Method and Apparatus for the Measurement and Medical Treatment Using an Ultrasonic Wave

This invention relates to a diagnostic technique for imaging the shape of a specific blood vessel, e.g., coronary artery, and measuring the blood flow speed in the blood vessel, and also relates to the apparatus used for the treatment of the specific blood vessel.

It is known that the presence of numerous microbubbles in a liquid provides a pronounced imaging effect for the ultrasonic echography. For example, a method disclosed in U.S. Pat. No. 4,265,251 introduces into blood a solid precursor, typically saccharide compound, and numerous microbubbles produced when the saccharide has melted in blood are used for the echography of a selected part of a blood vessel. European patent Laid-open No. 0052575 describes the use of a blood-melted precursor similar to the above-mentioned one, but in the form of particles, each being integrated finer particles so that spaces among finer particles are filled with gas. Another method of U.S. Pat. No. 4,276,885 injects directly into the blood flow numerous microbubbles fixed by gelatin, thereby intensifying the ultrasonic image.

The conventional methods are either creating microbubbles in the blood flow under examination, or injecting microbubbles which have been created externally in advance into the blood flow under examination. However, neither of these methods are said to be appropriate for imaging only a specific blood vessel, particularly the coronary artery. The reason is that the injection through a vein causes the bubbles or precursor to reach peripheral blood vessels in the heart and lung before arriving at the coronary artery. Although an artery catheter for introducing bubbles or precursor to the root of the aorta enables the contrast medium to reach the coronary artery promptly, the use of the artery catheter is undesirable in many cases from the viewpoint of time and labor for the examination and the risk imposed on the patient.

Similar to the delivery of a contrast medium to the intended part of a blood vessel in ultrasonic imaging as described above, it is also difficult to deliver another agent, e.g., thrombus liquefacient, to the intended part, e.g., the end of the coronary artery, effectively by the introduction of the agent through a vein.

Accordingly, it is an object of this invention to provide a method and apparatus for delivering a contrast medium or other agent to an intended specific blood vessel effectively.

Depending upon the agent used, this invention is characterized in that the agent is packed in fine capsules which are breakable by shock wave pressure or packed among particles of integrated fine particles, with the fine capsules or integrated particles being distributed in a liquid in a state of emulsion. The fine capsules or integrated particles have such a size that they can penetrate capillaries. After numerous capsules or integrated particles introduced to vein blood have encircled the patient's body and reached a proper position, they are broken by the application of a shock wave and the agent is dispersed in the blood.

In accordance with the apparatus, this invention is characterized by means of injecting numerous fine capsules, with an agent being packed therein, into the patient's body, and means of applying a shock wave with a dominant positive pressure from outside of the body to the intended position so that only capsules, among all dispersed in the body, located in the intended position are broken selectively.

In the aspect of the effective introduction of agent to the coronary artery, the apparatus features the inclusion of means of detecting the heart beat and means of timing the generation of shock wave in relation with the heart beat.

FIG. 1 is a block diagram showing an embodiment of the invention;

FIGS. 2A-2D are timing charts showing the timing of activation with respect to the heart beat; and

FIGS. 3A and 3B are diagrams showing the arrangement of the shock wave transmitter and the waveform of sound pressure produced by it, respectively.

FIG. 1 shows the arrangement of the inventive apparatus which is intended for both the observation and treatment of the coronary artery. An injecting device 1 is used to inject an agent such as the contrast medium into the patient's body. The agent 2 supplied to the injecting device 1 consists typically of numerous particles of fine capsules made of fatty acid ester or lecithin, in which is contained a material such as hydrogen bicarbonate soda which produces gas when in contact with water, distributed in an aqueous carrier liquid such as physiologic salt solution in a state of emulsion. The size of particles is determined such that all particles can penetrate the pulmonary capillaries, and it is few micrometers in diameter at most. Typically, the particle diameter has a mean value of 1.9 .mu.m, and 90.degree. of particles have diameters of 3.0 .mu.m or less. More preferably, all particles have diameters of 2.0 .mu.m or less. Injected agent particles are dispersed in blood in the patient's body and delivered to the aorta by way of the right heart, lung and left heart.

A shock wave transmitter 3 emits a pulsative shock wave by being energized by a driver 4. In this embodiment, the transmitter 3 is positioned and directed so that the shock wave is emitted toward the root of aorta indicated by 22, with the intention of imaging the coronary artery indicated by 21 and measuring the blood flow speed in it. The agent particles which have reached the root of aorta are broken by being hit by the shock wave and the agent is released into the blood. Consequently, microbubbles are created in the blood and a number of them are introduced to the coronary artery.

A timing controller 12 operates on the driver 4 so that the shock wave is generated at a prescribed moment on the cardiogram of the patient's body presented by an electrocardiograph 7. FIGS. 2A-2D are timing charts used to explain this timing control. FIG. 2A shows the cardiographic waveform provided by the cardiograph 7. The systolic period of the heart begins at around the Q-wave of cardiogram and lasts until around the end of the T-wave, and thereafter the heart enters the diastolic period. Since artery blood is introduced into the coronary artery during the diastolic period of the heart, the most preferable timing of emitting the shock wave is between the end of the systolic period and the beginning of the diastolic period, in order to introduce microbubbles created at the root of aorta efficiently into the coronary artery. In addition, for the avoidance of premature beat, the shock wave must not be emitted at least in an end portion of the diastolic period.

In this embodiment, the timing controller issues a trigger signal for shock wave generation to the driver 4 upon expiration of a certain time length t following the R-wave on the cardiogram, as shown in FIG. 2B. The delay time t is set on a setting dial 13 in compliance with the heart beat period of the patient's body. After several heart beat periods following the injection of agent particles into the vein, the concentration of particles within the aorta rises as shown in FIG. 2C. The timing controller 12 counts heart beats following the commencement of agent injection by the injecting device 1 on the basis of the output of the cardiograph 7, and issues the trigger signal several times at each specified beat count.

The cardiograph 7 constantly displays the immediate cardiogram and also the time point of shock wave emission based on the timing display signal returned from the timing controller 12 on a display 7A. Specifically, the emission time point is displayed as a "cut" or break in the waveform of the cardiogram, as shown in FIG. 2A.

A B-mode an ultrasonic diagnostic apparatus emits a supersonic or ultrasonic wave and provides an ultrasonic echograph on the basis of the well-known sectorial ultrasonic scanning. The emission of shock wave creates numerous microbubbles in artery blood, and the bubbles in the coronary artery which serve as effective reflectors, intensify the echo image of the coronary artery. The agent dispersed in blood inside the heart and pulmonary capillaries still remains in particles, producing a weaker reflected sound wave as compared with that from bubbles, and therefore the resulting echograph has its image of only coronary artery intensified selectively.

Moreover, the presence of the high-reflective substance in blood inside the coronary artery enables the measurement of blood flow speed inside the coronary artery through the provision of a doppler flow speed meter 8. In this case, the position of coronary artery is detected from the echograph provided by the B-mode ultrasonic diagnostic apparatus 5 so that the probe 6 is positioned and directed properly, and the ultrasonic impulse beam is emitted to measure the doppler shift of the reflected wave. It should be noted that the measurement of blood flow speed in the circumflex coronary artery in the rear of heart is only feasible by the foregoing selective bubble generation.

The B-mode ultrasonic diagnostic apparatus 5 and doppler flow speed meter 8 are given an inhibit signal for the prevention of noise contamination in the resulting image and detected signal caused by the shock wave from the transmitter 4. The inhibit signal provided by the timing controller rises simultaneously with the shock wave trigger signal and falls after a certain time length. During the active period of the inhibit signal, the B-mode diagnostic apparatus 5 and doppler flow speed meter 8 are prohibited from writing to their internal display memories. Alternatively, the measuring operation of these instruments may be halted by the inhibit signal. In any case, the inhibit signal needs to last at least the time length in which the disturbing sound wave caused by the shock wave exists, and it is around 10 ms.

FIG. 3A shows a specific arrangement of the transmitter 3 and driver 4. The transmitter 3 has a structure, with a nonmagnetic, conductive diaphragm 31 being disposed in close proximity to a spiral coil 32. The diaphragm 31 is provided on its concave front side with a cover 34 so that liquid 35 for propagating the sound wave is held. Indicated by 33 is a frame for supporting the diaphragm, coil and cover, and the frame 33 has a sufficiently greater mass than the diaphragm. The transmitter is used in such a way that the cover 34 is brought in tight contact with the patient's body surface.

The spiral coil 32 is connected to a drive circuit which includes a capacitor 41, charging means 42, switch 43 and discharging resistor 44. The capacitor 41 is charged by the charging means 42 when the switch 43 is open, and it supplies a discharging current to the spiral coil 32 at the moment when the switch 43 is closed. The nonmagnetic, conductive diaphragm 31 responds to the current to emit a shock wave derived from the magnetic repellence force.

FIG. 3B shows on the time axis the sound pressure at the focal point of the diaphragm. When the switch is closed at t.sub.0, the sound pressure rises sharply, and an impulse sound pressure with a dominant positive pressure is produced. The impulse sound wave with the dominant positive pressure causes less suffering and damage to the patient as compared with a sound wave with a dominant negative pressure, and the intended destruction of agent particles in the blood flow can be carried out safely.

In the foregoing embodiment, it is possible to display the cardiogram produced by the cardiograph 7, the ultrasonic echograph produced by the B-mode diagnostic apparatus 5, and the blood flow speed measured by the doppler flow speed meter 8 simultaneously on a single display unit with a proper separation provided on the screen. It is also possible to display the measured value of doppler flow speed meter in a color code on the ultrasonic echograph. Furthermore, the B-mode ultrasonic diagnostic apparatus 5 and doppler flow speed meter 8 may share a single probe on a time slice basis.

Although the agent used in the foregoing embodiment is a bubble-sourcing substance contained in particles of fine capsules which are distributed in a carrier liquid, it may be formed in particles, each being fine integrated particles, which are distributed in a carrier liquid. Such integrated particles disperse in the blood flow when hit by the shock wave, releasing gas which has been held in spaces among particles as bubbles, more quickly to release gas which has been captured in. The material of the agent is chosen such that it does not melt quickly in the blood while it is in the integrated state. The produced gas must be harmless for the human body, and it is preferably oxygen or carbon dioxide since it is absorbed in blood quickly.

Although the foregoing embodiment has been aimed at the creation of bubbles as a contrast medium for ultrasonic diagnosis, the agent injected by the injecting device 1 may be the medicament for treatment. For example, a thrombus liquefacient such as urokinase is encapsulated together with the bubble-sourcing agent in microcapsules and distributed in a carrier liquid. After the encapsulated substance has been injected, the shock wave is applied to the position of blood vessel to be treated or the upstream position thereof, so that capsules are broken and the medicament is delivered only to the necessary portion.

Although the foregoing embodiment is the case of medical apparatus, the invention is also applicable to other industrial repairing apparatus by appropriately choosing the agents.