Patent Grant
8200309
This invention generally relates to magnetic resonance and more particularly to the measurement of electrical impedance, complex permittivity, and/or complex conductivity by the application of time-varying electric fields in an imaging volume (especially as it enables detection and evaluation of sample, e.g., human breast, pathology) or in a homogeneous sample volume (especially as it relates to industrial materials testing).
Magnetic resonance imaging of the human breast with and without gadolinium enhancement is a standard procedure in clinical medicine. S. A. Mirowitz et al., “Magnetic Resonance Imaging Clinics of North America,” W.B. Saunders Co., vol. 9, no. 2 (May 2001). Current techniques generally utilize the injection of e.g., gadolinium contrasting agents for breast imaging. The dielectric properties of breast carcinoma have been extensively investigated in vitro. A. J. Suroweic, et al., “Dielectric Properties of Breast Carcinoma and Surrounding Tissues,” IEEE Trans. On Biomedical Engineering, vol. 35, no. 4, pp. 257-263 (April 1988): Electrical impedance imaging in vivo is an FDA approved method for breast cancer detection. J. C. Hayes, “Electrical impedance images for breast gain FDA approval,” Diagnostic Imaging, pp. 19-20 (June 1999). U.S. Pat. Nos. 5,412,322, 5,757,187, 6,166,540 and 6,342,784 (incorporated by reference herein for all purposes) describe various effects produced by superposition of time varying electric fields in magnetic resonance devices. The production of gradients by an electric conduction current and the measurement of non-uniform conduction current density by magnetic resonance are described in the prior art. Holz, M. et. al., “NMR Measurements of Internal Magnetic Field Gradients Caused by the Presence of an Electric Current in Electrolyte Solutions,” Journal of Magnetic Resonance, vol. 40, pp. 595-599 (1980); G. C. Scott, et al., “Measurement of Nonuniform Current Density by Magnetic Resonance,” IEEE Trans. On Medical Imaging, vol. 10, no. 3, pp. 362-374, (September 1991). Complex permittivity is reviewed in other prior art. C. A. Balanis, “Advanced Engineering Electromagnetics,” Wiley & Sons, Section 2.8, (1989). Further background information can be found in other art. “The Transforms and Applications Handbook,” A. D. Poularikas (ed.), CRC Press, pp. 221-222 (1996).
The present invention provides a method for large population screening for breast cancer without the use of ionizing radiation or the parenteral administration of medications. It also provides a method for continuously measuring the dielectric properties of materials in a manufacturing process at variable frequencies.
An object of this invention is to provide a non-invasive, non-contrast, non-ionizing radiation imaging method for screening a sample for cancer by providing an attachment to existing magnetic resonance imaging (“MRI”) machines. By non-contrast, it is meant that injection of a contrast agent (e.g., Gadolinium compounds) is not required (but still could be used). It is possible, however, to use a contrast agent. An additional object of this invention is to provide a method for measuring the electrical impedance, complex permittivity, and/or complex conductivity of a homogeneous sample in a materials testing or production control application by providing an attachment to existing magnetic resonance analysis machines.
According to one embodiment of the present invention, a method of detecting and evaluating spatially distributed sample pathology may include placing a sample to be measured in a magnetic resonance imaging device, providing a Faraday shield device having an electrode array, applying a potential distribution to the Faraday shield device which produces a time varying electric field {right arrow over (E)} in the sample, which creates a spatially distributed current field {right arrow over (J)}, which generates time varying focal periodic aberrations in the local magnetic field {right arrow over (b)}0 that periodically vary the phase of spins within the sample, and measuring or mapping at least one of complex permittivity, complex conductivity, and electrical impedance of the sample. This embodiment is applicable to, e.g., spatially ordered anatomic and pathological analysis of sample pathology utilizing a conventional magnetic resonance imaging device with a detection circuit attachment. In another aspect, the method may further comprise measuring the complex permittivity at a phase modulating frequency of the time varying potential distribution.
According to another embodiment of the present invention, a method of detecting and evaluating sample spatially ordered pathology may comprise: placing a human breast to be measured in a Faraday shield device having electrodes; applying to the Faraday shield device a time varying potential having a phase modulating frequency, which creates a time varying electric field {right arrow over (E)} in the breast, which creates a time varying current field in the breast, which periodically varies a phase of spins within the breast; and measuring a complex permittivity distribution of the breast at the phase modulating frequency.
According to another embodiment of the present invention, a method of measuring dielectric properties by the application of time-varying electric fields in a sample may include placing the sample in a magnetic resonance device, providing a Faraday shield device, and applying a potential distribution V to the Faraday shield device, which generates a time varying electric field {right arrow over (E)} in the sample, which creates a time varying current field {right arrow over (J)} in the sample, which creates/generates a periodic magnetic field {right arrow over (b)}0 that periodically varies the phase of spins within the sample, and measuring at least one of complex permittivity, complex conductivity, and electrical impedance of the sample with a detection circuit attachment. This embodiment is applicable to continuous measurement of dielectric properties at a controllable frequency Ω.
According to another embodiment of the present invention, a system of detecting and evaluating spatially distributed sample pathology may include a magnetic resonance imaging device to produce an image of a sample (the magnetic resonance imaging device generating a static magnetic field {right arrow over (B)}0 and gradient fields {right arrow over (G)}, a radio frequency generator operating near the Larmor frequency ω0 and including receiving coils and transmitting coils or transmitter-receiver coils). The system further includes a Faraday shield that includes parallel electrodes oriented orthogonal to the static magnetic field to produce a time varying electric field in the sample. A voltage source may also be provided and adapted to apply a periodic voltage V at a frequency Ω to the Faraday shield device. A detector may also be provided to detect one of a complex permittivity, a complex conductivity, and an electrical impedance of the sample.
According to a preferred aspect of the present invention, the sample may be a human breast. The Faraday shield device may comprise a pair of compression paddles and the electrodes may be oriented in parallel to each other. The electrodes may be embedded in an insulating material. The insulating material may have a high dielectric constant and may comprise one or more ferroelectric materials. According to another preferred aspect of the present invention, the electrodes may be further oriented substantially perpendicular to the main magnetic field B0 of the magnetic resonance imaging device.
According to another preferred aspect of the present invention, the Faraday shield device may comprise a pair of compression paddles, and the method may further comprise: placing the Faraday shield within an imaging region of the magnetic resonance imaging device; and placing one of the receiver coil and the transmitter-receiver coil of the magnetic resonance imaging device near the compression paddles.
According to another preferred aspect of the present invention, the method may further comprise detecting orthogonal components of each sideband of a line spectrum resolved with respect to the phase of a voltage applied to the Faraday shield device. The method may further comprise determining a ratio of the resolved real and imaginary components of the sidebands. The method may further comprise determining an electric loss angle of the sample. The method may further comprise detecting orthogonal components of each sideband of a line spectrum resolved with respect to the phase of a voltage applied to the Faraday shield device at a frequency Ω<<(or much less than) ω0, the Larmor frequency of the magnetic resonance imaging device. The method may further comprise identifying focal aberrations contained in an image produced by the magnetic resonance imaging device.
According to another embodiment of the present invention, a method of measuring electrical impedance by the application of time-varying electric fields in an imaging volume may comprise: placing a sample in a magnetic resonance device; providing a detector to the magnetic resonance device; providing a Faraday shield device about the sample, where the Faraday shield device may include electrodes oriented parallel to each other; applying a periodic potential distribution across the Faraday shield device to create a time varying electric field in the sample, which creates a local time varying current field in the sample, wherein the local time varying current field creates a periodic aberration in a local magnetic field that periodically varies a phase of spins within the sample; and measuring an electrical impedance of the sample with the detector.
According to another embodiment of the present invention, a system of detecting and evaluating sample pathology may comprise: a magnetic resonance imaging device to produce an image of a sample, the magnetic resonance imaging device generating a static magnetic field and including one of receiving coils and transmitter-receiver coils; a Faraday shield device that includes parallel electrodes oriented orthogonal to the static magnetic field connected to a voltage source adapted to generate a periodic voltage V at a frequency Ω; and a detector to detect one of a complex permittivity, a complex conductivity, and an electrical impedance of the sample.
In a preferred aspect of the present invention, the detector may comprise: first demodulators supplied with a quadrature output at a Larmor frequency ωo′ from a magnetic resonance master radio frequency oscillator; a first amplifier to sum first output signals from the first demodulators; a second amplifier to receive a second output signal from the summing amplifier; and second demodulators coupled to the second amplifier to provide cross-correlated outputs corresponding to at least one of real and imaginary components that correspond to a signal received by the one of receiver and transmitter-receiver coils from a location x in the sample, and corresponding to the frequency ωo′ resolved with respect to a phase of V. The second demodulators may comprise a series n of double-balanced demodulator pairs, each double balanced demodulator pair coupled to the second amplifier, to provide cross-correlated outputs corresponding to real and/or imaginary components of the signal received by the one of receiver coils and transmitter-receiver coils from the location x in the sample. The second demodulators may be supplied with frequency sources sin (nΩt) and cos(nΩt).
In another preferred aspect of the present invention, the system may further comprise a processor to analyze the cross-correlated outputs of the second demodulators and to provide the complex permittivity at the location x at frequency Ω. The Faraday shield may include a pair of non-conductive compression paddles, each compression paddle comprising an electrode array contained in an insulating portion thereof and coupled to the voltage source. At least one of receiving coils and transmitter-receiver coils may be disposed near at least one of the compression paddles. In another preferred aspect of the present invention, the periodic voltage may be either continuously applied or pulsed.
According to another embodiment of the present invention, a system for measuring the electrical impedance of a sample may comprise: a magnetic resonance device; a Faraday shield device disposed about the sample, where the Faraday shield device may include a pair of electrode arrays oriented substantially parallel to each other and substantially orthogonal to the static magnetic field of the magnetic resonance device; a voltage source to apply a periodic potential distribution across the Faraday shield device to create a time varying electric field in the sample, which creates a local time varying current field in the sample, which creates a periodic aberration in a local magnetic field that periodically varies a phase of spins within the sample; and a detector coupled to the magnetic resonance device to measure a value corresponding to an electrical impedance of the sample.
Further features and advantages of the invention, as well as the structure and operation of various embodiments of the invention, are described in detail below with reference to the accompanying drawings.
The accompanying drawings, which are incorporated in, and form a part of, the specification, illustrate some embodiments of the present invention and, together with the description, serve to explain the principles of the invention. In the drawings:
According to the present invention, a non-invasive device and method is provided to permit the measurement an/or mapping of electrical impedance, complex permittivity and complex conductivity of a sample with distributed physical properties and/or the electrical impedance of a homogeneous sample. A magnetic resonance imaging (“MRI”) device can be implemented to permit the measurement of electrical impedance, complex permittivity and complex conductivity of a sample, such as a human breast. In this embodiment, measurement can be made by the application of a potential distribution across a Faraday shield device implemented with the magnetic resonance imaging device which produces a time varying electric field {right arrow over (E)} in the sample, which creates a spatially distributed current field {right arrow over (J)}, which generates time varying focal periodic aberrations in the local magnetic field {right arrow over (b)}0 that periodically vary the phase of spins within the sample. The device and method of this embodiment can thus provide the location of sample pathology for detection and both anatomic and pathological evaluation. In a homogeneous sample embodiment, a magnetic resonance device measurement can be made by the application of a potential distribution across a Faraday shield device implemented with the magnetic resonance imaging device which produces a time varying electric field in the sample, which creates a current field, which generates time varying periodic aberrations in the local magnetic field that periodically vary the phase of spins within the sample. A detection circuit is provided to yield an output that corresponds to the electrical impedance, complex permittivity and/or complex conductivity.
According to one embodiment of the present invention, the sample or object to be measured or mapped, for example a human breast, is placed within a Faraday shield device connected to a time-varying voltage source V of frequency Ω so as to produce a time varying electric field Ē about the Faraday shield device, where
through Poisson's equation (in the quasi-static state)
∇·({hacek over (∈)}∇{hacek over (V)})={hacek over (ρ)} Eq. 2
where {hacek over (∈)} is the complex permittivity and {hacek over (ρ)} is the charge distribution. This time-varying electric field creates a current distribution {right arrow over (J)} in the sample or object whose intensity and phase is related to the applied electric field through the spatial distribution of the complex permittivity, complex conductivity, or electrical impedance of the sample or object. The Faraday shield device is arranged so that the current distribution in the sample being tested or object being imaged is essentially orthogonal to the main magnetic static field (present as an essential component of all magnetic resonance imaging devices as is known in the art). The time varying current field in the sample or object creates a periodic magnetic field {right arrow over (b)}0 superimposed on the main magnetic field {right arrow over (B)}0 and the gradient fields {right arrow over (G)} which periodically varies the phase of the spins within the sample or object, inducing a line-spectrum of sideband frequencies in a receiver coil of the MRI device centered at the Larmor frequencies of the spins of the sample or object, (as is known in the art, Larmor frequencies ω0 can be made to be a function of spin location by the application of gradient fields) which sidebands are spaced by integral multiples of the phase modulating frequency Ω. Each sideband amplitude and sideband temporal phase is functionally related to the known applied voltage distribution {hacek over (V)} through the complex permittivity, complex conductivity, or electric impedance distribution. The frequency at which the complex permittivity, complex conductivity, or electrical impedance distribution is mapped or measured is the frequency Ω of the periodic voltage distribution {hacek over (V)} applied to the Faraday shield device.
In an embodiment of the present invention, a breast screening application using a magnetic resonance device, a human breast is positioned in a compression device (e.g., such as that shown in
The component of the image produced by the magnetic resonance imaging device during each individual “read” period will contain spatially ordered focal aberrations marking the location of suspected pathology. According to an embodiment of the present invention, the temporal analysis of the signal received from these focal aberrations, resolved with respect to the phase of the applied voltage {hacek over (V)} produces an estimation of the relative permittivity, complex conductivity, and/or electrical impedance yielding information about the pathology present as a function of position x corresponding to the Larmor frequency ωo. Thus, the nature, extent, and distribution of pathology can be better estimated for biopsy, medical or surgical treatment, or conservative management without the use of ionizing radiation and preferably without the injection of magnetic resonance contrast agents.
The parallel electrodes of the Faraday shield are oriented perpendicular to the main magnetic field {right arrow over (B)}0 of the magnetic resonance (imaging) device. A purpose of the Faraday shield of the present invention is to apply a potential distribution {hacek over (V)} across the breast to be imaged or to the sample to be analyzed without significantly affecting the B1 radio frequency field intrinsic to conventional magnetic resonance devices (as in known in the art). This purpose can be achieved by orienting the parallel electrodes of the Faraday shield perpendicular to the main magnetic field B0 so as not to provide a conduction path either for the electric field associated with the B1 radio frequency field or additionally for eddy currents resulting from the application of gradients {right arrow over (G)} (intrinsic in all magnetic resonance imaging devices, as is known in the art). The electrode arrays are connected to a time varying voltage source (V) 10 of frequency Ω via connections 12 or 14 so as to produce a time varying electric field {right arrow over (E)} in the object. The voltage ({hacek over (V)}) can be applied continuously during the imaging sequence. Alternatively, the voltage ({hacek over (V)}) can be switched on only during the “read” period. Alternatively, the voltage ({hacek over (V)}) can be synchronized with the event sequence of the MRI device.
Applying a potential distribution {hacek over (V)} across the Faraday shield device creates a time varying electric field {hacek over (E)} in the sample, which creates a current distribution {hacek over (J)} in the sample or object whose local intensity and phase is related to the applied electric field through the spatial distribution of the complex permittivity, complex conductivity, or electrical impedance of the sample or object. The frequency Ω of the periodic voltage V is related to the Larmor frequency ωo as follows: Ω<<ωo. Example frequency values would be apparent to one of ordinary skill in the art given the present teachings.
As an example implementation,
Using the paddles as illustrated, the current distribution {hacek over (J)} in the sample or object is essentially orthogonal to the main magnetic static field. The local time varying current field in the sample or object creates a periodic aberration in the local magnetic field, which periodically varies the phase of the spins within the sample or object, producing a line-spectrum of frequencies (see e.g.,
In particular, a detector according to an embodiment of the present invention can be used to resolve the complex permittivity, complex conductivity, and/or electrical impedance detected in the sample. An example detector/detection circuit is shown in
where ωo′=γ(Bo+Gx), Eq. 3
and where γ is the gyro magnetic ratio. See e.g.,
Each spin then produces a voltage by magnetic induction in the receiver coil whose frequency spectrum consists of equally spaced sidebands nΩ centered at a Larmor frequency ωo′ corresponding to the location x of each spin. The amplitude of each sideband is given by:
The instantaneous periodic angular velocity:
ω′=γb Eq. 5
where b0=μh0 Eq. 6
of each spin is in phase with the time-varying component of its ambient magnetic field b0 which is a function of the current flux distribution J. If the current distribution is uniform, the instantaneous angular velocity of each spin will be in phase with, and the angular phase of each spin will be displaced from, the applied electric field and from the applied voltage V by the loss angle δ as would occur in a uniform sample in the measurement application. If there are focal aberrations in complex permittivity, complex conductivity, and/or electrical impedance as are associated with spatially distributed focii of breast pathology, then there will be local aberrations in the magnetic field phase and intensity, focally distorting the image produced by the conventional magnetic resonance imaging machine identifying the spatial location of pathology for further evaluation or for treatment. Analysis of the signal from these regions of distortion will produce an estimate of the complex permittivity, complex conductivity, and/or electrical impedance of the aberration which would help identify the nature of the pathology. The detector circuit 130 (see
The detector of
The detector of
The detection circuit 130 shown in
In
According to alternative embodiments, the frequency Ω can be made continuously variable yielding the electric susceptibility as a function of the frequency.
According to an alternative embodiment of the present invention, the above methodology is also applicable to electron spin resonance magnetic resonance devices for measurements at extremely high frequencies.
The invention provides several advantages. The present method and system can be used for non-invasive breast cancer screening. For example, injection of Gadolinium compounds is not required, but may be performed for supplemental imaging, as is known in the art. Further, there is no ionizing radiation. Additionally, the frequency of measurement or mapping can be varied for further analysis. Further, the signal from fatty tissue need not be suppressed, as it must be in magnetic resonance mammography.
The foregoing description of the invention has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed, and modifications and variations are possible in light of the above teachings or may be acquired from practice of the invention. The drawings and description were chosen in order to explain the principles of the invention and its practical application. It is intended that the scope of the invention be defined by the claims and their equivalents.
This application claims benefit of priority to PCT Application No. PCT/US03/27122, filed on Aug. 29, 2003 and Provisional Application No. 60/406,924, filed on Aug. 30, 2002, incorporated by reference herein in its entirety.
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| Number | Date | Country | |
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| Parent | PCT/US03/27122 | Aug 2003 | US |
| Child | 10902263 | US |
