Systems and methods for locating and defining a target location within a human body

TECHNICAL FIELD

[0001] Several aspects of the present invention relate to systems and methods for locating a target tissue within a human body with wireless markers. Other aspects of the invention relate to wireless markers, instruments, user interfaces, and methods for using such systems in treating or monitoring a target location.

BACKGROUND

[0002] Many medical procedures require monitoring or treating an internal tissue mass or other body part within a human body. In such applications, medical procedures must accurately locate a small target location within a soft tissue region, an organ, a bone structure, or another body part (e.g., colon, vascular system, etc.). The small target location can be a lesion, polyp, tumor, or another area of interest for monitoring or treating a patient. One particular application involving the surgical treatment of cancer is particularly challenging because physicians often need to treat small, non-palpable lesions that cannot be observed. This problem is compounded in soft tissue applications because the soft tissue is mobile and can move with respect to a reference point on the patient. In the case of breast cancer, for example, the location of a non-palpable lesion in the breast is identified at a preoperative stage using an imaging system. The actual surgical procedure, however, occurs in an operating room at a subsequent point in time, and the patient is typically in a different position during the surgical procedure than during the preoperative imaging stage. The breast and the lesion may accordingly be in a different location relative to a reference point on the patient during the surgical procedure than the imaging stage. The physician, therefore, generally estimates the location of lesion during surgery.

[0003] One problem with treating non-palpable lesions in soft tissues is that the physicians may incorrectly estimate the location of the lesions. As a result, the physician may not remove all of the lesion, which is not desirable because some of the lesion will accordingly remain in the soft tissue. Another result is that the physicians may remove a significant amount of tissue proximate to the lesion, which can cause undesirable collateral damage to healthy tissue. Therefore, it would be desirable to know the precise location of the lesion or other type of target location during the surgical procedure.

[0004] A current technique for performing an excisional biopsy of a non-palpable breast lesion that has been identified by mammogram or other method involves placement of a needle or guide wire (e.g., a “Kopanz wire”), with or without blue dye, to guide the surgeon to the lesion. The tip of the needle is generally placed directly in or as close as possible to the lesion. When larger or more complex lesions are encountered, two or more guide wires are sometimes placed at each edge of the lesion. The entry point of the needle through the skin of the breast is usually several centimeters from the lesion due to the logistics of needle placement. The surgeon does not cut along the shaft of the needle from the skin because the distance is too great. Instead, the surgeon must estimate where in the breast the lesion is located by making reference to the location of the needle.

[0005] This technique is not optimal because it can be difficult to properly define the margins of the tissue that is to be removed, both during and after insertion of the needle(s), in tissue that is amorphous and pliable (e.g., breast tissue). Also, it is often difficult for the surgeon to detect the exact depth of the lesion based on the placement of the needles. For these reasons it is not uncommon that the biopsied tissue does not contain the mammographically positive specimen. In other cases, as a result of the difficulty of estimating the proper location of the boundaries of the volume of tissue to be removed, the lesion ends up being eccentrically positioned within the volume of tissue excised. This calls into question the adequacy of the margin of normal tissue surrounding the lesion. In still other cases, more normal tissue is removed than is required, which is disadvantageous in this era of tissue-conserving therapies.

[0006] In other fields of surgery it is known to target portions of a human body using various devices, and then refer to such devices in connection with the removal or treatment of such portions. For example, U.S. Pat. No. 5,630,431 to Taylor (the “'431 patent”) describes a surgical manipulator that is controlled, in part, by information received from beacons that are positioned proximate to a region of a human body to be treated. As another example, U.S. Pat. No. 5,397,329 to Allen (the “'329 patent”) describes fiducial implants for a human body that are detectable by an imaging system. The fiducial implants are implanted beneath the skin and are spaced sufficiently from one another to define a plane that is detectable by the imaging system and is used in connection with creation of images of a body portion of interest. These images are then used, for instance, in eliminating a tumor by laser beam.

[0007] Unfortunately, the devices described in the '431 and '329 patents are vastly more complex, and hence expensive, than is appropriate for many surgical procedures. This problem is particularly disadvantageous with the emphasis on containing costs in managed health care. Furthermore, due to the amorphous, pliable nature of certain tissue, the systems of the '431 and '329 patents cannot be used effectively. Systems of the type described in the '431 and '329 patents require that the devices (e.g., beacons or fiducial implants) defining the body portions of interest be substantially fixed relative to one another and relative to such body portions. These systems generally function effectively when the devices defining the body portion of interest are inserted in bone, e.g., in a skull in connection with brain surgery or treatment, but are not believed to operate as intended when the devices are inserted in amorphous, pliable tissue.

[0008] Breast lesions are typically excised with a scalpel manipulated directly by the surgeon. With the current emphasis on surgical therapies that conserve breast tissue, the above-described procedure for removing a breast lesion is typically performed through a narrow opening in the skin created by slitting and then pulling apart the skin. It tends to be difficult to manipulate the scalpel within this opening so as to remove the desired volume of tissue. The amorphous, pliable nature of breast tissue exacerbates removal of such tissue inasmuch as application of force to the scalpel causes movement of the breast tissue relative to the opening in the skin.

[0009] Circular cutting tools are not widely used in surgery. Recently, however, United States Surgical Corporation of Norwalk, Conn., introduced a relatively small diameter, e.g., 5-20 mm, circular cutting tool identified by the trademark ABBI for removing a cylinder of breast tissue for biopsy purposes. The ABBI tool includes an oscillating, motorized, circular cutting blade that incises the breast tissue. While use of the ABBI tool is believed to be a relatively effective way to perform a core biopsies of breast tissue, it is not apparently designed to remove cylinders of tissue having a diameter much in excess of about 20 mm. As such, it is not adapted for use in surgeries involving the removal of relatively large tissue portions in a single cutting sequence. In addition, the effectiveness of the ABBI tool in therapeutic, rather than diagnostic, surgeries has not been confirmed.

[0010] Detectors are used to locate organs or other portions of the body that have taken up a radioactive material, e.g., an antibody labeled with a radioactive material. For example, the gamma ray probe described in U.S. Pat. Nos. 5,170,055 and 5,246,005, both to Carroll et al., and sold by Care Wise Medical Products Corporation, Morgan Hill, Calif., and identified by the trademark C-TRAK, provides an audio output signal, the pitch of which varies with changes in relative proximity between the probe and a body portion that has taken up an antibody labeled with a gamma ray producing material, e.g., technetium 99. Once the body portion is detected, it is removed by known surgical techniques.

[0011] Even with the systems and techniques described above, it remains difficult for a surgeon to remove a tissue mass in amorphous, pliable tissue, such as breast tissue, so as to ensure that the entire tissue mass is removed while at the same time conserving portions of adjacent tissue. As a result, more tissue surrounding the targeted tissue mass is typically removed than is desired.

SUMMARY

[0012] The present invention is directed toward methods, systems, and system components for finding a target location within a human body. In one aspect of the invention, a system comprises a first wireless implantable marker configured to be implanted within the human body at a location relative to the target location, an instrument having a function-site and a first instrument marker connected to the instrument at a first predetermined site relative to the function-site, a position detection system, and a user interface. The position detection system can have a sensor that detects (a) a position of the first wireless implantable marker relative to a reference location and (b) a position of the first instrument marker relative to the reference location. The position detecting system can also include a computer that determines a relative position between the first wireless implantable marker and the first instrument marker based on the positions of the first wireless marker and the first instrument marker relative to the reference location. The user interface is operatively coupled to the position detection system. The user interface can have an indicator that denotes the position of the function-site of the instrument relative to the target location based on the relative position between the first wireless implantable marker and the first instrument marker.

[0013] In another aspect of the invention, a wireless implantable marker comprises a biocompatible casing configured to be implanted into a human body relative to a target location within the human body, a signal element in the casing, and a fastener. The signal element is configured to emit a response energy in reaction to an excitation energy. The fastener is configured to hold the wireless marker at a reference location in a human body relative to the target location within the human body.

[0014] Yet another aspect of the invention is an instrument for manipulation within a human or proximate to the human. The instrument can comprise a handle, a function-site coupled to the handle, and a first wireless instrument marker. The function-site is aligned with an alignment axis, and the first wireless instrument marker can be positioned along the alignment axis. The first wireless instrument marker is also configured to emit a wireless signal that can be detected by a position detection system to determine a position of the first wireless instrument marker relative to a reference location.

[0015] The systems and components can be used in many applications in which it is desirable to accurately know the relative position between an instrument and a target location within a human body. For example, one embodiment of a method of treating a target location within a human body comprises exciting a wireless marker implanted in the body by emitting an excitation energy in a manner that causes the marker to emit a response energy. The method can continue by sensing the response energy and determining a position of the wireless marker relative to a reference location based on the sensed response energy. In other aspects, the method can also include determining a position of an instrument with a marker relative to the reference location, and displaying the relative position between the instrument and the target location. Other aspects of the invention are described in the following detailed description of the invention and the claims, and the accompanying drawings illustrate several embodiments of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0016]FIG. 1 is an isometric view representative of a tissue mass and surrounding tissue volume that is bracketed by the markers, with two markers being positioned on opposite ends of each of mutually orthogonal X, Y and Z-axes intersecting the tissue mass so as to define the boundary of the tissue volume, and with the probe and detector being positioned adjacent the tissue volume in accordance with one embodiment of the invention.

[0017]FIG. 1A is an isometric view of the tissue mass illustrated in FIG. 1, with two markers being positioned on opposite ends of each of mutually orthogonal X1, Y1 and Z-axes and with two markers being positioned on opposite ends of mutually orthogonal X2 and Y2-axes which are mutually orthogonal with respect to the Z-axis and offset along with Z-axis with respect to the X1 and Y1-axes.

[0018]FIG. 1B is an isometric view of the tissue volume illustrated in FIG. 1, with two markers being positioned on opposite ends of each of V, W, X and Y-axes, all of which lie in a common plane and are mutually orthogonal with respect to a Z-axis, all of these axes intersecting the tissue mass.

[0019]FIGS. 2<i>a</i>-<b>2</b><i>g </i>are schematic representations of various embodiments of the markers of the present invention and their associated detection characteristics.

[0020]FIG. 3<i>a </i>is a block diagram of the elements of one embodiment of the marker illustrated in FIG. 2<i>c. </i>

[0021]FIG. 3<i>b </i>is a block diagram of the RF exciter used with the marker illustrated in FIG. 3<i>a. </i>

[0022]FIG. 4 is a block diagram of the elements of one embodiment of the marker illustrated in FIG. 2<i>e. </i>

[0023]FIG. 5 is a block diagram of the RF exciter used with the marker illustrated in FIG. 4.

[0024]FIG. 6 is a perspective view of one embodiment of the marker illustrated in FIG. 2F, with details of internal construction being illustrated in phantom view.

[0025]FIG. 7 is a block diagram of the probe and detector used with the marker illustrated in FIG. 2<i>b. </i>

[0026]FIG. 8 is a block diagram of the probe and detector used with the marker illustrated in FIG. 2<i>c. </i>

[0027]FIG. 9 is a front elevation view of a tissue anchor in accordance with one embodiment of the invention, with the cannula and rod of the cutter being shown in broken view to facilitate illustration.

[0028]FIG. 10 is an enlarged view of the tissue anchor in FIG. 9, with the rod and cannula both being broken at first location and the rod alone being broken at a second location to facilitate illustration, also with the rod being shown in a retracted position relative to the cannula.

[0029]FIG. 11 is similar to FIG. 10, except that the rod is shown in the extended position relative to the cannula, with the anchor members attached to the end of the rod being shown in an extended position engaged in a portion of a tissue mass.

[0030]FIG. 12 is a top view of a breast of woman in a supine position, with a tissue mass being surrounded by markers of one embodiment of the present invention so as to define the tissue volume to be removed, and with an incision formed in the skin of the breast above the tissue volume.

[0031]FIG. 13 is a cross-sectional view of the breast of FIG. 12 taken along line <b>13</b>-<b>13</b> in FIG. 12.

[0032]FIG. 14 is similar to FIG. 12, except that the skin adjacent the incision has been pulled apart to provide access to underlying breast tissue.

[0033]FIG. 15 is an enlarged view of the incision of FIG. 14, with the tissue anchor illustrated in FIGS. <b>9</b>-<b>11</b> being positioned in the tissue mass, and the two portions of a cutter illustrated being positioned adjacent the surgical cavity.

[0034]FIG. 16 is similar to FIG. 13, except that an incision has been formed in the skin of the breast and retracted to provide access to the underlying tissue mass to be removed and the tissue anchor has been positioned above the breast.

[0035]FIG. 17 is an enlarged view of the portion of the breast illustrated in FIG. 16 containing the tissue mass to be removed, with the tissue anchor being positioned in the tissue mass in the extended position so that the anchor members of the tissue anchor engage the tissue mass.

[0036]FIG. 18 is similar to FIG. 15, except that two portions of a cutter are illustrated in engaged, cooperative relationship and are positioned under the skin in contact with the tissue volume to be removed.

[0037]FIG. 19 is similar to FIG. 16, except that the tissue cutter is illustrated surrounding the tissue anchor and in cutting engagement with the tissue volume to be removed.

[0038]FIG. 20 is similar to FIG. 19, except that the tissue volume has been completely removed from the breast and is illustrated immediately above the surgical opening in engagement with the tissue anchor and cutter.

[0039]FIG. 21 is an isometric view of a system for locating and defining a target location within a human body in accordance with an embodiment of the invention.

[0040]FIG. 22 is a schematic elevation view illustrating a portion of a system for locating and defining a target location within a human body.

[0041] FIGS. <b>23</b>A-D are isometric cut-away views of wireless resonating markers in accordance with embodiments of the invention.

[0042] FIGS. <b>24</b>-<b>30</b> are side elevation views of several wireless implantable markers in accordance with embodiments of the invention.

[0043] FIGS. <b>31</b>-<b>33</b> are side elevation views of several wireless implantable markers in accordance with additional embodiments of the invention.

[0044] FIGS. <b>34</b>-<b>39</b> are isometric views of arrangements for implanting the wireless implantable markers relative to a target location T in accordance with embodiments of the invention.

[0045] FIGS. <b>40</b>-<b>43</b> are side cut-away views of instruments in accordance with embodiments of the invention.

[0046]FIGS. 44 and 45 are schematic views of wireless controls for instruments in accordance with embodiments of the invention.

[0047] FIGS. <b>46</b>-<b>52</b> are isometric views illustrating several instruments in accordance with various embodiments of the invention.

[0048]FIG. 53 is a partially schematic view illustrating an aspect of operating a system for locating and defining a target location within a human body in accordance with an embodiment of the invention.

[0049]FIG. 54A is a front elevation view of an embodiment of a user interface in accordance with the invention.

[0050]FIG. 54B is a graphical representation of calibrating a display coordinate system.

[0051] FIGS. <b>55</b>-<b>57</b> are front elevation views of several embodiments of user interfaces in accordance with various embodiments of the invention.

[0052] FIGS. <b>58</b>A-<b>58</b>C are front elevation views of an embodiment of a user interface illustrating a method of operating the system in accordance with an embodiment of the invention.

[0053] FIGS. <b>59</b>-<b>61</b> are front elevation views of several additional user interfaces in accordance with more embodiments of the invention.

DETAILED DESCRIPTION

[0054] The following description is directed toward systems and methods for locating and defining a target location within a human body. Several aspects of one system in accordance with an embodiment of the invention directed toward bracketing a target location with at least one marker are described below in Section I. Similarly, aspects of other systems in accordance with embodiments of the invention directed toward locating a target mass within a human body using the relative orientation between an implanted marker and an instrument are described below in Section II. Other aspects of embodiments of the invention directed toward defining and displaying a virtual boundary relative to a target location based on the location of an implanted marker are also described below in Section II.

[0055] I. Systems and Methods for Delineating a Target Location Using Bracketing

[0056] FIGS. <b>1</b>-<b>20</b> illustrate a system and several components for delineating a target location within a human body in accordance with several embodiments of invention. Several of the components described below with reference to FIGS. <b>1</b>-<b>20</b> can also be used in the systems set forth with respect to FIGS. <b>21</b>-<b>61</b>. Therefore, like reference numbers refer to like components and features throughout the various figures.

[0057] Referring to FIG. 1, one aspect of the present invention is a system <b>20</b> for defining the boundaries of, i.e., bracketing, a tissue volume <b>22</b> in a tissue portion <b>24</b>. Typically, tissue volume <b>22</b> will include a tissue mass <b>26</b>, e.g., a breast lesion, that is targeted for removal and a tissue margin <b>28</b> of unaffected tissue surrounding the tissue mass. After tissue volume <b>22</b> is bracketed, system <b>20</b> can be used to locate the defined boundaries of the tissue volume, e.g., in connection with the surgical removal of tissue mass <b>26</b>. It will be appreciated that the invention can have other applications including radiation therapy, colo-rectal treatments, and many other applications in which it is useful to locate a target location other than a tissue volume within a human body.

[0058] As described in more detail below, other aspects of the present invention are also directed to a method of bracketing tissue volume <b>22</b> using system <b>20</b>, and a method of removing tissue volume <b>22</b> using system <b>20</b>. These methods can be accomplished with other aspects of the present invention, such as markers, instruments, stabilizers/anchors, position detection systems and user interfaces described below.

[0059] System <b>20</b> comprises a plurality of markers <b>30</b>, a probe <b>32</b> and a detector <b>34</b> connected to the probe. As described in more detail below, markers <b>30</b> are implanted in tissue portion <b>24</b> under the guidance of a conventional imaging system not forming part of the present invention, so as to bracket tissue volume <b>22</b>. Such imaging systems may include ultrasound, magnetic resonance imaging (“MRI”), computer-aided tomography (“CAT”) scan, and X-ray systems. Markers <b>30</b> are imageable with the imaging energy generated by the imaging system. For example, if an ultrasound imaging system is used to implant markers <b>30</b>, the latter are configured and made from a material that strongly reflects ultrasound energy. Materials that are imageable with the energy generated by such systems are well known to those skilled in the art, and so are not described in detail here. Following implantation of markers <b>30</b>, probe <b>32</b> and detector <b>34</b> are used to locate the markers, as described in more detail below.

[0060] The terms “probe <b>32</b>” and “detector <b>34</b>” are used generically herein to refer to all embodiments of the probe and detector described below. Specific embodiments of the probe <b>32</b> and detector <b>34</b> are identified using a prime notation described below, i.e., probe <b>32</b>′ or detector <b>34</b>″. Additionally, the probes described below define one type of instrument, and the detectors described below define one type of position detection system in accordance with embodiments of the invention.

[0061] A. Markers

[0062] The markers <b>30</b> can be biologically inert (biocompatible) and are relatively small so that they do not impair procedures for removing or treating a tissue volume <b>22</b>. Markers <b>30</b> may have different geometric configurations, e.g., spherical, disk-like, cylindrical, and other shapes. In one particular embodiment, the greatest dimension of a marker <b>30</b> measured along a Y-axis extending through the marker from one surface to an opposite surface is not more than about 5 mm. The markers <b>30</b> can be even smaller, e.g., the greatest dimension is about 1-2 mm, or they can also be larger. Although several of the markers with respect to FIGS. <b>2</b>-<b>8</b> are described in connection with this aspect of the invention, they can also be used in connection with other aspects.

[0063] In addition, markers <b>30</b> each have a detection characteristic to enable detection by probe <b>32</b> and detector <b>34</b>, or by a separate detection system with an array of sensors relative to a reference location. The detection characteristics of the various embodiments of markers <b>30</b> can be characterized as active or passive. In the active category, the detection characteristic of a first embodiment of marker <b>30</b>, illustrated in FIG. 2<i>a </i>as marker <b>30</b><i>a</i>, is gamma radiation <b>40</b>. In this regard, marker <b>30</b><i>a </i>may include materials such as technetium 99, cobalt isotopes or iodine isotopes. Such materials may be obtained from DuPont of Billerica, Mass. Preferably, each marker <b>30</b><i>a </i>generates gamma radiation <b>40</b> having a field strength in the range of 1-100 microCuries.

[0064] Also in the active category, in a second embodiment of marker <b>30</b>, illustrated in FIG. 2<i>b </i>as marker <b>30</b><i>b</i>, the detection characteristic is magnetic field <b>42</b>. Markers <b>30</b><i>b </i>of the second embodiment thus contain ferromagnetic materials in which a magnetic field can be induced, or alternatively are permanently magnetized and so have an associated permanent magnetic field. In FIG. 2<i>b</i>, magnetic field <b>42</b> represents both the induced and inherent magnetic fields. Strong permanent magnets, such as those made from Samarium-Cobalt, can be suitable magnets for markers <b>30</b><i>b</i>. Alternatively, the markers may communicate with the position detection system by resonating markers (e.g., AC magnetic coupling using coils of wire as receiving and emitting antenna), as described below with reference to FIGS. <b>23</b>A-D.

[0065] Referring to FIG. 2<i>c</i>, in a third embodiment, again in the active category, marker <b>30</b><i>c </i>emits radio frequency (“RF”) signal <b>44</b> in response to a triggering signal <b>46</b>. Various energy sources may be used for triggering signal <b>46</b>, including a magnetic field, ultrasound or radio frequency energy. In this latter case, marker <b>30</b><i>c </i>is preferably designed to receive triggering signal <b>46</b> which has a first RF wavelength, and in response thereto, emit signal <b>44</b> of a second RF wavelength. In the simplest case, no data, other than the specific radio frequency itself, is carried in signal <b>44</b>. Alternatively, markers <b>30</b><i>c </i>may all transmit signal <b>44</b> at a single frequency, with data uniquely identifying each marker being carried in signal <b>44</b> emitted by each marker.

[0066] A suitable marker <b>30</b><i>c </i>is illustrated in FIG. 3<i>a</i>. This marker <b>30</b><i>c </i>includes a transmit/receive antenna <b>52</b> for receiving an RF signal at a first frequency and transmitting an RF signal at a second frequency. Also included is a power detect/regulate circuit <b>54</b> connected to antenna <b>52</b> that detects the presence of, and regulates, the RF signal received by the antenna. The regulated RF signal is provided from circuit <b>54</b> to drive radio frequency generator <b>56</b> which generates an RF signal at a second frequency. As discussed in more detail below, when multiple markers <b>30</b><i>c </i>are used together in a given bracketing procedure, preferably each marker transmits RF signals at a second frequency which is unique to the marker. The frequency of the received RF signal <b>46</b>, however, is preferably common with respect to all of the markers <b>30</b><i>c </i>used in the bracketing procedure. The RF signal generated by radio frequency generator <b>56</b> is then provided to antenna <b>52</b> where it is transmitted as an RF signal.

[0067] Referring to FIG. 3<i>b</i>, an RF exciter device <b>60</b> for generating RF signal <b>46</b> is illustrated. RF exciter <b>60</b> includes a radio frequency generator <b>62</b> for generating RF signal <b>46</b> at a predetermined frequency and an RF amplifier <b>64</b> for amplifying the output from the radio frequency generator. The sensitivity of amplifier <b>64</b> may be controlled using gain adjustment <b>62</b> coupled to the amplifier. The output of RF amplifier <b>64</b> is provided to transmit antenna <b>68</b> which transmits RF signal <b>46</b>. Transmit antenna <b>68</b> of RF exciter <b>60</b> is preferably placed in relatively close proximity to marker <b>30</b><i>c</i>, with appropriate gain adjustment of RF amplifier <b>64</b> being achieved by control gain adjustment <b>66</b> until a suitable return signal is absorbed from detector <b>34</b>″, discussed below and illustrated in FIG. 8.

[0068] In a fourth embodiment, again in the active category, marker <b>30</b><i>d</i>, illustrated in FIG. 2<i>d</i>, continuously emits signal <b>44</b> at specific frequencies in the radio frequency spectrum. The marker <b>30</b><i>c </i>illustrated in FIG. 3A and described above can be satisfactorily employed as marker <b>30</b><i>d </i>by adding a battery (not shown) in place of power detector portion of circuit <b>54</b> of marker <b>30</b><i>c</i>. RF exciter <b>60</b> is not required in connection with marker <b>30</b><i>d</i>, insofar as the battery generates the energy used by the marker in producing RF signal <b>44</b>. The embodiments of the RF Markers are one example of a resonating marker having an electrical circuit in accordance with an embodiment of a wireless implantable marker.

[0069] As a fifth embodiment in the active category, marker <b>30</b><i>e</i>, illustrated in FIG. 2<i>e</i>, is designed to vibrate following implantation. This vibration is a detection characteristic that is chosen to enhance image contrast when marker <b>30</b> is intended to be detected using a probe <b>32</b> and detector <b>34</b> that perform ultrasound imaging. More specifically, incoming ultrasound signal <b>74</b> is reflected off marker <b>30</b><i>e </i>as reflected ultrasound signal <b>76</b>, with a Doppler shift component being added to the reflected signal due to the vibration of the marker to enhance imageability of the marker. The vibration frequency of marker <b>30</b><i>e </i>will vary depending upon the frequency of ultrasound energy generated by probe <b>32</b>, but is preferably lower than the frequency of incoming ultrasound signal <b>74</b> which is typically 7.5 MHz, i.e., the vibration frequency is preferably in the 50 Hz to 50 kHz range. This embodiment is an example of a mechanical resonating marker in accordance with another embodiment of a wireless implantable marker.

[0070] A suitable marker <b>30</b><i>e </i>that achieves the functionality described above is illustrated in FIG. 4. This marker <b>30</b><i>e </i>includes an antenna <b>80</b> for receiving an RF signal that provides the energy driving the marker. A power detection and regulation circuit <b>82</b> is connected to antenna <b>80</b> for detecting when the antenna is receiving an RF signal and for regulating the signal for use by oscillator and waveform generator circuit <b>84</b> connected to circuit <b>82</b>. Circuit <b>84</b> converts the regulated RF signal received from circuit <b>82</b> into an oscillating electrical signal, preferably in the audio frequency range (i.e., 20 Hz-20 kHz), having a waveform that is optimized to drive piezoelectric device <b>86</b> connected to circuit <b>84</b>. Piezoelectric device <b>86</b> is a conventional piezoelectric device of the type that converts an oscillating electrical input signal into mechanical oscillations. Piezoelectric device <b>86</b> is attached via support <b>88</b> to outer housing <b>90</b> of marker <b>30</b><i>e</i>. Housing <b>90</b> is designed to resonate at the mechanical oscillation frequency of piezoelectric device <b>86</b>.

[0071] Referring to FIG. 5, an RF coupled acoustic exciter <b>92</b> is provided for generating the RF signal received by antenna <b>80</b> of marker <b>30</b><i>e</i>. Exciter <b>92</b> includes a radio frequency generator <b>94</b> for generating an RF signal. RF amp <b>96</b>, with a gain adjustment <b>98</b> connected thereto, is provided for receiving and amplifying the output signal from generator <b>94</b>. A transmit antenna <b>100</b> is provided for receiving the output of amp <b>96</b> and transmitting the RF signal used to drive marker <b>30</b><i>e</i>. In use, gain <b>98</b> of amp <b>96</b> is adjusted to amplify the RF signal produced by generator <b>94</b> such that marker <b>30</b><i>e </i>is caused to mechanically oscillate so it is most clearly observable by the ultrasound imaging system (not shown) used in conjunction with marker <b>30</b><i>e. </i>

[0072] As those skilled in the art will appreciate, other circuit configurations may be used in marker <b>30</b><i>e </i>to cause piezoelectric device <b>86</b> to vibrate. For example, a frequency divider circuit (not shown) may be used in place of oscillator/waveform generator circuit <b>84</b>. With such alternative, exciter <b>92</b> is modified to include a variable frequency oscillator (not shown) in place of radio frequency generator <b>94</b>.

[0073] In the passive category, the detection characteristic in a sixth embodiment of marker <b>30</b>, illustrated as marker <b>30</b><i>f </i>in FIG. 2<i>f</i>, is opacity to incoming ultrasound signal <b>74</b>. That is, marker <b>30</b><i>f </i>reflects incoming sound energy sufficiently to create a strong image in reflected signal <b>76</b> so as to enhance imageability using a conventional ultrasound imaging system. In many cases, it will be advantageous to incorporate the detection characteristics of marker <b>30</b><i>f </i>in marker <b>30</b><i>e. </i>

[0074] While those skilled in the art are familiar with materials and configurations that can be used for marker <b>30</b><i>f</i>, one suitable marker <b>30</b><i>f </i>is illustrated in FIG. 6. This marker <b>30</b><i>f </i>includes plate <b>102</b>, plate <b>104</b> and plate <b>106</b>, all of which are preferably arranged in mutually orthogonal relationship. It is preferred that each of the plates <b>102</b>-<b>106</b> has a square configuration and the length of each edge of the plates, e.g., the length of edge <b>108</b> of plate <b>104</b>, is preferably about twice the wavelength of incoming ultrasound signal <b>74</b>. For example, when incoming ultrasound signal <b>74</b> has a wavelength of 7.5 MHz, edge <b>108</b> has a length of about 2 mm. Plates <b>102</b>-<b>106</b> are made from a material that strongly reflects ultrasound energy, e.g., aluminum, and typically have a thickness in the range of 10-100 μm. Plates <b>102</b>-<b>106</b> ideally are enclosed in a biologically non-reactive casing <b>110</b>. The latter is preferably made from a material that does not have strong ultrasound reflection characteristics, e.g., a soft polymer.

[0075] Also in the passive category, marker <b>30</b><i>g </i>of the seventh embodiment, illustrated in FIG. 2<i>g</i>, comprises a capsule (not shown) filled with a colored dye <b>78</b>, e.g., a vital dye. Either or both the capsule and dye <b>78</b> of marker <b>30</b><i>g </i>are made from a material that is imageable by the imaging system, e.g., ultrasound, used to implant the markers, as described in more detail below. The capsule is made from gelatin or other suitable material that is selected to be sufficiently tough to withstand insertion into tissue volume <b>22</b>, but is relatively easily cut by the cutting tool used to remove the tissue volume, e.g., a conventional surgical scalpel or cutting tool <b>200</b> described below. Marker <b>30</b><i>g </i>provides a visual guide as to its location by releasing colored dye <b>78</b> when severed by a surgical cutting tool. In this regard, probe <b>32</b> and detector <b>34</b> are not used in connection with marker <b>30</b><i>g. </i>

[0076] Markers <b>30</b><i>a</i>, <b>30</b><i>b </i>and <b>30</b><i>f </i>may be made from a solid structure containing material having the desired detection characteristic. Alternatively, markers <b>30</b><i>a</i>, <b>30</b><i>b </i>and <b>30</b><i>f </i>may be made from a capsule filled with a dye, such as is used for marker <b>30</b><i>g</i>, containing material having the desired detection characteristic. As another alternative, all embodiments of markers <b>30</b> may include a dye contained in an outer capsule having the requisite toughness and severability characteristics noted above.

[0077] B. Probe and Detector

[0078] The probe <b>32</b> shown in FIG. 1 is one embodiment of an instrument, and the detector <b>34</b> shown in FIG. 1 is one embodiment of a user interface for any system in accordance with the invention. The design and configuration of the probe <b>32</b> and the detector <b>34</b> depend upon the embodiment of marker <b>30</b> used. However, for all embodiments of marker <b>30</b> (except marker <b>30</b><i>g</i>), detector <b>34</b> is designed to provide humanly recognizable information when probe <b>32</b> is positioned within a selected proximity, e.g., 1-5 cm, of a given marker. This information may take one of a variety of forms, including a burst of humanly perceivable sound, constant or intermittent illumination of a light, movement of a needle on a dial, a short burst of air, change of data in a visual display, increased image brightness or contrast (in the case when detector <b>34</b> is an ultrasound imaging system, as discussed below), a tactile response, or other humanly perceivable proximity information. In this regard detector <b>34</b> may include a dial <b>112</b>, light <b>114</b>, speaker <b>116</b>, or other appropriate devices for generating the selected form of humanly perceivable information.

[0079] Preferably, although not necessarily, detector <b>34</b> provides humanly recognizable information that indicates changes in proximity of probe <b>32</b> to a given marker <b>30</b>. Thus, rather than merely providing static or threshold information that probe <b>32</b> is within a predetermined range of a given marker <b>30</b>, detector <b>34</b> preferably provides proximity information having an attribute or characteristic that varies as a function of changes in proximity of the probe relative to the marker. For example, if the proximity information is sound, the pitch is varied with changes in proximity. Or, as another example, if the proximity information is light, the brightness of the light changes with changes in proximity.

[0080] A probe and detector that may be satisfactorily employed as probe <b>32</b> and detector <b>34</b>, respectively, when the latter is intended to detect maker <b>30</b><i>a</i>, is sold by Care Wise Medical Products Corporation of Morgan Hill, Calif., and is identified by the trademark C-TRAK. The C-TRAK probe, which is described in U.S. Pat. Nos. 5,170,055 and 5,246,005 to Carroll et al., which are incorporated herein by reference, provides a humanly audible sound, the pitch of which varies with changes in proximity of the probe to tissue labeled with gamma ray producing material.

[0081] Referring to FIGS. 1, 2<i>b </i>and <b>7</b>, when probe <b>32</b> and detector <b>34</b> are intended for use in detecting marker <b>30</b><i>b</i>, which generates a magnetic field <b>42</b>, probe <b>32</b>′ and detector <b>34</b>′ illustrated in FIG. 7 may be satisfactorily employed. Probe <b>32</b>′ includes a conventional Hall effect sensor (not shown) that provides an output signal on line <b>120</b>, the voltage of which varies as a function of proximity of the probe to the magnetic field generated by a marker <b>30</b><i>b</i>. Detector <b>34</b>′ is connected to probe <b>32</b>′ via line <b>120</b>, and includes an amplifier <b>122</b> connected to line <b>120</b> for amplifying the signal from the Hall effect sensor in probe <b>32</b>′. Amplifier <b>122</b> includes an offset adjustment <b>126</b> and a gain adjustment <b>128</b>. Offset adjustment <b>126</b> is provided to cancel the effects of any ambient magnetic fields, such as that of the earth. Gain adjustment <b>128</b> is provided to control the overall sensitivity of detector <b>34</b>′. The amplified signal from amplifier <b>122</b> is delivered on line <b>124</b> to signal meter <b>126</b>, which may comprise a dial with a movable needle, an LED or other device for representing signal strength. Also connected to line <b>124</b> is voltage-controlled oscillator <b>128</b>, the output of which is provided to amplifier <b>130</b>. The output of amplifier <b>130</b> drives speaker <b>116</b>. The frequency of the output signal from voltage controlled oscillator <b>128</b> varies as function of changes in voltage of the signal delivered on line <b>124</b>, which in turn causes the pitch of the sound produced by speaker <b>116</b> to vary as a function of changes in the voltage of the signal on line <b>124</b>. As those of ordinary skill in the art will appreciate, other devices for providing humanly recognizable information representing changing proximity, e.g., a light, may be employed instead of speaker <b>116</b>.

[0082] Referring to FIGS. 1, 2<i>c </i>and <b>8</b>, for markers <b>30</b><i>c </i>and <b>30</b><i>d</i>, which generate radio frequency energy, probe <b>32</b>″ and detector <b>34</b>″ are provided for use in detecting the markers. Probe <b>32</b>″ includes a conventional coil antenna <b>140</b> for receiving an RF signal. Detector <b>34</b>″ includes a selectable notch filter <b>142</b> connected to antenna <b>140</b> which permits tuning of the detector to the unique RF frequency of signal <b>44</b> emitted by markers <b>30</b><i>c </i>or <b>30</b><i>d</i>. A tuning knob or other user adjustable mechanism (neither shown) is attached to selectable notch filter <b>142</b> to permit a user to perform such tuning. The output of selectable notch filter <b>142</b> is provided to RF amplifier <b>144</b>, the overall sensitivity of which may be controlled by gain adjustment <b>146</b> attached to the amplifier. The output of RF amplifier <b>144</b> is provided to rectifier/integrator circuit <b>148</b> which rectifies and time filters the signal. The output of rectifier/integrator circuit <b>148</b> is provided to analog signal strength display <b>150</b> which provides a visual indication of the proximity of probe <b>32</b>″ to marker <b>30</b><i>c</i>. In addition, the output of rectifier/integrator circuit <b>148</b> is provided to voltage oscillator <b>152</b> which generates an output signal, the frequency of which varies as a function of the voltage level of the signal provided by rectifier/integrator circuit <b>148</b>. The output signal of the voltage control oscillator <b>152</b> is amplified by audio amplifier <b>154</b>, which in turn drives speaker <b>116</b>. Accordingly, the pitch of the sound generated by speaker <b>116</b> varies as a function of the strength of the RF signal received by probe <b>32</b>″, and hence as a function of the proximity of probe <b>32</b>″ to markers <b>30</b><i>c </i>or <b>30</b><i>d. </i>

[0083] A suitable probe <b>32</b> and detector <b>34</b> for use with the markers <b>30</b><i>e </i>and <b>30</b><i>f </i>is the ultrasound imaging system available from Dornier Surgical Products, Inc., Phoenix, Ariz., is identified by the name Performa, and generates ultrasound energy having a frequency of 7.5 MHz.

[0084] C. Tissue Anchor

[0085] Turning now to FIGS. <b>9</b>-<b>11</b>, another aspect of the present invention is tissue anchor <b>300</b>. The latter is designed to stabilize tissue mass <b>26</b> during surgical removal of the mass using system <b>20</b>, as described in more detail below.

[0086] Tissue anchor <b>300</b> includes a ring <b>302</b> sized to receive the thumb or finger of a user, and a rod <b>304</b>. The latter includes a proximal end <b>305</b>, which is attached to ring <b>302</b>, and a distal end <b>306</b>. Rod <b>304</b> includes an outwardly projecting pin <b>308</b> that serves as a stop, as described below. Tissue anchor <b>300</b> also includes a plurality of, e.g., four, anchor members <b>310</b> that are attached to rod <b>304</b> at or adjacent its distal end <b>306</b>. Typically, anchor members <b>310</b> are attached to rod <b>304</b> so as to extend away from its distal end <b>306</b>, as illustrated in FIGS. 9 and 10. However, as an alternative design, anchor member <b>310</b> may be attached to rod <b>304</b> so as to extend away from distal end <b>306</b> toward proximal end <b>305</b> (not shown). Each anchor member <b>310</b> may terminate with a barb <b>312</b> (FIG. 11), if desired. Anchor members <b>310</b> preferably have a curved configuration when in an unbiased state, as illustrated in FIGS. 9 and 11. Anchor members <b>310</b> are preferably made from spring steel, although other “memory” metal alloys made also be satisfactorily used. In certain applications it may be unnecessary to provide a curve in anchor member <b>310</b>, i.e., the anchor member may be substantially straight.

[0087] Rod <b>304</b> preferably, although not necessarily, has a circular cross section. The outside diameter of rod <b>304</b> depends upon its intended application, but is typically in the range of 0.3-10 mm, preferably about 1-2 mm. The length of rod <b>304</b>, as measured between proximal end <b>305</b> and distal end <b>306</b>, also depends upon its desired application, but typically ranges from 5-20 cm.

[0088] Tissue anchor <b>300</b> also includes a cannula <b>320</b> having a central bore <b>322</b>, a proximal end <b>324</b> and a pointed distal end <b>326</b>. Central bore <b>322</b> has an inside diameter that is sized to receive rod <b>304</b> with a close sliding fit. Cannula <b>320</b> has an outside diameter that is selected based on the intended application but is typically in the range 0.5 mm-12 mm, preferably about 1-3 mm. Cannula <b>320</b> also includes an elongate slot <b>328</b> that runs parallel to the long axis of the cannula and is sized to receive pin <b>308</b> with a close sliding fit. The length of slot <b>328</b> is substantially the same as the length of anchor members <b>310</b>. Slot <b>328</b> includes a pocket <b>329</b> at its end closest to distal end <b>326</b> of cannula <b>320</b> that extends orthogonally to the long axis of the slot and is sized to receive pin <b>308</b>.

[0089] Cannula <b>320</b> also includes a plurality of apertures <b>330</b> extending through the wall of the cannula. Apertures <b>330</b> are positioned adjacent distal end <b>326</b> of cannula <b>320</b> when anchor members <b>310</b> are attached to rod <b>304</b> to extend away from distal end <b>306</b> as illustrated in FIGS. 10 and 11. If anchor members <b>310</b> extend from distal end <b>306</b> toward proximal end <b>305</b> (not shown), then apertures <b>330</b> are moved toward the proximal end so that they are spaced from the distal end <b>326</b> at least about the length of the anchor members. One aperture <b>330</b> is typically provided for each anchor member <b>310</b>. The lengths of anchor members <b>310</b>, cannula <b>320</b>, and slot <b>328</b> are together selected so that a small portion, e.g., about 1 mm, of each anchor member <b>310</b> projects from its respective aperture <b>330</b> when tissue anchor <b>300</b> is in the retracted position illustrated in FIG. 10. In this position, pin <b>308</b> engages the end of slot <b>328</b> closest to proximal end <b>324</b>. Anchor members <b>310</b> are sized in this manner to ensure the anchor members remain positioned in their respective apertures <b>330</b> when tissue anchor <b>300</b> is in the retracted position illustrated in FIG. 10.

[0090] The lengths of anchor members <b>310</b>, cannula <b>320</b>, and slot <b>328</b> are also together selected so that most, if not substantially the entire, length of the anchor members <b>310</b> projects from their respective apertures <b>330</b> when tissue anchor is in the extended position illustrated in FIGS. 9 and 11. In this position, pin <b>308</b> engages the end of slot <b>328</b> closest to distal end <b>326</b>.

[0091] The elements of tissue anchor <b>300</b> are preferably made from stainless steel, a plastic such as polystyrene or polyurethane, or other materials suitable for the intended application of the tissue anchor (as described in more detail below) known to those skilled in the art. As noted above, in many cases it is desirable to make anchor members <b>310</b> from spring steel or a “memory” metal alloy.

[0092] D. Bracketing

[0093] Referring now to FIGS. 1, 12 and <b>13</b>, markers <b>30</b> may be used to bracket (i.e., define the boundaries of) tissue volume <b>22</b> in a tissue portion <b>24</b> in accordance with the following method. In the following description of the method of bracketing tissue volume <b>22</b>, the latter is contained in a human breast. However, it is to be appreciated that tissue volume <b>22</b> may be present in other hollow or solid organs and structures, e.g., a liver, or may constitute an entire organ or structure. Additionally, a plurality of the markers <b>30</b> may be implanted to completely bracket the tissue volume <b>22</b>, or one or more markers <b>30</b> can be used to bracket or otherwise mark the location of the tissue volume <b>22</b>.

[0094] As the first step in bracketing tissue volume <b>22</b>, a tissue mass <b>26</b> of interest is identified through conventional imaging methods, e.g., ultrasound, MRI, X-ray or CAT scan. Next, markers <b>30</b> are implanted in tissue portion <b>24</b> surrounding tissue mass <b>26</b> and defining outer boundaries of tissue volume <b>22</b>. The number of markers <b>30</b> used, and the placement of the markers relative to tissue mass <b>26</b>, will vary depending upon the location of the tissue mass relative to other types of tissue, e.g., bone or muscle, surgeon preference, size and configuration of the tissue mass and the desired amount of tissue margin <b>28</b> (FIG. 1) beyond the edge of tissue mass <b>26</b>. However, in many applications, it may be desirable to use at least six markers <b>30</b> to bracket tissue volume <b>22</b>, preferably two on each of axes X, Y and Z (see, e.g., FIGS. 1, 12 and <b>13</b>). Two of the markers <b>30</b> can be positioned on each of axes X, Y and Z so as to lie on opposite boundaries of tissue volume <b>22</b>. For example, as illustrated in FIG. 1, marker <b>30</b>, lies on the Z-axis at the upper surface of tissue volume <b>22</b>, marker <b>302</b> lies on the Z-axis at the lower surface of the tissue volume, marker <b>303</b> lies on the X-axis at a first location on the outer surface of the tissue volume, marker <b>304</b> lies on the X-axis at a second location on the outer surface of the tissue volume diametrically opposite marker <b>303</b>, marker <b>305</b> lies on the Y-axis at a third location on the outer surface of the tissue volume, and marker <b>306</b> lies on the Y-axis at a fourth location on the outer surface of the tissue volume diametrically opposite marker <b>305</b>.

[0095] Although the axes X, Y and Z can be mutually orthogonal, as illustrated, this is not mandatory and can be difficult to precisely implement in practice. In this particular embodiment, the tissue volume <b>22</b> should be completely surrounded by markers <b>30</b>, i.e., the tissue volume should be defined in three dimensions by the markers. One notable exception to this that the marker <b>30</b>, such as marker <b>302</b> shown in FIGS. 1 and 13, positioned at the base of, i.e., underneath, tissue volume <b>22</b> is not typically required when a different type of tissue, such as pectoral muscle <b>400</b> (FIG. 13) is located at or near where the marker would be positioned. The illustration of marker <b>302</b> in FIG. 13 is not inconsistent with this recommended placement regime for markers <b>30</b> because of the relatively great spacing between the marker <b>302</b> and pectoral muscle <b>400</b>. Similarly, when the marker <b>30</b>, such as marker <b>30</b>, shown in FIG. 1, to be positioned on top of tissue volume <b>22</b> is near the skin overlying the tissue volume, such marker is not typically required. Also, while the X, Y and Z-axes are illustrated in FIG. 1 as intersecting at a common point centrally located within tissue mass <b>26</b>, this is not required. For example, it may be desirable to offset the X and Y-axes somewhat, as measured along the Z-axis. Furthermore, in some cases it may be desirable to define tissue volume <b>22</b> with markers <b>30</b> in only two dimensions or in only one dimension.

[0096] In some cases, it will be desirable to use more than two markers <b>30</b> on X, Y and Z-axes. Referring to FIG. 1A, in a first case, ten markers <b>30</b> are used, two on the Z-axis, two on an axis X₁, two on an axis X₂that is offset along the Z-axis with respect to axis X₁, two on an axis Y₁, and two on an axis Y₂that is offset along the Z-axis with respect to axis Y₁. Referring to FIG. 1B, in a second case, ten markers <b>30</b> are used, two on the X-axis, two on the Y-axis, two on the Z-axis, two on the V-axis which bisects the X and Y-axes and two on the W-axis which also bisects the X and Y-axes, but at a different location. Other numbers and relative placements of markers are also encompassed by the present invention.

[0097] Markers <b>30</b> are preferably spaced from tissue mass <b>26</b> so as to define tissue volume <b>22</b> such that tissue margin <b>28</b> is large enough to ensure none of the tissue mass of interest lies outside the tissue volume. This precise spacing will vary with the nature of the tissue mass <b>26</b>, the size of the tissue mass, surgeon preference and other factors. However, tissue margin <b>28</b>, as measured outwardly along an axis extending perpendicular to a surface location on tissue mass <b>26</b>, is generally about 0.5 cm to 3 cm, and is preferably about 1 cm to 2 cm. It will be appreciated that other margins may be more appropriate in other circumstances.

[0098] Markers <b>30</b> may be implanted in tissue portion <b>24</b> in a variety of different ways using a variety of different tools. In general, markers <b>30</b> are implanted using a conventional imaging system (not shown) that simultaneously generates an image of tissue mass <b>26</b> and the markers. By frequently comparing the location of markers <b>30</b> to tissue mass <b>26</b> during implantation of the markers into tissue portion <b>24</b>, based on image information received from the imaging system, the markers may be positioned so as to define tissue volume <b>22</b> in the manner described above. As noted above, markers <b>30</b> are made from a material that provides good image contrast with respect to the imaging energy used. In other aspects of the invention, only one or two markers may be implanted in or proximate to the tissue mass <b>26</b>, and the margin <b>28</b> can be defined on a display by a virtual line or shape based upon the relative location between at least one of the implanted markers and the tissue mass <b>26</b>.

[0099] It is preferable to at least partially immobilize tissue portion <b>24</b> during implantation of markers <b>30</b>. However, this is not necessary because, by comparing the relative location of a marker <b>30</b> to tissue mass <b>26</b>, the desired relative placement can typically be achieved even if tissue portion <b>24</b> is moving during marker implantation.

[0100] E. Marker Implantation

[0101] Various techniques may be used to implant markers <b>30</b> in tissue portion <b>24</b>. With reference to FIGS. 12 and 13, one approach is to insert markers <b>30</b> percutaneously through skin <b>402</b> overlying tissue portion <b>24</b> using known needle pushers or implanters (neither shown) of the type used to implant “seeds” of radioactive material for various cancer treatments. For example, needle pushers of the type sold by Best Industries of Springfield, Va., may be satisfactorily employed. These needle pushers include a central needle surrounded by an outer tube having an end plate or cup for supporting the radioactive “seed.” Following insertion of the needle pusher into the selected tissue mass, the radioactive “seed” is released by pressing the central needle downwardly relative to the surrounding outer tube, with the point of the needle ejecting the “seed” from the end plate or cup of the outer tube.

[0102] To percutaneously insert marker <b>30</b> in accordance with this first approach, the marker is positioned on the end of the needle pusher (in place of the radioactive “seed”), is forced through skin <b>402</b> and, using feedback from the imaging system, is guided to the region where it is desired to implant the marker. Then the marker <b>30</b> is ejected from the needle pusher by urging the central needle forwardly into the inner tube.

[0103] A second approach for implanting markers <b>30</b> involves creating a small, e.g., 5-10 mm, incision (not shown) in the skin <b>402</b> overlying tissue portion <b>24</b>. Next, a scalpel is inserted through the incision so as to form a slit in the underlying tissue portion extending to the position where it is desired to implant a maker <b>30</b>. Then a marker <b>30</b> is inserted through the slit to such position using a tweezers, needle pusher, trocar or other suitable tool. Other markers <b>30</b> are implanted through separate incisions in skin <b>402</b> in similar manner so as to bracket tissue volume <b>22</b>.

[0104] Referring now to FIGS. 1 and 12-<b>14</b>, a third approach for implanting markers <b>30</b> is to form a relatively large, e.g., 1-3 cm, incision <b>404</b> (see FIG. 12) in skin <b>402</b> overlying tissue mass <b>26</b>. Next, incision <b>404</b> is pulled open as illustrated in FIG. 14 using retractors or other conventional devices to form a relatively large open region <b>406</b> above tissue mass <b>26</b>. Markers <b>30</b> are then implanted into tissue portion <b>24</b> using either the first or second approaches described above. Other approaches for implanting markers <b>30</b> so as to bracket tissue mass <b>26</b> are also encompassed by the present invention. The speed and accuracy with which markers <b>30</b> may be implanted, and the trauma associated with implantation should be considered in selecting other approaches for implanting markers <b>30</b>.

[0105] F. Marker Identification

[0106] Once tissue mass <b>26</b> has been bracketed or otherwise marked, tissue volume <b>22</b> can be removed. As described in more detail below, one procedure involves identifying the boundaries of tissue volume <b>22</b> using an embodiment of probe <b>32</b> and detector <b>34</b> that is appropriate for the type of marker <b>30</b> used, as discussed above. Using information from detector <b>34</b> regarding such boundaries, tissue volume <b>22</b> is then removed using a scalpel or other tool, with tissue anchor <b>300</b> preferably, but not necessarily, being used to stabilize the tissue volume during removal. Another procedure is similar to the first, except that tissue anchor <b>300</b> is not used.

[0107] For both of these procedures, as the first step the surgeon typically identifies the boundaries of the tissue volume using system <b>20</b> or otherwise marks the location of the tissue mass <b>26</b> as described in more detail below. This step is generally needed because in practice markers <b>30</b> will often be implanted by another doctor, e.g., a radiologist, as a separate procedure. The boundaries of tissue volume <b>22</b> are identified by moving probe <b>32</b> in the general region of the tissue volume and then monitoring the detection information (e.g., sound, light, dial movement, image clarity and the like) provided by detector <b>34</b>. As noted above, detector <b>34</b> may provide this information when probe <b>32</b> is moved within a predetermined proximity of a given marker <b>30</b>, or may provide this information in a form that changes with changes in proximity of the probe to the marker (e.g., a light gets brighter as the probe is moved toward a marker and dimmer as it is moved away).

[0108] The interaction between marker <b>30</b> and probe <b>32</b> and detector <b>34</b> depends upon the detection characteristic of the marker. In the case of marker <b>30</b><i>a</i>, which emits gamma radiation <b>40</b> (FIG. 2<i>a</i>) on a continuous basis, a probe and detector of the type described in U.S. Pat. Nos. 5,170,055 and 5,246,005 to Carroll et al. (the “C-TRAK probe”), as discussed above, may be satisfactorily used to detect the markers. The C-TRAK probe includes a radiation detector, e.g., a scintillation crystal, which provides an output signal that is believed to vary as a function of the flux density of the gamma rays <b>40</b> emitted by marker <b>30</b><i>a</i>. Changes in this output signal are then converted into humanly recognizable detection information, e.g., sound, having a characteristic, e.g., pitch or tempo in the case of sound, that varies with changes in gamma ray flux density. By observing the location of probe <b>32</b> when the detection information from detector <b>34</b> indicates the probe is closest to a given marker <b>30</b><i>a</i>, the surgeon can mentally note where the marker is located. Repetition of this process will result in identification of the location of all markers <b>30</b><i>a. </i>

[0109] Referring to FIGS. 2<i>b </i>and <b>7</b>, in the case of marker <b>30</b><i>b</i>, which generates a magnetic field <b>42</b>, probe <b>32</b>′ and detector <b>34</b>′ are used to detect the marker. To locate a marker <b>30</b><i>b</i>, the surgeon moves probe <b>32</b>′ in the general region of tissue volume <b>22</b>, with the result that as the probe approaches a given marker <b>30</b><i>b </i>its Hall effect sensor (not shown) generates an output signal having a voltage that increases as the probe is moved toward the marker. Similarly the voltage of the output signal decreases as probe <b>32</b>′ is moved away from the marker <b>30</b><i>b</i>. The output signal of probe <b>32</b>′ is provided via line <b>120</b> to amplifier <b>122</b>, which amplifies the output signal from the probe. As discussed above, the amplified voltage signal from probe <b>32</b>′ is displayed on signal meter <b>126</b> and is also delivered to voltage controlled oscillator <b>128</b>. The latter generates an oscillating signal, the frequency of which varies as a function of the voltage of the amplified signal provided to voltage controlled oscillator <b>128</b>. This signal is then amplified by amplifier <b>130</b>, and the amplified signal then drives speaker <b>116</b> such that the pitch of the sound provided by the speaker <b>116</b> varies as a function of proximity of probe <b>32</b>′ to marker <b>30</b><i>b</i>. By observing signal meter <b>126</b> and/or listening to speaker <b>116</b>, the surgeon can assess when the probe <b>32</b>′ is positioned closest to a selected marker <b>30</b><i>b</i>. Repetition of this process will result in identification of the location of all of markers <b>30</b><i>b. </i>

[0110] Turning now to FIGS. 2<i>c</i>, <b>3</b><i>a</i>, <b>3</b><i>b </i>and <b>8</b>, marker <b>30</b><i>c</i>, which generates an RF signal <b>44</b>, is identified using probe <b>32</b>″ and detector <b>34</b>″ in the following manner. RF exciter <b>60</b> is operated so as to produce an RF exciter signal <b>46</b>. More particularly, radio frequency generator <b>62</b> (FIG. 3B) generates a radio frequency signal which is amplified by RF amplifier <b>64</b>, following sensitivity adjustment using gain adjustment <b>66</b>, with the amplified signal being provided to antenna <b>68</b> for transmission to markers <b>30</b><i>c</i>. RF exciter <b>60</b> is positioned sufficiently close to markers <b>30</b><i>c </i>that RF exciter signal <b>46</b> is received by antenna <b>52</b> of the markers and is of sufficient strength to drive radio frequency generator <b>56</b> of the markers. Following detection and regulation by circuit <b>54</b> (FIG. 3A) of the signal <b>46</b> received by antenna <b>52</b>, radio frequency generator <b>56</b> generates an RF signal which is transmitted by antenna <b>52</b> as RF signal <b>44</b>. Each marker <b>30</b><i>c </i>can transmit RF signal <b>44</b> at a frequency that is unique to the marker, while an RF exciter signal <b>46</b> having a single frequency can be used for all of the markers <b>30</b><i>c</i>, with the frequency of signal <b>46</b> being different than the frequencies of signals <b>44</b>.

[0111] Once exciter <b>60</b> has been activated so as to cause marker <b>30</b><i>c </i>to generate RF signal <b>44</b>, detection of the marker commences. This is achieved by positioning probe <b>32</b>″ (FIG. 8) on or adjacent skin <b>402</b> adjacent tissue volume <b>22</b>, and then monitoring proximity information provided by analog signal strength display <b>150</b> and/or speaker <b>116</b> of detector <b>34</b>″. More specifically, following receipt of RF signal <b>44</b> by receive antenna <b>140</b> of probe <b>32</b>″, the signal is filtered by selectable notch filter <b>142</b> of probe <b>32</b>″. By correlating a given marker <b>30</b><i>c</i>, e.g., marker <b>30</b><i>c</i>₁, with a corresponding representation on the adjustment knob (not shown) that controls selectable notch filter <b>142</b>, e.g., the reference number “1,” the surgeon can identify the location of the given marker. The knob for adjusting selectable notch filter <b>142</b> is then moved to a different position when detecting a second marker <b>30</b><i>c</i>, e.g., marker <b>30</b><i>c</i>₂.

[0112] Signals from receive antenna <b>140</b> that are passed through selectable notch filter <b>142</b> are then amplified by RF amplifier <b>144</b> with the adjustment of the amplifier gain being provided as needed using gain adjustment <b>146</b>. The amplified signal is then provided to rectifier/integrator <b>148</b> where the signal is rectified and time filtered. The strength of signal <b>144</b> detected by detector <b>34</b>″ is then displayed via analog signal strength display <b>150</b> and is provided to voltage controlled oscillator <b>152</b>. The latter creates an oscillating signal, the frequency of which varies as a function of the voltage of the signal provided by rectifier/integrator <b>148</b>. The output signal from voltage controlled oscillator <b>152</b> is then amplified by audio amplifier <b>154</b> and delivered to drive speaker <b>116</b>. The pitch of the sound provided by speaker <b>116</b> will vary as a function of the frequency of the signal provided by voltage controlled oscillator <b>152</b>, and as an ultimate function of the proximity of probe <b>32</b>″ to a given marker <b>30</b><i>c</i>. By observing the location of probe <b>32</b>″ when the detection information from detector <b>34</b>″ indicates the probe is closest to a given marker <b>30</b><i>c</i>, the surgeon can mentally note where the marker is located. By repeating this process for each of the markers <b>30</b><i>c </i>with appropriate adjustment of selectable notch filter <b>142</b>, all of the markers <b>30</b><i>c </i>may be located.

[0113] Referring to FIGS. 2<i>d</i>, <b>3</b><i>a</i>, <b>3</b><i>b </i>and <b>8</b>, marker <b>30</b><i>d </i>may also be detected using detector <b>34</b>″ in substantially the same manner discussed above with respect to marker <b>30</b><i>c</i>. One significant difference, however, is the fact that RF exciter <b>60</b> (FIG. 3B) is not used insofar as marker <b>30</b><i>d </i>contains its own power source.

[0114] Turning next to FIGS. 2<i>e</i>, <b>2</b><i>f</i>, and <b>4</b>-<b>6</b>, for markers <b>30</b><i>e </i>and <b>30</b><i>f</i>, which are designed to provide high image contrast when imaged with ultrasound, probe <b>32</b> includes a conventional ultrasound transducer (not shown) that generates ultrasound in a conventional frequency range, e.g., 7.5 MHz, and receives back reflection of the ultrasound signal. Detector <b>34</b> is the image processor and display (neither shown) of a conventional ultrasound apparatus which is connected to the ultrasound transducer. Markers <b>30</b><i>e </i>or <b>30</b><i>f </i>are identified by scanning the general region of tissue volume <b>22</b> with probe <b>32</b>, and monitoring the ultrasound image of the markers provided by detector <b>34</b>. This ultrasound image permits the surgeon to identify the placement of all of the markers, and hence the boundaries of tissue volume <b>22</b>.

[0115] In the case of marker <b>30</b><i>e</i>, the latter is caused to vibrate at a frequency that is generally significantly less than that of the ultrasound generated by the ultrasound transducer in probe <b>32</b>. This creates, through what is believed to be a Doppler shift phenomenon, enhanced image contrast in the ultrasound signal reflected off markers <b>30</b><i>e</i>. Vibration of a marker <b>30</b><i>e </i>is effected by operating RF exciter <b>92</b> so that radio frequency generator <b>94</b> generates a radio frequency signal which is amplified by amp <b>96</b> and then transmitted by antenna <b>100</b>. Antenna <b>80</b> of marker <b>30</b><i>e </i>receives this RF signal, which is detected and regulated by circuit <b>84</b> so as to generate an oscillating electrical signal that is provided to piezoelectric device <b>86</b>. This signal causes the piezoelectric device <b>86</b> to mechanically oscillate, which oscillations are transferred via support <b>88</b> to outer housing <b>90</b> of marker <b>30</b><i>e</i>, thereby causing the housing (and hence the marker) to vibrate.

[0116] G. Tissue Removal

[0117] Following identification of tissue volume <b>22</b> using the procedures outlined above, surgical removal of the tissue volume commences. Referring to FIGS. 12 and 14, the first of the two procedures for removing tissue volume <b>22</b> referenced above commences with the formation of an incision <b>404</b> (FIG. 12) in skin <b>402</b> above tissue volume <b>22</b>. The length of incision <b>404</b> is typically about equal to, or slightly greater than, the distance between two markers <b>30</b> lying on a given axis, e.g., the Y-axis as illustrated in FIG. 12. Next, portions of skin <b>402</b> adjacent incision <b>404</b> are pulled apart by retractors or other known devices, so as to form open region <b>406</b> (FIG. 14) and expose tissue portion <b>24</b> beneath.

[0118] Referring now to FIGS. <b>9</b>-<b>11</b> and <b>15</b>-<b>17</b>, as the next step, tissue anchor <b>300</b> is inserted in tissue mass <b>26</b> so as to assume the extended position illustrated in FIG. 11. This is achieved by inserting a finger into ring <b>302</b>, then pulling rod <b>304</b> upwardly (as illustrated in FIG. 10) with respect to cannula <b>320</b> so that pin <b>308</b> moves in slot <b>328</b> toward the end thereof closest to proximal end <b>324</b> of the cannula. In this retracted position, cannula <b>320</b> is grasped and is inserted through open region <b>406</b> into tissue volume <b>22</b> so that its distal end <b>326</b> is positioned substantially in the center of tissue mass <b>26</b>. This placement may be achieved under the guidance of an imaging system (not shown) that is capable of imaging tissue anchor <b>300</b>, e.g., ultrasound or X-ray imaging systems. Alternatively, using system <b>20</b>, the location a marker <b>302</b> lying beneath tissue volume <b>22</b>, as illustrated in FIGS. 16 and 17, is identified using the procedure described above to identify the tissue volume. By identifying the depth at which marker <b>302</b> is located and comparing this to the length of cannula <b>320</b> inserted into tissue volume <b>22</b>, distal end <b>326</b> may be positioned centrally within tissue mass <b>26</b>.

[0119] Next, ring <b>302</b>, and hence rod <b>304</b> attached thereto, is forced downwardly (as viewed in FIG. 15) relative to cannula <b>320</b> until pin <b>308</b> contacts the end of slot <b>328</b> closest to distal end <b>326</b>. As rod <b>304</b> moves within cannula <b>320</b> toward this extended position, anchor members <b>310</b> are forced out through apertures <b>330</b> and into tissue mass <b>26</b> (see FIG. 17). Then, ring <b>302</b>, and hence rod <b>304</b>, is rotated slightly so as to cause pin <b>308</b> to move into pocket <b>329</b>.

[0120] The next step in the removal of tissue volume <b>22</b> is assembly and placement of a cutter <b>200</b> in open region <b>406</b>. Referring to FIGS. 15 and 18-<b>20</b>, the cutter <b>200</b> includes cutter portions <b>202</b> and <b>204</b> that can be positioned adjacent open region <b>406</b>, as illustrated in FIG. 15. Next, the cutter portion <b>202</b> is positioned in open region <b>406</b>, and a curved plate <b>206</b> of the cutter portion <b>202</b> is inserted under portions of skin <b>402</b> adjacent the open region, as illustrated in FIG. 18. Next, the cutter portion <b>204</b> is similarly positioned in open region <b>406</b>. Then, cutter portions <b>202</b> and <b>204</b> are moved toward one another so that cannula <b>320</b> of tissue anchor <b>300</b> is received in an elongate groove <b>232</b> in a central handle section <b>222</b> and in an elongate groove <b>255</b> in a central handle section <b>252</b>. Cutter portions <b>202</b> and <b>204</b> are moved even closer to one another so that central handle sections <b>222</b> and <b>252</b> engage one another. When positioned in this manner, ends of curved portion <b>206</b> of cutter portion <b>202</b> engage ends of curved portion <b>236</b> of cutter portion <b>204</b> so as to form a substantially continuous curved cutting edge. Also when positioned in this manner, a longitudinal axis of cutter <b>200</b> extends substantially parallel to the elongate axis of cannula <b>320</b>, both of which are substantially co-axial with the Z-axis extending through tissue volume <b>22</b>. (See FIGS. 16 and 19).

[0121] Next, the position of cutter <b>200</b> relative to markers <b>30</b> is determined by comparing the location of markers, which is typically determined by using probe <b>32</b> and detector <b>34</b> in the manner described above, to the position of the cutter. Then, the location of cutter <b>200</b> is adjusted so that the longitudinal axis of cutter <b>200</b> is substantially co-axial with the Z-axis of the tissue volume <b>22</b>, as illustrated in FIG. 19. In some cases the surgeon will recall the location of markers <b>30</b> from the prior marker identification step, and so it will be unnecessary to again locate the markers. However, when tissue portion <b>24</b> is amorphous and pliable, as is the case when breast tissue is involved, it is recommended that this alignment of cutter <b>200</b> with tissue portions <b>30</b> using probe <b>32</b> and detector <b>34</b> be performed before any cutting of tissue volume <b>22</b> commences.

[0122] In connection with the initial insertion of cutter <b>200</b> in open portion <b>406</b>, an appropriately sized cutter <b>200</b> is selected such that the radius of curved plates <b>206</b> and <b>236</b>, as measured radially outwardly from the longitudinal axis, is substantially the same as the radius of tissue volume <b>22</b> as measured radially outward from the Z-axis. While this relationship between the radii of curved plates <b>206</b> and <b>236</b> of cutter <b>200</b> and the radius of tissue volume <b>22</b>, as measured with respect to Z-axis, is preferred, in some cases it may be satisfactory to use a cutter having a radius that is greater than or less than the radius of the tissue volume <b>22</b>. Also, the height of curved portions <b>206</b> and <b>236</b> is another factor considered in selecting an appropriate cutter <b>200</b>.

[0123] Referring to FIGS. <b>16</b>-<b>20</b>, as the next step in the removal of tissue volume <b>22</b>, ring <b>302</b> of tissue anchor <b>300</b> is typically pulled upwardly in the direction of arrow F (see FIGS. 17 and 19) sufficiently to tension tissue volume <b>22</b> and adjacent portions of tissue portion <b>24</b>. By this tensioning of tissue volume <b>22</b> and tissue portion <b>24</b> the tendency of the tissue portion to compress under the force of a cutting device is reduced. Also, this tensioning of tissue volume <b>22</b> serves to stabilize the tissue volume during the surgical removal process.

[0124] In some cases, sufficient tissue stabilization can be achieved merely by holding tissue anchor <b>300</b> in a substantially fixed position relative to tissue volume <b>22</b>. In other words, no force in the direction of arrow F is applied to tissue anchor <b>300</b> except as may be necessary to hold the tissue anchor in a stable position.

[0125] Then, while stabilizing tissue volume <b>22</b> with tissue anchor <b>300</b>, preferably, but not necessarily by maintaining an upward force on the tissue anchor, the surgeon grips cutter <b>200</b> and begins pressing downwardly toward tissue volume <b>22</b>, i.e., in the direction of arrow D (see FIG. 21). At the same time, the cutter is rotated about its longitudinal axis in either or both a clockwise and counterclockwise direction, e.g., in the direction indicated by curved arrow R (see FIG. 19). The elongate grooves <b>232</b> and <b>255</b> (FIG. 15) are sized to permit cutter <b>200</b> to rotate relatively freely about cannula <b>320</b> positioned therein.

[0126] As cutter <b>200</b> is rotated about its longitudinal axis and is urged downwardly towards tissue volume <b>22</b>, it cuts tissue volume <b>22</b> along its outer boundary. Progress in removing tissue volume <b>22</b> is generally periodically determined by comparing the position of curved plates <b>206</b> and <b>236</b> of cutter <b>200</b> relative to markers <b>30</b> using probe <b>32</b> and detector <b>34</b> to identify the locations of markers <b>30</b> and then comparing such locations with the location of the cutter. In particular, a determination can be made as to when tissue volume <b>22</b> has been severed from tissue portion <b>24</b> to a depth defined by marker <b>302</b> (FIG. 21) defining the bottom or innermost portion of the tissue volume. Thus, by iteratively comparing the position of cutter <b>200</b> to the locations of markers <b>30</b> using marker location information acquired from detector <b>34</b> based on proximity information provided by the detector, a surgeon can determine when the cutting operation is completed and cutter <b>200</b> can be removed from tissue portion <b>24</b>, as indicated in FIG. 20.

[0127] Depending upon the size of cutter <b>200</b> relative to the placement of markers <b>30</b>, the latter may remain in place in tissue portion <b>24</b> following removal of tissue volume <b>22</b>, as indicated in FIG. 20. If such as the case, markers <b>30</b> are then subsequently removed by first locating the markers using probe <b>32</b> and detector <b>34</b> and then removing the markers with a suitable instrument, e.g., tweezers. In other cases, the markers will be included in the tissue volume <b>22</b>.

[0128] In some cases, it will be necessary to sever the bottom or innermost portion of tissue volume <b>22</b> from tissue portion <b>24</b> so as to permit removal of the tissue volume. A scalpel or other conventional tool may be used to perform this final severing of the tissue volume. The precise location where this final incision is made may be determined by again locating the position of marker <b>302</b> using probe <b>32</b> and detector <b>34</b>. By leaning tissue anchor <b>300</b> and cutter <b>200</b> to one side, a surgeon can typically follow the incision created by cutter <b>200</b> with a scalpel or other tool down to the region where marker <b>302</b> is located and tissue volume <b>22</b> remains attached to tissue portion <b>24</b>.

[0129] As noted above, in some circumstances a marker <b>302</b> is not required when the bottom or innermost portion of tissue volume <b>22</b> is positioned immediately above a different type of tissue, e.g., a pectoral muscle <b>400</b>. In such case, the surgeon can assess when cutter <b>200</b> has been inserted sufficiently deep into tissue portion <b>24</b> by merely observing when bottom cutting edges of the cutter are about to engage the different type of tissue.

[0130] Referring to FIG. 1A, by inserting markers <b>30</b> at staggered locations along the Z-axis, the relative depth of cutter <b>200</b> in tissue portion <b>24</b> can be determined by locating specific markers using probe <b>32</b> and detector <b>34</b>. The location of such markers <b>30</b> is then compared with the location of cutter <b>200</b> to determine the depth of the cut. For example, if markers <b>30</b><i>c </i>are installed at positions X₁and X₂in FIG. 1<i>a</i>, and each marker has a unique frequency, these markers can be uniquely identified by detector <b>34</b>″ (FIG. 8) in the manner described above.

[0131] Referring to FIG. 1B, by positioning more than four markers, e.g., eight markers as illustrated in FIG. 1B, the boundaries of tissue volume <b>22</b> can often be more readily defined during the removal of the tissue volume. This is so because increasing the number of markers <b>30</b> used increases the quantity of information received from detector <b>34</b> regarding the boundaries of tissue volume <b>22</b>.

[0132] While the use of cutter <b>200</b> in connection with the removal tissue volume <b>22</b> often expedites removal of the tissue volume, many other cutters or instruments can be used to remove, treat, monitor, or otherwise perform some procedure on the tissue volume. In this regard, a conventional scalpel may often be satisfactorily employed in place of cutter <b>200</b>. Also, under certain circumstances it may be desirable to initiate an incision with cutter <b>200</b>, and then complete the incision with a scalpel. It will be appreciated that other types of cutters and systems for manipulating the tissue can be used, such as using as vacuum to pull-up on the tissue, extending an “umbrella” at the end of a stabilizer to pull-up on the tissue, vibrating the cutter to cut the tissue (either in lieu of or in addition to rotating the cutter), and using rotational electrocautery.

[0133] The process of removing tissue volume <b>22</b> using a scalpel also preferably commences by inserting tissue anchor <b>300</b> in tissue volume <b>22</b> in the manner described above. The location of markers <b>30</b> are also determined prior to and during the removal of tissue volume <b>22</b> by scalpel in the manner described above. Thus, during the removal of tissue volume <b>22</b>, the boundaries thereof may be repeatedly identified by locating markers <b>30</b> using probe <b>32</b> and detector <b>34</b>. As noted above, it is generally advantageous to use tissue anchor <b>300</b> when removing tissue volume <b>22</b> with a scalpel because by stabilizing the tissue volume and surrounding regions of tissue portion <b>24</b>, it is easier to maintain alignment of the scalpel with the boundaries of the tissue volume. However, it is to be appreciated that the use of tissue anchor <b>300</b> is a preferred, but not essential, aspect of the present method of bracketing and removing tissue volume <b>22</b>.

[0134] Referring now to FIG. 2<i>g </i>and FIG. 13, as noted above, probe <b>32</b> and detector <b>34</b> are not used in connection with marker <b>30</b><i>g</i>. The detection characteristic of markers <b>30</b><i>g </i>is the release of a colored dye <b>78</b> in surgical cavity adjacent the markers. In an alternative embodiment, the markers can be capsules that each have a different color, and the colored markers can be implanted in a manner to define the desired margin for guidance during a percutaneous biopsy procedure, excisional procedures, and other procedures. Removal of a tissue volume <b>22</b> bracketed by markers <b>30</b><i>g </i>differs from the removal of tissue volume when bracketed by the other embodiments of marker <b>30</b> in that the location of marker <b>30</b><i>g </i>is not determined by the surgeon prior to initiation of the removal of tissue volume <b>22</b>. Practically speaking, this is more a difference in the process for removing tissue volume <b>22</b> than a difference in the composition and construction of marker <b>30</b><i>g</i>. This is so because for implantation purposes, marker <b>30</b><i>g </i>must necessarily be imageable by some form of imaging system, which imaging system could, in most cases, also be used by the surgeon to identify the location of marker <b>30</b><i>g </i>prior to and in connection with the removal of tissue volume <b>22</b>. For example, if marker <b>30</b><i>g </i>is initially implanted by imaging the marker using an ultrasound system, then marker <b>30</b><i>g </i>is actually a marker <b>30</b><i>f </i>Thus, in connection with the following description of the process of removing tissue volume <b>22</b> bracketed with markers <b>30</b><i>g</i>, it is assumed the markers are not located by the surgeon prior to, or in connection with, the removal of tissue volume other than by visual observation, as discussed below.

[0135] Removal of tissue volume <b>22</b> bracketed by markers <b>30</b><i>g </i>also preferably commences by installing tissue anchor <b>300</b> as described above. Again, the use of tissue anchor <b>300</b> is preferred, but not mandatory. Next, the surgeon commences cutting the general region of tissue volume <b>22</b>, which can be defined by colored marks, Kopanz needles or other known techniques. Then, the removal of tissue volume <b>22</b> proceeds using either cutter <b>200</b>, or a scalpel or other cutting device. As this removal of tissue volume <b>22</b> is performed, tissue anchor <b>300</b>, if used, is manipulated to stabilize tissue volume <b>22</b> in the manner described above. As cutter <b>200</b>, the scalpel or other cutting device (e.g., a vacuum assisted cutting device) encounters a marker <b>30</b><i>g</i>, the capsule of the marker is severed releasing the colored dye <b>78</b>. This advises the surgeon that a boundary of tissue volume <b>22</b> has been encountered. It may be advantageous to use a given color of dye in markers <b>30</b><i>g </i>defining one side of the boundary of tissue volume <b>22</b>, while the markers <b>30</b><i>g </i>defining an opposite side include a different color of dye. By defining the boundary of tissue volume <b>22</b> with a sufficient number, e.g., 10-25, of markers <b>30</b><i>g</i>, the boundary of tissue volume <b>22</b> can typically be identified by iteratively cutting and observing whether dye appears in the surgical cavity.

[0136] As noted above, marker embodiments <b>30</b><i>a</i>-<b>30</b><i>f </i>may all include colored dye <b>78</b> within an outer capsule that is sufficiently tough to withstand insertion and yet is relatively easily cut by cutter <b>200</b>, a scalpel or other cutting device. Such use of dye in markers <b>30</b> provides another source of information for the surgeon regarding the boundary of tissue volume <b>22</b>.

[0137] One advantage of certain embodiments of the tissue bracketing system <b>20</b> is that they permit the relatively precise identification of the boundaries of tissue volume <b>22</b> without the need for needles, wires or other cumbersome apparatus projecting from tissue portion <b>24</b>. As such, bracketing system <b>20</b> permits a surgeon to relatively quickly and easily identify the tissue boundary of tissue volume <b>22</b> and remove the tissue volume. In addition, system <b>20</b> is ideally adapted for bracketing a tissue volume <b>22</b> in amorphous, pliable tissue, such as breast tissue.

[0138] Another advantage of certain embodiments of the cutter <b>200</b> is that they permit a tissue volume <b>22</b> of relatively large diameter to be removed through a relatively small incision <b>404</b> or percutaneously. This advantage is useful in this era when tissue-conserving therapies are being emphasized.

[0139] By stabilizing tissue volume <b>22</b> using tissue anchor <b>300</b>, the accuracy with which a surgeon can remove tissue volume <b>22</b> is also enhanced compared to techniques that do not use a tissue stabilizer or anchor. Also, the accuracy of removing tissue may be further enhanced by docking the tissue stabilizer or anchor to the first implanted tissue marker by using a first marker in the tissue stabilizer and the position detection system. This advantage of the present embodiment arises because tensioning of the tissue volume <b>22</b> by pulling upwardly on tissue anchor <b>300</b> serves to retain the tissue portion in a relatively stable position. Indeed, even holding tissue anchor <b>300</b> in a substantially fixed position relative to the tissue volume <b>22</b> with which it is engaged typically provides beneficial stabilization of the tissue volume.

[0140] While cutter <b>200</b> and tissue anchor <b>300</b> may be advantageously employed in connection with the present method of bracketing and removing tissue volume <b>22</b>, it is to be appreciated that the cutter and tissue anchor have application in many other contexts. More specifically, in any application in which it is desired to remove a volume of tissue through as small an incision as possible, cutter <b>200</b> has utility. Similarly, when it is desired to stabilize a piece of tissue in connection with surgical removal or other treatment of the piece of tissue, whether or not within the bracketing context of the present invention, tissue anchor <b>300</b> also has important application. Likewise, the system of bracketing a tissue mass is also useful in other applications, such as radiation therapy, and in connection with other body parts.

[0141] Certain changes may be made in the above apparatus and processes shown in FIGS. <b>1</b>-<b>20</b> without departing from the scope of the present invention. As such, it is intended that all matter contained in the preceding description or shown in the accompanying drawings shall be interpreted in an illustrative and not in a limiting sense. For example, as explained below with reference to FIGS. <b>21</b>-<b>61</b>, additional embodiments in accordance with other aspects of the invention are also useful for locating, monitoring, and or treating tissue masses and other body parts within a human body.

[0142] II. Alternate Systems and Methods for Locating, Monitoring and/or Treating Target Locations Within a Human Body

[0143] A. Overview of System Components and Operation

[0144]FIG. 21 is an isometric view of a system <b>1000</b> for locating a target location T within a human body H in accordance with one embodiment of the invention. The target location T shown in FIG. 21 can be a lesion, tumor, or other area of interest on or within a soft tissue region (e.g., a breast “B”), an organ, the colon, a bone structure, or another body part. The particular components of the system <b>1000</b> are best understood in light of the relationship between the components and the operation of the system. Therefore, the following description will initially explain an overview of the components and the general operation of the system <b>1000</b>.

[0145] In one embodiment, the system <b>1000</b> includes a wireless implantable marker <b>1100</b>, an instrument <b>1120</b>, a position detection system <b>1200</b>, and a user interface <b>1300</b>. The wireless implantable marker <b>1100</b> can be implanted at a precise location with respect to the target location <b>1000</b> using stereotactic imaging systems and other procedures known in the art as explained above. In operation, the position detection system <b>1200</b> determines the location of the wireless implantable marker <b>1100</b> and the location of the instrument <b>1120</b> relative to a reference location to determine the relative position between the target location T and the instrument <b>1120</b>. The position detection system <b>1200</b> is coupled to the user interface <b>1300</b> to convey the relative position between the target location <b>1000</b> and the instrument <b>1120</b> in a manner that allows a surgeon to intuitively understand the position and the orientation of the instrument <b>1120</b> relative to the target location <b>1000</b> without additional imaging equipment. As a result, the system <b>1000</b> is particularly useful for applications in which the patient cannot immediately proceed from an imaging procedure to another procedure, or when intraoperative imaging is not practical or economical.

[0146]FIG. 22 is an elevational view illustrating selected embodiments of the wireless implantable marker <b>1100</b>, the instrument <b>1120</b>, and a portion of the position detection system <b>1200</b> in greater detail. The wireless implantable marker <b>1100</b> can be one of the markers described above with reference to FIGS. <b>1</b>-<b>20</b>. Alternatively, the wireless implantable marker <b>1100</b> can be a resonating marker or another type of marker as described below in more detail with reference to FIGS. <b>23</b>A-<b>33</b>. In general, at least one wireless implantable marker <b>1100</b> is implanted at a location relative to the target location <b>1000</b>. In the embodiment shown in FIG. 22, one wireless implantable marker <b>1100</b> is implanted within the target location T and another wireless implantable marker <b>1100</b> is implanted adjacent to the target location T. In several embodiments, the wireless implantable markers <b>1100</b> emit a response energy in reaction to an excitation energy emitted by the position detection system <b>1200</b>. The position detection system <b>1200</b> can sense the intensity of the response energy and determine the location of the individual implantable markers <b>1100</b> relative to a reference location.

[0147] This implementation could be used with a device that is at a known location relative to the position detection system reference location. For example, an external beam radiation could be applied to a target location defined by the first implantable marker or otherwise monitored when the position of the beam applicator is known relative to the reference location of the position detection system. A suitable external beam radiation device is the PRIMIS Linear Accelerator from Siemens Medical of Concord, Calif.

[0148] The instrument <b>1120</b> can include a handle <b>1121</b>, a function-site <b>1124</b> coupled to the handle <b>1121</b>, and at least one instrument marker <b>1130</b>. The function-site <b>1124</b> can be a tip of the instrument <b>1120</b> or a portion of the instrument <b>1120</b> that cuts, ablates, deposits, images or otherwise treats or monitors the target location T. Several embodiments of various types of instruments with different function-sites are described in more detail below with reference to FIGS. <b>40</b>-<b>52</b>. The instrument markers <b>1130</b> can be the same type of wireless markers as the implantable marker <b>1100</b>, or alternatively the instrument markers <b>1130</b> can be a different type of wireless marker. The instrument markers <b>1130</b> can also be “wired” markers that are directly coupled to the position detection system <b>1200</b>. The position detection system <b>1200</b> can also gauge the instrument markers <b>1130</b> to determine the position of the instrument relative to a reference location.

[0149] In the embodiment shown FIG. 22, the instrument <b>1120</b> includes three instrument markers <b>1130</b> including two instrument markers <b>1130</b> that are attached to the instrument <b>1120</b> along an alignment axis A-A, and a third instrument marker <b>1130</b> that is offset from the alignment axis A-A. By knowing the distance between the function-site <b>1124</b> and the array of instrument markers <b>1130</b>, the position detection system <b>1200</b> can determine the position and the orientation of the function-site <b>1124</b> based upon the positions of the three instrument markers <b>1130</b>.

[0150] Referring to FIGS. 21 and 22 together, the position detection system <b>1200</b> (FIG. 21) can include a processor <b>1202</b> (FIG. 21), a detection array <b>1204</b> having a plurality of sensors <b>1210</b>, and a transmitter <b>1220</b> (FIG. 21). The transmitter <b>1220</b> can emit an excitation energy that causes the implantable markers <b>1100</b> to emit a response energy. Each sensor <b>1210</b> can include three coils arranged orthogonally around a magnetic core to measure the response energy emitted from the implantable markers <b>1100</b> and instrument <b>1130</b>. The processor <b>1202</b> calculates the distance between each sensor <b>1210</b> and each of the markers <b>1100</b> and <b>1130</b> based upon the intensity of the response energy measured by the sensors <b>1210</b>. The processor <b>1202</b> also correlates the distance measurements between each of the markers <b>1100</b> and <b>1130</b> to determine the individual locations of the markers <b>1100</b> and <b>1130</b> relative to a reference location <b>1230</b> (e.g., a reference coordinate system). Based upon this data, the processor <b>1202</b> and/or another processor of the user interface <b>1300</b> can determine the relative position between the function-site <b>1124</b> of the instrument <b>1120</b> and the target location T. Suitable position detection systems <b>1200</b> and resonating signal elements that can be adapted for use with the implantable markers <b>1100</b> and/or the instrument markers <b>1130</b> are available from Polhemus, Inc. of Burlington, Vt.

[0151] B. Embodiments of Wireless Markers

[0152]FIG. 23A is a cut-away isometric view of a resonating marker that can be used for the implantable markers <b>1100</b> and/or the instrument markers <b>1130</b> in accordance with one embodiment of the invention. In this embodiment, the resonating marker includes a casing <b>1140</b> composed of a biocompatible material, a signal element <b>1150</b> within the casing <b>1140</b>, and a fastener <b>1160</b>. The biocompatible material of the casing <b>1140</b> can be a suitable polymeric material, metal, medical grade epoxy, glass, or other compound that can reside within a human body for a period of time. The signal element <b>1150</b> can be a resonating circuit that includes a core <b>1152</b>, a coil <b>1154</b> wrapped around the core <b>1152</b>, and a capacitor <b>1156</b> connected to the coil <b>1154</b>. The core <b>1152</b> may be a magnetically permeable material, such as a ferrite. The signal element <b>1150</b> emits a response signal in reaction to an excitation energy at the resonate frequency of the circuit. As explained above, the excitation energy can be generated by the transmitter <b>1220</b> (FIG. 21) of the position detection system <b>1200</b>. In other embodiments, the signal element <b>1150</b> can be a mechanical resonator (e.g., piezoelectric actuator), an RF emitter, a fluorescent material, a bipolar semiconductor, or another suitable device or material that emits a response signal in reaction to an excitation energy. The fastener <b>1160</b> can have several different embodiments. In this particular embodiment, the fastener <b>1160</b> is a shape-memory material that is straight in a stored position and coils to form a loop in a deployed position. The shape-memory material can be a spring, or it can be a substance that is straight at room temperature and coils at body temperature.

[0153]FIG. 23B is an isometric cut-away view of another resonating marker in accordance with an embodiment of the invention. In this embodiment, the resonating marker includes a biocompatible casing <b>1140</b> and a signal element <b>1150</b><i>a</i>. The marker can also include a fastener (not shown in FIG. 23B). The signal element <b>1150</b><i>a </i>has three resonating members <b>1151</b><i>a</i>-<i>c </i>arranged orthogonally with respect to each other. The resonating members <b>1151</b><i>a</i>-<i>c </i>can also be configured in a non-orthogonal arrangement or any other suitable arrangement. Additionally, the signal element <b>1150</b><i>a </i>can include two or more resonating members such that this embodiment of the resonating marker is not limited to having three resonating members <b>1151</b><i>a</i>-<i>c</i>. Each resonating member <b>1151</b><i>a</i>-<i>c </i>can have a ferrite core <b>1152</b>, a coil <b>1154</b> wrapped around the core <b>1152</b>, and a capacitor <b>1156</b> coupled to each coil <b>1154</b>. Each resonating member <b>1151</b><i>a</i>-<i>c </i>can be tuned to resonate at the same frequency or at different frequencies. When the resonating members <b>1154</b><i>a</i>-<i>c </i>resonate at different frequencies, this embodiment of a resonating marker can thus provide three different signals from a single marker so that the position detection system can detect not only the point position of the marker (e.g. an X-Y-Z location), but also the pitch, roll and yaw of the marker relative to a coordinate system.

[0154]FIGS. 23C and 23D illustrate a resonating marker in accordance with still another embodiment of the invention. In this embodiment, the resonating marker has a single core <b>1152</b> and three coils <b>1154</b><i>a</i>-<i>c</i>. Each coil <b>1154</b><i>a</i>-<i>c </i>can be coupled to a capacitor (not shown), and each coil <b>1154</b><i>a</i>-<i>c </i>can generate a different signal. As such, this marker can be located in a manner similar to the marker described above with reference to FIG. 23B. The core <b>1152</b> can accordingly be a ferrite block, and the coils <b>1154</b><i>a</i>-<i>c </i>can be wrapped around the block orthogonally to each other as shown in FIG. 23D.

[0155] The resonating markers shown in FIGS. 23A and 23B are particularly useful because they can remain within a human body for a long period of time. These resonating markers can also have frequencies that are useful in applications in which a plurality of wireless markers <b>1100</b> are implanted. In such situations, it may be necessary to distinguish the implanted markers from one another. By using resonating markers that resonate at different frequencies, the position detection system <b>1200</b> can identify the “signature” of each marker by its unique frequency. A surgeon, therefore, can easily identify the relative location between a particular implanted marker <b>1100</b> and an instrument <b>1120</b>.

[0156] FIGS. <b>24</b>-<b>30</b> are side elevation views of several implantable markers <b>1101</b>-<b>1107</b> in accordance with embodiments of the invention. Each implantable marker <b>1101</b>-<b>1107</b> shown in FIGS. <b>24</b>-<b>30</b> has a biocompatible casing <b>1140</b>. Additionally, the implantable markers <b>1101</b>-<b>1107</b> can also include a signal element <b>1150</b> or <b>1150</b><i>a </i>for emitting a resonating signal, such as a magnetic resonator, a mechanical resonator (e.g., a piezoelectric actuator), an RF emitter, a magnet, a fluorescent material, or other suitable elements that can emit a signal for detection by the position detection system <b>1200</b> (FIG. 21).

[0157] The implantable markers <b>1101</b>-<b>1107</b> have different types of fasteners <b>1160</b>. The implantable marker <b>1101</b> shown in FIG. 24 includes a fastener <b>1160</b> defined by legs that project away from the casing <b>1140</b> in the deployed position. The legs can be molded projections of the casing <b>1140</b>, or the legs can be small springs that are biased to project away from the casing <b>1140</b>. The implantable marker <b>1102</b> shown in FIG. 25 includes a fastener <b>1160</b> defined by shape-memory loops on both ends of the casing <b>1140</b>. In FIG. 26, the implantable marker <b>1103</b> has a fastener <b>1160</b> defined by a surface texture, such as scales, that project away from the casing <b>1140</b>. The surface texture of the implantable marker <b>1103</b> can be integrally formed with the casing <b>1140</b>. Referring to FIG. 27, the implantable marker <b>1104</b> can include a fastener <b>1160</b> defined by one or more barbs or hooks. Referring to FIGS. 28 and 29, the implantable markers <b>1105</b> and <b>1106</b> have fasteners <b>1160</b> defined by a perforated material through which tissue can grow, such as a mesh. The implantable marker <b>1105</b> shown in FIG. 28 has a perforated tip, and the implantable marker <b>1106</b> shown in FIG. 29 has a perforated tail. Referring to FIG. 30, the implantable marker <b>1107</b> includes a fastener <b>1160</b> defined by a spring or a serpentine element extending from the rear of the casing <b>1140</b>. It will be appreciated that the fasteners <b>1160</b> can have different configurations than the particular types of fasteners <b>1160</b> shown in FIGS. <b>24</b>-<b>30</b>.

[0158] FIGS. <b>31</b>-<b>33</b> are side elevation views of several embodiments of implantable markers <b>1108</b>-<b>1110</b> in accordance with additional embodiments of the invention. The implantable markers <b>1108</b>-<b>1110</b> can include the biocompatible casing <b>1140</b> for implantation into a human body. The implantable markers <b>1108</b>-<b>1110</b> also include at least one identifier <b>1170</b> that is on and/or in the casing <b>1140</b>. The identifier <b>1170</b> can be a radiopaque material that reflects radiation energy, an echogenic material that reflects ultrasound energy, and/or a groove or channel in the casing <b>1140</b> that can be observed by an imaging system. Alternatively, the identifiers <b>1170</b> can be a color or other marking that is visually distinguishable for viewing with a human eye. The identifiers <b>1170</b> provide another feature for distinguishing one marker from another that can be used in addition to, or in lieu of, using signal elements <b>1150</b> that emit different frequencies. The implantable markers <b>1108</b>-<b>1110</b> can also include fasteners <b>1160</b> as described above with reference to FIGS. <b>24</b>-<b>30</b>, and/or signal elements <b>1150</b> or <b>1150</b><i>a </i>as described above with reference to FIGS. 23A and 23B.

[0159]FIGS. 34 and 35 are isometric views of arrangements for implanting the wireless implantable markers <b>1100</b> relative to the target location T in accordance with embodiments of the invention. FIG. 34 illustrates an embodiment in which only a first wireless implantable marker <b>1100</b><i>a </i>is implanted in the target location T, and FIG. 35 shows an embodiment in which only the first wireless implantable marker <b>1100</b><i>a </i>is implanted adjacent to or otherwise outside of the target location T. In either embodiment, the location of the implantable marker <b>1100</b><i>a </i>relative to the target location T is determined when the marker <b>1100</b><i>a </i>is implanted or at another imaging procedure so that the marker <b>1100</b><i>a </i>provides a reference point for locating the target location T in subsequent procedures. The user interface <b>1300</b> can electronically generate a virtual margin <b>1301</b> relative to the target location based upon parameters defined by the physician and the location of the implantable marker <b>1100</b><i>a</i>. In other embodiments, it is not necessary to generate the virtual margin <b>1301</b> relative to the target location T. The physician can determine the shape of the virtual margin <b>1301</b> so that it defines a boundary for performing a particular procedure at the target location T. The virtual margin <b>1301</b> is typically configured so that it defines the desired boundary for the particular procedure at the target location T without unduly affecting adjacent areas. In the case of a lesion in a soft tissue region, for example, the physician can define a virtual margin <b>1301</b> that encompasses the lesion and an appropriately sized safety zone around the lesion that mitigates collateral damage to tissue proximate to the lesion. The virtual margin <b>1301</b> can be spherical as shown in FIGS. 34 and 35, or it can have any desired shape including rectilinear shapes, oval shapes, or compound shapes.

[0160] FIGS. <b>36</b>-<b>39</b> are isometric views of additional arrangements for implanting the wireless implantable markers <b>1100</b> relative to the target location T in accordance with other embodiments of the invention. FIG. 36 illustrates an embodiment in which six individual implantable markers <b>1100</b><i>a</i>-<b>1100</b><i>f </i>are implanted in pairs along three orthogonal axes to define an excision boundary or another type of margin around the target location T. FIG. 37 shows an embodiment in which two individual implantable markers <b>1100</b><i>a </i>and <b>1100</b><i>b </i>define a cylindrical margin around the target location T. FIG. 38 illustrates an embodiment in which individual implantable markers <b>1100</b><i>a </i>and <b>1100</b><i>b </i>define an ovoid margin around the target location T, and FIG. 39 illustrates an embodiment in which four implantable markers <b>1100</b><i>a</i>-<b>1100</b><i>d </i>define a rectilinear margin around the target location T. The individual implantable markers <b>1100</b><i>a</i>-<b>1100</b><i>f </i>can define an actual margin by bracketing the target location T, or the positions of one or more of the individual markers <b>1100</b><i>a</i>-<b>1110</b><i>f </i>can be used to generate a virtual margin <b>1301</b> for use with the user interface. Additionally, it will be appreciated that other arrangements for implanting the implantable markers <b>1100</b> and other types of margins can be used depending upon the particular procedure, the type of body part, and the shape of the target location T.

[0161] C. Embodiments of Instruments

[0162] FIGS. <b>40</b>-<b>42</b> are cut-away side elevation views of instruments <b>1120</b> in accordance with embodiments of the invention. The instruments <b>1120</b> include the handle <b>1121</b>, the function-site <b>1124</b> coupled to the handle <b>1121</b>, and at least one instrument marker <b>1130</b>. The position detection system <b>1200</b> (FIG. 1) can determine the position of the instrument markers <b>1130</b> relative to a reference location. Referring to FIG. 40, this embodiment of the instrument <b>1120</b> includes a single instrument marker <b>1130</b><i>a </i>at a predetermined location relative to the function-site <b>1124</b>. The embodiment of the instrument <b>1120</b> shown in FIG. 40 provides at least a single position point for tracking by the position detection system <b>1200</b>. When the instrument marker <b>1130</b> is a single-axis marker, such as the marker shown in FIG. 23A, the instrument <b>1120</b> can be displayed as a single point by the user interface <b>1300</b> (FIG. 1). The orientation of this particular embodiment of the instrument <b>1120</b> cannot be displayed by the user interface <b>1300</b> because the single-axis marker does not provide sufficient data to determine the angle of the alignment axis A-A relative to a plane through the target location T (FIG. 1) or the rotational position of the instrument <b>1120</b> around the alignment axis A-A. It may be possible, though, to have a single instrument marker <b>1130</b> define the location and orientation of the instrument <b>1120</b> if the position detection system <b>1200</b> and the instrument marker <b>1130</b> are sensitive enough to pinpoint the location and orientation of the single instrument marker <b>1130</b>. For example, the multiple-axis markers shown in FIGS. <b>23</b>B-D are expected to provide sufficient data to define the location and orientation of the instrument <b>1120</b> using a single marker.

[0163]FIG. 41 illustrates another embodiment of the instrument <b>1120</b> having a first instrument marker <b>1130</b><i>a </i>and a second instrument marker <b>1130</b><i>b</i>. The first instrument marker <b>1130</b><i>a </i>is positioned at a first predetermined location relative to the function-site <b>1124</b>, and the second instrument marker <b>1130</b><i>b </i>is positioned at a second predetermined location relative to the function-site <b>1124</b>. The first and second instrument markers <b>1130</b><i>a </i>and <b>1130</b><i>b </i>can be positioned along the alignment axis A-A as shown in FIG. 41, or at least one of the markers <b>1130</b><i>a </i>or <b>1130</b><i>b </i>can be offset from the alignment axis A-A. The embodiment of the instrument <b>1120</b> shown in FIG. 41 accordingly provides two position points that the position detection system <b>1200</b> can track. As a result, the position detection system <b>1200</b> can determine the angle of the alignment axis A-A relative to a reference plane so that the user interface <b>1300</b> can display the instrument <b>1120</b> as (a) a vector of varying length when the alignment axis A-A is not normal to the reference plane, or (b) as a point when the alignment axis A-A is at least approximately normal to the reference plane. When the instrument markers <b>1130</b><i>a </i>and <b>1130</b><i>b </i>are multiple-axis markers, the rotational orientation of the instrument <b>1120</b> relative to the alignment axis A-A can be determined such that both the position of the function-site <b>1124</b> and the orientation of the instrument <b>1120</b> can be displayed by the user interface <b>1300</b>.

[0164]FIG. 42 illustrates yet another embodiment of the instrument <b>1120</b> having a first instrument marker <b>1130</b><i>a</i>, a second instrument marker <b>1130</b><i>b</i>, and a third instrument marker <b>1130</b><i>c</i>. The first and second instrument markers <b>1130</b><i>a </i>and <b>1130</b><i>b </i>can be positioned along the alignment axis A-A, but the third instrument marker <b>1130</b><i>c </i>is offset from the alignment axis A-A. This embodiment of the instrument <b>1120</b> provides three position points for tracking by the position detection system <b>1200</b>. As a result, the position detection system <b>1200</b> can determine (a) the angle of the alignment axis A-A relative to a reference plane, and (b) the rotational orientation of the instrument <b>1120</b> around the alignment axis A-A. The embodiment of the instrument <b>1120</b> shown in FIG. 42 accordingly permits the user interface <b>1300</b> to show the angle of the function-site <b>1124</b> relative to a reference plane, and the orientation of a leading edge of the function-site <b>1124</b> relative to the motion of the instrument <b>1120</b>.

[0165]FIG. 43 is a side elevational view of an embodiment of the instrument <b>1120</b> including a wireless control <b>1132</b> for controlling an aspect of (a) the instrument <b>1120</b>, (b) the position detection system <b>1200</b>, and/or (c) the user interface <b>1300</b> in accordance with another embodiment of the invention. The instrument <b>1120</b> shown in FIG. 43 has three instrument markers <b>1130</b><i>a</i>-<i>c</i>, but will be appreciated that the instrument <b>1120</b> can have any of one or more instrument markers <b>1130</b>. The wireless control <b>1132</b> includes an actuator <b>1133</b> and a transmitter <b>1134</b> coupled to the actuator <b>1133</b>. The transmitter <b>1134</b> transmits or otherwise emits a signal indicating a control parameter. The transmitter <b>1134</b>, for example, can be another marker that the position detection system <b>1200</b> can track. In one particular embodiment, the transmitter <b>1134</b> is a resonating magnetic marker having a signal element <b>1150</b> as set forth above with respect to FIG. 23. One advantage of using a resonating marker for the transmitter <b>1134</b> is that the system <b>1000</b> (FIG. 21) can be controlled by a wireless instrument <b>1120</b> using the position detection system <b>1200</b> without additional types of receivers (e.g., RF systems) that add to the complexity and cost of the system <b>100</b>. Alternatively, the transmitter <b>1134</b> can be an RF device, a mechanical resonator, a permanent magnet, or another type of device that emits a frequency or another form of energy. When the transmitter <b>1134</b> is a marker, the position detection system <b>1200</b> detects the position of the transmitter <b>1134</b> and generates a control signal according to the position of the transmitter <b>1134</b>.

[0166]FIG. 44 is a schematic view of one embodiment of the wireless control <b>1132</b>. In this embodiment, the transmitter <b>1134</b> of the wireless control <b>1132</b> is a resonating marker having a resonating signal element <b>1150</b><i>b </i>similar to one of the signal elements <b>1150</b> or <b>1150</b><i>a </i>shown above in FIG. 23A or <b>23</b>B. The signal element <b>1150</b><i>b </i>includes a ferrite core <b>1152</b>, a coil <b>1154</b> wrapped around the core <b>1152</b>, a capacitor <b>1156</b> coupled to the coil <b>1154</b>, and a cut-off switch <b>1157</b> between the coil <b>1154</b> and the capacitor <b>1156</b>. The actuator <b>1133</b> can be a push-button coupled to the cut-off switch <b>1157</b> that breaks the circuit to deactivate the signal element <b>1150</b><i>b</i>. In operation, the physician can press the actuator <b>1133</b> to close the cut-off switch <b>1157</b> so that the signal element <b>1150</b><i>b </i>emits a resonating signal. The position detection system <b>1200</b> detects the signal from the signal element <b>1150</b><i>b </i>and generates a control signal that changes a parameter of the system <b>1000</b>. The position detection system <b>1200</b>, for example, can send a message to the user interface <b>1300</b> to change a display of the user interface <b>1300</b> to show the relative position between the instrument <b>1120</b> and one of several implanted markers <b>1100</b>. This is particularly useful when a plurality of markers <b>1100</b> are implanted, such as the implanted markers <b>1100</b><i>a</i>-<i>f </i>in FIG. 36, and the physician needs to know the position relative to a particular marker. In one embodiment, the control <b>1132</b> can be used to cycle through the various markers <b>1100</b><i>a</i>-<i>f </i>by depressing the actuator <b>1133</b> to move from one marker to the next. The wireless control <b>1132</b> can also have several other applications that allow the position detection system <b>1200</b> to control other aspects of the system <b>1000</b> based upon input at the instrument <b>1120</b>.

[0167]FIG. 45 is a schematic view of another embodiment of the wireless control <b>1132</b>. In this embodiment, the actuator <b>1133</b> is a slider mechanism that moves along the handle <b>1121</b>, and the transmitter <b>1134</b> is another marker that can be detected by the position detection system <b>1200</b>. The actuator <b>1133</b>, for example, can be a linear slider or a rotational slider that has “click-stops” to indicate various control positions. In operation, the relative distance between the transmitter <b>1134</b> and a fixed marker attached to the instrument (e.g., the second instrument marker <b>1130</b><i>b</i>) is determined by the position detection system <b>1200</b>. A parameter of the instrument <b>1120</b>, the position detection system <b>1200</b>, and/or the user interface <b>1300</b> can be controlled according to the relative distance between the transmitter <b>1134</b> and the fixed marker. For example, if the distance between the transmitter <b>1134</b> and the second instrument marker <b>1130</b><i>b </i>is D₁, the user interface <b>1300</b> may display the distance between the function-site <b>1124</b> of the instrument <b>1120</b> and a first implanted marker. Similarly, if the distance between the transmitter <b>1134</b> and the second instrument marker <b>1130</b><i>b </i>is D₂, the user interface <b>1300</b> may display the relative distance between the function-site <b>1124</b> and a second implanted marker.

[0168] FIGS. <b>46</b>-<b>52</b> illustrate several instruments <b>1120</b><i>a</i>-<i>g </i>in accordance with various embodiments of the invention. The instruments <b>1120</b><i>a</i>-<i>g </i>can each include a handle <b>1121</b>, a function-site <b>1124</b> coupled to the handle <b>1121</b>, and at least one instrument marker <b>1130</b> similar to the instruments <b>1120</b> described above with reference to FIGS. <b>40</b>-<b>42</b>. The instruments <b>1120</b><i>a</i>-<i>g </i>can also include a wireless control similar to the wireless controls <b>1132</b> described above with reference to FIGS. <b>43</b>-<b>45</b>. The differences between the instruments <b>1120</b><i>a</i>-<i>g </i>is generally the type of function-site <b>1124</b>.

[0169]FIG. 46 illustrates a smart Bovie <b>1124</b><i>a </i>that has a function-site <b>1124</b><i>a </i>defined by an RF cutting blade. Suitable RF cutting devices without the instrument markers <b>1130</b> are available from Valley Lab of Boulder, Colo., under the part number E2516 Reusable Electrosurgical Pencil. FIG. 47 illustrates a scissors <b>1120</b><i>b </i>that has a function-site <b>1124</b><i>b </i>defined by the cutting blades. FIG. 48 illustrates a harmonic scalpel <b>1120</b><i>c </i>having a function-site <b>1124</b><i>c </i>defined by a harmonic cutting tip. Suitable harmonic scalpels without the instrument markers <b>1130</b> are available from Ethicon Endo Surgery of Cincinnati, Ohio, under the part name ULTRACISION HARMONIC SCALPEL®. FIG. 49 illustrates a laproscope <b>1120</b><i>d </i>having a function-site <b>1124</b><i>d </i>defined by a distal end of the laproscope. Suitable laproscopes without the instrument markers <b>1130</b> are available from US Surgical of Norwalk, Conn., under the part name SURGIVIEW® Multi-Use Disposable Laproscope. FIG. 50 illustrates an RF ablation device <b>1120</b><i>e </i>having a function-site <b>1124</b><i>e </i>with RF elements <b>1137</b> through which RF energy is delivered to the target site T. The RF elements <b>1137</b> can be retractable into a cannula in a manner similar to the tissue anchors <b>310</b> described above with reference to FIGS. 10 and 11. Suitable RF ablation devices <b>1120</b><i>e </i>without the instrument markers <b>1130</b> are available from Radio Therapeutics Sunnyvale, Calif., under the part name LeVeen Needle Electrodes. FIG. 51 illustrates a robotic probe <b>1120</b><i>f </i>having a function-site <b>1124</b><i>f </i>defined by a distal tip of the probe <b>1120</b><i>f </i>The probe <b>1120</b><i>f </i>can be used to mark reference fiducials just prior to a surgical procedure to map out a desired cutting path. FIG. 52 illustrates a scalpel <b>1120</b><i>g </i>having a function-site <b>1124</b><i>g </i>defined by a cutting blade. Suitable scalpels without instrument markers <b>1130</b> are available from Bard-Parker of Franklin Lake, N.J., such as single-use Scalpel No. 11. It will be appreciated that FIGS. <b>46</b>-<b>52</b> illustrate only a few of the types of instruments for use with the system <b>1000</b> (FIG. 21), and that other types of instruments can be used with the system <b>1000</b> by adding instrument markers <b>1130</b> that the position detection system <b>1200</b> can track.

[0170] D. Embodiments of User Interfaces

[0171] FIGS. <b>53</b>-<b>61</b> illustrate several embodiments of user interfaces <b>1300</b> and methods for using the systems <b>20</b> and <b>1000</b> in accordance with the invention. The user interfaces <b>1300</b> can be used with any of the implantable markers <b>30</b> and <b>1100</b>, and any of the instruments <b>200</b>, <b>300</b> and <b>1120</b> described above with reference to FIGS. <b>1</b>-<b>52</b>. The user interface <b>1300</b> is generally a computer display for graphically illustrating or otherwise presenting the position data generated by the position detection system <b>1200</b> to a user. The user interface <b>1300</b> can alternatively be an audio signal, a visual pattern based on light and/or color, a tactile or mechanical signal (e.g., vibrational), or other indicators that can inform a physician of the relative position between the instrument and the target location.

[0172]FIG. 53 is a schematic diagram illustrating an embodiment of the system <b>1000</b> for displaying the relative position between an instrument <b>1120</b> and the target location T. In this embodiment, the system <b>1000</b> includes an implantable marker <b>1100</b> implanted in the body part B, an instrument <b>1120</b> for performing a procedure on the target location T, the position detection system <b>1200</b>, and the user interface <b>1300</b>. The implantable marker <b>1100</b> and the instrument <b>1120</b> can be any one of the embodiments of these devices described above. The instrument <b>1120</b>, more specifically, has an instrument coordinate system <b>1129</b> defined by the orthogonal axes X_i-Y_i-Z_i. The Z_i-axis is aligned with the alignment axis A-A, and the X_i-axis and Y_i-axis define an operating plane normal to the Z_i-axis. The instrument coordinate system <b>1129</b> moves with the instrument during the procedure. The position detection system <b>1200</b> generally includes the same components described above with reference to FIGS. 21 and 22. As such, the position detection system <b>1200</b> can include an array <b>1204</b> having sensors <b>1210</b> and a transmitter <b>1220</b> for emitting an excitation energy that drives the implanted marker <b>1100</b> and the instrument markers <b>1130</b>. The position detection system <b>1200</b> can also include a reference coordinate system <b>1212</b> defined by three orthogonal axes X_r-Y_r-Z_r. In operation, the position detection system <b>1200</b> determines the position of the implanted marker <b>1100</b> and the positions of the instrument markers <b>1130</b> relative to the reference coordinate system <b>1212</b> to determine the relative position between the function-site <b>1124</b> of the instrument <b>1120</b> and the target location T. The position detection system <b>1200</b> can also include a processor.

[0173] The user interface <b>1300</b> provides a display or another type of indicator of the relative position between the function-site <b>1124</b> and the target location T based on data from the position detection system <b>1200</b>. In this embodiment, the user interface <b>1300</b> includes a processor <b>1302</b>, a memory <b>1304</b> coupled to the processor <b>1302</b>, an input device <b>1306</b> for controlling parameters of the system <b>1000</b>, and an output display <b>1310</b>. The processor <b>1302</b> and the memory <b>1304</b> can be a computer available from many sources. The input device <b>1306</b> can be a keyboard, a computer mouse, a touch screen, or any other suitable device for inputting commands to the processor <b>1302</b>. The output display <b>1310</b> is preferably a display screen, but it can also be another type of output device that generates an output that can be detected and understood by a user. The user interface <b>1300</b> also includes a display coordinate system <b>1308</b> defined by three orthogonal axes X_d-Y_d-Z_d. The display coordinate system <b>1308</b> can initially correspond to the reference coordinate system <b>1212</b> of the position detection system <b>1200</b>. In many applications, however, it may not be desirable to view the display <b>1310</b> based upon the reference coordinate system <b>1212</b>. The processor <b>1302</b> can accordingly calibrate the display coordinate system <b>1308</b> so that the display <b>1310</b> shows a desired two-dimensional plane or a desired three-dimensional space.

[0174] In operation, the user interface <b>1300</b> processes data from the position detection system <b>1200</b> in real-time to show the relative motion between the function-site <b>1124</b> and the target location T. For example, the processor <b>1302</b> receives signals from the position detection system <b>1200</b> and produces output signals that can be represented by the output display <b>1310</b>. As explained in more detail below, the user can set the parameters for generating the virtual margin <b>1301</b> and controlling other aspects of the user interface <b>1300</b> using the input device <b>1306</b>.

[0175]FIG. 53 also illustrates an orientation between the instrument <b>1120</b> and the target location T that generally corresponds to a calibrating stage of a procedure for treating, probing, or monitoring the target location T. The surgeon typically holds the instrument <b>1120</b> so that the alignment axis A-A of the instrument <b>1120</b> defines a desired Z_ielevation axis along which the surgeon moves the instrument <b>1120</b> up and down relative to the target location T. The X_i-Y_iplane normal to the Z_i-axis defines the desired operating plane in which the surgeon moves the instrument <b>1120</b> along a margin M around the target location T during a procedure. When the physician holds the instrument <b>1120</b> relative to the target location T in a desired orientation for performing the procedure, the instrument coordinate system <b>1129</b> (X_i-Y_i-Z_i) may not be aligned with the reference coordinate system <b>1212</b> (X_r-Y_r-Z_r) and the display coordinate system <b>1308</b> (X_d-Y_d-Z_d). The user interface <b>1300</b> accordingly calibrates the display coordinate system <b>1308</b> to coincide with the instrument coordinate system <b>1129</b> so that the user interface <b>1300</b> indicates movement of instrument <b>1120</b> (a) along the alignment axis A-A as an elevation relative to the target location T, and (b) through the operating plane X_i-Y_ias a location in an X-Y grid of the display <b>1310</b>.

[0176]FIG. 54A illustrates one embodiment of the user interface <b>1300</b> showing the relative position between the instrument <b>1120</b> and the target location T before calibrating the position detection system <b>1200</b> to align the display coordinate system <b>1308</b> (FIG. 53) with the instrument coordinate system <b>1129</b> (FIG. 53). In this embodiment, the display <b>1310</b> has a two-dimensional grid <b>1320</b> that shows the X_d-Y_dplane of the display coordinate system <b>1308</b>. The display <b>1310</b> can also include a numerical elevation indicator <b>1332</b> and/or a graphical elevation indicator <b>1334</b>. The elevation indicators <b>1132</b> and <b>1134</b> show the position along the Z_d-axis of the display coordinate system <b>1308</b>. The instrument <b>1120</b> is displayed as a line on the grid <b>1320</b> because the user interface <b>1300</b> has not yet been calibrated to align the display coordinate system <b>1308</b> with the instrument coordinate system <b>1129</b>. The function-site <b>1124</b> of the instrument <b>1120</b> appears as a point at one end of instrument <b>1120</b>, and the elevation of the function-site <b>1124</b> relative to the target location T is displayed by one or both of the elevation indicators <b>1332</b> and <b>1334</b>. At this stage before calibrating the user interface <b>1300</b>, it may be difficult for a physician to determine the relative position between the function-site <b>1124</b> and the target location T because moving the instrument <b>1120</b> along the alignment axis A-A simultaneously changes the position of the function-site <b>1124</b> on the grid <b>1320</b> and on the elevation indicators <b>1332</b> and <b>1334</b>. Therefore, to provide a more intuitive display of the motion of the instrument <b>1120</b>, the position detection system <b>1200</b> aligns the display coordinate system <b>1308</b> with the instrument coordinate system <b>1129</b>.

[0177] Referring to FIG. 54B, an example of an algorithm for performing the calibration transformation is described as follows. The definitions include Azimuth=ψ; Elevation=θ; Point before transformation=(a,b,c). The mathematical equation to convert this point into the X′,Y′,Z′ coordinate system; (a′,b′,c′). In the user interface, the marker would be at (0,0,0) after the implementation of the algorithms. The X, Y, Z axis would still be oriented with the original coordinate system of the system reference. First rotate about the z-axis by the azimuth angle or ψ. The point in this intermediary coordinate system is now defined as:

<i>p=a</i>*cos(ψ)+<i>b</i>*sin(ψ)

<i>q=b</i>*cos(ψ)−<i>a</i>*sin(ψ)

r=c

[0178] Next, rotate about the y-axis so that the z-axis is in line with the probe. Effectively rotation will be about the y-axis by the elevation angle −90° or (θ−90°). The point in the X′,Y′,Z′ coordinate system would now be defined as:

<i>a′=p</i>*sin(θ)−<i>r</i>*cos(θ)

b′=q

<i>c′=p</i>*cos(θ)+<i>r</i>*sin(θ)

[0179] Substituting the values of p, q, and r into these equations the following equation is obtained in terms of the original coordinates and the azimuth and elevation angles:

<i>a′=[a</i>*cos(ψ)+<i>b</i>*sin(ψ)]*sin(θ)−<i>c</i>*cos(θ)

<i>b′=b</i>*cos(ψ)−<i>a</i>*sin(ψ)

<i>c′=[a</i>*cos(ψ)+<i>b</i>*sin(ψ)]*cos(θ)+<i>c</i>*sin(θ)

[0180] The point (a′,b′,c′) represents the original point (a,b,c) transformed into the new coordinate system. The user interface display probe tip projection math length projection on X-Y display plane is defined by the equation:

Display Length=length probe tip*cosine(Elevation angle)

[0181] Based on these algorithms, a person skilled in the art can program the user interface <b>1300</b> to perform the calibration without undue experimentation.

[0182]FIG. 55 illustrates an embodiment of the user interface <b>1300</b> of FIG. 54 after the position detection system <b>1200</b> calibrates the user interface <b>1300</b> to align the display coordinate system <b>1308</b> with the instrument coordinate system <b>1129</b>. In this embodiment, the instrument <b>1120</b> and the function-site <b>1124</b> are both displayed as a point location on the grid <b>1320</b>. The elevation of the function-site <b>1124</b> relative to the target location T still appears as a numeric or graphical readout on the elevation indicators <b>1332</b> and <b>1334</b>. After calibrating the coordinate systems, the user interface <b>1300</b> accordingly shows (a) movement of the instrument <b>1120</b> solely along the alignment axis A-A by changing only the readout on the elevation indicators <b>1332</b> and <b>1334</b> without changing the location of the instrument <b>1120</b> on the grid <b>1320</b>, and (b) movement of the instrument <b>1120</b> solely through the operating plane X_i-Y_iby changing only the location of the instrument <b>1120</b> on the grid <b>1320</b> without changing the readout on the elevation indicators <b>1332</b> and <b>1334</b>. The position detection system <b>1200</b> and/or the user interface <b>1300</b> can alternatively continuously calibrate the system <b>1000</b> so that the display coordinate system <b>1308</b> continuously coincides with the instrument coordinate system <b>1129</b>. In such an embodiment, the grid <b>1320</b> is continuously normal to the alignment axis A-A of the instrument <b>1120</b> such that the display <b>1310</b> continuously displays the instrument <b>1120</b> as a point location (as shown in FIG. 55) irrespective of the orientation of the instrument <b>1120</b>.

[0183]FIGS. 54A and 55 also illustrate one embodiment for defining a virtual margin <b>1301</b> relative to the target location T for use on the display <b>1310</b> of the user interface <b>1300</b>. As described above with reference to FIGS. <b>34</b>-<b>39</b>, the virtual margin <b>1301</b> can be generated based upon the position of an implantable marker <b>1100</b> or a plurality of implantable markers <b>1100</b>. The virtual margin <b>1301</b> is generally defined by a physician based upon information from an imaging procedure, such as when the markers <b>1100</b> are implanted. The virtual margin <b>1301</b> can be configured to include a lesion, tumor, or other mass that defines the area of interest at the target location T. The virtual margin <b>1301</b> should be configured to avoid removing or otherwise performing a procedure on material outside of the virtual margin <b>1301</b>. As such, after determining the relative position between the implantable marker <b>1100</b> and the target location T using an imaging process (e.g., radiation, MRI, ultrasound, etc.), the physician determines the desired virtual margin <b>1301</b> to input into the user interface <b>1300</b>.

[0184] The physician can input the desired virtual margin <b>1301</b> into the user interface <b>1300</b> using the input device <b>1306</b> of the user interface <b>1300</b> or an instrument <b>1120</b> (e.g., the probe <b>1120</b><i>f </i>shown in FIG. 51). In one embodiment using a keyboard, the physician can enter a desired radius relative to the target location T to define a spherical or cylindrical virtual margin <b>1301</b> that is displayed as a circle on the grid <b>1320</b> of the display <b>1310</b>. As explained above, the virtual margin <b>1301</b> can also be configured to be rectilinear, a compound shape, or any other suitable two-dimensional or three-dimensional shape that is defined by the physician. The user interface <b>1300</b> accordingly displays the selected a virtual margin <b>1301</b> to define a boundary relative to the target location T. For example, the virtual margin <b>1310</b> is often configured to completely surround or encompass a tissue mass or other body part within the target location T. Referring still to FIGS. 54 and 55, this embodiment of the invention illustrates a single implantable marker <b>1100</b> disposed in the target location T and a spherical or cylindrical virtual margin <b>1301</b> around the implantable marker <b>1100</b>.

[0185]FIG. 56 illustrates another embodiment for defining a virtual margin <b>1301</b> relative to a target location T. In this embodiment, the user interface <b>1300</b> can display an outline of the target location T (shown in broken lines), but it will be appreciated that the target location T may not be displayed on the grid <b>1320</b>. This embodiment of the invention illustrates a single implantable marker <b>1100</b> disposed outside of the target location T by an offset distance having coordinate differentials of “X” along an X-axis of the grid <b>1320</b>, “Y” along the Y-axis of the grid <b>1320</b>, and “Z” (not shown) along an axis normal to a plane defined by the grid <b>1320</b>. The offset distance can be determined during a previous imaging procedure or when the implantable marker <b>1100</b> is implanted using known radiation, MRI, ultrasound and other imaging techniques. Based upon the position of the implantable marker <b>1100</b> and the offset distance between the implantable marker <b>1100</b> and the target location T, the user interface <b>1300</b> can generate the virtual margin <b>1301</b> around the actual location of the target location T. One advantage of implanting the marker <b>1100</b> outside of the target location T is that the implantable marker <b>1100</b> does not pierce the tissue mass or other body part of the target location T. This feature can be particularly useful in applications for removing cancerous tissue masses or other types of tissue/bone masses that are desirably left intact until they are removed from the patient.

[0186]FIG. 57 illustrates another embodiment for defining a virtual margin <b>1301</b> relative to the target location T. In this embodiment, two implantable markers <b>1100</b><i>a </i>and <b>1100</b><i>b </i>have been implanted at two separate offset distances relative to the target location T. The physician can input two separate virtual margins <b>1301</b><i>a </i>and <b>1301</b><i>b </i>relative to the individual implantable markers <b>1100</b><i>a </i>and <b>1100</b><i>b</i>, respectively. In this particular embodiment, the virtual margin <b>1301</b><i>a </i>is relative to the first implantable marker <b>1100</b><i>a </i>and defines a cylindrical boundary. Similarly, the virtual margin <b>1301</b><i>b </i>is relative to the second implantable marker <b>1100</b><i>b</i>, but it defines a spherical boundary. The virtual margins <b>1301</b><i>a </i>and <b>1301</b><i>b </i>together define a compound virtual margin relative to the target location T. It will be appreciated that several other virtual margins can be developed using different combinations of one or more implantable markers, and different combinations of markers that are implanted in and/or offset from the target location T. In any of the embodiments of the virtual margins <b>1301</b> described above, the physician can manipulate an instrument <b>1120</b> relative to the target location T using the user interface <b>1300</b> to display the relative position between the function-site <b>1124</b> of the instrument <b>1120</b> relative to the virtual margin <b>1301</b>.

[0187] FIGS. <b>58</b>A-<b>58</b>C illustrate a procedure for operating the system <b>1000</b> in accordance with one embodiment of the invention. In this example, a single implantable marker <b>1100</b> has been implanted within the target location T and the user interface <b>1300</b> has generated a cylindrical or spherical virtual margin <b>1301</b> around the target location T. Referring to FIG. 58A, the instrument <b>1120</b> is shown after the display coordinate system has been calibrated to be aligned with the instrument coordinate system in the manner explained above with reference to FIGS. <b>53</b>-<b>55</b>. The user interface <b>1300</b> initially displays the instrument <b>1120</b> as a point at a location A. Based upon this display, the physician understands that the alignment axis A-A of the instrument <b>1120</b> is normal to the grid <b>1320</b> of the display <b>1310</b>, and that the function-site <b>1124</b> of the instrument <b>1120</b> is at an elevation of 5 cm above a predetermined reference plane relative to the target location T and/or the implanted marker <b>1100</b> (see the elevation indicator <b>1332</b>). The physician then moves the instrument <b>1120</b> transverse relative to the alignment axis A-A to a location B on the virtual margin <b>1301</b>. In this particular embodiment, the physician held the instrument <b>1120</b> at a constant elevation of 5 cm above the reference plane shown by the elevation indicator <b>1132</b>.

[0188]FIG. 58B illustrates a subsequent stage of operating the system <b>1000</b>. After moving the instrument <b>1120</b> from location A to location B (FIG. 58A), the physician inserts the function-site <b>1124</b> of instrument <b>1120</b> into the body part to move the function-site <b>1124</b> from the location B to a location C. Referring to both FIGS. 58A and 58B, the elevation indicator <b>1132</b> shows that the elevation of the function-site <b>1124</b> relative to the reference plane has moved from 5 cm above the reference plane to 2 cm below the reference plane. In an application in which the physician wants to excise a cylindrical tissue mass having a base 2 cm below the reference plane, the instrument <b>1120</b> at location C is accordingly ready to be moved along the virtual margin <b>1301</b> to excise a mass of tissue. Referring to FIG. 58C, the user interface <b>1300</b> displays the motion of the instrument as the physician or robot moves it along the virtual margin <b>1301</b>. The virtual margin <b>1301</b> accordingly provides a guide to the physician that allows the physician to excise a precise volume of tissue without cutting into the target mass or damaging tissue outside of the target location T.

[0189]FIG. 59 illustrates another embodiment of the user interface <b>1300</b> in accordance with the invention. In this embodiment, the display <b>1310</b> includes a first grid <b>1320</b> illustrating a top view relative to a reference plane and a second grid <b>1420</b> illustrating a front view normal to the reference plane. For purposes of convention, the reference plane can be parallel to the table on which the patient is positioned during a procedure, but it can also be at an angle to the table. The display <b>1310</b> can also include an elevation indicator <b>1132</b> showing the elevation of the function-site <b>1124</b> relative to the target location T and a distance indicator <b>1432</b> showing the point-to-point distance between the function-site <b>1124</b> and the target location T. The embodiment of the display <b>1310</b> shown in FIG. 59 provides the physician two separate views that the physician can use to more accurately position the function-site <b>1124</b> relative to the target location T. The operation and the advantages of the display <b>1310</b> illustrated in FIG. 59 are expected to be similar to those described above with reference to FIGS. <b>55</b>-<b>57</b>.

[0190]FIGS. 60 and 61 illustrate additional embodiments of the user interface <b>1300</b> in accordance with the invention. Referring to FIG. 60, the display <b>1310</b> provides a three-dimensional solid or opaque representation of the virtual margin <b>1301</b>. FIG. 61 illustrates an embodiment in which the display <b>1310</b> provides a holographic representation of the virtual margin <b>1301</b> such that the target location T can be represented within the holographic representation. Suitable software for generating the three-dimensional representations of the virtual margin <b>1301</b> illustrated in FIGS. 60 and 61 is available from Medical Media System of West Lebanon, N.H. The three-dimensional representations of the virtual margin <b>1301</b> also provide a physician with an intuitive understanding of the relative position between the function-site <b>1124</b> of the instrument <b>1120</b> and the virtual margin <b>1301</b> relative to the target location T. It is expected, therefore, that the three-dimensional virtual margins <b>1301</b> will also allow physicians to accurately perform procedures or monitor internal target locations within a human body without additional imaging equipment or procedures.

[0191] From the foregoing, it will be appreciated that specific embodiments of the invention have been described herein for purposes of illustration, but that various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not limited except as by the appended claims.