Patent Description:
Before a biopsy or surgical procedure to remove a lesion within a breast, e.g., during a lumpectomy procedure, the location of the lesion must be identified. For example, mammography or ultrasound imaging may be used to identify and/or confirm the location of the lesion before the procedure. The resulting images may be used by a surgeon during the procedure to identify the location of the lesion and guide the surgeon, e.g., during dissection to access and/or remove the lesion. However, such images are generally two dimensional and therefore provide only limited guidance for localization of the lesion since the breast and any lesion to be removed are three-dimensional structures. Further, such images may provide only limited guidance in determining a proper margin around the lesion, i.e., defining a desired specimen volume to be removed.

To facilitate localization, immediately before a procedure, a wire may be inserted into the breast, e.g., via a needle, such that a tip of the wire is positioned at the location of the lesion. Once the wire is positioned, it may be secured in place, e.g., using a bandage or tape applied to the patient's skin where the wire emerges from the breast. With the wire placed and secured in position, the patient may proceed to surgery, e.g., to have a biopsy or lumpectomy performed.

One problem with using a wire for localization is that the wire may move between the time of placement and the surgical procedure. For example, if the wire is not secured sufficiently, the wire may move relative to the tract used to access the lesion and consequently the tip may misrepresent the location of the lesion. If this occurs, when the location is accessed and tissue removed, the lesion may not be fully removed and/or healthy tissue may be unnecessarily removed. In addition, during the procedure, the surgeon may merely estimate the location of the wire tip and lesion, e.g., based on mammograms or other images obtained during wire placement, and may proceed with dissection without any further guidance. Again, since such images are two dimensional, they may provide limited guidance to localize the lesion being treated or removed.

Alternatively, it has been suggested to place a radioactive seed to provide localization during a procedure. For example, a needle may be introduced through a breast into a lesion, and then a seed may be deployed from the needle. The needle may be withdrawn, and the position of the seed may be confirmed using mammography. During a subsequent surgical procedure, a hand-held gamma probe may be placed over the breast to identify a location overlying the seed. An incision may be made and the probe may be used to guide excision of the seed and lesion.

Because the seed is delivered through a needle that is immediately removed, there is risk that the seed may migrate within the patient's body between the time of placement and the surgical procedure. Thus, similar to using a localization wire, the seed may not accurately identify the location of the lesion, particularly, since there is no external way to stabilize the seed once placed. Further, such gamma probes may not provide desired precision in identifying the location of the seed, e.g., in three dimensions, and therefore may only provide limited guidance in localizing a lesion.

The document "<NPL>" discloses a system for localizing a marker within a target tissue within a patient's body. The document <CIT> discloses systems for locating lesions within a patient's body.

Accordingly, apparatus and methods for localization of lesions or other tissue structures in advance of and/or during surgical, diagnostic, or other medical procedures would be useful.

The present invention is directed to a system according to claim <NUM> and a method according to claim <NUM>. The systems and methods may be used during surgical procedures or other procedures, such as during lumpectomy procedures.

In accordance with one embodiment, a marker is provided sized for introduction into a target tissue region within a patient's body that includes an energy converter for transforming energy pulses striking the marker into electrical energy; a switch coupled to the energy converter such that the energy pulses cause the switch to open and close; and one or more antennas coupled to the switch, the switch configured to open and close to modulate radar signals reflected by the marker back to a source of the signals. The antenna(s) may include one or more wire elements extending from a housing of the marker, one or more antenna elements printed on a substrate, or one or more chip antennas. Optionally, the marker may include one or more additional components, such as an electro static discharge (ESD) protection device coupled to the switch to provide protection against an electrostatic discharge event, a processor coupled to the energy converter for identifying signals in the energy pulses, one or more coatings or filters, and the like.

In accordance with another embodiment, a marker is provided for introduction into a target tissue region within a patient's body that includes one or more photosensitive diodes configured to convert light pulses received from a light source to generate a voltage; a switch; one or more antennas coupled to the switch; and a processor coupled to the one or more photosensitive diodes and the switch, the processor configured to analysis light pulses received by the one or more photosensitive diodes to identify a first predetermined bit code in the light pulses, the processor delivering the voltage from the one or more photosensitive diodes to the switch to cause the switch to open and close only after the light pulses include the first predetermined bit code, the switch configured to open and close to modulate signals reflected by the one or more antennas back to a source of the signals.

In accordance with still another embodiment, a marker is provided for introduction into a target tissue region within a patient's body that includes one or more photosensitive diodes configured to convert light pulses received from a light source to generate a voltage; a switch; one or more antennas coupled to the switch; and a housing containing the one or more photosensitive diodes and the switch, the housing comprising a filter or coating overlying the one or more photosensitive diodes, the filter or coating only permitting a predetermined segment of infrared light to strike the one or more photosensitive diodes.

In accordance with another embodiment, a plurality of markers are provided for introduction into a target tissue region within a patient's body, each marker including one or more photosensitive diodes configured to convert light pulses received from a light source to generate a voltage; a switch; one or more antennas coupled to the switch; and a processor coupled to the one or more photosensitive diodes and the switch. The processor of each marker is configured to analysis light pulses received by the one or more photosensitive diodes to identify a predetermined bit code in the light pulses, the processor delivering the voltage from the one or more photosensitive diodes to the switch to cause the switch to open and close only after the light pulses include the predetermined bit code, the switch configured to open and close to modulate signals reflected by the one or more antennas back to a source of the signals, and wherein the predetermined bit code is different for each marker.

In accordance with still another embodiment, a plurality of markers is provided for introduction into a target tissue region within a patient's body, each marker including one or more photosensitive diodes configured to convert light pulses received from a light source to generate a voltage; a switch; one or more antennas coupled to the switch; and a housing containing the one or more photosensitive diodes and the switch, the housing comprising a filter or coating overlying the one or more photosensitive diodes, the filter or coating only permitting a predetermined segment of infrared light to strike the one or more photosensitive diodes, wherein the predetermined segment of infrared light is different for each marker.

The system may also include a marker sized for implantation within a patient's body, the marker including an energy converter configured to transform the energy pulses from the energy source into electrical energy, a switch coupled to the energy converter such that the energy pulses cause the switch to open and close to modulate the electromagnetic signals from the probe reflected by the marker, and one or more antennas coupled to the switch, the switch configured to open and close to modulate radar signals reflected by the marker back to a source of the signals.

In accordance with a reference example not covered by the present invention, a method is provided for localization of a target tissue region within a patient's body that includes implanting a marker within a patient's body, the marker including a switch, an energy converter, and one or more antennas; placing a probe adjacent the patient's body oriented towards the marker; and activating the probe to a) transmit electromagnetic signals into the patient's body, b) receive reflected signals from the patient's body, and c) deliver energy pulses into the patient's body such that the energy converter transforms the energy pulses into electrical energy to open and close the switch to modulate the electromagnetic signals from the probe reflected by the marker. The switch and antennas may modify an impedance of the marker and/or tissue within which the marker is implanted, e.g., in response to the electromagnetic signals that strike the marker. In an exemplary embodiment, delivering energy pulses into the patient's body may include delivering infrared light into the patient's body, and the energy converter may include one or more photosensitive diodes that transform the infrared light into electrical energy to open and close the switch to modulate the electromagnetic signals from the probe reflected by the marker. In addition, the probe may provide information related to the location of the marker within the patient's body and/or relative to the probe.

In accordance with yet another embodiment, a method is provided for localization of a marker within a target tissue region within a patient's body that includes implanting a marker within a patient's body; placing a tip of a probe adjacent the patient's body oriented towards the marker; and activating the probe to a) transmit a substantially continuous radar signal into the patient's body, b) receive a reflected signal from the patient's body, c) in synchronization with transmitting the radar signal, deliver light pulses into the patient's body such that the marker transforms the light pulses into electrical energy to open and close a switch in the marker to modulate the reflected signal reflected by the marker, and d) process the reflected signal using a synchronous detector to measure amplitude of modulation caused by the light pulses and provide an output identifying and/or indicative of range from the tip of the probe to the marker.

In accordance with another embodiment, a system is provided for localization of a marker within a target tissue region within a patient's body that includes a probe comprising one or more antennas for transmitting a radar signal into a patient's body towards a marker and receiving a reflected signal from the marker, and a light source for delivering infrared light pulses into the patient's body to cause the marker to change its reflective properties; a signal generator for generating a substantially continuous wave; a divider coupled to the signal generator for dividing the wave into first and second signals, the first signal delivered to the one or more antennas to transmit a substantially continuous transmit signal; a phase splitter coupled to the divider for receiving the second signal creating a replica signal out of phase with the second signal; first and second mixers coupled to the phase splitter for receiving the second signal and the replica signal, respectively, and coupled to the one or more antennas for receiving the reflected signal such that the first mixer mixes the second signal and the reflected signal and the second mixer mixes the replica signal and reflected signal to produce IF signals comprising components associated with modulation of amplitude and phase of the reflected signal caused by the light pulses changing the reflective properties of the marker; and a processor coupled to the mixers comprising a synchronous modulation detector that processes the IF signals to provide an output indicative of range from the one or more antennas to the marker based at least in part on the modulation of amplitude and phase synchronous with the light pulses delivered by the light source.

Other aspects and features of the present invention will become apparent from consideration of the following description taken in conjunction with the accompanying drawings.

These and other features, aspects, and advantages of the present invention will become better understood with regard to the following description, appended claims, and accompanying drawings where:.

In the following description, numerous details are set forth in order to provide a more thorough description of the system. It will be apparent, however, to one skilled in the art, that the disclosed system may be practiced without these specific details. In the other instances, well known features have not been described in detail so as not to unnecessarily obscure the system.

Turning to the drawings, <FIG> show a reflector marker or tag <NUM> that may be implanted within a patient's body, such as within a breast <NUM>, e.g., as shown in <FIG>. Generally, the marker <NUM> includes an electronics package <NUM> coupled to one or more wires or other antennas <NUM>. The marker <NUM> may be included in a system <NUM> for performing a procedure, such as a lumpectomy procedure, e.g., including a delivery device (not shown, see, e.g., <FIG>) for delivering one or more of the markers into tissue, a probe <NUM> for locating marker(s) implanted within tissue, and/or other components, e.g., as shown in <FIG> and described further below.

In an exemplary embodiment, each antenna <NUM> may be an elongate member, e.g., a solid or hollow structure having a diameter or other maximum cross-section between about half and two millimeters (<NUM>-<NUM>) and a length between about one and ten millimeters (<NUM>-<NUM>). The antennas <NUM> may be formed from elastic or superelastic material and/or from shape memory material, e.g., stainless steel, Nitinol, and the like, such that the antennas <NUM> are biased to a predetermined shape when deployed within tissue, but may be elastically deformed, e.g., to facilitate delivery, as explained elsewhere herein. As described elsewhere herein, the antennas <NUM> may act to modify a resonance impedance of the marker and/or tissue within which the marker <NUM> is implanted, e.g., in response to radar or other electromagnetic signals that strike the marker <NUM>, to enhance detecting and/or locating the marker <NUM> within a patient's body.

Optionally, the antennas <NUM> may carry one or more beads or other elements (not shown), e.g., similar to embodiments described in the applications referred to above. For example, the antennas <NUM> may include core wires that carry a plurality of beads or segments (not shown) including multiple surfaces, angles, and/or edges to enhance detection of the marker <NUM>. In an exemplary embodiment, the beads may include a plurality of individual annular bodies, e.g., each defining a portion of a generally cylindrical or spherical shape.

As shown in <FIG>, the antennas <NUM> may be biased to assume a substantially linear configuration, e.g., such that the antennas <NUM> extend substantially parallel to a longitudinal axis <NUM> of the marker <NUM>. Alternatively, the antennas <NUM> may be substantially rigid such that the marker <NUM> remains in a substantially fixed, e.g., linear or curved, shape. Optionally, one or both antennas <NUM> may be offset from the longitudinal axis <NUM>, which may enhance loading the marker <NUM> within a delivery device (not shown), as described elsewhere herein or in the applications referred to above.

As best seen in <FIG>, each antenna <NUM> may include a first end 44a coupled to a printed circuit board (PCB) or other substrate <NUM> within the package <NUM> and a second free end 44b terminating in an enlarged and/or rounded tip <NUM>. Optionally, the first ends 44a may include one or more bends, e.g., to facilitate coupling the first ends 44a to the substrate <NUM> and/or such that the antennas <NUM> extend tangentially from opposite sides of the package <NUM>, as best seen in <FIG>.

Alternatively, the antennas <NUM> may be biased to assume a curvilinear or other configuration, e.g., a helical, serpentine or other curved shape, around the longitudinal axis <NUM>. For example, the antennas <NUM> may be formed from elastic or superelastic material that is shape set such that the antennas <NUM> are biased to a helical configuration (not shown), yet may be resiliently straightened to a substantially linear configuration, e.g., to facilitate loading the marker <NUM> into a delivery device and/or otherwise introducing the marker <NUM> into a patient's body, e.g., as described in U. <CIT>, <CIT>, and <CIT>.

With additional reference to <FIG>, the marker <NUM> may include one or more circuits or other electrical components encased or embedded in the electronics package <NUM> and configured to modulate incident signals from a probe (not shown, such as the probe <NUM> shown in <FIG> and described elsewhere herein) used to locate the marker <NUM>, also as described elsewhere herein. For example, the components may be provided on a semiconductor chip, print circuit board (PCB), and/or other substrate <NUM> carried in the package <NUM>. In an exemplary embodiment, the components may include a voltage or power source or other power or energy converter <NUM>, a switch <NUM> that may be opened and closed when the energy converter <NUM> generate electrical energy, and an Electro Static Discharge (ESD) protection device <NUM>, e.g., mounted or otherwise provided on the substrate <NUM>.

The components may be encased within one or more components defining the package <NUM>. In an exemplary embodiment, the components may be soldered, glued, or otherwise mounted on a surface of the substrate <NUM> and encapsulated in epoxy or other insulating and/or protective material (not shown). For example, the components may be mounted within the package <NUM> such that the components are electrically isolated from one another other than as coupled in the schematic of <FIG>. Optionally, shrink tubing or other outer body may be applied around the epoxy material, e.g., to provide a desired finish and/or outer surface for the marker <NUM>.

In an exemplary embodiment, the energy converter <NUM> includes a plurality of photosensitive diodes capable of transforming incident light (e.g., infrared light) striking them into electrical energy (e.g., a predetermined minimum voltage). As shown, multiple pairs of diodes <NUM> may be connected in series, which may be arranged orthogonally to one another spatially within the package <NUM>. For example, given that photosensitive diodes are directional, at least two pairs of diodes <NUM> may be mounted within the package <NUM> offset one hundred eighty degrees (<NUM>°) or otherwise relative to one another, e.g., as best seen in <FIG>, such that at least one pair of diodes <NUM> may receive light from a light transmitter of the probe <NUM> regardless of the orientation of the marker <NUM> relative to the probe <NUM> after implantation. The package <NUM> may be at least partially transparent or the diodes <NUM> may be exposed such that light directed towards the package <NUM> may be received by the diodes <NUM>.

Optionally, the diodes <NUM> and/or any surfaces of the package <NUM> overlying the diodes <NUM> may include one or more coatings, filters, and the like (not shown), e.g., formed on the shrink tubing or other components of the package <NUM>, to limit the light that strikes the diodes <NUM> in a desired manner. For example, one or more coatings may be provided that only permit a desired band width of infrared light to strike the diodes <NUM>. In this manner, multiple markers may be provided that allow different band widths to activate the respective markers, e.g., such that a probe may activate a desired marker by transmitting infrared red limited to the particular band width of the desired marker.

In alternative embodiments, the energy converter <NUM> may include other components capable of transforming external energy into a desired voltage. For example, if the probe <NUM> includes another power source, e.g., a source of EMF, RF, or vibrational energy, the energy converter <NUM> may include a pick-up coil, antenna, or other device capable of transforming the incident energy into the desired voltage, e.g., including a capacitor and/or other components arranged to deliver the desired voltage to the switch <NUM>. One advantage of infrared energy is that it may pass sufficiently through tissue such that a probe <NUM> placed against a patient's skin may deliver sufficient energy to activate a relatively small marker <NUM> implanted several inches away within the patient's body, e.g., within a breast <NUM>, as shown in <FIG>.

In <FIG>, the switch <NUM> may be a field effect transistor (FET), e.g., a junction field effect transistor (JFET), with one end of the diodes <NUM> coupled to the gate (G) and the other coupled to the source (S), with a resistor <NUM> coupled between the gate (G) and the source (S), e.g., to discharge the diodes <NUM> when there is no IR light. In an exemplary embodiment, the switch <NUM> may include an enhancement mode pseudomorphic high electron mobility transistor (E-pHEMT), such as a VMMK-<NUM> manufactured by Avago Technologies US Inc. , and the resistor <NUM> may be a three mega-Ohm (3MΩ) resistor. In an alternative embodiment, the switch <NUM> may be a Schottky diode coupled to the diodes <NUM> (or other voltage source), e.g., with opposite ends of the diode coupled to the antennas <NUM>.

Also as shown, the source (S) of the switch <NUM> may be electrically coupled to one of the antennas <NUM> and the drain (D) may be coupled to the other antenna <NUM>. The antennas <NUM> may be bonded or otherwise attached to the package <NUM> such that ends of the antennas <NUM> are electrically coupled to the switch <NUM> as shown.

Each diode <NUM> may be capable of generating sufficient voltage (e.g., about a half Volt (<NUM> V)) when exposed to light to open and close the switch <NUM> when there is little or no load (i.e., current draw). Since the resulting circuit is intended to modulate signals from the probe <NUM>, little or no current is needed, and so the power required from the diodes <NUM> (and consequently from the probe <NUM>) may be minimal, thereby reducing power demands of the marker <NUM> and probe <NUM>.

With additional reference to <FIG>, light intermittently striking the diodes <NUM> may generate a voltage across the gate (G) and source (S) to provide a control signal that may open and close the switch <NUM>. For example, <FIG> shows the switch <NUM> in the open configuration when infrared light is absent, while <FIG> shows the switch <NUM> in the closed configuration when infrared light <NUM> strikes the diodes <NUM>, thereby connecting both antennas <NUM> together. Thus, the result is that the marker <NUM> provides a passive reflector tag that includes what equates to a high-frequency switch in the middle of the marker <NUM>. By being able to change the switch <NUM> from closed to open, the reflective properties of the effective antenna provided by the antennas <NUM> may be changed significantly. For example, the switch <NUM> may change the polarity or otherwise modulate signals reflected from the marker <NUM> as the switch <NUM> is opened and closed and/or may change a resonance impedance of the marker <NUM> and/or tissue within which the marker <NUM> is implanted.

Some of the challenges involved in detecting markers implanted within breast tissue (or elsewhere in a patient's body) include the relatively small radar cross-section (RCS) of such markers and contamination of the received reflected signal, e.g., due to (a) scattering caused by tissue inhomogeneity; (b) cross-talk between transmit and receive antennas of the probe; and (c) signal distortions due to near field effects and other factors. To deal with these complicating factors and distinguish the reflected marker signal from contaminating signals received by the probe, the switch <NUM> provides periodic modulation of reflective properties of the marker <NUM>.

Specifically, the marker <NUM> is made to periodically change its structure between two form factors, e.g., the reflectors shown in <FIG>. For example, as described further elsewhere herein, digital signal processing of the received signals using ultra-wideband (UWB) radar uses synchronous detection of the signal modulated with marker switching frequency. This significantly increases the signal-to-noise (SNR) on the marker signal because other contaminating signals remain unchanged within the modulation period. To provide a mechanism for a synchronous detector, the marker switching process is controlled in the probe <NUM> by illuminating breast tissue with near infrared (IR) light pulses that are received by the marker <NUM>.

Switching of the marker reflective form-factor is controlled with the set of diodes <NUM> operating in photovoltaic mode. When the diodes <NUM> receive light from the probe <NUM> (represented by arrows <NUM> in <FIG>), the diodes <NUM> generate voltage that is applied between the gate (G) and source (S) of the switch <NUM>,which closes and connects together the drain (D) and source (S) making both antenna wires <NUM> connected together, as shown in <FIG>. When the light is off, the switch <NUM> is open and the drain (D) and source (S) are electrically disconnected, as shown in <FIG>.

In addition, the ESD device <NUM> may be coupled in parallel across the switch <NUM>, e.g., between the drain (D) and source (S), to provide protection against an electrostatic discharge event. For example, use of an E-pHEMT device as switch <NUM> sets restrictions on the absolute maximal voltage between the drain (D) and source (S ) and, therefore, across the marker's antennas. In the exemplary embodiment of a VMMK-<NUM> E-pHEMT, the maximal voltage across the switch <NUM> may be no more than about five Volts (<NUM> V). Modern breast surgery often involves the use of electro-cutting tools, electocautery tools, and/or other tools (not shown), which can generate electrical pulses of a few kV. If such a tool gets close to the marker <NUM>, the tool can cause a very large voltage across antenna wires <NUM> and destroy the switch <NUM>.

To increase survivability of the marker <NUM> during operation of such tools, the ESD protection device <NUM> truncates voltage on the switch <NUM> device when the voltage approaches the maximal value. Generally, the ESD protection device <NUM> in the marker <NUM> should have low capacitance that does not shunt the antennas <NUM> for the frequency range of the small amplitude UWB signal coming from the signals from the probe <NUM>. In exemplary embodiments, the ESD protection device <NUM> may be a transient voltage suppressor, such as a Zener diode, a low-capacitance varistor, and the like.

Turning to <FIG>, a reflector marker <NUM> is shown that includes an electronics package <NUM> carrying a circuit board or other substrate <NUM> including top and bottom (or first and second) surfaces, having one or more antennas <NUM> printed or otherwise formed directly thereon. As shown, the marker <NUM> also includes an energy converter, e.g., diodes <NUM>, a switch, e.g., FET <NUM>, coupled to the diodes <NUM>, and an Electro Static Discharge (ESD) protection device <NUM> attached to one of the top and bottom surfaces, similar to other embodiments herein.

In addition, unlike the previous embodiments, the antennas <NUM> may be printed or otherwise formed directly on the top surface 150a of the substrate <NUM>. Each antenna <NUM> may include a first end 144a coupled to the FET <NUM> and a second free end 144b. As shown, each antenna <NUM> includes a sinusoidal or other zigzag section 144c adjacent the free end 144b, e.g., to maximize an effective length or profile of the antenna <NUM> relative to the available surface on the substrate <NUM>. In embodiments which include these features, the antennas <NUM> may be coupled, respectively, to the drain and source of the FET <NUM>, and the diodes <NUM> (in series) may be coupled between the gate and source, e.g., similar to the previous embodiments.

In a further alternative, shown in <FIG>, the marker <NUM>' may include one or more chip antennas <NUM>' mounted to the substrate <NUM>. ' For example, as best seen in <FIG>, a single chip antenna <NUM>' may be coupled to the drain of the FET <NUM>,' and a capacitor (not shown) may be coupled across the drain and the source, e.g., in parallel with the ESD protection device <NUM>. ' Alternatively, a pair of chip antennas (not shown) may be provided coupled to the drain and source of the FET <NUM>,' similar to the previous embodiments. In an exemplary embodiment, the chip antenna <NUM>' may be a ceramic chip antenna, such as the Model W3078 manufactured by Pulse Electronics Corporation.

In still a further alternative, one of the antenna elements <NUM> or <NUM> may be replaced with a capacitor (not shown). For example, <FIG> show a a marker <NUM>' similar to the marker <NUM> shown in <FIG>, i.e., including an electronics package <NUM>' carrying a circuit board or other substrate <NUM>' and including an energy converter, e.g., diodes <NUM>,' a switch, e.g., FET <NUM>,' coupled to the diodes <NUM>,' and an Electro Static Discharge (ESD) protection device (not shown). Unlike the marker <NUM>, the marker <NUM>' includes a single antenna <NUM>' coupled to the drain of the FET <NUM>,' and a capacitor <NUM>'coupled across the drain and the source, e.g., in parallel with the ESD protection device.

Returning to <FIG>, the substrate <NUM> may be formed from one or more electrically insulating materials, e.g., a ceramic plate or board, having desired dielectric properties. The antennas <NUM> and/or other leads may be formed on the top and/or bottom surface of the substrate <NUM>, e.g., by vapor deposition or other printing methods. As a result of the dielectric substrate <NUM>, the antennas <NUM> may have a dielectric constant higher than air, which may make the marker <NUM> appear electrically larger than its actual physical size. It will be appreciated that the construction of the antennas <NUM> and substrate <NUM> may be modified to provide a complex impedance that may be changed to provide desired detection characteristics for the final marker <NUM>, e.g., when being detected and/or located using the probe <NUM>.

Optionally, the marker <NUM> (or any of the other markers herein) may include a processor (not shown) coupled to the diodes <NUM> for identifying a code or message included in infrared signals transmitted to the marker <NUM>. For example, the processor may be coupled between the diodes <NUM> and the gate of the FET <NUM> such that the FET <NUM> is only switched when a predetermined code is included in the incoming infrared signals. Thus, the processor may selectively provide a control signal to the gate to open and close the FET <NUM> when a set of infrared pulses are received by the diodes <NUM>, e.g., to selectively apply a voltage across the drain and source of the FET. In an exemplary implementation, the code may include a sequence of infrared pulses with pulses separated in time and/or having different pulse lengths to provide a bit code that may be identified by the processor.

For example, with the FET <NUM> initially isolated from the diodes <NUM> (i.e., with the switch between the antennas <NUM> open), the processor may determine whether the pulses include a predetermined bit code assigned to the marker <NUM>. If so, the processor may couple the diodes <NUM> to the FET <NUM> such that subsequent infrared pulses close and open the switch between the antennas <NUM>, thereby modulating the reflective properties of the marker <NUM>, as described elsewhere. Optionally, the processor may allow the FET <NUM> to continue to open and close until another predetermined bit code is identified, whereupon the processor may once again isolate the diodes <NUM> from the FET <NUM>. Alternatively, the processor may activate the switching for a predetermined time and then open the FET <NUM> until reactivated.

In this manner, a plurality of markers (not shown) may be implanted within a patient's body that include respective processors assigned different bit codes. A probe, such as probe <NUM> shown in <FIG>, may transmit infrared pulses that may be preceded by a desired bit code to activate and/or deactivate individual markers. For example, the probe may use a first code to activate, detect, and/or located a first marker and then, deactivate the first marker and use a second code to activate, detect, and/or locate a second marker, optionally repeating the cycle to assist a user in identifying a region within a patient's body within which multiple markers are implanted, as described further elsewhere herein.

Turning to <FIG>, an exemplary embodiment of a system <NUM> is shown for localization of a target tissue region within a patient's body, such as a tumor, lesion, or other tissue structure within a breast <NUM> or other location within a body. As shown in <FIG>, the system <NUM> generally includes a delivery device <NUM> carrying one or more targets, tags, or markers <NUM> (one shown), a probe <NUM> for detecting and/or locating the marker <NUM>, e.g., using radar, e.g., ultra-wide band micro-impulse radar, narrow band continuous radar, and the like, and a controller and/or display unit <NUM> coupled to the probe <NUM>, e.g., using one or more cables <NUM>, similar to embodiments described in the applications referred to above.

For example, the probe <NUM> may be a portable device having electromagnetic signal emitting and receiving capabilities, e.g., a micro-power impulse radar (MIR) probe, similar to embodiments described in the applications referred to above. As shown in <FIG>, the probe <NUM> may be a handheld device including a first or distal end <NUM> intended to be placed against or adjacent tissue, e.g., a patient's skin or underlying tissue, and a second or proximal end <NUM>, e.g., which may be held by a user. Generally, the probe <NUM> includes one or more antennas, e.g., a transmit antenna and a receive antenna (not shown) mounted on a ceramic disk <NUM> (shown in <FIG>), e.g., to provide an interface between the antennas and contacted tissue. In addition, the probe <NUM> includes a light transmitter, e.g., a plurality of light fibers <NUM> (shown in <FIG>), LEDs (not shown), and the like, configured to transmit light pulses (represented by dashed lines 1038a in <FIG>) into tissue contacted by the distal end <NUM>, e.g., into breast tissue <NUM>, as shown in <FIG>. The light fibers <NUM> may be coupled to a light source, e.g., LEDs (not shown) within the probe <NUM> or display unit <NUM>, e.g., by coupling <NUM>, such that light from the light source passes through the light fibers <NUM> distally from the distal end <NUM> of the probe <NUM>.

In exemplary embodiments of the method, the light source is an infrared light source, e.g., capable of delivering near infrared light between, for example, eight hundred and nine hundred fifty nanometers (<NUM>-<NUM>) wavelength. Optionally, the light fibers may include one or lenses, filters, and the like (not shown), if desired, for example, to focus the light transmitted by the probe <NUM> in a desired manner, e.g., in a relatively narrow beam extending substantially parallel to the central axis of the probe <NUM>, in a wider beam, and the like.

Optionally, the light source may be capable of transmitting relatively narrow bandwidths within the infrared spectrum, e.g., to activate individual markers including coatings and/or filters that limit activation of the respective markers based on respective narrow bandwidths. For example, the light source may include a plurality of LEDs, each capable of transmitting a relatively narrow and distinct bandwidth than the others. Alternatively, the light source may transmit a broad bandwidth of infrared (or other broader spectrum) light, and the probe <NUM> may include a plurality of filters or other components (not shown) that limit the portion of the bandwidth that is transmitted by the probe <NUM>. In this manner, pulses of narrow band infrared light may be transmitted by the probe <NUM> to activate individual markers, as described elsewhere herein.

Alternatively, the probe <NUM> may include other energy sources instead of the light transmitter <NUM>. For example, a source of electromagnetic energy, radiofrequency (RF) energy, vibrational energy, and the like (not shown) may be provided on the distal end <NUM> of the probe <NUM> for delivering energy pulses to activate the marker <NUM>, as described elsewhere herein. The energy source(s) may be pulsed in a predetermined manner, e.g., to cause the circuits of the marker <NUM> to be alternately activated and deactivated.

The probe <NUM> may include a processor within the display unit <NUM> including one or more controllers, circuits, signal generators, gates, and the like (not shown) needed to generate signals for transmission by the transmit antenna and/or to process signals received from the receive antenna. The components of the processor may include discrete components, solid state devices, programmable devices, software components, and the like, as desired. For example, the probe <NUM> may include an impulse generator, e.g., a pulse generator and/or pseudo noise generator (not shown), coupled to the transmit antenna to generate transmit signals, and an impulse receiver for receiving signals detected by the receive antenna. The processor may include a micro-controller and a range gate control that alternately activate the impulse generator and impulse receiver to transmit electromagnetic pulses, waves, or other signals via the transmit antenna, and then receive any reflected electromagnetic signals via the receive antenna, e.g., similar to other embodiments herein. Exemplary signals that may be used include radio waves, such as micro-impulse radar signals, e.g., in the ultralow bandwidth region.

The probe <NUM> may be coupled to a display <NUM> of the display unit <NUM>, e.g., by cables <NUM>, for displaying information to a user of the probe <NUM>, e.g., spatial or image data obtained via the antennas. Optionally, the probe <NUM> may include other features or components, such as one or more user interfaces, memory, transmitters, receivers, connectors, cables, power sources, and the like (not shown). For example, the probe <NUM> may include one or more batteries or other internal power sources for operating the components of the probe <NUM>. Alternatively, the probe <NUM> may include a cable, such as one of the cables <NUM>, that may be coupled to an external power source, e.g., standard AC power, for operating the components of the probe <NUM>.

As shown in <FIG>, the internal components of the probe <NUM> may be provided in a housing or casing such that the probe <NUM> is self-contained. For example, the casing may be relatively small and portable, e.g., such that the entire probe <NUM> may be held in a user's hand. Optionally, a portion of the probe <NUM> may be disposable, e.g., a portion adjacent the distal end <NUM>, or a disposable cover, sleeve, and the like (not shown) may be provided if desired, such that at least a proximal portion of the probe <NUM> may be reusable, e.g., similar to embodiments described in the applications referred to above. Alternatively, the entire probe <NUM> may be a disposable, single-use device while the display unit <NUM> may be used during multiple procedures by connecting a new probe <NUM> to the display unit <NUM>, which may remain out of the surgical field yet remain accessible and/or visible, as desired. Additional information on construction and/or operation of the probe <NUM> may be found in the applications referred to above.

<FIG> is a block diagram <NUM> showing exemplary components of the probe <NUM> (although, alternatively, some of the components may be located within the display unit <NUM> of <FIG>). The probe <NUM> may include a signal generator <NUM>, an amplifier <NUM>, an analog-to-digital (A/D) converter <NUM>, and a digital signal processor (DSP) <NUM>. The signal generator <NUM>, e.g., a reference oscillator, produces an oscillating signal, such as a square wave signal, a triangular wave signal, or a sinusoidal signal.

For example, a square wave signal <NUM> may be sent from the signal generator <NUM> to the transmit antenna of the antenna portion <NUM> of the probe <NUM>. When the square wave signal <NUM> passes through the transmit antenna, the transmit antenna acts as a band pass filter ("BPF") and converts the square wave signal <NUM> to a series of pulses <NUM>. As such, the transmit signal 1034T (shown in <FIG>) transmitted by the probe <NUM> includes a series of pulses <NUM>. The transmit signals 1034T is transmitted into the tissue and reflected from the marker <NUM> (as shown in <FIG>), as represented by the receive signals 1034R. Once the transmit signal 1034T is reflected from the marker <NUM>, the reflected signal (i.e., the receive signals 1034R) includes a series of attenuated pulses <NUM> (shown in <FIG>).

The receive antenna of the antenna portion <NUM> of the probe <NUM> receives the receive signals 1034R (shown in <FIG>). As shown in <FIG>, the receive signals 1034R, which may include a series of attenuated pulses <NUM>, may be inputted into an amplifier <NUM> in order to amplify the gain of the pulses <NUM>. The output of the amplifier <NUM> may be inputted into an A/D converter <NUM> in order to convert the amplified analog signal into a digital signal. The digital signal output from the A/D converter <NUM> may be inputted into a DSP <NUM> for processing. The DSP <NUM> may perform a number of processing functions including, but not limited to, calculating a difference in time from the time the transmit signal <NUM> was sent to the time the receive signal <NUM> was received, determining the distance from the tip of the microwave antenna probe <NUM> to the marker <NUM>, determining the location of the marker <NUM> in relation to the tip of the probe <NUM>, measuring the amplitude of the receive signals 1034R, and/or determining the direction the marker <NUM> is located in relation to the tip of the probe <NUM>, e.g., as described in the applications referred to above. The output of the DSP <NUM> may be presented on the display <NUM> of the display unit <NUM>.

Turning to <FIG>, an antenna probe <NUM> is shown that may be used in any of the systems and methods described elsewhere herein. Generally, the probe <NUM> includes a housing <NUM>, an antenna subassembly <NUM>, and shielding <NUM>. Optionally, the probe <NUM> may include an outer sleeve or cover (not shown) surrounding one or more components of the probe <NUM>, e.g., surrounding openings in the housing <NUM>, for reducing contamination, exposure, and/or otherwise protecting the internal components of the probe <NUM>.

With additional reference to <FIG>, the antenna subassembly <NUM> includes a transmit antenna 960t and a receive antenna 960r, each having a bowtie configuration, combined to form a Maltese cross antenna. As shown in <FIG>, each antenna <NUM> includes a pair of antenna elements <NUM> offset ninety degrees (<NUM>°) from one another on a disk or other base of dielectric material <NUM>. Each of the antenna elements <NUM> may be formed separately and then attached to the disk <NUM> or may be deposited directly onto the disk <NUM>. In an exemplary embodiment, the antenna elements <NUM> may be formed from silver film or other material deposited onto the top surface of ceramic disk <NUM>.

Circuitry <NUM> may be coupled to the antennas <NUM>, e.g., including a PCB <NUM> on which are provided one or more transformers <NUM> and connectors <NUM> coupled to the respective antenna elements <NUM> by appropriate leads. Coaxial cables <NUM> may be coupled to the connectors <NUM> to allow the antennas <NUM> to be coupled to other components of the system, similar to other embodiments described elsewhere herein.

As best seen in <FIG>, the disk <NUM> includes a plurality of radial slots <NUM> between the antenna elements <NUM>. Thus, the antenna elements <NUM> may be substantially isolated from one another by air within the slots <NUM>, which may increase sensitivity, reduce crosstalk and/or other noise, and the like. Alternatively, the slots <NUM> may be filled with other insulating material, e.g., foam and the like (not shown), which may have a desired relatively low dielectric constant to substantially isolate the antenna elements <NUM> from one another.

As best seen in <FIG>, the disk <NUM> may be mounted within the shielding <NUM>, which may in turn, be coupled to the tip <NUM> of the housing <NUM>, e.g., by one or more of bonding with adhesive, sonic welding, fusing, cooperating connectors (not shown), and the like. As shown, the shielding <NUM> includes an inner insulation layer, e.g., formed from a collar of nylon or other polymeric material, surrounded by a relatively thin outer shield <NUM>, e.g., formed from copper or other material, to provide a Faraday shield. In an exemplary embodiment, a layer of copper tape may be wrapped around the inner shield <NUM> with the ends secured together. Alternatively, the outer shield <NUM> may be a sleeve of shielding material into which the inner shield <NUM> is inserted and attached, e.g., by bonding with adhesive, interference fit, and the like.

As shown in <FIG>, the shielding <NUM> may have a length substantially greater than the thickness "t" of the disk <NUM>. For example, the inner shield <NUM> may include an annular recess <NUM> into which the disk <NUM> may be inserted and attached, e.g., by interference fit, bonding with adhesive, and the like. As shown, the bottom surface of the disk <NUM> may be substantially flush with the distal end of the shielding <NUM> such that the disk <NUM> may provide an interface to contact tissue during use, as described elsewhere herein. Optionally, a Mylar film or other relatively thin layer of material (not shown) may be provided over the bottom surface of the disk <NUM> and/or the shielding <NUM>, e.g., to prevent fluids or other material entering the tip, reduce contamination, and/or otherwise protect the tip of the probe <NUM>.

With continued reference to <FIG>, the top surface of the disk <NUM> (with the antenna elements <NUM>, not shown, thereon) may be exposed to a region of air within the shielding <NUM>. Because of the low dielectric constant of air, the transmission from the transmit antenna 960t is focused distally, i.e., towards the tissue contacted by the disk <NUM>. With the material of the disk <NUM> chosen to substantially match the dielectric constant of tissue, the depth of transmission into the tissue may be enhanced. The air behind the disk <NUM> may minimize lost energy that would otherwise be emitted by the transmit antenna 960t away from the tissue. Similarly, the disk <NUM> may focus the sensitivity of the receive antenna 960r directed towards the tissue. The air behind the disk <NUM> within the shielding <NUM> (as well as the slots <NUM> between the antenna elements <NUM>) may minimize crosstalk, noise and/or may otherwise enhance operation of the probe <NUM>. Additional information regarding the probe <NUM> and/or alternative embodiments may be found in the applications referred to above.

The system <NUM> of <FIG> may be used during a medical procedure, for example, in a breast biopsy or lumpectomy procedure, e.g., to facilitate localization of a lesion or other target tissue region and/or to facilitate dissection and/or removal of a specimen from a breast <NUM> or other body structure. It should be noted that, although the system <NUM> is described as being particularly useful in localization of breast lesions, the system <NUM> may also be used in localization of other objects in other areas of the body, e.g., as described in the applications referred to above.

Before the procedure, a target tissue region, e.g., a tumor or other lesion, may be identified using conventional methods. For example, a lesion (not shown) within a breast <NUM> may be identified, e.g., using mammography and/or other imaging, and a decision may be made to remove the lesion. A marker <NUM> (which may used in any of the embodiments described herein) may be implanted within the breast <NUM> within or adjacent the target lesion, e.g., using a needle or other delivery device, such as the delivery device <NUM> shown in <FIG>.

Once the marker(s) <NUM> is implanted, as shown in <FIG>, the probe <NUM> is placed against a patient's skin, e.g., against the breast <NUM>. Signals from the antenna of the probe <NUM> are delivered along with pulsed light from the light source to cause the switch <NUM> to open and close as the marker <NUM> receives and reflects the signals back to the probe <NUM>. If there is substantial clutter, crosstalk, or other noise being received by the probe <NUM>, e.g., due to the probe antennas, tissue or other structures within the patient's body near the marker <NUM>, and the like, the reflected signals from the two states (switch <NUM> open and closed) may be subtracted from one another, substantially eliminated the other noise, and allowing the probe <NUM> to identify and/or locate the marker <NUM>.

Thus, the probe <NUM> may use the modulated reflected signals to increase the signal-to-noise ratio of the signals. For example, the modulation of the marker <NUM> may modify the impedance of the marker <NUM> and/or the tissue within which the marker <NUM> is implanted. In particular, the antennas <NUM>, <NUM>' mounted on a ceramic substrate <NUM>, <NUM>' may modify the effective impedance of the tissue contacting or immediately surrounding the marker <NUM>, <NUM>' such that the probe <NUM>, using subtraction, may easily detect and/or locate the marker <NUM>, <NUM>' based on the changes in the impedance. Thus, the antennas <NUM>, <NUM>' may not behave as actual antennas but probes that allow modulation of the adjacent tissue.

Returning to <FIG>, the display <NUM> may display information to the user to facilitate locating the marker <NUM> within the breast <NUM>. For example, the display <NUM> may simply be a readout providing distance, angle, orientation, and/or other data based on predetermined criteria, e.g., based on the relative distance from the marker <NUM> to the probe <NUM>. The distance information may be displayed as a numerical value representing the distance in units of length, such as in inches (in. ) or centimeters (cm). In addition or alternatively, a speaker <NUM> on the display unit <NUM> may produce an audible indication of distance, e.g., spaced-pulses that increase in speed as the probe <NUM> is closer to the marker <NUM>. In another alternative, the display <NUM> may present a graphical image (e.g., a two-dimensional or three-dimensional image) depicting the marker <NUM>, the probe <NUM>, the distance from the probe <NUM> to the marker <NUM>, and/or a physiological picture of the body part containing the marker (e.g., the breast).

For example, as shown in <FIG>, the distal end <NUM> of the probe <NUM> is placed adjacent or in contact with the patient's skin, e.g., generally above the lesion, and/or otherwise aimed generally towards the lesion and marker <NUM>, and activated. The transmit antenna (not shown) of the probe <NUM> emits transmit signals 1034T that travel through the tissue and are reflected off of the marker <NUM>. Return signals 1034R are reflected back to the receive antenna (not shown) in the probe <NUM>, which may then determine a spatial relationship between the marker <NUM> and the distal end <NUM> of the probe <NUM>, e.g., a distance and/or orientation angle, to facilitate determining a proper direction of dissection for the surgeon.

In addition, substantially simultaneously, the probe <NUM> transmits light pulses 1038a, which may be received by the diodes <NUM> of the marker <NUM> (not shown, see, e.g., <FIG>). The diodes <NUM> may alternately generate a voltage, causing the switch <NUM> to open and close. This causes the marker <NUM> to change the phase of and/or otherwise modulate the signals reflected back to the probe <NUM>, which may process the signals, e.g., by subtraction, to identify and/or locate the marker <NUM>, and consequently the target lesion.

In one embodiment, the processor for the probe <NUM> may perform localization in two steps, namely an initial detection step to identify the marker <NUM>, and a range detection step to determine the distance from the probe <NUM> to the marker <NUM>. For example, in the detection step, the processor may simply use the amplitude of the return signals to identify the marker <NUM>. Once the marker <NUM> has been identified, the processor may be use time delay to determine the distance from the probe <NUM> to the marker <NUM>. For example, the time delay between the time the transmit signal 1034T is transmitted by the transmit antenna and the time the return signal 1034R is received by the receive antenna may be directly proportional to the distance from the probe <NUM> to the marker <NUM>, and the processor may determine the distance based on this time delay and present it to the user.

Tissue may then be dissected, e.g., by creating an incision in the patient's skin and dissecting intervening tissue to a desired depth, e.g., corresponding to a target margin around the lesion is reached. A tissue specimen may be excised or otherwise removed using conventional lumpectomy procedures, e.g., with the marker <NUM> remaining within the removed specimen <NUM>.

Optionally, the system shown in <FIG> may be used to detect and/or locate multiple markers implanted together within a tissue region. For example, a plurality of markers (not shown) may be implanted within a breast <NUM> spaced apart around a lesion, e.g., to define a desired margin for a lumpectomy. The probe <NUM> may be used to activate each of the markers, e.g., in a predetermined sequence or other procedure, such that information may be provided regarding each of the markers.

For example, as described above, each marker may be activated by a different relatively narrow bandwidth of infrared light, and the probe <NUM> may transmit infrared pulses sequentially in each of the different bandwidths to activate, detect, and/or locate the markers. For example, while transmitting MIR pulses, the probe <NUM> may transmit a first bandwidth to activate and detect a first marker, and thereafter transmit a second bandwidth to activate and detect a second marker, e.g., repeating the cycle in a desired manner to provide information regarding the locations of the markers. Alternatively, the probe <NUM> may include codes in the infrared pulses, e.g., to activate and/or deactivate individual markers such only an activated marker opens and closes the switch to modulate radar signals from the probe <NUM>. Thus, when the probe <NUM> subtracts the received modulated signals, the inactive markers produce no detectable response while the activated marker modulates the radar signals reflected back to the probe <NUM>.

In still another alternative, the characteristics of the individual markers may be set such that individual markers reflect only radar signals of a predetermined frequency range. For example, the materials and/or other properties of the antennas and/or substrates of the markers may be different, e.g., to provide different impedance characteristics that respond to different frequencies of radar signals This, in this alternative, the probe <NUM> may transmit radar signals at a first frequency to activate and detect a first marker, and thereafter transmit radar signals at a second different frequency to activate and detect a second marker, repeating the cycle, as desired to locate all of the markers.

Turning to <FIG>, a schematic of another exemplary embodiment of a system <NUM> is shown for identifying and/or detecting a marker <NUM> implanted within tissue (not shown). Generally, the system <NUM> includes one or more antennas, e.g., a transmit antenna 560t and a receive antenna 560r, and a light source, e.g., one or more infrared (IR) LEDs <NUM>, carried on a distal tip of a probe (not shown), and a processing and/or display unit (also not shown), e.g., similar to the probe and display unit shown in <FIG> and other embodiments described elsewhere herein and in the applications referred to above. Alternatively, as shown in <FIG>, the system <NUM>' may include a single antenna <NUM>' and a circulator <NUM>' that controls transmission and reception of signals via the antenna <NUM>,' as described further elsewhere herein.

Unlike the previous embodiments, as shown in <FIG>, when activated, the probe of the system <NUM> (or <NUM>') transmits a substantially continuous, e.g., sinusoidal, radio frequency or microwave signal <NUM> via the transmit antenna 560t (or antenna <NUM>'). Rather than a broadband micro-impulse radar signal, the signal <NUM> may be a narrow band signal, e.g., having a frequency centered between about <NUM> and <NUM>, or between about one and ten Gigahertz (<NUM>-<NUM>), e.g., about <NUM>. In synchronization with the RF signal <NUM>, light pulses <NUM> are transmitted via the LED(s) <NUM>, thereby generating a return RF signal <NUM> that is reflected off of the marker <NUM> and modulated by the infrared pulses <NUM>. As shown in <FIG>, the system <NUM> may include one or more controllers, processors, circuits, signal generators, gates, and/or other components that generate the signals <NUM>, <NUM> transmitted by the transmit antenna 560t and LED(s) <NUM>, and/or that process the return signal <NUM> received from the receive antenna 560r, e.g., as represented by IF signal <NUM> shown in <FIG> and described further below. The components of the system <NUM> may include discrete components, solid state devices, programmable devices, software components, and the like, which may be distributed between the probe and display unit, as desired.

For example, with continued reference to <FIG>, the system <NUM> includes a wave generator <NUM>, e.g., generating a continuous radio frequency or microwave sinewave signal at a desired frequency, that is split by power divider <NUM> such that a first signal 522a is delivered through an amplifier <NUM> to the transmit antenna 560t, which transmits signal <NUM> (e.g., signal <NUM> shown in <FIG>), and a second signal 522b is delivered to a first input 526a of a mixer <NUM>. In addition, the mixer <NUM> receives return signal <NUM> (e.g., signal <NUM> shown in <FIG>) from the return antenna 560r at a second input 526b via another amplifier <NUM>, and produces an intermediate frequency (IF) signal (e.g., signal <NUM> shown in <FIG>) that contains components associated with the modulation of the amplitude and phase of the return signal <NUM>. For example, the mixer <NUM> may remove the high frequency, RF, components in the return signal <NUM> to produce a signal, e.g., signal <NUM>, that includes only relatively low frequency components resulting from the modulation caused by the infrared pulses.

In particular, similar to other embodiments herein, the IR light from the LED(s) <NUM> causes the marker <NUM> to alternate between two form factors, e.g., opening and closing a switch (not shown) coupled to antennas of the marker <NUM> to modulate the reflective properties of the marker <NUM> and/or surrounding tissue, e.g., similar to the configurations shown in <FIG>. For example, <FIG> shows the alternating configuration of the marker antennas and the regions of the IF signal <NUM> corresponding to the two configurations. Because other reflections in the return signal <NUM> do not depend on the IR light modulation, they remain unchanged and can be removed from the IF signal <NUM>, e.g., by subtraction of portions of the signals corresponding to the two reflective states of the marker <NUM>.

The system <NUM> includes one or more processors, e.g., microprocessor <NUM>, that may control the various components and process the IF signal from the mixer <NUM>, e.g., after being filtered and amplified by a band-pass filter <NUM> and amplifier <NUM>, e.g., a programmable gain amplifier (PGA). For example, as shown in <FIG>, the microprocessor <NUM> may include an analog-to-digital converter (ADC) 530a coupled to a synchronous modulation detector 530b, which, in turn, is coupled to an IR controller 530c and an output controller 530d. The IF signal from the mixer <NUM> may be applied to the BP filter <NUM>, which is tuned to the frequency of the LED switching amplified by the PGA <NUM> controlled by the microprocessor <NUM>, e.g., by gain controller 530e. The filtered and amplified signal is then digitized at the ADC 530a (or alternatively, using an external ADC, not shown), and processed using the synchronous modulation detector 530b, which evaluates the amplitude of the synchronously switching components in the return signal <NUM> from the return antenna 560r. The values of the computed amplitude at the detector 530b may be output to the user, e.g., via output controller 530d to one or more output devices <NUM> as an indicator of the location and/or distance from the probe to the marker <NUM>.

Due to propagation losses, the strength of the return signal <NUM> is inversely proportional to the range from the antennas <NUM> to the marker <NUM>. Thus, the resulting amplitude determined by the detector 540b is inversely proportional to the distance from the probe to the marker <NUM>, and may be used to indicate relative distance from the probe to the marker <NUM> as the probe is moved around over the tissue region within which the marker <NUM> is implanted, e.g., similar to other embodiments herein and in the applications referred to above. For example, in one embodiment, the output device <NUM> may be a speaker that produces a clicking or other pulsed output that increases in pulse rate as the computed amplitude increases, thereby indicating that the probe is closer to the marker <NUM>, e.g., to identify the shortest path from the patient's skin to the target tissue region. In addition or alternatively, the output device <NUM> may include a display, which may include a numerical value, bar, or other visual output indicating the strength of the computed amplitude and, consequently, the relative distance from the probe to the marker <NUM>.

The system <NUM>' shown in <FIG> generally operates in a similar to manner to the system <NUM>. However, in this embodiment, the probe only includes a single antenna <NUM> that both transmits and receives signals. To accomplish this, the system <NUM>' includes a circulator circuit <NUM>' including an in/out terminal <NUM>' connected to the antenna <NUM>. ' For example, the transmit signal 522a' from the signal generator <NUM>' may be directed to an input of the circulator <NUM>,' after amplification by amplifier <NUM>,' and the circulator <NUM>' directs the signal to the in/out terminal <NUM>' such that the antenna <NUM>' transmits the signal <NUM> towards the marker <NUM>. The return signal <NUM> is received by the antenna <NUM>' and in/out terminal <NUM>' and is redirected by the circulator <NUM>' to an output of the circulator <NUM>' coupled to the amplifier <NUM>' and mixer <NUM>. ' The mixer <NUM>,' microprocessor <NUM>,' and other components then process the return signal, similar to the previous embodiment, to provide an output indicating the range from the probe to the marker <NUM>.

Turning to <FIG>, a schematic of yet another exemplary system <NUM> is shown for identifying and/or detecting a marker <NUM> (which may be any of the embodiments herein) implanted within tissue (not shown). Generally, the system <NUM> includes a probe (not shown) including one or more antennas, e.g., a single transmit/receive antenna <NUM> coupled to a circulator circuit <NUM> (or alternatively separate transmit and receive antennas, not shown), and a light source, e.g., one or more infrared (IR) LEDs <NUM>, carried on or within a distal tip thereof, and a processing and/or display unit (also not shown), e.g., similar to other embodiments herein. For example, similar to the previous embodiments, the system <NUM> may include a wave generator <NUM>, e.g., generating a continuous radio frequency or microwave sinewave signal at a desired frequency, that is split by power divider <NUM> into first and second signals 622a, 622b, with the first signal 622a delivered through an amplifier <NUM> to the antenna <NUM>, which transmits radar transmit signal <NUM> (e.g., similar to signal <NUM> shown in <FIG>).

Unlike the previous embodiments, the system <NUM> utilizes quadrature detection to enable evaluation of changes in amplitude and phase of radar signals separately to locate and/or determine distance to the marker <NUM>. For example, to provide quadrature detection, the system <NUM> may include a quadrature phase splitter <NUM> that receives the second signal 622b from the divider <NUM> and is coupled to mixers 626I, 626Q. The phase splitter <NUM> delivers an input signal <NUM> to the first mixer 626I that is the same as the second signal 622b and creates a ninety degree (<NUM>°) shifted replica 665Q that is delivered to the second mixer 626Q. The mixers 626I, 626Q also each receive return signal <NUM> (e.g., similar to signal <NUM> shown in <FIG>) from the antenna <NUM> and circulator <NUM>, e.g., via another amplifier <NUM>.

The mixers 626I, 262Q use the input signals <NUM>, 665Q and return signal <NUM> to produce two intermediate frequency (IF) signals I and Q that contain components associated with the modulation of the amplitude and phase of the return signal <NUM>, similar to the previous embodiments. The I and Q signals may then be band-pass filtered by filters 632I, 632Q and amplified by amplifiers 634U, 634Q, e.g., with the same gain IF amplifiers controlled by gain control 630e, and digitized simultaneously by ADC 630a for processing at the processor <NUM>. Alternatively, as shown in <FIG>, a system <NUM>' may be provided in which a high resolution analog-to-digital converter 630a' is provided, which may avoid need for the band-pass filters <NUM> and amplifiers <NUM> (otherwise, system <NUM>' includes similar components and functions similar to system <NUM>). The processor <NUM> may include one or more microprocessors, controllers, and/or other components to control the various components and process the IF signals I, Q from the mixers 626I, 626Q.

In another alternative, shown in <FIG>, the system <NUM>" may include components similar to the system <NUM> (with similar components numbered similarly but with " after the corresponding reference number), in which the modulation signal from the marker <NUM> is separated from DC components of I and Q using analog Band-Pass Filters 632I" and 632Q. " These, usually very small amplitude, signals may be amplified with Programmable Gain Amplifiers 634I" and 634Q" before being digitized using ADC <NUM>. " This amplification may be used to increase the range of marker detection and distance evaluation.

Similar to other embodiments, the IR light from the LED(s) <NUM> causes the marker <NUM> to alternate between two form factors, e.g., opening and closing a switch (not shown) coupled to antennas of the marker <NUM> to modulate the reflective properties of the marker <NUM>. Due to the periodic switching of reflective properties of the marker <NUM> caused by periodic IR LED modulation, both quadrature components (I and Q) contain the modulation signal. The amplitudes of these modulation components in I and Q data are computed using an algorithm by the synchronous quadrature modulation detector <NUM> to get IA and QA, respectively. Then, the amplitude A associated with the RF signal attenuation and phase shift (ϕ) associated with the propagation delay may be computed as:
<MAT>.

Using these quantities, the processor <NUM> may compute relative changes in propagation time and attenuation and, therefore, range change knowing propagation velocity or the range using a calibration method. The resulting values may be output to the user, e.g., via output controller 630d to one or more output devices <NUM> as an indicator of the location and/or distance from the probe to the marker <NUM>.

In an exemplary method, the system <NUM> may initially use amplitude of the return signal to identify and/or detect the marker <NUM>, e.g., similar to other embodiments herein. Once the marker <NUM> has been identified, the system <NUM> may use both amplitude and phase shift to provide range detection, i.e., the distance from the antenna <NUM> to the marker <NUM>. <FIG> is a schematic of the system <NUM> showing an exemplary method for range detection of the marker <NUM> implanted within tissue <NUM> using various paths defined by the system <NUM>.

As shown in <FIG>, IQ demodulator, which may include the phase splitter <NUM>, <NUM>' and mixers 626I, 626Q, 626I',626Q' shown in <FIG> or <FIG>, produces quadrature components I and Q from the return signal from the antenna <NUM> with respect to the transmit signal generated by the signal generator <NUM>. The complex amplitude of the return signal (SIQ) includes two components,<MAT>
where Sinterface is the signal resulting mostly from the propagation delay along path <NUM>-<NUM>-<NUM> in <FIG>, i.e., from the signal generator <NUM> to the antenna <NUM> and back through the circulator <NUM> to the IQ demodulator, and Smarker is the signal resulting from the propagation delay along path <NUM>-<NUM>-<NUM>, i.e., from the signal generator <NUM> through the antenna <NUM> and tissue <NUM> to the marker <NUM> and back to the IQ demodulator, which are defined as:
<MAT>
<MAT>
where D<NUM> is twice the distance or range from the interface of the antenna <NUM> to the marker <NUM>. AI and AM are complex amplitudes of the interface and marker reflections, respectively, capturing propagation attention and reflection phase shift, respectively. Due to relatively small reflection from the marker <NUM>, AI >> AM and the phase of SIQ is mainly determined by the phase of Sinterface. The value of AM amplitude changes in time due to modulation of the marker reflection by the light pulses, as described previously, and so the return signal may alternate between the following:
<MAT>
<MAT>.

The IQ demodulator may take the original signal from the signal generator <NUM> (e.g., split by divider <NUM>, shown in <FIG>), corresponding to path <NUM>-<NUM> in <FIG>, and mix it with signal <NUM> to produce two DC signals I and Q that can be considered as a vector in plane I, Q, e.g., as shown in FIGS. 20A and 20B. This vector changes as the reflection properties of the marker <NUM> changes due to the periodic light pulses turning on and off, e.g., between SIQ LED on and SIQ LED off. Vector SIQ consists of two main components representing two reflections in the transmit-return path, i.e., Sinterface and Smarker, as described above. Sinterface includes environmental reflections, which is mostly a contribution from the antenna interface with the tissue surface and remains constant, while Smarker represents the signal reflected from the marker <NUM>.

The IQ demodulator may take the resulting vector components and use a best-fit approximation or other algorithm to provide an output corresponding to the range, i.e., distance from the antenna to the marker <NUM>. For example, with reference to the system <NUM>" shown in <FIG>, the processor <NUM>" may evaluate complex amplitude AI as a DC component of the digitized values of I and Q and evaluate complex amplitude of modulation AM using synchronous detection with the IR LED modulation signal. Based on these amplitudes, the processor <NUM>" may evaluate propagation delay D<NUM> and, therefore, the distance between the antenna <NUM>" and marker <NUM>. The distance may be presented on output device <NUM>," e.g., displayed visually as numeric values on a display or encoded within an acoustic signal generated by a speaker.

Claim 1:
A system (<NUM>, <NUM>, <NUM>', <NUM>, <NUM>") for localization of a marker (<NUM>, <NUM>) within a target tissue region within a patient's body, comprising:
a probe (<NUM>, <NUM>) comprising one or more antennas (<NUM>, <NUM>, 560t, 560r, <NUM>', <NUM>, <NUM>') for transmitting a radar signal (1034T, <NUM>, 522a', <NUM>) into a patient's body towards a marker (<NUM>, <NUM>) and receiving a reflected signal (1034R, <NUM>) from the marker, and a light source (<NUM>) for delivering infrared light pulses (<NUM>) into the patient's body to cause the marker to change its reflective properties;
a signal generator (<NUM>, <NUM>, <NUM>') for generating a substantially continuous wave; characterised in that the system further comprises
a divider (<NUM>) coupled to the signal generator for dividing the wave into first (522a, 622a) and second (522b, 622b) signals, the first signal delivered to the one or more antennas to transmit a substantially continuous transmit signal;
a mixer (<NUM>, <NUM>', 626I, 626Q, 626I', 626Q') coupled to the divider for receiving the second signal (522b) and coupled to the one or more antennas for receiving the reflected signal, the mixer mixing the second signal and the reflected signal (<NUM>, <NUM>) to produce an intermediate frequency (IF) signal comprising components associated with modulation of amplitude and phase of the reflected signal caused by the light pulses changing the reflective properties of the marker; and
a processor (<NUM>, <NUM>, <NUM>', <NUM>, <NUM>") coupled to the mixer comprising a synchronous modulation detector (530b) that processes the IF signal to provide an output indicative of range from the one or more antennas to the marker based at least in part on the modulation of amplitude and phase synchronous with the light pulses delivered by the light source.