WO2006119379A1

WO2006119379A1 - Time-reversal-based microwave hyperthermia treatment of cancer

Info

Publication number: WO2006119379A1
Application number: PCT/US2006/017023
Authority: WO
Inventors: Jian Li; Bin Guo; Luzhou Xu
Original assignee: University Of Florida Research Foundation, Inc.
Priority date: 2005-05-04
Filing date: 2006-05-04
Publication date: 2006-11-09

Abstract

A microwave hyperthermia cancer treatment system is provided. The system includes a source of broadband microwave radiation and an array of antennas coupled to the source. At least one of the antennas transmits broadband microwave radiation toward a target region, and backscattered signals from the target region are received by the array of antennas. The system also includes a processor coupled to the antenna array. The processor includes a time-gating unit to time gate the backscattered signals, a weighting unit that calculates beamforming weights corresponding to each of the antennas based upon the time-gated signals, a time-reversal unit to time reverse the time-gated signals, and a control unit for causing the antenna array to transmit to the target region time-reversed signals weighted by the beamforming weights. The time-reversed weighted signals thus generated have enhanced focus proximate to the target region.

Description

TIME-REVERSAL-BASED MICROWAVE HYPERTHERMIA TREATMENT OF CANCER

FIELD OF THE INVENTION

[0001] The invention relates to the field of hyperthermia for treating diseases, and more particularly, to hyperthermia based on time-reversal signal processing.

BACKGROUND

[0002] Hyperthermia refers generally to above-normal rises in body temperature.

Under properly controlled conditions and procedures, hyperthermia can be used to treat cancer by exposing targeted body tissue to high temperatures in order to kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [0003] Over the last two decades, various studies have reported on the effectiveness of local, microwave-induced hyperthermia in treating certain cancers, particularly breast cancer. Owing to differences in the dielectric and thermal properties of normal host tissue and a cancerous tumor, the heat absorption of the tumor is much greater than that of the host tissue over a wideband of microwave frequencies.

[0004] However, regarding certain tissues - and breast tissue in particular - certain challenges persist with respect to microwave thermotherapy treatment. First, because the heat absorption properties of the breast skin are similar to the tumor but quite different from the normal breast tissue, the breast skin can burn easily during thermotherapy. Second, the heterogeneous properties of the breast tissue make it difficult to focus the microwave energy onto the tumor.

[0005] Current clinical thermotherapy systems use a single microwave frequency, with an adaptive antenna array being utilized to focus the microwave energy onto the tumor cells. Clinical results indicate that using such a system for thermotherapy can reduce the need for additional surgery by approximately one-half. Owing to the long wavelength of the microwaves, however, focusing only through an array with limited aperture is not highly effective.

[0006] A recent study, using finite-difference time-domain (FDTD) simulations shows that instead of using a single frequency, ultra-wideband (UWB) microwave array thermotherapy can provide better focusing of the microwave energy onto the tumor. See M. Converse, EJ. Bond, S. C. Hagness, and B.D. Van Veen, Ultrawide-Band Microwave Space- Time Beamformingfor Hyperthermia Treatment of Breast Cancer: A Computational Feasibility Study, IEEE Transactions on Microwave Theory and Techniques, Vol. 52, No. 8, pp. 1876-1889, August 2004. The array employed for the study was a non-adaptive array. The improved focusing was achieved by transmitting properly aligned, super narrow - and, thus, ultra-wideband - pulses from each antenna element in the array so that theoretically the pulses would arrive at the tumor at the same time.

[0007] The heterogeneous properties of some tissues, such as breast tissue, however, can make it very difficult to align super narrow pulses with the accuracy that is needed to enhance the effectiveness of microwave hyperthermia treatment of breast and other cancers. Accordingly, there is a need for an effective and efficient mechanism for enhancing the focus of microwave hyperthermia signals on or proximate to a target region identified as or suspected of being cancerous.

SUMMARY

[0008] The present invention is directed to a system, device, and related methods for enhancing the focus of microwave hyperthermia signals. One aspect of the invention is a time-reversal-based ultra-wideband microwave procedure for enhancing the focus of microwave hyperthermia signals proximate to a target region where a tumor has been located or which is suspected of being cancerous. The procedure can shape the transmitted signals both temporally and spatially. By doing so, the focus of electromagnetic (EM) energy onto a tumor or cancerous region can be significantly enhanced and the necessary temperature gradients required for effective hyperthermia can be achieved.

BRIEF DESCRIPTION OF THE DRAWINGS

[0009] A fuller understanding of the present invention and the features and benefits thereof will be accomplished upon review of the following detailed description together with the accompanying drawing, in which:

[00010] FIG. 1 is a schematic view of an exemplary time-reversal based microwave hyperthermia system for treating cancer, according to an embodiment of the invention. [00011 ] FIG. 2 is a schematic view of an exemplary processor used for generating weighted timer-reversed microwave hyperthermia signals, according to another embodiment of the invention.

[00012] FIG. 3 is a cross-sectional view of a target area of a patient undergoing treatment using the system illustrated in FIG. 1.

[00013] FIG. 4 is a perspective view of a lensed TEM horn antenna element used in the system illustrated in FIG. 1 for effective ultrawideband (UWB) irradiation of biological tissue, such as a patient's breast.

DETAILED DESCRIPTION

[00014] The present invention is directed to systems, devices, and methods of medical therapy based on ultra-wideband (UWB) microwave hyperthermia. As described herein, one aspect of the invention is the utilization of robust weighted Capon beamforming based upon time reversal. Time-reversal-based robust weighted Capon beamforming, according to the invention, can shape transmitted signals both temporally and spatially. The temporally and spatially shaped signals generated according to the invention focus electromagnetic energy and provide the needed temperature gradients for effective hyperthermia. The invention can be used to treat various forms of cancer, especially breast cancer.

[00015] FIG. 1 is a schematic view of a time-reversal-based microwave hyperthermia system 100, according to one embodiment of the invention. The system 100 illustratively includes a source 110 of broadband microwave radiation, such as a microwave generator. The broadband microwave radiation source 110 can be a specialized ultra- wideband microwave generator. The broadband radiation source, accordingly, provides broadband RF signals, including UWB signals.

[00016] As illustrated, the system 100 further includes an antenna array 120 comprising a plurality of antenna elements 111, which, although shown as being equally spaced-apart, can be alternately spaced at unequal distances. Microwave transmission lines 115, such as coaxial lines, guide to the antenna elements 111 the output of the broadband radiation source 110. Accordingly, the output generated by the broadband microwave radiation source 110 can be emitted by the antenna elements 111 of the antenna array 120 as transmitted microwave signals.

[00017] As further illustrated, a processor 160 is communicatively linked to the broadband microwave radiation source 110. The processor can comprise, for example, a network-connected workstation, a standalone computer, a laptop computer, or other type of computing device capable of performing the functions described herein. As explained more particularly below, the processor 160 operates to adjust and control output power, frequency (or pulse shape) and pulse duration of the output of the microwave generator 110. An array processor 135 is illustratively linked communicatively to the processor 160. In an alternative embodiment, however, the array processor 135 can be integrated with the processor 160. As also explained more particularly below, the array processor 135 operates to control the antenna array 120.

[00018] Operatively, the antenna array 120 coupled to the broadband microwave radiation source 110 transmits focused broadband microwave radiation toward a targeted region. The target region backscatters some of the incident broadband radiation, the backscattered radiation being received by the antenna array 120. The backscatter signals can optionally be amplified by signal amplifiers 130 before the signals are conveyed to the processor 160 for processing.

[00019] Referring additionally to FIG. 2, the processor 160 illustratively includes a time-gating unit 202, which can be implemented in hardwired, dedicated circuitry and/or machine-readable code configured to run on one or more logic-based processors. The time- gating unit 202 time gates the backscattered signals to form time-gated signals. [00020] Additionally, the processor 160 illustratively includes a weighting unit 204 that also can be implemented in dedicated circuitry and/or machine-readable code. The weighting unit 204 analyzes the time-gated signals and calculates bearnforming weights corresponding to each of the antennas 111 in the antenna array 120 according to the weighting procedures described more particularly below. Illustratively, the processor 160 further includes a time-reversal unit 206 that time reverses the time-gated signals according to the time-reversal procedures also described more particularly below. The time-reversal unit also can be implemented in hardwired circuitry and/or machine-readable code. [00021] Additionally, the processor 160 illustratively includes a control unit 208. Like each of the other exemplary units of the processor 160, the control unit can be implemented in dedicated, hardwired circuitry and/or machine-readable code. Operatively, the control unit 208 weights the time-reversed signals and causes the antenna array 120 to retransmit to the target region time-reversed signals weighted by the beamforming weights. By effecting the above-described procedures, the time-reversal-based microwave hyperthermia system 100 provides weighted time-reversed signals, which are then transmitted, or rather retransmitted, from the antennas 111 of the antenna array 120 to the target. Due to the reciprocity of microwave propagation, the retransmitted signals - which are processed versions of the backscattered signals - can be focused proximate to the targeted region. [00022] Optionally, the processor 160 further includes a pre-processing unit (not explicitly shown) implemented in hardwired circuitry and/or machine-readable code. The pre-processing unit can pre-process the backscattered signals prior to the signals undergoing the procedure for time reversing the backscattered signals. Pre-processing is performed to remove interference and noise components from the backscattered signals. As described more particularly below, the signal noise can be induced by various factors, including particularly coupling between the antenna elements of the antenna array 120 as well as reflections from skin covering a targeted region or location suspected of being cancerous. [00023] A microwave, as generally defined, is an electromagnetic wave having a wavelength from 10 mm to 3000 mm and corresponding to a frequency of 0.1 GHz to 30 GHz. However, the microwave pulses used according to the invention are generally in a frequency range from about 1 GHz to 10 GHz, so as to provide sufficient penetration depth into normally lossy biological tissue. The target tissue region absorbs the microwave energy and heats up as a result.

[00024] The microwave penetration depth in biological tissue is known to depend on the fundamental properties of the tissue at the particular microwave frequency. Microwaves interact with biological tissue differently than do those in the infrared, optical and X-ray ranges. Microwaves interact with biological tissue primarily according to the water content of the tissue. Different water content in tissue results in different dielectric properties of the tissue, for example, different dielectric permittivity (or relative permittivity ε_r) and conductivity (σ) for microwaves. Permittivity is also referred to as the dielectric constant, as will be readily appreciated by one of ordinary skill in the art. For biological tissues, high permittivity is generally associated with high conductivity (σ). For breast tissue, specifically, both permittivity and conductivity are functions of frequency, so that at higher frequency, the permittivity becomes smaller while the conductivity becomes larger. [00025] Although generally described relative to breast cancer, the invention is not limited to treatment of breast cancer. The system and methods described herein also can be used for treatment of brain cancer, lung cancer, prostate cancer, and a variety of other cancers.

[00026] Due to the different water content in normal breast tissue (characterized by high-fat, low-water, and low-salt) as compared to malignant tumors (characterized by low- fat, high- water, and high-salt), the microwave energy absorbed by the tumor and the normal breast tissue are different. Thus the amount of microwave radiation backscattered from such tissues will be significantly different. From about 10 MHz to about 20 GHz, tissue energy absorption is predominantly a function of the conductivity (σ) of the tissue which increases with bound- water content, as well as salt content of the tissue. Due to the higher the conductivity (σ) of a malignant tumor, a malignant tumor absorbs more microwave radiation and backscatters less microwave radiation as compared to the surrounding normal breast tissue.

[00027] Referring still to FIG. 1, the time-reversal-based microwave hyperthermia system 100 can be used for treating cancer. A patient 180 has a confirmed tumor or other suspicious mass 182 in a breast 185. The initial diagnosis and identification of the tumor or suspicious mass can be based on a determination made in an earlier procedure. For this purpose, as is well known in the art, a radiotherapy planning system can be used to acquire planning images of a diseased portion and surrounding regions. Such radiotherapy planning systems generally include a computed tomography (CT) or magnetic resonance imaging (MRI) simulator. CT or MRI radiography is carried out to acquire a plurality of sectional 2- D images. These sectional images are combined using known algorithms to produce 3-D images, which are generally referred to as planning images. These 3-D planning images are displayed and then analyzed to identify the location of a diseased portion to be treated, such as the tumor of suspicious mass 182 illustrated in FIG. 1.

[00028] For treating the patient 180, a sufficiently high temperature is needed for inducing programmed cell death (apoptosis) of the tumor cells. Too high a temperature, however, can cause normal cells bordering the tumor or suspicious mass 182 to undergo necrosis, or otherwise damage the normal neighboring cells. A currently accepted target window of temperatures for therapy is between about 42°C and 45°C, with 43°C considered to be an ideal temperature for apoptosis of tumor cells without harming neighboring normal cells. If additional power is required to heat the tissue to the desired temperature, a power amplifier (not shown) can amplify the signal provided by the broadband microwave radiation source 110, such as a microwave generator. The broadband microwave radiation source 110 can be an UWB microwave pulse generator.

[00029] In a preferred embodiment, the radiation pulses are UWB signals. UWB is believed by many to have been first fully described in a series of patents including U.S. Pat. Nos. 4,641,317 and U.S. Pat. No. 5,363,108 to Fullerton. A second generation of FuUerton UWB patents include U.S. Pat. Nos. 5,677,927, 5,687,169, 6,031,862. However, the present invention is not limited to ultrawideband signals. UWB technology is sometimes referred to as impulse radio which is one of its most common forms. UWB signals have also come to signify a number of other terms, such as impulse, carrier-free, baseband, time domain, nonsinusoidal, orthogonal function and large-relative-bandwidth radio/radar signals. As used herein, the term "UWB" is intended to include each of these. [00030] UWB systems transmit signals across a much wider frequency than conventional systems. The bandwidth of a UWB signal is generally at least 25% of the center frequency. Thus, a UWB signal centered at 2.4 GHz would have a minimum bandwidth of 600 MHz and the minimum bandwidth of a UWB signal centered at 4 GHz would be about 1 GHz. The most common technique for generating a UWB signal is to transmit pulses with durations less than about 1 nanosecond. UWB wireless technology provides very low power consumption (microwatts), virtual immunity from RF noise that makes it well suited for use with this invention.

[00031] The term "antenna" generally comprises only the mechanical construction which transforms free electromagnetic (EM) waves into radio frequency (RF) signals traveling on a shielded cable and vice versa. However, in the context of antennas used herein, the term "antenna" has an extended meaning, functioning as a complete transceiver. Antenna array 120, accordingly, is a smart antenna array which includes the plurality of radiating elements 111 as well as the array processor 135, which, in turn can include a control unit as known in the art though not explicitly shown. The array processor 135 provides the smart antenna intelligence, normally realized using a digital signal processor (DSP). The array processor 135 controls feeder parameters of each antenna 111, based on several inputs, in order to optimize the radiated pattern. Different optimization criteria can be used, in the case of the invention, including time reversal algorithms based on pre-processed, time-gated backscatter signals.

[00032] The antennas 111 comprising the antenna array 120 are preferably ultra- wideband antennas if the generator 110 is an ultrawideband microwave pulse generator. Non- dispersive antennas, such as the bow-ties, TEM horns, pyramidal horns, a corrugated horns, or other resistively-loaded monopoles as well as dipole antennas, are preferred since they typically can be designed to achieve high radiation efficiency with relatively small size. The antennas 111 of the antenna array 120 are designed to support a traveling wave so that the signal is being radiated while it is traveling along the antenna structure. Therefore, the non- dispersive antennas can be used for transmitted pulse shape control since these antennas do not significantly broaden the pulse shape upon transmission and are preferred for pulsed radiation. Once the pulse is transmitted by the antenna elements 111, the frequency response of the antennas 111 causes the pulse to resonate at the antenna center frequency, with the pulse width equal to the inverse of the antenna bandwidth. To maintain the desired pulse shape and minimize the reflections from the end of an antenna, the shapes of the antenna arms and the resistance distributions on the antenna structure are preferably designed to minimize the reflection from the antenna ends.

[00033] The breast 185 of the patient 180 acts as a load to the radiating antenna. In one embodiment, a horn antenna with curved antenna arms is used. The resistance distributions on the antenna arms are used to absorb the reflected waves along the arms. The lens will also provide better impedance match between the horn and the load (e.g., the breast 185 of the patient 180) to further reduce further the reflection at the arm ends.

[00034] Antenna 120 is generally unbalanced, while the transmission line 115, such as a coaxial feed line, is generally balanced. Thus, impedance matching can provide improved transmission efficiency and minimizes signal ringing. In a preferred embodiment of the invention, a balun (not shown) is provided between the transmission line 115 which delivers the microwave pulses and the antenna array 120 to provide an impedance match. A single balun can generally be used provided the respective antenna elements in antenna array are substantially identical.

[00035] Tumor or suspicious mass 182 must be aligned with regard to antenna array

120 to direct the focused beam toward tumor 182. The time-reversal-based microwave hyperthermia system 100 can utilize registration using registration systems known in the art for this purpose. In a typical registration, an irradiation field shape is determined to coincide with an outline of an image of the diseased portion appearing in the planning images. An irradiating angle is determined from sectional images of a wide region including the diseased portion or a transmitted image, seen from a particular direction, produced by the 3-D images. A transmitted image seen from the irradiating angle is displayed. The operator then determines a shape of an irradiation field on the image displayed, and sets an isocenter (reference) to the irradiation field.

[00036] Subsequently, the patient 180 is positioned relative to the simulator. An irradiating angle corresponding to the irradiating angle determined as above is set to the simulator, and an image is generally photographed on a film through radiography for use as a reference photograph for collation.

[00037] The patient 180 is then positioned and restrained relative to the time-reversal- based microwave hyperthermia system 100. An irradiating angle is set to the irradiating angle determined as above, and film radiography is carried out by emitting radiation from antenna array 120. This radiation film image is correlated with the above film image acting as the reference photograph to confirm that the patient has been correctly positioned according to plan before proceeding with radiotherapy. Some repositioning may be required, but once acceptable patient positioning is confirmed, radiotherapy is begun. [00038] Besides emitting microwave radiation, antenna array 120 also receives the backscatter signals emanating from the region in breast 185 proximate to tumor 182. Although in a preferred embodiment, antenna array 120 functions as a detector for backscattered signals, separate detectors may also be used. The backscatter signals are preferably amplified by signal amplifiers 130 before being sent to processor 160 for processing, as described above. Processor 160 provides processing and control of signals received from the amplifiers 130. [00039] The time-reversal-based microwave hyperthermia system 100 uses thus utilizes the time reversal based processing of the received backscatter signals to optimize the transmitted thermotherapy signal. Time reversal processing is based on the spatial matched filtering principle. However, as noted above, prior to time reversal processing, both preprocessing to remove interference/noise components and then time gating of the pre- processed signal to select only direct scatter components are preferably performed. It is preferable to perform pre-processing before commencing the time gating. Pre-processing and time gating are both performed as described above. Pre-processing eliminates or at least significantly reduces noise related effects including coupling between the respective antenna elements comprising the antenna array as well as reflections from the skin being irradiated. [00040] An exemplary pre-processing of the received backscattered signal is schematically illustrated in FIG. 3, which models the breast as an ideal hemisphere, and in which the antenna elements A1-A7 of an antenna array are equally spaced apart and disposed to form a hemisphere. A more complex arrangement and procedure can model the breast in a non-hemispherical shape, since the breasts of different patients can have various shapes. Moreover, the antenna elements A1-A7 of the antenna array can be also non-equally spaced and disposed in formations other than a hemisphere (e.g., a linear array). [00041] Each antenna element A1-A7 in turn can be considered to transmit a pulse.

The backscattered signal is received by all antennas. The respective backscattered signals are denoted as Xj _j(t) (i=l , 2, ... , M; j=l , 2, ... , M), which represent the signals received by the j^th antenna when the pulse is sent by the i^th antenna. The received backscatter signals contain the tumor response, but also can contain other undesired signals owing to the coupling among antennas and the reflections from the skin, for example. Since the distance between the transmitter and the nearest breast skin is fixed and the properties of the skin are generally substantially uniform, it can be assumed that the backscattered signals recorded at different antennas with the same relative locations contain similar antenna coupling and skin reflections. The relative location refers to the location of the receiver relative to the location of the transmitter, as shown in FIG. 2. Thus, for example, when the 1^st antenna Al and the 3^rd antenna A3 work as the transmitter and receiver, respectively, the received signal is x₁₎₃(t), which has the same relative location with the signal X₂,₄(t) (the 2^nd antenna A2 is the transmitter, and the 4^th antenna A4 is the receiver). Based on this assumption, a calibration signal is formed as an average of the signals received by an antenna group with the same relative locations. The antenna coupling and the skin reflections can thus be removed when the calibration signal is subtracted out from the received signals in the group. [00042] Time gating is then applied to the pre-processed signals to form time-gated signals. Time gating generally is used to retain only the direct paths of backscattered signals from the tumor location. Indirect paths result in longer path lengths that take longer times to reach the antenna detector as compared to the desired backscattered signals that traverse a direct path.

[00043] Following pre-processing and then time gating as described above, time- reversal processing is used. Different time-reversal techniques have been developed in many distinct fields, including detection of defects in solids, underwater acoustics, and room acoustics, as well as ultrasound medical imaging and therapy. Time-reversal is possible because the underlying physical process of wave propagation is theoretically unchanged if time is reversed. In a nondissipative medium, the equations governing the waves guarantee that for every wave that diverges from a source there exists, in theory, a set of waves that can precisely retrace the path of the wave back to the source. This remains true even if the propagation medium is heterogeneous and presents variations of density and compressibility that reflect, scatter, and refract the EM wave. Point-like sources allow focusing back on the source, whatever is the medium complexity. For this reason, time reversal represents a very powerful adaptive focusing technique for complex media. Time reversal is described, for example, in U.S. Patent No. 6,490,469 to Candy and U.S. Published Patent Application No. 2003/0138053 to Candy and Meyer. The disclosures of U.S. Patent No. 6,490,469 and U.S. Published Patent Application No. 2003/0138053 are incorporated herein by reference. [00044] As used in cancer therapy generally, and breast cancer therapy in particular, time reversal processing can turn the disadvantage of the heterogeneous breast tissue and the presence of breast skin into an advantage to achieve better focusing. Although desirable from a performance standpoint, time reversal processing according to the invention applied to cancer therapy is substantially more challenging as compared to conventional ultrasound, such as used for breaking up kidney stones into small pieces, or communications. For example, applied to breast and other cancer therapy applications, strong backscattering noise signals from the skin (e.g. breast skin) are encountered.

[00045] Time reversal uses an array to receive and process the backscattered signals from an initial low energy microwave irradiation of the breast, time reverse and magnify them, and retransmit them. This re-focusing, achieved by using all the antennas in the antenna array to transmit the time reversed and processed versions of their received signals, causes an accurate confluence of energies at the tumor. As a result of time reversal, the heterogeneous properties of the breast tissue, which degrade the performance of the existing approaches, can help improve the energy focusing onto the tumor. For example, the breast skin will generally act as reflection boundaries for the backscattered signals and can improve the energy focusing as well. Since the time reversal can be done quickly, breast motion during a given procedure can generally be neglected. The generation of this reconverging wave is generally provided by microwave source coupled to the antenna array that can record the wavefield coming from the sources and send back a time-reversed version in the medium. [00046] For such applications, a three-step procedure can be used. One part of the antenna array 120, such as single array element can be caused to radiate a brief pulse to illuminate the region of interest. If the region contains a point reflector, the reflected wave front is selected by means of a temporal window and then the acquired information is time- reversed and reemitted. The reemitted wave front then refocuses on the target through the medium.

[00037] Although not explicitly illustrated in the figures, the time-reversal-based microwave hyperthermia system 100 can include structure for measuring the temperature proximate to the tumor, and a feedback and control system which automatically maintains the desired tumor temperature. The measured temperatures can be used as real-time feedback signals to control the microwave output power, which is generally set and maintain the focal temperature at around 43 ⁰C. For example, the structure for measuring temperature can be one or more infrared thermometer for measuring the local temperature at the focus and in the surrounding tissues during treatment. Nuclear magnetic resonance (NMR) may also be used. In one embodiment, a fiber optic light pipe having a temperature sensor on its distal end may be inserted into the tumor region of the patient.

[00038] FIG. 4 illustrates a lensed TEM horn antenna 400 that can be used in the antenna array 120 for effective ultrawideband irradiation of biological tissue, such as breast tissue. A TEM horn antenna is a typical ultrawideband antenna, which can provide a satisfactory UWB irradiation pattern for breast irradiation. Antenna 400 includes TEM horn 415 and a feed point 405 for receiving a UWB signal from the broadband microwave radiation source 110 (e.g., microwave generator) via the microwave transmission line 115. Antenna 400 also includes a lens 410 which surrounds TEM horn 415 and focuses the radiated beam, reduces the size of the antenna 400, maintains an effective radiation aperture, and minimize the microwave reflections. [00039] For efficient microwave irradiation, the antenna can be designed to achieve desired parameters, such as polarization, radiation pattern, gain, and beam width. For example, antenna polarization can play an important role in tumor heating. Antenna design software can be used for initial antenna design parameters based on the desired antenna parameters. Testing of the design generally follows, followed by one or more design and test iterations until the desired parameters are achieved.

[00040] In a preferred embodiment, time reversal processing is combined with adaptive signal processing. In a highly preferred embodiment, UWB irradiation is used together with time reversal based robust Capon beamformer, for hyperthermia treatment cancer. Thus, two high-resolution techniques, time reversal and robust Capon beamforming, are used together to shape the transmitted signals both temporally and spatially. This combination provides substantially better EM energy focusing ability than the existing methods, and can provide the necessary temperature gradients required for effective hyperthermia.

[00041] In a preferred embodiment as described above, the processor 160, or other processor, processes the received backscattered signals to eliminate as much as possible undesired components in them before time reversing them and retransmitting them using optimized antenna weights through use of an adaptive beamforming algorithm. Adaptive approaches are ideally suited for a systems according to the invention due to the large amount of information gathered by the system. The adaptive beamforming approaches can have much better resolution and much better interference rejection capability, which means much lower peak sidelobe levels and hence much better clutter suppression, than data-independent beamformers. Moreover, state-of-the-art robust adaptive array techniques are preferably used to further improve the energy focus onto the tumor cells while placing nulls in the beam patterns to avoid potential burns in other areas, such as critical organs. [00042] The robust Capon beamformer disclosed in U.S. Pat. No. 6,798,380 to Li, et al. (hereinafter '380 Patent) can be used with the present invention. The '380 patent and the present application are commonly assigned and include some of the same inventors. The '380 patent is hereby incorporated by reference into the current application in its entirety. The beamformer described in the '380 patent is referred to as a Robust capon beamformer (RCB). The RCB disclosed includes the steps of providing a sensor array including a plurality of sensor elements, such as a antenna array 120, wherein an array steering vector corresponding to a signal of interest (SOI) is unknown. The array steering vector is represented by an ellipsoidal uncertainty set. A covariance fitting relation for the array steering vector is bounded with the uncertainty ellipsoid. The matrix fitting relation is solved to provide an estimate of the array steering vector. The RCB has better resolution and much better interference rejection capability than data-independent beamformers, provided that the steering vector of the antenna array corresponding to each pixel of the image is known to within some uncertainty set. Careful calibration of the antenna array can assure the desired knowledge within an uncertainty set.

[00043] The RCB also provides a simple way of eliminating the scaling ambiguity when estimating the power of the desired signal. Additional information on adaptive beamforming is provided in J. Li and P. Stoica, eds., ROBUST ADAPTIVE BEAMFORMING, New York, NY: John Wiley & Sons 2005. Various adaptive beamforming techniques can be readily applied in the context of the present invention.

[00044] In an exemplary method, a 3-D region to be treated (e.g. breast) is irradiated with low energy UWB pulses using one or more antennas comprising the antenna array. The backscattered signals received at all antenna outputs are than modeled and processed. Based on time delays, amplitudes, shapes, as well as other factors in a pre-processing step, the components identified as clearly not due to the tumor are eliminated. Super resolution time series analysis methods can be used for improved processing performance by better separating the desired tumor signal from undesired interference. Time series analysis analyzes the frequency components of a time domain signal. The processed backscattered signals are then time reversed, magnified and weighted with adaptive weights (calculated based on the processed backscattered signals), and retransmitted.

[00045] The invention is expected to substantially improve the heating and killing of cancer cells due to significantly improved ability to focus the microwave energy onto the tumor cells while avoiding unnecessary burns. Applied to breast cancer, the improved thermotherapy may considerably reduce cancer recurrence after lumpectomy. [00046] It is to be understood that while the invention has been described in conjunction with the preferred specific embodiments thereof, that the foregoing description as well as the examples which follow are intended to illustrate and not limit the scope of the invention. Other aspects, advantages and modifications within the scope of the invention will be apparent to those skilled in the art to which the invention pertains.

Claims

CLAIMS We claim:

1. A microwave hyperthermia cancer treatment system, comprising: a source of broadband microwave radiation; an antenna array coupled to the source and comprising a plurality of antennas, wherein at least one of the antennas transmits broadband microwave radiation toward a target region, and wherein backscattered signals from the target region are received by the antenna array; and a processor coupled to the antenna array, the processor including a time-gating unit to time gate the backscattered signals, a weighting unit that calculates beamforming weights corresponding to each of the antennas based upon the time-gated signals, a time-reversal unit to time reverse the time-gated signals, and a control unit for causing the antenna array to transmit to the target region time-reversed signals weighted by the beamforming weights, wherein the time-reversed weighted signals have enhanced focus proximate to the target region.

2. The system of claim 1, wherein said computer and control unit further includes a preprocessing unit to pre-processes the backscattered signals so as to mitigate signal noise prior to time gating of the backscattered signals.

3. The system of claim 1 , wherein the weighting unit calculates the beamforming weights by implementing an adaptive beamforming procedure.

4. The system of claim 3, wherein the adaptive beamforming procedure comprises a robust capon beamforming (RCB) procedure.

5. The system of claim 4, wherein the RCB procedure comprises the steps of representing an array steering vector for the antenna array using an ellipsoidal uncertainty set, compiling a covariance fitting relation for the array steering vector by bounding with the uncertainty ellipsoid, and solving a matrix-fitting relation to provide an estimate of the array steering vector.

6. The system of claim 1, wherein the broadband radiation comprises ultra- wideband (UWB) radiation.

7. A method of treating cancer, comprising the steps of: providing an array of antennas; transmitting a pulse from one of the antennas toward a target location suspected of being cancerous; receiving backscattered signals from the target by the antennas, time reversing the backscattered signals and retransmitting the time reversed signals to the target, wherein the retransmitted time reversed signals have enhanced refocus proximate to the target location.

8. The method of claim 7, further comprising the steps of pre-processing the backscattered signal to remove noise components and time gating the backscattered signals to retain only direct backscattered paths from the target before performing the time reversing step.

9. The method of claim 8, wherein further comprising calculating beamforming weights corresponding to the array of antennas, the weights being calculated based upon the time- gated signals using a robust capon beamforming (RCB) procedure.

10. The method of claim 9, wherein the RCB procedure comprises the steps of representing an array steering vector for the antenna array using an ellipsoidal uncertainty set, compiling a covariance fitting relation for the array steering vector by bounding with the uncertainty ellipsoid, and solving a matrix fitting relation to provide an estimate of the array steering vector.

11. A method of time-reversal-based microwave hyperthermia, the method comprising: transmitting a pulse microwave signal that generates a plurality of backscattered signals by impinging on a target; time gating the backscattered signals; determining a plurality of beamforming weights based upon the time-gated backscattered signals; time reversing the time-gated backscattered signals; weighting the time-reversed backscattered signals based upon the calculated beamforming weights; and retransmitting at the target the time-reversed weighted signals.

12. The method of claim 11 , further comprising amplifying the time-reversed weighted signals prior to the retransmitting step.

13. The method of claim 11 , wherein the determining step comprises calculating robust weighted Capon beamforming (RWCB) weights.

14. The method of claim 13, wherein calculating the RCB weights comprises representing an array steering vector for an antenna array using an ellipsoidal uncertainty set, compiling a covariance fitting relation for the array steering vector by bounding with the uncertainty ellipsoid, and solving a matrix fitting relation to provide an estimate of the array steering vector.

15. The method of claim 11 , further comprising removing signal noise induced by at least one of antenna coupling and skin reflections from the backscattered signals prior to the time gating step.

16. A processor for generating signals to effect time-reversal-based microwave hyperthermia, the processor comprising: a time-gating unit for time gating backscattered signals generated in response to a microwave pulse impinging on targeted tissue; a weighting unit for calculating a plurality of beamforming weights based upon the time-gated backscattered signals; a time-reversing unit for time reversing the time-gated backscattered signals; and a control unit for weighting the time-reversed signals with the beamforming weights and causing the weighted time-reversed signals to be transmitted from an antenna array to the targeted tissue.

17. The processor of claim 16, further comprising a pre-processing unit for removing signal noise from the backscattered signals prior to the backscattered signals being time gated by the time-gating unit.

18. The processor of claim 17, wherein the signal noise comprises noise induced by at least one of antenna coupling and skin reflection.

19. The processor of claim 16, wherein the weighting unit is configured to calculate robust weighted Capon beamforming (RWCB) weights.

20. The processor of claim 19, wherein the weighting unit is configured to calculate the RWCB weights by representing an array steering vector for an antenna array using an ellipsoidal uncertainty set, compiling a covariance fitting relation for the array steering vector by bounding with the uncertainty ellipsoid, and solving a matrix fitting relation to provide an estimate of the array steering vector.