WO2018083492A1

WO2018083492A1 - A breast density meter and method

Info

Publication number: WO2018083492A1
Application number: PCT/GB2017/053324
Authority: WO
Inventors: Chris Frank BORE
Original assignee: Micrima Limited
Priority date: 2016-11-04
Filing date: 2017-11-03
Publication date: 2018-05-11

Abstract

There is provided a breast density meter for measuring the density of breast tissue, comprising at least one microwave antenna configured to transmit microwave signals over a range of frequencies so as to illuminate a breast of a patient and to receive the microwave signals following scattering within the breast. A processor is configured to obtain a set of scattering parameters for the microwave signals and to determine a density value or a cancer risk score based on a density value for the breast from a predetermined correlation between density and the scattering parameters which is in turn derived from a predetermined correlation between density and a change in permittivity with frequency, the change in permittivity being calculatable from the scattering parameters.

Description

A BREAST DENSITY METER AND METHOD

The invention relates to a breast density meter and method for measuring the density of breast tissue in vivo.

According to the World Health Organization, breast cancer is the second most common type of cancer and the fifth most common cause of cancer death. In view of the commonality of breast cancer, diligent individuals subject themselves to regular mammograms for the purpose of detecting an existence of breast cancer.

An ancillary benefit of having a mammogram conducted is the ability of the radiologist to determine a radiographical density of the participant's breast tissue due to the fact that there is a prognostic relationship between breast density and cancer risk. In general, it is known in the art that the radiographical density of a breast illustrated within a mammogram may vary due to differences in the amount of fat, connective tissues, and epithelial tissues that are present.

For example, because fibroglandular and connective tissues (i.e. glands, ducts, and fibers) have a relatively high x-ray attenuation, fibroglandular and connective tissues may appear to be radiographically dense/light on radiographic films. By contrast, fat has a relatively low x-ray attenuation and therefore appears to be the least radiographically dense/dark, when compared to the remaining breast tissue. Because of the distinct differences in x-ray attenuation between fat and fibroglandular tissue, segmentation of fibroglandular tissue from the rest of the breast is possible.

A known breast density estimation standard may be based upon a four-category Breast Imaging Reporting and Data Systems (BI-RADS) lexicon. Upon visually assessing a mammogram, a radiologist may classify the radiographical image of the breast into one of four BI-RADS compositional categories defined as:

1 : Fatty - the breasts are almost entirely fatty;

2: Scattered - there are scattered areas of fibroglandular density;

3: Heterogeneous - the breasts are heterogeneously dense, which may obscure small masses; and

4: Dense - the breasts are extremely dense, which lowers the sensitivity of mammography. Women whose breasts are categorized in the densest, fourth category are four-to-six times more likely to develop breast cancer than those categorized in the first, fatty category.

The above standard in breast density estimation involves a radiologist's visual assessment of a mammogram, and so is a subjective assessment which relies on the perception of the radiologist. While such a subjective density classification is quick to use and widely employed, it has been proven to be limited due to considerable intra- and inter-reader variability of a radiologist.

Accordingly, it is desirable to provide an improved system and method for determining breast density. In this regard, the Applicants have recognised that there is a correlation between the density of breast tissue and the extent of microwave scattering there through, and that scattering parameters obtained for a breast (by appropriate measurements) can then be used to determine (an indication of) the density of the breast. Thus, in accordance with an aspect of the invention, there is provided a breast density meter for measuring the density of breast tissue comprising: at least one microwave antenna configured to transmit microwave signals over a range of frequencies so as to illuminate a breast of a patient and to receive the microwave signals following scattering within the breast; and a processor configured to obtain a set of scattering parameters for the microwave signals over the range of frequencies and to determine a density value or a cancer risk score based on a density value for the breast from a predetermined correlation between density and the scattering parameters which is in turn derived from a predetermined correlation between density and a change in permittivity with frequency, the change in permittivity being calculatable from the scattering parameters.

In an embodiment, the set of scattering parameters obtained by the processor is compared to reference data that corresponds to and/or is representative of a predetermined correlation between density and the scattering parameters. The reference data may, for example, be in the form of a look-up table that is stored in memory and includes plural entries corresponding respectively to the scattering parameters and their corresponding density values. The predetermined correlation between density and the scattering parameters may be a predetermined correlation between density and a change in scattering parameters with frequency. In such cases, each entry in the look-up table may correspond to a (e.g. identified or determined) change in scattering parameters with frequency and its corresponding density value.

The at least one microwave antenna may comprise a plurality of antennas that are spaced from one another to form an array, the plurality of antennas defining a transmitting antenna and receiving antennas.

The microwave antenna array may be formed on a substrate which is contoured or contourable to conform to the body part. The substrate may be hemispherical.

The processor may be further configured to generate an image of the internal structure of the breast based on the measured scattering parameters. The processor may generate a plurality of density values for different volumes within the breast.

The processor may generate an average of the plurality of density values to give a density value for the breast as a whole.

In accordance with another aspect of the invention, there is provided a method for measuring the density of breast tissue comprising: illuminating a breast of a patient with microwave signals emitted by at least one microwave antenna; receiving the microwave signals following scattering within the breast at said at least one microwave antenna; measuring scattering parameters for the microwave signals over a range of frequencies; and determining a density value or a cancer risk score based on a density value for the breast from a predetermined correlation between density and the scattering parameters which is in turn derived from a predetermined correlation between density and a change in permittivity with frequency, the change in permittivity being calculatable from the scattering parameters. In an embodiment, the measured set of scattering parameters is compared to reference data that corresponds to and/or is representative of a predetermined correlation between density and scattering parameters. The reference data may, for example, be in the form of a look-up table that includes plural entries corresponding respectively to the scattering parameters and their corresponding density values.

The predetermined correlation between density and the scattering parameters may be a predetermined correlation between density and a change in scattering parameters with frequency. In such cases, each entry in the look-up table may correspond to a (e.g. identified or determined) change in scattering parameters with frequency and its corresponding density value.

The at least one microwave antenna comprises a plurality of antennas that are spaced from one another to form an array, the plurality of antennas defining a transmitting antenna and receiving antennas.

The method may further comprise generating an image of the internal structure of the breast based on the measured scattering parameters. A plurality of density values may be generated for different volumes within the breast.

The method may further comprise determining an average of the plurality of density values to give a density value for the breast as a whole. For a better understanding of the invention, and to show more clearly how it may be carried into effect, reference will now be made, by way of example, to the accompanying drawings, in which:-

Figure 1 is a system diagram of a medical imaging system according to an embodiment of the invention;

Figure 2 is a schematic view of the medical imaging system;

Figure 3 is a flowchart depicting a sampling method; and Figure 4 shows two graphs illustrating the polarisation intensity Δε and static conductivity a_s, respectively, for three adipose-defined groups of samples.

Figure 1 shows a medical imaging system 2 according to an embodiment of the invention. The medical imaging system generally comprises a processor 4 and a microwave antenna array 6 in communication with the processor 4.

As shown in Figure 2, the antenna array 6 comprises a plurality N of antennas 16 which are arranged over the surface of, or within, a shell substrate 18. The shell 18 has a curved profile as shown. In particular, the shell 18 is part or hemi-spherical and is configured to approximate the shape of a breast. The antennas 16 are arranged over the shell 18 such that they all point to a common focal point.

The antennas 16 are each electrically connected to a switching matrix 20. The switching matrix 20 is in turn connected to both a transmit path and a receive path. The transmit path comprises a signal generator 22 coupled to an amplifier 24. The receive path comprises an amplifier 26 coupled to a detector 28 and the processor 4.

The switching matrix 20 selectively couples each of the antennas 16 to either the transmit path or the receive path.

The antenna array 6 is operated in a multi-static fashion. Specifically, the switching matrix 20 is controlled so as to connect one of the antennas 16 to the transmit path and the remaining antennas 16 to the receive path. The signal generator 22 generates a stepped frequency continuous wave (CW) signal which is amplified by the amplifier 24 and then transmitted by the antenna 16 connected to the transmit path. The stepped frequency continuous wave signal is a sequential series of pulses of continuous wave energy, where each pulse has its frequency stepped up across a range of frequencies, typically within the 3-8 GHz range. The other antennas 16 receive the transmitted signal and the received signal is detected and then recorded by the processor 4.

As shown in Figure 2, the shell 18 receives a cup 30. The cup 30 has a complementary shape to the shell 18 such that it fits tightly within the shell 18. A layer of coupling fluid (dielectric constant controlled fluid) may be inserted in the gap 31 between the shell 18 and the cup 30 so as to improve the coupling between the antennas 16 and the cup 30 in order to minimise signal loss and thus improve transmission of the microwave signal. An actuator (not shown), such as a motor, may be connected to the microwave antenna array 6. The actuator is configured to move the microwave antenna array 6 relative to the cup 30 which remains stationary against the breast 36. Specifically, the actuator causes the microwave antenna array 6 to rotate relative to the cup 30 about the breast 36. The microwave antenna array 6 rotates about the center of the shell 18 (i.e. its axis of symmetry). This may be enabled by a threaded engagement between the cup 30 and the shell 18. In particular, the outside of the cup 30 and the inside of the shell 18 may have threaded portions which engage to allow the shell 18 and the antenna array 6 to be rotated relative to the cup 30. This may also allow the cup 30 to be quickly and easily removed so as to enable the coupling fluid to be replaced.

The antennas 16 may be as described in WO 2009/060181. In particular, the antennas 16 may comprise a slot 16 formed in a conductive element, the slot having a rectangular external boundary defined by a substantially closed internal edge of the conductive element. A microstrip feed line may be spaced from the conductive element by a dielectric substrate with the distal end of the line positioned at the geometric centre of the slot. In use, a patient lies in a prone position such that their breast 36 sits in the cup 30. A layer of coupling fluid may also be provided in the gap 35 between the cup 30 and the breast 36 in order to improve coupling between the antennas 16 and the breast 36.

Although not shown, one or more inserts may be placed inside the cup 30 so as to enable a better fit between the internal surface of the cup 30 and the breast 36. For example, a plurality of such inserts may be provided, each having different shapes and sizes, to enable the system to be better adapted to breasts of different shapes and sizes. The inserts may be made from the same material as the cup (e.g. ceramic). Figure 3 shows a flowchart of a data acquisition method. As shown, the switching matrix 20 connects an antenna m of the N antennas to the transmit path. All other antennas 16 (n = 1...N, n≠m) are connected to the receive path. The antenna 16 connected to the transmit path illuminates the breast 36 with the microwave signal. The signal is scattered by the breast tissue and the scattered signal is received at each of the non-transmitting antennas 16 where it is detected (possibly in a time-sharing arrangement) and recorded. If m≠N, the switching matrix 20 steps to the next antenna 16 (m = m + 1) to be connected to the transmit path. This is repeated until all antennas 16 have been connected to the transmit path.

If additional data sets are required, then the actuator is used to rotate the array 6 relative to the breast 36 while retaining the breast in position. The acquisition process is then repeated with the antenna array 6 in the new configuration.

The processor 4 may record the relative difference between the measured phase and amplitude of the transmitted signal as compared to the phase and amplitude of the scattered signal, recorded as a complex number (having real and imaginary parts).

The signal detected at each antenna 16 is affected by scattering arising from objects within the imaged volume (i.e. the breast 36). In particular, tumours can generate significant reflections as they exhibit much higher dielectric properties than adipose and connective tissues due to their significant water content and so can be identified in the acquired data.

The acquired data may be used by the processor 4 to construct an image of the internal structure of the breast 36. The Data reconstruction may be performed using Phased Array (frequency domain), Delay and Sum (DAS - time domain) techniques or any other suitable technique, such as 3D Fourier Transformation, Back Projection, etc. From this, the processor 4 is able to identify (possibly, with additional user input or confirmation) a region of interest (if present) in which a possible tumour or other pathology may exist. It has been found that there is a correlation between the scattering parameters measured by the processor 4 and the density of the breast 36, and that this is in turn derived from a predetermined correlation between a change in permittivity with frequency and density.

In particular, the frequency dependent scattering coefficient (parameter) at a boundary is defined as:

Ζ₂(ω) - Ζ₁(ω)

Ζ₂ (ω) + Ζ₁{ω)

Where Z₁ (ω) is the frequency dependent impedance on the incident side of the boundary and Ζ₂(ω) is the impedance on the transmitting side of the boundary. The impedance is related to permittivity through:

Where μ is permeability and ε is the complex permittivity.

It can be assumed for biological tissues that μ₁ = μ₂ = μ₀, where = μ₀ is the permeability of free space. Wth this assumption the equation for S can be rewritten as:

Where ε {ω) is the frequency dependent permittivity on the incident side of the boundary and ε₂ (ω) is the permittivity on the transmitting side of the boundary. Making ε₂ (ω) the subject:

(To determine the reference permittivity ε^ω) the calculation in the imaging domain is extended into the known ceramic dielectric which has well defined electrical properties.)

Therefore, the frequency dependent permittivity (and thus the change in permittivity with frequency) on the transmitting side of the boundary can be calculated from the scattering parameter(s) and vice versa by manipulating the above equation.

The correlation between the change in the permittivity (i.e. the change in ε₂ (ω)) with frequency and density may be predetermined in any suitable or desired manner. However, in an embodiment this is done using a single pole Drude model of permittivity for biological tissues in the low microwave band (0.5-20GHz):

Where ε_∞ is the relative permittivity at infinite frequency, ε₀ is the permittivity of free space, Δε is the polarisation intensity, ω is the angular frequency, τ is the time constant, a is an exponent parameter, which takes a value between 0 and 1 , allowing the description of different spectral shapes and a_s is the static conductivity contribution.

The values of Δε and a_s can be derived directly by fitting the Drude model to the values of ε₂ (ω) calculated from the scattering parameters obtained for the microwave signals over the range of frequencies. It was shown by Lazebnik et al (Phys Med Biol. 2007 Oct 21 ;52(20):6093-6115. A large- scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries) that, while there is little or no correlation between ε_∞, τ and a and adipose content (i.e. breast density), there is a correlation between the polarisation intensity Δε and breast density and static conductivity a_s and breast density. These relationships are illustrated in Figure 4.

In particular, Figure 4 shows two graphs illustrating the polarisation intensity Δε and static conductivity a_s, respectively, for three adipose-defined groups of samples, where the upper and lower bounds indicate 25th and 75th quartile values. As can be seen in Figure 4, there is a clear correlation between adipose content (and thus density) and polarisation intensity Δε and static conductivity a_s.

The change in permittivity with frequency therefore provides a good measure of breast density. Alternatively, it may be noted that the change in permittivity relates to the 'colour' of the image or the change in the scattering parameters as a function of frequency. The colour or microwave scattering (parameter) value(s) may therefore be correlated to density. This may be achieved empirically by generating test data for samples of known density or through calculation using, for example, equations linking permittivity and scattering coefficient through the impedance, as presented above. Alternatively, any other suitable method of correlating the data produced by the medical imaging system 2 to density may be used.

It may be required that the effects of the imaging system, wider environment or transmission path be removed from the scattering data before the data is analysed, by means of a calibration of magnitude of the signal, phase of the signal or both magnitude and phase. As the medical imaging system 2 generates data for the entire breast 36, it is possible to estimate the change in permittivity over the complete volume (e.g. for each voxel). The medical imaging system 2 may enable the image to be toggled from scattering to density data or may allow the data to be overlaid in a single image. The density values for each voxel may be averaged or assessed using some other statistical technique to provide a density value for the breast as a whole. This may be used to provide a classification which corresponds to the BI-RADS compositional categories or some other system. Alternatively, or in addition, the density values may be used to provide a risk score for the patient. In this instance, the density values themselves need not be presented to the user or patient.

Although the derivation of the density information has been described in the context of the medical imaging system 2, it will be appreciated that the density information may be generated from the raw data without generating an image of the breast 36. In fact, the density information may be provided separately in a standalone test where there is no cause for scanning the breast 36 for suspicious lesions. The system may therefore be embodied as a density measurement apparatus or meter which may or may not have the capability of imaging the breast. This information may serve as a useful pre- screening tool to identify the patient's risk score based on the breast density. This could be used to determine the screening frequency for the patient or other preventative measures based on the density assessment.

It will be appreciated that where only density information is required and a separate image of the breast for diagnostic purposes is not required, the system may be simplified from that described above. In particular, the system may use a single antenna which serves to transmit and receive the microwave signal or a pair of antennas which transmit and receive. This may provide a single density value for the breast as a whole which is expected to correspond to the average value described above for the more complex antenna array.

To avoid unnecessary duplication of effort and repetition of text in the specification, certain features are described in relation to only one or several aspects or embodiments of the invention. However, it is to be understood that, where it is technically possible, features described in relation to any aspect or embodiment of the invention may also be used with any other aspect or embodiment of the invention. The invention is not limited to the embodiments described herein, and may be modified or adapted without departing from the scope of the present invention.

Claims

1. A breast density meter for measuring the density of breast tissue comprising: at least one microwave antenna configured to transmit microwave signals over a range of frequencies so as to illuminate a breast of a patient and to receive the microwave signals following scattering within the breast; and

a processor configured to obtain a set of scattering parameters for the microwave signals over the range of frequencies and to determine a density value or a cancer risk score based on a density value for the breast from a predetermined correlation between density and the scattering parameters which is in turn derived from a predetermined correlation between density and a change in permittivity with frequency, the change in permittivity being calculatable from the scattering parameters.

2. A breast density meter as claimed in claim 1 , wherein said at least one microwave antenna comprises a plurality of antennas that are spaced from one another to form an array, the plurality of antennas defining a transmitting antenna and receiving antennas.

3. A breast density meter as claimed in claim 2, wherein the microwave antenna array is formed on a substrate, wherein the substrate is contoured or contourable to conform to the body part.

4. A breast density meter as claimed in claim 3, wherein the substrate is hemispherical.

5. A breast density meter as claimed in any preceding claim, wherein the processor is further configured to generate an image of the internal structure of the breast based on the measured scattering parameters.

6. A breast density meter as claimed in any preceding claim, wherein the processor generates a plurality of density values for different volumes within the breast.

7. A breast density meter as claimed in claim 6, wherein the processor generates an average of the plurality of density values to give a density value for the breast as a whole.

8. A method for measuring the density of breast tissue comprising: illuminating a breast of a patient with microwave signals emitted by at least one microwave antenna;

receiving the microwave signals following scattering within the breast at said at least one microwave antenna;

measuring scattering parameters for the microwave signals over a range of frequencies; and

determining a density value or a cancer risk score based on a density value for the breast from a predetermined correlation between density and the scattering parameters which is in turn derived from a predetermined correlation between density and a change in permittivity with frequency, the change in permittivity being calculatable from the scattering parameters.

9. A method as claimed in claim 8, wherein said at least one microwave antenna comprises a plurality of antennas that are spaced from one another to form an array, the plurality of antennas defining a transmitting antenna and receiving antennas.

10. A method as claimed in claim 8 or claim 9, further comprising generating an image of the internal structure of the breast based on the measured scattering parameters.

11. A method as claimed in any of claims 8 to 10, wherein a plurality of density values are generated for different volumes within the breast.

12. A method as claimed in claim 11 , further comprising determining an average of the plurality of density values to give a density value for the breast as a whole.