U.S. patent application number 09/973601 was filed with the patent office on 2002-08-15 for lysis method and apparatus.
Invention is credited to Eshel, Yoram, Furman, Vladimir, Kerner, Efim, Rosenschein, Uri.
Application Number | 20020111569 09/973601 |
Document ID | / |
Family ID | 25472893 |
Filed Date | 2002-08-15 |
United States Patent
Application |
20020111569 |
Kind Code |
A1 |
Rosenschein, Uri ; et
al. |
August 15, 2002 |
Lysis method and apparatus
Abstract
An apparatus a method for the application of ultrasound to a
location within the body is provided. The apparatus can
advantageously operate at a pulse duration below about 100
milliseconds and in the range 0.1 milliseconds to 100 milliseconds
and a pulse repetition period below about 1 second and in the range
of 1 millisecond to 1 second. Duty ratios over 5 and preferably
over 8 are also advantageous. Therapeutic applications of
ultrasound such as for assisting in the treatment of medical
conditions such as cancer and/or other ailments are also
provided.
Inventors: |
Rosenschein, Uri; (Kefar
Daniel, IL) ; Eshel, Yoram; (Tel Aviv, IL) ;
Furman, Vladimir; (Ashelon, IL) ; Kerner, Efim;
(Rehovot, IL) |
Correspondence
Address: |
William H. Dippert
Cowan, Liebowitz & Latman, P.C.
1133 Avenue of the Americas
New York
NY
10036
US
|
Family ID: |
25472893 |
Appl. No.: |
09/973601 |
Filed: |
October 9, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09973601 |
Oct 9, 2001 |
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09653801 |
Sep 1, 2000 |
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09653801 |
Sep 1, 2000 |
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08939289 |
Sep 29, 1997 |
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Current U.S.
Class: |
601/4 ;
600/439 |
Current CPC
Class: |
A61B 2017/00106
20130101; A61B 2018/00011 20130101; A61B 2017/22007 20130101; A61B
17/22012 20130101 |
Class at
Publication: |
601/4 ;
600/439 |
International
Class: |
A61B 017/22 |
Claims
What is claimed is:
1. A method of applying therapeutic ultrasound to a location within
a body, comprising: activating a transducer to produce ultrasound
at a pulse repetition period of T.ltoreq.1000 milliseconds and
directing this ultrasound to a location within a body.
2. The method of claim 1, wherein the ultrasound is directed to a
location within the body in an invasive manner, with an ultrasound
device which is inserted into the body.
3. The method of claim 1, wherein the ultrasound is directed to a
location within the body with a non-invasive ultrasound producing
device.
4. The method of claim 2, wherein T= about 1 millisecond to 1000
milliseconds.
5. The method of claim 3, the transducer is operated to produce
ultrasound at a frequency of about 100 to 1000 KHz.
6. The method of claim 5 wherein T= about 1 to 100
milliseconds.
7. The method of claim 3 wherein T= about 2.5 to 90
milliseconds.
8. The method of claim 5 wherein T=2.5 to 75 milliseconds.
9. The method of claim 3, wherein .tau.= about 0.01 to 2.0
milliseconds.
10. The method of claim 3, wherein .tau.= about 0.02 to 1.1
milliseconds.
11. The method of claim 3, wherein .tau.=0.1 to 0.3
milliseconds.
12. The method of claim 9, wherein the transducer is producing
ultrasound at a frequency of about 100 to 1000 KHz.
13. The method of claim 3, wherein the intensity of the ultrasound
applied is I.gtoreq. about 750 W/cm.sup.2.
14. The method of claim 6, wherein the intensity of the ultrasound
applied is I.gtoreq. about 750 W/cm.sup.2.
15. The method of claim 9, wherein the intensity of the ultrasound
applied is I.gtoreq. about 750 W/cm.sup.2.
16. The method of claim 12, wherein the intensity of the ultrasound
applied is I.gtoreq. about 750 W/cm.sup.2.
17. The method of claim 13, wherein the transducer produces
ultrasound at a pulse duration of .tau..ltoreq.100
milliseconds.
18. The method of claim 1, including the steps of initiating
cavitation within the body by applying a first amount of power to
the transducer, initiating cavitation at the location within the
body, then reducing the power supplied, while maintaining
cavitation.
19. A method of applying therapeutic ultrasound to a location
within a body, comprising: producing ultrasound with a pulse
duration of .tau..ltoreq.100 milliseconds and transmitting the
ultrasound to a location within a body via a transmission member
which is at least partially inserted into the body.
20. The method of claim 19, wherein the frequency of the ultrasound
produced in about 20 to 100 KHz.
21. The method of claim 19, wherein the pulse repetition period
T.ltoreq.about 1000 milliseconds.
22. The method of claim 21, wherein T is about 100 to 500
milliseconds.
23. The method of claim 19, wherein .tau. is about 20-60
milliseconds.
24. The method of claim 20, wherein .tau. is about 10-100
milliseconds.
25. The method of claim 22, wherein .tau. is about 10-100
milliseconds.
26. The method of claim 25, wherein the frequency of the ultrasound
produced is about 20 100 KHz.
27. The method of claim 19, wherein the ultrasound is produced with
a transducer operated at a peak power output of 10 to 40 watts.
28. The method of claim 22, wherein the ultrasound is produced with
a transducer operated at a peak power output of 10 to 40 watts.
29. The method of claim 25, wherein the ultrasound is produced with
a transducer operated at a peak power output of 10 to 40 watts.
30. The method of claim 27, wherein the peak power output is about
15 to 30 watts.
31. The method of claim 23, wherein the peak power output is about
15 to 30 watts.
32. The method of claim 23, wherein substantially no cooling fluid
is pumped around the transmission member.
33. The method of claim 19, wherein the device is operated at a
duty ratio T/.tau. about .gtoreq.5.
34. The method of claim 19, wherein the device is operated at a
duty ratio T/.tau. about .gtoreq.8.
35. The method of claim 3, wherein the device is operated at a duty
ratio of about .gtoreq.5.
36. The method of claim 3, wherein the device is operated at a duty
ratio of about .gtoreq.8.
37. The method of claim 19, wherein the transmission member is
located within a guide catheter and is substantially unsheathed
within the guide catheter.
38. A system for delivering ultrasound energy into a body,
comprising: a signal generator, a transducer coupled to the signal
generator and a transmission member coupled to the transducer; the
signal generator, transducer and transmission member constructed
and arranged to transmit ultrasound produced by the transducer to a
location within the body by inserting at least a first portion of
the transmission member into the body, the transmission member
including substantially no sheathing for the transportation of
cooling fluid around the first portion of the transmission
member.
39. The system of claim 38, wherein the signal generator,
transducer and transmission members are constructed and arranged to
deliver ultrasound energy to the coronary artery at a peak power
output of over 10 watts.
40. The system of claim 38 including a sound detection device
capable of detecting cavitation within the body caused by energy
transmitted via the transmission member and displaying the presence
of the detected cavitation.
41. A system for delivering ultrasound energy into a body,
comprising: a signal generator, a transducer coupled to the signal
generator and a transmission member coupled to the transducer; the
signal generator, transducer and transmission member constructed
and arranged to transmit ultrasound to a location within the body
by inserting at least a portion of the transmission member into the
body; and a sound detection device and a display therefore capable
of detecting the sound caused by cavitation within the body
generated by ultrasound transmitted via the transmission member and
displaying the presence of sound caused by the presence of
cavitation.
Description
BACKGROUND OF THE INVENTION
[0001] The invention relates generally to medical devices and more
particularly to a method and apparatus for delivering ultrasound
energy to a treatment location within a human or other mammal.
[0002] The use of ultrasound devices for ablating, lysing or
removing material obstructing blood vessels in humans and to
otherwise apply ultrasound to locations within the body for
therapeutic purposes has been proposed in the art. One such device
for removing material obstructing blood vessels is in the form of
an elongated ultrasound transmitting probe. This device includes a
cavitation generating tip at the distal end of an elongated
transmission member. A transducer is used to convert an electrical
signal into longitudinal mechanical vibration, which is transmitted
to the tip by the transmission member and causes cavitation within
the blood vessel to ablate or lyse the obstruction.
[0003] One drawback to such a device is the need to insert and
advance the device through a blood vessel to the treatment
location. This raises various concerns, such as the opportunity for
breakage of apparatus parts within the body, injury to the body
from the probe itself and so forth. Another drawback is the need to
pump cooling fluid down the length of the device. Examples of such
devices are discussed in the following patents, applications and
publications, the contents of which are incorporated herein by
reference: U.S. Pat. No. 5,163,421, issued Nov. 17, 1992;
5,269,297, issued Dec. 14, 1993; 5,324,255; 4,474,180; Ser. No.
08/858,247, filed May 19, 1997 and Julian Frederick, "Ultrasonic
Engineering", John Wiley and Sons (1965). However, it is desirable
to provide an improved system and method which overcome drawbacks
of these conventional devices and methods.
[0004] The non-invasive use of ultrasound has also been proposed.
For example, U.S. Pat. No. 5,524,620 dated Jun. 11, 1996, the
contents of which are incorporated herein by reference, describes a
non-invasive apparatus and method in which focused acoustic energy
is used to ablate a thrombus without the need for invasive devices
or drugs. However, non-invasive ultrasound systems can exhibit
insufficiently satisfactory results. For example, high power is
generally needed to cause adequate lysis. This high power is
potentially dangerous and thus, it is desirable to operate a
non-invasive system more efficiently, at lower average power, in
order to provide a greater margin of safety. The effects of
non-invasive ultrasound devices on various locations within the
body can also be difficult to predict.
[0005] Accordingly, it is desirable to provide an improved system
and method for the non-invasive application of ultrasound which
overcomes inadequacies of the prior art.
SUMMARY OF THE INVENTION
[0006] Generally speaking, in accordance with the invention, an
apparatus and method for the application of ultrasound to a
location within the body is provided. The apparatus can
advantageously operate at a pulse duration below about 100
milliseconds and in the range 0.1 milliseconds to 100 milliseconds
and a pulse repetition period below about 1 second and in the range
of I millisecond to 1 second. Duty cycle ratios over 5 and
preferably over 8 are also advantageous. Therapeutic applications
of ultrasound such as for assisting in the treatment of medical
conditions such as cancer and/or other ailments are also
provided.
[0007] Accordingly, it is an object of the invention to provide an
improved apparatus and method for treating locations within the
body with ultrasound.
[0008] A further object of the invention is to provide a method and
apparatus for determining ultrasound application parameters.
[0009] Yet another object of the invention is to provide an
apparatus and method for therapeutic applications of
ultrasound.
[0010] Still other objects and advantages of the invention will in
part be obvious and will in part be apparent from the specification
and drawings.
[0011] The invention accordingly comprises the several steps and
the relation of one or more of such steps with respect to each of
the others, and the apparatus embodying features of construction,
combinations of elements and arrangements of parts which are
adapted to effect such steps, all as exemplified in the following
detailed disclosure, and the scope of the invention will be
indicated in the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] For a fuller understanding of the invention, reference is
had to the following description taken in connection with the
accompanying drawings, in which:
[0013] FIG. 1A is a schematic perspective view of a system for the
non-invasive use and testing of ultrasound energy;
[0014] FIGS. 1B and 1C are front and side views of the transducer
shown in FIG 1A;
[0015] FIG. 2 is a graph showing hydrophone output, in decibels, as
a function of transversal displacement of the hydrophone along the
Y axis to establish the focal width of ultrasound in the Y
direction;
[0016] FIG. 3 is a graph showing hydrophone output voltage as a
function of transducer input voltage, showing that electric
potential above 160 volts, and therefore increased wattage, caused
a decrease in hydrophone output as a result of exceeding the
cavitation threshold of the medium;
[0017] FIG. 4 is a graph showing hydrophone output voltage as a
function of displacement of the transducer along the Z-axis for
both short duration pulses and relatively longer duration pulses,
showing that a longer pulse duration (.tau.) can initiate
cavitation;
[0018] FIG. 5 is a graph showing hydrophone output voltage as a
function of Z-axis displacement for various pulse durations,
showing that longer pulse durations were associated with larger
decreases in acoustic amplitude after exceeding the cavitation
threshold;
[0019] FIG. 6 is a graph showing hydrophone output voltage as a
function of Z-axis displacement for transducer inputs of varying
voltage, showing that cavitation was evidenced by a decrease in
actual hydrophone output from the theoretical output;
[0020] FIG. 7 is a graph showing change in percentage of clot mass
dissolution as a function of change in the pulse repetition period
(T), showing that an appropriate pulse repetition period has a
significant effect on the efficiency of clot lysis;
[0021] FIG. 8 is a graph showing percentage of clot mass
dissolution as a function of pulse duration (.tau.), showing a
strong dependency of clot dissolution and danger to the blood
vessel on pulse duration;
[0022] FIG. 9 is a graph showing rate of clot mass dissolution as a
function of intensity at the focal area;
[0023] FIGS. 10A and 10B are ultrasound images of a clot within an
artery segment, before and after ultrasound treatment;
[0024] FIGS. 11 and 12 are graphs showing microphone output voltage
as a function of ultrasound peak intensity in a buffer solution and
in a clot, showing that ultrasound initiated randomly, but that
once initiated, it could be maintained at decreased intensities and
that the threshold and slope are different for the buffer and
clot;
[0025] FIGS. 13 and 14 are graphs showing microphone output as a
function of ultrasound intensity, when blood is acted upon by
ultrasound of different pulse repetition periods (T), showing that
shorter T's correlate to lower intensity thresholds and ultimately
lower cavitation intensity;
[0026] FIGS. 15 and 16 are graphs showing the influence of pulse
duration on cavitation activity of a buffer solution and blood,
respectively;
[0027] FIG. 17 is a graph showing microphone output, which is
related to cavitation activity, as a function of pulse duration in
both a blood and a buffer solution;
[0028] FIG. 18 is a graph showing percentage of weight loss of a
clot as a function of ultrasound intensity for a non-degassed and
degassed sample, showing a lower intensity threshold and lower
intensity requirement for the non-degassed system;
[0029] FIGS. 19A and 19B are two graphs showing percentage of clot
dissolution as a function of pulse duration at two different power
settings, at T=7 ms, showing increased clot dissolution with
increased intensity and that optimal pulse durations exist for
certain other parameters;
[0030] FIGS. 20A, 20B and 20C are three graphs showing percentage
of clot dissolution as a function of pulse duration (.tau.), pulse
repetition period (T), and pulse duration (.tau.), respectively, at
intensities of 1400 W/cm.sup.2, 1400 W/cm.sup.2 and 1300 W/cm.sup.2
respectively and shows that optimal parameters can be intensity
independent;
[0031] FIG. 21 is a graph showing percentage of clot dissolution as
a function of ultrasound intensity, manifesting threshold for clot
lysis;
[0032] FIG. 22 is a graph showing the weight of unlysed clot as a
function of ultrasound intensity, manifesting a threshold for clot
lysis;
[0033] FIG. 23 is a perspective view of an invasive type ultrasound
transmission system, constructed in accordance with an embodiment
of the invention;
[0034] FIGS. 24-27 are graphs showing cavitation activity as a
function of transducer power, showing the difference between
continuous and pulsed activation; and
[0035] FIGS. 28-30 show ultrasound probe temperature in activated
and unactivated states, both with and without the use of cooling
fluid, in a continuous wave mode of probe operation, and in duty
cycles of 8.
DESCRIPTION OF PREFERRED EMBODIMENTS
[0036] Significant therapeutic effects can be achieved by applying
ultrasound to locations within a living body. Generally, a
transducer converts an electrical signal to mechanical vibration,
which causes the propagation of ultrasound waves through some
medium or media. If these waves are of sufficient intensity, they
create cavitation within a medium at a desired location as micro
bubbles are formed and collapse. This generates extraordinarily
high activity at the cavitation site.
[0037] A transducer can be operated in a continuous mode or in a
pulsed mode. In a continuous mode, the signal to the transducer is
always causing the transducer to generate sufficient vibration to
maintain cavitation at the desired location. In a "pulse" mode, the
signal amplitude is reduced sufficiently (or eliminated) to permit
cavitation to pause between pulses of high amplitude during which
cavitation occurs. Certain conventional pulsing methods apply
ultrasound in one to several second doses, followed by pauses of
approximately equal duration or even durations longer than the
duration of the activating signal. This is conventionally performed
to permit objects which became hot during the activation process to
cool down. It has been discovered that applying ultrasound in an
improved pulsed mode can provide substantial advantages, compared
to conventional pulsing modes of operation.
[0038] Referring to FIG. 1A, an example of a system for providing
the non-invasive application of ultrasound to a test sample in a
model representing a body part, which can be readily modified to
apply ultrasound to a location within a living body, is shown
generally as non-invasive ultrasound application system 100.
Non-invasive ultrasound system 100 includes a therapeutic focused
ultrasound transducer 110, which is activated by an electrical
signal from a signal generator 120. Therapeutic transducer 110 can
be constructed to operate at up to 750 KHz and can be formed with a
1-3 ceramic composite. A 1-3 composite transducer includes rods of
PZT inserted into a polymer support and has very high energy
transfer efficiency. Front and side views of one embodiment of
transducer 110 are shown in FIGS. 1B and 1C. Therapeutic transducer
110 includes a hole 111 at the center thereof. Hole 111 permits the
use of an optional ultrasound imaging probe (not shown) which can
guide and monitor the therapy with ultrasound during application.
One example of a suitable transducer, which was used in experiments
presented herein, is about 45 mm thick, has an overall radius of 46
mm, a central active area with a radius of 40 mm and a central bore
with a radius of about 10 mm. Electrical connections are on either
side of the central bore at disk shaped depressions having an 8 mm
radius. Alternative transducers can be substituted.
[0039] To operate transducer 110, generator 120 sends a signal 121
through a pair of electric wires 112, which are coupled to
transducer 110 at attachment points 113a and 113b. Signal 121 is
formed with a plurality of energy pulses 122 of duration .tau. at
an amplitude (A) and a frequency (f). As used herein, a pulse will
be considered the "on" portion 122 of signal 121, which is of
sufficient amplitude to maintain cavitation and is followed by an
"off" section 123 of signal 121 of insufficient amplitude to
maintain cavitation. The duration of time between the beginning of
successive pulses 122 is referred to as pulse repetition period T.
It has been determined that pulse duration .tau. is advantageously
significantly smaller than pulse repetition period T.
[0040] To model the effects ultrasound emitted from therapeutic
transducer 110 would have on a location within a living body, a
model system 140 was constructed. Model system 140 includes an open
Plexiglas water tank 141 with a hole in a front side 142 for
inserting therapeutic transducer 110. Tank 141 was filled with
water, which was either degassed or non-degassed, depending on the
particular experiment to be run. When water was not degassed, it
included small air bubbles which served as a nuclei for cavitation
initiation. Decreasing the number of bubbles in the water increases
the energy needed to initiate cavitation.
[0041] To obtain information about the focal region of ultrasound
emitted from transducer 110, a hydrophone (not shown) was
positioned at various locations within a dedicated tank. It was
found that when activated by generator 120 at low intensities below
the cavitation threshold, transducer 110 creates an acoustic field
with a focal region having an elongated ellipsoid or cigar
shape.
[0042] To obtain information regarding the effects of ultrasound on
clots within a living body, a bovine vessel 150 having a clot 151
therein or a clot attached to the front of a bovine vessel wall was
suspended within tank 141 by a specimen holder 152. Depending on
the experiment to be run, vessel 150 was filled with either blood
or a buffer solution. The vessel 150 and the clot 151 were moved by
a computerized x-y positioning a system 180 through a mounting 181
and a computer controller 182. Certain information regarding the
effects of applied ultrasound were compiled with an ultrasound
imaging device 160, formed with an imaging ultrasound transducer
161, coupled to a processor 162 for interpreting information
received from transducer 161 and displaying an image thereof.
Additional information was compiled through the use of a microphone
170 attached to tank 141, coupled to a frequency analyzer 171
through an amplifier 173, which also receives a trigger signal 172
from generator 120. Trigger signal 172 corresponds to transducer
activation signal 121, so that only sound transmitted from
microphone 170 when transducer 110 is activated will be
analyzed.
[0043] It was determined that advantageous benefits can be achieved
when ultrasound is applied at a pulse duration .tau. not greater
than about 100 milliseconds (msec). A range of about 0.01 to 100
milliseconds is preferred. Also, pulse repetition periods T below
about 1 second are preferred, as are pulse repetition periods in
the range 1 millisecond to 1 second. Duty ratios T/.tau..gtoreq.
about 5, and preferably .ltoreq.8 are preferred.
[0044] Non-invasive therapeutic ultrasound can be practiced at a
frequency of about 100 to 1000 KHz and far broader. Invasive-type
(probe-based) therapeutic ultrasound can be practiced at a
frequency range of 20 to 100 KHz and far broader. At a frequency of
preferably 100 to 1000 KHz advantageous operating parameter include
T= about 1 to 100 milliseconds, preferably about 2.5 to 90
milliseconds and more preferably 2.5 to 75 milliseconds and/or
.tau.=0.01 to 2.0 milliseconds, preferably 0.02 to 1.1 milliseconds
and more preferably 0.1 to 0.3 milliseconds. These parameters are
particularly well suited for a non-invasive-type device,
particularly one applying ultrasound at I .gtoreq. about 750
W/cm.sup.2, more preferably .gtoreq. about 1000 W/cm.sup.2.
[0045] At a frequency range preferably of 20 to 100 KHz,
advantageous operating parameters include T .ltoreq. about 1000
milliseconds preferably .ltoreq. about 600 milliseconds, more
preferably about 100 to 500 milliseconds and/or .tau..ltoreq. about
100 milliseconds, preferably about 10 to 100 milliseconds, more
preferably 20 to 60 milliseconds. These parameters are particularly
well suited for use with an invasive-type device, especially one
operated at a peak power output of over 10 watts, such as one
operated at 10-40 watts, preferably 15-30 watts. When pulse
parameters are correctly selected, an invasive-type probe can be
operated with substantially no cooling fluid.
[0046] The following examples illustrating the non-invasive
application of ultrasound were conducted in a water tank with a
system having the general construction shown in FIG. 1A. These
examples are provided for purpose of illustration only, and are not
intended to be construed in a limiting sense.
EXAMPLE 1
[0047] The transducer was operated at a frequency of 750 KHz, at a
pulse duration of .tau.=20 .mu.s, a pulse repetition period of T=74
ms and a potential of 46 V. The hydrophone output was measured in
decibels as a function of transversal displacement in mm along the
Y axis, parallel to the transducer plane and corresponded to the
predicted cigar shape at a distance of 5 cm from the transducer.
The results are shown in FIG. 2.
EXAMPLE 2
[0048] The hydrophone response at the focal point both above and
below the cavitation threshold was measured. Referring to FIG. 3,
it can be seen that when .tau.=20 .mu.s and T=74 ms and transducer
input was increased above about 160 volts, the effects of
cavitation can be determined by a decrease in hydrophone response
at the focal point, as energy is absorbed before the focal point,
leading to a decrease of sound energy at the focal point
itself.
EXAMPLE 3
[0049] The effects of pulse duration on cavitation were measured by
operating the transducer at an input potential of 180 V, T=75 ms
and measuring hydrophone output in a water filled tank at
.tau.=1100 .mu.s (curve 51 in FIG. 4) and 20 .mu.s (curve 52 in
FIG. 4). As shown in FIG. 4, the longer pulse duration led to
cavitation, whereas the shorter pulse duration exhibited no
breakdown in focal depth. Accordingly, the initiation of cavitation
depends not only on input voltage as has been believed, but also on
pulse duration.
EXAMPLE 4
[0050] The effects of pulse duration on cavitation were also
analyzed for seven different pulse durations at 190 V and T=11 ms.
Referring to FIG. 5, curve 61 is from a duration of 20 .mu.s, curve
62 is from a duration of 40 .mu.s, curve 63 is from a duration of
60 .mu.s, curve 64 is from a duration of 80 .mu.s, curve 65 is from
a duration of 100 .mu.s, curve 66 is from a duration of 150 .mu.s
and curve 67 is from a duration of 200 .mu.s. Longer pulse
durations were shown to be directly proportional to larger
decreases in hydrophone output and consequentially, increased
cavitation activity.
EXAMPLE 5
[0051] The effects of increased voltage (increased power and
intensity) on cavitation were analyzed more fully, by measuring
hydrophone output as a function of Z-axis displacement at T =200 ms
and .tau.=20 .mu.s, at various input voltages. Referring to FIG. 6,
curve 80 shows a theoretical plot at 190 volts, if no cavitation
had occurred, curve 81 is from 100 volts, curve 82 is from 142
volts, curve 83 is from 155 volts and curve 84 is from 190 volts.
Higher electrical input corresponded to higher amplitude and larger
decreases in acoustic amplitude, compared to a theoretical
prediction and hence, greater cavitation effect.
EXAMPLE 6
[0052] The apparatus shown in FIG. 1A was used to dissolve a blood
clot attached to the front of a wall taken from a bovine blood
vessel. Referring to FIG. 7, the transducer was operated at a duty
cycle (T/.tau.)=8 and an intensity of 1300 W/cm.sup.2 and the pulse
repetition period was varied over a range of about 0.5 to 27 ms.
Optimal results were achieved in a range of about T=4 to 10 ms,
with peak clot dissolution efficiency at a pulse repetition period
of about 8 ms and a pulse duration of about .tau.=1 ms. Thus, the
operating parameters including a duty cycle of about 8 were deemed
acceptable.
EXAMPLE 7
[0053] The use of non-invasive ultrasound to lyse a clot attached
to a vessel wall at parameters of I=1300 W/cm.sup.2 and T=8 ms, for
pulse durations ranging from about 0.07 ms to about 5 ms were
performed and the results are presented in FIG. 8. The results show
optimal clot dissolution at pulse durations of about .tau.=0.5 to
1.0 ms. It was also determined that increasing the pulse duration
above about 2.3 ms began damaging the vessel wall. It is believed
that lysis is mechanical in nature and depends on various pulse
parameters. Damage to the vessel (and to a probe in the case of
invasive applications of ultrasound) is related to thermal effects,
which are related to the accumulated energy transferred to a volume
over time. Thus, by operating at a sufficiently short pulse
duration, a clot can be lysed, without building up a dangerously
high amount of heat. It appears that operating above the cavitation
threshold, but less than about 50% of the pulse duration which can
damage the vessel, can be both a safe and effective operating
parameter.
EXAMPLE 8
[0054] Referring to FIG. 9, the rate of clot mass dissolution as a
function of ultrasound intensity at the focal area was analyzed
with T=8 ms and .tau.=1 ms. A non-linear increase in dissolution
rate with intensity was observed with fastest dissolution at
intensities in the 1200-1400 W/cm.sup.2 range.
EXAMPLE 9
[0055] The use of an ultrasound imaging system similar to system
160 shown in FIG. 1A provided additional information regarding the
use of ultrasound for blood clot lysis. It is possible to visualize
the clot during ultrasound application.
[0056] A bovine artery segment was filled with non-degassed PBS.
The transducer was operated at frequency, f=650 KHz, transducer
excitation voltage, U.sub.p/p=116 volts, T=7 ms and .tau.=0.5 ms.
Bright reflection images corresponding to cavitation were seen only
at the posterior artery wall. This indicated that the transducer
was located too close to the vessel. After the transducer was moved
away from the vessel, reflection spots, indicating cavitation
within the vessel were observed, indicating proper positioning of
the transducer.
[0057] After the transducer was moved still farther away, bright
reflection corresponding to cavitation was observed only at the
anterior artery wall, indicating that the transducer was located
too far from the vessel. Thus, by combining conventional imaging
ultrasound with non-invasive ultrasound lysis, it is possible to
assure that the ultrasound focal point is at a desirable location
within the body.
EXAMPLE 10
[0058] A successful non-invasive clot lysis procedure was conducted
under the following conditions: driving frequency=650 KHz,
transducer excitation voltage=116 V, pulse repetition period, T=7
millisecond and pulse duration, .tau.=0.5 msec. Referring to FIG.
10A, an ultrasound image of a clot (right side) and buffer solution
(dark left side) within a bovine vessel is shown. The focal point
of the therapeutic transducer was advanced along the longitudinal
axis of the artery segment from left to right. Ultrasound treatment
was stopped at approximately the middle of the clot. Referring to
FIG. 10B, it can be seen that the dark section indicative of liquid
has grown from left to right in the vessel, and the clot has been
reduced in size from the ultrasound treatment.
EXAMPLE 11
[0059] Measurements of acoustic emission (microphone output) in the
audible range were conducted as a manifestation of the degree of
cavitation activity by placing a microphone on a water filled tank.
Referring to FIG. 11, microphone output was measured as a function
of ultrasound peak intensity at T=7 ms, for both .tau.=0.070 ms and
.tau.=0.100 ms. As shown in FIG. 11, a well defined threshold to
the peak intensity was observed.
[0060] In addition, above the intensity threshold, the correlation
between cavitation activity and intensity was linear. For data
points corresponding to .tau.=70 .mu.s, virtually no microphone
output was observed until intensity exceeded approximately 1100
W/cm.sup.2. For measurements made at .tau.=100 .mu.s, virtually no
microphone output (cavitation) was observed until ultrasound peak
intensity exceeded about 600 W/cm.sup.2.
[0061] As shown, cavitation activity increased with increased pulse
duration. It was also observed that above the threshold, cavitation
initiation was random, occurring in the range of I=600-2800
W/cm.sup.2. However, if, for example, cavitation initiated at
I=2,000 W/cm.sup.2, microphone output would always be in the high
range relative to if cavitation initiated at I=800 W/cm.sup.2. It
was also determined that after cavitation is initiated, the
intensity can be decreased. Although cavitation activity will
decrease, cavitation was maintained at the intensity shown in FIG.
11.
[0062] It was also determined that placing a microphone on the
outside of the body of the subject receiving ultrasound treatments
can provide an excellent method of obtaining feedback regarding
whether cavitation is occurring. Thus, if an operator is applying
ultrasound to a subject, he can watch or listen to a display from
the microphone and determine whether cavitation is occurring under
parameters where cavitation should be occurring. In addition, the
microphone output can be fed to a data processor, which can display
a warning signal or deactivate the ultrasound device if the device
is fully powered, but cavitation is not being detected by the
microphone. Also, the feedback can permit an operator to reduce
power to the transducer to obtain the minimal amount of power
needed to sustain cavitation.
EXAMPLE 12
[0063] Referring to FIG. 12, a comparison was conducted between
cavitation activity produced in a buffer and in a clot for T=7 ms
and .tau.=0.1 ms. Both the threshold and slope of the increase of
cavitation activity with intensity were different for the buffer
solution and the clot. The linear correlation (R) of the buffer and
clot plots were R=0.94 and R=0.61, respectively.
[0064] After cavitation had been initiated the voltage could be
decreased to decrease the ultrasound intensity, but maintain
cavitation, i.e., it is an inertial phenomenon. Thus, in order to
promote additional safety of operation, once cavitation of a clot
has begun, the intensity can be decreased to maintain cavitation
within the blood vessel but diminish a chance to injure the vessel
itself.
[0065] Cavitation in blood and buffer solution was analyzed for
degassed and non-degassed media. Operating conditions were T=7 msec
and .tau.=0.1 msec. The cavitation threshold for a degassed medium
is higher than in a non-degassed medium. Also, there was no
difference in cavitation threshold between blood and the buffer
solution for the parameters tested.
[0066] The cavitation threshold for non-degassed buffer and blood
was in the range of 1000 to 1500 W/cm.sup.2, closest to about 1200
W/cm.sup.2. With respect to degassed buffer and blood, the
cavitation threshold centered around 2000 W/cm.sup.2.
[0067] The cavitation thresholds for non-degassed and degassed
clots were also analyzed at T=7 msces and .tau.=0.1 msec. As with
the above experiments, the cavitation threshold of a degassed
sample was higher than the non-degassed sample.
EXAMPLE 13
[0068] Referring to FIG. 13, the activity of cavitation in blood,
as a function of ultrasound intensity, was analyzed at .tau.=40
.mu.s for pulse repetition periods of T=8 ms, 16 ms, 20 ms, 30 ms,
40 ms, 50 ms, 70 ms, and 90 ms as shown in curves 751-758,
respectively. As shown in FIG. 13, there is an intensity threshold
for inducing cavitation and the threshold was inversely
proportional to pulse repetition period. For T=8 ms, cavitation
occurred at an intensity of about I=1250 W/cm.sup.2 and for T=90
ms, cavitation was first observed at I=1750 W/cm.sup.2 .
EXAMPLE 14
[0069] Referring to FIG. 14, an experiment similar to that
discussed with reference to FIG. 13 was performed, in which blood
was tested at .tau.=150 .mu.s and pulse repetition periods of 8,
16, 20, 30, 40, 50, 70 and 90 ms, which are depicted by curves 451
through 458, respectively. Longer pulse repetition periods were
associated with higher intensity requirements to initiate
cavitation and higher cavitation activity.
EXAMPLE 15
[0070] Referring to FIG. 15, the influence of pulse duration on
cavitation activity was analyzed. Shorter pulse durations were
associated with greater cavitation activity. Also, a pulse
repetition period T=between about 10 and 50 ms created maximum
cavitation activity for pulse durations from about 150 .mu.s to
about 700 .mu.s, correlating to duty ratios ranging from about 15
to 500.
[0071] A buffer solution was subjected to ultrasound at an
intensity of 2400 W/cm.sup.2. The pulse repetition period was
varied from about T=5 ms to about 90 ms for the following pulse
durations: 0.100 ms (curve 151), 0.150 ms (curve 152), 0.250 ms
(curve 153), 0.400 ms (curve 154), 0.700 ms (curve 155).
[0072] The experiment described above was repeated with pulse
durations of 0.100 ms, 0.150 ms, 0.250 ms, 0.400 ms and 0.700 ms at
an intensity I=2200 W/cm.sup.2. The results are similar to those
shown in FIG. 15, except that the cavitation activity decreased
slightly with the decreased intensity. Maximum cavitation activity
occurred in the range T<50 ms.
[0073] An experiment similar to that discussed above was performed
at an intensity of I=2080 W/cm.sup.2 at pulse durations of 0.100
ms, 0.150 ms, 0.250 ms, 0.400 ms. and 0.700 ms, respectively.
Again, cavitation activity decreased with decreased ultrasound
intensity and optimal pulse repetition periods were in the range
T<40 ms. Shorter durations were associated with higher activity.
As ultrasound intensity and hence cavitation activity decreased,
the width of the range of optimal pulse repetition periods also
decreased.
[0074] An experiment similar to that discussed with reference to
FIG. 15 was performed, in which ultrasound intensity was set at
I=1800 W/cm.sup.2. Maximum cavitation occurred above T<30 for
all but experiments run at a pulse duration of 0.700 .mu.s, which
exhibited cavitation to about T=50 ms.
EXAMPLE 16
[0075] Another experiment similar to that discussed with reference
to FIG. 15 was performed, except that the medium tested was blood,
rather than a buffer solution. Referring to FIG. 16, the intensity
was set at 2400 W/cm.sup.2 and results are shown for pulse
durations of 0.100 ms, 0.150 ms, 0.250 ms, 0.400 ms and 0.700 ms
for curves 251, 252, 253, 254 and 255 respectively. The parameters
for causing cavitation in blood were found to be different than
those for causing cavitation in the buffer solution. For example,
cavitation in blood was sustained over a much wider range of pulse
repetition periods, to over T=100 ms. Again, however, the shorter
pulse durations exhibited higher microphone output.
EXAMPLE 17
[0076] FIG. 17 shows cavitation as a function of pulse duration for
a blood sample (curve 351) and a buffer sample (curve 352), at T=50
ms and intensity I=2400 W/cm.sup.2. Optimal cavitation for the
blood sample was in a pulse duration range of about .tau.=100 to
250 .mu.s and a duty ratio of about 500 to about 200. It was
evident that cavitation could still be achieved above .tau.=700
.mu.s. For the buffer solution, the range of most effective pulse
durations was narrower, and ranged from about 80 to about 150
.mu.s. However, it was evident that cavitation would still occur
above .tau.=700 .mu.s.
[0077] The experiment discussed with reference to FIG. 17 was
repeated at T=8 ms and the same intensity (2400 W/cm.sup.2). The
shorter pulse repetition periods slightly decreased the cavitation
activity for the blood sample and increased the cavitation activity
for the buffer sample, relative to the values shown in FIG. 17 and
caused the cavitation activity for the buffer samples to be more
similar. Cavitation was sustained from .tau.=50 to 700 .mu.s.
Accordingly, different materials will exhibit different activity
with respect to different pulse repetition periods. Thus, it can be
advantageous to lyse a clot with parameters which cause high
cavitation in blood, and will have a less pronounced effect on the
blood vessel.
EXAMPLE 18
[0078] Referring to FIG. 18, the efficiency of clot lysis was
analyzed by measuring percentage of clot weight loss as a function
of ultrasound intensity for both a non-degassed (curve 551) and a
degassed blood clot sample (curve 552). Lysis was performed with
T=7 ms and .tau.=0.1 ms, at Vm=15 mm/min. Percentage of weight loss
was determined by visual inspection and accordingly, the data are
reasonable approximations. As shown in FIG. 18 the non-degassed
clot was lysed at lower ultrasound intensities, with intensities
above I=1600 W/cm.sup.2 judged effective on the non-degassed sample
and above I=2200 W/cm.sup.2 on the degassed sample. Thus, the T and
.tau. values and a duty cycle of 70 were deemed suitable.
EXAMPLE 19
[0079] Referring to FIG. 19A, a clot was lysed at I=1900 W/cm.sup.2
at pulse durations of 100, 200 and 300 .mu.s. One hundred percent
clot dissolution was achieved at 200 and 300 .mu.s. Referring to
FIG. 19B, under the same conditions, except for a reduction of
intensity to I=1400 W/cm.sup.2, optimum clot dissolution was
achieved at .tau.=200 .mu.s, with clot lysis at reduced efficiency
at .tau.=100 and 300 .mu.s. As shown, at lower intensities, high
efficiency was achieved at T/.tau.=35, compared with T/.tau.=70 or
23.
[0080] Referring to FIG. 20A, at T=14 ms and V=15 mm/min and an
intensity of I=1400 W/cm.sup.2, the results of curve 571, were
achieved. Referring to FIG. 20B, when .tau. was set at 200 .mu.s, V
was set at 10 mm/min and the pulse repetition period was varied
from about 2.5 to 20, optimal clot dissolution was achieved at T=5
ms, or T/.tau.=25, in a range of about 12 to 50, as shown by curve
572. Clot dissolution also be achieved above T=20 ms.
[0081] Referring to FIG. 20C, curve 581, T=5 ms, .tau.=0.2 ms and
V=10 mm/min, pulse duration was varied from 100 .mu.s to 300 .mu.s
at an ultrasound intensity of 1300 W/cm.sup.2. Optimal efficiency
was achieved at .tau.=200 .mu.s, with the most efficient range from
about 175 to 225 .mu.s. Lysis was effective above .tau.=0.150
ms.
[0082] Referring to FIG. 21, curve 582, intensity of ultrasound was
varied from about 900 W/cm.sup.2 to about 1700 W/cm.sup.2 The
cavitation threshold occurred at approximately 1250 W/cm.sup.2 with
maximum efficiency of intensities over 1300 W/cm.sup.2 at T=5 ms
and .tau.=0.2 ms. Increasing intensity maintained full clot
dissolution.
EXAMPLE 20
[0083] Referring to FIG. 22, the efficiency of clot lysis was
assessed by measuring the weight of unlysed clot after ultrasound
application, as a function of ultrasound intensity. Parameters were
T=5 ms, .tau.=0.2 ms, f=650 KHz, V=5 mm/min and intensity ranged up
to 2500 W/cm.sup.2. Unlysed clot material was separated with an 80
.mu.m size filter. As shown in FIG. 22, above the threshold for
clot lysis, only a small portion of the clot remained unlysed. At
the parameters investigated, this intensity threshold was in the
range 750 to 1250 W/cm.sup.2.
[0084] The following examples present data illustrating from the
application of ultrasound with a probe designed for the invasive
application of ultrasound operated at about 44.4 KHz. Ultrasound
was applied with a probe, similar to that depicted in U.S. Ser. No.
08/858,247, filed May 19, 1997 (the contents of which are
incorporated herein by reference), having a proximal transducer
coupled to an elongated transmission member with a distal tip
constructed to cause cavitation within a blood vessel when
activated by ultrasound transmitted from the transducer through the
transmission member.
[0085] A non-limiting embodiment of an invasive-type ultrasound
probe is illustrated generally as probe 1200 in FIG. 22, and in a
copending application entitled COOLING SYSTEM FOR ULTRASOUND DEVICE
under Application Serial No. 60/047,022, filed May 19, 1997, the
contents of which are incorporated herein by reference.
[0086] Probe 1200 is formed with a tapered member 1225, formed with
a proximal end 1229 of diameter Ai constructed to be coupled to a
source of ultrasound energy such as a transducer 1248. When coupled
to a source of ultrasound energy, proximal end 1229 is preferably
located at a displacement maximum relative to the standing
ultrasound wave supported by the overall device. From proximal end
1229, tapered member 1225 tapers to a reduced diameter distal end
of diameter A.sub.f.
[0087] Proximal end 1229 must be large enough to receive sufficient
energy to treat a thrombus, occlusions and the like. However, in
order to provide optimal flexibility, it is desirable to reduce the
diameter of distal portions of probe 1200 as much as possible,
without significant loss of energy, strength or guidability.
Furthermore, the reduction in diameter is preferably accomplished
in such a manner as to amplify, or increase the amplitude of, the
ultrasound vibrations.
[0088] Ultrasound device 1200 is understood to operate in the
resonant frequency mode; i.e., it supports a standing wave when
energized by ultrasonic stimulation at proximal end 1229.
Consequently, it is preferred that a cavitation tip 1250 is located
at a displacement maximum (anti-node).
[0089] To dissipate energy lost as heat, a probe in accordance with
the invention can be bathed with a coolant. The coolant can be
directed over and around the probe, for example, by incorporating a
sheath 1245 around some or all sections of the probe. Sheathing
1245 may be affixed to the probe at one or more of the displacement
nodes of the standing wave. Additional sheathing may be
incorporated for providing a passageway for a guidewire or other
auxiliary tool which may serve to steer or position the device to
its intended location. Sheathing 1245 if formed of a high-strength,
thin-walled, low-friction material, preferably polyimide.
[0090] Probe 1200 includes a horn 1225, having a tapered section T
and a first constant diameter section S, is constructed to be
coupled to an ultrasound energy source. Ultrasound energy is
provided by the controller at a power source 1246 via a coaxial
cable 1247 to a quick disconnect 1249, which connects coaxial cable
1247 to transducer 1248. Transducer 1248 is intimately connected to
horn 1225. Probe 1200 also includes a transmission member 1240
coupled to horn 1225 and a tip 1250 coupled to the distal end of
transmission member 1240. Ultrasound energy sources disclosed in
U.S. Pat. No. 5,269,297, and in a copending application entitled
FEEDBACK CONTROL SYSTEM FOR ULTRASOUND PROBE under Application
Serial No. 60/046,938, filed May 19, 1997, the contents of which
are incorporated herein by reference, are suitable.
[0091] Tip 1250 is coupled to three fine wires joining section 1240
and tip 1250 by means of three openings in tip 1250. In a preferred
embodiment, the three openings in tip 1250 are spaced so as to form
an equilateral triangle, concentric with the central axes of
coupling tip 1250. Tip 1250 may also be provided with an opening
for a guidewire, and a guidewire tube may be installed in the
opening and extended proximally from the distal end. The fine wires
may be separately sheathed, and any sheathing may extend between
tip 1250 and a coupling joint. Wire 1240 may also be sheathed and
the sheathing may be connected to the separate sheathing of the
fine wires and may extend proximally to a coolant port through
which coolant may be injected to bathe all or part of the
transmission member.
[0092] The entire probe was placed in a straight configuration in a
Plexiglas tube with an inner diameter of 3.5 mm and the tube was
placed inside a water tank. A microphone was placed on the outside
of the water tank and measured acoustic output which correlates to
cavitation activity. The probe was operated in both continuous mode
and pulse mode under various operating parameters and data was
compiled.
EXAMPLE 21
[0093] Referring to FIG. 24, at T=1000 ms and .tau.=500, 250, 750,
125, 875, 164 ms, corresponding to curves 601-607 respectively and
curve 608 corresponding to the probe activated in continuous mode,
a cavitation threshold existed in the range 5 to 10 watts for
pulsed mode of operation and non-degassed water.
EXAMPLE 22
[0094] An additional experiment was run in non-degassed water at
T=500 ms and .tau.=250, 125, 64 and 32 ms. A control was also run
in continuous mode. The results were similar to those shown in FIG.
24, with a threshold to cavitation in the range 10 to 20 watts and
relatively no cavitation generated from operation in the continuous
mode at up to 20 watts.
EXAMPLE 23
[0095] Referring to FIG. 25, an experiment similar to that
discussed with reference to FIG. 24 was conducted, wherein
non-degassed water received ultrasound from an invasive-type probe,
but at T=250 ms. Electric power was increased over the range 0 to
40 watts at .tau.=125, 64, 32 and 16 ms, corresponding to curves
125, 64, 32 and 16 ms, corresponding to curves 651, 652, 653 and
654, respectively. Curve 655 shows operation in the continuous
mode. As shown in FIG. 25, an ultrasound threshold occurred at
about 20 watts and there was essentially no cavitation generated
from the continuous mode operation at this power level.
EXAMPLE 24
[0096] Still another experiment was conducted, in which ultrasound
was applied from an invasive-type transducer to non-degassed water
at T=125 ms and .tau.=64, 32, 16 and 8 ms. Cavitation initiated in
the range 15 to 20 watts for the pulse mode of operation, but not
in the continuous mode operation, demonstrating advantages of
pulsed operation in accordance with the invention.
EXAMPLE 25
[0097] Referring to FIG. 26, the procedure discussed with reference
to FIG. 24 was performed at T=64 ms. Pulse durations of .tau.=32,
16, 8, and 4 ms are shown in FIG. 25 as curves 661, 662, 663 and
664, respectively. Continuous mode operation is shown as curve 665.
The cavitation threshold occurred in the range 15 to 20 watts for
the pulsed mode of operation, but not the continuous mode of
operation, demonstrating advantages of pulsed operation in
accordance with the invention.
EXAMPLE 26
[0098] Referring to FIG. 27, the above procedure was repeated at
T=32 ms and .tau.=16, 8 and 4 ms, corresponding to curves 671, 672
and 673, respectively. Continuous mode operation is shown by curve
674. A cavitation threshold occurred in the range of about 15 to 20
watts for pulsed operation, but with less overall cavitation
activity than for some of the longer pulse durations. It is
believed that the liquid medium requires a recovery period for
optimum cavitation efficiency.
COMPARATIVE EXAMPLE 27
[0099] The invasive-type probe was operated under 18 watts of
power. A thermocouple in contact with the tip inside the tube
provided real time data with respect to temperature. Referring to
FIG. 28, the system was initially at 37.degree. C., 10 ml/min of
24.degree. C. cooling water was pumped through the tube. As shown
in FIG. 28, this reduced temperature at the probe tip to
approximately 24.degree. C. At point 681, the probe was turned on
and activated with 18 watts of power. This quickly raised the
temperature to over 41.degree. C. (point 682).
[0100] At point 683, power was turned off and the temperature
quickly returned to the cooling water temperature. At point 684,
cooling water was turned off and the probe returned to
approximately 34.4.degree. C. At point 685, cooling water was
turned on and the temperature of the probe quickly returned to
approximately 27.degree..
[0101] At point 685, the probe was turned back on and the
temperature quickly rose to above 41.degree. C. After the power was
turned off, the temperature of the probe returned to the
temperature of the cooling water and then returned to the
temperature of the tank after the cooling water was turned off.
EXAMPLE 28
[0102] Considerably different results were achieved when the probe
was operated in pulse mode at a duty cycle of 8 (T=250 ms .tau.=32
ms) when 24.degree. C. cooling water at 10 ml/min was turned on,
the temperature of the probe quickly dropped to about 24.degree. C.
At point 691 power was turned on at a level of 20 watts. As shown
in FIG. 29, the probe temperature increased to only slightly over
27.degree. C., for a temperature increase of only about 3.degree.
C. At point 682, power to the probe was turned off and at point
683, the cooling water was turned off. At point 684, cooling water
was turned back on and at point 685, power to the probe was turned
back on. The probe was operated at 18 watts until it was turned off
at point 686. As shown, probe temperature only increased about
2.degree. C.
[0103] Similar results were achieved at a duty cycle of 16 (T=250,
.tau.=16) (FIG. 30). At point 691, cooling water was turned on and
at point 692, the probe was activated with 20 watts of power and
turned off at point 693. As shown, probe temperature increased only
1 to 2.degree. C. At point 694, cooling water was turned back on,
the probe was turned on with 18 watts of power at point 696 and
turned off at point 697. As shown, only a minimal increase in
temperature occurred.
[0104] Tables 1 and 2 below provide evidence from additional
experiments showing a minimal temperature rise when the probe is
operated in a pulsed mode, particularly at a duty cycle ratio of 8
or more. In view of their minimal temperature increase using the
described pulsing parameters in conjunction with the lower
cavitation threshold and high cavitation activity, it is believed
that invasive-type probes can be operated without cooling fluid and
also, without a covering sheath. This will permit the use of
substantially smaller guide catheters in view of an overall
reduction in the outer dimensions of the probe. Another advantage
is a considerable reduction in metal fatigue.
1TABLE 1 Study on the temperature rise at different flow rates of
the cooling buffer and at different excitation modes. # Flow Rate
Duty Cycle Power Temp Rise Max Temp 1 10 Continuous 18 16.8 41.7 2
10 Continuous 18 15.4 41 3 10 8 20 2.4 28.1 4 10 8 18 1.7 27.6 5 10
16 20 1.2 27.1 6 10 16 18 0.7 26.6 7 10 8 30 4.6 31.8 8 10 8 30 4.1
31.6 9 10 8 40 5.3 33.3 10 10 8 40 5.3 33.3 11 10 16 30 3.8 29.7 12
10 16 30 4.1 29.2 13 10 16 40 4.8 30.8 14 10 16 40 4.6 30.7 15 5 8
30 8.2 35 16 5 8 30 8.4 35 17 5 8 30 7.2 36.2 18 5 8 30 7.2 36.1 19
5 16 30 4.6 33.5 20 5 16 30 4.3 33.5 21 5 16 40 8.2 37.5 22 5 16 40
6.2 34.1 23 2.5 16 30 3.7 35.7 24 2.5 16 30 4.1 35.7 25 0 16 20 3.1
39.8 26 0 16 20 3.1 39.8 27 0 16 30 4.6 41.1 28 0 16 30 4.1 40.9 29
0 16 40 Destruction -- 30 10 Continuous 18 16.1 45.8 31 10
Continuous 18 16.8 44.3 32 10 Continuous 18 17.8 45.3 33 10 16 18
2.2 30 34 10 16 18 1.7 30.5 35 10 16 18 2.6 29.8 36 10 8 18 1.2
29.9 37 10 8 18 1.2 29.9 38 10 8 18 1.2 29.9 39 5 16 18 1.5 31.8 40
5 16 18 1.7 32.1 41 5 16 18 1.5 31.9 42 0 16 18 2.4 39.6 43 0 16 18
2.4 39.6 44 0 16 18 2.6 39.8 45 0 16 18 2.6 39.8 46 0 16 18 2.6
39.8 47 0 16 18 2.6 39.8 48 10 16 18 1 28.8 49 10 16 18 1.2 29.1 50
10 16 18 1.2 29.1 51 5 16 18 1.5 31.4 52 5 16 18 1.7 31.4 53 5 16
18 1.7 31.4 54 10 8 18 1.2 28.9 55 10 8 18 1 29.1 56 10 8 18 1.2
29.4 57 10 Continuous 18 16.6 43.9 58 10 Continuous 18 16.1 43.6 59
10 Continuous 18 16.6 43.6
[0105]
2TABLE 2 Study on the temperature rise at different flow rates of
the cooling buffer and at different excitation modes. Flow Rate
Pulse Rep. Pulse Length Power Frequence Temperature Max Temp #
ml/min Duty Cycle Period (mS) (mS) (watt) y (KHz) Rise (grad)
(grad) 1 10 Continuous -- -- 18 44.6 16.1 41.3 2 10 8 256 32 20/18
44.6 2.4/1.7 27.9 3 10 16 256 16 20/18 44.6 1.2/1.0 26.9 4 10 8 256
32 30 44.4 4.6 31.7 5 10 8 256 32 40 44.4 4.8 33.3 6 10 16 256 16
30 44.4 2.9 29.5 7 10 16 256 16 40 44.4 4.3 38 8 5 8 256 32 30 44.4
7.9 35 9 5 8 256 32 30 44.3 7.2 36.2 10 5 16 256 16 30 44.3 3.8
33.5 11 5 16 256 16 40 44.3 7 36 12 2.5 16 256 16 30 44.3 3.8 35.7
13 0 16 256 16 20 44.3 3.1 39.8 14 0 16 256 16 30 44.3 4.3 41 15 0
16 256 16 40 44.3 Destruction -- 16 10 Continuous -- -- 18 44.5
16.9 45 17 10 16 256 16 18 44.5 2.2 30 18 10 8 256 32 18 44.5 1.2
29.9 19 5 16 256 16 18 44.5 1.6 31.9 20 0 16 256 16 18 44.5 2.5
39.7 21 10 16 256 16 18 44.5 1.1 29 22 5 16 256 16 18 44.5 1.6 31.4
23 10 8 256 32 18 44.5 1.1 29.1 24 10 Continuous -- -- 18 44.5 16.4
43.8
[0106] It is understood that the techniques described for the
invasive and non-invasive application of ultrasound are also
applicable to systems that promote or focus ultrasound energy to
enhance the absorption of drugs, induce apoptosis in cells, and/or
treat tissue, tumors, obstructions, and the like, within and
without the body, systems to be utilized in or for laproscopic
surgery, for ultrasonic scalpels, and to induce tissue hyperthermia
such as for cancer radiation therapy, for example. Furthermore,
drugs, such as streptokinase, urokinase, whose function or efficacy
would be enhanced by ultrasound or that would enhance the
application of ultrasound at the treatment site, may be infused
within the coolant fluid for cooling the ultrasound probe or
delivered through a separate passageway within or without the
ultrasound probe to the treatment site.
[0107] The following is a partial list of applications for pulsed
ultrasound:
3 Clot lysis Cell function manipulation (eg. migration, adhesion,
etc.) Plaque ablation Drug delivery manipulation Coagulation Drug
activity enhancement Cancer treatment Biological product
manipulation (eg. genes, anti-sense DNA) Phonopheresis Induction of
Apoptosis Molecule manipulation Induction of Necrosis Cavitation
initiation manipulation Liposuction Cavitation sustaining
manipulation Heat generation manipulation
[0108] It will thus be seen that the objects set forth above, among
those made apparent from the preceding description, are efficiently
attained and, since certain changes may be made in the above
composition of matter without departing from the spirit and scope
of the invention, it is intended that all matter contained in the
above description shall be interpreted as illustrative and not in a
limiting sense.
[0109] It is also to be understood that the following claims are
intended to cover all of the generic and specific features of the
invention herein described and all statements of the invention
which, as a matter of language, might be said to fall
therebetween.
* * * * *