Abstract:
Devices and methods for extraction of body tissue from an enclosed body cavity are disclosed. The devices can have one or more whisks extending from the distal end of flexible or rigid cannula. The devices can have aspiration and/or irrigation systems configured to provide aspiration pressure and/or irrigate with fluid at the distal end of the cannula. The cannula can be configured to rotate and/or oscillate. Methods for using the devices to disrupt the matrix of cancellous bone or bone marrow and extract in vivo cancellous bone or bone marrow from a subject are also disclosed.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
       [0001]     This is a continuation-in-part of U.S. patent application Ser. No. 10/454,846 filed Jun. 4, 2003, which claims priority to U.S. Provisional Patent Application Ser. No. 60/384,998 filed Jun. 4, 2002, each of which is incorporated herein by reference in its entirety. 
     
    
     BACKGROUND OF THE INVENTION  
       [0002]     i. Field of the Invention  
         [0003]     The invention related to a device and method for extraction of tissue from an enclosed body cavity.  
         [0004]     ii. State of the Related Art  
         [0005]     Bone Marrow is a rich source of pluripotent hematopoietic stem cells from which red blood cells, white blood cells, and platelets are formed. Bone marrow also contains additional populations of mesenchymal stem cells and other stem and progenitor cells which have the potential to repair and regenerate other tissues.  
         [0006]     Since the early 1970&#39;s bone marrow and hematopoietic stem cell transplantation has been used to treat patients with a wide variety of disorders, including but not limited to cancer, genetic and autoimmune diseases. Currently over 60,000 transplants for a variety of indications are performed worldwide each year.  
         [0007]     In autologous transplants, the patient has their own bone marrow collected prior to receiving high dose chemotherapy. Following high dose, myeloablative chemotherapy, which kills the majority of the patients&#39; marrow stem cells, the stored autologous marrow or hematopoietic stem cells purified or enriched from the marrow are infused, and serves to improve the patient&#39;s hematolymphoid system.  
         [0008]     In allogeneic transplants bone marrow, or other sources of hematopoietic stem cells derived from a full or partially human leukocyte antigen (HLA) matched sibling, parent or unrelated donor is infused into the recipient patient and following engraftment, serves to reconstitute the recipients hematopoietic system with cells derived from the donor.  
         [0009]     Following myeloablative or non-myeloablative conditioning of a patient with chemotherapy and/or radiation therapy, the marrow is regenerated through the administration and engraftment of hematopoietic stem cells contained in the donor bone marrow.  
         [0010]     In addition to hematopoietic stem cells and hematopoietic progenitors, bone marrow contains mesenchymal and other stem cell populations thought to have the ability to differentiate into muscle, myocardium, vasculature and neural tissues and possibly some organ tissues such as liver and pancreas. Research in preclinical animal studies and clinical trials suggest that bone marrow or some portion of the cells contained within marrow can regenerate tissues other than the hematopoietic system. This includes the ability for cells contained within the marrow to regenerate or facilitate repair of myocardial tissue following a myocardial infarction, and in the setting of congestive heart failure as evident by improved cardiac function and patient survival.  
         [0011]     Bone marrow derived stem cells also show evidence for their ability to regenerate damaged liver and hepatic cells and portions of the nervous system including spinal cord. Additional organ systems including kidney and pancreas show benefit from bone marrow derived cells. Use of bone marrow and the stem cells contained within bone marrow may be of increasing clinical utility in the future treatment of patients. Furthermore a patient&#39;s own marrow has multiple applications in orthopedic procedures, including but not limited to spinal fusions, treatment of non-union fractures, osteonecrosis, and tissue engineering.  
         [0012]     Stem cells utilized in transplantation are usually collected using one of two methods. In a first method known as a bone marrow harvest, bone marrow is directly accessed in and removed from the patient usually by multiple aspirations of marrow from the posterior ileac crest. The bone marrow harvest procedure is often performed in the operating room.  
         [0013]     To perform a harvest of 500-1500 milliliters of marrow, multiple separate entries into the marrow cavity are required to in order to remove a sufficient amount of bone marrow. A bone marrow aspiration needle, such as a sharp metal trocar, is placed into the marrow space through the soft tissue and the outer cortex of the ileac crest. The aspiration needle enters less than 2 cm into the marrow cavity. Negative pressure is applied through the hollow harvest needle, usually by the operator pulling on an attached syringe into which 5-10 ml of marrow is aspirated. The needle and syringe are then removed.  
         [0014]     After removing the collected marrow, the aspiration needle accesses a separate location on the ileac bone for another aspiration. This method of inserting the needle into the bone, removing the marrow, and removing the needle from the bone is performed on the order of 100-200 separate entries for an average patient to remove a volume of bone marrow required for transplantation.  
         [0015]     Each puncture and entry into the marrow cavity accesses only a limited area of the marrow space, and the majority of practitioners only remove 5-10 milliliters of marrow with each marrow penetration. Pulling more marrow from a single marrow entry site otherwise results in a collected sample highly diluted by peripheral blood.  
         [0016]     The bone marrow harvest procedure requires general anesthesia because the ileac crest is penetrated 100-300 times with a sharp bone marrow trocar. Local anesthesia is generally not possible given the large surface area and number of bone punctures required.  
         [0017]     The donor needs time to recover from general anesthesia, and frequently suffers from days of sore throat, a result of the endotracheal intubation tube placed in the operating room.  
         [0018]     Pre-operative preparation, the harvest procedure, recovery from anesthesia, and an overnight observation stay in the hospital following the procedure requires considerable time on behalf of the donor and the physician, and similarly additional expense. The cost of the procedure is often $10,000 to $15,000, which includes costs for operating room time, anesthesia supplies and professional fees, and post-operative care and recovery.  
         [0019]     In addition to general operating room staff, the traditional bone marrow harvest procedure requires two transplant physicians. Each physician aspirates marrow from the left or right side of the ileac crest. The procedure itself usually takes approximately one and half hours for each operating physician.  
         [0020]     Many donors experience significant pain at the site of the multiple bone punctures which persists for days to weeks.  
         [0021]     Traditional bone marrow aspiration incurs a significant degree of contamination with peripheral blood. Peripheral blood contains high numbers of mature T-cells unlike pure bone marrow. T-cells contribute to the clinical phenomenon termed Graft vs. Host Disease (GVHD), in both acute and chronic forms following transplant in which donor T-cells present in the transplant graft react against the recipient (host) tissues. GVHD incurs a high degree of morbidity and mortality in allogeneic transplants recipients.  
         [0022]     In a second method to collect stem cells for transplantation, mononuclear cells are removed from the donor&#39;s peripheral blood. The peripheral blood contains a fraction of hematopoietic stem cells as well as other populations of cells including high numbers of T-cells. In this procedure peripheral blood stem cells are collected by apheresis following donor treatment with either chemotherapy—usually cyclophosphamide—or with the cytokine Granulocyte Colony Stimulating Factor (GCSF). Treatment with cyclophosphamide or GCSF functions to mobilize and increase the numbers of hematopoietic stem cells circulating in the blood.  
         [0023]     This collection method can be slow and time consuming. It requires the donor to first undergo five or more days of daily subcutaneous injections with high doses of the cytokine GCSF prior to the collection. These daily injections can be uncomfortable and painful and bone pain is a common side effect. Peripheral blood stem cells can not be obtained without this seven-plus day lead time.  
         [0024]     Each day of apheresis costs approximately $3,000 including but not limited to the cost of the apheresis machine, nursing, disposable supplies and product processing. The patient often has to come back on multiple days in order to obtain an adequate number of stem cells. Costs for the GCSF drug alone approximate $6,000-$10,000 depending upon the weight of the patient.  
         [0025]     Given the multiple days required to collect adequate numbers of hematopoietic stem cells, individual bags of peripheral blood product must processed and frozen separately. These bags are then thawed, and given back to the recipient patient at the time of transplant. The volume, and chemicals contained in the product freezing media can cause some complications, such as mild side effects, at the time of infusion.  
         [0026]     Accordingly, there is a need for a minimally invasive, less expensive, time-efficient bone marrow harvest procedure with minimal complications which does not require general anesthesia, offers fast recovery time, and does not cause significant pain to the bone marrow donor.  
       SUMMARY OF THE INVENTION  
       [0027]     Devices and methods for manipulation and extraction of body tissue from an enclosed body cavity are disclosed. The device can have a hollow introduction or entry cannula that can have a trocar. The introduction cannula and a core element can penetrate body tissue, such as the marrow space contained within the ileac. A flexible aspiration cannula can then be inserted through the introduction cannula into body tissue and can be advanced through the body cavity.  
         [0028]     Within the aspiration cannula there may be a stylet (e.g., an aspiration stylet). The stylet can aid in advancing the cannula through the cavity. The stylet can be removed to facilitate extraction of body tissue through the aspiration cannula.  
         [0029]     The aspiration cannula can have inlet openings near the distal tip through which tissue is aspirated. At the proximal end of the aspiration cannula a negative pressure (i.e., suction) source can provide controlled negative pressure, for example, to increase the aspiration of tissue through the aspiration cannula into a collection reservoir. The aspiration cannula can be withdrawn and positioned for multiple entries through the same tissue entry point, for example, following different paths through the tissue space for subsequent aspiration of more tissue.  
         [0030]     A device or apparatus that can disrupt and aspirate bone marrow and/or other tissue rapidly and for large volumes of cancellous bone (i.e., marrow) from a target bone such as the ileac, femur, humerus, other bone, or combinations thereof is disclosed. The target bone can be in vivo or in vitro.  
         [0031]     The apparatus can include a lumen adapted to receive an elongated aspiration cannula. Following entry through the bone wall, the aspiration cannula maybe controlled to move in a linear or non-linear fashion within the marrow cavity. The aspiration cannula, for example while moving non-linearly, can access a majority of the bone marrow space through a single point of entry. Suction may be optionally applied to the aspiration cannula while accessing the marrow space to increase the harvest of the bone marrow or other aspiratable substances. The apparatus can also optionally check for a threshold amount of aspiratable substance obtained. Additionally, a controller in the apparatus can adjust the aspiration cannula or signal for the operator to adjust the aspiration cannula to enable further harvesting from the same bone wall entry point, or in the alternate from an alternative bone wall entry point.  
         [0032]     As the devices and methods can access large volumes of marrow with each catheter insertion, the devices and methods can be moved to directly contact more of the marrow space and aspirate a more concentrated, less diluted aspirant. The aspirated bone marrow can be more concentrated in stem cells, for example, because the device can penetrate the pelvic cavity more broadly and thus the extracted material can be less diluted with blood drawn into the void created by the extraction. The decreased numbers of contaminating T-cells can lead to less Graft vs. Host Disease (GVHD) in allogeneic bone marrow recipients. Less total volume of bone marrow can be removed (e.g., as it is more concentrated).  
         [0033]     As mentioned, the harvest (i.e., aspiration, extraction) performed with the devices and methods disclosed herein can utilize one access point into the marrow cavity on one or both sides of the body to remove a minimal total volume of material that is highly concentrated. A marrow access site can be the anterior ileac crest access site which can be easy to locate and access on a broad array of patients (from thin to obese) and utilizing this access site can also reduce harvest time.  
         [0034]     The method described herein can be performed by a single operator with no operating room time, reduced support personnel, no anesthesiologist, and can also be performed with no significant lead or preparative time. The method can be performed on, among others, critically ill subjects, or bone marrow donors who could not easily tolerate multiple surface puncture wounds for rapidly obtaining marrow and/or stem cells derived from marrow for use in immediate or long-term follow-on therapeutic interventions. Furthermore, the devices and methods disclosed herein can aspirate bone marrow, remove fat, aspirate blood and muscle, or combinations thereof, through a single skin (and bone, where applicable) puncture site into the tissue space (e.g., marrow cavity).  
         [0035]     The device and method disclosed herein can also control the directionality of the cannula enough within the marrow cavity such that the device can access a majority of bone marrow space in a single bone or marrow cavity in vivo through a single point of entry. Alternatively, the device and method can access multiple diagnostic samples of bone marrow from disparate sites within a single marrow cavity. The device and method can also have aspiration suction controlled to aspirate bone marrow or fat, for example.  
         [0036]     The device can have an elongated cannula having a flexible length, a hollow channel, a cannula first end and a cannula second end. The cannula first end can be open to provide fluid communication between the hollow channel and the outside of the cannula. Additionally, the device can include a motor which is rotatably connected to the cannula. The cannula may additionally include a tissue disruptor which is attached to or integral with the cannula, e.g., a whisk having a first end and a second end where the first end can be fixed to the cannula such that the whisk extends from the cannula. The second end can also be fixed to the cannula such that the whisk is configured in a semi-circular or closed loop configuration. The cannula can additionally include a second whisk extending from the cannula end.  
         [0037]     The whisk can be configured to be rigid enough to substantially disrupt a first portion of a cancellous bone matrix when rotated by the motor to make the first portion removable from a surrounding portion of cancellous bone matrix while remaining flexible enough so as to inhibit or prevent its puncturing through cortical bone surrounding the body cavity.  
         [0038]     To rotate the cannula and whisk, the motor can be configured to rotate the cannula at least at one operating speed from about 30 rpm to about 160 rpm. The device can include a mechanical transmission between the motor and the cannula to transmit the torque. A rotation-limiting resistor or slip-clutch in mechanical communication with the motor and the cannula may additionally be included to further control or limit the rotation of the cannula and whisk within the body space.  
         [0039]     A pump in fluid communication with the hollow channel through the cannula may include an aspirant reservoir such that the hollow channel is in fluid communication with the reservoir. Additionally, an aspirant filter in fluid communication with the hollow channel and the aspirant reservoir may also be included to filter out undesirable material or debris. An irrigant reservoir holding a fluid, e.g., saline solution, may additionally be included for providing irrigation fluid which may be optionally perfused into the body space to facilitate tissue removal.  
         [0040]     One method for removing cancellous bone or bone marrow from an in vivo bone in a subject may entail inserting the tissue disrupter into a first section of the cancellous bone or bone marrow into a patient by inserting a flexible hollow shaft into the first section of the cancellous bone. Prior to or upon insertion into the cancellous bone or bone marrow, the cannula and tissue disruptor may be rotated within the patient to disrupt the tissue matrix prior to or while optionally aspirating the disrupted portion of first section of cancellous bone or bone marrow into the cannula.  
         [0041]     The method can also include re-positioning the flexible shaft into a second section of the cancellous bone and aspirating the disrupted tissue. The re-positioning of the flexible shaft into the second section of the cancellous bone can include completely or partially removing the tissue disrupter, e.g., a whisk-like disrupter, from the body cavity.  
         [0042]     Additionally, the method can include irrigating the tissue matrix with a solution that can have saline, anesthetic, analgesic, anti-inflammatory, osteogenic powder or slurry, or combinations thereof. The method can further include filtering the aspirated disrupted portion. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0043]      FIG. 1  illustrates an exploded, partially schematic, view of a variation of the device for tissue disruption and aspiration.  
         [0044]      FIG. 2  illustrates an assembled, partially schematic view of a variation of the device for tissue disruption and aspiration.  
         [0045]      FIG. 3  illustrates an exploded, partially schematic, view of a variation of the device for tissue disruption and aspiration.  
         [0046]      FIG. 4  illustrates an assembled, partially schematic view of a variation of the device for tissue disruption and aspiration.  
         [0047]      FIG. 5  is a see-through view of a variation of the entry cannula with the core element.  
         [0048]      FIG. 6  is a see-through view of a variation of the aspiration cannula.  
         [0049]      FIG. 7  illustrates a variation of the aspiration cannula with one or more steering wires.  
         [0050]      FIGS. 8   a - 8   c  illustrate variations of the perforated wall and cross-section of the aspiration cannula.  
         [0051]      FIG. 9  illustrates a variation of the universal joint of the aspiration cannula.  
         [0052]      FIG. 10  illustrates a variation of the squash plate of the aspiration cannula.  
         [0053]      FIG. 11   a  and  11   b  illustrate variations of the preset degree of curvature of the aspiration cannula.  
         [0054]      FIG. 12  illustrates a variation of the groove cup.  
         [0055]      FIGS. 13-18  illustrate variations of the distal tip.  
         [0056]      FIG. 19  illustrates a variation of inlet openings near the distal tip of the aspiration cannula.  
         [0057]      FIGS. 20, 22 ,  25 , and  27  are side views of variations of the distal tip of the aspiration cannula.  
         [0058]      FIG. 21  is a front view of a variation of the distal tip of  FIG. 20 .  
         [0059]      FIGS. 23 and 24  are front views of variations of the distal tip of  FIG. 22 .  
         [0060]      FIG. 26  is a front view of a variation of the distal tip of  FIG. 25 .  
         [0061]      FIG. 28  is a front view of a variation of the distal tip of  FIG. 27 .  
         [0062]      FIG. 29  is a front view of a variation of the distal tip.  
         [0063]      FIG. 30  illustrates a variation of the ports on the aspiration cannula.  
         [0064]      FIG. 31  illustrates a variation of a method for using the tissue disruption and aspiration device.  
         [0065]      FIG. 32  illustrates a variation of a method for entry on one side of the body with multiple aspiration paths.  
         [0066]      FIG. 33  illustrates a variation of a method for harvesting bone marrow through one bone entry point.  
         [0067]      FIG. 34  illustrates a variation of a method for harvesting bone marrow using several bone punctures and separate volume aspirations.  
         [0068]      FIGS. 35-39  illustrate a variation of a method for using the tissue disruption and aspiration device.  
         [0069]      FIG. 40  illustrates a variation of a method for rapid aspiration and collection of body tissue from within an enclosed body space.  
         [0070]      FIG. 41  illustrates a variation of a method for entry on one side of the body with multiple aspiration paths. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0071]      FIG. 1  illustrates a tissue disruption and aspiration device  100  that can aspirate and collect body tissue from within an enclosed body space in vivo or in vitro (also referred to as “aspiration device”). The aspiration device can have a drill  302 , a connector and aspiration assembly  304 , an aspiration cannula  105 , an access trocar  306 , and one or more fluid circuits  308 .  
         [0072]     The aspiration cannula  105  can attach to the connector  304  and/or drill  302  for ease of holding and operation such that the aspiration cannula  105  is in mechanical communication with the drill  302 . The aspiration cannula  105  can be configured to be flexible or rigid and it may also include indentations, ridges, rings, visualization markers  312 , or combinations thereof, for example to alter the flexibility of the aspiration cannula  105  along the entire length or a portion of the length of the aspiration cannula  105 . The visualization markers  312  can be optionally radio-opaque and/or echogenic.  
         [0073]     The aspiration cannula  105  may further include a rotational interface  314  configured to rotationally attach or couple to the connector  304  and/or the drill  302  for transmitting the rotational torque from the drill  302  to the cannula  105 .  
         [0074]     The aspiration cannula  105  can further include a guard and/or a squash plate  110  to prevent over-insertion of the aspiration cannula into the connector  304  and/or the drill  302 . The guard can non-rotationally attach to the connector  304  and/or the drill  302  such that during use, the guard can remain rotationally constant. The guard may further cover a gap between the aspirant cannula  105  and the connector  304  and/or drill  302 , for example, to prevent the operator from pinching his/her hands in the device  100  while the aspirant cannula  105  is rotating.  
         [0075]     The aspirant cannula  105  can further include one or more control wires along the length of the aspirant cannula  105  (e.g., see  FIG. 10 ). The squash plate  110  can be attached to the control wires such that the squash plate  110  can be manipulated by hand and/or by the connector  304  and/or by the drill  302  to steer, bend, flex, or combinations thereof, the distal end of the aspiration cannula  105 .  
         [0076]     The distal end of the aspiration cannula  105  can have a tissue disruptor, e.g., a whisk  310 , which may be fixed, coupled, or otherwise integrated with the distal end of the aspiration cannula  105 , as described in further detail below. The aspiration cannula  105  can facilitate aspiration and/or irrigation by defining one, two, or more lumens, for aspirating concurrently or subsequently to irrigating.  
         [0077]     To provide an initial entry pathway into and through the cortical bone and into the medullary cavity, an access trocar  306  may be used which has an entry cannula  101  which defines an entry cannula channel that can pass through the length of the access trocar  306 . The access trocar  306  can have one or more handles extending laterally and the entry cannula  101  can be configured to drive through cortical bone. Once the trocar  306  has been inserted and desirably positioned within the cortical bone creating an entry point, the aspiration cannula  105  may be passed through the entry cannula channel  101  and into the tissue matrix; accordingly, the channel  101  has a diameter which can reasonably accommodate the outer diameter of the aspiration cannula  105 .  
         [0078]     The connector and aspiration assembly  304  can have a drill interface  316  which mechanically couples the drill  302  and the connector  304  to one another via a removable interface which allows the drill interface  316  to couple and de-couple from the drill  302  itself. The connector and aspiration assembly  304  and/or the drill  302  can additionally include a mechanical transmission, for example, to increase and/or decrease the transmitted torque or speed from the drill  302  to the cannula  105 . The connector and aspiration assembly  304  and/or the drill  302  can further include a governor, for example, to limit the rotational speed of the drill  302  transmitted to the aspiration cannula  105 . Such a governor can be configured as a resistor, slip-clutch, etc., or combinations thereof. The maximum rotational speed of the aspiration cannula  105  can be from about  30  rpm to about  160  rpm, for example about  120  rpm.  
         [0079]     The connector and aspiration assembly  304  can be further configured to direct and/or control aspiration and/or irrigation between the fluid circuit  308  and the first and/or second lumen of the aspiration cannula  105 . The connector and aspiration assembly  304  can removably attach to the aspiration cannula  105  at a cannula port  318  and the connector and aspiration assembly  304  can further include an irrigation port  320  and/or aspiration port  322 , each of which can be configured to be removably attached to fluid lines. The connector and aspiration assembly  304  can be configured to place the irrigation port  320  in fluid communication with a lumen in the aspiration cannula  105 , for example a first lumen. The connector and aspiration assembly  304  can be further configured to place the aspiration port  322  in fluid communication with a lumen in the aspiration cannula  105 , for example a second lumen, or the same lumen the irrigation port  320  is in fluid communication with.  
         [0080]     The fluid circuit  308  can further include a pump  324  which is in fluid communication with an irrigant reservoir  161  and/or an aspirant reservoir  326 . The irrigant reservoir  161  can have an irrigant, for example, saline solution. The pump  324  can deliver positive fluid pressure, as shown by arrows, to the irrigant reservoir  161  while also providing negative fluid pressure (i.e., suction), as shown by arrows, to the aspirant reservoir  326 . The pump  324  can also be configured to reverse direction, i.e., providing negative pressure to the irrigant reservoir  161 , and positive fluid pressure to the aspirant reservoir  326 , for example, during cleaning to backwash the fluid system or to perfuse fluid into the tissue matrix to facilitate aspiration of the disrupted tissue. In this case, the irrigant perfusion rate can be, for example, from about 1 to 2 cc/min to about 30 cc/min.  
         [0081]     An optional first aspiration filter  328  can be positioned in the flow between the aspiration port  322  and the aspirant reservoir  326  while an additional optional second aspiration filter  330  can be positioned in the aspirant reservoir  326 , e.g., near the inlet port. An optional irrigation filter  332  can also be positioned between the irrigant reservoir  161  and the irrigation port  320 . The first aspiration filter  328  and/or the second aspiration filter  330  can have pore sizes about 10 μm. While filters are shown positioned within the fluid lines or reservoirs, filters may alternatively be positioned within the cannula  105  itself, e.g., near or at the distal tip, for filtering out undesirable debris during aspiration such that the debris is prevented from passing through the cannula  105  and/or connector and aspiration assembly  304 .  
         [0082]     The drill  302 , having a handle  102  and controls  103 , can include any number of drills which are available for surgical purposes as interface  316  may be configured with a standard interface to couple and de-couple from any conventional drill interface. Examples of such drills  302  may include, for example, drills from DePuy Mitek, Inc. (Raynham, Mass.), Aesculap, Inc. (Center Valley, Pa.), Universal Driver or C.O.R.E. Micro Drill, Impaction Drill, Universal Series Drill (e.g., UHT Drill, U Drill), or Saber Drill commercially available from Stryker Corp. (Kalamazoo, Mich.), etc..  
         [0083]      FIG. 2  illustrates another variation showing the aspirant reservoir  326  and the irrigant reservoir  161  integrated and/or attached to one another. As further shown, drill  302  is engaged to connector and aspiration assembly  304 .  
         [0084]      FIG. 3  illustrates another variation where the fluid circuit  308  can have separated irrigation and aspiration fluid flow sub-circuits. The irrigation sub-circuit can have an irrigation pump  324  while the aspiration sub-circuit can have an aspiration pump  324   a  separated from the irrigation pump  324   b.    
         [0085]      FIG. 4  illustrates an optional steering control  140  for steering, guiding, advancing, and/or retracting aspiration cannula  105  while aspiration cannula  105  in outside and/or inside bone marrow space (or other body tissue area). The aspiration cannula  105  can have one or more steering wires  107  (as shown in  FIG. 10 ). The activation of the steering control  140  can contract or pull one or more of the steering wires  107 . Contracting or pulling the steering wires  107  can result in the bending, curvature, and/or changing of direction of the aspiration cannula  105 .  
         [0086]     The steering control  140  can have a manual control, such as a handle, which can be moved to steer or manipulate the aspiration cannula  105 . For example, forward movement of device  100  can advance the aspiration cannula  105  while backward movement of the device  100  can withdraw the aspiration cannula  105 . Movement of the steering control  140  handle to different sides (e.g., to the left, right, up or down) curves or bends the aspiration cannula  105  to the corresponding side (e.g., to the left, right, up or down). The steering control  140  can have a powered control, such as a multi-way thumb-stick or one or more buttons for steering and/or advancing and retracting aspiration cannula  105  (shown in  FIG. 4 ).  
         [0087]      FIG. 5  illustrates entry cannula  101  with a core element  104 . The entry cannula  101  comprises a needle with hollow central lumen accommodating a core element  104  for initial insertion into a bone marrow cavity or body tissue, for example through the anterior ileac crest, posterior ileac crest, lateral trocanter of the femur, or other location for example, for aspiration of bone marrow, fat, or other body tissue. The aspiration cannula  105  can enter the body tissue through the central lumen of the entry cannula  101 , for example when the core element  104  is removed from the entry cannula  101 .  
         [0088]     The core element  104  comprises a rod, trocar or other element for breaking or piercing through the bone wall or other tissue boundary and creating an entryway for subsequent aspiration. The entry cannula  101  can be strong enough, or may not be strong enough, to break or pierce through the bone wall (e.g., cortical bone) without the help of core element  104 .  
         [0089]     An entry site in the bone wall can be created using a tool other than entry cannula  101  and/or core element  104 , such as by a separate trocar or other sharp tool for breaking or piercing the bone wall. The aspiration cannula  105  can enter the bone through the break or piece in the bone wall (or other tissue area) for example, for the entry of aspiration cannula  105 .  
         [0090]     Once an entryway or entry site is created in the bone marrow and the entry cannula  101  can enter the bone marrow (or other body tissue intended for aspiration), the core element  104  can be removed leaving a hollow entryway or entry lumen with access to the medullary cavity.  
         [0091]      FIG. 6  illustrates that the aspiration cannula  105  can translate through a hollow channel of the entry cannula  101 . The aspiration cannula  105  can pass through the bone wall, or other tissue surface, and enter into the marrow or other tissue space. The aspiration cannula  105  can be flexible, for example flexing and curving to follow the bone marrow cavity or other tissue area. The aspiration cannula  105  can have a length of about 15 cm (6 in.) to about 41 cm (16 in.). The size of the aspiration cannula  105  can be selected for the size and anatomy of the patient and/or the bone marrow cavity or other body tissue area intended for harvest.  
         [0092]     The aspiration cannula  105  optionally comprises a stylet  106  (e.g., an aspiration stylet). When inserted into the aspiration cannula  105 , the aspiration stylet  106  can increase the structural strength of the aspiration cannula  105 . The aspiration stylet  106  can transmit force to aid in advancing the aspiration cannula  105  through the marrow space or other tissue area. The marrow space can be the intramedullary bone marrow space of the ileac or femur bone. The aspiration stylet  106  can be straight or have a curvature prior to and following entry into body cavity through the entry cannula  101 . The aspiration stylet  106  can be removed from the aspiration cannula  105  to allow aspiration of marrow (or other body tissue) through aspiration cannula  105 . The aspiration stylet  106  can remove and/or disrupt tissue blockages within the aspiration cannula  105 . The tissue blockages can be made from bone fragments, fat, coagulation, blood clots, other substances, or combinations thereof.  
         [0093]      FIG. 7  illustrates that the aspiration cannula  105  can be steerable and directable. The aspiration cannula  105  can be equipped with one or more steering wires  107 . Contraction or pulling of a steering wire  107  by an operator can flex (e.g., curve) the aspiration cannula  105  according to the direction and/or location of contracted or pulled steering wire  107 .  
         [0094]      FIG. 8  illustrates that the aspiration cannula  105  can be rigid or flexible. The aspiration cannula  105  can have grooves, slots or perforations  108  on the wall of aspiration cannula  105 , as shown in  FIG. 8a . The perforations  108  allowing for curvature and increased lateral flexibility, and/or oval cross-section for limiting axes of curvature. The aspiration cannula  105  can have or be made from material with shape-memory, for example a shape memory alloy (such as Nitinol), a shape memory plastic, or other metallic or non-metallic material with shape-memory, for example resulting in a curved profile of aspiration cannula  105 , for providing directionality to aspiration cannula  105  upon aspiration cannula&#39;s  105  entry into the body tissue or body cavity. Alternatively, the cross-sectional profile of the cannula  105  may be varied as well from a circular profile, as shown in  FIG. 8   b,  to an elliptical profile, as shown in  FIG. 8   c,  to alter the flexibility characteristics.  
         [0095]      FIG. 9  illustrates that the aspiration cannula  105  can have a universal joint  109 . The universal joint can be a pivot point. The universal joint can allow the contraction or pulling of steering wires  107  to result in steering and/or change of direction of aspiration cannula  105 .  
         [0096]      FIG. 10  illustrates that the aspiration cannula  105  can have a squash plate  110 , as mentioned above, allowing the contraction or pulling of steering wires  107  to result in steering and/or change of direction of aspiration cannula  105 .  
         [0097]      FIGS. 11   a  and  11   b  illustrate the aspiration cannula  105  in a configuration advanced out of the entry cannulas  101 , as shown by arrow. The aspiration cannula  105  can have a preset degree of curvature such that after passing through the entry cannula  101  and into the bone cavity, the aspiration cannula  105  can assume a curvature according to the preset curvature, thereby assisting its direction when advancing within the cavity.  
         [0098]      FIG. 12  illustrates that a groove cup  120  can guide the aspiration cannula  105 , for example, through the bone surface  342  and into bone marrow  340  or other body tissue. The aspiration cannula  105  can be attached and/or slidably attach to an aspiration cannula entry  346  with a groove dial  122 . Groove cup  120  comprises one or more grooves  121 , a groove  121  providing directional entry of aspiration cannula  105  into bone marrow  340 . The placement of the aspiration cannula  105  into an appropriate groove  121  allows entry of the aspiration cannula  105  into the bone marrow with directionality according to selected groove  121 . The groove cup  120  can have a groove dial  122  for convenient selection of groove  121  and guiding of aspiration cannula  105  through selected groove  121  and into the bone marrow space. Various possible paths of the groove cup are shown by arrows,  344 .  
         [0099]      FIG. 13  illustrates that the device  100  can have a distal tip  130  at the distal end of aspiration cannula  105  or at the distal end of optional aspiration stylet  106 , for advancing through the bone marrow cavity (or other body tissue).  
         [0100]      FIG. 14  illustrates that the distal tip  130  can have a sharp tip  131 .  FIG. 15  illustrates that the distal tip  130  can have a transducer  133 , such as a sonication device. The transducer can disrupt tissue, for example for penetrating and/or advancing through the cortical bone, cancellous bone (i.e., marrow) or other body tissue.  
         [0101]      FIG. 16  illustrates that the distal tip can have a rotating drill tip  132 . The rotating drill tip can be manual or motor-powered, for example powered by an electric motor  162  as shown in  FIG. 4 , with the motor  106  using power from batteries  163  or from an outside electrical source. The device  100  can have a variable speed controllable motor and/or reversible drill tip.  
         [0102]      FIG. 17  illustrates that the distal tip  130  can have an ultrasound transducer or other navigation element  134  for providing navigation and/or visual guidance within bone marrow space (or other body tissue) to assist steering of aspiration cannula  105 , such as providing feedback indicating proximity of distal tip  130  or aspiration cannula  105  to bone wall (or to other tissue boundary).  
         [0103]      FIG. 18  illustrates that the distal tip  130  can be modified to have a rounded blunt tip  135 . The distal tip  130  can be configured to not puncture out of the body space or cavity. For example the distal tip  130  can be dulled or softened to not pass through cortical bone during normal use. Upon encountering a wall or boundary (e.g., cortical bone) while the distal tip  130  is under pressure, the distal tip  130  can be configured to instead move sideway along a wall or boundary (e.g., cortical bone) upon encountering such a wall or boundary.  
         [0104]     The device  100  can have radio-opaque and/or radio-transparent and/or echogenic markers or other materials. For example, the device  100  can be used with an imaging device, such as an X-ray or ultrasound device, for visual location of the aspiration cannula  105 . The aspiration cannula  105  and/or other elements of the device  100  can be radio-transparent, and the aspiration cannula  1   05  can have a radio-opaque visual marker, such as a strip with visual distance markings showing how far aspiration cannula  105  has advanced into bone marrow space or other body tissue area, along the length of aspiration cannula  105 .  
         [0105]      FIG. 19  illustrates that the aspiration cannula  105  can have one or more inlet openings  150  near the distal tip  130 . Marrow or other tissues can be aspirated by the application of negative pressure through the inlet openings  150 . A negative pressure element, such as the aspiration pump, can be placed in fluid communication with the proximal end of aspiration cannula  105 . The negative pressure element can apply a negative pressure resulting in aspiration (i.e., suction) of bone marrow or other body tissue into the aspirant reservoir. The negative pressure element can have a syringe. The negative pressure element can have a powered device. The negative pressure element powered device can be a wall-mounted continuous negative pressure device or other powered device for providing controlled negative pressure. The handle  102  can have a trigger element  103  (see  FIGS. 1-4 ) that can control the aspiration negative pressure or degree of suction, for example by controlling a pressure gate for allowing a desired degree of negative pressure.  
         [0106]     The aspiration device  100  can have a pain attenuating device for dampening pain and/or sensation during the aspiration procedure. The aspiration cannula  105  can have one or more elements for providing electrical nerve stimulation to the tissue harvest area. The electrical nerve stimulation can be configured to attenuate pain, for example, as shown in U.S. Pat. No. 6,159,163, Strauss et al, May/1998, which is incorporated herein in its entirety.  
         [0107]     The inside wall of the entry cannula  101  and/or the aspiration cannula  105  can have an anticoagulant material such as heparin. The inside wall of the entry cannula  101  and/or the aspiration cannula  105  can be coated or otherwise lined. The anticoagulant can be configured to prevent blood and/or marrow from coagulating, for example to minimize hindering aspiration of marrow or body tissue. The entry cannula  101  and/or the aspiration cannula  105  can be flushed with anticoagulant solution to prevent and/or dissolve clots.  
         [0108]      FIGS. 20 and 21  illustrate additional variations of the aspiration cannula  105  incorporating a tissue disruptor end effector configured in this variation as a whisk  310 , as mentioned above. The whisk  310  can have a whisk first end  314   a  and a whisk second end  314   b  which can be attached to, or integral with, the distal end of the aspiration cannula  105 . While the whisk  310  is illustrated as having a semi-circular or looped configuration, it may be configured in any number of shapes so long as clearance between the whisk  310  and cannula opening  350  is provided to allow for entry of the disrupted tissue therethrough. The whisk  310  can be resilient or deformable or alternatively flexible or rigid. The whisk  310  is also preferably rigid enough to disrupt cancellous bone yet flexible enough so as to not penetrate cortical bone during normal use.  
         [0109]      FIG. 22  illustrates another variation with the cannula  105  utilizing two or more whisks  310   a  and  310   b.  The first and second ends of the whisks  310   a,    310   b  can be attached to and/or integral with the distal end of the cannula  105 .  FIG. 23  illustrates an end view of a variation where that the first whisk  310   a  can be non-integral, unattached, or unconnected from the second whisk  310   b  while  FIG. 24  illustrates likewise illustrates an end view of another variation where the first whisk  310   a  can be integral, coupled, or otherwise attached with the second whisk  310   b.    
         [0110]      FIGS. 25 and 26  illustrate side and end views, respectively, of yet another variation where the whisk  310  can have a whisk second end  314   b  that is not attached to, or integral with, the aspiration cannula  105 . Instead, the whisk  310  can have a helical or generally conical configuration where the second end  314   b  extends distally from cannula  105 .  
         [0111]      FIGS. 27 and 28  illustrate side and end views, respectively, of yet another variation in which a single whisk  310  can have a helical configuration where its first and second ends  314   a  and  314   b  can be integral with or attached to the distal end of the aspiration cannula  104 .  FIG. 29  illustrates a similar variation where the whisk  310  has a configuration similar to multiple oppositely-directed conical helixes.  
         [0112]      FIG. 30  illustrates that the aspiration cannula  105  can have one or more additional ports  160  through which material or liquid (such as the anticoagulant described above) can be administered. The ports in the aspiration cannula  105  can be ports through which a stylet can be passed into the aspiration cannula for unblocking or removing any blood or tissue clots which may occur. As shown in  FIGS. 1 through 4 , the aspiration device  100  can have an irrigant reservoir  161  for materials or liquids (such as anticoagulant described above) for administration, as shown in  FIG. 9 .  
         [0113]      FIG. 31  illustrates a method of access where the access trocar  306  can be inserted percutaneously, as shown by the arrow, through the subject&#39;s skin  360  and into the target site, such as the ileac crest  362 . With the trocar  306  desirable positioned through the ileac crest  362  and providing a entry port, the aspiration cannula  105  can then be introduced through the entry cannula  101 , through the access trocar  362 , and directly into the ileac crest  362 .  
         [0114]      FIG. 32  illustrates that the length and/or diameter and/or flexibility and/or curvature of entry cannula  101  and/or aspiration cannula  105  can be chosen to accommodate different anatomies (e.g., different ages, bone sizes, amount of body fat, and other anatomical factors) and for the harvest of a range of body tissues, such as bone marrow, fat (e.g., liposuction), fluid in the abdomen of a patient (e.g., liver disease symptoms), or minimally invasive removal of a soft tissue mass such as a tumor. For example, a child may require a shorter, more flexible aspiration cannula  105 . As another example, aspiration of bone through the lateral trocanter of the femur, or via the anterior ileac crest may require a shorter entry cannula  101  and/or aspiration cannula  1   05  than aspiration of bone marrow through the posterior ileac crest which may have more soft tissue above the bone.  FIG. 32  shows various paths  364  that can be taken by the aspiration catheter  105  during the procedure through a single entry site  366  through the cortical bone.  
         [0115]      FIG. 33  illustrates that a single operator can harvest marrow  340 , fat or other tissue through a single bone entry point in the cortical bone  368 .  FIG. 34  illustrates that one operator can harvest marrow, fat or other tissue through several dozen to hundreds of (bone) punctures and separate aspirations with one or more aspiration cannulas  105 .  
         [0116]      FIG. 35  illustrates a detail view illustrating the aspiration cannula  105  being translated, as shown by the arrow, through an entry port  370  cut into the cortical bone  368  by the access trocar  306  or another tool.  FIG. 36  illustrates that once the whisk  310  is positioned wholly or at least partially within the cancellous bone  340 , the aspiration cannula  105  can be rotated via the drill  302 , as indicated by the arrows. As the matrix of the cancellous bone  340  around the whisk  310  is disrupted, as shown in disruption zone  372  illustrated in  FIG. 37 , the pump  324  can be activated (e.g., by a trigger or switch on the handle of the drill  302  or on the connector  304 ). The pump  324  can force, as shown by arrow  374 , saline solution under pressure through one of the lumens  350  of the aspiration cannula  105 . The irrigant can then mix under pressure with the disrupted cancellous bone. The pump  324  can produce suction, as shown by arrow  376 , in one of the lumens  350  of the aspiration cannula  105  to remove the disrupted zone  372  of cancellous bone  340 , as well as bone between the disrupted zone  372  and the lumen  350  through which the suction is delivered. The cannula  105  may be advanced distally along a first path into the cancellous bone  340  while rotating the cannula  105  and/or aspirating and/or perfusing.  
         [0117]      FIG. 38  illustrates that the aspiration cannula  105  can be adjusted and repositioned, as shown by arrows  378 . The adjustment and reposition can be concurrent with rotation of the aspiration cannula  105 , for example to disrupt additional cancellous bone  340 , or the adjustment and repositioning can occur without rotating the aspiration cannula  105 . The aspiration cannula  105  can be repositioned through the same entry port  370  through the cortical bone  368 .  
         [0118]      FIG. 39  illustrates that in the repositioned configuration, the whisk  310  can be surrounded by the cancellous bone  340  and the method shown in FIGS.  36  though  39  and described above can be repeated. The aspiration cannula  105  can be rotating throughout the method or the rotation can be stopped during repositioning.  
         [0119]      FIG. 40  illustrates a method for rapid aspiration and collection of body tissue from within an enclosed body space. After providing  200  an entry into the marrow using entry cannula  101  (and/or using core element  104 , in which case the core element  104  of the entry cannula  101  is removed after providing the entry), ahollow entry lumen is left with access to the medullary cavity. Next, aspiration cannula  105  is placed  201  through the hollow entry cannula  101  and introduced into the marrow space. The aspiration cannula  105  is then manipulated  202  (using steering control  140 ) to move and follow the bone marrow cavity, assisted by the distal tip  130  the aspiration cannula.  
         [0120]      FIG. 41  illustrates that the aspiration cannula  105  will have a degree of flexibility and/or curvature allowing the aspiration cannula  105  to follow the cavity (e.g., the intramedullary bone marrow space of the ileac or femur bone). The aspiration cannula can have an ultrasound transducer device at the distal tip  130  of the aspiration cannula  105 , for example to visualize the cavity (e.g., define the width of the cavity).  
         [0121]     Once the aspiration catheter  105  is fully introduced into the body cavity, negative pressure can be initiated  203 , using a syringe or a powered negative pressure device (e.g., the pump). As bone marrow is aspirated, the aspiration cannula  105  can be slowly withdrawn  204 , with aspiration continuing as the aspiration cannula  105  is withdrawn. If  205  sufficient amount of bone marrow is aspirated  205 , the aspiration process is complete  206 . Otherwise  207 , after withdrawal of aspiration cannula  105 , the curvature and/or directionality of the aspiration cannula  105  can be adjusted  208 , and the aspiration cannula  105  can be redirected through the entry into the bone marrow space and manipulated to follow a different path through the space and aspirating more bone marrow. This process can be repeated for example 3-4 times, resulting in its aspiration of bone marrow from the majority of the bore marrow space (for example the ileac crest). This process can be repeated on both sides of the body as needed (e.g.,  FIG. 32  shows an entry site on one side of the body with multiple aspiration paths).  
         [0122]     Stem cells may be utilized to regenerate or improve function of damaged myocardium following a myocardial infarction, and may be useful in treating and preventing congestive heart failure. For example; a patient who has recently been diagnosed with a significant myocardial infarction and is brought to the catheterization suite, where interventional cardiologists perform angioplasty to open up a blocked coronary artery. Before, during or after the angioplasty procedure, a significant volume of bone marrow would be harvested. The bone marrow could be rapidly processed to enrich for hematopoietic stem cells or other populations or fraction of cells contained within bone marrow. These cells would then be delivered via catheter of other delivery device to the region of the heart which has undergone infarction and injury or death secondary to acute cardiac ischemia or other acute or chronic insults to the myocardial tissue. The delivered bone marrow or stem cell component contributes to regeneration of the myocardium or otherwise acts to improve cardiac function in the area of the infarct and leads to improved cardiac function and patient functional status and mortality. Optionally, marrow could be harvested separately from the initial cardiac catheterization procedure (for example 7 days after the MI, and in a separate procedure, stem cells or marrow enriched for stem cells could be delivered by any number of delivery mechanisms, for example by intracoronary or intramuscular injection. Use of a minimally invasive harvest device  100  would facilitate ease of harvest in patients who may be critically ill and not able to easily tolerate traditional marrow harvest procedures. In addition, minimally invasive harvesting of marrow has a role in intraoperative bone marrow harvesting for orthopedic applications.  
         [0123]     As described above, there is the option of utilizing one or more aspiration cannulae  105  with preset or modifiable degrees of curvature and/or length and/or diameter and/or flexibility to adapt to different individual patients&#39; anatomy and degree of ileac or other bone anatomy. Aspirated bone marrow can go directly into a bone marrow reservoir (e.g., the aspirant reservoir) or container through a closed system for initial storage and/or follow-on manipulation, such as filtering, stem cell enrichment, or other follow-on manipulation or treatment of bone marrow.  
         [0124]     The apparatus and method shown herein provide many advantages for rapid aspiration and collection of body tissue from within an enclosed space. The directional control of the aspiration cannula by the operator enables the cannula to directly contact more of the marrow space and thereby aspirate a bone marrow that is more concentrated with stem cells than that available in the prior art. In addition, the harvest performed with the apparatus shown herein proceeds faster than prior art harvesting with a trocar since only one access point is required on each side of the body and less total volume of material is extracted. Finally, the procedure outlined above requires less time and reduced support personnel, thereby reducing costs for a procedure for harvesting bone marrow and/or tissue.  
         [0125]     It is apparent to one skilled in the art that various changes and modifications can be made to this disclosure, and equivalents employed, without departing from the spirit and scope of the invention. Elements shown with any variation are exemplary for the specific variation and can be used on or in combination with any other variation within this disclosure.