Patent Description:
Current methods for performing liver biopsies may include an inherent risk of severe complications, which may often result in patients opting to delay the biopsy procedure, thus delaying subsequent diagnosis and intervention of liver dysfunction. The methods may include open surgery, percutaneous liver biopsy (PLB), and transjugular liver biopsy (TJLB).

Open surgery liver biopsy is the direct removal of liver tissue during a laparoscopic, or surgical procedure. Open surgical liver biopsy in modern practice may be utilized when there is already a surgical procedure underway.

Percutaneous liver biopsy (PLB) may involve extracting a core sample of liver tissue using a biopsy needle inserted through the abdominal wall. In PLB, the liver capsule is punctured, and a high penetration depth is needed to reach the parenchyma. This procedure may often provide good biopsy samples, but the procedure is invasive, painful, and may carry a risk of significant complications, including a risk of death (<NUM> in <NUM>). If the first biopsy fails and additional biopsy samples are needed, additional needle punctures further increasing the risk of complications. Thus, PLB patients may be kept under observation for several hours after the procedure to ensure that there is no bleeding into the peritoneal cavity due to the puncturing of the liver capsule or vessels.

Transjugular liver biopsy (TJLB) involves accessing the liver through the insertion of a stiff metal catheter into the right jugular vein, and navigated thru the right chamber of the heart and into the hepatic vein of the liver. A large bore needle directed down the catheter is used to core the liver tissue. Multiple samples are often needed for satisfactory analyses.

TJLB may avoid the risk of undetected bleeding into the peritoneum since any bleeding from the needle punctures as in PJB run back into the hepatic vein. TJLB involves navigating a stiff metal catheter through major organs and blood vessels. Thus, TJLB procedures may also result in significant complications such as hemorrhaging, arrhythmia vessel perforation, pneumothorax, or death. Although TJLB may be considered to be safer than PLB, TJLB does incur new risks of complications related to its jugular access site.

Furthermore, the use of soft tissue (e.g., liver, kidneys and pancreas) biopsy needles may be broadly classified into two biopsy methods: fine needle aspiration and core needle biopsy. Since the core needle biopsy method may preserve the native tissue structure, this method may be useful for the diagnosis of many soft tissue pathologies. Core needle biopsy may include, for example, the Tru-cut mechanism. Tru-cut needles systems are typically stiff and with lengths no longer than <NUM>. As a result, the stiffness and length of the Tru-cut needles preclude the possibility of navigating the Tru-cut needles into the liver via peripheral vascular access routes, that are generally considered to be safer with less risk to the patient. Hence, much effort been put into the design of flexible, long (><NUM> length) Tru-cut biopsy needles that could allow the use of peripheral access routes.

<FIG> schematically illustrates a long, flexible Tru-cut biopsy needle <NUM> as disclosed, for example, in <CIT> and <CIT>. A stylet <NUM> and a cutting cannula <NUM> at a distal end of a flexible sheath <NUM> of needle <NUM> are used to implement the Tru-cut mechanism. What has changed in migrating from a stiff Tru-cut needle to a flexible tru-cut needle, however, are the additions of long, flexible, co-axial cutting cannula tube <NUM> and a stylet wire <NUM> that respectively connect cutting cannula <NUM> and stylet <NUM> at the distal end of flexible Tru-cut biopsy needle <NUM> to a handle <NUM> at a proximal end of flexible Tru-cut biopsy needle <NUM>, which includes with a spring-loaded firing mechanism. Stylet wire <NUM> may be pushed or pulled from the handle to control the stylet. Firing of the spring-loaded mechanism in handle <NUM> pushes cutting cannula tube <NUM> forward, which subsequently pushes cutting cannula <NUM> forward to shear through the soft tissue of the liver and collect to the soft tissue sample for the biopsy.

No such peripheral access (e.g., transcephalic) possibilities using core needle biopsy have been realized since flexible Tru-cut biopsy needles <NUM> have the following problems: Firstly, flexible Tru-cut biopsy needle <NUM> exhibit diminished force transfer along a length of flexible sheath <NUM> in that the flexible components dampen the propagation of force from the spring-loaded firing mechanism in handle <NUM> at the proximal end, to cutting cannula <NUM> at the distal end of needle <NUM>. This results in an insufficient force applied to cutting cannula <NUM> to cleanly shear the soft tissue to obtain viable-sized, tissue samples in terms of sample diameter and length.

Secondly, the flexibility and length of flexible Tru-cut biopsy needle <NUM> also lead to insufficient in vivo stabilizing of cutting cannula tube <NUM> in the blood vessels resulting in a loss of pushability of needle <NUM> and the inability to maintain the position of stylet <NUM> when the spring-loaded mechanism in handle <NUM> is fired so as to perform the shearing and/or cutting of the soft tissue sample. (This is analogous to a fireman holding on to the end of a water hose to maintain directionality of the steam of water, and wherein the failure to hold onto the end will result in the water hose flopping around).

Finally in long flexible Tru-cut biopsy needle <NUM>, cutting cannula <NUM> and stylet <NUM> in a flexible configuration may lose their optimal rotational and longitudinal alignments to one another during the navigation of the distal end of catheter <NUM> to the target organ. This may then require a technically challenging realignment step under fluoroscopic and/or ultrasound guidance. This realignment step might also not be always accomplished, given the limited fluoroscopic precision in current visualization systems as well as the limited pushability and torquability of flexible cutting cannula tube <NUM> and stylet wire <NUM>.

<FIG> schematically illustrates optimal alignments of cutting cannula <NUM> with stylet <NUM> of a non-flexible Tru-cut biopsy needle in a closed configuration <NUM>. <FIG> schematically illustrates optimal alignments of cutting cannula <NUM> with stylet <NUM> of a non-flexible Tru-cut biopsy needle in an open configuration <NUM>. The optimal rotational and longitudinal alignments of cutting cannula <NUM> and stylet <NUM> of the non-flexible Tru-cut needle's operation are shown in <FIG>.

In closed configuration <NUM>, a space between cutting cannula <NUM> and stylet <NUM> forms a specimen chamber <NUM>. Cross-section <NUM> illustrates that cutting cannula <NUM> and stylet <NUM> are substantially opposite to one another in closed configuration <NUM>. Stylet <NUM> is navigated through the venous system, for example, to the target region of the liver. The spring-loaded mechanism in handle <NUM> is then fired pushing stylet <NUM> into the soft liver tissue as shown in an open configuration <NUM>. Cross-section <NUM> illustrates that cutting cannula <NUM> and stylet <NUM> still remain substantially opposite to one another in open configuration <NUM>. When stylet <NUM> is retracted, cutting cannula <NUM> shears the soft tissue of the liver into specimen chamber <NUM>.

In the case shown in <FIG>, the alignment between cutting cannula <NUM> and stylet <NUM> are easily maintained since the cutting cannula and stylet are sufficiently stiff. Cutting cannula <NUM> and stylet <NUM> will not reversibly bend or twist to the point where their differing flexibilities lead to loss of alignment. Thus, the high pushability and torquability due to the stiffness of cutting cannula <NUM> and stylet <NUM> ensures that their alignment in the elements of the biopsy needle in the handle at the proximal end of the biopsy needle guarantees the alignment of cutting cannula <NUM> and stylet <NUM> at the distal end.

However, when cutting cannula tube and stylet wire are fabricated with the desired flexibility for peripheral access, the reverse occurs - the alignments are easily lost because both the cutting cannula tube and stylet wire are sufficiently flexible such that they will reversibly bend or twist to a point where their differing flexibilities lead to loss of alignments of the cutting cannula and stylet at the distal end of the flexible biopsy needle. A biopsy needle fabricated with more flexibility and length, results in lower pushability and torquability.

Thus, there is a need for a transvenous biopsy device that can be introduced into the peripheral venous system of the arm into the patient's body via the basilica/cephalic veins, for example, and flexibly navigated through the venous system for performing a soft tissue biopsy on a target organ, such as the liver, so as to reduce the risk of major complications associated with PLB and TJLB procedures. In patent application no. <CIT> an intravascular ultrasound "(IVUS") device having an intrinsic or attachable needle guide is disclosed. This document describes a sheath having a needle guide used in connection with the IVUS device, to perform minimally invasive image-guided surgical procedures. The devices may be configured to maintain a needle placed through guide in the plane of the IVUS-array to improve visualization of the needle. However, the needle of this device cannot be pushed into liver parenchyma. At certain angles, the liver parenchyma at biopsy site cannot be entered without flopping.

There is thus provided, in accordance with the present invention, a balloon-anchored, biopsy device for acquiring a biopsy sample of a target organ in a subject comprising the features defined in independent claim <NUM>.

Furthermore, in accordance with some embodiments of the present invention, the flexible biopsy needle may include a Tru-cut biopsy needle.

Furthermore, in accordance with some embodiments of the present invention, the first elongated tube and the second elongated tube respectively may include a balloon catheter and a guide catheter.

Furthermore, in accordance with some embodiments of the present invention, the target organ may include a liver.

Furthermore, in accordance with some embodiments of the present invention, the blood vessel may include a hepatic vein of the liver.

Furthermore, in accordance with some embodiments of the present invention, the biopsy device may include a locking mechanism coupled to the second proximal end for fixing the position of the flexible biopsy needle at the distal end of the wire in the second lumen.

Furthermore, in accordance with some embodiments of the present invention, components of the locking mechanism may be selected from the group consisting of a Tuohy Borst adapter, a luer lock, and a compressible clamp.

Furthermore, in accordance with some embodiments of the present invention, the flexible biopsy needle may include a cutting cannula and a stylet.

Furthermore, in accordance with some embodiments of the present invention, the flexible biopsy needle may include a flattened band and an alignment notch for maintaining an alignment of the cutting cannula and the stylet.

Furthermore, in accordance with some embodiments of the present invention, the biopsy device may include an outer tube with the predefined length into which the first elongated tube and the second elongated tube are inserted so as to longitudinally attach the first elongated tube and the second elongated tube to one another.

Furthermore, in accordance with some embodiments of the present invention, the diameter of the inflated balloon is larger than the diameter of the blood vessel.

Furthermore, in accordance with some embodiments of the present invention, the diameter of the inflated balloon is no larger than <NUM>% of the diameter of the blood vessel.

Furthermore, in accordance with some embodiments of the present invention, the predefined angle is in the range of <NUM>-<NUM> degrees.

Furthermore, in accordance with some embodiments of the present invention, the biopsy device may include a connecting tube for insertion into the second lumen for guiding the flexible biopsy needle at the distal end of the wire to the biopsy site.

Furthermore, in accordance with some embodiments of the present invention, the flexible biopsy needle may include a stylet joined to a stylet wire in an end-to-end joint.

Furthermore, in accordance with some embodiments of the present invention, the flexible biopsy needle may include a hollow stylet and a stylet wire inserted into an overlapping joint.

Furthermore, in accordance with some embodiments of the present invention, the flexible biopsy needle may include an inner stylet and outer stylet with a cutting edge arranged in a concentric configuration.

Furthermore, in accordance with some embodiments of the present invention, the flexible biopsy needle is configured to acquire the biopsy sample by rotating the outer stylet with the cutting edge relative to the inner stylet when the flexible biopsy needle is within the tissue of the target organ.

Furthermore, in accordance with some embodiments of the present invention, the flexible biopsy needle is configured to encapsulate the acquired biopsy sample in a specimen notch when the outer stylet remains in a rotated position substantially opposite to the inner stylet.

Furthermore, in accordance with some embodiments of the present invention, the biopsy device may include a rigid contoured section coupled to the distal end of the second elongated tube for increasing the predefined angle when the balloon is inflated.

Furthermore, in accordance with some embodiments of the present invention, the balloon may include a distal balloon and a proximal balloon, which are inflatable separately or together in the blood vessel.

Furthermore, in accordance with some embodiments of the present invention, the second elongated tube may be coupled to a pressure transducer for measuring a hepatic venous pressure gradient (HVPG) by processing a signal from the pressure transducer in a signal processing unit.

There is further provided, in accordance with some non-claimed examples, a method for acquiring a biopsy sample of a target organ of a subject using a balloon-anchored biopsy device may include percutaneously inserting a biopsy device into a vein of a limb of a subject, the biopsy device including a first elongated tube, a second elongated tube, and a flexible biopsy needle. The first elongated tube may enclose a first lumen with a first proximal end and a distal tip, wherein a section of the first elongated tube near the distal tip may include a balloon that when inserted into a blood vessel of a target organ of a subject and inflated, anchors the section in the blood vessel near a biopsy site in the target organ. The second elongated tube may enclose a second lumen with a second proximal end and a second distal end may include a beveled distal exit of the second lumen, which is positioned at the biopsy site of the target organ when the first elongated tube is anchored in the blood vessel by the inflated balloon, wherein a predefined length of the first and the second elongated tubes are longitudinally attached to one another such that the beveled distal exit is positioned at a proximal end of the section of the first elongated tube. The flexible biopsy needle may be attached to a distal end of a wire for insertion into the second lumen of the second elongated tube for navigation to the biopsy site, wherein the flexible biopsy needle is configured to exit the beveled distal exit of the second lumen for penetration into tissue of the target organ at the biopsy site at a predefined angle between a longitudinal axis of the section of the first elongated tube and a longitudinal axis of the flexible biopsy needle. The distal tip may be navigated from the vein through a vascular system of the subject and into the blood vessel of the target organ near the biopsy site. The balloon may be inflated in the blood vessel. The flexible biopsy needle may be pushed into the tissue of the target organ at the biopsy site at the predefined angle. A biopsy sample of the target organ at the biopsy site may be acquired using the flexible biopsy needle. The wire may be withdrawn from the second lumen so as to retrieve the acquired biopsy sample.

Furthermore, in accordance with some non-claimed examples, the limb may include an arm of the subject and the vein may include a cephalic vein of the arm.

Furthermore, in accordance with some non-claimed examples, the limb may include a leg of the subject and the vein may include a femoral vein of the leg.

Furthermore, in accordance with some non-claimed examples, percutaneously inserting the biopsy device into the vein of the limb of the subject may include inserting the biopsy device through a lumen of a sheath in the vein.

Furthermore, in accordance with some non-claimed examples, the balloon may include a distal balloon and a proximal balloon, and the method may include inflating the balloon comprises inflating the distal balloon and the proximal balloon separately or together in the blood vessel.

Furthermore, in accordance with some non-claimed examples, the second elongated tube may be coupled to a pressure transducer, and the method may include measuring a hepatic venous pressure gradient (HVPG) by processing a signal from the pressure transducer.

In order for the present invention, to be better understood and for its practical applications to be appreciated, the following Figures are provided and referenced hereafter. It should be noted that the Figures are given as examples only and in no way limit the scope of the invention. Like components are denoted by like reference numerals.

However, it will be understood by those of ordinary skill in the art that the invention may be practiced without these specific details. In other instances, well-known methods, procedures, components, modules, units and/or circuits have not been described in detail so as not to obscure the invention.

Although embodiments of the invention are not limited in this regard, discussions utilizing terms such as, for example, "processing," "computing," "calculating," "determining," "establishing", "analyzing", "checking", or the like, may refer to operation(s) and/or process(es) of a computer, a computing platform, a computing system, or other electronic computing device, that manipulates and/or transforms data represented as physical (e.g., electronic) quantities within the computer's registers and/or memories into other data similarly represented as physical quantities within the computer's registers and/or memories or other information non-transitory storage medium (e.g., a memory) that may store instructions to perform operations and/or processes. Although embodiments of the invention are not limited in this regard, the terms "plurality" and "a plurality" as used herein may include, for example, "multiple" or "two or more". The terms "plurality" or "a plurality" may be used throughout the specification to describe two or more components, devices, elements, units, parameters, or the like. Unless explicitly stated, the method embodiments described herein are not constrained to a particular order or sequence. Additionally, some of the described method embodiments or elements thereof can occur or be performed simultaneously, at the same point in time, or concurrently. Unless otherwise indicated, use of the conjunction "or" as used herein is to be understood as inclusive (any or all of the stated options).

Embodiments of the present invention herein describe a balloon-stabilized core needle biopsy device for peripheral access (e.g., transcephalic access) that overcomes problems of insufficient force transfer from the handle to the cutting cannula and stylet at the biopsy site as well as the loss of alignment between the cutting cannula and the stylet for long, flexible Tru-cut needles. The balloon-stabilized core needle biopsy device includes an endovascular in vivo stabilizing system (e.g., a dual catheter body with an inflatable balloon anchor) and a distally self-aligned flexible Tru-cut needle.

<FIG> schematically illustrates a liver biopsy procedure <NUM> performed on a subject <NUM> with a balloon-stabilized biopsy device <NUM>, in accordance with some embodiments of the present invention. A doctor <NUM> may percutaneously insert a distal end of balloon-stabilized biopsy device <NUM> into an arm <NUM> of subject <NUM> lying on a gurney <NUM>. Doctor <NUM> may navigate balloon-stabilized biopsy device <NUM> through the venous system of subject <NUM> into a hepatic vein <NUM>, such as a middle hepatic vein, for example, to a biopsy target site <NUM> of a liver <NUM>.

<FIG> schematically illustrates balloon-stabilized catheter body <NUM>, in accordance with some embodiments of the present invention. Balloon-stabilized catheter body <NUM> includes a guide catheter <NUM>, a balloon catheter <NUM>, a beveled distal exit <NUM>, and an inflatable (semi-compliant) balloon <NUM> with angled edges <NUM>. Inflatable balloon <NUM> may be placed at a section <NUM> of balloon catheter <NUM> of length L and positioned a predefined distance from a distal tip <NUM> (e.g. denoted LB). If the peripheral route for inserting balloon-stabilized catheter body <NUM> into the body of subject <NUM> is transcephalic (e.g., in <FIG>), or transfemoral, the overall profile of the balloon-stabilized catheter body should be kept smaller than <NUM>.

In some embodiments of the present invention, the outer walls of guide catheter <NUM> and balloon catheter <NUM> may be longitudinally attached <NUM> to one another over any suitable predefined length of balloon-stabilized catheter body <NUM>. Stated differently, attachment curve <NUM> between guide catheter <NUM> and balloon catheter <NUM> may be substantially parallel to the longitudinal axes (e.g., <NUM> and <NUM>) of those catheters through the respective catheter lumens when attached.

In some embodiments this may be enabled by fabricating a dual lumen catheter body. In other embodiments, an outer tube may be used to hold guide catheter <NUM> and balloon catheter <NUM> longitudinally attached <NUM> to one another over any suitable portion of the length of balloon-stabilized catheter body <NUM>. Any suitable means may be used to hold guide catheter <NUM> and balloon catheter <NUM> longitudinally attached <NUM> to one another, such that guide catheter <NUM> and balloon catheter <NUM> move together with one another when balloon-stabilized catheter body <NUM> may be navigated through the venous system. A cross-sectional cut <NUM> of schematically illustrates a lumen <NUM> of guide catheter <NUM> and a lumen <NUM> of balloon catheter <NUM>.

In some embodiments, balloon-stabilized catheter body <NUM> may include a handle adapter <NUM>, which is configured to enable the handle of any Tru-cut needle (e.g. handle <NUM>, for example) to be coupled securely to the stabilizing system.

Balloon-stabilized catheter body <NUM> may be also referred to herein as a "catheter body", a "balloon-anchored catheter body", or a "stabilizing system". Similarly, balloon-stabilized biopsy device <NUM> may be referred to herein as a "balloon-stabilized biopsy device", or a "balloon-anchored biopsy device" which may include balloon-stabilized catheter body <NUM> and a biopsy needle including the associated biopsy needle/stylet wire inserted through balloon-stabilized catheter body <NUM> to the target organ, such as liver <NUM>, and used to acquire the soft tissue biopsy sample from the target biopsy site.

In some embodiments of the present invention, balloon <NUM> may be fabricated with a semi-compliant construction with a length no longer than <NUM>. A proximal end <NUM> of balloon catheter <NUM> may include a hub <NUM>, common to over-the-wire balloon catheters. Hub <NUM> may include an inflation port <NUM> and a guidewire inlet/exit port <NUM>. Balloon <NUM> may be inflated by air coupled into inflation port <NUM>. Any suitable air valve or stopper mechanism, for example, may be used to hold the air within balloon <NUM> to keep it inflated or opened to deflate balloon <NUM>.

Section <NUM> of balloon catheter <NUM> of a length L, typically <NUM>, may be configured to be inserted into a blood vessel of the target organ, such as the hepatic vein of the liver, for example. Section <NUM> of balloon catheter <NUM> terminates in distal tip <NUM>. Once inserted, balloon <NUM> may be inflated so as to anchor section <NUM> of balloon catheter <NUM> within the blood vessel. The maximum balloon diameter may be sized to be no larger than the target vessel diameter by a factor of <NUM>%. (See, for example, Cook Medical G26902 - Advance ATB Percutaneous Transluminal Angioplasty (PTA) Dilation Catheter, whose specification is disclosed herein by reference. The length of the Cook Medical G26902 catheter is <NUM> with an inflated balloon diameter of <NUM>.

The shaft of guide catheter <NUM> may be formed from a braid-reinforced polymer tube, typically at least <NUM> in length, with a maximum distal curvature <NUM> of about <NUM>° so as permit the Tru-cut needle to pass through guide catheter <NUM> in the tortuous regions of the venous system, such as through brachiocephalic/superior vena cava junction, for example. A distal end <NUM> of the guide catheter <NUM> may be terminated with a beveled distal exit <NUM>, where a longer edge of beveled distal exit <NUM> may terminate at a proximal end <NUM> of the balloon catheter shaft (e.g., section <NUM>) at <NUM> - <NUM> proximal (e.g. L<NUM>) of inflatable balloon <NUM>. The bevel angle may be between <NUM> - <NUM>°. Beveled distal exit <NUM> may be formed by melting a polymer tube, whose inner diameter may be slightly larger than the combined diameters of balloon catheter <NUM> and guide catheter <NUM>, over distal end <NUM> of guide catheter <NUM> and balloon catheter <NUM>. The melted polymer tube may then be skived to shape to form beveled distal exit <NUM>.

A proximal end <NUM> of guide catheter <NUM> may be joined to a Tuohy Borst adapter <NUM>, which when fully loosened, allows free passage of a braid-reinforced polymer connecting tube <NUM> through Tuohy Borst adapter <NUM>. Connecting tube <NUM> may have outer diameter sized to fit smoothly into guide catheter <NUM>. Once Tuohy Borst adapter <NUM> may be sufficiently tightened, it locks connecting tube <NUM> firmly in place, thus preventing any further axial movement. The proximal end of connecting tube <NUM> is joined to a luer lock <NUM>. The inner diameters of luer lock <NUM> and connecting tube <NUM> may be sized to allow free movement of the desired long, flexible cut biopsy needle within them.

A second luer lock <NUM> with a spin lock connector, complementary to luer lock <NUM> of connecting tube <NUM>, may be present on the distal end of Tru-cut needle handle <NUM> for example, (or additional embodiments of handles shown herein) such that when the luer locks are connected, Tru-cut needles may be securely fastened to balloon-stabilized catheter body <NUM>. Typically, Tru-cut needle handles <NUM> are not be fabricated with such a second luer lock <NUM> with spin lock connector at its distal end, thus a handle adapter <NUM> may be used. Handle adapter <NUM> may include second luer lock <NUM> with spin lock connector for coupling to luer lock <NUM> of connecting tube <NUM>. Handle adapter <NUM> may include on its proximal end a clamp <NUM> customized to fit with the desired Tru- cut needle handle <NUM>. The inner diameter of second luer lock <NUM> may be sized to allow free passage of a cutting cannula and cutting cannula tube as in <FIG> below.

<FIG> schematically illustrates a second embodiment of a balloon-stabilized catheter body 100B, in accordance with some embodiments of the present invention. The region near distal tip <NUM> of balloon-stabilized catheter body 100B may include a rigid contoured section <NUM> of guide catheter <NUM> such that beveled distal exit <NUM> may be positioned over inflatable balloon <NUM> and not in front of inflatable balloon <NUM> as shown in <FIG>.

<FIG> schematically illustrates a two-sectioned inflatable balloon 120B, in accordance with some embodiments of the present invention. Two-sectioned inflatable balloon 120B positioned near distal tip <NUM> of balloon catheter <NUM> may include a proximal balloon <NUM> with angled edges <NUM> and a distal balloon <NUM> with angled edges <NUM> with an intermediate section <NUM> between proximal balloon <NUM> and distal balloon <NUM>. In some embodiments, proximal balloon <NUM> and distal balloon <NUM> may be inflated separately or inflated together. In other embodiments, two-sectioned inflatable balloon 120B may be used in <FIG> and <FIG> in place of inflatable balloon <NUM>. Two-sectioned inflatable balloon 120B may have a dog-bone shape, which provides better anchoring in the hepatic vein. Distal balloon <NUM> may be positioned at the beginning of the hepatic vein and may be used to control how far into the liver the biopsy device may go. Over insertion of the biopsy device into the liver may pose a risk that stylet <NUM> may pierce through the other side of the liver.

<FIG> schematically illustrates a longitudinal cross-sectional view of a long, flexible Tru-cut needle <NUM> with distal self-alignment, in accordance with some embodiments of the present invention. Flexible Tru-cut needle <NUM> with distal self-alignment may include a cutting cannula <NUM> and a stylet <NUM>. Stylet <NUM> may have a tubular form with notches in two separate sections: a specimen notch <NUM> and an alignment notch <NUM>. Specimen notch <NUM> in a stylet distal section <NUM> of flexible Tru-cut needle <NUM> may be used to hold the soft tissue biopsy specimen after shearing the soft tissue of the target organ with cutting cannula <NUM>. Alignment notch <NUM> may be located in a stylet proximal section <NUM> of flexible Tru-cut needle <NUM>.

In some embodiments of the present invention, the distal self-alignment of flexible Tru-cut needle <NUM> may be enabled as follows. Stylet <NUM> may be threaded through a flattened band <NUM>, where flattened band <NUM> may begin as a circular band of the same outer and inner diameters as cutting cannula <NUM>, threaded over alignment notch <NUM>, then progressively flattened until stylet <NUM> is unable to rotate about alignment notch <NUM>. However, stylet <NUM> may be free to move longitudinally along alignment notch <NUM>, but bound by a stylet middle section <NUM> and stylet proximal section <NUM>.

Flattened band <NUM> may be bonded at its distal end to the proximal end of cutting cannula <NUM>, and at its proximal end to the distal end of cutting cannula tube <NUM>. Such a bonding <NUM> may be enabled using conventional fabrication techniques, such as melting an overtube or using heat shrink tubing reinforced with medical grade adhesives. Bonding <NUM> may be strengthened by using overtube or heat shrink tubing of sufficiently high hardness (>70D), increasing the roughness of the proximal end of cutting cannula <NUM> (e.g., by sandblasting), and using cutting cannula tube <NUM> with a coiled wire construction where the overtube can melt into the grooves of the coil, for example.

<FIG> schematically illustrates a first embodiment of a handle <NUM> for use with flexible Tru-cut needle <NUM>, in accordance with some embodiments of the present invention. The handle <NUM> is similar to handle <NUM> of <FIG> with the exception of changes in an actuator <NUM> and the addition of a pin vise <NUM> at the proximal end of actuator <NUM>. A stylet wire <NUM> may be threaded through to extend out of pin vise <NUM>. When pin vise <NUM> is loosened, stylet wire <NUM> may be free to slide longitudinally as well as rotate. However, once pin vise <NUM> is tightened, stylet wire <NUM> may be firmly held in position by pin vise <NUM>. Actuator <NUM> may not be bonded to stylet wire <NUM>, as in <FIG>, for example, but instead includes a hole that allows stylet wire <NUM> to pass through unrestricted. The rest of the structure and functionality of handle <NUM> may be similar to handle <NUM> as shown in <FIG>. Cocking the spring-loaded firing mechanism in handle <NUM> may be enabled by operator <NUM> pulling back actuator <NUM> until carriage may be caught in a catch <NUM>.

In the context of this disclosure, the term flexible Tru-cut needle <NUM> as used herein may not only refer to the stylet apparatus shown in <FIG>, but may also include any suitable wire such as stylet wire <NUM>, for example, connected at the wire's proximal end to handle <NUM> and to stylet <NUM> at the wire's distal end wherein the stylet end of flexible Tru-cut needle <NUM> may be fed through proximal end <NUM> of catheter <NUM>, for example.

Methods for performing a liver biopsy using balloon-stabilized biopsy device <NUM> introduced into arm <NUM> of subject <NUM> and navigated to a target organ, such as liver <NUM>, via a transcephalic route are described herein below in accordance with some embodiments of the present invention. An operator, such as doctor <NUM>, may connect preloaded flexible Tru-cut needle <NUM> to handle adapter <NUM> via customized clamp <NUM>. Operator <NUM> may then insert flexible Tru-cut needle <NUM> into connecting tube <NUM>, and may use luer lock <NUM> of connecting tube <NUM> and second luer lock <NUM> of handle adapter <NUM> to lock the position of flexible Tru-cut needle <NUM>. Tuohy borst adapter <NUM> may be loosened, and connecting tube <NUM> with locked Tru-cut needle <NUM> may be inserted into the shaft of guide catheter <NUM>.

Connecting tube <NUM> may be slid through guide catheter <NUM> until stylet <NUM> may be positioned, but safely held within guide catheter distal end <NUM>. The tip of stylet <NUM> may be held in guide catheter distal end <NUM> at a distance of <NUM>, for example, from beveled distal exit <NUM>. Touhy borst adapter <NUM> may then be locked to keep the connecting tube with flexible Tru-cut needle <NUM> in place with respect to the shaft of guide catheter <NUM>.

In some embodiments of the present invention, operator <NUM> may gain access to the venous system by placing an introducer sheath in arm <NUM> of subject <NUM>. The introducer sheath may then be exchanged for balloon-stabilized biopsy device <NUM>. In this step, venous access of balloon-stabilized biopsy device <NUM> may be aided by its streamlined profile provided by deflated balloon <NUM> and beveled distal exit <NUM>. Balloon-stabilized biopsy device <NUM> may be introduced into a lumen of the introducer sheath and into the venous system.

In some embodiments of the present invention, the introducer sheath may be elongated so that it reaches beyond the first bend where the subclavian vein joins with the superior vena cava above the heart. The introducer sheath may be armored, such as by using a coil-wire design. The introducer sheath may not be removed, but left in place and connected by an interference fit for providing additional stability on the other end. The introducer sheath may extend protection and improved trackability around the first and most acute bend (e.g., subclavian to superior vena cava) from the biopsy needle.

<FIG> schematically illustrates balloon-stabilized biopsy device <NUM> with a retracted flexible Tru-cut needle <NUM> for navigation, in accordance with some embodiments of the present invention.

<FIG> schematically illustrates balloon-stabilized biopsy device <NUM> with an extended flexible Tru-cut needle <NUM> for soft tissue acquisition, in accordance with some embodiments of the present invention.

Balloon-stabilized biopsy device <NUM> may be navigated through the venous system to liver <NUM>, For example, operator may introduce balloon-stabilized biopsy device <NUM> into the basilic/cephalic vein in arm <NUM>. Balloon-stabilized biopsy device <NUM> may then be navigated through the brachiocephalic/superior vena cava junction into the superior vena cava, through the heart into inferior vena cava <NUM> and finally into hepatic vein <NUM>, such as the middle hepatic vein, for example. The navigation of distal tip <NUM> of balloon-stabilized biopsy device <NUM> may be further enabled using guidewire support in balloon catheter <NUM> until beveled distal exit <NUM> may no more than <NUM> distal of a hepatic vein ostium <NUM>. Throughout the navigation and tracking step, sharp stylet <NUM> may not injure the veins during tracking because stylet <NUM> may be kept safety within the shaft of guide catheter <NUM> near guide catheter distal end <NUM> as shown in <FIG>.

Once beveled distal exit <NUM> is positioned at biopsy target site <NUM> with section <NUM> of balloon catheter <NUM> in hepatic vein <NUM>, balloon <NUM> may inflated to a diameter (e.g., up to <NUM>% larger than the vein diameter) so as to anchor section <NUM> of balloon catheter <NUM> in hepatic vein <NUM>. At this point, the guidewire in balloon catheter <NUM> may be left in position, so as to provide additional stability to the system. Since beveled distal exit <NUM>, from where cutting cannula <NUM> and stylet <NUM> exit is proximal to inflated balloon <NUM>, cutting cannula <NUM> and stylet <NUM> should be directed obliquely towards liver parenchyma <NUM>, instead of co-axially with hepatic vein <NUM> towards balloon <NUM>.

To achieve this, balloon catheter <NUM> is designed to be more flexible than guide catheter <NUM>, which enables guide catheter distal end <NUM> to tilt relative to a longitudinal axis <NUM> of section <NUM> (see <FIG>) of balloon catheter <NUM> with inflated balloon <NUM> and to remain fixed, and not co-axial or parallel with hepatic vein <NUM>, as shown in <FIG>. As a result, stylet <NUM> of flexible Tru-cut needle <NUM> may be pushed into liver parenchyma <NUM> at an angle ϕ between a longitudinal axis <NUM> of flexible Tru-cut needle <NUM> and longitudinal axis <NUM> of section <NUM> (see <FIG>) with balloon <NUM> as shown in <FIG>. ϕ may be in the range of <NUM>-<NUM> degrees. In this configuration, stylet <NUM> may cleanly enter liver parenchyma <NUM> at biopsy site <NUM> without flopping around as described previously for the non-anchored or stabilized case. Moreover, this oblique configuration may prevent stylet <NUM> from popping inflated balloon <NUM>. In some embodiments, more flexibility of balloon catheter <NUM> may be achieved by reducing the diameter of balloon catheter <NUM> from <NUM> Fr to <NUM> Fr on the French scale.

In some embodiments, the outer walls of guide catheter <NUM> and balloon catheter <NUM> may no longer be longitudinally attached <NUM> in the region of balloon-stabilized catheter body <NUM> near to guide catheter distal end <NUM> so as to facilitate achieving the oblique configuration with predefined angle ϕ as shown in <FIG>.

In some embodiments of the present invention, once balloon-stabilized biopsy device <NUM> and retracted flexible Tru-cut needle <NUM> are positioned at biopsy target site <NUM>, operator <NUM> may then loosen Tuohy borst adapter <NUM>. Connecting tube <NUM> and Tru-cut needle <NUM> may be pushed forward out of the shaft of guide catheter <NUM> until extended stylet <NUM> and cutting cannula <NUM> fully enters liver <NUM>. Once cutting cannula <NUM> and stylet <NUM> have entered the tissue of liver <NUM>, operator <NUM> may then tighten Tuohy borst adapter <NUM> to hold connecting tube <NUM> with handle <NUM> in place.

From this point onward, in some embodiments, operator <NUM> may perform the biopsy by firing the spring-loaded mechanism to drive cutting cannula <NUM> in liver parenchyma <NUM> toward stylet <NUM> (e.g., as any Tru-cut needle is operated). If the liver is not anchored, the liver may move forward if the stylet is slowly advanced, reducing the chance of a successful biopsy. In other embodiments, both the stylet and the cutting cannula may be spring loaded. They may be separately fired or fired together. The stylet may be fired followed by the cutting cannula in quick succession, which increases the chance of a successful liver biopsy.

If flexible Tru-cut needle <NUM> is fired at this point on its own without the balloon-anchored stabilization system, cutting cannula tube <NUM> will whip around starting from the cutting cannula tube proximal end just bonded to the carriage, because of the cutting cannula tube's flexibility. As a result of this whipping, most of the energy provided by the spring loaded mechanism in handle <NUM> that is meant to be transferred to cutting cannula <NUM> via cutting cannula tube <NUM> will be dissipated away before reaching the cutting cannula <NUM>, leading to biopsy failure.

The balloon-anchored stabilizing system may significantly reduce this whipping effect through several means. Firstly, guide catheter <NUM> may provide support to cutting cannula tube <NUM> by encasing it in-vivo in a non-compliant, close fit environment such that the flexibility of cutting cannula tube <NUM> may be inhibited in the transverse direction, thereby improving its pushability, so long as cutting cannula tube <NUM> has sufficient column strength to withstand the energy from the spring-loaded firing mechanism in handle <NUM>. Secondly, the securing the shaft of guide catheter <NUM>, connecting tube <NUM>, and handle adapter <NUM> provides additional support of cutting cannula tube <NUM> ex vivo. Thirdly, any recoil experienced by flexible Tru-cut needle <NUM> during its operation will not dislodge the stabilizing system due to the anchorage provided by inflated balloon <NUM>, thereby increasing the efficiency of the support provided by guide catheter <NUM>. Once cutting cannula tube whipping is reduced significantly, cutting cannula tube <NUM> may perform its intended function of energy transfer from the spring-loaded firing mechanism in handle <NUM> to cutting cannula <NUM> so as to perform the biopsy.

Once the biopsy sample has been obtained, balloon <NUM> may be deflated to restore blood flow in hepatic vein <NUM>. With balloon-stabilized biopsy device <NUM> left in place, luer lock <NUM> of connecting tube <NUM> and second luer lock <NUM> of handle adapter <NUM> are loosened, and flexible Tru-cut needle <NUM> may be retracted out of the body. Using methods normal to Tru-cut needles operation, operator <NUM> may expose stylet <NUM> to inspect the quality of the biopsy sample stored in specimen notch <NUM>.

If subsequent biopsy passes are needed, balloon-stabilized catheter body <NUM> for each new pass may be withdrawn until beveled distal exit <NUM> may be located just outside biopsy site <NUM>, leaving deflated balloon still inside hepatic <NUM>. Flexible Tru-cut needle <NUM> may then be reinserted back into balloon-stabilized catheter body <NUM> and tracked back to biopsy site <NUM> to obtain subsequent biopsy samples by the methods previously described herein.

<FIG> schematically illustrates a second embodiment of a balloon-stabilized biopsy device with rigid contoured section <NUM> with a retracted flexible Tru-cut needle for navigation, in accordance with some embodiments of the present invention.

<FIG> schematically illustrates a second embodiment of a balloon-stabilized biopsy device with rigid contoured section <NUM> with an extended flexible Tru-cut needle for soft tissue acquisition, in accordance with some embodiments of the present invention.

In the second embodiment, rigid contoured section <NUM> of guide catheter <NUM> may include distal beveled <NUM> positioned over and resting on angled edge <NUM> over inflatable balloon <NUM>. When the balloon is inflated, this configuration may be used to increase angle ϕ between longitudinal axis <NUM> of flexible Tru-cut needle <NUM> during biopsy acquisition and longitudinal axis <NUM> when flexible Tru-cut needle <NUM> is extended for soft tissue acquisition relative to the first embodiment shown in <FIG> without rigid contoured section <NUM>.

<FIG> schematically illustrates a distally-aligned flexible Tru-cut needle <NUM> in a closed configuration <NUM>, in accordance with some embodiments of the present invention.

<FIG> schematically illustrates a distally-aligned flexible Tru-cut needle <NUM> in an open configuration <NUM>, in accordance with some embodiments of the present invention.

The operation of long, flexible Tru-cut needle <NUM> is described hereinbelow in accordance with some embodiments of the present invention. Flexible Tru-cut needle <NUM> may be first laid out straight on sufficiently large surface, with pin vise <NUM> in handle <NUM> loosened. Cutting cannula <NUM> and stylet <NUM> may be aligned in the closed configuration as shown in <FIG>, with the corresponding position of flattened band <NUM> in alignment notch <NUM>. Cocking the spring-loaded firing mechanism in handle <NUM> may be enabled by operator <NUM> pulling back actuator <NUM> until carriage may be caught in catch <NUM>. As the carriage is being pulled back, the cutting cannula - flattened band - cutting cannula tube assembly may be pulled along in the same manner, whereby the existing friction between flattened band <NUM> and alignment notch <NUM> causes stylet <NUM> and cutting cannula <NUM> to retract as one unit, maintaining closed configuration <NUM>. Once the spring is fully loaded, flexible Tru-cut needle <NUM> is ready for insertion into patient <NUM>.

Operator <NUM> may manipulate the flexible Tru-cut needle <NUM> to desired biopsy site <NUM> through endovascular or endoscopic means in a tracking step. During this tracking step, stylet <NUM> and cutting cannula <NUM> should remain in the optimal closed configuration <NUM> for tracking. While tracking, both cutting cannula tube <NUM> and stylet wire <NUM> will be bending in accordance to how their differing flexibilities adapt to the tortuosity of the anatomy/working channel being navigated. As there is higher friction on Tru-cut needle distal section <NUM> between flattened band <NUM> and alignment notch <NUM> relative to the proximal end of balloon-stabilized biopsy device <NUM> where stylet wire <NUM> may freely move longitudinally about loosened pin vise <NUM>, any bending differences between cutting cannula tube <NUM> and stylet wire <NUM> may be transferred to the proximal end of balloon-stabilized biopsy device <NUM> based on the path of least resistance. Therefore, this property of balloon-stabilized biopsy device <NUM> may ensure that cutting cannula <NUM> and stylet <NUM> may maintain their longitudinal alignment <NUM> of the closed configuration <NUM> throughout tracking.

In some embodiments to further ensure longitudinal alignment <NUM>, the length of alignment notch <NUM> may be carefully controlled such that it corresponds closely to the expected movement distance of cutting cannula <NUM>. For example, cutting cannula <NUM> with an allowed movement of <NUM> with flattened band <NUM> with a <NUM> length, the length of alignment notch <NUM> may be <NUM>. In this manner, even if stylet <NUM> may attempt to retract into cutting cannula <NUM> during tracking, the proximal end of stylet mid-section <NUM> may be blocked by flattened band <NUM> that is fixed by cutting cannula tube <NUM>, thereby ensuring adequate longitudinal alignment <NUM>.

Similarly, as flexible Tru-cut needle <NUM> is being manipulated to desired biopsy site <NUM> through endovascular or endoscopic means, both cutting cannula tube <NUM> and stylet wire <NUM> may be twisting in accordance with how their differing torquabilities react to the tortuosity of the anatomy/working channel being navigated. Since there is space at the distal end of flexible Tru-cut needle <NUM> for flattened band <NUM> to twist about alignment notch <NUM> as compared to the proximal end where stylet wire <NUM> may be free to rotate about loosened pin vise <NUM>, any twisting differences between cutting cannula tube <NUM> and stylet wire <NUM> may be transferred to the proximal end based on the path of least resistance, therefore ensuring that cutting cannula <NUM> and stylet <NUM> maintain their rotational alignment <NUM> throughout tracking.

Once flexible Tru-cut needle <NUM> reaches desired biopsy site <NUM>, operator <NUM> may advance Tru-cut needle <NUM> into the organ parenchyma, preferably until the tip of cutting cannula <NUM> may be safely inside the parenchyma. During this advancement step, the cutting cannula and stylet longitudinal alignment <NUM> should be maintained in the closed configuration <NUM> as shown in <FIG>. This is achieved by the same alignment notch length control as previous described by way of example.

Once tip of cutting cannula <NUM> is inside the parenchyma, operator <NUM> may push out stylet <NUM> to open position <NUM> as shown in <FIG>, penetrating into the parenchyma of the target organ while maintaining the position of cutting cannula <NUM>. During this stylet penetration step, the cutting cannula and stylet will reach a final longitudinal and rotational alignments <NUM> in open configuration <NUM> as shown in <FIG>.

Maintaining longitudinal alignment may also be enabled using alignment notch length control. Using the same lengths previously described of cutting cannula <NUM> that is allowed to move <NUM>, a <NUM> long flattened band and the corresponding alignment notch length of <NUM>, the lengths may be designed such that when stylet <NUM> may be fully extended to final open configuration <NUM>, the distal end of stylet proximal-section will be blocked by the proximal end of the flattened band, thereby preventing any over-extension away from the final longitudinal alignment.

The freedom of movement of the stylet wire proximal section by loosened pin vise <NUM> may also assist in achieving longitudinal alignment, as the pushability of stylet wire <NUM> may be overcome by allowing stylet wire <NUM> to be pushed as much as possible from outside patient <NUM> until the distal end of stylet proximal-section may be blocked by the proximal end of the flattened band, which may be tactilely sensed by operator <NUM> (e.g., tactile feedback) from stylet wire <NUM>. With regards to rotational alignment, the close fit between flattened band <NUM> and alignment notch <NUM> throughout the stylet extension movement may ensure that both cutting cannula <NUM> and stylet <NUM> may be forced to turn and rotate as one single unit, thereby ensuring rotational alignment.

Once stylet <NUM> has been fully extended, operator <NUM> may tighten pin vise <NUM> to lock stylet wire <NUM> at its proximal end and fire the spring-loaded mechanism in handle <NUM> to drive cutting cannula <NUM> distally toward the tip of stylet <NUM> so as to cut and obtain the soft tissue specimen in the organ parenchyma. Note that locking stylet wire <NUM> via tightening pin vise <NUM> is crucial at this point as this ensures that the cutting cannula - flattened band - cutting cannula tube assembly may be propelled forward as one unit without stylet <NUM> being moved along with it. After the spring-loaded mechanism has been fired and the tissue specimen obtained in specimen notch <NUM>, cutting cannula <NUM> and stylet <NUM> may be returned to the same longitudinal and rotational alignments in closed configuration <NUM>, so that the tissue specimen within specimen notch <NUM> may be safely encapsulated between the cutting cannula <NUM> and stylet <NUM>. This may be automatically ensured by careful control of the alignment notch length.

Furthermore using the same lengths described previously where cutting cannula <NUM> may move <NUM>, <NUM> long flattened band <NUM>, and a length of alignment notch <NUM> of <NUM>, these lengths may be designed such that once the stylet has been fully extended in the stylet penetration step, the cutting cannula distal end automatically ends up overlapping the stylet distal-section, achieving the encapsulation of the biopsy sample in specimen notch <NUM>. The alignment notch length of <NUM>, being longer than the combined cutting cannula and flattened band lengths of <NUM>, also provides additional allowance for flattened band movement, such that the flattened band, when propelled by high speeds by the spring-loaded mechanism in handle <NUM>, may not collide with the proximal end of stylet mid-section <NUM>.

With the tissue specimen safely encapsulated, operator <NUM> may loosen pin vise <NUM> allowing free stylet wire movement, and may withdraw flexible Tru-cut needle <NUM> out of the patient's body to retrieve the sample. In this withdrawal step, the same design aspects of the flexible Tru-cut needle <NUM> as described previously in the tracking step may also be used to keep cutting cannula <NUM> and stylet <NUM> in the proper longitudinal and rotational alignments in closed configuration <NUM>. Once flexible Tru-cut needle <NUM> may be withdrawn from the patient's body, operator <NUM> may extend the stylet to open configuration <NUM> for inspection and/or transfer of the tissue specimen out of specimen notch <NUM>. If operator <NUM> deems that another biopsy pass must be performed, flexible Tru-cut needle <NUM> may be reset by pulling stylet <NUM> back to closed configuration <NUM>, then pulling back actuator <NUM> to cock the spring-loaded firing mechanism.

In some embodiments of the present invention, a second method for using balloon-stabilized biopsy device <NUM> as a part of an endoscopic access to soft tissue/internal organs is described hereinbelow. Although ultrasound guided endoscopic transgastric access may be known, the use of Tru-cut biopsy needles within the endoscope has been documented to be technically challenging because of the stiffness of the biopsy needles. Thus, with the flexible, low profile and length of flexible Tru-cut needle <NUM> as described above, operator <NUM> may use it in conjunction with an endoscope, where the endoscope may be navigated through the gastro-intestinal system to a location closest to the target organ. Biopsy device <NUM> may be anchored by inflating the balloon, and firing the needle to pierce through the stomach/intestines directly into the target organ (such as the liver, kidney, etc.), so as to obtain the soft tissue biopsy sample.

In some embodiments of the present invention, during the venous access of balloon-stabilized biopsy device <NUM> in exchange with the introducer sheath, an additional long dilator may be sized to fit inside and throughout the shaft of guide catheter <NUM> so as to ease venous access. The dilator may be made in any suitable shape and construction.

In some embodiments of the present invention, although balloon-stabilized biopsy device <NUM> has been described herein for core needle biopsies, balloon-stabilized biopsy device <NUM> may be configured to work with fine needle aspiration biopsy systems, so long as the fine needle aspiration biopsy system is sufficiently long and flexible. This may be desirable for endovascular peripheral access for fine needle aspiration biopsy systems, as well as providing a stable platform for the fine needle aspiration biopsy systems.

In some embodiments of the present invention, although Tuohy borst adapter <NUM> may be used to control the mobility of the connecting tube as previously described, there are other methods to do so. For example, a compressible clip may be used to replace Tuohy borst adapter <NUM>, where the compressible clip may be configured to clamp onto and to hold connecting tube <NUM> firmly in position. When operator <NUM> may compress the compressible clip, the clamping action may be removed so as to permit movement of connecting tube <NUM>. In this manner, operator <NUM> may be free to adjust the longitudinal position of connecting tube <NUM>. Once the desired positions of cutting cannula <NUM> and stylet <NUM> have been attained, operator <NUM> may release the compressible clip, so as to re-clamp and fix the position of connecting tube <NUM>.

<FIG> schematically illustrates a handle adapter <NUM> with a middle shaft <NUM>, in accordance with some embodiments of the present invention. In cases where no braid-reinforced connecting tube <NUM> may be used, a second embodiment of handle adapter <NUM> may be used, which is configured to directly receive guide catheter shaft proximal end <NUM>. In this case, Tuohy borst adapter <NUM> of guide catheter shaft proximal end <NUM> may be first removed. Luer lock with spin connector of the handle adapter <NUM> may then be replaced by a second embodiment of a Tuohy borst adapter <NUM> that is large enough to accommodate easy passage of guide catheter shaft proximal end <NUM> when loosened. Next, handle adapter <NUM> may be lengthened by adding middle shaft <NUM> between Tuohy borst adapter <NUM> and customized clamp <NUM>, where middle shaft <NUM> may include a sufficiently large inner diameter so as to allow free movement of guide catheter shaft proximal end <NUM> within it, so that the position of cutting cannula <NUM> and stylet <NUM> relative to guide catheter <NUM> may be adjusted. Tuohy borst adapter <NUM> may then be tightened so as to secure or fix guide catheter shaft proximal end <NUM> in the proper position.

In some embodiments of the present invention, braid-reinforced connecting tube <NUM> and handle adapter <NUM> may also be modified to become a retractable sheath for the Tru-cut needle when placed inside guide catheter <NUM>. These modifications may include extending connecting tube <NUM> distally until it may sheath stylet <NUM>, changing the construction of connecting tube <NUM> to a coil-reinforced polymer for added flexibility, and adding a retracting mechanism in handle adapter <NUM>. In this manner, connecting tube <NUM> and flexible Tru-cut needle <NUM> may be inserted into balloon-stabilized catheter body <NUM> as a single unit. If additional biopsies are needed, only flexible Tru-cut needle <NUM> may be withdrawn without the need to withdraw any portions of balloon-stabilized catheter body <NUM>. This method may prevent any potential damage to the shaft of guide catheter <NUM> by having to remove only connecting tube <NUM> from patient <NUM>.

To perform the biopsy, connecting tube <NUM> may be retracted to unsheathe cutting cannula <NUM> and stylet <NUM> once the cutting cannula and stylet have reached desired biopsy target site <NUM>. Tuohy borst adapter <NUM> joined to guide catheter shaft proximal end <NUM> may be tightened to lock the connecting tube in place, thereby firmly securing the connecting tube - handle adapter - Tru-cut needle to the stabilizing system of biopsy device <NUM>.

<FIG> schematically illustrates a second embodiment of a section <NUM> of a balloon catheter <NUM>, in accordance with some embodiment of the present invention. If a smaller profile (e.g., diameter of balloon-stabilized biopsy device <NUM>) is desired, the guidewire lumen of balloon catheter <NUM> may be removed while keeping an inflation channel, with the trade-off that there will be no guidewire support for balloon-stabilized biopsy device <NUM>. In this embodiment, an inflatable balloon <NUM> of section <NUM> of balloon catheter <NUM> of length L may be positioned at a predefined distance from a distal tip <NUM> (e.g. denoted LB). At a proximal end of section <NUM>, a mid-section <NUM> of length Lm may couple balloon catheter <NUM> to section <NUM> and include a distal exit <NUM>.

The shaft section of balloon catheter <NUM> may include a braid-reinforced design so as to provide sufficient support for flexible Tru-cut needle <NUM>. In the embodiment shown in <FIG>, during tracking of flexible Tru-cut needle <NUM> to hepatic vein <NUM> of liver <NUM>, for example, the guidewire may be threaded through section <NUM>, mid-section <NUM>, and shaft of catheter <NUM>. After reaching hepatic vein <NUM> and inflating balloon <NUM> with mid-section <NUM> placed, for example, at hepatic vein ostium <NUM>, the guidewire may be exchanged for flexible Tru-cut needle <NUM> with its own retractable sheath. Mid-section <NUM> may be configured to be more flexible than shaft section <NUM> of catheter <NUM> due to the cut-out section of a distal exit <NUM>, being substantially more pliant than shaft <NUM> without the cut-out section. Mid-section <NUM> may then tilt relative to the longitudinal axis of section <NUM> anchored in hepatic vein <NUM>. Flexible Tru-cut needle <NUM> (e.g., cutting cannula <NUM> and stylet <NUM>) may exit from distal exit <NUM> at an angle ϕ as defined in <FIG> and may be directed into liver parenchyma <NUM> and away from balloon <NUM>.

In some embodiments of the present invention, for the portion of stylet wire <NUM> that travels past pin vise <NUM>, it may be desirable to increase the pushability of this section. Firstly, increasing the pushability may increase the tactile sensation by operator <NUM> during the extension of stylet <NUM> out from cutting cannula <NUM>. This may also increase the amount of pushing force that can be applied by operator <NUM> without kinking of stylet wire <NUM> so that stylet <NUM> maybe extended out to its maximum travel during the stylet penetration step.

This may be enabled in a first embodiment by sliding a metal cannula over stylet wire <NUM> in this portion, where the metal cannula may be formed from nitinol or stainless steel, and may be stiffer than stylet wire <NUM>. Furthermore, the metal cannula may be of sufficient length so that the metal cannula may function as a user interface (e.g., for operator access) for stylet wire <NUM>. The inner diameter of the metal cannula may be sized to fit closely to that of stylet wire <NUM> so that both the metal cannula and stylet wire may be spot welded to one another. Similarly, the outer diameter of the metal cannula may be sized so as to permit passage through loosened pin vise <NUM>, or pin vise <NUM> may be sized larger so as to accommodate a larger metal cannula.

<FIG> schematically illustrates a solid stylet <NUM> joined end-to-end with a stylet wire <NUM>, on accordance with some embodiments of the present invention.

<FIG> schematically illustrates a hollow stylet <NUM> overlappingly joined with stylet wire <NUM>, on accordance with some embodiments of the present invention.

Stylet <NUM> as shown in <FIG> may be formed as single solid component, which means that the stylet - stylet wire joint may include an end-to-end joint <NUM>, which may be technically challenging to fabrication. One way to overcome this is to have a hollow stylet design <NUM>, such that an overlapping joint <NUM> may be formed, as shown in <FIG>, while the outer profile remains substantially the same as solid stylet <NUM>. The hollow regions of the stylet at overlapping joint <NUM> may be filled with medical grade adhesives so as increase adhesion between stylet wire <NUM> in overlapping joint <NUM>.

<FIG> schematically illustrates a torque-based cut biopsy needle <NUM> with an outer stylet <NUM> and an inner stylet <NUM>, in accordance with some embodiments of the present invention.

<FIG> schematically illustrates a top view of torque-based cut biopsy needle <NUM> in an open configuration <NUM> and an encapsulation configuration <NUM>, in accordance with some embodiments of the present invention.

<FIG> schematically illustrates rotating an outer stylet grip <NUM> for performing a torque-based cut needle biopsy, in accordance with some embodiments of the present invention.

Outer stylet <NUM> may include a knife cutting edge <NUM>. Inner stylet <NUM> may include a specimen notch <NUM> as shown in <FIG>. In some embodiments, the width of outer stylet <NUM> may be <NUM> and the width of inner stylet <NUM> may be <NUM>.

Outer stylet <NUM> and inner stylet <NUM> may be respectively coupled to an outer stylet wire <NUM> and an inner stylet wire <NUM> as shown in <FIG>. The concentric inner <NUM> and outer <NUM> stylet wires may be connected at their proximal ends ex vivo to stylet grips for use by operator <NUM>. For example, an outer stylet grip <NUM> may be attached to outer stylet wire <NUM>, and an inner stylet grip <NUM> may be attached to inner stylet wire <NUM>. Outer stylet <NUM> and inner stylet <NUM> may be threaded through guide catheter <NUM> in balloon-stabilized catheter body <NUM> such that the inner <NUM> and outer <NUM> stylets may be pushed into by operator <NUM> and/or fired by the handle into liver parenchyma <NUM>.

In some embodiments of the present invention, torque-based cut biopsy needle <NUM> may be used to cut the soft tissue of liver parenchyma <NUM> using knife edge <NUM>. Once the stylets are within liver parenchyma <NUM>, operator <NUM> holding inner stylet grip <NUM> fixed may rotate outer stylet grip <NUM> ex vivo as shown in arrow <NUM> causing outer stylet <NUM> in vivo to rotate in liver parenchyma <NUM> relative to fixed inner stylet <NUM>. As outer stylet <NUM> rotates, for example, cutting edge <NUM> cuts soft tissue from liver parenchyma <NUM> in a cutting configuration <NUM> from open configuration <NUM> and to encapsulation configuration <NUM> (e.g., rotation of <NUM> degrees) whereby a soft tissue sample <NUM> may be sheared off and encapsulated in specimen notch <NUM>.

In other embodiments, the rotation of outer stylet <NUM> relative to inner stylet <NUM> may be enabled by any suitable rotating mechanism manual or automatic, for example, such as a computer-controlled rotational motor, for example. In some embodiments, a rotational torque of <NUM>-<NUM> may be applied to outer stylet grip <NUM> ex vivo to shear the soft tissue in vivo using the torque-based biopsy mechanism described herein.

After soft tissue sample <NUM> is encapsulated in specimen notch <NUM>, torque-based cut biopsy needle <NUM> may be withdrawn from the body of patient <NUM> (e.g., from guide catheter <NUM>) while maintaining encapsulation configuration <NUM> so as to inspect encapsulated soft tissue biopsy sample <NUM>.

<FIG> schematically illustrates an exploded view of a second embodiment of a handle <NUM>, in accordance with some embodiments of the present invention. Handle <NUM> may include a left handle portion <NUM>, a right handle portion <NUM>, a windlass axle <NUM>, a windlass handle <NUM>, windlass locking pins <NUM>, a handle luer holder <NUM>, an inner catheter bolt <NUM>, and a firing lever <NUM>.

<FIG> schematically illustrates handle <NUM> before firing <NUM>, in accordance with some embodiments of the present invention. An arrow <NUM> illustrates a position of a stylet wire <NUM> and inner catheter bolt <NUM> in the cocked position.

<FIG> schematically illustrates handle <NUM> after firing <NUM>, in accordance with some embodiments of the present invention. An arrow <NUM> illustrates the relative position of stylet wire <NUM> after firing as well as inner catheter bolt <NUM> revealing a spring <NUM>. Handle <NUM> may be used to hold and lock inner catheter bolt <NUM> so that cutting cannula <NUM> will not fire until firing lever <NUM> is squeezed.

In some embodiments of the present invention, handles <NUM> and <NUM>, for example, are typically configured to deliver an average maximum force applied by the stylet end of the cut biopsy needles to liver parenchyma <NUM> of about <NUM> N. Depending on the level of fibrosis in the liver tissue, the average force needed to penetrate liver parenchyma <NUM> may be in the range of <NUM>-<NUM> N. Hence, handles <NUM> and <NUM> shown herein deliver more force than is needed to penetrate liver parenchyma <NUM>.

Portal hypertension may be caused by chronic liver diseases, which is characterized by an increased portal pressure gradient (PPG) as the difference in pressure between the portal vein and the inferior vena cava [IVC]. In normal conditions, the PPG may range between <NUM> and <NUM> mmHg. Portal hypertension becomes clinically significant when the PPG increases to <NUM> mmHg or above. Values between <NUM> and <NUM> mmHg represent subclinical portal hypertension. However, PPG may also be assessed by measuring the hepatic venous pressure gradient (HVPG), which is the difference between the wedged hepatic venous pressure (WHVP) and the free hepatic venous pressure (FHVP).

The WHVP may be measured by occluding the hepatic vein, e.g., stopping the blood flow cases the static column of blood, so as to equalize pressure in the preceding vascular territory, in this case the hepatic sinusoids. Thus, WHVP is a measure of hepatic sinusoidal pressure, not of portal pressure.

In a normal liver, WHVP is slightly lower (e.g., by about <NUM> mmHg) than portal pressure, owing to pressure equilibration through the interconnected sinusoids. In liver cirrhosis, however, the static column of blood created by occluding the hepatic vein cannot be decompressed at the sinusoidal level because the connection between sinusoids are disrupted as a result of the presence of fibrous septa and nodule formation. In cirrhosis, therefore, WHVP gives an accurate estimate of portal pressure, as has been demonstrated both for alcoholic and viral cirrhosis. FHVP is a measure of the pressure of the unoccluded hepatic vein.

HVPG is a measure of portal pressure, so the value changes, when the factors that determine portal pressure (e.g., resistance and blood flow) are modified. Changes in hepatic resistance may be caused by structural pathologies (fibrosis, regenerative nodules, or thrombosis) or functional abnormalities (increased hepatic vascular tone), or by changes in the portal or collateral blood.

In some embodiments of the present invention, in addition to the acquisition of a liver biopsy sample using balloon-stabilized catheter body <NUM> or 100B, the biopsy device itself may be coupled to a measurement system for assessing HVPG.

<FIG> schematically illustrates an adapter <NUM> for coupling balloon-stabilized catheter body <NUM> or 100B to a hepatic venous pressure gradient (HVPG) measurement system, in accordance with some embodiments of the present invention. Adapter <NUM> may include a luer lock <NUM> coupled to a catheter <NUM>, a three-way tap <NUM>, a pressure transducer <NUM>, a tube <NUM> with pressured saline, and a cable <NUM> for coupling signals from pressure transducer <NUM> to a signal processor (not shown). Pressure transducer <NUM> may be used to measure HPVG from the pressure of blood in catheter <NUM>. In some embodiments, luer lock <NUM> and catheter <NUM> shown in <FIG> may be, for example, luer lock <NUM> and guide catheter <NUM> of balloon-stabilized catheter body <NUM> as shown in <FIG>.

Catheterization of the hepatic vein may be carried out under sedation in conjunction with noninvasive vital sign monitoring (e.g., by electrocardiography, arterial blood pressure, and pulse oximetry). Under local anesthesia, the right jugular vein (or the femoral or antecubital vein) may be catheterized. A venous introducer (e.g., introducer sheath) may be placed into the vein. Balloon-stabilized catheter body <NUM> or 100B may be inserted through the venous introducer and navigated under fluoroscopic control into inferior vena cava <NUM> and hepatic vein <NUM>, so as to measure WHVP, FHVP and pressure in the inferior vena cava with the balloon-stabilized catheter body that is coupled to an adapter <NUM> and HVPG measurement system.

<FIG> is a graph <NUM> of a hepatic venous pressure gradient (HVPG) measurement, in accordance with some embodiments of the present invention. FHVP <NUM> and <NUM> may be measured by maintaining distal tip <NUM> of the balloon-stabilized catheter body in the hepatic vein with balloons <NUM> or 120B deflated at about <NUM>-<NUM>, for example, from its opening into the inferior vena cava. The FHVP should be similar in value to the inferior vena cava pressure. A difference of more than <NUM> mmHg between FHVP and the inferior vena cava pressure may signify that the catheter may be inadequately placed, or that a hepatic vein obstruction may exist.

WHVP <NUM> and <NUM> may be measured by occluding the hepatic vein, either by wedging the catheter into a small branch of the hepatic vein or by inflating balloon <NUM> or 120B in balloon-stabilized catheter body <NUM> or 100B at distal tip <NUM>. Adequate occlusion of the hepatic vein may be confirmed by slowly injecting <NUM> of a contrast dye into the vein (e.g., a procedure that reveals a typical 'wedged' pattern) without observing reflux of the dye or washout through communications with other hepatic veins. However, occlusion of the hepatic vein using balloon inflation may include a larger volume of liver circulation that is detected relative to wedging the catheter. Balloon inflation HVPG may exhibit better measurement sensitivity or variability. WHVP <NUM> and <NUM> are measured until the value stabilizes usually after about <NUM>, for example.

A hepatic venous pressure gradient (HVPG) measurement system may include adapter <NUM>, a recorder, and a signal processing unit where cable <NUM> may couple the signal from pressure transducer <NUM> to the signal processing unit. All measurement are taken at least in duplicate as shown in graph <NUM>. Permanent tracings (e.g., graph <NUM>) may be obtained with a multichannel recorder and adequately calibrated transducers (e.g., pressure transducer <NUM>). The example HVPG measurement shown in graph <NUM> of <FIG> was made with a recorder speed of <NUM>/sec. The data was acquired in about <NUM> seconds. The signal processing unit may compute HVPG as is the difference between the measured wedged hepatic venous pressure (WHVP) and the measured free hepatic venous pressure (FHVP).

In some embodiment of the present invention, measuring FHVP may be performed by inserting the balloon-stabilized catheter body into a guidewire, removing the guidewire, connecting the balloon-stabilized catheter body to the pressure transducer, injecting contrast through lumen of the first elongated tube to check position, and plotting pressure on the recorder. Measuring WHVP may be performed by inflating balloon <NUM>, injecting contrast to verify that that the catheter was successfully wedged, and plotting pressure on the recorder. The guidewire may be reinsert and the biopsy procedure started using the balloon-stabilized catheter body.

In some embodiments of the present invention, a balloon-anchored, biopsy device <NUM> for acquiring a biopsy sample of a target organ in a subject may include a first elongated tube, a second elongated tube, and a flexible biopsy needle. The first elongated tube (e.g., balloon catheter <NUM>) may enclose a first lumen with a first proximal end and a distal tip, where a section of the first elongated tube near the distal tip may include a balloon that when inserted into a blood vessel of a target organ of a subject and inflated, anchors the section in the blood vessel near a biopsy site in the target organ.

The second elongated tube (e.g., guide catheter <NUM>) may enclose a second lumen with a second proximal end and a second distal end comprising a beveled distal exit of the second lumen, which is positioned at the biopsy site of the target organ when the first elongated tube is anchored in the blood vessel by the inflated balloon, where a predefined length of the first and the second elongated tubes are longitudinally attached to one another such that the beveled distal exit is positioned at a proximal end of the section of the first elongated tube.

The flexible biopsy needle may be attached to a distal end of a wire for insertion into the second lumen of the second elongated tube for navigation to the biopsy site, wherein the flexible biopsy needle is configured to exit the beveled distal exit of the second lumen for penetration into tissue of the target organ at the biopsy site at a predefined angle between a longitudinal axis of the section of the first elongated tube and a longitudinal axis of the flexible biopsy needle, and to acquire a biopsy sample of the target organ at the biopsy site.

In some embodiments of the present invention, the first and the second elongated tubes may be formed from extruded adjacent tubes. They may include multiple lumens, or any combination thereof.

In some embodiments of the present invention, the first elongated tube may include a multi-lumen tube with a <NUM>-lumen configuration: one lumen for guide wire and the other lumen to inflate balloon at the distal tip. The second elongated tube may be a single lumen. Both first and second elongated tubes may be formed by extrusion one lumen adjacent to the other. Additionally and/or optionally, the second elongated tube may be coextruded.

In some embodiments of the present invention, the second elongated tube may include a tougher inner layer so as to prevent the flexible biopsy needle from penetrating or damaging (e.g., such that debris is generated) the walls when navigating through bends from the peripheral veins to the hepatic veins. The tough inner layer may also include a metal coil.

In some embodiments of the present invention, the first and second elongated tubes may be held together using a heat shrink tube.

In some embodiments of the present invention, the second elongation tube may include a rigid contoured section <NUM> that may rest on the balloon such that when the balloon is inflated, the balloon may lift rigid contoured section <NUM> of the second elongation tube. This effect increases angle ϕ as shown in <FIG> so as to better allow the biopsy needle to face the wall of the hepatic vein when fired into the liver tissue. This effect may also increase the likelihood of a successful biopsy, since the biopsy needle is more likely to exit hepatic vein and enter into the liver tissue. Unlike the transjugular approach, there is no stiff metal tubing to permit rotation such that biopsy needle will be directed into the liver tissue. The effect may also prevent the biopsy needle piercing the balloon directly front of it.

In some embodiments of the present invention, the flexible biopsy needle may include a Tru-cut biopsy needle.

In some embodiments of the present invention, the first elongated tube and the second elongated tube may respectively include a balloon catheter and a guide catheter.

In some embodiments of the present invention, the target organ may include a liver.

In some embodiments of the present invention, the blood vessel may include a hepatic vein of the liver.

In some embodiments of the present invention, the biopsy device may include a locking mechanism coupled to the second proximal end for fixing the position of the flexible biopsy needle at the distal end of the wire in the second lumen.

In some embodiments of the present invention, components of the locking mechanism are selected from the group consisting of a Tuohy Borst adapter, a luer lock, and a compressible clamp.

In some embodiments of the present invention, the flexible biopsy needle may include a cutting cannula and a stylet.

In some embodiments of the present invention, the flexible biopsy needle may include flattened band and an alignment notch for maintaining an alignment of the cutting cannula and the stylet.

In some embodiments of the present invention, the first elongated tube is more flexible the second elongated tube. The term "more flexible" used in the context herein means that the first elongated tube (e.g., balloon catheter <NUM>) may be more pliant than the second elongated tube (e.g., guide catheter <NUM>). The first elongated tube may be capable of being flexed and/or bent more than the second elongated tube. In some embodiments, the first elongated tube may be formed from a first material more pliant than a second material forming the second elongated tube. In other embodiments, the geometries of the first elongated tube and geometries of the second elongated tube may cause the first elongated tube to be more pliant or bendable relative to the second elongated tube.

In some embodiments of the present invention, the biopsy device may include an outer tube with the predefined length into which the first elongated tube and the second elongated tube are inserted so as to longitudinally attach the first elongated tube and the second elongated tube to one another.

In some embodiments of the present invention, the diameter of the inflated balloon may be larger than the diameter of the blood vessel.

In some embodiments of the present invention, the diameter of the inflated balloon may be no larger than <NUM>% of the diameter of the blood vessel.

In some embodiments of the present invention, the predefined angle is in the range of <NUM>-<NUM> degrees.

In some embodiments of the present invention, the biopsy device may include a connecting tube for insertion into the second lumen for guiding the flexible biopsy needle at the distal end of the wire to the biopsy site.

In some embodiments of the present invention, the flexible biopsy needle may include a stylet joined to a stylet wire in an end-to-end joint.

In some embodiments of the present invention, the flexible biopsy needle may include a hollow stylet and a stylet wire inserted into an overlapping joint.

In some embodiments of the present invention, the flexible biopsy needle may include an inner stylet and outer stylet with a cutting edge arranged in a concentric configuration.

In some embodiments of the present invention, the flexible biopsy needle may be configured to acquire the biopsy sample by rotating the outer stylet with the cutting edge relative to the inner stylet when the flexible biopsy needle is within the tissue of the target organ.

In some embodiments of the present invention, the flexible biopsy needle may be configured to encapsulate the acquired biopsy sample in a specimen notch when the outer stylet remains in a rotated position substantially opposite to the inner stylet.

In some embodiments of the present invention, the biopsy device may include a rigid contoured section coupled to the distal end of the second elongated tube for increasing the predefined angle when the balloon is inflated.

In some embodiments of the present invention, the balloon may include a distal balloon and a proximal balloon, which are inflatable separately or together in the blood vessel.

In some embodiments of the present invention, the second elongated tube may be coupled to a pressure transducer for measuring a hepatic venous pressure gradient (HVPG) by processing a signal from the pressure transducer in a signal processing unit.

In some non-claimed examples, a method for acquiring a biopsy sample of a target organ of a subject using a balloon-anchored biopsy device may include percutaneously inserting a biopsy device into a vein of a limb of a subject. The biopsy device may include a first elongated tube, a second elongated tube, and a flexible biopsy needle.

The first elongated tube may enclose a first lumen with a first proximal end and a distal tip, wherein a section of the first elongated tube near the distal tip may include a balloon that when inserted into a blood vessel of a target organ of a subject and inflated, anchors the section in the blood vessel near a biopsy site in the target organ.

The second elongated tube may enclose a second lumen with a second proximal end and a second distal end may include a beveled distal exit of the second lumen, which is positioned at the biopsy site of the target organ when the first elongated tube is anchored in the blood vessel by the inflated balloon, wherein a predefined length of the first and the second elongated tubes are longitudinally attached to one another such that the beveled distal exit is positioned at a proximal end of the section of the first elongated tube.

The flexible biopsy needle may be attached to a distal end of a wire for insertion into the second lumen of the second elongated tube for navigation to the biopsy site, wherein the flexible biopsy needle is configured to exit the beveled distal exit of the second lumen for penetration into tissue of the target organ at the biopsy site at a predefined angle between a longitudinal axis of the section of the first elongated tube and a longitudinal axis of the flexible biopsy needle.

The method for acquiring the biopsy sample may further include the distal tip being navigated from the vein through a vascular system of the subject and into the blood vessel of the target organ near the biopsy site. The balloon may be inflated in the blood vessel. The flexible biopsy needle may be pushed into the tissue of the target organ at the biopsy site at the predefined angle. A biopsy sample of the target organ at the biopsy site may be acquired using the flexible biopsy needle. The wire may be withdrawn from the second lumen so as to retrieve the acquired biopsy sample.

In some examples, the limb may include an arm of the subject and the vein may include a cephalic vein of the arm.

In some examples, the limb may include a leg of the subject and the vein may include a femoral vein of the leg.

In some examples, percutaneously inserting the biopsy device into the vein of the limb of the subject may include inserting the biopsy device through a lumen of a sheath in the vein.

In some examples, the balloon may include a distal balloon and a proximal balloon, and the method may include inflating the balloon comprises inflating the distal balloon and the proximal balloon separately or together in the blood vessel.

In some examples, the second elongated tube may be coupled to a pressure transducer, and the method may include measuring a hepatic venous pressure gradient (HVPG) by processing a signal from the pressure transducer.

Claim 1:
A balloon-anchored, biopsy device (<NUM>) for acquiring a biopsy sample of a target organ in a subject (<NUM>), the biopsy device comprising:
a first elongated tube enclosing a first lumen (<NUM>) with a first proximal end and a distal tip, wherein a section of the first elongated tube near the distal tip comprises a balloon (<NUM>) that when inserted into a blood vessel of a target organ of a subject and inflated, anchors the section in the blood vessel near a biopsy site in the target organ;
a second elongated tube enclosing a second lumen (<NUM>) with a second proximal end and a second distal end comprising a beveled distal exit (<NUM>) of the second lumen, which is positioned at the biopsy site of the target organ when the first elongated tube is anchored in the blood vessel by the balloon which is inflated, wherein a predefined length of the first and the second elongated tubes are longitudinally attached to one another such that the beveled distal exit (<NUM>) is positioned at a proximal end of the section of the first elongated tube; and
a flexible biopsy needle (<NUM>) attached to a distal end of a wire for insertion into the second lumen of the second elongated tube for navigation to the biopsy site, wherein the flexible biopsy needle (<NUM>) is configured to exit the beveled distal exit (<NUM>) of the second lumen for penetration into tissue of the target organ at the biopsy site at a predefined angle between longitudinal axis of the section of the first elongated tube and longitudinal axis of the flexible biopsy needle (<NUM>), and to acquire a biopsy sample of the target organ at the biopsy site; and
characterized in that the first elongated tube is more flexible than the second elongated tube.