Abstract:
An intracorporeal marker delivery device includes a delivery tube which has a tapered, tissue penetrating distal tip, an inclined discharge orifice in the tapered distal tip and an inner bore extending to the orifice. A plurality of remotely detectable markers, which are formed at least in part of bioresorbable material, are slidably disposed within the inner bore. A plug having an inclined exposed surface, which is formed at least in part of bioresorbable material, is releasably secured within the inner bore of the delivery tube distal to the plurality of remotely detectable markers disposed therein to retain the plurality of remotely detectable markers within the inner bore. The plug is disposed at least in part within the inclined discharge orifice. A plunger is slidably disposed within the inner bore proximal to the plurality of remotely detectable markers.

Description:
RELATED APPLICATIONS 
     This application is a continuation of application Ser. No. 10/174,401, filed Jun. 17, 2002, now U.S. Pat. No. 7,651,505, which is incorporated by reference herein in its entirety and from which priority is claimed. 
    
    
     FIELD OF THE INVENTION 
     The invention is directed generally to devices and methods for delivering markers to a desired location within a patient&#39;s body. In particular, the invention is directed to devices, assemblies, and methods configured to retain a biological marker within a delivery device before delivery of the marker to a desired intracorporeal location. 
     BACKGROUND OF THE INVENTION 
     In diagnosing and treating certain medical conditions, it is often desirable to mark a suspicious body site for the subsequent taking of a biopsy, delivery of medicine, radiation, or other treatment, to mark a location from which a biopsy was taken, or at which some other procedure was performed. As is known, obtaining a tissue sample by biopsy and the subsequent examination are typically employed in the diagnosis of cancers and other malignant tumors, or to confirm that a suspected lesion or tumor is not malignant. The information obtained from these diagnostic tests and/or examinations is frequently used to devise a therapeutic plan for the appropriate surgical procedure or other course of treatment. 
     In many instances, the suspicious tissue to be sampled is located in a subcutaneous site, such as inside a human breast. To minimize surgical intrusion into patient&#39;s body, it is often desirable to insert a small instrument, such as a biopsy needle, into the body for extracting the biopsy specimen while imaging the procedure using fluoroscopy, ultrasonic imaging, x-rays, magnetic resonance imaging (MRI) or any other suitable form of imaging technique. Examination of tissue samples taken by biopsy is of particular significance in the diagnosis and treatment of breast cancer. In the ensuing discussion, the biopsy and treatment site described will generally be the human breast, although the invention is suitable for marking biopsy sites in other parts of the human and other mammalian body as well. 
     Periodic physical examination of the breasts and mammography are important for early detection of potentially cancerous lesions. In mammography, the breast is compressed between two plates while specialized x-ray images are taken. If an abnormal mass in the breast is found by physical examination or mammography, ultrasound may be used to determine whether the mass is a solid tumor or a fluid-filled cyst. Solid masses are usually subjected to some type of tissue biopsy to determine if the mass is cancerous. 
     If a solid mass or lesion is large enough to be palpable, a tissue specimen can be removed from the mass by a variety of techniques, including but not limited to open surgical biopsy, a technique known as Fine Needle Aspiration Biopsy (FNAB) and instruments characterized as “vacuum assisted large core biopsy devices”. 
     If a solid mass of the breast is small and non-palpable (e.g., the type typically discovered through mammography), a biopsy procedure known as stereotactic needle biopsy may be used. In performing a stereotactic needle biopsy of a breast, the patient lies on a special biopsy table with her breast compressed between the plates of a mammography apparatus and two separate x-rays or digital video views are taken from two different points of view. A computer calculates the exact position of the lesion as well as depth of the lesion within the breast. Thereafter, a mechanical stereotactic apparatus is programmed with the coordinates and depth information calculated by the computer, and such apparatus is used to precisely advance the biopsy needle into the small lesion. Depending on the type of biopsy needle(s) used, this stereotactic technique may be used to obtain cytologic specimens, e.g., obtained through FNAB or it may be used to obtain histologic specimens e.g., obtained through coring needle biopsy. Usually at least five separate biopsy specimens are obtained from locations around the small lesion as well as one from the center of the lesion. 
     The available treatment options for cancerous lesions of the breast include various degrees of mastectomy or lumpectomy and radiation therapy, as well as chemotherapy and combinations of these treatments. However, radiographically visible tissue features, originally observed in a mammogram, may be removed, altered or obscured by the biopsy procedure, and may heal or otherwise become altered following the biopsy. In order for the surgeon or radiation oncologist to direct surgical or radiation treatment to the precise location of the breast lesion several days or weeks after the biopsy procedure was performed, it is desirable that a biopsy site marker be placed in or on the patient&#39;s body to serve as a landmark for subsequent location of the lesion site. A biopsy site marker may be a permanent marker (e.g., a metal marker visible under X-ray examination), or a temporary marker (e.g., a bioresorbable marker detectable with ultrasound). While current radiographic type markers may persist at the biopsy site, an additional mammography generally must be performed at the time of follow up treatment or surgery in order to locate the site of the previous surgery or biopsy. In addition, once the site of the previous procedure is located using mammography, the site must usually be marked with a location wire which has a hook on the end which is advanced into site of the previous procedure. The hook is meant to fix the tip of the location wire with respect to the site of the previous procedure so that the patient can then be removed from the confinement of the mammography apparatus and the follow-up procedure performed. However, as the patient is removed from the mammography apparatus, or otherwise transported the position of the location wire can change or shift in relation to the site of the previous procedure. This, in turn, can result in follow-up treatments being misdirected to an undesired portion of the patient&#39;s tissue. 
     As an alternative or adjunct to radiographic imaging, ultrasonic imaging and visualization techniques (herein abbreviated as “USI”) can be used to image the tissue of interest at the site of interest during a surgical or biopsy procedure or follow-up procedure. USI is capable of providing precise location and imaging of suspicious tissue, surrounding tissue and biopsy instruments within the patient&#39;s body during a procedure. Such imaging facilitates accurate and controllable removal or sampling of the suspicious tissue so as to minimize trauma to surrounding healthy tissue. 
     For example, during a breast biopsy procedure, the biopsy device is often imaged with USI while the device is being inserted into the patient&#39;s breast and activated to remove a sample of suspicious breast tissue. As USI is often used to image tissue during follow-up treatment, it may be desirable to have a marker, similar to the radiographic markers discussed above, which can be placed in a patient&#39;s body at the site of a surgical procedure and which are visible using USI. Such a marker enables a follow-up procedure to be performed without the need for traditional radiographic mammography imaging which, as discussed above, can be subject to inaccuracies as a result of shifting of the location wire as well as being tedious and uncomfortable for the patient. 
     Placement of a marker or multiple markers at a location within a patient&#39;s body requires delivery devices capable of holding markers within the device until the device is properly situated within a breast or other body location. Accordingly, devices and methods for retaining markers within a marker delivery device while allowing their expulsion from the devices at desired intracorporeal locations are desired. 
     SUMMARY OF THE INVENTION 
     The invention provides devices and systems for delivery of markers to a site within a patient&#39;s body. Delivery systems embodying features of the invention include a marker delivery tube with a removable plug. Plugs embodying features of the invention are held within an orifice at the tip of the delivery tube, retaining markers within the delivery tube, until it is desired that the markers be ejected. The plug may then be ejected or removed from the orifice, allowing the delivery of the markers to a desired site within a patient&#39;s body. Plugs and delivery tubes embodying features of the invention may have retaining features, such as recesses or protuberances, configured to releasably retain a plug within a delivery tube until ejection of the plug from the delivery tube is desired. The retaining features are typically complementary pairs, such as a plug protuberance configured to fit into a recess in the delivery tube. 
     Assemblies embodying features of the invention include marker delivery devices having a delivery tube with an orifice at its distal tip, an inner bore leading to an orifice, and at least one marker (preferably more than one) within the bore of the delivery tube. A plug is disposed at least in part within the bore and orifice to prevent markers from prematurely passing through the orifice and to prevent tissue from entering the bore when the delivery tube is advanced through tissue. The plug may itself serve as a marker, and may be the sole marker, although typically the delivery tube contains a plug and at least one other marker. The plug is releasably secured within or adjacent to the orifice in order to retain a marker within the delivery tube bore proximate thereto but to allow passage of the marker out of the orifice when the plug is ejected from the orifice. The plug may partially or completely occlude the orifice, and is configured to retain the marker within the delivery tube before the marker is to be placed at a desired location within a patient&#39;s body, and to allow the marker to pass out of the orifice when delivery of the marker is desired. A movable plunger may be slidably disposed within the tube from an initial position accommodating the marker or markers and the plug within the tube, to a delivery position to push a marker against the plug to push the plug out of the orifice and to then eject one or more markers through the orifice. 
     The plug is preferably configured to be releasably retained within the delivery tube, and may be aligned in a preferred orientation within the delivery tube, to properly orient an inclined face within the orifice. A plug may be configured to fit tightly within a part of the bore of a delivery device so as to be retained by pressure; may have a portion configured to contact a slot, hole, notch, ridge, tab, lip, or other feature of a delivery tube; may be configured to be retained by a tab; may include an internal retention element, such as a coil, a spring, a clip, a loop, an arch, or a resilient core, that is configured to press an outer portion of a plug against a delivery tube wall or to contact a retaining feature such as a tab, slot, notch or hole; may be pressed against at least part of the bore of a delivery tube by an external retention element such as a pin, wedge, clip, spring, coil or other element applied to a plug; or by otherwise engaging a portion of a delivery tube effective to be releasably retained within a delivery tube. 
     The plug is preferably biocompatible, and may itself be a marker that is detectable within a patient&#39;s body visually, tactilely, by imaging (including ultrasound, radiographic, magnetic resonance, or other form of imaging), or is otherwise detectable. A plug may be a bio-resorbable temporary marker made up of bio-resorbable materials, or may be a permanent marker including non-bio-resorbable materials as well. A plug may also include bio-active materials (e.g., hemostatic materials, anesthetic materials, absorbent materials, antibiotic materials, antifungal materials, antiviral materials, chemotherapeutic materials, radioactive materials, and other pharmaceutical materials) as well as biologically inert materials. 
     Systems and devices embodying features of the invention may have markings or indicators to aid in placement of the delivery tube in a desired location. In addition, methods of using systems and devices embodying features of the invention include guiding the insertion of the delivery tube with the aid of an imaging device, such as an ultrasound imaging device, an x-ray imaging device, and a magnetic resonance imaging device, which may be used to image the plug, a marker retained within the delivery device, a portion of the delivery device, or combinations of these. 
     The invention provides the advantages of securely retaining markers within a marker delivery device, improving accuracy and avoiding errors in of placement of markers at desired locations within a patient&#39;s body, preventing ingress of tissue into the distal tip of the device when it is advanced through tissue, and guiding the device by use of an imaging device. These and other advantages of the invention will become more apparent from the following description when taken in conjunction with the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1A  is a partly cut-away perspective view of a marker delivery assembly embodying features of the invention showing several markers within a marker delivery device and a plug embodying features of the invention occluding the tip of the delivery device. 
         FIG. 1B  is a transverse cross-sectional view of the marker delivery assembly of  FIG. 1A  taken at line  1 B- 1 B. 
         FIG. 1C  is a transverse cross-sectional view of the marker delivery assembly of  FIG. 1A  taken at line  1 C- 1 C. 
         FIG. 1D  is a transverse cross-sectional view of the marker delivery assembly of  FIG. 1A  taken at line  1 D- 1 D. 
         FIGS. 2A-2C  and  2 E- 2 H are longitudinal cross-sectional views of a delivery tube distal portion embodying features of the invention configured to retain a plug, containing markers and a plug embodying features of the invention. 
         FIG. 2D  is a transverse cross-sectional view of the delivery tube distal portion and plug shown in  FIG. 2C . 
         FIG. 3A  is a longitudinal cross-sectional view of a compressible plug embodying features of the invention disposed outside a distal portion of a delivery tube. 
         FIG. 3B  is a longitudinal cross-sectional view of the compressible plug of  FIG. 3A  embodying disposed within the distal portion of the delivery tube. 
         FIG. 3C  is a longitudinal cross-sectional view of an alternative embodiment of a compressible plug. 
         FIG. 3D  is a longitudinal cross-section of a plug containing an internal retention element configured to press against the wall of a delivery tube. 
         FIG. 4A  is a longitudinal cross-sectional view of a plug embodying features of the invention disposed outside a distal portion of a delivery tube. 
         FIG. 4B  is a longitudinal cross-sectional view of an external retention element and of a plug embodying features of the invention disposed within a distal portion of a delivery tube. 
         FIG. 4C  is a longitudinal cross-sectional view of the external retention element inserted into the plug of  FIG. 4B  embodying disposed within the distal portion of the delivery tube. 
         FIG. 4D  is a perspective view of a sharp tip of a delivery tube distal portion embodying features of the invention having slits forming a tab configured to retain and align a plug. 
         FIG. 4E  is a longitudinal cross-section of a delivery tube distal portion embodying features of the invention having a tab configured to retain a plug, and containing a plug configured to be retained and aligned by a tab. 
         FIG. 4F  is a longitudinal cross-section of a delivery tube distal portion embodying features of the invention having a tab configured to retain and align a plug, and containing a plug configured to be retained by a tab. 
         FIGS. 5A-5H  are alternating plan and elevation views of distal portions of delivery tubes of marker delivery devices embodying features of the invention configured to retain a plug by having holes or slots through the tube wall. 
         FIG. 6  is a partially cut away, perspective view of a human breast having a lesion from which a biopsy specimen has been removed, and showing a guide cannula and a marker delivery assembly embodying features of the invention inserted into the breast, the assembly having markers and a plug configured to retain the markers within a delivery tube of a delivery device. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Marker delivery assemblies embodying features of the invention are illustrated in  FIGS. 1A-1D . Such assemblies include marker delivery devices, markers, and a plug occluding a distal portion of the delivery device. The assembly  10  shown in  FIG. 1A  includes a delivery device  12 , delivery tube  14  with a bore  16 , a distal portion  18 , and a proximal portion  20  with a handle  22 . Several markers  24 , and a plug  26  are shown disposed within the bore  16 . A plunger  28  with a plunger handle  30  and a plunger distal end  32  is movable within the tube bore  16 , and is configured to push markers  24  and plug  26  out of orifice  34  at the distal tip  36  of delivery tube  14  when the distal end  32  of plunger  28  moves in a distal direction. Plunger handle  30  allows an operator to readily manipulate plunger  28 . A device  12  may include a plunger locking mechanism to prevent inadvertent longitudinal movement of plunger  28 ; for example, a plunger  28  and a handle  22  may be configured so that plunger  28  must be rotated some amount before it is able to be moved in a longitudinal direction (by, e.g., having a lateral tab protruding from a portion of the plunger  28  that prevents longitudinal plunger movement until the tab is moved to a channel configured to accept it). 
     Plug  26  may substantially fill orifice  34 , as shown in  FIG. 1A , or may occupy or block only a portion of orifice  34 . A plug  26  preferably does not interfere with the sharp edge of orifice  34  or pointed tip  36  of a delivery tube  14 . Where distal tip  36  of delivery tube  14  is sharp, as shown in  FIG. 1A , the distal surface  38  of plug  26  is preferably configured with an inclined surface to closely follow the conformation of distal tip  36  to provide more effective penetration. 
     Markers  24  are preferably configured to slide readily within tube bore  16 . Plug  26  is configured to be releasably secured within a portion of tube bore  16 , such as a distal portion  18  or orifice  34 , effective to prevent inadvertent exit or release of markers  24  from delivery tube  14 . The engagement of plug  26  with delivery tube  14  is further configured to be readily releasable when desired. For example, plug  26  is configured to release its engagement with delivery tube  14  effective to allow exit of markers  24  upon distal movement of plunger  28 . Markers  24  are made with detectable, biocompatible materials, and may include a radiopaque element  40 . Plug  26  may be made from the same or similar materials as a marker  24 , and may also include a radiopaque element  40 . 
       FIG. 1A  shows a marker delivery device  12  having a delivery tube  14  with a Distal tip  36  having a notch  42  configured to retain a plug  26 . A notch  42  is effective to retain a plug  26 , particularly if a portion of the plug  26  is formed to engage with the notch  42 , or is pressed or otherwise introduced into at least a portion of the notch  42 . The delivery tube  14  also has markings  44  which aid in placement of the device in a desired location within a patient&#39;s body. The markings  44  may serve as visual landmarks for guiding an operator in placing the device, and may also be radiopaque, ultrasound-reflective, or otherwise configured to be detectable by imaging devices and imaging methods. 
     In  FIG. 1B , the plug  26  is shown in place within tube bore  16  at the distal portion  18  of delivery tube  14 . In  FIG. 1C , a marker  24  with radiopaque element  40  is shown within tube bore  16  of delivery tube  14 . In  FIG. 1D , a portion the plunger  28  is shown in place within tube bore  16  of delivery tube  14 . 
       FIGS. 2A-2H  illustrate several alternative embodiments of a plug  26  having features of the invention. The plugs  26  in  FIGS. 2A-2C  and  2 E- 2 H are shown in longitudinal cross-section within a distal portion  18  of a delivery tube  14  of a marker delivery device  12  embodying features of the invention.  FIG. 2A  illustrates a plug  26  configured to be retained within a delivery tube  14  and to occlude an orifice  34 . Plug  26  of  FIG. 2A  is configured to provide a surface  38  following a configuration generally perpendicular to wall  46  conforming to the sharp tip  36 , effective to aid the penetration of sharp tip  36  into a patient&#39;s tissue as well as to retain markers  24  within a delivery device  12 . A plug  26  embodying features of the invention may be retained within a delivery tube  14  effective to occlude an orifice  34  and to retain a marker  24  in any one or in more than one way. For example, a plug  26  may be retained by friction, adhesion, tension, pressure, or other mechanisms; may be retained mechanically, as by a notch, hole, slot, tab, ridge, lip or other feature of a tube  14 , of the plug  26  itself, or by any combination of such elements; or by any other mechanism or method suitable to releasably retain a plug while allowing its removal at a desired time. Some examples of such features and elements are illustrated in the figures, although the devices, assemblies and elements embodying features of the invention are not limited to these examples. Any feature, element, or means of retaining a plug in a location effective to occlude an orifice  34  and to retain a marker  24  within a delivery tube  14 , while allowing its removal at a desired time, is suitable for the practice of the invention. 
       FIG. 2B  illustrates a plug  26  having a protrusion  48  configured to engage a passage  50  through tube wall  46 , aiding in the retention of plug  26  within bore  16  of delivery tube  14 . A passage  50  may be a hole, slot, notch, or other void through a tube wall  46 . Alternatively, a protrusion  48  of a plug  26  may engage a slot, notch, or crease along a bore  16  that does not completely pass through the wall  46 , yet still provides purchase for retaining a plug  26  within a delivery tube  14 . 
       FIG. 2C  illustrates a plug  26  embodying features of the invention having a gap  52  allowing compression of plug  26  effective to allow insertion of plug  26  into distal portion  18 , where plug  26  occludes orifice  34 . Resilience of plug  26  provides outward pressure following such compression, effective to provide lateral pressure against a wall  46  of a delivery tube  14  and so to retain the plug  26  within distal portion  18  of tube  14 . The embodiment of a plug  26  illustrated in  FIG. 2C  also has a lip portion  54  effective to limit the extent of insertion of plug  26  into delivery tube  14 . It will be understood that a lip portion  54  is optional, and is not present in some plugs  26 , including resilient plugs  26  embodying features of the invention. Preferably, lip portion  54  is configured to leave a sufficient amount of distal tip  36  exposed so as to not substantially interfere with penetration of sharp tip  36  into the tissue of a patient. For example, a lip portion  54  preferably comprises less than a full circumference a plug  26  having a round cross-section, and may comprise one or a few extensions  56  extending radially outwardly form a plug body  58 , as illustrated in  FIG. 2D  in a transverse cross-sectional view of the plug  26  and tube  14  of  FIG. 2C . A plug body  58  may surround a gap  52 , as in the plug  26  illustrated in  FIGS. 2C and 2D , or, in other embodiments, may not have a gap  52 , as, e.g., in the plugs  26  illustrated in  FIGS. 2A and 2B . 
     The plug  26  illustrated in  FIG. 2E  is an irregularly-shaped plug  26  embodying features of the invention, configured to occlude an orifice  34  and to retain markers  24  within a delivery tube  14  until the plug  26  is removed or moved away from its blocking position. An irregularly-shaped plug  26  may be put into place, for example, by the application of a liquid, flexible or pliable material that sets or hardens after placement in or around an orifice  34 . Alternatively, a material may be placed in or around an orifice  34  and then treated with heat, solvent, hardener, or other treatment in order to fix the plug  26  in its final form. 
     As illustrated by the embodiment of a plug  26  shown in  FIG. 2F , an orifice  34  need not be completely occluded; partial occlusion of an orifice  34  by a plug  26  is sufficient to retain a marker  24  within a delivery tube  14 . Such a plug  26  may be retained within the bore  16  of a delivery tube  14  by adhesion or other bonding to a tube wall  46 , or by a feature of a tube  14  embodying features of the invention such as a tab, lip, hole, notch, slot, or other retaining element. 
     The embodiments of a plug  26  shown in  FIGS. 2G and 2H  include marker material effective to mark a location within a patient&#39;s body, and thus is configured to act as a marker  24  as well as a plug  26 . For example, a plug  26  as illustrated in  FIGS. 2G and 2H  may be a plug  26  having a lip portion  54  and a body portion  58  configured to press against a tube wall  46  so as to retain plug  26  within the delivery tube  14 , and including marker material so as to be able to serve as a marker  24  following ejection from orifice  34  and delivery into a desired location within a patient&#39;s body. Preferably, a lip portion  54  does not extend so far as to interfere with the cutting action of sharp tip  36 . A plug  26  configured to serve as a marker  24  may include bioresorbable marker materials, and be a temporary marker, or may include non-bioresorbable marker materials, and so be a permanent marker. For example, the embodiment of a plug  26  shown in  FIG. 2H  is also configured to serve as a marker  24 , and further includes a radiopaque element  40 . Typically, a radiopaque element  40  is a permanent marker element, so that plug  26  shown in  FIG. 2H , for example, may be a permanent marker. 
     A compressible plug  26  as illustrated in  FIGS. 2C and 2D  may be inserted into a delivery tube  14  through an orifice  34  as shown in  FIGS. 3A and 3B .  FIG. 3A  shows a longitudinal cross-section of a compressible plug  26  disposed distal to an orifice  34  of a delivery tube  14 . Compression of body  58  effective to reduce the size of gap  52  also reduces a lateral dimension of the plug  26  enabling a portion of the plug body  58  to be inserted through orifice  34  into tube bore  16  to be disposed in position within delivery tube  14  as shown in  FIG. 3B . Resiliency of plug body  58  is effective to create pressure against a tube wall  46  so as to retain plug  26  in position within bore  16  in distal tube portion  18 . In the embodiment shown in  FIGS. 3A and 3B , gap  52  is disposed so as to face bore  16  of delivery tube  14 . Alternatively, as shown in  FIG. 3C , a gap  52  may face away from a tube bore  16 . In either embodiment, plug body  58  is resiliently compressible and snugly retained within a distal tube portion  18 . 
     In addition, a further embodiment of a plug  26  embodying features of the invention is illustrated in  FIG. 3D . A plug  26  may contain an internal retention element  60  configured to press itself or a portion of a plug body  58  against a wall  46  of a delivery tube  14 . Such an internal retention element  60  may be radiopaque internal retention element  60 , and thus, in that case, the plug  26  will also be configured to be a radiopaque marker  24 . An internal retention element  60  may be any element, including a spring, a coil, a clip, a loop, an arch, a resilient core, or other element that is configured to help retain a plug  26  within a delivery tube  14 . For example, a resilient core may be a portion of a plug body  58  which includes a resilient material and which provides outward force when a plug  26  is disposed within a bore  16  of a delivery tube  14 . A plug  26  as illustrated in  FIG. 3D  is a further example of a compressible plug  26 . It will be understood that a compressible plug  26  need not have a gap  52  in order to be resiliently compressible effective to be inserted into and releasably retained within a delivery tube  14 ; for example, a plug  26  may be a compressible plug including an internal retention element  60 , or where the entire plug body  58  is formed of a resilient material, such as, for example, a foam or spongy material which tends to re-expand after compression, or which tends to resist compression by exerting counteracting force against compression. 
     A plug  26  may be releasably retained within a bore  16  of a delivery tube  14  upon addition or insertion of an external retention element  62 .  FIG. 4A  illustrates a plug  26  embodying features of the invention disposed distal to a distal portion  18  of a delivery tube  14 .  FIG. 4B  illustrates the plug  26  of  FIG. 4A  disposed within distal portion  18 , in which plug body  58  does not tightly contact a tube wall  46  and plug  26  is not snugly held within delivery tube  14 . Also shown in  FIG. 4B  is an external retention element  62  in the form of a conical pin.  FIG. 4C  illustrates a plug  26  embodying features of the invention including external retention element  62  mounted in a gap  52 . Following insertion of external retention element  62  into plug  26 , at least a portion of plug body  58  contacts tube wall  46  effective to releasably retain plug  26  within a distal portion  18  of delivery tube  14  effective to occlude orifice  34  and to retain a marker  24 . In other embodiments, an external retention element  62  may be a wedge, a screw, a mandrel, or any other element configured to tend to expand a portion of a plug body  58  effective to exert force against a tube wall  46 , such as by tending to expand a plug body  58 , or otherwise to aid in retaining a plug  26  within a distal portion  18  of a delivery tube  14 . 
     A delivery tube  14  may be configured to retain and optionally to align a plug  26 . For example, a delivery tube  14  may have a retaining feature  64 , illustrated in  FIGS. 4D ,  4 E and  4 F as a tab, configured to engage a plug  26  and to hold it in place. The retaining feature  64  shown in  FIG. 4D  is a tab of metal formed by two longitudinal slots in the distal end of the wall  46  of delivery tube  14  that has been deflected inwardly to engage a plug  26  disposed within the bore  16 , as shown in  FIGS. 4E and 4F  (the tab shown in  FIG. 4F  may be formed by one radial and two longitudinal slots). A retaining feature  64 , such as a tab, may also help to align a plug  26  within a delivery tube  14 . A plug  26  may optionally also be configured to be retained by a retaining feature  64 , such as a tab, as illustrated in  FIGS. 4E and 4F , although a retaining feature  64  may be effective to retain a plug  26  without any particular configuration of a plug  26 . A plug  26  may also be configured to be aligned by a retaining feature  64 , e.g., by having a notch, depression, ridge or other feature configured to engage a retaining feature  64 . 
     Upon expulsion of a plug  26 , as may be caused by distal movement of a plunger  28 , a retaining feature  64  may become reconfigured to allow passage of a marker  24  out of an orifice  34  for delivery into a patient. For example, where the retaining feature  64  is a tab intruding into a tube bore  16 , as shown in  FIGS. 4D ,  4 E and  4 F, the expulsion of a plug  26  may be effective to bend the tab outwardly so it more closely approaches tube wall  46  and does not prevent movement of a marker  24  through the bore  16  of a delivery tube  14 . Alternatively, a retaining feature  64  may be unaffected by movement of a plug  26  or a marker  24 . For example, a retaining feature  64  may be configured to impede movement of a plug  26  or of a marker  24 , without preventing such movement, and so act to releasably retain a plug  26  effective to retain a marker  24  within a delivery tube  14  until the delivery of the marker  24  is desired. 
     Several examples of alternative embodiments of retaining features  64  are illustrated in  FIGS. 5A through 5H , representing some, but not all, suitable types and configurations of retaining features  64  embodying features of the invention. A retaining feature  64  may be disposed at any location on, within, or through a wall  46  of delivery tube  14 , although a distal portion  18  of a delivery tube  14  is preferred. A retaining feature may be continuous with an orifice  34  at the distal tip  36  of a delivery tube, or may be disposed proximally of the distal tip  36  of a delivery tube  14 . A delivery tube  14  may include more than one retaining feature  64 , and may include more than one shape or type of retaining feature  64 . 
       FIG. 5A  is a plan view, and  FIG. 5B  is an elevation view, of a distal portion  18  of a delivery tube  14  of a marker delivery device  12  embodying features of the invention, with a retaining feature  64  that is a rectangular slot  51  through tube wall  46 . In  FIGS. 5C and 5D , a distal portion  18  of a delivery tube  14  is shown having two retaining features  64 : a rectangular slot  51  and a round hole  53  through tube wall  46 . The distal portion  18  of delivery tube  14  shown in  FIGS. 5E and 5F  has retaining features  64  that are a round hole  53  and a rectangular slot  51  connecting to orifice  34 . The retaining features  64  illustrated in  FIGS. 5G and 5H  are all round holes  53  spaced around delivery tube  14 . Retaining features  64  may also take other shapes and may be disposed in other positions on a distal portion  18 . For example, a retaining feature may be an irregularly-shaped slot, combining in part a round hole and a slot with angled sides, and may connect with orifice  34  at tube distal tip  36 . 
     A marker delivery assembly  10  embodying features of the invention may be used to deliver a marker  24  to a desired location within a patient&#39;s body. Such a desired location is typically a lesion site from which a biopsy sample has been, or is to be, taken, or a lesion has been or will be removed. Assemblies, devices, and methods embodying features of the invention find use, for example, in marking a breast biopsy site. By way of illustration, the use of assemblies, devices and methods embodying features of the invention will be discussed below in terms of breast biopsies and similar uses involving marking sites within a breast of a human female. It will be understood that the assemblies, devices and methods embodying features of the invention find use in a variety of locations and in a variety of applications, in addition to the human breast. 
     An assembly  10  or delivery device  12  can be inserted into a breast  66  through a guide cannula  72 , as illustrated in  FIG. 6 . Alternatively, an assembly  10  or delivery device  12  can be inserted directly into a breast  66 , using a distal tip  36  that is sharp and so is configured to pierce or puncture tissue  68 , with or without an initial incision through the skin  70  of a patient. In either case, markings  44  along a delivery tube  14  may be used to aid in the proper placement of the orifice  34  of a delivery tube  14 , and so to aid in the proper delivery of a marker  24  to a desired location within a breast. 
     A plug  26  and marker  24  may be introduced into a breast  66  of a patient at a lesion site  74  adjacent or within a biopsy cavity  76 , from which a biopsy sample or tissue from a lesion has been taken, as illustrated in  FIG. 6 . Alternatively, a plug  26  and marker  24  may be introduced into a patient&#39;s body in the absence of a biopsy cavity. This could be useful, for example, to mark a location from which to take a biopsy at a later time. A lesion site  74  may be the site of a suspected lesion, or a lesion site  74  may be the site of a known lesion. A biopsy cavity  76  may be an existing cavity, filled, if at all, with gas or fluid, or may be a virtual cavity, substantially filled with tissue that has collapsed into, or grown into, a site from which tissue has been previously removed. A biopsy cavity  76  may adjoin, or be lined with, or be at least in part surrounded by suspicious tissue  78 , which may be remaining tissue of a lesion, newly grown tissue at least partially filling a biopsy cavity, tissue injured when the biopsy was taken, or other tissue. 
     Assemblies, devices and methods embodying features of the invention may be used to deliver a marker to a desired location within a body of a patient, by inserting a delivery device  12  into a patient having markers  24  retained within the bore  16  of the delivery tube  14  by a plug  26 , and expelling a marker  24  from the orifice  34  into the desired location. A marker  24  may be expelled, for example, by depressing plunger  28  by moving plunger handle  30 . Depression of plunger  28 , pushing on a marker  24 , is preferably effective to expel plug  26  from the orifice  34 , allowing a marker  24  to exit the delivery tube  14  for delivery within a patient. 
     An operator may grasp a device handle  22  to guide the device  12  during insertion, and to steady the device  12  during depression of the plunger  28 . Insertion of a device  12  results in the placement of at least a portion of the device  12  adjacent a desired location. The device  12 , in particular the distal tip  36  and orifice  34  of the device  12 , may be guided adjacent a desired location such as a lesion site, or a biopsy cavity, or other internal body site where delivery of a marker  24  is desired. 
     An initial scalpel incision in the skin is typically made in order to introduce a device  12  into the body tissue of a patient, although in many cases the sharp edge  34  or pointed tip  36  tip may be used to gain access to tissue beneath the skin without the use of an incision by a surgical tool. Insertion of the device  12  into a patient, e.g. into a breast  66  of a patient, may be guided by an operator with the aid of an imaging device. A delivery tube  14 , and/or markings  44 , as well as markers  24  and optionally plug  26 , may be detectable by an imaging device, such as an ultrasound imaging device, an X-ray imaging device, a magnetic resonance imaging device, or other imaging device. Alternatively, or additionally, insertion may be visually guided, or may be guided by palpation or by other means. 
     As illustrated in  FIG. 6 , insertion of the device  12  into a patient, e.g. into a breast  66  of a patient, may be guided by a guide cannula as well. Such insertion may be performed with or without the aid of an imaging device, such as an ultrasound imaging device, an X-ray imaging device, a magnetic resonance imaging device, or other imaging device. Alternatively, or additionally, insertion may be visually guided, or may be guided by palpation or by other means. 
     A plug  26  may be made with any suitable material. Typically, a plug  26  is made with the same materials as a marker  24 . A plug  26  may serve as a marker after its expulsion from orifice  34  and placement into a patient&#39;s body. Preferably, a plug  26  is made with a biocompatible material, and provides sufficient structural strength as to retain a marker  24  within a delivery tube  14  and, where insertion of a delivery device embodying features of the invention is performed without the aid of a guide cannula, a material used in making a plug  26  preferably has sufficient structural strength to withstand the forces encountered during insertion into tissue or through skin. Materials suitable for use in making a plug  26  embodying features of the invention include polymers, plastics, resins, waxes, glasses, ceramics, metals, metal oxides, and composites, combinations and mixtures of these materials. For example, a wax such as bone wax, or other biocompatible material is suitable for use in making a plug  26 . In presently preferred embodiments, a plug  26  is made with bioresorbable polymers such as poly-lactic acid and poly-glycolic acid. A plug may be made of more than one material, as illustrated, for example, in  FIG. 3D , showing a plug  26 , which may be made primarily with a plastic or a polymer, and having an internal retention element  60 , which may be, for example, a metal clip or spring. 
     A marker  24 , including a plug  26  when configured to also serve as a marker  24 , is preferably readily visible by ultrasonic imaging (USI), or by conventional imaging methods, such as x-ray and magnetic resonance imaging methods, or by more than one imaging technique. Suitable bio-compatible materials which may be used in a marker  24  or a plug  26  include polyethylene, polytetrafluoroethylene, PEBAX (made by Autochem Corp.), and the like. 
     Thus, biocompatible plugs  26  or markers  24  embodying features of the invention are preferably made using materials including a bioresorbable material. Some particularly suitable bioresorbable materials include bio-resorbable polymers including, but not limited to, polymers of lactic acid, glycolic acid, caprolactones, and other monomers; thus, for example, suitable bio-resorbable polymers may include poly(esters), poly(hydroxy acids), poly(lactones), poly(amides), poly(ester-amides), poly(amino acids), poly(anhydrides), poly(ortho-esters), poly(carbonates), poly(phosphazines), poly(thioesters), poly(urethanes), poly(ester urethanes), polysaccharides, polylactic acid, polyglycolic acid, polycaproic acid, polybutyric acid, polyvaleric acid, and copolymers, polymer alloys, polymer mixtures, and combinations thereof. 
     A marker  24  typically should remain in place and detectable within a patient for up to at least 2 weeks to have practical clinical value. Thus, a marker  24 , including a plug  26  configured to serve as a marker, is detectable at a biopsy site within a patient for a time period of at least 2 weeks, preferably at least about 6 weeks, and may remain detectable for a time period of up to about 20 weeks, more preferably for a time period of up to about 12 weeks. In some embodiments, a marker material for use in markers  24  and plugs  26  embodying features of the invention is preferably not detectable about 6 months after placement at a biopsy site, and is more preferably not detectable with ultrasound about 12 weeks after placement at a biopsy site. Thus, a preferable in-vivo lifetime for a marker material for use in markers  24  and plugs  26  having features of the invention is between about 6 weeks and about 12 weeks. 
     In embodiments of the invention, a marker  24 , and a plug  26  configured to serve as a marker  24  following expulsion from a delivery tube  14 , may be detectable by ultrasound. Ultrasound-detectable markers  24  and plugs  26  may be formed with ultrasound detectable materials, such as stainless steel, titanium, platinum and the like, other bio-compatible metals, ceramics, metal oxides or polymers, or composites or mixtures of these materials. Typically, any material which reflects ultrasound energy may be suitable for use in an ultrasound-detectable marker. For example, materials having bubbles, internal voids, or gas-filled spaces, are detectable by ultrasound. A marker  24  or a plug  26  may be formed so as to include voids, such as cavities, to enhance their detectability by ultrasound. For example, a cavity size of between about 10 microns and about 500 microns, preferably between about 50 microns to about 200 microns, may be suitable to enhance the ultrasound-detectability of a marker  24  or plug  26 . 
     Plugs  26  and markers  24  are configured to fit within a bore  16  of a delivery tube  14 . A delivery tube  14  maybe configured to fit within a guide cannula  72 , such as a guide cannula sized to accept a Mammotome®, Tru-Cut®, or SenoCor® biopsy device. Typically, a plug  26  or marker  24  will have a diameter determined by the size of a bore  16 , typically between about 0.02″ (0.5 mm) and about 0.5″ (12 mm), preferably between about 0.04″ (1 mm) and about 0.3″ (8 mm). In addition, a plug  26  or marker  24  may have a length of between about 0.04″ (1 mm) and about 0.8″ (20 mm), preferably between about 0.1″ (2.5 mm) and about 0.6″ (15 mm). 
     A radiopaque element  40  may be made with any suitable radiopaque material, including stainless steel, platinum, gold, iridium, tantalum, tungsten, silver, rhodium, nickel, bismuth, other radiopaque metals, alloys and oxides of these metals, barium salts, iodine salts, iodinated materials, and combinations of these. Radiopaque materials and markers may be permanent, or may be temporary and not detectable after a period of time subsequent to their placement within a patient. MRI contrast agents such as gadolinium and gadolinium compounds, for example, are also suitable for use with plugs  26  and/or markers  24  embodying features of the invention. Colorants, such as dyes (e.g., methylene blue and carbon black) and pigments (e.g., barium sulfate), may also be included in markers  24  and/or plugs  26  embodying features of the invention. 
     Markers  24 , and plugs  26  configured to serve as markers, may also include other materials besides marker materials, including anesthetic agents, hemostatic agents, pigments, dyes, materials detectable by magnetic resonance imaging (MRI), inert materials, and other compounds. 
     In any of the above-described embodiments of the invention, a plug  26  may include an adhesive component to aid the plug  26  to adhere to a delivery tube  14 . In addition, an adhesive component may be useful to aid a marker  24  (and a plug  26  after expulsion from a delivery tube  14 ) to adhere to adjacent tissue within the body of a patient, such as at a biopsy site. The adhesive component may comprise a biocompatible adhesive, such as a polyurethane, polyacrylic compound, polyhydroxymethacrylate, fibrin glue (e.g., Tisseal™), collagen adhesive, or mixtures thereof. 
     While particular forms of the invention have been illustrated and described, it will be apparent that various modifications can be made without departing from the spirit and scope of the invention. Accordingly, it is not intended that the invention be limited to the specific embodiments illustrated. It is therefore intended that this invention be defined by the scope of the appended claims as broadly as the prior art will permit, and in view of the specification if need be. All patents and patent applications referred to above are hereby incorporated by reference in their entirety.