GB2356932A - Measuring tissue properties - Google Patents

Abstract

Tissue properties, eg bone density are determined by disposing an ultrasound detector 31 comprising a plurality of ultrasound receiving elements adjacent the tissue, insonifying the tissue with a broad-band ultrasound field from an ultrasound transmitter 30 and capturing the signal transmitted through the tissue with each ultrasound receiving element. The transmitted signal is captured substantially simultaneously at each ultrasound receiving element; and the attenuation of ultrasound within the tissue is determined at more than one frequency for the paths between the transmitter and each of the receiving elements. The apparatus may be used for in vivo diagnosis of osteoporosis; or it may be used to inspect animal tissue or vegetative tissue such as wood.

Description

2356932 Systerns for Measuring Tissue Properties The present invention

relates to systems for determining properties of tissue, and in particular to methods and apparatus for determining the properties of tissue in vivo using ultrasound. The tissue includes both non-mineralised tissue and mineralised tissue, such as bone.

The incidence of the disease osteoporosis, which is the loss of bone mineralisation, is increasing. One reason for this is that the disease occurs primarily in people who lead inactive lives and do not eat balanced diets, and the number of these people is increasing as a result of the general shift of jobs away from manual labour to non manual labour, and as a result of the increasingly poor diet, for example low in calcium.

The increasing average life span of humans is also contributing to the increased incidence of the disease. There is therefore a need for a simple test for osteoporosis, so that the onset of the disease can be detected as soon as possible and its progress monitored.

There are known invasive techniques for investigating the conditions of the bones of a person. These are, however, undesirable to use as a routine screening measure to determine whether a person is suffering from the early stages of the disease. As a routine screening measure, a non-invasive technique that can be carried out without requiring hospitalisation of a patient is highly desirable.

Canadian Patent No. 1,323,090 discloses an ultrasonic densitometer device. This consists of two ultrasonic transducers, and the device is used by placing one transducer on either side of a limb of a patient, such as a leg. Ultrasound radiation is emitted by one transducer, and is detected by the second transducer after passage through the tissue 2 and bone of the limb. It is possible to determine the attenuation of the ultrasound radiation by the bone and/or the speed of propagation of ultrasound radiation within the bone, and these properties provide information about the condition of the bone. The attenuation of ultrasound radiation in a bone is an indication of the mineral content of the bone, whereas the velocity of ultrasound radiation in a bone is proportional to the density of a bone. The attenuation and velocity of ultrasound are therefore useful parameters in the diagnosis of osteoporosis, and also are predictors of the possible risk of fracture of a bone.

The transducers described in Canadian Patent No. 1,323,090 each consist of an array of elements, with the array of elements on one transducer being a mirror image of the array of elements on the other transducer. In use, one element of one transducer is caused to emit ultrasound, and this is detected by the corresponding element on the other transducer. The remaining elements of the first transducer are then activated in sequence, with the ultrasound emitted by each element being detected by the corresponding element of the other transducer.

Since the elements of the emitting transducer are actuated in sequence, it takes a relatively long time to activate all the elements and so build up a ultrasound scan over the entire area of the transducer. This means that the time taken to scan a patient is undesirably long, and it is difficult to immobilise the limb sufficiently for this length of time. With current systems the patient must remain still for 3-4 minutes, which is very difficult. This is particularly so because movement of one part of the body can affect another - for example even a small knee movement can move the heel bone sufficiently to affect a measurement.

According to a first aspect of the invention there is therefore provided apparatus for determining tissue properties comprising: an ultrasound transmitter; excitation means to cause the transmitter to emit an ultrasound radiation field at a plurality of frequencies; an ultrasound receiving transducer comprising a plurality of ultrasound receivers, each having a receiver output, to provide a corresponding plurality of receiver output signals; 3 and processing means, coupled to the plurality of receiver outputs, to process the receiver output signals and to record representations or characteristics of output signals corresponding to ones of the plurality of frequencies.

According to a second aspect of the invention there is provided method of determining tissue properties comprising the steps of. disposing an ultrasound detector comprising a plurality of ultrasound receiving elements adjacent the tissue; insonifying the tissue with an ultrasound field at more than one frequency from an ultrasound transmitter and capturing the signal transmitted through the tissue with each ultrasound receiving element, the transmitted signal being captured substantially simultaneously at each ultrasound receiving element; and determining the attenuation of ultrasound within the tissue at more than one frequency for the paths between the transmitter and each of the receiving elements.

According to a further aspect of the invention there is provided a method of determining tissue properties comprising the steps of: disposing an ultrasound detector comprising a plurality of ultrasound receiving elements adjacent the tissue; insonifying the tissue with an ultrasound field from an ultrasound transmitter and capturing the signal transmitted through the tissue with each ultrasound receiving element, the transmitted signal being captured substantially simultaneously at each ultrasound receiving element; and determining the velocity within the tissue of ultrasound transmitted along the paths between the transmitter and each of the receiving elements.

In the present invention, an ultrasound source that can insonify all the receiving elements of the detector simultaneously is used, so that the whole area of the detector may be scanned simultaneously. The present method is potentially therefore considerably quicker than the method disclosed in Canadian Patent No. 1, 323,090 in which, as noted above, the transmit elements are scanned sequentially. The correct alignment of the transducers is also less critical than in '090.

4 Figure 1 is a schematic view of a device of the present invention prior to positioning for scanning a patient; Figure 2 is a cross sectional view of the receiving transducer of the device of Figure I; Figure 3 is a transverse section of the receiving transducer of Figure 1 taken along the line III-III of Figure 2; Figure 4 is a partial enlarged, schematic perspective view of the receiving transducer of the device of Figure I; and Figure 5 is a block circuit diagram of the receiving transducer of the device of Figure 1.

Figure 1 is a schematic view of a device for use in a method of the present invention. It consists essentially of a transmissive transducer or transmitter 30 for emitting ultrasound radiation, and a receiving transducer 31 for detecting ultrasound radiation. A member 32 of a patient, such as the heel of the patient, is disposed between the transmitter 30 and the receiving transducer 3 1. The member 32 is shown in cross-section, and contains a bone 33 surrounded by tissue 34.

A dry coupling pad 35, 36 is provided on each of the transducers 30, 31. These coupling pads 35,36 are provided to improve the acoustic coupling between the transducers and the member 32, by conforming the profile of the transducers to the profile of the tissue. The dry coupling pads may consist of, for example, a compliant silicone pad, with a small quantity of ultrasound gel (not shown) disposed between the pad and the member 32. The coupling pads 35,36 are compliant and compress onto the gel-coated limb as the transducers are moved towards the limb.

The transmitter 30 emits, when activated, an ultrasound wave, preferably planar, with a centre frequency typically in the range 530-55OkHz. The transmitter 30 can be made of, for example, a piezo-ceramic material, or another suitable material.

2 The transmitter 30 has a plane wave transmission area of approximately 45 cm. The transmitter is disposed in a protective casing made of, for example, hard anodised aluminium. An integral connector 38 is mounted on the rear of the casing, for making electrical connections to the transmitter The front face of the transmitter may be provided with an acoustically transparent wear face, in order to protect the front face of the transmitter from degradation and damage.

The receiving transducer 31 is a multi-element transducer and contains two or more receiving elements. The receiving elements are preferably arranged in a two dimensional array.

One embodiment of the receiving transducer 31 is illustrated in Figures 2 and 3. In Figures 2 and 3, the receiving transducer 31 contains forty-five receiving elements 2, which are arranged in a nine-by-five two-dimensional grid which occupies an area of approximately 25cm 2. The invention is, however, not limited to a receiving transducer having precisely this number and arrangement of receiving elements and a preferred arrangement has an even number of elements in each direction, for example 8 by 16 elements.

The receiving transducer 31 consists of an array of electrodes 2 embedded in an insulating matrix 4. Any material that provides suitable electrical isolation between the pins, and has sufficient mechanical strength and suitable acoustic properties can be used as the material for the insulating matrix 4. Suitable materials include, for example, epoxy resins, silicone rubbers, polyurethane, and polybutadiene based materials.

6 A PV13F (polyvinylidenediflouride) layer 8 is disposed over the upper surface of the insulating matrix 4. A layer of adhesive 12 is disposed between the upper surface of the insulating matrix 4 and the lower face 10 of the PVW film 8. The adhesive is required to be electrically non-conducting, so as not to short out the electrodes 2 to one another.

An electrode 18 is disposed over the upper surface of the PVDF layer. The electrode 18 is, for example, a gold film.

The insulating matrix 4 is contained within a casing 6 made of an electrically conductive material. The outer casing 6 is connected to the electrode layer 18 by one or more connectors 20 (two are shown in Figure 2) which consist of, for example, conducting epoxy resin.

One end 22 of each of the electrodes 2 projects from the insulating matrix 4, to enable the electrodes to be electrically connected to appropriate measuring circuitry. A connector (not shown) may be provided to mate to the projecting ends 22 of the electrodes 2, or wires or other connections may be attached directly to the projecting ends 22 of the electrodes 2, for example by soldering. As a ftirther alternative, the projecting ends 22 of the electrodes may be polished flat to provide an array of pads for touch or pressure connection.

The principle of operation of the detector of Figures 2 and 3 is that the upper end surfaces 24 of the electrodes 2 are coupled electrically to the casing 6 (via at the film 8 and electrode 8) by ohmic/capacitive coupling. When the PVW film 8 is stressed by ultrasound radiation, the coupling between the electrodes 2 and the outer casing 6 changes, and detection of this change in coupling enables detection of received ultrasound radiation. It has been found that the end surfaces 24 of the electrodes are coupled only to the area of the PVW film immediately in front of them, and that fringing effects from the surrounding area are not significant. Thus, the receiving transducer of Figures 2 and 3 effectively operates as if it were an array of discrete receiving transducers.

7 The receiving transducer of Figures 2 and 3 is generally of the type disclosed in W096/25244, the contents of which are hereby incorporated by reference.

Figure 4 is an enlarged partial view of another receiving transducer. This differs from the transducer of Figures 2 and 3 in that an electrical ground is disposed within the insulating matrix 4, between each pair of adjacent conductors. The electrical ground consists of a first array of conductive plates 26 and a second array of conductive plates 27; the conductive plates 26 in the first array extend in a direction that is substantially perpendicular to the direction in which the conducting plates 27 in the second array extend. All the conductive plates extend over substantially the entire thickness of the insulating matrix 4, and are earthed which improves isolation between individual elements.

In operation, an ultrasound radiation field is emitted by the transmitter 30. The ultrasound radiation is received by the receiving transducer, and is detected by each of the detecting elements in the array of detecting elements in the receiving transducer. It is thus possible to obtain details of the spatial variation of the received ultrasound field at the receiving transducer. From this, it is possible to obtain information on the structure of the bone 33 through which the ultrasound radiation has passed.

In the present invention, an ultrasound source that can insonify all the receiving elements of the receiving transducer 31 is used as the transmitter 30. Turthermore, since the receiving elements 2 of the receiving transducer 31 are independent from one another, it is possible to detect the ultrasound field received at each receiving element 2 substantially simultaneously. The time taken to capture data at each element is typically 10 milliseconds. Although we will describe the use of multiplexers to simplify the electronics, it is possible to capture the data from all the elements simultaneously, for example by not multiplexing the outputs together.

8 Figure 5 is a schematic block circuit diagram of suitable processing electronics for the present invention.

The ultrasound transmitter 30 is controlled by a function/sync generator 40. The function/sync generator generates a pulse or a series of fixed frequency tone bursts of suitable amplitude to excite the ultrasound transmitter 30 and cause it to emit ultrasound radiation.

The receiving transducer 31 is connected to a multi-element buffer circuit 42 via an acoustically optimised backing having electro-magnetically shielded connections. A multiplexer 43 enables the buffered signal from any particular element of the detector array to be selected for further processing.

The signal from the receiver element selected by the multiplexer circuit 43 is passed to a computer 50, for example a personal computer (PC), by means of a gain control circuit 44, an anti-aliasing filter 45, a drive amplifier and isolation circuit 46, an electro magnetically shielded cable 47, an input pre-amplifier 48 and an analogue- to-digital converter 49. The multiplexer circuit 43, the gain control circuit 44 and the anti aliasing filter 45 are controlled by the computer 50, by means of electronically controlled decoder circuits 51, 52.

Once a signal from an element of the receiving transducer has been processed by the computer 50, it can be displayed on a VDU, stored on a floppy disc, stored in the computer's memory, printed out onto paper, or treated in other conventional ways.

The multiplexer 43 is able to switch between receiving elements in less than Ims and thus the acoustic signal which has been transmitted through the tissue can be recorded in near real-time. Near real-time, so far as the patient is concerned, is sufficiently fast for the patient to have little or no difficulty in remaining still during the measurement procedure. Potential limitations on the total time required to scan all the elements in the receiving transducer are the time taken to acquire data in the data acquisition system, 9 and/or the time taken to transfer the acquired data to the computer 50. The total time needed depends on the number of data points, but typically 1000 data points can be acquired in less than 10 seconds. The multiplexer can be synchronised to function/sync generator 53, to sequentially select receiver elements in sync with emitted ultrasound pulses. If desired, faster sample acquisition can be achieved with greater parallelism, using a plurality of A/D converters 49 each with associated multiplexer circuity 43.

One potentially rate limiting step to the speed of operation of the system is the transit time of the ultrasonic signal through the tissue. As a rule of thumb, this transit time can be roughly estimated at 1.5 microsecond per millimetre, giving, for example, a transit time of approximately 300 microseconds for 200 millimetres of tissue.

The A/D converter 49 will generally require a high frequency clock (72WIZ in one embodiment) in order to properly capture the received ultrasound signal. Account should preferably also be taken of the tendency of a ceramic ultrasound transducer to ring after an ultrasound pulse, and preferably this ring should be allowed to decay. The transit time of the ultrasound signal can be made the rate limiting step of the system by arranging the transmit pulse and signal capture so that the pulse ringing decays whilst the ultrasound signal is in transit through the tissue, and so that the signal A/D conversion and capture occurs whilst a subsequent pulse issues and is in transit from the transmitter 30.

Thus it is possible to arrange the system so that emitted ultrasound pulses (tone bursts or discrete pulses) are emitted and processed in less than 100 milliseconds, preferably less than 10 milliseconds, and especially preferably less than 1 millisecond.

Multiplying this time by the number of receiving elements gives the time it takes to build up an ultrasound image of the tissue under investigation. If, for example, the receiving array has 192 elements and the system takes 1/60th of a second to process each element (a relatively generous allowance of time), an ultrasound image can be acquired in approximately 3 seconds which, as far as the patient is concerned, approximates to real-time.

This time can, if desired, be reduced by processing sets of elements of the 2D array in parallel. First, for example, the array could be divided into sixteen banks (or, in general, a plurality of banks) each of twelve elements. Each bank is then provided with its own multiplexer circuitry 43, and corresponding signal processing circuitry, to provide signals from the sixteen banks in parallel to computer 50. In the example given this would reduce the time to capture the data for an ultrasound image to approximately 0.2 seconds.

In operation, it is preferable that the receiving array is first calibrated. One method of doing this is to transmit ultrasound radiation through a uniform sample of a control material having well known ultrasound transmission properties. Any variations between elements that are detected in this calibration step can be allowed for in the processing of subsequent data, for example by making a flat field correction, and this ensures that any inter-element variations will have no effect on the measurement procedure. Examples of a suitable calibrant for carrying out the calibration step are water, a compliant coupling medium such as a silicon gel pad, and a phantom. The phantom is typically made from any material with attenuation comparable to bone, such as a ceramic held in a structural matrix.

One method of measuring the structural properties of a limb of a patient is carried out as follows.

The transmitter 30 is caused by function/sync generator 53 to emit an ultrasound radiation field having a predetermined frequency spectrum. The detecting elements 2 of the receiving transducer 31 detect the ultrasound radiation that is transmitted through the limb to the receiving transducer 31. The electrodes 2 are selected in sequence by the multiplexer circuit 43, and the signal captured at each electrode is processed by the computer 50.

The transmitting transducer 31 is then caused to emit a second ultrasound radiation field, having a different frequency spectrum from the first ultrasound radiation field, and the signal received at the receiving transducer 31 is again detected by the electrodes 2. The electrodes 2 are again selected in sequence by the multiplexer circuit 43, and the signal captured at each electrode is processed by the computer 50.

The transmitting transducer 30 can be caused to emit one or more further ultrasound radiation fields having different frequency spectra from each of the preceding ultrasound fields.

From knowledge of the frequency spectra of the ultrasound fields emitted by the transmitter 30, and from knowledge of the frequency spectra of the corresponding ultrasound signals received at each detector of the receiving transducer 3 1, it is possible to determine the attenuation, as a function of frequency, of the signal received at each detector of the receiving transducer 3 1. Furthermore, since the time at which the ultrasound field is emitted from the transmitter 30 is known, it is also possible to calculate the transit time of the ultrasound signal from the transmitter 30 to each detector in the receiving transducer 3 1. The acoustic signal transit time is measured by measuring the time at which the transmitter is excited and comparing it to the time at which the signal is recorded at the receiver. This enables the velocity of ultrasound radiation between the transmitter 30 and each individual receiving element of the receiving transducer 31 to be calculated.

It is thus possible to calculate the velocity of ultrasound through the bone of the patient, for paths corresponding to paths from the transmitter 30 to the individual receiving elements of the receiving transducer 3 1. The velocity of sound in the bone is related to the stiffness of the bone, so that knowledge of the velocity of sound at points of the bone provides information about the bones structure and integrity. Further details of the Broadband Ultrasonic Attenuation (BUA) of bone can be found in Langton et al., Eng.Med., 13, p.89-91.

12 In one embodiment, the transmitter 30 emits, in sequence, a plurality of ultrasound fields each containing ultrasound radiation of a predetermined frequency. The frequency of the ultrasound radiation in each field is different from the frequency of the ultrasound radiation in other fields. For example, the transmitter 30 can be excited with a series of fixed frequency tone bursts of suitable amplitude. In one embodiment there are eight tone bursts each eleven cycles in duration. Thus a tone burst typically lasts between 10ps and 20Vs, depending on the frequency of the tone. The frequencies are chosen to ensure that there is enough penetration of the tissue and to provide a broad range of frequencies from which to make the BUA measurement. Typically six or seven discrete frequencies between, say, 500 kHz and 700kHz are employed.

In this method, it is again possible to calculate the attenuation as a function of frequency, and to calculate the transit time, for ultrasound radiation transmitted from the transmitter 30 to each individual element of the receiving transducer 3 1. This again provides information about the properties of the bone on the paths from the transmitter to each receiving element of the receiving transducer 3 1.

In an alternative embodiment of the invention, the transmitter emits a pulsed ultrasound radiation field and the signal received by the receiving transducer 31 (or corresponding processed and/or stored data) is Fourier transformed before it is processed. This provides information on the attenuation as a function of the frequency. The pulse is typically around I ps in length (say, between 0.5ps and 5ps), and of a higher amplitude then that needed for a time burst, to deliver sufficient energy for reliable reception.

The acoustic data captured by the receiving element array can be presented in the form of an image to display, for example the signal attenuation, if desired at a plurality of frequencies, for each point in the receiving array. To achieve improved display resolution the array can be mechanically manoeuvred and/or electronically phased to provide additional data points.

13 In more detail, an image is formed by placing a coupling medium between the transmitter (30) and receiver (31), transmitting a signal between these and then acquiring a time domain trace for each element.

The fast Fourier transform (FFT) of each trace is taken to provide a set of frequency information for each transmitter/receiver element. The tissue to be imaged is then inserted between the transmitter and receiver and again a signal is transmitted from transmitter (30), a time domain trace is acquired for each element of receiver (3 1), and the FFT of each trace is calculated to provide a second set of frequency information.

The ratio of the two sets of frequency measurements is then taken to determine the attenuation as a function of frequency for each transmitter/receiver element. This provides Broad Band Ultrasonic Attenuation information for each element position, which can be used to generate the image Other alternative arrangements will occur to the skilled person and the invention is not limited to the described embodiments. For example, the invention can be used for vegetative tissue such as wood as well as animal tissue, for example, for non-invasive investigation of infestation of wooden beams or furniture.

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Claims (19)

CLAIMS:

1. Apparatus for determining tissue properties comprising:

an ultrasound transmitter; excitation means to cause the transmitter to emit an ultrasound radiation field at a plurality of frequencies; an ultrasound receiving transducer comprising a plurality of ultrasound receivers, each having a receiver output, to provide a corresponding plurality of receiver output signals; and processing means, coupled to the plurality of receiver outputs, to process the receiver output signals and to record representations or characteristics of output signals corresponding to ones of the plurality of frequencies.

2. Apparatus as claimed in claim I wherein the emitted ultrasound radiation field comprises a series of tone bursts of different frequencies.

3. Apparatus as claimed in claim I or 2 wherein the ultrasound transmitter consists of a single transmitting element and wherein the processing means is adapted to capture the ultrasound emitted from this element at the plurality of receivers.

4. Apparatus as claimed in claim 1, 2 or 3 wherein said processing means comprises:

means to sequentially select an output signal from each receiver.

5. Apparatus as claimed in claim 4 wherein said selecting means is responsive to said excitation means.

6. Apparatus as claimed in claim 1, 2 or 3 wherein said processing means is adapted to capture the receiver output signals substantially simultaneously.

7. Apparatus is claimed in any preceding claim further comprising means to determine an attenuation of the ultrasound field along a path between the transmitter and a said receiver.

8. Apparatus as claimed in claim 3 wherein the processing means further comprises means to Fourier transform data corresponding to a receiver output signal.

9. Apparatus as claimed in any preceding claim further comprising means to graphically display the processed receiver output signals, or data derived therefrom, as an image.

10. Apparatus substantially as hereinbefore described with reference to Figures I to 5.

11. A method of determining tissue properties comprising the steps of:

disposing an ultrasound detector comprising a plurality of ultrasound receiving elements adjacent the tissue; insonifying the tissue with an ultrasound field at mo re then one frequency from an ultrasound transmitter and capturing the signal transmitted through the tissue with each ultrasound receiving element, the transmitted signal being captured substantially simultaneously at each ultrasound receiving element; and determining the attenuation of ultrasound within the tissue at more than one frequency for the paths between the transmitter and each of the receiving elements.

12. A method as claimed in claim 11 wherein the step of determining the attenuation at more than one frequency comprises:

insonifying the tissue with a first ultrasound f ield having a first frequency and capturing the signal transmitted through the tissue with each ultrasound receiving element, determining, for ultrasound of the first frequency received at each ultrasound receiving element, the attenuation within the tissue; 16 insonifying the tissue with a second ultrasound field having a second frequency and capturing the signal transmitted through the tissue with each ultrasound receiving element.

determining, for ultrasound of the second frequency received at each ultrasound receiving element, the attenuation within the tissue; and determining a relationship between attenuation and frequency from the attenuation of ultrasound at the first and second frequencies.

13. A method as claimed in claim 12 and comprising insonifying the tissue with an ultrasound field containing ultrasound of the first and second frequencies.

14. A method as claimed in claim 12 and comprising insonifying the tissue with, successively, a first ultrasound field containing ultrasound of thefirst frequency and a second ultrasound field containing ultrasound of the second frequency.

15. A method as claimed in any one of claims 11 to 14 and further comprising the step of determining the velocity within the tissue of ultrasound transmitted along the paths between the transmitter and each of the receiving elements.

16. A method of determining tissue properties comprising the steps of.

disposing an ultrasound detector comprising a plurality of ultrasound receiving elements adjacent the tissue; insonifying the tissue with an ultrasound field from an ultrasound transmitter and capturing the signal transmitted through the tissue with each ultrasound receiving element, the transmitted signal being captured substantially simultaneously at each ultrasound receiving element, and determining the velocity within the tissue of ultrasound transmitted along the paths between the transmitter and each of the receiving elements.

17 17. A method as claimed in any one of claims 11 to 16 further comprising determining the attenuation of ultrasound within the tissue as a function of frequency over a predetermined range of frequencies.

18. A method as claimed in any one of claims 11 to 17 further comprising graphically displaying the attenuation for the said paths as an image.

19. Apparatus for carrying out the method of any one of claims 11 to 18.