61180187 |
May 21, 2009 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 2017/00106
20130101; A61N 7/00 20130101; A61B 2090/378 20160201; A61N
2007/0052 20130101; A61N 7/02 20130101 |
International
Class: |
A61N 7/00 20060101
A61N007/00 |
Claims
1. A method of operating a high intensity focused ultrasound (HIFU)
system to treat a target treatment site by: transmitting one or
more test signals into a tissue site; detecting signals from the
area of the tissue site that are created by the one or more test
signals; determining a response curve for the tissue site that
indicates how a signal characteristic of the detected signals
changes in response to the one or more test signals; and using the
determined response curve to select a treatment parameter of the
HIFU signals that will be used to treat the target treatment site
and applying HIFU signals with the selected treatment parameter to
the target treatment site with the HIFU system.
2. The method of claim 1, wherein the test signal includes two or
more test signals transmitted at different power levels with a
fundamental frequency and the response curve relates how an energy
level of a detected signal at a harmonic of the fundamental
frequency varies with different power levels.
3. The method of claim 1, wherein the response curve relates how an
energy level of a detected signal in two different frequency ranges
varies with depth in the tissue site.
4. The method of claim 1, wherein the test signal includes two or
more test signals transmitted at different power levels with a
fundamental frequency and the response curve relates how an energy
level of a detected signal at the fundamental frequency varies with
different power levels.
5. The method of claim 1, wherein the test signal includes two or
more test signals transmitted at different power levels and the
response curve relates how an energy level of a detected signal at
two different frequency ranges varies with different power
levels.
6. The method of claim 1, wherein the test signal includes two or
more test signals transmitted at different power levels and the
response curve relates how an energy level of a detected signal in
a range of frequencies varies with different power levels.
7. The method of claim 1, wherein response curve is used to select
the treatment parameter by determining a closest match of the
response curve to a number of predetermined response curves each
having a treatment parameter associated therewith, and selecting
the treatment parameter associated with the predetermined response
curve that best matches the response curve of the detected
signal.
8. The method of claim 1, wherein response curve is used to select
the treatment parameter by determining a characteristic of the
response curve and selecting a treatment parameter associated with
the characteristic.
9. The method of claim 8, wherein the characteristic of the
response curve is a saturation point of the response curve.
10. The method of claim 8, wherein the characteristic of the
response curve is a shape of the response curve.
11. The method of claim 1, wherein the test signal includes two or
more test signals transmitted at different power levels and the
response curve relates how a dispersion of a detected signal varies
with different power levels.
12. The method of claim 1, wherein the test signal includes two or
more test signals transmitted at different power levels and the
response curve relates how a speckle shift related to changes in
temperature at the target treatment site varies with different
power levels.
13. The method of claim 1, wherein the test signal includes two or
more test signals transmitted at different power levels and each
test signal transmitted at the same power level includes a pair of
test signals having opposite phases.
14. A high intensity ultrasound (HIFU) system to treat tissue at a
target treatment site, comprising: an ultrasound transducer that is
configured to deliver a test signal and HIFU signals to a tissue
site; a controller that is configured to control the ultrasound
transducer to deliver HIFU signals to the target treatment site
with a selectable treatment parameter; a receiver that is
configured to detect signals from the tissue site created by the
one or more test signals; and a processor programmed to analyze the
detected signals to determine a response curve for the tissue site
that indicates how a signal characteristic of the detected signals
changes in response to the test signal, wherein the processor is
programmed to select a treatment parameter for the HIFU signals to
be used in treating the target treatment site based on the response
curve determined.
15. The system of claim 14, wherein the test signal includes two or
more test signals transmitted at different power levels with a
fundamental frequency and the response curve relates how an energy
level of a detected signal at a harmonic of the fundamental
frequency varies with different power levels.
16. The system of claim 14, wherein the response curve relates how
an energy level of a detected signal in two different frequency
ranges varies with depth in the tissue site.
17. The system of claim 14, wherein the test signal includes two or
more test signals transmitted at different power levels with a
fundamental frequency and the response curve relates how an energy
level of a detected signal at the fundamental frequency varies with
different power levels.
18. The system of claim 14, wherein the test signal includes two or
more test signals transmitted at different power levels and the
response curve relates how an energy level of a detected signal at
two different frequency ranges varies with different power
levels.
19. The system of claim 14, wherein the processor is programmed to
select the treatment parameter by determining a closest match of
the response curve to a number of predetermined response curves
each having a treatment parameter associated therewith, and
selecting the treatment parameter associated with the predetermined
response curve that best matches the response curve of the detected
signal.
20. The system of claim 14, wherein processor is programmed to
select the treatment parameter by determining a characteristic of
the response curve and selecting a treatment parameter associated
with the characteristic.
21-41. (canceled)
Description
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. patent
application Ser. No. 12/187,318, filed Aug. 6 2008, and also claims
the benefit of U.S. Patent Application No. 61/180,187, filed May
21, 2009, both of which are expressly incorporated herein by
reference.
BACKGROUND
[0002] As an alternative to more invasive types of surgical
procedures, many physicians are employing the use of High Intensity
Focused Ultrasound (HIFU) as a technique to therapeutically treat
internal body tissues. With HIFU, an ultrasound signal of
sufficient power (pressure and particle velocity) and time is
focused on a target volume of tissue in order to change a state of
the tissue by heating and/or by cavitation.
[0003] To be effective in treating tissue, the delivered energy of
the HIFU signal must be sufficient to cause the desired physical
effect. Additionally, the energy must not be so great or
uncontrolled as to cause unintended collateral damage to healthy
tissues surrounding the target volume. The non-homogenous nature of
tissue(s) in the body creates variations in attenuation,
propagation velocity, and acoustic impedance that modify the
expected acoustic wave propagation and deposition of HIFU energy
delivered to a target tissue volume when compared to homogeneous
material. The technology disclosed herein is a method and apparatus
for dynamically controlling and/or selecting parameters that affect
the energy of a HIFU signal and/or the location where the energy is
directed so that the desired physical effect in tissue is obtained
and collateral damage to surrounding tissue is minimized.
SUMMARY
[0004] As indicated above, the technology disclosed herein is a
method and apparatus for selecting and/or controlling one or more
treatment parameters such as the energy of a HIFU signal delivered
by a transducer to a desired location in a patient. The one or more
treatment parameters are selected or controlled based on an
analysis of harmonic distortion or other changes in a detected
signal characteristic that occur as a result of a high amplitude
pressure waveform traveling through tissue.
[0005] To select a treatment parameter of a HIFU signal that will
be used to treat a target tissue site, one or more test signals are
delivered to the tissue. Each test signal is a continuous wave (CW)
or pulsed mode ultrasound signal that is focused on a target volume
in the patient. Signals created by the test signals are received
and analyzed to determine a response curve of the tissue that
indicates how a signal characteristic changes in response to the
one or more test signals. Examples of detected signal
characteristics include but are not limited to: energy, power,
amplitude, frequency, energy at one or more frequencies or range of
frequencies, duration, temperature change, dispersion or acoustic
radiation force. The treatment parameter is selected or controlled
based on the response curve(s).
[0006] In one embodiment, a response curve is compared to find a
match against predefined response curves having treatment
parameters associated therewith and the treatment parameter(s) of
the closest matching response curve is selected.
[0007] In another embodiment, a treatment parameter is selected by
analyzing a characteristic of the response curve, such as a
saturation point or slope and the treatment parameter(s) associated
with the characteristic is selected.
[0008] In yet another embodiment, a treatment parameter is selected
by comparing the response curves to threshold values.
[0009] In one embodiment, the response curve is determined by
comparing the energy of the received signals created from the test
signals in one frequency range to the energy of the received
signals in a second frequency range. This comparison is used to
calculate K, which is the ratio of the energy in the two frequency
ranges. In one embodiment, the energy in the harmonic content of
the waveform is compared to the energy in the fundamental
frequency. In another embodiment, the energy in a single harmonic,
such as the second harmonic, is compared to the energy at the
fundamental frequency. In yet another embodiment, the energy in one
group of frequencies is compared to the energy in another group of
frequencies, of which one may contain the fundamental frequency. In
yet another embodiment, the phase difference for the harmonics can
be used to calculate K.
[0010] The ratio K may be found for a multitude of spatial
positions from the transducer. This may be accomplished through
windowing of the received signals from the tissue at a specific
time and calculating the Fourier transform. The response curve
formed by the values of K as a function of spatial location may be
compared to a baseline response curve, and the excitation signal
may be adjusted to optimize the HIFU energy delivered to the
intended target volume.
[0011] In one particular embodiment, the disclosed technology
relates to a method and apparatus for selecting a power level for a
high intensity focused ultrasound (HIFU) signal to be delivered by
a HIFU transducer that operates by: transmitting a test signal
having a fundamental frequency to a target volume; receiving
ultrasound echoes from one or more positions; determining an energy
of the received echoes in a first frequency range and an energy of
the echo signals in a second frequency range; comparing the energy
of the received echoes in the first frequency range and the energy
of the echo signals in the second frequency range; and based on the
comparison, adjusting one or more characteristics of the HIFU
signal to adjust the energy of the HIFU signal delivered by the
HIFU transducer.
[0012] In still a further embodiment, the method and apparatus
operate such that the first frequency range does not include the
fundamental frequency of the test signal and the second frequency
range does include the fundamental frequency of the test
signal.
[0013] In still a further embodiment, the method and apparatus
operate such that the first frequency range includes one or more
harmonics of the fundamental frequency of the test signal.
[0014] In still a further embodiment, the method and apparatus
operate such that the energy of the received echoes in the first
frequency range and the energy of the echoes in the second
frequency range are compared by determining a ratio of an energy of
the echoes in the first frequency range to an energy of the echoes
in the second frequency range.
[0015] In yet another embodiment, the method and apparatus operate
such that the delivered energy of the HIFU signal is adjusted by
determining if the ratio at a selected position is less than a
threshold, and if so, adjusting a characteristic of the HIFU signal
to increase the delivered energy of the HIFU signal at the selected
position.
[0016] In yet another embodiment, the method and apparatus operate
so that the delivered energy of the HIFU signal is adjusted by
determining if the ratio at a selected position is greater than a
threshold, and if so, adjusting a characteristic of the HIFU signal
to decrease the delivered energy of the HIFU signal at the selected
position.
[0017] In yet another embodiment, the method and apparatus operate
so that the energy of the echoes in the first frequency range and
the energy of the echoes in the second frequency range are compared
by determining a difference in phase between the echoes in the
first frequency range and the second frequency range.
[0018] In yet another embodiment, the method and apparatus operate
so that the adjustment of one or more characteristics of the HIFU
signal is made based on the magnitude of the difference in
phase.
[0019] In another embodiment, the response curve of the signal
characteristic relates a dispersion of an echo signal to variations
in test signal power. The dispersion may be detected as an amount
of speckle shift toward the HIFU transducer. The one or more
treatment parameters are controlled or selected based on the amount
of speckle shift detected.
[0020] In another embodiment, the response curve of the signal
characteristic relates how the energy contained in a received
signal at one harmonic or at the fundamental frequency of the test
signals varies in response to variations in test signal power.
[0021] In another embodiment, the response curve of the signal
characteristic relates how a speckle shift due to heating within
the tissue changes with changes in test signal power.
[0022] In one embodiment, a single test signal at each power level
is used to measure the response of the signal characteristic. In
another embodiment, two interrogations signals are used for each
power level tested. The interrogation signals have the same overall
power, but are 180 degrees out of phase. In this case, the signals
received from tissue created by the two signals are added together
to suppress the fundamental frequency and give a record of the
harmonics generated within tissue.
[0023] 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.
DESCRIPTION OF THE DRAWINGS
[0024] The foregoing aspects and many of the attendant advantages
of the disclosed technology will become more readily appreciated as
the same become better understood by reference to the following
detailed description, when taken in conjunction with the
accompanying drawings, wherein:
[0025] FIG. 1 illustrates a basic system for controlling the energy
of a delivered HIFU signal, in accordance with an embodiment of the
disclosed technology;
[0026] FIG. 2A shows a received echo as a function of time;
[0027] FIG. 2B shows a received echo as a function of distance;
[0028] FIG. 3 shows windowed sections of a received echo at three
different distances;
[0029] FIG. 4 shows the frequency spectrum of a windowed echo
(distance of 35 mm) with the fundamental, 3rd and 5th harmonics
identified;
[0030] FIG. 5 shows a surface plot of the power in decibels as a
function of frequency and distance mapped to a grayscale;
[0031] FIG. 6 shows an expected K value curve as a function of
distance `r`;
[0032] FIGS. 7A-7C show a surface plot of the power in decibels as
a function of frequency and depth taken at three different times,
t0, t1 and t2;
[0033] FIG. 8 shows a graphical representation of K value matrices
for different distances and acquisition times;
[0034] FIG. 9 shows a graphical representation of the steps
performed to obtain K value curves and change the energy/power of a
delivered HIFU signal in accordance with an embodiment of the
disclosed technology;
[0035] FIGS. 10A-10C illustrate the differences between burst
length, burst interval, pulse length, and pulse rate interval of a
pulsed HIFU signal;
[0036] FIG. 11 illustrates an embodiment of a HIFU treatment system
in which the disclosed technology can be implemented;
[0037] FIGS. 12A and 12B illustrate different types of transducer
probes that transmit HIFU signals and receive echo signals from the
patient;
[0038] FIGS. 13A and 13B illustrate different feedback control
systems to adjust the energy of a delivered HIFU signal; and
[0039] FIG. 14 illustrates a system for adjusting the delivered
energy of a HIFU signal in accordance with another embodiment of
the disclosed technology;
[0040] FIG. 15 illustrates the amplitude versus depth of an echo
signal created in tissue as a result of a HIFU signal;
[0041] FIG. 16 is a graph of the energy in the echo signal at the
fundamental frequency of the HIFU signal versus depth;
[0042] FIG. 17 is a graph of the energy in the echo signal at the
second harmonic of the HIFU signal versus depth;
[0043] FIG. 18 is a two dimensional plot of the energy in the echo
signal at the second harmonic of the HIFU signal versus depth and
power level of a HIFU signal;
[0044] FIG. 19 is a plot of the energy in the echo signal at the
second harmonic of the HIFU signal versus the power level of a HIFU
signal.
[0045] FIG. 20 is a plot of dispersion created in echo signals in
response to HIFU signals transmitted at different power levels;
[0046] FIG. 21 is a plot of dispersion created in echo signals in
response to HIFU signals transmitted at different power levels;
[0047] FIG. 22 is a flowchart of steps performed to select a power
level for HIFU signals to be used to treat a tissue site in
accordance with an embodiment of the disclosed technology; and
[0048] FIG. 23 illustrates a system for adjusting a focus point of
a delivered HIFU signal in accordance with another aspect of the
disclosed technology.
DETAILED DESCRIPTION
[0049] Although the technology disclosed herein is described with
respect to its currently preferred embodiments and the best mode
known for practicing the technology, the description is not to be
construed as limiting. The disclosure is directed to all new and
non-obvious features and aspects of the disclosed embodiments
either taken alone or in combination. As discussed above, the
technology disclosed herein relates to techniques for adjusting or
selecting one or more treatment parameters of a HIFU signal such as
the energy of a HIFU signal and/or the location at which the energy
is delivered. For the purposes of this application, the energy of a
HIFU signal may be characterized by its power, pressure or other
related characteristic. Other treatment parameters that can be
controlled or selected include the treatment times of the HIFU
signals, pulse repetition frequency, pulse duration of the HIFU
signals or other parameters that effect the amount or rate at which
energy is deposited at a tissue treatment site.
[0050] As will be described in further detail below, the one or
more treatment parameters of the HIFU signals that are used to
treat a tissue site are controlled or selected based on an analysis
of how the signal characteristics of received signals vary in
response to one or more test signals. In a currently preferred
embodiment, the test signals are one or more HIFU signals. However,
the test signals could be any type of ultrasound signal including
non-focused or imaging ultrasound signals. The same transducer may
be used to deliver both the therapeutic HIFU signals and the test
signals or different ultrasound transducers could be used.
[0051] In one embodiment, to select the value of a treatment
parameter, a number of test signals at different power levels are
transmitted into the tissue. The test signals may be transmitted to
the same tissue region as the target treatment site or the test
signals may be transmitted into tissue into tissue that is nearby
the target treatment site.
[0052] As the power level of the test signals increase, the
transmitted test signals become increasingly non-linear in the
tissue in the focal zone of the ultrasound transducer. The
non-linearity creates a corresponding response curve of a signal
characteristic that can be detected and used to select the
appropriate treatment parameter. In one embodiment, the response
curve is analyzed for a power level of a test signal that causes
the detected signal characteristic to saturate. The saturation
power level is used as a basis for selecting the treatment
parameter.
[0053] The treatment parameter may be selected for each tissue site
to be treated. Alternatively, the selected treatment parameter may
be used to treat several different areas or cross-sections of the
tissue site to be treated.
[0054] FIG. 1 shows a diagram of a system for selecting a treatment
parameter such as the energy of a HIFU signal for use in treating a
tissue site in accordance with an embodiment of the disclosed
technology. The system 10 includes a HIFU transducer 12 that
delivers a HIFU signal to tissue 14 and HIFU electronics 16 that
excites the transducer 12. A voltage probe 18 detects an electrical
signal at the HIFU transducer 12. The system further includes an
oscilloscope or other data acquisition system 20. In this case, an
excitation signal from the HIFU electronics 16 stimulates the HIFU
transducer 12 such that a high energy ultrasound signal is
transmitted to the intended target in tissue 14. The energy in the
HIFU signal is scattered, reflected, transmitted and absorbed as it
propagates within the tissue. The absorbed energy is converted to
heat and causes the temperature of the tissue to rise. The amount
of energy absorbed depends on the pressure amplitude and frequency
as well as the tissue characteristics. Typically, a HIFU device is
designed such that the greatest pressure and absorption occur at
the focal point of the device in the tissue. Energy of the signal
that is not absorbed is either transmitted to deeper tissues or
reflected and scattered. In one embodiment of the disclosed
technology, it is the reflected and scattered energy (ultrasound
echoes) that can be detected and analyzed for harmonic distortion.
Some of this scattered acoustic energy is detected by the HIFU
transducer 12 and converted into an electrical signal. The
electrical signal is sensed using the voltage probe 18 and
displayed/acquired on the oscilloscope or other data acquisition
system 20.
[0055] FIG. 2A shows a representative signal captured at the data
acquisition system 20 with three regions identified, namely
transmit, pulse-echo saturation, and pulse-echo signal. For this
example, the focal depth is 35 mm for the HIFU transducer. If it is
assumed that acquisition starts immediately when transmit begins,
then the first detected signal will contain mostly information from
the transmit pulse (transmit region). After transmit ends, it is
expected that some of the first few echoes may cause clipping in
the detection system (pulse-echo saturation). The issues with
pulse-echo saturation may be mitigated by properly designing the
detection circuit to ensure satisfactory dynamic range and
bandwidth (e.g. time-gain control). After the initial large
amplitude echoes have been received, the echoes from the tissue may
be detected without any additional distortion added from the
detection system (pulse-echo signal). Since in the embodiment
shown, the HIFU transducer and detection transducer are the same,
the time axis also represents depth through knowledge of the
propagation velocity in the tissue as shown in FIG. 2B.
[0056] The energy of the echo signals as a function of frequency
may be computed at different depths or spatial locations. In one
case, the received echo signal is multiplied by a windowing
function centered at a specific depth and the Fourier transform
operator is applied. In the example shown in FIG. 3, echo signals
are isolated at depths centered at 25, 35 and 45 mm with a
rectangular function which is 5 mm in width. It is expected that
the window width and amplitude will be adjusted to optimize the
frequency representation of the echo signal. A Fourier transform of
the echo signals at each depth signal is calculated to determine
the energy of the echo signals as a function of frequency. FIG. 4
shows the frequency spectrum for the signal windowed at 35 mm. In
this case, the fundamental frequency, 3.sup.rd harmonic, and
5.sup.th harmonic are identified. The even harmonics are typically
not as easy to detect due to therapy transducer limitations.
Although only three depths are shown in FIG. 3, the window function
can run along the entire length of the pulse-echo signal or vector.
In this case, a matrix of data is computed such that one axis is
depth and the other axis is frequency. FIG. 5 shows a three
dimensional surface plot in grayscale of a continuous analysis
along the depth dimension. In this representation, the fundamental
frequency of 1.1 MHz has been removed using a digital filter, which
highlights the harmonics seen at 3.3 MHz and 5.5 MHz.
[0057] The Fourier transform determines the energy that occurs in a
number of frequency bins. Therefore, the energy in a particular
frequency bin may be compared to the energy in other frequency bins
or the energy over multiple frequency bins may be summed and
compared. For example, frequencies around the fundamental frequency
(e.g. bandwidth) may be a better representation of the power.
EQUATIONS 1A and 1B show two different cases for calculating a
ratio K, of the energy as represented by the power at two different
frequencies or in different frequency ranges.
[0058] As with many signal processing schemes, signal conditioning
may be required to detect and properly represent the energy of the
echo signals at the various frequencies. For example, the
sensitivity of the detection transducer or attenuation as a
function of frequency and depth may need to be introduced to fully
appreciate differences in the energy at the various frequencies in
tissue.
K f 1 f 0 ( r ) = P ( f 1 , r ) P ( f 0 , r ) ( 1 A ) K f 1 f 0 ( r
) = f = f 1 - .DELTA. f f 1 + .DELTA. f P ( f , r ) f = f 0 -
.DELTA. f f 0 + .DELTA. f P ( f , r ) ( 1 B ) ##EQU00001##
[0059] FIG. 5 shows that the K values can be calculated as a
function of spatial position or depth; therefore, K is a function
of r or spatial distance. It is important to note that the
calculation may include one frequency or multiple frequencies. For
example, the K value may represent the energy in the harmonics
compared to the energy in the fundamental.
[0060] FIG. 6 shows an example of how the K values are expected to
vary as a function of depth. In this example, the energy around the
fundamental is compared to the energy in the harmonics. As can be
seen, the ratio K has a maximum at or adjacent the focal point of
the HIFU signal and then decreases with increasing distance away
from the transducer.
[0061] As described, it is possible to map the energy ratio as a
function of frequency and spatial location for an echo. If the
excitation level at the transducer is modified, then it is also
possible to compare K values for different HIFU transducer
pressures. The echoes are also available at different sampling
intervals (pulse repetition interval). For example, if a pulse mode
HIFU excitation is used, then the echo may be detected and analyzed
between the excitation signals. This allows the K values to be
compared for multiple excitation levels and/or multiple times.
FIGS. 7A-7C show multiple surface plots that have been acquired
from different echoes at times t0, t1 and t2. This may be due to
variation in excitation level or just processing between excitation
times. The frequency spectrum at each spatial location is
calculated, and then K is calculated.
[0062] FIG. 8 shows a representative format for storing K data in a
computer memory. In one embodiment, the data is stored in a table
50 where one axis 52 is spatial location (depth) and another axis
54 is acquisition time. Each entry for a particular depth and time
contains a matrix, e.g., 56, wherein the power ratio between two
frequencies is calculated and stored. In this representation,
K.sub.f2f0 is the power ratio in the third harmonic to the
fundamental frequency. K.sub.f2f1 is the power ratio in the third
harmonic to the second harmonic. Since K is just a ratio of the
power in two frequencies, K.sub.f2f1 is simply the multiplicative
inverse of K.sub.f1f2. If it is necessary to compare the power in
the fundamental to all harmonics, then essentially the column needs
to be summed as set forth in EQUATION 2.
K.sub.total(r.sub.0, t.sub.0)=K.sub.f.sub.1.sub.f.sub.0(r.sub.0,
t.sub.0)+K.sub.f.sub.2.sub.f.sub.0(r.sub.0,
t.sub.0)+K.sub.f.sub.3.sub.f.sub.0(r.sub.0, t.sub.0)+ . . .
+K.sub.f.sub.N.sub.f.sub.0(r.sub.0, t.sub.0) (2)
[0063] FIG. 8 also shows that the K values may be calculated at
different excitation times t0, t1, t2, etc. By comparing the K
values at these times (note: the excitation may vary at these
different times) between each other or to a baseline, the
approximate location of the focus may be determined as well as an
estimate of the energy of the HIFU signal delivered to the
tissue.
[0064] The values of K can be used to select a treatment parameter
for the HIFU signals to be used in treating a tissue site by
analyzing the K curve determined for the tissue. As indicated
above, the system transmits one or more test signals into the
patient and detects signals created by the test signals. The ratio.
K, of the energy detected in different frequency bands versus depth
can be used to create a K curve. The K curve of the detected
signals can be compared against known K curves for which treatment
parameters have already been determined. For example, breast tissue
may be associated with a K curve having a first set of one or more
treatment parameters. Fibroid tissue may be associated with another
K curve having different treatment parameters. In one embodiment, a
processor compares the K curve for the detected signals with a
library of K curves to determine the closest match and selects the
treatment parameters associated for the closest match.
[0065] In another embodiment, one or more individual points on a K
curve for the detected signals can be compared with a predetermined
baseline K curve. The value for the treatment parameter can be
adjusted based on the comparison. For example, if the
characteristic curve formed by K as a function of spatial location
for the detected signals shows significantly higher ratios than the
baseline curve, then the output energy (pressure) may be reduced.
Similarly, if the characteristic curve formed by K as a function of
spatial location for the detected signals shows significantly lower
ratios (or flatter) than the baseline curve, then the output energy
may be increased.
[0066] It is also possible to show harmonic saturation (maximum
value for the ratio K) by graphing the K values as a function of
the excitation amplitude for a particular depth. In this case, a
number of test HIFU signals are transmitted at different power
levels and the K values for the detected signals are computed. A
curve or plot of the change in K versus changes in HIFU power for a
particular depth are computed. The curve or plot can then be
compared against known plots having treatment parameters associated
with them. Alternatively, the K curve can be compared with a
baseline K curve and the treatment parameters selected.
[0067] In one embodiment, one or more points on the K curve for the
detected signals are used to select the treatment parameters. In
one embodiment, the K curve can be searched for a HIFU power level
that causes the value of K to saturate. The treatment parameters of
the HIFU signals used to treat a tissue sample can therefore be
selected based on the HIFU power which causes the K value to
saturate. For example, if the HIFU power that causes the value of K
to saturate is 1500 watts, then the treatment parameters associated
with a 1500 watt level can be used to treat the tissue. In some
cases it may be useful to use the same power to treat the tissue as
the power that causes the value of K to saturate. In other cases,
other power levels (greater or lessor) could be used.
[0068] In yet another embodiment, other characteristics of the K
curve for the detected signals can be used to select the treatment
parameters. For example, the slope of the K curve can be compared
with slopes of K curves having treatment parameters associated with
them or the slope of the K curve for the detected signals can be
compared with a baseline and the treatment parameters adjusted
accordingly.
[0069] If the excitation level is constant during the treatment,
the energy level of the harmonics and their location may suggest
the amount of heating occurring throughout the tissue. This would
help determine a limit to the amount of energy delivered to the
intended target.
[0070] It should be also noted that although the power spectrum has
been calculated at different depth and acquisition times, the phase
may also be used to determine the amount of heating in tissue.
[0071] Since the K-value may be derived by the taking the Fourier
transform of the echo signals, the power (energy per unit time)
falling within each frequency bin as well as the phase is available
for computation. The magnitude and phase in a particular frequency
bin may be expressed in the following equation:
H(f.sub.1)=A(f.sub.1)*e.sup.-j2.pi..phi.(f.sup.1.sup.) (3)
where A(f.sub.1) is the amplitude of the signal at frequency
f.sub.1 (the power is simply the square of A) and .phi.(f.sub.1) is
the phase of the signal at frequency f.sub.1. Therefore, the phase
difference between two frequency bins may be computed by taking the
ratio of Equation 3 with the magnitude normalized to 1:
.di-elect cons. f 1 f 0 = - j 2 .pi. .PHI. ( f 1 ) - j 2 .pi. .PHI.
( f 0 ) ( 4 ) ##EQU00002##
Equation 4 may be rewritten as
.di-elect
cons..sub.f.sub.1.sub.f.sub.0=e.sup.-j2.pi.(.phi.(f.sup.1.sup.)-.phi.(f.s-
up.0.sup.)) (5)
The argument in Equation 5 is the phase difference between the two
signals. The phase difference as a function of depth at different
excitation levels may also be used as a relative measure of energy
in different frequencies or frequency bands, which in turn may be
used to dynamically control or select a treatment parameter of a
HIFU signal. For example, the magnitude of the phrase difference
can be compared to a threshold previously known to relate the phase
difference to delivered energy in the tissue. One or more
characteristics of the HIFU signal can then be adjusted in
accordance with the comparison.
[0072] FIG. 9 shows a summary of the basic steps to acquire the K
values in accordance with one embodiment of the disclosed
technology. First, the HIFU transducer is excited with a single
frequency (f.sub.0) as shown in graph 1. The HIFU signal may be a
continuous wave (CW) or a pulsed sinusoid with a fundamental
frequency f.sub.0. In the case of CW, the pulse repetition interval
is equal to the pulse length. As shown in graph 1, the HIFU
excitation signal generated at the HIFU transducer probe has a
signature spectrum where the energy of the frequency components
that are different from the fundamental frequency of the HIFU
signal, such as the harmonics, f.sub.1, f.sub.2, f.sub.3, etc., are
negligible compared with the energy of the fundamental frequency
f.sub.0. The high pressures created from the transmitted HIFU
signal converts the energy at the fundamental to harmonics and in
the tissue (graph 2). In particular, the energy of the signal at
frequencies that are different from the fundamental frequency
f.sub.0 the HIFU signal (such as the frequency of one or more of
the harmonics f.sub.1, f.sub.2, f.sub.3, etc.) changes in
comparison to the energy of the signal at the fundamental frequency
f.sub.0 as shown in graph 2. K values are calculated by combining
the energies at these various frequencies as shown in graphs 3a, b
and c. For example, the energy in one or more of the harmonics may
be compared to the fundamental frequency. The energy in several
lower order harmonics and the fundamental may be compared to that
of the high frequency harmonics. Alternatively, the energy in the
fundamental may only be compared to that of the higher order
harmonics. These graphs by no means exhaust the possibilities of
combining and comparing the energies at the various frequencies. As
will be appreciated by those skilled in the art, the value of K may
vary depending on the range of frequencies or particular harmonics
used in computing the numerator and denominator.
[0073] Graph 4 shows that the K values may be graphed as a function
of position. The ratio K may vary with the depth in the tissue as
well as with different levels of transmit excitations. In one
embodiment, the ratio K is expected to be a non-linear curve that
increases with increasing depth in the tissue, but tends to reach a
maximum (or saturate) at approximately the depth of the focal point
of the HIFU signal. If K values are calculated after each transmit
pulse (graph 5), then multiple K value curves may be generated as
shown in graph 4.
[0074] Graph 5 shows that the frequency of the transmit pulses may
occur at the pulse repetition interval. FIGS. 10A-10C illustrate a
pulse length and a pulse repetition interval in a burst. Many pulse
lengths make up a burst. Each burst has a defined burst length, and
the time between the start of each burst is the burst interval as
shown in FIG. 10A. Each HIFU burst includes a number of HIFU pulses
having a pulse length, where, the time between the start of each
pulse is the pulse rate interval as shown in FIG. 10B. The total
time of the transmit excitation is the pulse length as shown in
FIG. 10C. Each HIFU pulse is a sinusoidal waveform having a
fundamental frequency f.sub.0.
[0075] Returning to FIG. 9, a first curve 70 in graph 4 illustrates
the ratio K for a first delivered energy level of the HIFU signal
and a second curve 74 illustrates the ratio of K for a higher level
of energy. By observing the changes in the K values as a function
of depth, time, or transmit excitation, then a relative measure of
the energy deposited spatially may be approximated.
[0076] The energy of the HIFU signal can be modified by increasing
or decreasing any of the burst length, the burst interval, the
pulse length, the pulse rate interval, or other characteristics
such as the pulse amplitude. In one embodiment, the HIFU treatment
system automatically varies the acoustic output energy or power as
a function of both the characteristic K curve relative to the
baseline characteristic curve and whether the device is within an
acceptable range for the values of K. An acceptable range for K may
have an upper limit for pre-focal and focal values of K, based on
safety levels. Other treatment parameters such as treatment time or
pulse repetition frequency of the HIFU signals can be selected in a
similar manner.
[0077] FIGS. 1 through 10 illustrate an embodiment of the disclosed
technology starting with a simple block diagram. As one trained in
the art will appreciate, there are other versions of this
technology that generate similar benefits. FIG. 11 is another block
diagram of a HIFU treatment system for implementing the technology
disclosed herein. In the embodiment, a HIFU controller 110 delivers
electronic driving signals to an external or internal transducer
probe 116 that in turn converts the driving signals into acoustic
HIFU signals. In FIG. 11, the HIFU transducer probe 116 is shown in
a wand-like apparatus. It is important to note that the HIFU
transducer many have a plurality of elements in multiple dimensions
that are mechanically or electronically steered to properly direct
the ultrasound signal to the intended target. For example, the HIFU
signals may be directed to a focal zone that is aimed at a target
volume 118 through electronic or mechanical means. The target
volume 118 may include all or a portion of a fibroid in a uterus
120. The HIFU signals create corresponding echo signals from tissue
that are intercepted by the acoustic propagation. In most cases,
the HIFU signal energy is concentrated on an axis that is located
between the transducer probe 116 and the focal zone.
[0078] The echo signals are received by the transducer probe 116,
converted into an electronic form and supplied to the HIFU
controller 110. The detection of the echo signals may take place in
the HIFU transducer or another specially designed device contained
within the transducer probe 116. Furthermore, the detection device
may be in a separate holder not contained within the transducer
probe 116.
[0079] As previously described, the K values from the echo signals
are calculated (FIG. 9), analyzed, and used to control or select
one or more treatment parameters. An ultrasound processor 124 that
is connected to or incorporated within the HIFU controller 110
analyzes the received echo signals and computes the K values. Based
on the analysis, one or more treatment parameters or
characteristics of the HIFU excitation signal (e.g., peak power,
average power, pulse duration, pulse repetition interval, etc.) are
automatically or semi-automatically adjusted by the ultrasound
processor 124. In some cases, the operator may be alerted via an
audible, visible, or tactile alert 130 to manually adjust one of
the device parameters through a control on the device (e.g., main
console control 112, applicator, footswitch). A safety mechanism to
ensure treatment does not continue without proper feedback signals
may also be employed. In some instances, the system may also
include ultrasound imaging capabilities that produce images of the
tissue on a video display 132. The images may be obtained with a
separate or integrated imaging ultrasound transducer. These images
may be used to confirm proper adjustment of the HIFU excitation
characteristics.
[0080] To estimate how much of the incident HIFU energy is being
absorbed by the tissue at various positions at or adjacent to the
focal point of the HIFU signal, the value of the ratio K is
determined from the echo signals received from a given point in the
tissue. In one embodiment, the ratio is compared to a desired value
of K that was determined from prior testing. The value of the ratio
K for the detected signals can therefore be used as a feedback
signal to adjust one or more characteristics of the HIFU signal to
affect absorption and hence HIFU effects on tissue at a given
point. Detection of saturation (acoustic shock waves) or the slope
of the increase in the K value as a function of the transmit
excitation may also be used as feedback mechanisms to adjust one or
more characteristics of the HIFU signal rather than depending on
prior testing.
[0081] In one embodiment, if the determined value of K for detected
signals is below a threshold value for a particular position in the
patient, then a signal characteristic such as the amplitude, peak
or average power, duty cycle, pulse repetition rate, or other
characteristic of the delivered HIFU signals can be electronically
or manually increased to increase the ratio K at that position.
Conversely, if the determined value of K is above a threshold, then
one or more of the amplitude, power, duty cycle, pulse repetition
rate, or other characteristic of the HIFU signal can be decreased
to decrease the value of K. Different threshold values of K may be
used to analyze echo signals received from within the target volume
and outside that target volume in the body.
[0082] FIGS. 12A and 12B illustrate two possible applicator
configurations that deliver HIFU signals to a target volume and
detect echo signals at the fundamental frequency of the HIFU signal
and at harmonics or other frequencies. In the example shown in FIG.
12A, a HIFU transducer probe 200 delivers one or more HIFU signals
to a target volume. The HIFU transducer probe may have a fixed or
variable focal point. Echo signals are received by a separate
receiving transducer 220. The receiving transducer 220 has a
bandwidth that is sufficient to detect echo signals over a range of
frequencies that may include the fundamental frequency of the HIFU
signals produced by the transducer probe 200 and its harmonics. The
receiving transducer 220 may be an ultrasound imaging transducer, a
non-imaging transducer such as a polyvinylidene fluoride (PVDF)
transducer, a fiber optic hydrophone or other form of hydrophone.
The receiving transducer 220 may be positioned to detect echo
signals reflected back from the focal point. Alternatively the
receiving transducer 220 may be positioned to detect signals that
are transmitted through the focal point and away from the HIFU
transducer.
[0083] In the example shown in FIG. 12B, a combination HIFU
transmitting and receiving transducer probe 230 includes HIFU
transmitting elements 232 that produce the HIFU signals and an
array of higher bandwidth receiving elements 234 that are used to
detect echo signals over a range of frequencies that may include
the fundamental frequency of the HIFU signals and may also include
one or more harmonics. The transducer in FIG. 12B may utilize a
PVDF or other type of sensor.
[0084] FIGS. 13A and 13B illustrate two different feedback
mechanisms to adjust a treatment parameter of a HIFU signal to be
delivered. In FIG. 13A, a control signal 239 from the HIFU
controller 110 is applied to a waveform generator 240 to produce a
waveform of the HIFU signals that will be applied to the patient. A
control signal 249 is also applied to the waveform generator 240 by
a signal processing unit 248 such as a programmable microprocessor
or special purpose microprocessor within the ultrasound processor
224 that correlates the transmission and receipt of HIFU signals.
Alternatively, the signal processing unit 248 may be a stand-alone
device. The signals from the waveform generator 240 are supplied to
a pulser 242 that increases the voltage of the signals to the level
required by a HIFU transducer 244 to produce ultrasound acoustic
signals. Echo signals are received by the HIFU transducer 244 where
they are converted back into an electronic form for supply to a
receiver 246. From the receiver 246, the echo signals are supplied
to the signal processing unit 248 that analyzes the echo signals in
accordance with the control to determine the ratio K described
above. The signal processing unit 248 produces the control signal
signals 249 that are fed back to the waveform generator 240 to
electronically change one or more characteristics of the HIFU
signals in order to change the energy or other characteristic of
the HIFU signals delivered to the patient such that the detected
ratio K falls within a desired range.
[0085] The feedback mechanism shown in FIG. 13B is similar to that
shown in FIG. 13A except that a separate transducer 245 is used to
detect the echo or other (e.g. transmitted) signals from the
patient. For example, the transducer 245 may be a high bandwidth
single element transducer such as a transducer with a PVDF
material, or it may be an imaging transducer. Echo or non-reflected
signals received by the transducer 245 are supplied to the receiver
246 and the signal processing unit 248 that determines the value of
the ratio K and what, if any, characteristics of the HIFU signals
should be electronically adjusted to control the energy or other
characteristic of the HIFU signals delivered to the patient.
[0086] In yet another embodiment, the system includes an integrated
or separate ultrasound imaging system that produces ultrasound
images such as B-mode images of the tissue. The value of the ratio
K is determined for various points in the body and is color coded
or otherwise made visually distinct. The visually distinguished K
values in the tissue can then be combined with a B-mode or other
type of ultrasound image. In one embodiment, the color coded K
values 134 are overlaid onto a B-mode image on the display 132 as
shown in FIG. 11. By viewing the various levels of K, the physician
can see where the higher frequency components of the HIFU signals
are being created. The physician can then adjust the position of
the HIFU transducer probe so that the HIFU signals are being
delivered into the desired area. In addition or alternatively, the
physician can see if one or more characteristics of the HIFU
signals should be adjusted to change the amount of energy delivered
to the patient.
[0087] In another embodiment, the system may calculate the center
of mass, also called a centroid, for use in the physician's
on-screen display, by analyzing the harmonics received by the
system. This reduces the overall clutter in the on-screen
display.
[0088] In another embodiment, the system records the value of the
inputs that provide the K ratio value. This allows the system to
detect a correlation between pulses in order to build a successive
picture of trends in feedback characteristics. This may, for
example, provide information valuable in determining whether
cavitation or other tissue characteristics have occurred. The
system may also make use of pulse inversion in order to create a
data set of K ratio values over time for use in feedback analysis
that eliminates the fundamental.
[0089] FIG. 14 illustrates another embodiment of the disclosed
technology where instead of calculating the value K by Fourier
transform, a number of filters 300 detect the energy of the echo
signals in various frequency ranges. The filters can be digital
(e.g., FIR or IIR) or analog (e.g., bandpass, notch, etc.). The
value K can then be determined digitally or with an analog circuit
302.
[0090] Another possible embodiment of this technique is to use
baseband detection along with low pass filtering to determine the
energy in a detected signal at the fundamental as well as at one or
more of the harmonics. The acquired rf vector at a particular power
setting is detected and multiplied by sine and cosine waves at the
fundamental or harmonic frequencies to obtain baseband data:
B.sub.n(t)=x(t)*exp(-j2.pi.nft)
[0091] where f is either the fundamental frequency, n the order of
the harmonic (e.g. n is one for the fundamental and 2 for the
second harmonic), t is the time vector, x(t) is the original rf
waveform, and B.sub.n is the baseband detected signal.
[0092] After mixing with the sine and cosine waves, the signal is
low pass filtered to eliminate energy from other harmonics. The
bandwidth of the low pass filter is driven by the bandwidth of the
original excitation. After the low pass filter, the signal may be
decimated to a lower sampling frequency. The baseband detected
signal is associated with a specific transmit power and is a
function of depth.
[0093] In addition or as an alterative to controlling treatment
parameters based on the ratio of the energy in different frequency
regions, other characteristics of the detected signals can also be
used to select or control the treatment parameters.
[0094] FIG. 15 shows an original ultrasound echo obtained from an
in-vivo porcine subject in which a HIFU signal was targeted at 107
mm. FIGS. 16 and 17 show the baseband detected signals for the
fundamental and second harmonic of the echo signal respectively. As
more signals are acquired at different power levels, a filter may
be applied over the ensemble of detected signals to reduce noise
artifacts. Furthermore, additional filtering in depth and power
dimension may be applied due to the expected transitions. FIG. 18
shows a 2D image of the second harmonic energy as a function of
depth and excitation power. To select a treatment parameter such as
the desired transmit power, a search region may be defined around
the expected focus. The size of the search region will vary
depending on the depth-of-field of the transducer and potential
variances in propagation velocity.
[0095] As will be described below, the response of a signal
characteristic to changes in the power of a transmitted HIFU signal
is used to select one or more treatment parameters of HIFU signals
that will be used to treat a tissue site. FIG. 19 illustrates a
response curve showing how the energy of a received signal at the
second harmonic of the HIFU test signals varies with changes in
HIFU power for a tissue area near the focal point of the
transducer. Depending on how many test signals are used, the
response curve would be created from a series of discrete data
points obtained for different transmit powers that are then
mathematically smoothed.
[0096] In the example shown, the response curve shown in FIG. 19 is
computed from received echo signals at the second harmonic of the
HIFU transmit frequency. However t will be appreciated that the
signal detected could be a signal that passes through the treatment
site or could be computed for another harmonic or range of
frequencies or combination of harmonics. In general, the response
curve will be computed for a signal characteristic that exhibits a
measurable change with changes in transmitted HIFU power.
[0097] In one embodiment, to select the one or more treatment
parameters to be used in treating a tissue site, the response curve
for the tissue is determined using a number of test signals
transmitted at different power levels. The response curve may be
compared to previously known response curves having treatment
parameters associated with them. The treatment parameters
associated with the previously known response curve that best
matches the response curve for the tissue site in question can be
used to treat the tissue site. Alternatively, one or more points on
the response curve for the tissue can by analyzed to select the one
or more treatment parameters.
[0098] In one embodiment, the response curves can be analyzed to
determine a saturation point, slope or other characteristic such as
the shape of the curve. FIG. 19 shows a saturation point for the
second harmonic signal near the focus with a power saturation value
of approximately 1500 W. The treatment parameters associated with a
1500 watt saturation point can therefore be used to treat the
tissue.
[0099] To automate the determination of the saturation levels in
the focal region the response curve is analyzed with a suitably
programmed processor or computer. In one embodiment, the goal is to
identify the power which exhibits the highest level of scattered
energy and thus energy absorption. Ideally regions with significant
amounts of harmonic energy would be used to maximize
signal-to-noise ratio. For example, the peaks throughout the search
region may be selected rather than each sample.
[0100] In one embodiment, a look-up-table (LUT) of expected
response curves is used to determine the saturation values around
the focus. This LUT may consist of response curves predicted
theoretically with different characteristics such as attenuation
and isentropic non-linearity parameter B/A. Statistical techniques
such as correlation are used to compare the theoretical curves to
the detected response curve. In this case, it is possible to obtain
the saturation power as well as the effective characteristics of
the tissue path such as attenuation that can be used to determine
the length of treatment time to treat the tissue site.
[0101] In another embodiment, the processor or computer is
programmed to determine the first and second derivatives of the
determined response curve. Next, regions that are concave down with
both positive and negative slopes on either side are identified and
considered the saturation value.
[0102] In yet another embodiment, the expected first and second
derivatives are used to code the waveform at a particular depth.
Rather than look for a place that has a slope of zero and is
concave down, the processor or computer is programmed to use other
characteristics of the expected curve predicted by theory or other
controlled experiments to increase the confidence that the correct
saturation value was chosen. A code is assigned to the expected
waveform and the code of the experimental data is determined based
on the sign of the first and second derivative. For example, a code
of zero is assigned to a slope of zero, a code of one to a negative
slope and code of two to a positive slope. In this case, each point
analyzed on the response curve could have one of nine possible
codes (e.g. 00, 01, 02, 10, 11 etc.). The code is modified only if
there is a change between the value of the first and second
derivatives between samples, which further compresses the data. A
correlation value may be determined between the coded expected
value and the coded experimental value to increase the reliability
of the algorithm. If the correlation is not above a certain value,
then the saturation cannot be determined.
[0103] In some embodiments, the curve with the lowest saturation
value is used as the prediction. Another method is to average the
results through the search region and utilize this for treatment.
Ideally, the process for determining the saturation value occurs in
real-time such that exorbitant power values are not used.
[0104] This idea may be extended to lesions at different depths. In
this case, interrogations at different lesion locations are
completed. The estimated saturation levels are compared. This
allows for the possible calculation of the effective attenuation in
the treatment region.
[0105] In yet another alternative embodiment of the disclosed
technology, the response curve for the detected signals that is
analyzed to determine the treatment parameters is related to the
temperature change at the focal zone. In this case, HIFU test
signals are transmitted and a change in temperature is determined
based a detected speckle shift of a reflected signal (echo) or
transmitted signal. Speckle shifts are determined for a number of
HIFU signals transmitted at different power levels in order to
generate the response curve. Preferably the test HIFU signals are
sufficiently short so that the tissue in the focal zone does not
undergo sustained heating prior to treatment or between test
signals. The response curve is analyzed by comparing against
predetermined response curves or by determining some characteristic
such as its saturation point, whereby the speckle shift no longer
increases or decreases with increases in delivered HIFU signal
power. Once the response curve has been analyzed either by
comparison to previously determined response curves or by analyzing
selected points on the response curve, the treatment parameters can
be selected.
[0106] In yet another alternative embodiment, a response curve
related to the dispersion of the waveform transmitted into the
tissue is used to control or select the treatment parameter for the
HIFU signals to be used to treat the target tissue site.
[0107] Dispersion occurs in acoustic waves and is noted by a slight
velocity difference of the wavefront that is a function of
frequency although the group velocity may remain constant. In high
intensity acoustics, dispersion in the wave pulse naturally occurs
in regions of high compression due to the production of harmonics.
The high pressure and non-linear ties of tissue eventually lead to
acoustic shock at the highest compressional pressures. The
production of harmonics and dispersion are less likely to occur in
low pressure pulses. As the pressure is increased, the amount of
dispersion increases since harmonics are more easily generated.
This dispersion is detected as a phase shift in the waveform as the
amplitude of the excitation moves from low pressure to high
pressure. The dispersion is seen as movement of the rf signal
toward the transducer and is localized by the area of high
pressure. This is unique when compared to other effects such as
acoustic radiation force (ARF) and apparent phase shifts due to
temperature changes. In both of these cases, the expectation is the
phase shift is away from the transducer. Furthermore, velocity
changes due to temperature are an integrative effect in tissue. In
other words, where the local temperature has increased, the shift
will appear at that point as well as for every point behind the
thermal increase.
[0108] FIG. 20 shows the changes that occur in the pressure pulse
at the focus at increasing transmit pressures 400, 402, 404, 406.
Each pulse has been normalized for purposes of illustration. In
this case, the fiber optic pressure hydrophone (FOPH) is receiving
the transmitted pulse at the focus (in this case 64 mm). The high
compressional pressure produces the shock that appears between 2.9
usec and 3.1 usec in FIG. 20. As the pressure is increased, the
shock front is produced prior to the focus which yields to the
detected dispersion at the focus. FIG. 20 captures the movement of
the compression peak from a low excitation level (400) to a high
excitation level (406). In this case, the movement is approximately
0.1 usec. FIG. 21 shows the received echo from a point target at
the focus at the same transmit power levels 400, 402, 404, 406. The
PVDF sensor shows dispersion occurring for negative as well as
positive pressures. This is due to the PVDF sensor impulse
response. When a wide bandwidth wavefront such as that shown in
FIG. 21 impinges the PVDF sensor surface, the sensor will
mechanically vibrate equally in compression and rarefaction.
[0109] The resulting phase shifts shown in FIGS. 20 and 21 are
detected as a spatial shift in an ultrasound image. This spatial
shift may be detected on rf as well as detected data. Furthermore,
the detected phase shift may be used to localize areas of high
pressure. Therefore, it is possible to create a pressure map of the
body based on dispersion.
[0110] Dispersion may be detected as a slight shift in the image or
speckle toward the HIFU transducer as test signals of successively
higher power are applied to the tissue. This is illustrated in
FIGS. 20 and 21 in which the higher level DAQ settings correspond
to higher power levels and the time to receive the wavefront
corresponds to its position relative to the transducer.
[0111] As the power level is increased, there is a corresponding
increase in production of harmonics at the focal region--which in
turn reduces the time to receive the signal scattered from the
focal region, due to dispersion. This reduced time can be perceived
as a spatial shift in the ultrasound image towards the transducer,
assuming the signals are displayed graphically.
[0112] As shown in the attached flowchart of FIG. 22, to determine
a treatment parameter such as a power level setting for HIFU to be
delivered to a tissue treatment site, a therapy transducer is
briefly excited at a number of test power level settings. At each
such setting, a backscattered ultrasound signal is detected with
the same transducer that delivers the signals or with a different
transducer. The backscattered signals are stored until each of the
possible power levels are tested or until an optimal power level is
determined.
[0113] After delivering the test signals with the different power
level settings, the speckle shift associated with adjacent power
level settings is determined. A response curve showing the change
in the speckle shift versus changes in HIFU power is created with a
programmed processor or computer. The response curve is analyzed
and used to select one or more treatment parameters. For example, a
programmed processor can analyze the response curve to determine a
power level at which the speckle shift saturates i.e. doesn't
change with further increases in power or the amount of speckle
shift decreases with further increased power. In one embodiment,
the treatment parameters are selected based on the power level of
the HIFU that causes saturation. Other signals characteristics such
as the slope of the response curve can be used to select the
treatment parameters. In yet another alternative embodiment, the
response curve can be compared with predefined response curves
having treatment parameters associated with them. The treatment
parameters associated with the response curve that best matches the
determined response curve can be used to treat the tissue.
[0114] In one embodiment, treatment of each location within an
intended treatment volume may be immediately preceded by
determination of the treatment parameters for that location. In
another embodiment, the treatment parameters may be determined at a
variety of locations within an intended treatment volume prior to
commencing treatment of any such location. The treatment parameters
for each location are then stored in a memory or other computer
readable media. Once treatment begins, the selected treatment
parameters are recalled for each such location and used to treat
that location. In yet another embodiment, the treatment parameters
selected for one location can be used to treat an entire volume of
tissue.
[0115] To maximize the accuracy and consistency of this method for
selecting treatment parameters, the successive test HIFU signals
should be spaced together closely in time so as to minimize any
spatial shifts that might occur due to tissue motion (e.g. due to
breathing or other patient motion).
[0116] In addition, the test signals should be applied in a manner
which minimizes local heating of tissue, so as to avoid shifts that
might occur due to changes in local sound velocity.
[0117] In yet another embodiment, the energy in a received signal
at harmonics of the fundamental frequency of the HIFU signal can be
estimated by measuring the energy at the fundamental frequency.
This technique allows a more narrow band detection system to be
used.
[0118] If a HIFU signal is delivered to the tissue at power P.sub.1
(that is selected to be low enough not to create energy at the
harmonics in the tissue) and at a distance r, the HIFU signal will
produces a signal with energy at the fundamental frequency of the
HIFU signal that is defined by a function:
Xf(P1, r) (6)
[0119] If the tissue behaved linearly, then the energy at the
fundamental of a signal created from a HIFU signal that is
transmitted at a higher power level P.sub.2, should be related to
the different power level by the function:
Xf ( P 2 , r ) = P 2 P 1 Xf ( P 1 , r ) ( 7 ) ##EQU00003##
[0120] However the tissue generally does not respond linearly to
higher power levels of HIFU signals. Therefore the measured energy
at the fundamental frequency of a signal that is created in
response to a higher power HIFU signal will differ from the
prediction. The difference is related to the energy that is being
converted into the energy at the harmonics.
[0121] To estimate the energy at the harmonics, the energy of a
received signal at the fundamental frequency of the HIFU signal
that is delivered at a power level P.sub.2 is determined. The
difference between the energy measured and the energy predicted is
calculated, according to the function:
Xh = P 2 P 1 * Xf ( P 1 , r ) - Xf ( P 2 , r ) ( 8 )
##EQU00004##
[0122] where Xh is the energy at the harmonics. The ratio of the
energy in the harmonics to the energy at the fundamental frequency
of the HIFU signals is therefore given by the function:
Xh ( P 2 , r ) Xf ( P 2 , r ) = P 2 P 1 Xf ( P 1 , r ) Xf ( P 2 , r
) - 1 ( 9 ) ##EQU00005##
[0123] A response curve can therefore be created that relates the
energy of the harmonics to increases in the energy of the HIFU
signals delivered. The response curve can be analyzed by a
programmed processor or computer and used to select the treatment
parameters either by comparison against predetermined response
curves having treatment parameters associated therewith or by
analyzing characteristics of the response curve and selecting
treatment parameters associated with the characteristics.
[0124] In yet another embodiment, the "focal gain" i.e. the
increased energy absorption caused by the energy level of the
harmonics that is created in the tissue can be estimated by
comparing the energy of the signals created from HIFU signals at
different powers. If the tissue were linear, then the following
relationship should hold for different HIFU power levels.
X ( P 2 , r ) P 2 P 1 X ( P 1 , r ) = 1 ( 10 ) ##EQU00006##
[0125] However as the power level increases, more energy is
transferred to the harmonics and the ratio should become less than
one with a drop in the detected energy at the HIFU power level that
causes a saturation if measured with a narrow band receiver or a
gain in the detected energy at the energy level that causes
saturation if measured with a wide band receiver. Therefore, a
response curve can be determined that relates the ratio of detected
energy to predicted energy at several different HIFU power levels.
The response curve can then be analyzed or compared to other
response curves in order to select one or more treatment
parameters.
[0126] As will be appreciated by those skilled in the art, the
deposition of energy at a treatment site is effected by the
tissue's "alpha" value that is related to attenuation as well as
its "B/A" value that is related to the tissue's isentropic
non-linearity parameter B/A.
[0127] The alpha value for the tissue treatment site can be
estimated by measuring the energy of a signal created in response
to a test HIFU signal at a fixed power. The transducer can then be
moved away from the treatment site and the space filled with a
medium of known attenuation e.g. water. A second test HIFU signal
is then applied to the tissue and the energy detected. A response
curve in this example therefore relates the difference in energies
detected and the distance that the transducer was moved. From the
estimated attenuation of the tissue, a treatment regimen (power and
treatment duration or other treatment parameter) can be selected
based on predetermined clinical data performed on tissue types with
similar alpha values. The alpha value for the tissue can be
determined by comparing response curves for different spatial
locations in the tissue.
[0128] The B/A value for a tissue site to be treated can be
estimated based on comparison of the tissue's response curve with
response curves computed for tissue types with known B/A
values.
[0129] As indicated above, the treatment parameters such as power
level, pulse duration, pulse repetition frequency etc. are selected
based on an analysis of the response of the tissue to be treated to
a HIFU pulse. The particular values for these treatment parameters
will be based on clinical data and stored in a manner that can be
indexed based on an analysis of the response curve for the
treatment site. The parameter data is typically stored in a
computer readable media, hard drive, CD ROM, solid state memory
etc, that is accessed by a local or remote computer. When needed,
the recalled treatment parameters are applied to the HIFU control
hardware so that the tissue can be treated.
[0130] In addition or as an alternative to selecting or adjusting
the energy of the delivered HIFU signals, the disclosed technology
can be used to redirect the focus point of the delivered signals.
In the embodiment shown in FIG. 23, a therapy transducer 350
delivers a number of test signals to a tissue site at the same or
different power levels. A detection transducer 352 receives the
corresponding echo or other signals, which are provided to a
processor (not shown) that computes response curves, such as the K
values described above or response curves based on other signal
characteristics, at a number of positions in the tissue. In the
example shown, the K values have a maximum value at a point 360
which is offset from an intended focus point 362 of the test
signals. By comparing the location of the maximum K value to the
intended focus point, the processor can determine if the focus
point is misaligned. By computing the offset between the location
of the maximum K value at 360 and the intended focus point at 362,
a difference vector can be determined and the difference vector
supplied to a beam forming equation used by a waveform generator to
cause the therapy transducer 350 to redirect the focus point of the
HIFU process towards the desired focus point 362. Alternatively,
the difference vector can be supplied to a mechanical mechanism
(not shown) that physically reorients the focus of the HIFU
transducer. The process can continue by continuing to measure K
values from the received echo signals and computing the location of
the maximum K value and comparing it to the desired focus point
until such time as the maximum K value is within a predetermined
distance of the desired focus point.
[0131] If the response curves are created based on other signal
characteristics, the focus can be redirected based on the response
curves determined for each of the spatial locations.
[0132] Although illustrative embodiments of the disclosed
technology have been illustrated and described, it will be
appreciated that various changes can be made therein without
departing from the scope of the technology. For example, the
response curves may also be produced for a change in acoustic
radiation force (ARF) that relates movement of the tissue to
changes in power of the test signals. In addition, the disclosed
technology is not limited to the delivery of HIFU signals to the
patient but can be applied to the delivery of any waveform such as
non-focused ultrasound to a non-linear medium such as tissue.
Therefore, the scope of the technology is to be determined solely
by the following claims and equivalents thereof.
* * * * *