WO1991015999A1

WO1991015999A1 - Ultrasound imaging technique using non linear scattering from bubbles

Info

Publication number: WO1991015999A1
Application number: PCT/GB1991/000649
Authority: WO
Inventors: Alun Roy Williams
Original assignee: The Victoria University Of Manchester
Priority date: 1990-04-26
Filing date: 1991-04-24
Publication date: 1991-10-31
Also published as: PT97481A; IE911392A1; ZA913182B; GB9009423D0; AU7761691A

Abstract

An improved scanning method and apparatus using ultrasonic imaging techniques, wherein microscopic bubbles present in a liquid are scanned and detected by measurement of the ultrasonic energy radiated from the bubbles at a frequency different from that transmitted (i.e. a harmonic) so that the position and/or flow of the bubble-containing liquid can be studied. This is applicable to study of a wide variety of materials, in which such a bubble-containing liquid can be introduced, but is especially applicable to the study of blood in the vascular system, especially in the micro-vasculature in tissue. By also measuring the Doppler shift of the harmonics, a measure of the speed of flow of the liquid can be obtained in addition to its position.

Description

ULTRASOUND IMAGING TECHNIQUE USING NON LINEAR SCATTERING FROM BUBBLES

This invention relates to an improved scanning method and apparatus using ultrasonic imaging techniques, more particularly for the study of the position and/or flow of liquids, and especially for the study of the position and/or flow of liquids within tissues, for example of blood in the vascular system.

It is known to use ultrasonic radiation for the study of various masses, for example body tissues, and to produce images of the internal structure of these. This technique is sometimes referred to as "pulse-echo imaging." It has the advantage that the study does not require any intrusive procedures. However, ultrasonic radiation does not distinguish between similar tissues and components, and especially cannot distinguish between the tissues and liquid-containing channels within them — especially blood vessels and other parts of the vascular system.

It has been proposed to use minute gas bubbles as a means for making the blood respond to ultrasonic scanning in a manner which enables the site of the blood (e.g. blood vessels) to be distinguished from surrounding tissues which would otherwise respond similarly and so be indistinguishable. The minute gas bubbles oscillate when driven by the ultrasonic radiation, in a manner which the surrounding tissues and bubble-free blood cannot do. As a means for getting these minute bubbles in place, it has been proposed to make compositions containing large numbers of microscopic gas bubbles (of the order of 1 to 10 um diameter) and introduce these into the vascular system to be studied, and then detect and study them by ultrasonic scanning techniques.

This is not entirely satisfactory, as both the introduction of bubbles into the vascular system and the use of ultrasonic radiation require care if hazards are to be avoided. Bubbles of microscopic size pose least potential risk, but even when using these it can be difficult to secure a satisfactory contrast between the blood and the surrounding tissues when the blood vessels are very small (the micro-vasculature) as the intensity of the ultrasonic radiation required to produce the desired contrast may approach a level at which tissue damage may result.

It has now been found Lha.- this problem can be overcome, and the scanning results (images) can be improved considerably by modifying the method and apparatus for ultrasonic scanning and the analysis of the responses obtained from the bubbles in the bloodstream of the subject under examination.

This is based on the fact that conventional ultrasound scanning and imaging systems, in normal operating mode, work by transmitting pulses of ultrasound of a given frequency and then measuring the time interval between this transmission and the reception of the reflected "echoes" from within the subject tissue being studied. The large number of very small bubbles behave collectively as a large reflector. This system (as in any normal scanning system) relies on measurement of reflected radiation of the same frequency as that transmitted.

We have now found that the method can be greatly improved by utilising the ability of the gas bubbles to transform the frequency of the ultrasonic radiation to which they are subjected (i.e. emit frequencies different than those they receive), and therefore using measurements of these other frequencies. The bubbles respond virtually instantaneously to the ultrasound pulse they receive and radiate variations (harmonics) of the driving frequency.

Thus according to the present invention there is provided an improved method for the study of the position and/or flow of liquid by an ultrasonic imaging procedure wherein microscopic bubbles are present in the said liquid and these are detected by their ability to respond to the ultrasonic radiation, which comprises the step of including a measurement of the ultrasonic energy which is radiated from said bubbles and has a frequency which is different from the frequency as transmitted by the ultrasonic source in the imaging procedure.

The invention also provides an apparatus for the study of the position and/or flow of liquid by an ultrasonic imaging procedure wherein microscopic bubbles are present in the said liquid and these are detected by their ability to respond to the ultrasonic radiation, which comprises means for transmitting pulses of ultrasonic radiation into the subject to e studied and means for measuring the ultrasonic energy- which is radiated from said bubbles and has a frequency which is different from the frequency as transmitted by the ultrasonic source in the imaging procedure.

Alternatively stated, the invention provides an apparatus for the study of the position and/or flow of liquid which comprises means for transmitting pulses of ultrasonic radiation into the subject to be studied and means for detecting the radiations from said bubbles in response to the said pulses at one or more frequencies different from that transmitted, a means for processing or analysing the radiated pulses from the subject under examination to separate and/or select data relating to at least one frequency which is different from that transmitted, and means for recording and/ r displaying the data.

These different frequencies radiated from the bubbles may be higher or lower than the transmitted frequency used for excitation of the bubbles and are conveniently referred to respectively as "harmonics or sub-harmonics" and the transmitted frequency is usually referred to as the "fundamental." It is important for the purposes of this invention to recognise that it is these transformed frequencies radiated from the micro-bubbles under excitation by the pulses of ultrasound which are relevant and used. These should not be confused with any changes of the fundamental which may be produced by mere movement of the bubbles as a result of a Doppler shift of simply reflected radiation; this Doppler effect is not at the root of the present invention, and the term "different frequency" as used herein does not include changed frequencies which owe their change solely to a Doppler shift of the fundamental.

The invention may thus be seen as a modification of the conventional ultrasound scanner system (method and apparatus) so that it can detect or select one or more of the new frequencies (conveniently referred to as "harmonics") radiated from the micro-bubbles for display (e.g. on a screen) using the conventional "time of flight" concept except that the in this case it is the time delay between sending out the exciting pulse and receiving a radiated harmonic at a different frequency. The intensity of these radiated signals can be measured and used more easily because the usual back-scattered signals from the same bubble (i.e. at the frequency as transmitted) can be filtered out, and the surrounding tissue will not be reflecting or emitting ultrasound at the same frequency as these radiated signals, with the result that the signal-to-noise ratio is very much improved and limited only by electronic noise.

The parameters of the ultrasound pulse emission (for example the frequency, pulse duration, frequency and duration of the pulse emission, and the intensity of the ultrasound transmitted) may be varied according to the particular circumstances and the choice for any particular case will be well within the skill of the expert in the art. Care should be taken to ensure that these factors are kept within safe limits and cause no damage or undesirable effects, for example to adjacent blood cells or the walls of the vessels of the micro-vasculature. The invention is especially applicable to the study of body tissues when the liquid is blood (i.e. the bloodstream) but may be applied to other liquids within the tissues if desired. It is especially suited to the study of live tissue and subjects.

The invention is especially applicable to the study of liquids within body tissues, and in this case is most applicable to the study of blood (i.e. the bloodstream) , but may be applied to other liquids within the tissues if desired. It is especially suited to the study of live tissue and subjects. However, use of the invention is not limited to the study of organic tissues, live or dead, but may also be applied to the study of other liquid systems within body tissues. For example it may be applied to the study of cavities or areas within a tissue or body, if that can be filled (wholly or partly) with a liquid in which the requisite micro-bubbles can be present. This renders the invention useful as a means for studying, by ultrasound scanning, a variety of body cavities and internal channels which may be difficult to study or "image" by other techniques.

Further, therefore, the invention provides a method and apparatus for the study of any system in which there are areas (channels, cavities or the like) in which a liquid containing micro-bubbles can be present or can be introduced.

The invention thus provides a method for the study of cavities and the like by introducing into them a liquid containing microscopic bubbles and then detecting these by scanning with the ultrasound and measuring the ultrasonic energy which is radiated from said bubbles and has a frequency which is different from the frequency as transmitted by the ultrasonic source in the imaging procedure.

The method and apparatus of the invention are especially valuable when the liquid under study is blood, and especially for the study of blood within tissues. This is most difficult when the blood is in very small channels (i.e. the vasculature is much smaller than the veins and arteries) as methods for examining them are not easily available, and even with the micro- ubble method as hitherto proposed the amount of bubble-containing blood reaching them can be so small that the signals obtained by conventional ultrasonic scanning may be too weak to give much information.

As the essence of the present invention lies in providing an improved method for detecting a liquid containing micro-bubbles, using ultrasound scanning techniques, the method may also be applied to the study of areas (e.g. spaces or cavities) which would not normally contain such a liquid (or, indeed, any liquid at all) but into which a bubble-containing liquid can be introduced so that, by the presence of the micro-bubbles, the areas can be rendered detectable by ultrasonic scanning. This may be applied for example to the study of a wide variety of body tissues, for example organs (e.g. kidneys) or tracts or parts of these (for example the fallopian tubes) to discover their form and any peculiarities or faults in them. It is not essential that the subject examined be an organic tissue, and it can be anything — natural or artificial — containing spaces in which the bubble-containing liquid can be introduced, and the material surrounding the said liquid is permeable to the ultrasonic radiation and does not itself resonate in a manner which obscures the effect of the bubbles and does not hinder the freedom of the micro-bubbles to resonate. Thus the invention may be applied to the study of natural, artificial or synthetic materials, or articles made from them.

The invention also provides an apparatus for the study of the position and/or flow of liquid by an ultrasonic imaging procedure wherein microscopic bubbles are present in the said liquid and these are detected by their ability to respond to the ultrasonic radiation, which comprises means for transmitting pulses of ultrasonic radiation into the subject to be studied and means for measuring the ultrasonic energy which is radiated from said bubbles and has a frequency which is different from the frequency as transmitted by the ultrasonic source in the imaging procedure.

Alternatively stated, the invention provides an apparatus for the study of the position and/or flow of liquid which comprises means for transmitting pulses of ultrasonic radiation into the subject to be studied and means for detecting the radiations from said bubbles in response to the said pulses at one or π re frequencies different from that transmitted, a means for processing or analysing the radiated pulses from the subject under examination to separate and/or select data relating to at least one frequency which is different from that transmitted, and means for recording and/or displaying the data.

In one form, the present invention may utilise the measurement of a single received frequency which is different from the frequency transmitted (i.e. is transformed by the micro- bubbles) , and in this case the data from measurement of the received radiation can be used to form a single image which can be used for study. Alternatively, the invention may be used to include the measurement of several frequencies, and in this case these frequencies may all be different from the transmitted frequency or may include the transmitted frequency; the data fro

^S measurement of these frequencies may be used to form multiple images (corresponding to different frequencies) and these can be compared.

The signals received may be processed or analysed by a variety of methods, for example by making the receiving transducer selective towards the desired harmonic or harmonics (so that it partly or completely ignores the fundamental), or by using filters to separate the various frequencies and accept or reject them appropriately, or by any combination incorporating such means.

An apparatus according to the invention therefore preferably includes means for comparing data relating to one or more components of the received pulses which are of different frequency from the transmitted frequency with data relating to other received frequencies, which may optionally include reflections which are of the same frequency as transmitted.

The size of the bubbles and the methods and compositions which may be used for getting these minute bubbles in place (e.g. introducing them into the vascular system to be studied) are essentially the same as hitherto proposed, for example the preparation SHU 454 (also called "Echovist") manufactured by Schering AG, Berlin. Further modifications of this preparation (for example SHU 508) contain gas bubbles which are able to pass through the lungs and give ultrasound contrast within the left side of the heart and arterial circulation even though the agent has been introduced into the venous circulation.

The bubble size is usually in the range 1 to 10 am, and especially in the range 1 to 5 um, but may be larger or smaller if desired and may be optimised so as to resonate at the frequency of the ultrasound used. The nature of the gas in the bubbles may be any that is not harmful to the subject under examination, and especially as used in the known art.

Likewise, the methods and apparatus used for carrying out the scanning or imaging according to the present invention and the procedures used for collecting, processing and presenting the data, may employ the same general principles as those hitherto employed in conventional ultrasonic scanning or imaging. The modifications requires are those appropriate to allow the detection (reception) and measurement of the frequencies which are not the same as those transmitted, and to allow these to be distinguished and processed so that data relating to them can be examined either alone or in comparison with other data, for example that relating to the conventional echoes received at the same frequency as that transmitted.

The characteristics of the ultrasound pulses used are comparable with those in current standard use for ultrasonic scanning, Thus, the transmitted ultrasound frequency used is conveniently in the range 1 to 20 MHz, and this and such factors as the power levels, pulse length and interval between pulses may be optimised for the particular frequency and the various circumstances of any particular use.

In the presentation of the data it is preferred to use means for comparing the image derived from (a) the detection and measurement of ultrasound radiated from the bubbles and different frequency from that transmitted with that derived from (b) the detection and measurement of reflected radiation of the same frequency as that transmitted.

The present invention also provides a method as defined above wherein the subject tissue under examination is examined twice, (a) with the micro-bubbles present and (b) without them being present, and comparing the results from these two examinations.

Advantageously, the method comprises examining the subject by multiple scans, with and without the bubbles present, and comparing the results of the different scans. Thus, in the case of the examination of tissues, it comprises ultrasound scanning of the subject:-

(a) after administration of the bubble-containing composition to introduce it into the bloodstream and the bubbles have reached the the site under particular study, and (b) without the presence of the introduced bubbles, and comparing the results from these two examinations.

^SUB^STITUTE SH The two measurements may be made in either _.order, and may be repeated if desired. The sequence may be determined as may be most convenient for clinical practice.

The analysis, separation, display or any combination of these are achieved most conveniently by electronic means, many of which are well known and either available or readily devised by any expert in the art of electronics to meet any stipulated specification of performance.

Such means for analysis and/or separation of the data relating to the different frequencies may be sited anywhere which is most convenient for the constructor or the user. For example, it may be most convenient to site them in or near the unit for the recording and/or display of the data, but if desired they may be incorporated in the transducer unit ( transmitter or transmitter/receiver) so as to concentrate the main new features of the circuitry in a convenient single unit.

The display system may use any convenient means or mode known or available for this purpose. A very convenient mode for this comprises superimposing a record corresponding to the echoes for the "different" and the "original" frequencies on a single display medium (e.g. a video screen) . To emphasise the difference, the traces or data may be in different colours to assist the observer to distinguish between them.

This may be done, for example, by using a CRT (cathode ray tube) display in which the different traces are produced simultaneously, or the records corresponding to different frequencies may be displayed in sequence (especially alternately — sometimes termed "an alternating frame display") to simulate simultaneous display. Alternative forms of display devices may be used if desired.

A very convenient mode of display is to process the incoming signals (ultrasonic energy) and present those which correspond to frequencies other than that transmitted on a video screen in a manner which enables the user to observe it concurrently (simultaneously) with other data.

For the purposes of putting the invention into practice with

^S minimum cost and minimum need to replace existing equipment, the invention also provides modification units, adapted to be suitable for use in conjunction with existing scanning or imaging equipment. Especially, such modifying units these may be modified ultrasonic transducer units, signal processing units, and data display units adapted for use in the method of the invention as defined above. These modifying units include:-

(1) an ultrasonic transducer assembly for use in the apparatus and method defined above, which comprises a combination of means for transmitting pulses of ultrasonic radiation into the subject to be studied together with means for detecting ultrasonic energy which has a frequency which is different from the frequency as transmitted by the ultrasonic source. This is adapted so that it can (a) transmit pulses of ultrasonic radiation of a chosen frequency and (b) receive ultrasonic radiation of at least one frequency which is different from the frequency used for transmission. This may, if desired, be adapted to receive over a band of frequencies (a "broad band" transducer) or at one or more different chosen frequencies, optionally including that at which it transmits.

The same transducer may be used to generate the transmitted pulses and to receive the incoming radiated frequencies induced by the pulses. As an alternative, one or more additional sensitive transducers may be used to detect the radiated frequencies; these may be separate from the transmitter or may be incorporated within the transducer assembly.

This may be constructed of conventional materials and components, arranged in any manner or form which can achieve the desired result. This will be easily determinable by an expert in the art of transducer production.

Such an ultrasonic transducer assembly can be one wherein the transmitting and receiving means are combined to constitute a single unit, i.e. a combined transmitting/receiving transducer assembly. This is preferably constructed so that separate

^SUB transmitting and receiving transducer elements are used. This is because the conventional construction of a transducer for ultrasonic scanning employs a single transducer which transmits the ultrasonic pulses but is constructed so that, after transmitting, its vibration is quickly stopped (usually by material which loads it or damps its vibrations) so that it is then ready to receive the reflected "echo" from the target and be excited by it. Unfortunately, this makes the transducer very inefficient as a receiver and have poor sensitivity. so, by employing one transducer for the pulse transmission and a separate transducer for the reception of the incoming "echo," it is possible for the transmitting transducer element to have the customary damped form while the receiving element can be made in a form which is more sensitive to the frequency to be received, thus improving the overall effectiveness and sensitivity of the system. This "receiving" transducer element may function either by greater sensitivity (e.g. through reduction in the damping action) or by being made more selective to the incoming frequency as that will, in the present invention, no longer be the same as that transmitted. This selective effect may be part of the construction of the transducer itself, or may be in associated means for processing the signal received, especially by "tuning" the transducer so as to enhance its sensitivity to the desired harmonic or to reject unwanted frequencies, especially the fundamental.

(2) a display system for use in the apparatus and method defined above, which comprises a combination of means for preparing a record of the incoming radiated frequencies induced by the transmitted pulses at one or more frequencies different from that transmitted. this may such as to record data relating to one selected frequency or to several frequencies, and may optionally be such as to produce a record in a form suitable for permanent or temporary retention (e.g. storage for future use) or such as to produce the data in the form of an immediate display, or any combination of these.

The preferred form of display is one which processes signals representative of the incoming ultrasonic frequencies from the subject and presents signals which correspond to a frequency other than that transmitted with signals corresponding to another frequency (which may be either the transmitted frequency or another also different from the transmitted frequency) .

For some applications, the one- or two-dimensional displays of the echoes at the fundamental frequency and at harmonic frequency or frequencies may be visualised on different display monitors. (3) a signal processing unit for use in the apparatus and method defined above, which comprises means for receiving the incoming frequencies of the transmitted ultrasonic pulses detected by a detecting transducer and processing them to distinguish at least one component which has a frequency different from that of the transmitted pulse.

Such an analyser may function in a variety of modes, for example by use of filters or other selective circuitry, so that the incoming frequencies are either separated (so that more than one can be used) or so that only selected ones are retained and others, regarded as unwanted, are rejected.

Another variant which can have advantages in practice, for minimising the need to modify existing equipment, comprises irradiating the target area of the subject with pulses of ultrasound from transmitting transducers positioned separately from the receiving transducer. The receiving transducer may then be used and adapted as appropriate and by whatever means are most convenient, so that the desired harmonic frequencies are detected for display.

The acoustic spectrum radiated by a gas bubble driven to oscillate by an ultrasonic pulse is complex and is also changed by the physical constraints placed upon that bubble. Thus, it may be necessary to to detect a higher harmonic or a lower harmonic (a sub-harmonic) frequency (or both) to enable the bubbles to be detected when they are within the capillary micro- vasculature of a tissue as against the same bubble within a large blood volume. It may be necessary to detect two related

S harmonics or sub—harmonics or one or more of both a harmonic or sub-harmonic in coincidence to derive an unambiguous signal characteristic of that bubble in a particular environment.

The generation and subsequent emission of harmonics and sub- harmonics by a bubble is virtually instantaneous and so the time delay between the moment the fundamental acoustic pulse was emitted and the harmonic signals were received can be processed in exactly the same way as the fundamental echoes are processed to obtain the analogous spatial distribution of the bubbles within the irradiated volume.

If the bubbles are moving, then the received harmonics are sub-harmonics will be Doppler-shifted by an amount proportional to the magnitude of the velocity of the bubbles and their orientation relative to the exciting and/or receiving transducers. Measurement of this Doppler shift can be very useful as an aid for providing information on the speed of movement of the bubbles (and hence of the liquid carrying them) in addition to the information about the location of the bubbles.

For some applications there may be additional advantages to be obtained if the received harmonic signals are electronicall combined with an appropriate constant frequency signal to obtain the magnitude of the Doppler-shift as the beat frequency.

Another method of presenting the additional information provided by the presence of the gas bubbles is to subtract the magnitude of the fundamental and/or higher or lower harmonic signal obtained from a given tissue volume before the gas bubble contrast agent has been administered away from the same signal obtained from the same tissue volume after the gas bubble contrast agent has been administered. The magnitude of the signal resulting from this subtraction process is a direct indication of the bubble density within that tissue volume.

A very convenient mode for operating the method of the invention comprises making an examination of the subject tissue twice, once before administration of the bubble-containing composition so as to introduce it into the bloodstream and again after the administration has been made and the bubbles have

^S reached the the site under particular study. This "before and after" mode of examination can be of especial value in the study of very small vessels in the vascular system, and can diminish the susceptibility of the method to interference and increase its sensitivity. The data for the two scans can be compared in any appropriate or convenient manner.

The invention also comprises the use of the known components as integers for making an apparatus and/or for operating a method of imaging as described above. The invention can be used to provide positional information for the presence of blood-borne gas bubbles, which can be superimposed on top of the "existing" anatomical display to demonstrate whether or not those tissues are being perfused with blood. This new technique greatly extends the range of clinical investigations that can be performed using diagnostic ultrasound imaging systems.

It can permit both qualitative and quantitative information to be obtained concerning the vascular perfusion of selected regions of tissue and has many applications in medical practice. Scsne examples of the medical applications where these gas-bubble induced signals would provide additional and valuable clinical information include:-

(a) The detection of ischaemic regions of cardiac muscle following a heart attack. (The trauma associated with the intravenous injection of a gas bubble preparation which can pass through the lungs and be detected by an ultrasound device would be much less than attempting to get the same information using X-ray techniques. )

(b) The detection of ischaemic regions in kidneys or within the maternal side of the placenta.

(c) The detection and quantification of the size of ischaemic regions within the brain following a stroke.

(d) The detection of stenoses and partial or even complete occlusion of blood vessels. In this application the Doppler display presentation mentioned above can be the most efficaceous, as the blood velocity is especially significant

^SU in diagnosis and treatment, (e) The examination of organ transplants to check whether the required degree of perfusion of the vasculature is taking place. (This is very important in determining the success or failure of a transplant and can give some warning of whether failure of the transplant is imminent or emergency action may be required to save the patient. )

Claims

CLAIMS: -

1. A method for the study of the position and/or flow of liquid by an ultrasonic imaging procedure wherein microscopic bubbles are present in the said liquid and these are detected by their ability to respond to the ultrasonic radiation, which comprises the step of including a measurement of the ultrasonic energy which is radiated from said bubbles and has a frequency which is different from the frequency as transmitted by the ultrasonic source in the imaging procedure.

2. A method as claimed in Claim 1 adapted for the study of areas in which a liquid containing micro-bubbles can be present or can be introduced, which comprises introducing into the said areas a liquid containing microscopic bubbles and then detecting these by scanning with ultrasound and measuring the ultrasonic energy which is radiated from said bubbles and has a frequency which is different from the frequency as transmitted by the ultrasonic source in the imaging procedure.

3. A method as defined in Claim 1 or Claim 2 wherein the subject under examination is examined (a) after administration of the bubble-containing composition to introduce it into the liquid and the bubbles have reached the the site under particular study, and (b) without the presence of the introduced bubbles, and the results from these examinations are compared.

4. A method as claimed in any of Claims 1 to 3 wherein the frequency of the received ultrasonic radiation (and especially that which has a frequency different from that transmitted) is compared with the frequency received from the introduced bubbles when these are static, so as to determine the rate of movement of the said bubbles within the subject under study by their difference and reference to the Doppler effect.

5. A method as claimed in any of Claims 1 to 4 wherein the liquid studied is blood within the vascular system of body tissues.

6. A method for the study of cavities and the like by introducing into them a liquid containing microscopic bubbles

S and then .detecting these by scanning with the ultrasound and measuring the ultrasonic energy which is radiated from said bubbles and has a frequency which is different from the frequency as transmitted by the ultrasonic source in the imaging procedure, using a method as claimed in any of Claims 1 to 5.

7. An apparatus for the study of the position and/or flow of liquid by an ultrasonic imaging procedure wherein microscopic bubbles are present in the said liquid and these cure detected by their ability to respond to the ultrasonic radiation, which comprises means for transmitting pulses of ultrasonic radiation into the subject to be studied and means for measuring the ultrasonic energy which is radiated from said bubbles and has a frequency which is different from the frequency as transmitted by the ultrasonic source in the imaging procedure.

8. An apparatus for the study of the position and/ r flow of liquid which comprises means for transmitting pulses of ultrasonic radiation into the subject to be studied and means for detecting the radiations from said bubbles in response to the said pulses at one or more frequencies different frccn that transmitted, a means for processing or analysing the radiated pulses from the subject under examination to separate and/or select data relating to at least one frequency which is different from that transmitted, and means for recording and/or displaying the data.

9. An apparatus as claimed in Claim 7 or Claim 8 which includes means for comparing data relating to one or more components of the received pulses which are of different frequency from the transmitted frequency with data relating to other received frequencies, which may optionally include reflections which are of the same frequency as transmitted.

10. An ultrasonic transducer assembly for use in the method claimed in any of Claims 1 to 6 or in an apparatus s claim-ad in any of Claims 7 to 9, which comprises a combination of means for transmitting pulses of ultrasonic radiation into the subject to be studied together with means for detecting ultrasonic energy which has a frequency which is different from the frequency as transmitted by the ultrasonic source.

11. An ultrasonic transducer assembly as claimed in Claim 10 wherein the transmitting and receiving means are combined to constitute a combined transmitting/receiving transducer and is constructed so that separate transmitting and receiving transducer elements are used, the transmitting element being of customary damped form and the receiving element being of a form which is more sensitive to a harmonic of the transmitted frequency.

12. A display system for use in the method claimed in any of Claims 1 to 6 or in an apparatus as claimed in any of Claims 7 to 9, which comprises a combination of means for preparing a record of the incoming radiated frequencies induced by the transmitted pulses at one or more frequencies different from that transmitted and may be such as to record data relating to one selected frequency or to several frequencies, and may optionally be such as to produce a record in a form suitable for permanent or temporary retention (e.g. storage for future use) or such as to produce the data in the form of an immediate display, or any combination of these.

13. A form of display as claimed in Claim 12 which processes signals representative of the incoming ultrasonic frequencies from the subject and presents signals which correspond to a frequency other than that transmitted with signals corresponding to another frequency (which may be either the transmitted frequency or another also different from the transmitted frequency) .

14. A signal processing unit for use in the method claimed in any of Claims 1 to 6 or in an apparatus as claimed in any of Claims

7 to 9, which comprises means for receiving the incoming frequencies of the transmitted ultrasonic pulses detected by a detecting transducer and processing them to distinguish at least one component which has a frequency different from that of the transmitted pulse.

15. A modification unit, for use in conjunction with existing ultrasonic scanning or imaging equipment, comprising ultrasonic transducer means adapted to (a) transmit pulses of ultrasonic radiation of a chosen frequency and (b) receive ultrasonic radiation of at least one frequency which is different from the frequency used for transmission.

16. A method for the study of the position and/or flow of a liquid by an ultrasonic imaging procedure, substantially as described.

17. An apparatus for the study of the position and/or flow of a liquid by an ultrasonic imaging procedure, substantially as described.

18. A transducer, signal processing device, display or any modification unit adapted for the modification of an ultrasound imaging apparatus, substantially as described.