US20150320406A1

Movatterモバイル変換

Info

Publication number: US20150320406A1
Application number: US14/803,312
Authority: US
Inventors: Amrita SETHI
Original assignee: Columbia University in the City of New York
Current assignee: Columbia University in the City of New York
Priority date: 2012-01-31
Filing date: 2015-07-20
Publication date: 2015-11-12
Also published as: WO2013116529A1; US20140336528A1; US9113857B2

Abstract

A sampling catheter encloses a sampling brush which can be selectively extended and retracted from and into the catheter assembly to allow insertion and movement of the catheter while presenting a smooth surface to the body lumen. The selective extension and retraction of the brush allows it to be withdrawn while limiting contamination by contact with tissue outside of the sampled region. The catheter may simultaneously or separately house a cutting tool for slice sampling tissue.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a division of U.S. application Ser. No. 14/341,978, filed Jul. 28, 2014, which is a continuation of International Application No. PCT/US13/24160, filed Jan. 31, 2013, which claims the benefit of U.S. Provisional Application No. 61/593,295, filed Jan. 31, 2012, all of which are hereby incorporated by reference herein in their entireties.

BACKGROUND

Diagnostic sampling catheters are used in the diagnosis of illnesses or for other purposes in which a microbiological sample from a site within a living animal is desired. The microbiological sample, in some catheters, may use a brush to scrape a sampling site to remove a sample of the material or microorganisms at the sampling site. Slicing-type biopsy devices are also known.

SUMMARY

Objects and advantages of embodiments of the disclosed subject matter will become apparent from the following description when considered in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments will hereinafter be described in detail below with reference to the accompanying drawings, wherein like reference numerals represent like elements. The accompanying drawings have not necessarily been drawn to scale. Where applicable, some features may not be illustrated to assist in the description of underlying features.

FIG. 1 shows a catheter, which is a hollow cannula or sheath with ports at the end which, in embodiments, serve triple duty as cutting devices, openings for bristles, and the aspiration ports, according to embodiments of the disclosed subject matter.

FIG. 2 shows an inner sheath that fits in the hollow cannula ofFIG. 1 and has a cutting tool at its end, according to embodiments of the disclosed subject matter.

FIG. 3 shows a shaft with a brush it its end whose bristles may be selectively extended through the ports at the end of the cannula ofFIG. 1, according to embodiments of the disclosed subject matter.

FIG. 4 shows the elements illustrated inFIGS. 1-3 assembled with the brush bristles in an extended but withdrawn configuration, according to embodiments of the disclosed subject matter.

FIG. 5 shows the assembly ofFIG. 4 with the brush bristles fully extended, according to embodiments of the disclosed subject matter.

FIG. 6 shows the assembly ofFIGS. 4 and 5 with the brush in a retracted configuration to permit cutting of tissue samples, according to embodiments of the disclosed subject matter.

FIG. 7 shows the elements illustrated inFIGS. 1 and 3 assembled with the brush bristles in an extended but withdrawn configuration, according to embodiments of the disclosed subject matter.

FIG. 8 shows the assembly ofFIG. 7 with the brush bristles fully extended, according to embodiments of the disclosed subject matter.

FIG. 9 shows the assembly ofFIGS. 7 and 8 with the brush retracted, according to embodiments of the disclosed subject matter.

FIG. 10 shows the elements illustrated inFIGS. 1 and 2 assembled, with the openings of the cutting tool being out of alignment with the ports of the outer sheath, according to embodiments of the disclosed subject matter.

FIG. 11 shows the elements illustrated inFIGS. 1 and 2 assembled, with the openings of the cutting tool being in alignment with the ports of the outer sheath, according to embodiments of the disclosed subject matter.

FIG. 12 shows the elements illustrated inFIGS. 1 and 2 assembled with the cutting tool retracted according to embodiments of the disclosed subject matter.

FIGS. 13A and 13B show features of embodiments which allow a guide wire to be fed through a separate opening from a main lumen of an outer sheath, according to embodiments of the disclosed subject matter.

FIG. 14A shows a section of a catheter with bristles of a brush extended, according to embodiments of the disclosed subject matter.

FIG. 14B shows a section of a catheter with the bristles of a brush partially retracted by rotation of the brush, according to embodiments of the disclosed subject matter.

FIG. 14C shows a section of a catheter with the bristles of a brush fully retracted and a cutting tool rotated relative to the outer sheath, according to embodiments of the disclosed subject matter.

FIG. 15 shows, in section, a brush with a single tuft of bristles and a single opening in a catheter as an alternative to the multiple tuft and opening embodiments, according to embodiments of the disclosed subject matter, the single opening configuration being a variant of all the embodiments disclosed herein except for those lacking a brush.

FIGS. 16A to 16C describe embodiments in which brush bristles are aligned with a catheter axis and bent into a radial alignment at their tips when they will be used for brushing, according to embodiments of the disclosed subject matter.

FIGS. 17A through 17H are for describing embodiments in which a cutting tool carries brush bristles and transitions between brushing and cutting configurations, according to embodiments of the disclosed subject matter.

FIGS. 18A through 18D show, along with related features, embodiments in which a balloon is used to change the stiffness properties of portions of a brush catheter, according to embodiments of the disclosed subject matter.

FIGS. 19A through 19E show, along with related features, a brush catheter arrangement for brushing entrance or branching regions of a lumen, according to embodiments of the disclosed subject matter.

FIGS. 20A through 20E show, along with related features, a combined cutter and brushing tool, according to embodiments of the disclosed subject matter.

FIGS. 21A through 21E show, along with related features, a cutting tool and a brush that slides over it which compresses the cutting tool, according to embodiments of the disclosed subject matter.

DETAILED DESCRIPTION

Referring to the figures, the embodiments include a wire-guided, endoscopic, tapered catheter that contains a brush for obtaining cytology samples, as well as a moveable sheath system that provides at least one or more of the following functions:

- 1. Penetration of body lumens and selective positioning of a distal end with guidance through curved passages;
- 2. Shaving and/or entrapment of tissue samples under vacuum with closure by the sheath of a large exposure opening in the catheter;
- 3. Aspiration of samples through distal ports under vacuum;
- 4. Brush sampling of cells and/or tissue;
- 5. Scraping or disruption of tissue using brush bristles or cutting elements;
- 6. Selective projection and withdrawal of brush bristles;
- 7. Selective projection and withdrawal of brush bristles through the same openings as used for aspiration and/or cutting of tissue samples;
- 8. Capture of samples and retrieval thereof; and
- 9. Isolation of samples to prevention of cross-contamination of, or by, parts of the body.

Referring toFIGS. 1,2, and3, a catheter outer sheath orcannula104 houses aninner sheath108, which houses ashaft116. Theouter sheath104 has one or moredistal ports106. The distal ports may have cutting edges to facilitate cutting as discussed below. Thedistal ports106 are in flow communication with aproximal aspiration port102 to which a vacuum may be selectively applied to draw tissue into thedistal ports106. Theinner sheath108 has acutting tool110 with one ormore openings111 at least one of which may carry one or

more cutting edges

103,112. Theshaft116 carries, at a distal end thereof, a brush whose bristles may be extended throughdistal ports106 and, if inserted simultaneously, theopenings111. The bristles may also be withdrawn from the openings selectively by suitable positioning of theshaft116 relative to the outer104 sheath and if present theinner sheath108.

The outer and

inner sheaths

104 and108 as well as theshaft116 may be of monolithic or composite construction which may include plastic and/or metal or other suitable materials or combinations thereof according to known materials and structure in the field of medical catheter design. In addition, the outer sheath may have followers for a wire guide (115 inFIGS. 4-12) or may be of an articulating type. Theshaft116 may be hollow or solid. Thebrush118 may be of nylon bristles or other material, including metal. The bristles may be fastened to theshaft116 by means of clips, by an adhesive or potting compound, or by forming a molded part that includes the bristles which fits over the end of theshaft116.

The catheter may include a variety of functional components to allow it to be articulated and or steered as required. The proximal end may be fitted with controls to permit a surgeon to steer the catheter. These components are known in the art and include, for example, articulation control and one or more wires extending along the catheter. Examples of prior art devices with suitable mechanisms include biopsy sampling devices, endoscopes, laparoscopic instruments, etc. In wire guide embodiments push or pull forces on one or more wires extending along the catheter can curve the catheter to steer the distal end by deflecting it at angles selected by the displacement of the wires. Forces may be applied in other ways, for example by shape memory materials and selective heating, linear motors, artificial muscles that are activated by embedded electrical final control signals, hydraulic bladders, and other devices and methods.

FIGS. 4,5, and6 show a cannula assembled from the elements ofFIGS. 1,2, and3, namely, the catheterouter sheath104 houses theinner sheath108 which houses theshaft116.FIGS. 7,8, and9 show another embodiment in which theshaft116 is housed only by theouter sheath104.FIGS. 10,11, and12 show another embodiment in which only theinner sheath116 is housed by theout sheath104 and used for cutting with aspiration and suction. In addition to illustrating alternative embodiments,FIGS. 7,8, and9 andFIGS. 10,11, and12 illustrate the functions of the catheterouter sheath104 withports106, theinner sheath108 withopenings111 and cutting

edges

103,112 and theshaft116 with abrush118. In embodiments, thecutting edge112 may be in the position indicated at103 to allow tissue to be sliced by moving thecutting tool110 in the axial direction (toward and away from the distal end along the longitudinal axis of the outer sheath104). In this way the cutting can be performed by torqueing the inner sheath, drawing, and/or pushing it. Note that cutting

edges

103 or112 can be positioned on the opposite sides of theopenings111 or on both sides. Also the number ofopenings111 and the number of cutting edges in each may be varied.

Referring now toFIG. 4, a vacuum may be applied to theproximal aspiration port102 to generate a vacuum at thedistal ports106 located at the distal end of theouter sheath104. Thecatheter100, which contains thebrush118, can be inserted into a body lumen or stricture which is facilitated by a tapered contour ofdistal end130 of theouter sheath104. Rather than advancing thebrush118 out of the catheter, as in prior art devices, the inner sheath108 (shown inFIG. 2) is withdrawn (as illustrated inFIGS. 7,8, and9), retracted partially (to the position shown inFIG. 12) or rotated as shown inFIG. 5 to alignopenings111 withdistal ports106 in order to allow the brush bristles to emerge from within thecatheter100.

InFIG. 5,openings111 in theinner sheath108 are aligned withaspiration ports106 in theouter sheath104 to expose the bristles ofbrush118. In this configuration, brushing may be performed with a forward and backward motion of thecatheter100. In alternative embodiments, theopenings111 and theports106 may be configured to permit thebrush118 to be moved back and forth or rotated reciprocally to generate a controlled disruption of the surface of the body lumen into which thecatheter100 is inserted. Thecatheter100 may also be rotated as a whole to disrupt the lumen surface. Thecatheter100 may be stabilized in position by controlling the proximal portion of thecatheter100.

InFIG. 6, theinner sheath108 may be translated axially or rotated across thedistal ports106 which results in “shaving” off of tissue from the duct into the catheter. In addition, suction may be applied via theproximal aspiration port102 to generate a suction at thedistal ports106 to draw tissue into thecatheter104 as the sheath is advanced or rotated across thedistal ports106. This may be done after the brush has been used to disrupt the tissue to be sampled or at any other desired time. Suction may also be applied while disrupting the surface with thebrush118 to suck liquid and scraped cells from the lumen surface.

Referring momentarily also toFIG. 1, in the present and further embodiments an outer sheath (also may be referred to as a housing of the catheter), asouter sheath104, encloses elements that permit a brush to be presented outside an outer radius R from an axis of the sheath, such asaxis109. It will be evident that this description applies to further embodiment described hereinbelow as well as the present embodiment of a catheter assembly100 (e.g., as shown inFIG. 4). The outer radius R may be uniform along the length of the catheter housing or may vary along the length. The distal end of the catheter housing (e.g., outer sheath104) may have a constant radius R and may taper for a final interval of the length of the catheter housing. The bristles may be presented from the distal end of the catheter such that at least some of the bristle tips are positioned at a radial distance from the axis that is greater than the outer radius of the catheter (i.e., the outer radius of the outer sheath or catheter housing). Some bristles may remain inside the outer sheath, for example, bent, and some may be shorter than others.

In method embodiments, the catheter100 (FIGS. 4,5,6),200 (FIG. 7,8,9), or300 (FIGS. 10,11,12) can be used to obtain tissue from pancreaticobillary strictures as well as intralumenal lesions within the GI tract via an endoscope. Brush cytology samples are used in Endoscopic Retrograde Cholangiopancreatoscopy (ERCP) to help diagnosis strictures as a first line method of obtaining tissue. The catheter is inserted into the working channel of a duodenoscope during ERCP over a wire, into the bile duct. It is advanced until it traverses the area of interest such as a stricture. Radiopaque markers may indicate the location of the catheter. No additional procedures or technology are required to use this device which makes it available to all endoscopists and those performing ERCP.

The embodiments include one or more of the following features: 1) brush remains within catheter and wire guided, 2) catheter serves as dilator, 3) mechanism for tissue to be “shaved” into catheter, functioning as a biopsy device, 4) potentially rotatable brush, 5) opening for introduction of additional devices such as biopsy forceps. The embodiments may be easier to insert due to improved stiffness and continual wire and catheter guidance, allow for improved accuracy of targeting the area of interest, result in increased amount of tissue to be acquired, provide dilation if needed for correct positioning in the stricture, allows for stability of the brush within the stricture such as in distal bile duct strictures, and allow for introduction of additional sampling tools such as small-caliber biopsy forceps.

Other applications for this invention include wire-guided procedures such as interventional radiologists, pulmonologists, and urologists. To facilitate wire-guided procedures,

catheters

100,200, and/or300 may be provided with a channel for aguide wire115.

As discussed, thecatheter100 may be used for increased tissue yield in the sampling of pancreaticobiliary strictures. Housed within thecatheter100 are devices that provide for both brush cytology as well as shaving biopsy tissue. In method embodiments, both types of samples can be obtained in a single insertion maneuver. The configuration allows for dilation of the stricture and maintenance of stability during tissue acquisition. With increased tissue in the sample, the diagnostic accuracy of cytology specimens can be improved.

In the embodiments, various catheters are described herein. The catheter of any embodiment may be no more than 20 mm in diameter. In further embodiments, the catheter of any embodiment may be no more than 15 mm in diameter. In still further embodiments the catheter of any embodiment may be no more than 10 mm in diameter. In still further embodiments, the catheter may be no more than 7 mm in diameter. In still further embodiments, the catheter of any embodiment may be no more than 5 mm in diameter.

In any of these embodiments, the catheter may be configured to be positioned and actuated by an endoscope or other larger instrument that is insertable in the body of an animal Any embodiments may be implemented as a biliary sampling catheter device. The term sampling may apply to material that is retrieved by the brush bristles or by the slicing feature of the embodiments. The size, proportion, flexibility, and other dimensional aspects may be selected to facilitate insertion in a bile duct (possibly including branching portions thereof). The biliary sampling catheter embodiments may be extended from an endoscope or other support instrument, for example inserted in the intestine of a person. The bristles of some of the embodiments extend from the end of the catheter in a radial direction but remain within the longitudinal extent of the catheter, which distinguishes from embodiments or devices which extend a brush past the distal terminal end of the catheter, as in prior art catheter devices.

The tissue diagnosis of pancreaticobiliary strictures is of critical importance in allowing for appropriate therapy such as chemotherapy or surgery. Current sampling methods during ERCP include brush cytology, forceps biopsy, and fine needle aspiration. Sensitivities of brush cytology specimens are 20-57%. Combining brush specimens and forceps biopsy specimens can increase sensitivity to 55%, however, this requires multiple devices. Directly visualized biopsies, which is another method of sampling, requires use of an additional system that can be costly and requires advanced training, thereby limiting its use.

Another benefit of the

embodiments

100 and200 is the support of theshaft116 by theouter sheath104. In some brush cytology devices, the brush is pushed through the end of an endoscope or other catheter device supported on its shaft. The support and controllability of the brush is poor in such systems due to the difficulty of advancing the catheter through the working channel of the endoscope (or catheter) and bile duct. Resistance can be encountered advancing the brush out of the catheter into the stricture. At this point it is no longer wire guided and has tolerance for a limited pushing force. The lack of guidance can also result in the brush veering into another direction and missing the target tissue.

A further function produced by the present apparatus is that the catheter may be positioned once and either brush or cutting devices may be selected and deployed at precisely the same location without having to reacquire the position. This avoids instability or failure to reproduce a position when brushing strictures at a target position as the catheter remains outside the duct. In current brush systems, the brush is the only way to obtain tissue. Systems that allow for multi-modality sampling require insertion of separate devices into the catheter, adding to time and cost. This also results in additional specimens for processing, increasing cost.

The disclosed device and method may improve accuracy of positioning of the brush, allow for multi-modality sampling (brushing and biopsy) with one device during the same maneuver, and increase tissue yield.

According to embodiments, the disclosed subject matter includes a wire-guided catheter with a large hole or opening (i.e., within a circumferential surface of the catheter), which allows for contact by a brush held within the catheter. In a variation of the embodiments, the brush sheath itself may also be wire guided and may lie within the catheter. This catheter may be made of stiffer plastic material than currently available brushes, which may assist in advancing the brush through the endoscope. The tip of the catheter may be tapered which allows for some dilation of tight strictures in order for brushing to occur. Fluoroscopic markers may be visible on the catheter to indicate the exact location of the distal port(s)106.

Theinner sheath108 may be of tubular construction or may be a panel that can be advanced or rotated across the catheter port or ports. Thecutting tool110 at the end of the inner sheath may be used for shaving tissue that projects into thedistal ports106 as a result of the application of a vacuum or passively due to insertion into a narrow lumen portion. The amount of tissue projecting into the “opening” can be increased by applying suction at an aspiration port at the distal end of the catheter. The sheath may be a part of the catheter forming a unitary device.

Thebrush118 may remain within the catheter at all times as opposed to being projected outside of the catheter as with other cytology brush devices. The bristles extend out of thedistal ports106 of theouter catheter104 when theinner sheath108 is withdrawn or rotated, thus exposing the stricture to the brush. This technique may be used to ensure that the brush is targeting the area of interest at all times. The brush use is facilitated given that the brush alone does not have to be pushed through the tissue, but rather can move freely within the catheter. In embodiments, the shaft may be constructed to permit torque to be transferred along its length from a manipulation end (proximal end) of the catheter to thebrush118. By maintaining the brush within the catheter, there may be greater retention of the tissue acquired.

Theguide wire115 can pass through a central opening of the outer sheath with a distal opening at an end thereof or it can pass through a separate opening of the outer sheath that is isolated from the inner lumen of the outer sheath. In the latter case, the outer sheath can convey a vacuum applied at the proximal port to the distal port(s). Note that self-sealing openings can be provided to allow the proximal ends ofshaft116 to pass through theinner sheath108 while providing a vacuum seal. Similarly a seal may be provided for theinner sheath108 to pass through theouter sheath104 while permitting a vacuum to be sustained within the outer sheath. In alternative embodiments, the vacuum may be applied only to theinner sheath108 and thecutting tool110 may form a close fit to the inner lumen of the outer sheath thereby permitting a vacuum to be conveyed to theopenings111 in thecutting tool110. In this case the brush may remain within thecutting tool110 and be selectively permitted to extend out of theopenings111 when theopenings111 are rotated so that they coincide withdistal ports106.

In alternative embodiments, theouter sheath104 may be guided into a target body structure and theinner sheath108 with theshaft118 inserted afterward. Aguide wire115 may be inserted and theouter sheath104 guided by the insertedguide wire115. Then theguide wire115 may be withdrawn and theinner sheath108 with theshaft118 inserted. In alternative embodiments, the

entire catheter

100,200, or300 may be guided by theguide wire115 since spaces may exist to accommodate theguide wire115. It should clear by inspection that a variety of channels may remain with both theinner sheath108 and theshaft118 inserted in theouter sheath104.

Referring toFIG. 13A, an embodiment of anouter sheath172 is shown in cross-section. Theouter sheath172 may be used in place ofouter sheath104 in embodiments.Sheath174 has alumen174, a thinouter wall portion172, and a thickerouter wall portion177, which is thick enough to permit anadditional lumen176 to be provided for passage of aguide wire115. The thickenedportion177 may be provided continuously along the length of the catheter to permit it to be manufactured as an extrusion or may be provided at intervals along the length of asheath162 as indicated at166 inFIG. 13B. Aclosed end164 may be provided on the catheter. The guide wire is indicated at168.

At the proximal end of the

catheter embodiments

100,200, or300 may be any type of control or primary support structure, for example, an endoscope. Various user interface configurations are known for axially displacing or applying torque to elongate structures such asshaft116 and

sheaths

108 and104.

Referring toFIGS. 14A,14B, and14C, note in embodiments, the extension ofbristles310 of thebrush110 past thedistal ports106 in the distal end of theouter sheath104 can be facilitated by rotating theshaft116 back and forth to help the bristles “find” a way out of theopenings112 in thecutting tool110 and thedistal ports106 in theouter sheath104. Retraction of thebristles310 can be facilitated by rotating against anon-cutting edge312 of the openings in thecutting tool110 as illustrated.FIG. 14A shows thebristles310 of abrush118 extended.FIG. 14B shows thebristles310 of abrush118 partially retracted by rotation of the brush.FIG. 14C shows thebristles310 of abrush118 fully retracted and the cutting tool rotated relative to the outer sheath. Retraction may be achieved in embodiments by moving the brush axially, in addition to or instead of rotating it, to accomplish both extension and retraction of the bristles.

FIG. 15 shows, in section, a brush with asingle tuft311 of bristles and asingle opening340 in a catheter with anouter sheath104. Thecutting tool110 may or may not be present in alternative embodiments. A feature of thepresent shaft116 which supports thetuft311 of bristles is that it is hollow to provide alumen332 for passage of aguide wire115. This feature may be applied to any of the foregoing embodiments having a brush. Where theshaft116 has a lumen, a seal may be provided which isolates thelumen332 from theannular space345 between theshaft116 and theouter sheath104 allowing a vacuum to be applied to theannular space345 and thereby to suck particles or liquid into theopening340. The configurations ofFIG. 15 are alternatives to the multiple tuft/multiple opening embodiments such as described elsewhere. The single opening configuration being a variant of all the embodiments disclosed herein except for those lacking a brush. The features ofFIG. 15 such as thelumen332 may be applied to other embodiments including those with multiple tufts and multiple openings in the distal end of the catheter.

FIGS. 16A to 16C show a brush catheter with anouter sheath402 and aninner sheath404. Ashaft410 carries axially aligned bristles406. Thebristles406 lie in achannel407 that curves toward the radial direction such that when theshaft410 is advanced relative to theinner sheath404, thebristles406 bend in the radial direction and extend radially through anopening409 in theouter sheath402. The

sheaths

402,404, and/or410 may be wire-guided and aguide wire412 is shown inFIG. 16A. Alternative embodiments may be non-wire guided and this feature is illustrated inFIG. 16B.FIG. 16B shows thebristles406 bent and extended radially. In the latter configuration, theinner sheath404 may be moved axially back and forth to capture material from a body lumen. Thus, room to accommodate this motion may be provided in the shape and or size of thespace403 within theouter sheath402.FIG. 16C shows an end view of theshaft410 with thebristles406 extending toward the viewer. Ahole416 accommodates aguide wire412. It will be observed that thebristles406 may be extended as described without being inhibited by aguide wire412, if present.

FIGS. 17A through 17D show acatheter400 with anouter sheath480 that carries acutting tool487 with brush bristles442 that extend fromresilient members440 attached atrespective points454 to thecutting tool486 which is generally cylindrical in shape. The cutting tool486 (as well as cuttingtool487 discussed below) is supported on the end of asheath477 which allows it to be moved back and forth axially as well as moved in a single cutting direction by forces applied from the proximal end by an operator. Thecutting tool486 hasmultiple openings493 each having acutting edge492, which is preferably razor sharp. In embodiments, thecutting edge492 may be an edge of a separate element blade portion of metal that is attached or molded into a cutting tool of polymer material to make the cutting tool more flexible to facilitate navigation in tortuous body lumens. Theouter sheath480 hasopenings484 that allow thebristles442 to make contact with a body lumen into which thecatheter400 is inserted. Theresilient members440 urge the brush bristles442 outwardly radially when aballoon448 is expanded from the configuration ofFIG. 17A to that ofFIG. 17B.FIGS. 17A and 17B show sections at a point in the middle of thecutting tool486. The assembly may be wire guided, a guide wire being indicated at482.

As shown inFIG. 17H, theresilient members446 may be formed as leaf springs and may be defined, at least in part, by cutting the wall of thecutting tool486 or attached as separate elements, for example by laser cutting a high strength material such as nickel-titanium allow used in medical stents. As illustrated theresilient members446 are attached at the ends thereof at respective points indicated in the cross-section view at454 and inFIG. 17H. These may be laser cut from the walls of the cylinder making up thecutting tool486 which may be bent inward, for example as illustrated by the arrows inFIG. 17H. In embodiments, the cut out walls may be cut as interlacing fingers extending circumferentially from a line connecting twopoints454 that are separated axially to allow them to extend further from thepoints454 to provide a large enough radial dimension to reach toward theballoon448 and lever the brush bristles442 as illustrated inFIGS. 17A and 17B. In other embodiments, theresilient members446 may be made from separate elements that are attached by a hinging device on the inside of the body of the cylindrical cutting tool to achieve a similar effect. Still other alternatives are possible such as attaching the brushes directly to theballoon448 with an intervening spring and providingopen openings492 on the cutting tool to allow the brush bristles to extend beyond the walls of the body ofcylindrical cutting tool486. In this case the balloon may be star-shaped so that portions of it contact and press against solid parts of the cutting tool to brace it against the cutting tool.

Theballoon448 may be any type of expanding element suitable for the disclosed function. In the embodiment, theballoon448 may be carried on ashaft450 having ahole452 for a guide wire. As is known balloon catheter designs, the balloon may be fed from its proximal end by a pumped fluid using known appliances and systems, for example endoscopic instruments as known in the medical field.

In the embodiment ofFIG. 17G, the portion of theresilient members446 that support the brush bristles442 has been cut intofingers470 with narrowednecks473. This configuration permits thefingers470 to feather as illustrated byFIGS. 17E and 17F when rubbed (by moving the cutting tool in the axial direction—relative motion indicated by arrows488) against thewall474 of a body lumen. Here thebristles472 yield by bending while thefingers470 yield by pivoting (as shown inFIG. 17F) at the neck, which may be characterized as “feathering.” The combination of the bending of the short bristles and the feathering, as well as the radial compliance of thefingers470 makes thebristles472 yield more like longer brush bristles.

In the embodiments discussed with reference toFIGS. 17A through 17H, a vacuum may be applied at the proximal end of theouter sheath480 to draw tissue into theopenings484. The expanding element may be reduced in size, for example, theballoon448 may be deflated. The

bristles

442,472 are thus retracted from theopenings484. This allows the tissue of the body lumen to extend below the cutting edge to permit slicing. Thecutting edge492 of cutting

tool

486 or487 or any of the alternative embodiments may be moved in the proximal direction from a point distal of theopenings484 so as to slice the tissue from the body lumen. The openings in the outer sheaths of these embodiments facilitates the slicing by the edge of the window serving to support the tissue against the force of cutting.

The embodiments discussed above in which a cutting tool carries bristles (or in which a balloon carries but is braced thereagainst), thesingle sheath477 is used to apply forces to both the bristles and the cutting edge used for slicing. As a result, the configurations avoid the need to provide two sheaths or shafts, one to support the brush and the other to support the cutting edge of the cutting tool. This allows an improved balance between stiffness required for manipulating the brush from the proximal end (i.e., reduced axial compliance) and the need for the catheter assembly (e.g.,400) to be flexible in order to navigate tortuous body lumens.

Referring toFIG. 18A, anouter sheath502 hasopenings506 for slicing tissue of a body lumen. Aninner sheath514 supports acutting tool504 at its distal end. The cutting tool has acutting edge510 that may be used to slice tissue drawn into theopenings506 or forced thereinto from the outside. Anopening508 at theouter sheath502 distal end is configured to allow a brush to extend therethrough. One of the problems with prior art brush catheters that are extended through the distal of a sheath is that they are supported on flexible shafts that have too much compliance along their lengths to allow them to be manipulated from the proximal end of the catheter. In the present embodiment, this problem is mitigated by bracing theshaft518 that carries thebrush520 using aballoon519 which inflates to press against the interior of thesheath514 carrying thecutting tool504 as shown inFIG. 18B. Thecatheter510 may be guided by aguide wire522 passing through theshaft518. This arrangement allows thebrush520 to be manipulated from the proximal end via theinner sheath514 because displacements thereof may be transmitted with little compliance owing to the grip of theballoon519 on thesheath514. In a variation, thesegment505 of theshaft514 may have a higher rigidity than theshaft514 as a whole thereby reducing compliance between theshaft514 and thebrush520.FIGS. 18C and 18D show a variation of the present design in which anadditional balloon catheter501 with aballoon540 supported on ashaft542 is inserted within the shaft518 (as shown inFIG. 18D). In this case, the guide wire may pass through theshaft542. Theballoon540 may form a bridge of rigidity between the distal end of theinner sheath514 and the brush when required at a time thebrush520 is to be manipulated. Here both

balloon

519 and540 convey the forces applied to the proximal end of theshaft514 to thebrush520. This may permit the

shafts

542 and518 to be made more flexible thereby contributing to the flexibility of thecatheter500 as a whole, making navigation of tortuous channels easier. As will be seen theballoon540 may serve the same function as the balloon558 (SeeFIG. 19A et seq.) as described next.

FIG. 19A showscatheter550 with anouter sheath551 that encloses an inner sheath554 carrying abrush552 at its distal end. Aballoon catheter553 has ashaft556 extending through the inner sheath554 and movable such that its distal end can project through the end of the inner sheath554 distal of thebrush552. The relative movement is accomplished by manipulation of the proximal ends of the inner554 and outer551 sheaths and theshaft556 according to known principles for actuating surgical and diagnostic instruments.FIGS. 19B through 19E illustrate stages of use of thecatheter550. An endoscope projects thecatheter550 toward abody lumen580 after guiding theguide wire560 thereinto. The directing of a guide wire is not discussed because this practice is well supported in the prior art. As shown inFIG. 19B, theouter sheath551 may be extended to dilate the lumen and/or to support the positioning of theballoon558 which is extended along theguide wire560 into the lumen and positioned. Theouter sheath551 may be used for indicating position, for example if it carries indicators visible under fluoroscopy. As shown inFIG. 19C, theballoon558 is extended into thelumen580 from the inner554 sheath and projects beyond theouter sheath551 by applying traction force to theshaft556. Theballoon558 is then inflated as shown inFIG. 19B providing an anchor forshaft556. Then theinner sheath552 rides along theshaft556 to brush themouth552 of the body lumen as indicated inFIG. 19E. The configuration addresses the problem of brushing a region of a body where a lumen extends from a chamber or canal or in which a lumen branches. Without supporting the catheter in position the brush could not be assured of remaining at the mouth of the body lumen. It will be seen that the present configuration addresses this concern.

FIGS. 20A through 20C disclose features of an embodiment of a combined cutter and brushing tool. In the embodiment, acutting tool605 is encased inside anouter sheath620 in a manner similar to elsewhere described embodiments except that in this case, brush bristles are directly attached to short-radius portions606 of thecutting tool605 at a smaller radial distance from its axis than cuttingedges612 thereof. As explained, but avoiding separate elements, asingle shaft609 may be used thereby providing more overall stiffness for cutting and brushing than if separate shafts or sheaths were used for each. This improves the flexibility of the catheter (combination of the cutting tool, brush, and shafts/sheaths). As in prior embodiments,openings624 are provided in theouter sheath620. Thecutting tool605 hasopenings608 for the brush bristles which stem from theportions606. The short-radius portions606 may be formed from a generally cylindrical member as illustrated inFIG. 20D in whichopenings608 have been cut for the short-radius portions606 and the short-radius portions formed from the cuts by pushing inwardly toward the cylindrical axis thereby creating the smaller radial distance from the axis of thecutting tool605.Openings611 may also be cut for forming thecutting edge612 and providing access for a tissue portion from a body lumen to be sliced. Thebristles610 may be attached by any suitable means, including welding metal bristles, epoxy or other adhesive bonding, potting, etc. Advantages of the smaller radial distance is that the bristles may be longer as illustrated in the cross-section view ofFIG. 20B and also enabled to be pushed aside to allow for cutting as illustrated in the cross-section view ofFIG. 20C. Since theshaft609 can be stiffer than in a multiple shaft/sheath embodiment, as explained above, it may be formed to provide torque transmitted from the proximal end. Theshaft609, when rotated relative to theouter sheath620, bends the brush bristles610 aside and aligns theopenings611 of thecutting tool605 with theopenings612 of theouter sheath620 as illustrated inFIG. 20C. In this configuration, thecutting tool605 may be used to slice tissue by drawing it in a proximal direction within theouter sheath620 while maintaining the latter in position relative to the body lumen, as in other embodiments. The slicing may be done under a vacuum or if external pressure is sufficient to push tissue into position to be sliced, in the absence of a vacuum.

FIG. 20E illustrates another way to obtain a combinedcutting tool643 and brush in which thecutting edge645 is at one radial distance from the axis while the brush bristles647 are supported from the surface of theshaft642 or another radial distance that is smaller than that of thecutting edge645 so that they extend outwardly to function in a manner that is as described relative to the embodiment ofFIGS. 20A to 20C. Thecutting tool643 may be attached to theshaft642 directly. Anopening644 may be provided for a guide wire.Openings648 may be provided to allow tissue to be accessed by the cuttingedges645 as well asopenings641 through which thebristles647 extend. The embodiment ofFIG. 20E may be employed in the same manner as that ofFIGS. 20A to 20C and provides similar advantages.

FIGS. 21A through 21D show acutting tool657, supported on ashaft656, that is selectively squeezed within abrush664

bearing sheath

650 by sliding the latter over thecutting tool657 from the position shown inFIG. 21A to that shown inFIG. 21B. Thebristles664 may be attached to thesheath650 in any suitable manner. As shown in the cross-section view ofFIG. 21C, thesheath650 may haveinternal features662 to facilitate the squeezing of thecutting tool657 thereinto, for example sloping ridges that progressively cause a ring shapedportion659 at the top of the cutting tool657 (shown in cross section inFIG. 21E) into a foldedshape661 seen in the cross-section view ofFIG. 21D. Note thatFIG. 21D shows the cross-section of the arrangement ofFIG. 21B in the region of the brush bristles664.

In most of the embodiments, the number of cutting tool openings whose one or more edges has a cutting edge, is the same in number as a number of brush portions, however the numbers need not be the same. For example, in the embodiment ofFIG. 20A, the

openings

611 and608 may differ in number. Also the number of openings in the outer sheaths of the embodiments may be different in number from the openings in the cutting tools to form varied embodiments. Also the openings of the sheaths and cutting tool need not be symmetrically positioned or equally spaced therearound. They may also be diagonal, or offset in various ways to achieve similar functions as described herein.

In any of the above embodiments, the outer sheath, forexample sheath104, may be provided with fluoroscopy-revealed markers (fiducials) to facilitate positioning of the distal port. In any of the above embodiments, any inner sheath or shaft may be provided with fluoroscopy-revealed markers (fiducials) to facilitate positioning of a brush, a cutting tool (which may be combined with a brush in embodiments as described above), or a balloon effecter. In any of the embodiments, instead of using a vacuum to draw tissue into a sheath to slice it, if the outer sheath is large relative to a resting size of the body lumen into which it is extended, the pressure from the body may be sufficient to cause the tissue to extend into the outer sheath openings to be sliced.

The longitudinal members generally referred to herein as sheaths and shafts of the respective embodiments may be of any suitable configuration including metal, plastic, or combinations thereof. Their major lengths may be of one material while distal and/or proximal ends may be of a different material or composition of multiple materials in order to provide different properties such as flexibility, torque or compression or tensile compliance, etc. The terms shaft and sheath, in the present context, are not mutually exclusive terms as used herein. In the embodiments, either may have a lumen therethrough. The term shaft has been used where, in variations of the embodiment, a lumen may not be present, for example, an innermost longitudinal member in an assembly.

In any of the disclosed embodiments, tissue may bulge into at least one opening in a distal end of the catheter forming a protrusion to be sliced as described according to the various embodiments. In any of the disclosed embodiments, a majority of the bristles at the distal end of the catheter may be positioned proximal of the very distal end of the catheter such that the bristles receive mechanical support from the catheter itself, including the catheter outer sheath, according to embodiments.

In the embodiments, a brush and cutting tool may reside simultaneously in the catheter or may be removed and inserted at separate times, according to respective apparatus embodiments and/or methods of use. In embodiments, the cutting tool carries bristles and is selectively reconfigurable between a cutting configuration and a brushing configuration. In the cutting configuration, the bristles are radially retracted. In the brushing configuration, the bristles are radially extended.

It will be evident that in many of the embodiments, the cutting tool and brush are movable within the sheath such that they can switch places, whereby the cutting tool can be used for cutting tissue extending through one or more openings in the outer sheath (or the catheter) and the brush can be used for brushing a body lumen into which the catheter is inserted without fully removing either the brush or the cutting tool from the catheter.

In alternative embodiments, the brush bristles may be replaced by other types of collection devices, depending on the embodiment. For example, an expandable screen may be used for collection by a brushing motion and may be extended from the distal end of the outer sheath.

Note that in any of the embodiments, the outer sheath distal openings may be made longer than the brushes to permit the brushes to be moved axially back and forth in order to gather sample material. Alternatively, the brush or brushes may remain fixed with respect to the outer sheath and the entire outer sheath moved to brush the surface of the body lumen.

According to first embodiments, the disclosed subject matter includes a sampling device with an elongate outer sheath that simultaneously houses a brush and a cutting tool. The sheath is generally adapted for sterilization and insertion in a living person in a manner of surgical instruments. The assembly may form an catheter and delivered as a disposable in a sterile package. In this embodiment, the elongate outer sheath, the brush, and the cutting tool having distal and proximal ends with the brush and cutting tool each having a portion extending over substantially an entire length of the outer sheath. The brush and cutting tool are configured such that each can be manipulated at a respective proximal end thereof to permit the cutting tool to cut tissue samples at the distal outer sheath end and to permit the brush selectively to extend outside the outer sheath distal end and retreat back into the outer sheath.

According to second embodiments, the disclosed subject matter includes an elongate outer sheath with one or more distal ports at a distal end thereof. An inner sheath has one or more ports alignable with the distal ports. A brush is enclosed within the inner sheath. The inner sheath is movable relative to the outer sheath and brush to permit the bristles thereof to extend through the distal ports.

Any of the second embodiments may be modified, where possible, to form additional second embodiments in which the inner sheath is rotatable within the outer sheath. Any of the second embodiments may be modified, where possible, to form additional second embodiments in which the inner sheath is translatable within the outer sheath. Any of the second embodiments may be modified, where possible, to form additional second embodiments in which the inner or outer sheath has at least one cutting edge to permit tissue projecting into the ports to be sliced.

According to third embodiments, the disclosed subject matter includes a method of using the device of any above claim. The method includes inserting the outer sheath in a tissue and exposing the brush. The method further includes drawing the brush within the inner sheath by moving the inner sheath relative to the outer sheath and withdrawing the outer sheath. The method further includes harvesting cells on the brush.

Any of the third embodiments may be modified, where possible, to form additional third embodiments that include, after the brush is confined within the inner sheath, cutting tissue by moving the inner sheath relative to the outer sheath. Any of the third embodiments may be modified, where possible, to form additional third embodiments that include applying a vacuum to the outer sheath.

According to fourth embodiments, the disclosed subject matter includes a method of performing a biopsy including inserting a catheter in a body lumen and extending brush bristles radially from a distal end of the catheter, scraping the body lumen and withdrawing the bristles radially. The fourth embodiment methods include withdrawing the catheter and retrieving samples from the brush.

Any of the fourth embodiments may be modified, where possible, to form additional fourth embodiments that include applying a vacuum to a proximal end of the catheter and conveying the vacuum to the distal end while performing the scraping. Any of the fourth embodiments may be modified, where possible, to form additional fourth embodiments in which the scraping includes displacing the bristles of the brush and bristles of the brush are supported by the catheter when the catheter is displaced. Any of the fourth embodiments may be modified, where possible, to form additional fourth embodiments that include, the extending includes extending the bristles in opposing directions about an axis of the catheter. Any of the fourth embodiments may be modified, where possible, to form additional fourth embodiments in which the bristles extend through openings in the catheter. Any of the fourth embodiments may be modified, where possible, to form additional fourth embodiments in which the catheter contains a brush and a cutting tool and the method further includes drawing tissue of the lumen into the openings by applying a suction and cutting the tissue with the cutting tool without removing the brush from the catheter. Any of the fourth embodiments may be modified, where possible, to form additional fourth embodiments in which the body lumen is a pancreaticobiliary stricture. Any of the fourth embodiments may be modified, where possible, to form additional fourth embodiments in which a proximal portion of the catheter is supported by an endoscope. Any of the fourth embodiments may be modified, where possible, to form additional fourth embodiments that include inserting a steerable guide wire.

According to fifth embodiments, the disclosed subject matter includes a method of sampling tissue from a body lumen. The method includes inserting an endoscope in a body passage and passing a guide wire into a further body passage to which access is provided by a portion of the endoscope. The method includes guiding a catheter housing a brush to a location in the further body passage along the guide wire. The method includes positioning a distal portion of the catheter at a predefined location of the further body passage. The method includes extending bristles of the brush from the distal portion and disrupting a target surface of the further body passage with the bristles while the bristles are positioned at a longitudinal position of the distal portion and are thereby supported by the catheter without extending distally from it.

According to sixth embodiments, the disclosed subject matter includes a method of sampling tissue from a body lumen including inserting an endoscope in a body passage and passing a guide wire into a further body passage to which access is provided by a portion of the endoscope. The method includes guiding a catheter housing a cutting tool to a location in the further body passage along the guide wire. The method further includes positioning a distal portion of the catheter at a predefined location of the further body passage. The method further includes moving the cutting tool to remove a sample of the further body passage and recovering the sample.

Any of the sixth embodiments may be modified, where possible, to form additional sixth embodiments in which the moving the cutting tool includes displacing it rotationally. Any of the sixth embodiments may be modified, where possible, to form additional sixth embodiments in which the moving the cutting tool includes displacing it axially. Any of the sixth embodiments may be modified, where possible, to form additional sixth embodiments in which the distal portion has an opening that faces radially away from an axis of the catheter and the cutting tool has a cutting edge that can be moved across the opening. Any of the sixth embodiments may be modified, where possible, to form additional sixth embodiments that include withdrawing the cutting tool while maintaining a position of the distal portion in the further body passage. Any of the sixth embodiments may be modified, where possible, to form additional sixth embodiments that include advancing a brush in the catheter and using the brush to disrupt tissue in the further body passage. Any of the sixth embodiments may be modified, where possible, to form additional sixth embodiments that include generating a vacuum in the catheter while advancing the cutting tool. Any of the sixth embodiments may be modified, where possible, to form additional sixth embodiments in which the brush is coaxially aligned with the cutting tool. Any of the sixth embodiments may be modified, where possible, to form additional sixth embodiments in which the further body passage includes a pancreaticobiliary duct.

According to seventh embodiments, the disclosed subject matter includes a catheter that includes a catheter device having an outer sheath with a longitudinal aspect, generally cylindrical in shape, and presenting a smooth surface over an outer radius of the outer sheath. The catheter device is configured such that bristles may be selectively directed from the catheter device at a distal end thereof such that at least some bristle tips extend to a radius greater than the outer sheath outer radius. At least some of the bristles are positioned proximal of the very distal end of the outer sheath such that the bristles receive mechanical support from the catheter device outer sheath. The catheter device is configured such that the bristles may be selectively repositioned such that they are confined within the outer sheath outer radius. The catheter device outer sheath has at least one opening, the catheter device having a cutting tool movable within the outer sheath to move across at least a portion of the at least one opening. The catheter device outer sheath is sized to permit insertion in a human bile duct.

According to eighth embodiments, the disclosed subject matter includes a biliary sampling catheter with an outer sheath that carries bristles extendable in a radial direction from a distal end of the outer sheath within a longitudinal extent of the outer sheath. The outer sheath has at least one opening for with a cutting tool having a cutting edge that is movable across the at least one opening and adapted for cutting tissue samples of a body lumen. The bristles and the cutting tool may be moved by applying axial forces to a shaft within the outer sheath from a proximal end thereof.

According to ninth embodiments, the disclosed subject matter includes a brush catheter that includes a brush on the end of a shaft and an outer sheath encasing the brush and shaft to form a brush catheter assembly. The shaft is movable between a brushing position and an insertion position. The insertion position is such that the brush is entirely encased within the outer sheath such that the outer sheath presents a smooth outer surface for insertion in a body lumen. The brushing position is such that bristles of the brush extend through one or more openings in the outer sheath. In both the brushing and insertion positions, the brush remaining proximal of the very distal end of the outer sheath.

According to tenth embodiments, the disclosed subject matter includes a brush catheter that includes an outer sheath having brush and a distal opening through which the brush may be extended and an inner sheath or shaft contained within outer sheath. An expanding member is configured to selectively form a rigid bridge, or to increase a rigidity of a connection between, between the inner sheath or shaft and the brush. Any of the tenth embodiments may be modified, where possible, to form additional tenth embodiments in which the expanding member includes a balloon. Any of the tenth embodiments may be modified, where possible, to form additional tenth embodiments in which the expanding member is within the inner sheath or shaft.

According to eleventh embodiments, the disclosed subject matter includes a method of sampling cells. The method includes inserting a catheter in a body lumen and extending bristles of a brush radially from a distal end of the catheter such that the bristles are within an axial extent of the catheter. The method further includes moving the bristles relative to an outer sheath of the catheter to obtain sample material from the body lumen and moving the bristles into the outer sheath with sample material. The method further includes withdrawing the catheter and recovering the sample material.

According to twelfth embodiments, the disclosed subject matter includes devices according to any of the above non-method embodiments further including, if not specified, a guide wire, wherein the catheter is configured to follow the guide wire.

According to thirteenth embodiments, the disclosed subject matter includes a brush sampling device that includes an outer sheath having brush carried on an inner sheath, the outer sheath having a distal opening through which the brush may be extended using the inner sheath. A guide wire is inside the inner sheath and a balloon catheter is on the guide wire, the balloon catheter having a shaft with a lumen through which the guide wire passes. The balloon catheter shaft is inserted through the inner sheath to permit the brush to move therealong guided by the balloon catheter. The guide wire, shaft, and inner sheath are extendable through the distal opening.

According to fourteenth embodiments, the disclosed subject matter includes a method of using the thirteenth embodiments, the method including positioning the guide wire in the entrance of a body lumen portion and extending the balloon catheter over the guide wire and positioning it in the body lumen at a point distal of the entrance. The method further includes expanding the balloon to anchor it in the body lumen and extending the brush and brushing the entrance.

The foregoing descriptions apply, in some cases, to examples generated in a laboratory, but these examples can be extended to production techniques. For example, where quantities and techniques apply to the laboratory examples, they should not be understood as limiting.

Features of the disclosed embodiments may be combined, rearranged, omitted, etc., within the scope of the invention to produce additional embodiments. Furthermore, certain features may sometimes be used to advantage without a corresponding use of other features.

It is, thus, apparent that there is provided, in accordance with the present disclosure, sampling catheter devices, systems, and methods. Many alternatives, modifications, and variations are enabled by the present disclosure. While specific embodiments have been shown and described in detail to illustrate the application of the principles of the invention, it will be understood that the invention may be embodied otherwise without departing from such principles. Accordingly, Applicant intends to embrace all such alternatives, modifications, equivalents, and variations that are within the spirit and scope of the present invention.