CA1221759A

CA1221759A - Ultrasonic imaging technique

Info

Publication number: CA1221759A
Application number: CA000446243A
Authority: CA
Inventors: Steven B. Feinstein
Original assignee: Individual
Current assignee: Individual
Priority date: 1983-01-27
Filing date: 1984-01-27
Publication date: 1987-05-12
Also published as: IL70784A0; AU571863B2; GB2143327A; SE8404797L; IL70784A; EP0135563A4; GB2143327B; NL8420041A; GB8423446D0; US4572203A; AU2576984A; AT397034B; SE466634B; DE3490013T1; JPS60500486A; NL191079C; NL191079B; DE3490013C2; EP0135563A1; EP0135563B1

Abstract

ABSTRACT OF THE DISCLOSURE

A method of ultrasonic imaging for use on medical procedures is disclosed. The method comprises injecting specifically defined microparticles or sonicated microbubbles into an animal or human to thereby alter the acoustic properties of an area to be imaged, and then ultrasonically scanning the area so as to obtain an image.

Description

ULTRASONIC IMMUNE TECHNIQUE
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BACKGROUND OF THE INVENTION
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1. Field of the Invention This invention relates to thy f ye' d of ultrasonic imaging techniques, and more specifically, to a medical procedure which utilizes these technique as a diagnostic tool.

2 . I PD6 5 0 6 .... . ..
Various technologies exist in which parts of an animal or human body may be imaged 50 us to aid in diagnosis and therapy. Some of these existing techniques are described on this section.
One of the most well known imaging techniques involves the use of X-rays to visualize skeletal and other internal structures within aimless and human.
There are, however, a number of problems associated with the use of X-rays. Fist, some areas of the Cody may not be Arrayed awful In addition, X-rays are dangerous if the amount of exposure is excessive; further, all Ray redline absorbed over a lifetime is cumulative. Flannel whip X-rays may produce images 15 of the skeletal and other internal structures, X-rays have proved to be relatively unsatisfactory for detailed viewing of certain organ systems and blood vessel Another widely used technique is angiogra~hy7 whereby a redip dye it injected into an artery Because the dye highlights the arteries through which it flow, an X ray Jay be used to obtain an image of major, large arteries and their ~igniflcant Blanche however, angloqraphy does not permit visualization of under~p2rfused~ ischemic area of tissue or heart muscle ox the m~crocirculation. In addition, certain ang~ographic observations are based upon measurement which may vary depending upon the apparatus used, the placement and angle of lenses purity skill and similar factors D Moreover, angio~raphy is invasive in that it requires the placement of a catheter into arteries a opposed to veins Beside requiring h~spitall~ation, angiography may be dangerous.
Another technique, often referred to a radio-knucklehead imaging involves the injection of radioactive substance such as thallium, into the blood stream Thus technique doe no require invasion of the arteries as does ~n~ography~ but it does require the use ox

3, PD6506 very expensive and sophisticated machinery. Further, radio-nuclide imaging produces images of only a limited number of views of the heart, and those image may not be of exceptional clarity Finally this type of radiation it cumulative over a lifetime and may be dangerous.
Recently, there have been advances in technique for ultrasonically imaging various parts of the body, these techniques when applied to the heart in particular are known as ~echocardlography.~ on ultrasonic scanner is used to generate and receive sound waves. The ultrasonic scanner is placed on the body surface overlying the area to be imaged. The wound waves generated by the scanner are directed toward the area to be imaged The scanner then detects sound waves reflected from the underlying area and translates thaw data into images While such ultrasonic scanners are known in the art, a brief review will be set forth in order o more fully explain the present invention When ultrasonic en ray is transmitted through a substance t he acoustic properties the substance will depend upon the velocity of the transmissions and the Dennis of the substance Change on the substance's acoustic properties (or aquatic impudency will be most prounion at the interface of different substances it oldies liquid and gases). A a eonsequen~e, when ultrasonic energy is directed through various media, the changes in acoustic properties will change the reflection characteristics, resulting in a more intense wound reaction signal received by the ul~ra-~onic wanner.
Early ultrasonic imaging techniques such as echo cardiograms suffered from a lark of clarity AS a result extPn~ive efforts were undertaken to improve the ultrasonic scanners and related equipment. In addition, beginning in 1968, contrast" agents were injected into the brood stream in an effort to obtain

4. PD6506 clearer or "enhanced ultrasonic images. The prior art contrast agents were liquids containing micro bubbles of gas, which sometimes were encapsulated with gelatin or saccharine and sometimes were produced by mechanically agitating, i.e. handshaking mixtures of various liquids. Other prior art contrast agents are disclosed in an article by J. Offer, et alp entitled Masonic Baxter from Contrast Produced by Collagen Microphones in ultrasonic Imaging by Academic Press, Inc. l9BO~
The contrast agents themselves are intense sound wave reflectors because of the acoustic difference between the liquid and the gas micro bubbles dissolved therein; thus, when the contrast agents are netted into and perfuse the microvasculature of tissue clearer images of such tissue may be produced however, notwithstanding the use I such contrast agents, the image produced for example of the myocardial tissue, is of relatively poor quality; is highly variable and is not quantifiable due to the variable size and persistence associated with prior art micro bubble Further, the problems of air embolism toxicity have not .
yet been investigated 3r3 SPRY OF THE INVENTION
One embodiment of the present invention is directed to an improvement associated with such prior art contrast agents by which smaller and more uniform micro bubbles are produced. A second embodiment is directed to the novel use of specifically defined metal-containing solid or semisolid contrast agents.
The Conrad agents of the present invention are I echogenic (i.e., capable ox reflecting sound waves), I small enough to pass through capillaries so as to perfuse tissue previously lnacces~ible to the prior art contrast agent injected into a peripheral venous site thereby producing enhanced image of such tissue and organs and permitting differentiation between well-perfused and poorly-perfused tissue, and (3) quantiflably reproducible In addition the metal-containlng solid or semi-solid contrast agents of the present invention are tree of the potential air embolism toxicity risks associated with the introduction of gaseous bubbles into the human or animal septum It no believed that such particulate matter has ever been used as a contrast agent in medical proceeder The method of the present inYe~tion (1) permits the imaging of organ systems which could not be imaged using prior art ultrasonic technique 7 and I permits clearer, more detailed imaging of certain area which were Lubell using such prior art techniques.
In the first embodiment of the preset invention, a viscous solution ego, 70% Dextrose 50% Dextrose, 70~ orbital Renogratin-76~ mixtures of these agents, and the like) is subjected to high frequency (Roy to Tao Ho) ultra only energy. As a royalty mierobubbles having a diameter of approximately 6 to 20 microns are produced. For ease of reference such micro bubble will be referred to herein as ~sonicated" micr~bubble~. As described in greater detail hereinbelow, such sonicated I

I PD65~6 micro bubbles have been found to be Improved con~ra5t agents .
The second embodiment of the present invention is directed to selected metal-containing micropartlcle~
used as contrast agents to reflect intense patterns of sound waves The contrast agents of the present invention are detected by conventional ultrasonic scanning equipment and translated into images in the manner described above.
The use of the microp~rticles it especially advantageous in that it orates the nerd to introduce gaseous bubbles as contrast agents in the human or animal Siam, and thus eliminates the air embolism toxicity risk inherent in that procedure. Depend upon whether the micro particles are to ye used exclusively on animal research or for diagnostic and therapeutic purposes the potential biocompatability of the particular type ox microparticl~ is a s~nl~cant consideration.
The metal-containing micr~pax~icles of the prevent invention are e~ho~enic (Joe., capable of reflecting sound wives being composed of material having acoustic properties which are significantly different from those of blood or Tess Their size is small enough to permit their passage through capillax~es 9 if Nasser without being filtered out prior to reaching the area to ye imaged ego. 8 where a peripheral venous injection site is used; husk they will by capable of perfusing tissue and producing an enhanced image of the tl~sue, organ and any diffe~ntlation between well-perfused and poorly-perfused tissue, wltho~-t being iniquity into the arteries or directly into the area to be imaged Thus, they may be injected into a peripheral vain or other predetermined area of the body resulting in considerably lets invasion than the arterial injections required for on angiogram~
In addition, unlike any of the gaseous bubbles known to the prior art the metal-containing micro particles of the present invention are quan~if~ably reproducible 7. PD6506 Further, use of microparti~les as a contrast agent does no require machinery which is as sophisticated or expensive as that required by radio-nuclide imaging, nor does their use require exposure to radioactive materials Thus, while overcoming many of the problems associated with the prior art, the present invention makes possible the production of unique images of various organ systems. although the invention technique it applicable Jo various animal and human Cody organ systems, its novel features and advantages may be better understood from the following description of it use in obtaining image of myocardial tissue and perfusion or blood flow patterns The description and accompanying drawing are included for purposes of illustration only, it being expressly understood that they are not intended to be a definition of the limits ox the invention D
In reviewing the description and drawings it should be kept in mind that the heart is a pump fed by many blood vessels which, during the course of time, may become partlall~ or totally blocked, causing damage to the heart tissue. In the past, information concerning the state of the blood vessels was primarily obtained through the involve angiog~aphy techniques described above or through surgery. on addition information concerning the heart tls~u~ was opined using radio-knucklehead imaging or surgery; the angiogram produced no direct data r2gardiny the tissue but rather required the drawing of inferences from data obtained with respect 3Q to the major blood vessels and wall motions of the heart.

I
8. PD6506 BRIEF DESCRIPTION OF TOE DRAWINGS
The invention will now be described with reference to the accompanying drawing, wherein:
FIGURE 1 is a schematic view showing the use of an ultrasonic scanner in echo cardiography; and FIGURES 2~5 are cross sectional images of the heart enhanced by the use of contrast agents flowing there through.

owe 9. PD6506 DETAINED DESCRIPTION OF TOE INVENTION
FIGURE 1 Is a schematic view of the heart and lungs, as well as of ultrasonic scanning equipment consisting of a scanner lo and imaging apparatus 12, The equipment produces visual images of a predetermined area, in this case, the heart region of a human Cody. Typically, the scanner lo is placed directly on the skin lo over the area to be mud 16~ The scanner 10 houses various electronic components including ultrasonic transducers.
lo The spanner lo produces ultrasonic waves 18 which perform a sector scan of the Lear region 16~ The ultrasonic waves lo are reflexed by the various portions of the heart region 16 and are received by the generating transducer and processed in accordance wow pulse-echo methods known on the art. After processing 7 signals are sent to the immune apparatus 12 (also well known in the art for viewing.
In the method of the present invention, after the patient is Warped" and the scanner lo it in place, the sonicated microbubbl~ or micro particle contrast agent it injected for example t through an arm vein r generally indicated at 24. The contrast agent flow through the vein 24 in the direction of the arrow 26~
through the fight (venous wide 28 ox the heart 30 p through the main pulmonary artery 29 leading to the lungs 32, across the lungs 32~ through the coupler 34 t into the pulmonary veins 35 and finally unto the left atrium 36 and the left ventricular cavity 37 of top heart 30.
The present invention is directed to both son~cated micro bubbles and microparti~ulate matter used as contrast agents. It has been found thaw the use of socketed micro bubbles or solid micro particulate matter such as glass or graphite produce images hiving vividly contrasting areas O particular r such ~icroparticles (lo are solid OX semi~5011dp to do not contain trapped air, I may be biocompatlble or biodegradable, I are I
I P~506 small enough to pass through the capillary buds which are about 8 to 10 microns in size, and (I have acoustic properties maying them echogenic. While not to be bound by any theory, both the sonicated micro bubbles and the micro particles of the present invention produce ~otlceably clearer and more detailed images of the myocardial tissue and microvasculature~ a compared with prior art contrast agent Referring now to FIGURES 2-5 J one can see con fast echocardiogra~ produced by the ut.tlizatio~ of the ssnicated micro bubble keenest agent of the present invention In the figures a horseshoe-~haped portion 50 represents the left ventricular wall muscle (or tissue) which encloses the left ventricular cavity 37. The ~icrobubbles were injected into the pulmonary artery of a dog and have roused the capillary beds of the lung Jo enter the let atrium 36 and the left ventricular cavity 37 unto the aorta through the coronary arteries and eventually unto the loft ventricular Tao 50 enhancing the image thereof.
Specifically, FIGURE 2 owe a two-dimensional ech3cardiogram ED image of the left ventricular suavity 37 and loft atrium 36, prior to the introduction of the ~onicated micro bubbles FIGURE 3 illustrates the injection of a 10 my sonicated Renografin~aCl mixture through a wedged pulmonary artery coauthor us Jan be seen the contrast agent appears in the left atrium 36 and flow into the left ventricle 379 In FIGURE 4, substantially complete opacity of the left ventricular cavity 37 has oc~urredD In FOE 5, subsequent pacification of the myocardial tissue 50 can be seen This is buckeyes the blood carrying the contrast agent has flowed through the aorta into the coronary arteries which supply toe blood to the ~yocardial tissue 50. Thus observations and diagnoses can be made with respect to the amount of tome required for thy brood to pass through the lungs, blood flow patterns, --.11~
1 the size of the left atrium, the competence of the mitral valve (which separates the left atrium and left ventricle, chamber dimensions on the left ventricular cavity and wall motion abnormalities. Upon ejector of the contrast agent from the left ventricle, the competence owe the aorta valve also may be analyzed, as well as the ejection fraction or percentage of volume ejected from the effete ventricle. Finally, the contrast patterns in the tissue will indicate which areas, if any, are not being adequately perfused.
In summary, such a pattern of images will help diagnose unusual blood flow characteristics within the heart, valvular competence, chamber sizes and wall motion, and will provide a potential indicator of myocardial perfusion.
In the example set forth above, the micro bubbles were produced from a mixture of Renogra~in~6 (a relatively non-toxic, biocompatable radio-opaque dye well known in the art) and saline in a one-to-one ratio. This mixture was sonicated, i.e.
subjected to high frequency energy, for about 30 seconds by a Heat System 375 watt sonicator. Such sonicators are well known in the art for other uses, and usually emit ultrasonic energy of 20,000 Ho, although energies of 5,000 to 30,000 Ho or even higher are within the scope of the-present invention Depending on the contrast agent selected, such as the mixture described above, sugar solutions or the like, varying bubble sizes are produced, usually however/ within the desired range of about 6 to 20 microns in diameter Besides the scanner 10 briefly described above, there exist other ultrasonic scanners, examples of which are disclosed in US. Patent Nos. 4,143,554 and 4,315,435. basically, these patents relate to various techniques including dynamic cross-sectional echography (DOE) for producing sequential two-dimensional images I P~6506 of cross-sectlonal slices of the animal or human anatomy by means of ultrasound energy at a frame rate sufficient to enable dynamic visualization of moving organs Types of apparatus u illzed in DOE are generally called DOE
scanners and transmit and receive short, sonic pulses in the form of narrow beams or lines The reflected s~gnalsl strength is a junction of time, which is converted to a position using a nominal wound speed and is displayed on a cathode ray tube or other suitable device on a manner somewhat analogous to radar or sonar displays. Whole DO can be used to produce image of many organ systems including the lover, gall bladder t pancreas and kidney it it frequently used for visualization of tissue and major blood vessel of the heart misting DOE scanners car be classified according to the geometry of their field of view (linear or sector scanning)/ according to the means used for scanning that field of view (mechanical or electronic scanning) 20 and according to ether the trar~sdu~er scan the patient or object thrc3ugh an intervening water bath or by direct corltact Waco the Sirius of the object a, for example the skin of a patient using an appropriate contact gel or oil. Linear scanner produce a scan of the anatomy 25 consisting of a jet so nominally parallel scan line I, displaced with respect 'co one another by a fine spacing roughly cornpara~le to the effects width of each llneg as detQxmined primarily by the trouncers used on the apparatus. the cross sectiorl imaged by such scanners 30 it therefore approximately rectangular in shape, its width being determined by the line spacing and total number ox line, while its depth is determined by the penetrations range of 'eke ultrasound energy into the Tao. Linear scanrlers are generally used where there 35 is a relatively extended region of shop body surface from which access to the part of interest of the anatomy I possible, such a in to abdominal orison 13. PD~506 Sector scanners produce a scan of the anatomy consisting of a fan of divergent lines spaced angularly from one another, but intersecting nominally) at a point. The angular spacing is even or uneven depending upon the apparatus, and is roughly comparable to the effective angular width of each fine. Sector scanners are generally used where the anatomical window or region of the body surface from which access Jo the anatomical part of intones is relatively small, as in the adult hear, the brain and the eye Another type of sector scanner is mechanical in nature and can be further divided into two subleases, oscillating transducer scanners and wrung transducer swooners An oscillating transducer spanner us one in which a single transducer is oscillated about an axis nominally lined in the front plane and pausing through the center of the transducer with an appropriate angle sensor being used to-monitor the angular position of the transducer at any time. In a typical rotating transducer scanner, several transducer spin inside a small do filled Wylie liquid, with one transducer at a iamb scanning the area of interest. These and other scanners are within the. scope of the present invention.
As squatted above r in attempting to find a safe, 25 reproducible, quantify table contrast agent for use in producing an enhanced ultrasonic image of the tissue under study, researches have used saccharine arid gelatin encapsulated micro bubbles of nltro~en or carbon dioxide gas having a mean size of approximately 75 micron, 30 pressurized gas Ida liquids (e.g. ~22~ 7 aid a~echanlcally agitated (hand shaken) mixtllres of Lowe d solution Ever, wince the pulmonary artery coupler are about 8 to 10 microns in do ampler the 75 micron encapsulated micro bubbles may not cross the capillary US bets and, as a royalty their us would require a direct in section unto the area to be imaged or an crier tat injection involving the same xlsk a the invasive 14~ PD6506 approach of angiography discussed above. Further, micro bubbles produced by agitating various liquids owner than by sonicating Tom) have wide variability of size.
Variable amount of such non-encapsulated aglta~ed micro bubbles can pass through capillaries, but the present state of the art has only produced qualitative data due to the inability to control the variable described above. These contrast agent all work to some degree, but suffer from 2 number of problems including the fact that the size of the bubbles is not uniform Those and other problems are overcome by the ~onicated micro bubbles of the present invention.
However, while son axed microbubblPs are more uniform in size and produce enhanced images, the lo potential problem associated with the introduct~n of air remain The danker of injecting microbubblesO
encapsulated or not into the heart is thaw the bubbles eventually collapse and the amount of dissolved elf may be toxic in the arterial stem ego., of the brain and 20 kidneys) a well a in other micro circulatory system Thus it it evident that the particular contrast agent selected will depend upon the purpose of the imaging or expel an aunts potential risk factors should be considered for diagno~ic or ~herapeutlc use the size of the contrast material I also of concern, If the particles are too large they will not past through the capillaries and thus ~111 require direct or ayatollah injec~lons if the aria to be imaged lies beyond the c~p;llar;esO On the other hand d of the contrast agent is zoo small, it may not wreck sound waves emitted by the ultrasonic transducer.
idea particulate matter which produces contrast-type enhanced images include graphite particles, lass beads, and similar substances. The present inanity Or has grossly examined many of the available solid particulate matter which theoretically may be used as a contrast agent t and has determined that one such agent, -15~ ~2~7~
1 although no-t previously disclosed as a contrast yenta has a number of very desirable properties. Such agent and associated liquid carriers are broadly disclosed in US. Patent No.
4,247,4~6. In the '406 patent, the solid particulate material comprises magnetically localizable, biodegradable carriers which comprise micro spheres formed from an amino acid polymer matrix with magnetic particles embedded therein. For example, albumin can be used as the matrix material and magnetize (Foe) can be used as the magnetic particles. The micro spheres have an average diameter of less than 1.5 microns and the magnetic particles contained therein have an average size of not more than 1,000 Angstroms. The micro spheres may contain from 50 to 350 parts by weight of the magnetic material per 100 parts of the amino acid polymer. The mierospheres may contain the magnetic particles uniformly distributed throughout the matrix, or, preferably, may be concentrated in the peripheral portions.
Other particles having similar characteristics are also within the scope of the present invention.
By the use of these specifically defined metal containing solid contrast agents, echo cardiograms having the desired resolution may be produced Further since the micro particles described above are biodegradable, their side effects are minimized.
The mieropartieles may be used for imaging a wide variety of areas, even when injected at a peripheral venous site.
Those areas include (without limitation): (1) the venous drainage system to the heart; I the myocardial tissue and perfusion characteristics during an exercise treadmill test or the like, and I myocardial tissue after an oral ingestion or intravenous injection of drugs designed to increase blood flow to the tissue.
Additionally, the micro particles may be useful in delineating changes in the myocardial tissue 16~ PD~506 perfusion due to interventions such as: I coronary artery vein grafting; 2) coronary artery angioplasty (balloon dilatation of a narrowed artery); 3) use of thrombolytic agents such as s~rep~okinse) to dissolve clots in coronary arteries; or 4) perfusion defects or changes due to recent heart attack.
Furthermore r at the time of a coronary angiogram (or a digital subtraction angiogram~ an injection of the micro particles may provide data with respect to tissue perfusion characteristics what would augment and complement the data obtained from the angiogram procedure, which identifies only the anatomy of the blood vessels Through the use of the micro particles of the present invention, other non cardiac organ systems including without limitation the liver spleen, kidney, etch that are presently imaged by ultrasonic techniques may be susceptible to an enhancement of such currently obtainable images, Andre the generation of new images showing perfusion and flow characteristics thaw had not previously been susceptible to imaging Using prior art ultrasonic imaging techniques In terms Jo method of operation, the use of the subject micro particle would be the Same as aye described bye with respect to gonica~ed micro bubbles. The amount of micropar~icles used would be defendant ox a number of factors lnclu~ing the choice of liquid carriers (water, sugar solution, etch degree of opacity dullard areas of the body to be imaged, site of injection and number of injections In all instances, however, sufficient m~cropart;~les would be used in the liquid carrier o achieve discernible images by the use of ultrasonic scanning.
Having described the invention, it is obvious thaw other modifications may be made by those skilled in the art. or example, other water soluble polymers can be used in place ox albumin lnclud~ng hemoglobin and other magnetic particles can be used in place of magnetites 17~ PD6506 etc., including magnetic iron oxides, carbonyl iron and the like. This invention, therefore, is to be limited only to the scope and spirit of the appended claims.

Claims

18.

What is claimed is:

CLAIM 1 A method of ultrasonic imaging for use in medical procedures, comprising the steps of:
(a) injecting biodegradable, metal-containing microparticles into a mammal to thereby alter the acoustic properties of a predetermined area; and (b) ultrasonically scanning an area including said predetermined area so as to obtain an image of said predetermined area.
CLAIM 2 The method according to Claim 1 wherein said microparticles have an average diameter of less than 1.5 microns and are formed from an amino acid polymer matrix with magnetic iron particles embedded therein, said magnetic particles have an average size of not more than 1,000 Angstroms.
CLAIM 3 The method according to Claim 1 wherein said predetermined area comprises the heart.
CLAIM 4 The method according to Claim 1 wherein said microparticles are injected into the coronary arteries.
CLAIM 5 The method according to Claim 1 wherein said microparticles are injected into the peripheral veneous system.
CLAIM 6 The method according to Claim 1 wherein, in lieu of said biodegradable microparticles, biocompatible microparticles are used.

19.
CLAIM 7 A method of ultrasonic imaging for use in medical procedures, comprising the steps of:
(a) subjecting a biocompatible liquid to high frequency energy in the range of about 5,000 to 30,000 Hz so as to produce microbubbles having substantially uniform diameter;
(b) injecting said microbubbles into a mammal to thereby alter the acoustic properties of a predetermined area; and (c) ultrasonically scanning an area including said predetermined area so as to obtain an enhanced image of said predetermined area.
CLAIM 8 The method according to Claim 7 wherein said microbubbles have a mean particle size of about 6 to 20 microns.
CLAIM 9 The method according to Claim 7 wherein said liquid is subjected to high frequency energy of about 20,000 Hz.
10. A method of ultrasonic imaging for use in medical procedures, comprising the steps of:
a) forming biocompatible microparticles comprising amino acid polymer matrix containing at least one ultrasound image enhancing material selected from the group consisting of glass, graphite, magnetic particles, magnetite, magnetic iron oxides and carbonyl iron;
b) injecting said microparticles into a mammal to thereby alter the acoustic properties of a predetermined area; and c) ultrasonically scanning said predetermined area to obtain an ultrasound scanning image thereof.
11. The method of Claim 7 wherein said biocompatible liquid is a viscous solution.
12. The method of Claim 11 wherein said viscous solution is selected from the group consisting of dextrose, sorbitol, relatively nontoxic radio-opaque dye, and mixtures thereof.
13. The method of Claim 12 further comprising saline as a diluent.
14. The method of Claim 11 wherein said viscous solution is a mixture of relatively non-toxic radio-opaque dye and sodium chloride.
15. The method of Claim 7 wherein the step of subjecting said biocompatible liquid to high frequency energy results in cavitation bubbles and said cavitation bubbles collapse resulting in by-product bubbles having substantially uniform diameter.
16. A method of ultrasound imaging for use in medical procedures, comprising the steps of:
a) subjecting a biocompatible liquid to high frequency ultrasound energy in the range of about 5,000 to 30,000 Hz thereby producing stable microbubbles having substantially uniform diameters in the range of 6 to 20 microns;
(b) injecting said microbubbles into a mammal to thereby alter the acoustic properties of a predetermined area thereof: and c) ultrasonically scanning an area including said predetermined area so as to obtain an enhanced image of said predetermined area.
17. A method of ultrasound imaging for use in medical procedures, comprising the steps of:
(a) providing a biocompatible liquid selected from the group consisting of dextrose, sorbitol, relatively non-toxic radio-opaque dye and mixtures thereof;
(b) subjecting said biocompatible liquid to ultrasound energy in the range of 5,000 to 30,000 Hz thereby producing stable microbubbles having substantially uniform diameters in the range of 6 to 20 microns;
c) injecting said microbubbles into a mammal to thereby alter the acoustic properties of a predetermined area of said mammal; and (d) ultrasonically scanning said mammal including said predetermined area thereby obtaining enhanced images of said predetermined area.
18. The method of Claim 17 wherein said biocompatible liquid is selected from the group consisting of 70% dextrose, 50% dextrose, 70% sorbitol, a non-toxic radio-opaque dye, and mixtures thereof.
19. The method of Claim 17 wherein said biocompatible liquid further comprises saline.
20. A contrast agent for diagnostic ultrasound imaging of organs in mammals comprising a biocompatible liquid containing stable microbubbles of substantially uniform diameters in the range of 6 to 20 microns, said microbubbles having been produced by subjecting the liquid to high frequency ultrasound energy in the range of 5,000 to 30,000 Hz.
21. The contrast agent of Claim 20 wherein said liquid comprises a viscous solution selected from the group consisting of dextrose, sorbitol, non-toxic radio opaque dye, and mixtures thereof.
22. A method of ultrasonic imaging for use in medical procedures, comprising the steps of:
a) forming biocompatible microparticles com-prising amino acid polymer matrix containing at least one ulstrasound image enhancing material selected from the group consisting of air, glass, graphite, nitrogen, carbon dioxide, magnetic particles, magnetite, magnetic iron oxides and carbonyl iron;
b) injecting said microparticles into a mammal to thereby alter the acoustic properties of a predetermined area; and c) ultrasonically scanning said predetermined area to obtain an ultrasound scanning image thereof.