US 20050021013 A1
Partial or total occlusions of fluid passages within the human body are removed by positioning an array of optical fibers in the passage and directing treatment radiation pulses along the fibers, one at a time, to generate a shock wave and hydrodynamic flows that strike and emulsify the occlusions. A preferred application is the removal of blood clots (thrombi and emboli) from small cerebral vessels to reverse the effects of an ischemic stroke. The operating parameters and techniques are chosen to minimize the amount of heating of the fragile cerebral vessel walls occurring during this photoacoustic treatment. One such technique is the optical monitoring of the existence of hydrodynamic flow generating vapor bubbles when they are expected to occur and stopping the heat generating pulses propagated along an optical fiber that is not generating such bubbles.
1. A method of opening to the flow of blood a human cerebral blood vessel that is blocked by a clot, comprising:
positioning within said cerebral vessel an array of optical fiber ends adjacent to and extending in a direction across a surface of the clot, said optical fibers individually having a core diameter less than 100 microns,
directing a sequence of one or more pulses of radiation along one of the plurality of optical fibers and out of its end and then repeating directing such a sequence of pulses along individual ones of others of said plurality of optical fibers at a time, said pulses individually containing less than 250 micro-Joules of energy and having a duration less than 100 nanoseconds in order to generate a shock wave followed by a bubble which together cause a portion of the clot to be emulsified,
introducing a flow of liquid into the vessel adjacent the surface of the clot while radiation is being directed out of said optical fibers, and
while so directing the radiation pulses and the liquid, advancing the catheter end through the clot as the clot becomes emulsified until the blockage to the flow of blood through the vessel is removed.
2. The method according to
3. The method according to
4. The method according to
5. The method according to
6. The method according to any one of claims 1-5, wherein positioning the array of optical fibers within the cerebral vessel includes inserting a catheter containing the array of optical fibers into a vessel of the human body a distance removed from said cerebral vessel and advancing the catheter through various vessels a distance of at least 50 centimeters to reach the cerebral vessel clot.
7. The method according to
8. The method according to
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10. The method according to
11. The method according to
12. The method according to any one of claims 1-5, wherein an average power of the radiation directed along the optical fibers to within said cerebral vessel is less than one-half of one watt.
13. The method according to any one of claims 1-5, wherein the flow of liquid introduced into the vessel is within a rate of from one-tenth to five cubic centimeters per minute.
14. The method according to
15. The method according to any one of claims 3-5, wherein positioning the array of optical fiber ends within said cerebral vessel includes positioning optical fibers that individually have a core diameter of 50 microns or less.
16. The method according to any one of claims 1-5, wherein the generation of individual bubbles is optically monitored through the same optical fibers that carry the pulses which generate the bubbles, and, in response to a failure to detect the existence of a bubble being generated by a pulse directed along one of the optical fibers, suppressing subsequent pulses from being directed along said one optical fiber.
17. The method according to
18. The method according to
19. A method of opening to the flow of blood human cerebral blood vessel that is blocked by a clot, comprising:
directing electromagnetic radiation through optical fiber transmission media within the cerebral vessel toward said clot at different locations across the clot in time sequence,
simultaneously directing a cooling liquid within the cerebral vessel in the vicinity of the clot, and
maintaining an average power level of the radiation directed within the cerebral vessel at less that one-half of one watt.
20. The method according
21. The method according to either of claims 19 and 20, wherein directing electromagnetic radiation includes directing said radiation through a plurality of optical fibers, one at a time, which individually have a core diameter less than 100 microns.
22. The method according to either of claims 19 and 20, wherein directing electromagnetic radiation includes directing said radiation in a manner to generate within the cerebral vessel a succession of a combination of a shock wave and vapor bubble that combine to emulsify the clot.
23. A method of opening to the flow of blood a human cerebral blood vessel that is blocked by a clot, comprising:
positioning an end of a catheter into a blood vessel of the human a distance from the cerebral blood vessel and advancing the catheter end at least 75 centimeters through various human vessels to within the cerebral vessel in a manner to position an open end of a lumen and ends of a plurality of optical fibers directed toward or imbedded in the clot, said optical fibers individually having a core diameter within a range of from 20 to 100 microns,
directing radiation along the plurality of optical fibers, one at a time in sequence, against the clot while a liquid is being discharged at a rate within a range of one tenth to five cubic centimeters per minute into the vessel through said lumen open end,
said radiation being directed along each of the plurality of fibers in the form of a plurality of pulses with a repetition rate within a range of from 1 to 20 kilo-Hertz, an amount of energy per pulse within a range of from 10 to 250 micro-Joules, and a duration of the individual pulses within a range of from 1 to 100 nanoseconds, in a manner that the pulses individually generate a shock wave followed by a bubble that together cause a portion of the clot to be emulsified and the average power delivered within the cerebral vessel is less than one-half of one watt, and
advancing the catheter end through the clot as the clot becomes emulsified until the blockage to the flow of blood through the vessel is removed.
24. A system for the removal of a clot from a blood vessel, comprising:
a catheter having a length in excess of 75 centimeters between first and second ends thereof and an outside diameter less than one-half of one millimeter alone at least a portion of the length adjacent the first end, said catheter including a plurality of optical fibers that individually have a core diameter less than 100 microns and a lumen extending along said length, said optical fibers terminating in a spatial array across a first end of the catheter,
a source of liquid connected to supply cooling liquid to the lumen at the second end of the catheter, the lumen having an inside diameter and the source having a capacity such that the liquid is discharged from the lumen at the first end of the catheter with a rate of flow within a range of from one-tenth to five cubic centimeters per minute, and
a source of electromagnetic radiation connected to the optical fibers at the second end of the catheter in a manner to direct individual pulses of said radiation along the optical fibers, one at a time in sequence, with the pulses individually having a duration within a range of from one to 100 nanoseconds and containing an amount of energy within a range of from 10 to 250 micro-Joules of energy, and with a maximum average power of less than one-half of one watt being delivered from the optical fibers at the first end of the catheter.
25. The system of
26. The system of either one of claims 24 or 25, wherein said source of electromagnetic radiation directs said pulses sequentially along individual ones of the plurality of optical fibers across the spatial array that are not adjacent one another.
The United States Government has, rights in this invention pursuant to Contract No. W-7405-ENG-48 between the United States Department of Energy and the University of California for the operation of Lawrence Livermore National Laboratory.
This invention relates generally to the removal of a partial or total occlusion from a blood vessel by generating pressure waves within the vessel through optical fiber media, and, more specifically, to the removal of a blood clot from a vessel within the human brain. The term “clot” is used herein to refer to a thrombus, embolus or some other total occlusion of a vessel.
Medical procedures to open a partially or totally blocked blood vessel are available. Angioplasty has long been used to restore full blood flow in a coronary artery by mechanically deforming deposits on the arterial walls but has been less successful to open a totally occluded vessel. Laser techniques have been proposed to directly ablate obstructing material from arteries, such as plaque and certain types of clots, by inserting optical fibers into the artery to the point of the obstructing material but these techniques have enjoyed only limited success in practice. Various uses of ultrasonic energy to generate acoustic waves directed against plaque or a clot within an artery to mechanically break up the obstructing material have also been proposed but medical procedures utilizing these techniques have not enjoyed widespread acceptance. Photoacoustic techniques have been proposed for vasodilation and the break-up of plaque and clots in arteries, wherein one or more optical fibers are inserted into the vessel and pulses of radiation delivered to the vessel through the fibers generate a pressure or acoustic wave directed against the obstruction.
Major blood vessels within the brain are very small, generally not exceeding three millimeters in diameter and being much smaller than that in most places. Most cerebral blood vessels decrease in diameter along their lengths until becoming capillaries. Besides being small, the walls of cerebral vessels are more fragile than those of vessels in other parts of the body and are more loosely connected to surrounding tissue.
When a thrombus is formed or an embolus is lodged in a blood vessel of the brain, an ischemic stroke results. The resulting sudden cut off of the supply of fresh blood to cerebral vessels terminates the supply of oxygen to these vessels and to the brain tissue they supply. The seriousness of a stroke depends upon the amount of brain tissue involved and its location. Generally, the more serious strokes result when the larger cerebral vessels become blocked, since they supply more volume of tissue than the smaller vessels, but the blockage of vessels having a diameter of less than one millimeter, or even one-half of one millimeter or less, can be quite serious.
If a cerebral vessel of a stroke victim can be unblocked within about six hours after the blood flow is totally stopped, the effects of the stroke on the oxygen starved brain tissue are often largely reversed. If unblocked within this time, deterioration of the walls of the blocked vessel to the point of hemorrhaging is prevented. As a result, many have tried to develop techniques for removing clots from cerebral vessels within a few hours after a stroke has occurred.
One such technique is to position a catheter into the blocked vessel to mechanically remove the clot. But this is very difficult to do without causing further damage because the vessels are so small, contain very sharp turns, are weakly constrained and have fragile walls. Alternatively, a lytic drug is often applied intravenously, in an attempt to dissolve the clot without having to dislodge it mechanically. In an attempt to improve the rate of success of the lytic drug, it has been introduced directly into the blocked vessel through a catheter at the point of the blockage. But none of these techniques have enjoyed a high rate of success.
Therefore, it is a primary object of the present invention to provide techniques for reopening clotted blood vessels of the human brain with an increased rate of success.
It is another important object of the present invention to provide techniques to remove partial or total occlusions from other parts of the body.
It is a further object of the present invention to provide techniques for removing obstructions from the human body, particularly clots from cerebral blood vessels, without causing collateral damage to the vessel.
It is another object of the present invention to provide a practical instrument and system to perform these functions.
These and other objects are accomplished by the various aspects of the present invention, wherein, briefly and generally, a catheter containing multiple small diameter optical fibers terminating in a two-dimensional pattern is positioned adjacent the occlusion and pulses of radiation are directed along the optical fibers, one at a time in sequence, with the individual pulses having a duration and amount of energy sufficient to generate a shock wave and, from an expansion and collapse of a bubble, a pressure wave, both of which are directed against the obstruction in order to break it up and restore the flow of blood through the vessel. Clots within either arteries or veins are emulsified in this manner.
It has been found that the use of very small diameter optical fibers allows the desired shock and pressure waves to be generated with a relatively low amount of radiation pulse energy, thereby keeping the amount of heat input to the vessel at a low level. Proper thermal management according to the present invention reduces the likelihood of damaging the walls of the blood vessel adjacent the occlusion, which is especially important for the relatively thin walled vessels of the brain. Further, it is desirable that radiation pulses not being efficiently converted into the desired pressure waves be terminated in order to prevent inputting energy that heats the region without doing useful work. In addition to keeping the power input low, a liquid coolant may be introduced through the catheter to carry heat away from the region of the occlusion during the treatment.
Additional objects, features and advantages of the various aspects of the present invention will be better understood from the following description of its preferred embodiments, which description should be taken in conjunction with the accompanying drawings.
FIGS. 7A-E schematically illustrate in time sequence the formation of shock and pressure waves by one of the optical fibers of the catheter of
FIGS. 12A-I form a timing diagram showing various signals of the system control circuit of
FIGS. 13A-E show a portion of the timing diagram of
The present invention may, in general, be applied to the removal of material forming a partial or total occlusion of any human vessel but is particularly directed to opening a blood vessel that is totally or substantially blocked to the flow of blood. More specifically, the preferred embodiment of the present invention is directed to the removal of a clot from a blood vessel in the brain that has caused an ischemic stroke. If the flow of blood is, restored in the vessel within a few hours of the onset of the stroke, permanent damage to the blocked vessels is avoided.
Before applying the techniques of the present invention to a patient with symptoms of a stroke, a physician first determines whether the stroke has been caused by a hemorrhage or a blockage of a cerebral vessel. This is usually determined by use of a standard computed tomography (CT) x-ray test. If it is determined by the CT test that the stroke has been caused by a blocked cerebral vessel, the blockage is located by use of a standard angiography test. This test may also be used to determine whether the blockage is a clot. This test is performed by injecting an x-ray contrast liquid into the vessels of at least that portion of the brain whose diminished function is believed to be responsible for the stroke, while taking x-rays of the brain. If a blockage exists in a vessel, a network of vessels beyond the blockage will not appear in the x-ray since the contrast liquid is prevented from flowing past the blockage. The vessel and position of the clot or other obstruction within the vessel is accurately determined in this manner.
A multiple optical fiber catheter having a lumen for carrying a cooling liquid is then inserted into that vessel with its end adjacent the blockage. One such insertion is illustrated in
The system of which the catheter 11 is a part is also shown generally in
The manifold 19 also extends the optical fibers of the catheter 11 as a bundle 29 to a multi-fiber connector 31 that is removably connected to an instrument 33. This instrument contains the optics and electronics required to perform the medical procedure. Included on its face are various control switches or a keypad 35 and a display 37.
Many of the cerebral vessels 17 (
This combination of flexibility to bending and strength along its length can be accommodated in a catheter having an outside diameter (OD) of less than one-half a millimeter, a diameter within a range of 300 to 450 microns being preferred, with a 350 micron diameter being typical. A number of different designs for a long catheter of this diameter can be employed in order to provide the desired combination of flexibility and longitudinal strength. This includes the choices of materials and their thicknesses that are made, whether the lumen tube 55 is used, whether the optical fibers are attached to the catheter structure along the catheter other than at the end 39, and similar factors. Flexibility is improved when the optical fibers 45-50 are unattached along most of the length of the catheter within the lumen 51 but this can have the effect of restricting the amount of flow of liquid that is practical through the lumen and the longitudinal strength is not as great. The outside diameter and number of optical fibers used also affects these issues. A proper balance of these competing goals is achieved in a useful catheter assembly. The same considerations apply if a larger catheter is used, which could have up to a one millimeter outside diameter for cerebral or other vessels.
Each of the optical fibers 45-50 is chosen to be very small in diameter for reasons given below but this also contributes to the flexibility of the catheter 11 A cross-sectional view of a short length of an end of each of these fibers is shown in
With reference to
Alternative to the radiation pulses being absorbed by the liquid, they may be absorbed by the clot 43 (
Although it is desired that the clot 43 be highly absorptive of the radiation pulses, it is also desired that the wall of the blood vessel have a low absorption since it is difficult to prevent the radiation pulses being directed against the vessel wall, at least for an instant, as the catheter 11 is manipulated by the physician. The prevention of damage to the vessel wall is an important goal of the present invention. Fortunately as shown in the curves of
Several of the specific techniques of the present invention have a purpose of minimizing the elevation of the temperature of the vessel wall in order to avoid damaging the wall. One such technique is to direct; radiation pulses along only one of the multiple fibers at a time. Another is to limit the number of successive radiation pulses from a single fiber, before switching to another, in order to avoid creating a “hot spot” that heats the vessel wall by conduction or convention. A single pulse from each fiber in sequence minimizes any hot spots but is not as effective in emulsifying the clot. The best emulsifying action occurs when the shock and pressure waves repeatedly impinge upon a common area of the exposed clot end surface at a high rate. In addition to maintaining a beneficial turbulence initiated by a set of shock and pressure waves, an extended series of such waves results an more finely emulsifying larger particles that are initially broken away from the clot before they drift too far away from the clot along the vessel. The smaller the particles resulting from the emulsification, the less risk that a particle will lodge somewhere else to block the same or another vessel.
Yet another thermal management technique involves directing successive bursts of pulses along fibers that are removed from one another in order to spread out the heat that is generated. For example, pulses from the fiber 46 can follow those from the fiber 49, followed by pulses from the fiber 47, then from the fiber 50, and so on, generally in a star pattern. Whatever specific sequence is used, it is usually desirable to have one fiber in between two fibers that carry radiation pulses in successive periods of time. In general, with reference to
Although such skipping techniques can be the best for thermal management, it is not always the best for efficient emulsification. Especially when each burst of pulses through one fiber is only a few, or even just one pulse, before moving to the next fiber, it can be more efficient to direct such bursts through adjacent fibers so that the turbulence created from one fiber is built upon by pulses from the adjacent fiber, rather that moving to a fiber so far away that a momentum of emulsification must be started all over again. This also operates to allow pulses from one fiber to more finely emulsify at least some of any larger particles earlier broken away from the clot by pulses from an adjacent fiber.
The ultimate goal is to remove the clot with the least amount of heat being generated. When one set of radiation pulses is not as efficiently emulsifying the clot as another set, it will take more pulses overall to remove the clot and thus deliver a greater amount of heat in the process. There is thus a balance that is desired to be achieved between the direct reduction of heat input to the region of the clot from a particular spatial pattern of exposure to radiation pulses and a reduction of the amount of heat generated when the radiation pulses are used more efficiently. It may even be of some advantage to direct radiation pulses out of two or more of the optical fibers at one time but this is not preferred. Whatever pulse sequence is implemented, it is controlled by the electro-optical system within the instrument 33.
Referring to FIGS. 7A-E, the effect believed to result from one radiation pulse being directed out of a single optical fiber core 71 against an exposed face of a clot 73 is explained. In this example, the radiation is absorbed by the liquid in front of the clot 73. The effects will be similar if the absorption is in the clot itself. In either case, radiation is absorbed according to an absorption coefficient of the material in which the radiation is directed, and this absorbed energy superheats water within the material. According to the present invention, each pulse contains a small amount of energy, in order to minimize the amount of heat generated in the region, but is delivered by a pulse having a very short duration. This increases the efficiency of the process, which is expressed in terms of the mass of the clot that is emulsified per unit of laser pulse energy delivered to the treatment site within the vessel.
Very shortly after the pulse has been delivered, as shown in
A short time later, as shown in
It has been found that the efficiency of the emulsification process is-improved when both of the shock wave and hydrodynamic effect are generated by individual radiation pulses but only one or the other of them may be satisfactory for some applications and/or circumstances. At a later time of
Preferred Process Parameters
In order to remove a clot without creating thermal effects that have a potential of damaging a vessel wall, certain ranges of relative parameters have been discovered to work best. As mentioned above, it is a goal to have an efficient process. This minimizes the amount of laser energy required, and thus the cost and complexity of the laser source used in the instrument, and also minimizes the amount of time required to remove a clot. Maximizing the efficiency is possibly most important in minimizing the heat imparted to the treatment site in the course of removing a given volume of the clot, thus reducing the chance for tissue damage, particularly to the thin blood vessel walls.
A first parameter of interest is the size of the individual optical fibers 45-50, which are preferably made to be the same. It has been found that efficiency is increased by using smaller fibers, contrary to what one might initially think. Optical fibers with a core diameter of 200 microns or less can be used but those with a core diameter of 100 microns or less are preferred. The fiber cores must be large enough, however, to withstand the destructive effects on the fiber of the shock wave and hydrodynamic flow being generated at its tip. Depending upon the other parameters, the smallest core diameter that is practical is about 20 microns. Another factor that affects the minimum size of the optical fiber is commercial availability and cost. Optical fibers with the 50 micron core diameters mentioned above are available, and 25 micron core fibers may soon be available at a reasonable cost
It has been found, as illustrated by the family of curves of
The amount of radiation energy delivered from the end of a single optical fiber by each of the individual pulses is chosen from the curve of
The width of each radiation pulse is made relatively short in order to generate the initial shock wave That is, the shock wave is generated as a result of a small volume of material at the end of the optical fiber (
A repetition rate of pulses directed against the same or adjacent regions of the clot should be high enough to keep the clot surface in a dynamic state and assure that any large particles are further emulsified before drifting away from the region. A pulse rate of about one kilo-Hertz or more is enough for this. The main consideration for an upper limit is to allow the bubble from one pulse to be fully formed and collapsed (FIGS. 7B-D) before the next pulse hits. A pulse rate of about 20 kilo-Hertz or less allows this to occur, although rates up to 50 kilo-Hertz may be possible in certain circumstances. A pulse repetition rate of 5 kilo-Hertz has been used with the other parameters of the specific implementation given above.
The average power delivered to the vessel and clot is maintained as low as possible in order to minimize thermal load of the treatment site within the vessel in a way that avoids damaging the vessel. A maximum average nominal operating power of 0.5 watt is desirably maintained over the time of the treatment, and preferably less than 300 milli-watts. The achievement of this low power level can require, in some cases, that the treatment be performed with a duty cycle of less than one, such as 0.6 or 0.8. That is, no radiation pulses are directed into the vessel during periodically occurring intervals such that the pulses are generated 60% or 80% of the time. The maximum power level that can be used without causing damage also depends upon whether a cooling liquid is discharged through the lumen 51, and if so, the rate of its flow. A liquid flow rate as little as 0.1 cubic centimeters per minute provides beneficial cooling results. A flow rate in excess of two cc./min. will seldom be necessary, and a rate in excess of five cc./min. is not contemplated. A rate of one cc./min. has been used with the other parameters given above for the specific implementation. The flow rate is chosen so as not to overburden the vascular system but yet provide sufficient cooling. The amount of teat generated, and thus the average power input to the blood vessel, is independent of the number of optical fibers that are used in the preferred case where pulses are directed through only one of the fibers at a
A comparison is illustrated in a three-dimensional graph of
The Opto-Electronic Instrument
The structure and function of the instrument 33 (
The galvanometer 97 preferably holds the beam a on a single optical fiber for a time to direct a burst of a given number of one to many pulses into that one fiber before moving the beam to another fiber. A drive signal 106 supplies the proper positioning voltage to the galvanometer, depending upon which optical fiber is to receive the output pulses of the laser 91. Movement from one fiber to another necessarily takes some time, during which none of the optical fibers receives a pulse it will usually be preferable to reduce or eliminate this gap in delivering radiation pulses to the fibers. This can be done by substituting an acousto-optic modulator for the galvanometer 97 and mirror 95, to controllably scan the beam from the laser 91 across the ends of the optical fibers 45-50 held in the connector 31.
As mentioned above, part of the thermal management of the clot removal process preferably also includes monitoring whether bubbles are being generated by each of the optical fibers. If not, delivery of radiation pulses along that fiber is terminated, at least temporarily, since those pulses are likely delivering only heat to the affected blood vessel without performing any emulsification. This bubble monitoring and radiation pulse control is accomplished by the system shown in
A second laser 105 is provided to monitor the existence of a bubble. It can be a simple continuous wave (cw) laser with an output within the visible portion of the radiation spectrum. Its output beam is chosen to have a sufficiently different wavelength from that (of the treatment laser 91 to enable the two laser beams to be optically separated from each other. A helium-neon laser is appropriate, as is a simpler diode laser with an appropriate wavelength.
An output beam of the monitoring laser 105 is directed through the dichroic mirror 93 to strike the mirror 95 coaxially with the beam from the treatment laser 91. The monitoring beam is then scanned across the optical fibers 45-50 together and coaxially with the treatment beam. If the galvanometer 97 and mirror 95 are replaced with an acousto-optical modulator for scanning the treatment beam, another such modulator is used for the monitoring beam.
When a bubble is present at the end of an optical fiber receiving both of the treatment and monitoring beams, as shown in
A block electronic circuit diagram for the system control 103 of
An output of the comparator 131 (
The operation of the system shown in
The timing signal of
In the example being given, a bubble is detected to be generated at the end of the fibers 45, 46 and 48 but, is not so detected at the end of the fiber 47. That is, when a bubble is present, the photodetector signal 110 (
The trailing edge 147 of the output of the one-shot. 127 is caused to -occur just prior to the treatment laser pulse 145. This is controlled by the length of the output pulse of the one-shot 127 and the rising edge of the timing signal of
If there is a difference in the voltage levels stored in the sample-and-hold circuits 127 and 129, as adjusted by the voltage bias 124, which exceeds a preset amount, the output of the comparator 131 goes high, resulting in the latch 134 remaining in its set state. But if there is not at least this difference in the voltages stored in the sample-and-hold circuits 123 and 125, then the output of the comparator 131 goes low and this causes the latch 134 to be reset at the trailing edge of the pulse output of the one-shot 129. This combination of events is shown to occur at 151 in
It will be noted that the existence or non-existence of the bubble is detected only after the first treatment laser pulse of each burst. If none is detected, as for the fiber 47 in this example, no further treatment pulses of that burst are allowed to occur. Further pulses are prevented by the latch 134 being reset at 151 (
Of course, this is only one of many specific arrangements and timing that can be implemented. For example, the existence or non-existence of a bubble can be determined after each treatment laser pulse. Further, the lack of the detection of a bubble can be used to disable that fiber for more than one cycle, and perhaps for the entire treatment. In the case where only one or a very few pulses are contained in each burst, the detection of the absence of a bubble at the end of one fiber can be used to disable the system from sending treatment radiation pulses down that fiber for a certain number of cycles and then trying again.
Although the various aspects of the present invention have been described with respect to their preferred embodiments, it will be understood that the invention is entitled to protection within the full scope of the appended claims.