Interventional MRI devices with functional distal region configurations

Abstract

An interventional medical device useful in a medical procedure guided under magnetic resonance imaging (MRI), such as a catheter or wire guide, includes an elongate member configured for insertion in a patient and having a flexible distal region. The flexible distal region has a preset curve shape in a relaxed condition and is resiliently configurable by the application of force to a second shape that differs from the preset curve shape. The device includes at least first and second passive MRI markers positioned on the elongate member, each configured to generate a respective artifact under MRI. Various MRI marker positional arrangements are described that facilitate recognition or tracking of position and / or configuration of the preset curve shape in a patient. Interventional systems are also described that include at least first and second MRI markers, one of which is positioned on a first elongate member and another of which is positioned on a second elongate member advanceable through the first elongate member. Related methods of manufacture and use are also described.

Description

[0001] INTERVENTIONAL MRI DEVICES WITH FUNCTIONAL DISTAL REGION CONFIGURATIONS

[0002] REFERENCE TO RELATED APPLICATION

[0003] This application claims the benefit of priority to United States Provisional Patent Application Serial No. 63 / 624,765 filed January 24, 2024, which is hereby incorporated by reference in its entirety.

[0004] BACKGROUND

[0005] The present disclosure relates generally to the field of interventional medical procedures and more particularly to elongate devices, such as guidewires or catheters, utilized in interventional medical procedures.

[0006] Guidewires and catheters are commonly utilized in a wide variety of interventional medical procedures. Oftentimes, it is beneficial that the guidewire or catheter have a curved portion in a distal region, for example to aid in navigation or to minimize trauma to patient tissue during use. In these or other procedures, it is also at times desirable to have imageable markers to facilitate navigation and determination of device position.

[0007] Interventional medical procedures have historically been conducted largely with X-ray guidance. Sometimes, radiopaque markers or marked lengths are included on catheters and guidewires that can be seen in images during X-ray guidance. However, X-ray-guided procedures expose the patient to significant ionizing radiation.

[0008] Needs exist, therefore, for improved and / or alternative medical devices and systems that can be effectively visually observed or tracked during procedures guided by other imaging modalities, such as in MRI-guided procedures. Aspects of the present disclosure are addressed to these needs. SUMMARY

[0009] In certain aspects, the present disclosure is directed to an interventional medical device, for example a percutaneously insertable medical device, useful in a procedure guided under magnetic resonance imaging (MRI). The medical device includes an elongate member configured for insertion in a patient and having a flexible distal region, the flexible distal region having a preset curve shape in a relaxed condition but being resiliently configurable by the application of force to a second shape that differs from the preset curve shape. A first passive MRI marker is provided at a first position along the elongate member, the first passive MRI marker configured to generate a first artifact under the MRI. A second passive MRI marker is provided at a second position distal of the first position and along the flexible distal region, the second passive MRI marker being configured to generate a second artifact under the MRI. A change in relative position of the first passive MRI marker with respect to the second passive MRI marker is visibly detectable under the MRI when the flexible distal region is moved from the second shape to the preset curve shape.

[0010] In other aspects, the present disclosure relates to an interventional medical device, for example a percutaneously insertable medical device, useful under magnetic resonance imaging (MRI). The device includes an elongate member configured for insertion in a patient and having a flexible distal region, the flexible distal region having a preset curve shape in a relaxed condition but being resiliently configurable upon the application of force to a straight condition. A first passive MRI marker is provided at a first position along the elongate member. A second passive MRI marker is provided at a second position along the elongate member, the second position being longitudinally spaced from the first position. The device is further characterized in that: (i) the first passive MRI marker is proximal of the flexible distal region having the preset curve shape and the second passive MRI marker is on the flexible distal region having the preset curve shape, wherein the second passive MRI marker is closer to the first passive marker when the distal region is in the preset curve shape than when the distal region is in the straight condition; or (ii) the first passive MRI marker and the second passive MRI marker are both on the flexible distal region having shape memory for a preset curve shape, and are longitudinally spaced from one another and configured to generate respective, discretely visible artifacts under MRI at a primary magnetic field strength of at least one of 0.55T, 1 ,5T and 3T, both when the flexible distal region is in the straight condition and in the preset curve shape; or (iii) one of the first passive MRI marker or the second passive MRI marker is positioned on the distal region so as to mark a distal-most position of the preset curve shape.

[0011] In still other aspects, the present disclosure relates to an interventional system, for example a percutaneously insertable interventional system, useful in medical procedures guided under magnetic resonance imaging (MRI) at a primary magnetic field strength. The system includes a first elongate medical device, such as a catheter, for treating a target region of a patient with a distal region of the first medical device. The first elongate medical device has a distal end and includes a first passive MRI marker. The system further includes a second elongate medical device, such as a wire guide, positionable through a lumen of the first elongate medical device so as to locate a distal region of the second elongate of the medical device distal of the distal end of the first elongate medical device. The distal region of the second elongate medical device incudes a first passive MRI marker. The first passive MRI marker of the first elongate medical device is configured to generate a first medical device-positioned artifact under the MRI having a maximum dimension. The first passive MRI marker of the second elongate medical device is configured to generate a second medical device-positioned artifact under the MRI having a maximum dimension. The maximum dimension of the second medical devicepositioned artifact is greater than the maximum dimension of the first medical devicepositioned artifact.

[0012] Additional aspects of the present disclosure relate to methods for making, and methods for using, interventional medical devices and systems as described herein. Still further aspects of the present disclosure, and features and advantages of aspects of the present disclosure, will be apparent to those skilled in the art from the descriptions herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] In the drawings wherein like reference numerals represent like parts:

[0014] FIG. 1 depicts a longitudinal view of an illustrative catheter of the present disclosure with a preset curve shape.

[0015] FIG. 1 A depicts a longitudinal view of another illustrative catheter of the present disclosure.

[0016] FIG. 1 B depicts a longitudinal view of another illustrative catheter of the present disclosure.

[0017] FIG. 1 C depicts a longitudinal view of another illustrative catheter of the present disclosure.

[0018] FIG. 2 depicts a magnified view of area M of FIG. 1 .

[0019] FIG. 3 depicts a longitudinal view of the catheter of FIG. 1 in a straightened condition. 20

[0020] FIG. 4 depicts a longitudinal view of the catheter of FIG. 3 after a first range of movement toward the preset curve shape shown in FIG. 1 .

[0021] FIG. 5 depicts a longitudinal view of the catheter of FIG. 4 after a second range of movement toward the preset curve shape shown in FIG. 1 .

[0022] FIG. 6 depicts a longitudinal view of the catheter of FIG. 5 after a third range of motion to reach the preset curve shape of FIG. 1 .

[0023] FIG. 7A depicts a magnified view of area M of FIG. 1 of an alternative catheter of the present disclosure.

[0024] FIG. 7B depicts a magnified view of area M of FIG. 1 of another alternative catheter of the present disclosure.

[0025] FIG. 7C depicts a magnified view of area M of FIG. 1 of another alternative catheter of the present disclosure.

[0026] FIG. 7D depicts a magnified view of area M of FIG. 1 of another alternative catheter of the present disclosure.

[0027] FIG. 8 depicts a longitudinal view of one embodiment of an alternative catheter of the present disclosure with a preset curve shape. FIGs. 9A and 9B depict, respectively, a cross-sectional view taken along line 1 X-1 X of FIG. 1 and a longitudinal view of a segment of the catheter of FIG. 1 in the region of line 1 X-1X, illustrating an embodiment of a passive MRI marker.

[0028] FIGs. 10A and 10B depict, respectively, a cross-sectional view taken along line 1 X-1 X of FIG. 1 and a longitudinal view of a segment of the catheter of FIG. 1 in the region of line 1 X-1X, illustrating another embodiment of a passive MRI marker.

[0029] FIGs. 1 1 A and 1 1 B depict, respectively, a cross-sectional view taken along line 1 X-1 X of FIG. 1 and a longitudinal view of a segment of the catheter of FIG. 1 in the region of line 1X-1 X, illustrating another embodiment of a passive MRI marker.

[0030] FIGs. 12A and 12B depict, respectively, a cross-sectional view taken along line 1 X-1 X of FIG. 1 and a longitudinal view of a segment of the catheter of FIG. 1 in the region of line 1 X-1X, illustrating another embodiment of a passive MRI marker.

[0031] FIGs. 13A and 13B depict, respectively, a cross-sectional view taken along line 1 X-1 X of FIG. 1 and a longitudinal view of a segment of the catheter of FIG. 1 in the region of line 1 X-1X, illustrating another embodiment of a passive MRI marker.

[0032] FIG. 14 depicts a longitudinal view of an illustrative wire guide of the present disclosure with a preset curve shape, in which portions of a jacket of the wire guide have been cut away to illustrate a core member within.

[0033] FIG. 15 depicts a cross-sectional view taken along line 14X-14X of FIG. 14.

[0034] FIG. 16A depicts a cross-sectional view taken along line 14Y-14Y of FIG. 14, illustrating one embodiment of a passive MRI marker.

[0035] FIG. 16B depicts a longitudinal view of a segment of the wire guide of FIG. 16A in the region of line 14Y-14Y.

[0036] FIG. 17A depicts a cross-sectional view taken along line 14Y-14Y of FIG. 14, illustrating another embodiment of a passive MRI marker.

[0037] FIG. 17B depicts a longitudinal view of a segment of the wire guide of FIG. 17A in the region of line 14Y-14Y.

[0038] FIG. 18A depicts a cross-sectional view taken along line 14Y-14Y of FIG. 14, illustrating another embodiment of a passive MRI marker.

[0039] 7

[0040] FIG. 18B depicts a longitudinal view of a segment of the wire guide of FIG. 18A in the region of line 14Y-14Y. FIG. 19A depicts a cross-sectional view taken along line 14Y-14Y of FIG. 14, illustrating another embodiment of a passive MRI marker.

[0041] FIG. 19B depicts a longitudinal view of a segment of the wire guide of FIG. 19A in the region of line 14Y-14Y. FIG. 20A depicts a cross-sectional view taken along line 14Y-14Y of FIG. 14, illustrating another embodiment of a passive MRI marker.

[0042] FIG. 20B depicts a longitudinal view of a segment of the wire guide of FIG. 20A in the region of line 14Y-14Y.

[0043] FIG. 21 depicts a partial cutaway longitudinal view of an interventional system including a catheter and a wire guide, each with passive MRI markers.

[0044] FIG. 22 depicts the system of FIG. 21 and graphically depicts visible artifacts generated by the passive MRI markers.

[0045] DETAILED DESCRIPTION

[0046] Reference will now be made to embodiments, some of which are illustrated in the drawings, and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the disclosure is thereby intended. Any alterations and further modifications in the described embodiments and any further applications of the principles as described herein are contemplated as would normally occur to one skilled in the art to which this disclosure relates.

[0047] As disclosed above, aspects of the present disclosure relate to interventional medical devices that are useful in MRI-guided procedures, such as catheters and / or guidewires, and to interventional medical systems, and to methods for making and using them. In preferred forms, the interventional medical devices and systems are configured for percutaneous insertion into a patient and / or for conducting an endoluminal procedure, such as an intravascular procedure. For example, catheter embodiments herein can be configured for use in infusing liquid therapeutic or diagnostic agents to a patient, and / or withdrawing bodily liquid such as blood from a patient, and / or for measuring fluid pressure, such as blood pressure, within a vessel of patient. A catheter herein may for example be an angiographic catheter in some embodiments.

[0048] As used herein, the term "attached" refers to one member being secured to another member such that the members do not completely separate from each other during use performed in accordance with the intended use of an item that includes the members in their attached form.

[0049] As used herein, the term "plug" refers to a member having a size and configuration suitable for disposition within a hole, passageway, recess, or void in another member. The term does not require any particular size or configuration, and the size and configuration of a particular plug will depend on the size and configuration of the hole, passageway, recess, or void into which the plug is intended to be disposed.

[0050] As used herein, the term "circumference" refers to an external, or internal, enclosing boundary of a body, element, or feature and does not impart any structural configuration on the body, element, or feature. As used herein, the term "passive MRI marker" refers to an amount of a first material positioned relative to a second material such that the first material generates a discrete visible artifact that is distinguishable from the second material under MRI. In embodiments herein the second material is typically represented by a material forming an elongate member such as a catheter shaft or wire guide and having a magnetic susceptibility that is less than the magnetic susceptibility of the first material.

[0051] As used herein, the term "passive," in relation to an MRI marker, refers to a marker that is either unpowered or powered exclusively by the electromagnetic field of a MR scanner.

[0052] As used herein, the "maximum dimension" of a visible artifact refers to the maximum edge-to-edge distance of the visible artifact under MRI. Where a numeric value for the maximum dimension of a visible artifact is referenced or required to determine a feature disclosed herein, it is as determinable according to ASTM F2119-07 (2013) and using a primary field strength of 0.55T and the following parameters:

[0053] Gradient echo sequence

[0054] Time to Echo (TE) [ms] 15

[0055] Repetition Time (TR) [ms] 317

[0056] Flip angle [°] 30

[0057] Matrix size 256 x 256

[0058] Slice thickness [mm] 10mm

[0059] Pixel bandwidth [Hz / px] 120

[0060] Field of View (FOV) [mm x mm] 400 x 400

[0061] As used herein, the term "magnetic susceptibility" refers to the intrinsic property of a material that relates to how much the material will become magnetized in an applied magnetic field. When numeric values for magnetic susceptibility are provided herein, they refer to volume-based magnetic susceptibility in International System of Units (SI) values at 25°C. Some magnetic susceptibility values are given herein as parts per million ("ppm"), and persons skilled in the pertinent art will understand that the reference to "ppm" is equivalent to a reference to "x 10'6". FIG. 1 depicts a longitudinal view of an illustrative flexible catheter 10 which includes an elongate catheter shaft 12. The shaft 12 includes a flexible distal region 14 having a preset curve shape 16. Preset curve shape 16 can be or include a curve shape that curves continuously around a point (an in-plane preset curve shape) or an axis (a preset curve shape that extends out of plane). The preset curve shape can be a pigtail shape, as illustrated. In some forms, the preset curve shape 16 can facilitate atraumatic positioning of the catheter past and / or within anatomical structures such as a chamber (e.g. left ventricle) of the heart or its associated valve structures. While in the illustrated embodiment the preset curve shape 16 turns through approximately 360 degrees, it will be understood that in other forms the preset curve shape can turn to a lesser or greater extent, for example including through at least 45 degrees, at least 90 degrees, at least 180 degrees, at least 270 degrees, or at least 360 degrees. In some typical forms, the preset curve shape 16 will turn through about 270 degrees to about 540 degrees. The flexible distal region defines a distal end 18 of the catheter shaft 12. The catheter shaft 12 has a generally straight proximal shaft portion 20 attached to a curved distal portion 22 defining the preset curve shape 16. The length of the catheter shaft that defines the curved distal portion is typically in the range of about 1 cm to about 20 cm, more typically about 5 cm to about 20 cm, or about 5 cm to about 15 cm. The catheter shaft 12 defines a longitudinal lumen 24 fluidly communicating with a distal end opening 26 at the distal end 18. The catheter 10 includes a first passive MRI marker 28, a second passive MRI marker 30, and a third passive MRI marker 32, longitudinally spaced (i.e. spaced along the longitudinal axis) from one another along the catheter shaft 12. The illustrative catheter 10 also includes a fourth passive MRI marker 33 positioned on the straight portion 20 a relatively large longitudinal distance proximally of the next-occurring passive MRI marker of the catheter 10 distal of the passive MRI marker 33 (providing a proximal reference marker), for example where such longitudinal distance is at least about two times, or at least about 3 times, the longitudinal distance between any two adjacent passive MRI markers of a plurality of passive MRI markers located distal of the passive MRI marker 33 on the catheter 10. For example, such adjacent passive MRI markers can be passive markers 28 and 30 as well as passive markers 30 and 32 in some forms, or can be passive MRI markers 28 and 32 in some forms (where passive MRI marker 30 is not included in the catheter), or can be passive MRI markers 28 and 30 in some forms (where passive marker 32 is not include in the catheter), or can be passive MRI markers 30 and 32 in some forms (where passive marker 28 is not included in the catheter). The length of the catheter 10 between passive MRI marker 33 and the nextoccurring passive MRI marker distal of the passive MRI marker 33, can be free from any discrete MRI marker (i.e. free from any passive or active discrete MRI marker). In this manner, under MRI, the relatively large spacing between respective visible artifacts generated by passive MRI marker 33 and the next-occurring discrete MRI marker distal of the passive MRI marker 33 (e.g. passive MRI marker 28) can be observed or tracked, rendering marker 33 and its corresponding visible artifact a beneficial positional reference for the catheter 10 when used under MRI. In addition or alternatively, the passive MRI marker 33 can in some forms be configured to generate under MRI a visible artifact that differs from, for example has a maximum dimension larger than (for example at least about 1 .25 times that of) or instead that is smaller than, the visible artifact generated by at least the next-occurring discrete MRI marker distal of the passive MRI marker33 (e.g. passive MRI marker 28) and in some forms the respective visible artifacts generated by each of a plurality of passive MRI markers occurring distal of the passive MRI marker 33, e.g. passive MRI markers 28, 30 and 32. This can also aid in the function of passive MRI marker 33 as a positional reference for catheter 10 and its distal region 14.

[0062] While four passive MRI markers are shown in the illustrated embodiment, any suitable number of passive MRI markers can be included on catheters as disclosed herein, including fewer, or more passive MRI markers than four. In the illustrated form, the catheter 10 includes passive MRI markers 28 and 33 located on the straight portion 20 of the catheter shaft 12, proximate to the distal region 14, and the passive MRI markers 30 and 32 located on the distal region 14 of the catheter shaft 12. Other arrangements are contemplated for other catheter embodiments or other medical device embodiments herein, including in some forms arrangements in which at least one passive MRI marker is located on the straight portion 20 (e.g. at least marker 28 or at least marker 33) and at least one passive MRI marker (e.g. at least marker 30 or at least marker 32) or at least two passive MRI markers (e.g. both of markers 30 and 32) is / are located on the distal region 14; or, arrangements in which at least two passive MRI markers (e.g. both of markers 28 and 33) are located on the straight portion 20 and at least one passive marker (e.g. at least marker 30 or at least marker 32) or at least two passive MRI markers (e.g. both of markers 30 and 32) are located on the distal region 14.

[0063] With reference now to FIG. 1 in combination with FIG. 2, shown in FIG. 2 is a magnified view of area M of FIG. 1 . Passive MRI markers 28, 30 and 32 are configured to generate respective visible artifacts 28A, 30A, and 32A under MRI. In particular forms, passive MRI markers 28, 30, and 32 are configured to generate respective visible artifacts 28A, 30A and 32A under MRI that have a maximum dimension that is about 1 .5 to about 50 times the outer diameter of the longitudinal segment of the catheter shaft 12 on which they occur, more preferably about 2 to about 20 times. The visible artifacts generated by the passive MRI markers under MRI at a given primary magnetic field strength may be the same as, or may differ from, each other. Also, while the preferred maximum dimensions are given above in reference to MRI under a primary field strength of 0.55T, it will be understood that the devices herein will also generate visible artifacts and may be used in MRI under other primary field strengths, for example 1 .5T or 3T.

[0064] With reference now to FIGs. 3 to 6, illustrated are several stages of a deployment of the distal region 14 of the catheter from a generally straight configuration in which it is held, e.g. by a guidewire extending through lumen 24, to resiliently move to the preset curved condition 16, e.g. by withdrawing the guidewire proximally. References to relative positions of the passive MRI markers 28, 30 and 32 and their respective artifacts 28A, 30A and 32A will be made in discussions below and, as will be understood, refer to their relative positions in the overall shape of the catheter shaft 12 (as opposed to referring to their relative longitudinal positions along the catheter shaft 12). FIG. 3 shows the distal region 14 held in the straight condition. As seen, the passive MRI markers 28, 30 and 32 generate respective visible artifacts 28A, 30A and 32A that are discretely visible and that are spaced from one another. Marker 30 and its artifact 30A are positioned distal of marker 28 and its artifact 28A, respectively. Marker 32 and its artifact 32A are positioned distal of marker 30 and its artifact 30A, respectively. Marker 28 is positioned a distance D1 from marker 32. In a first stage of deployment, shown in FIG. 4, marker 32 and its artifact 32A remain distal of marker 30 and its artifact 30A which in turn remain distal of marker 28 and its artifact 28A, respectively. Compared to the condition shown in FIG. 3, marker 32 and its artifact 32A have moved laterally with respect to marker 28 and its artifact 28A, and also with respect to the axis of the generally straight portion 20 of catheter shaft 12. Also in this form and at this stage, marker 30 and its artifact 30A have moved laterally with respect to marker 28 and its artifact 28A, and also with respect to the axis of straight portion 20.

[0065] FIG. 5 shows a second stage of deployment following the first stage. Compared to the condition shown in FIG. 3, marker 32 and its artifact 32A are now positioned proximal of marker 30 and its artifact 30A, respectively. Thus, during deployment, marker 30 and its artifact 30A have moved, respectively, from a position distal of marker 32 and its artifact 32A to a position proximal of marker 30 and its artifact 30A. This relative movement between artifact 32A and artifact 30A during deployment of the preset curve shape 16 can be visually observed by a user and / or tracked by the MRI system to provide confirmation of deployment and to estimate a position of the preset curve shape 16. While in the illustrated embodiment the marker 32 and its artifact 32A remain distal of the marker 30 and its artifact 30A, respectfully, until a point after which the shaft 12 segment bearing marker 30 has been released from constraint (e.g. by the guidewire), it will be understood that in other forms the marker 32 and its artifact 32A can move from the distal position to the proximal position relative to marker 30 and its artifact 30A while the shaft 12 segment bearing marker 30 remains constrained. The longitudinal spacing of the markers 30 and 32, the preset curve shape, or other factors, can be controlled to achieve these and other relative marker / artifact movements before and during deployment of the distal region 14 to the preset curve shape 16. Also in illustrated form, the movement of the artifact 32A from distal of to proximal of the artifact 30A is accompanied by an orbital movement of the artifact 32A around artifact 30A, which can facilitate visual observation and / or MRI system tracking to determine deployment and / or position of the distal region 14. As well, in the stages illustrated in FIGs. 3, 4 and 5, the artifact 32A has progressively moved closer to the artifact 28A as compared to their respective positions in the generally straight undeployed condition shown in FIG. 1 . This relative movement between artifact 28A and 32A can be observed by a user and / or tracked by the MRI system to provide confirmation of deployment and to estimate a position of the preset curved shape 16, instead of or in addition to the relative movements between artifacts 32A and 30A discussed above.

[0066] FIG. 6 illustrates the distal region 14 of the catheter in the preset curve shape 16 (also illustrated in FIG. 1 ). As can be seen, the marker 32 and its artifact 32A remain proximal of, and have moved further proximally of, the marker 30 and its artifact 30A, and the marker 32 and its artifact 32A have reached their closest position to marker 28 and its artifact 28A, with passive marker 28 positioned a distance D2 from passive marker 32. These positions, and the associated movements of the artifacts 28A, 30A and 32A in reaching them during deployment of the distal region to the preset curve shape 16, can also be used to provide confirmation of deployment of and / or to estimate a position of the preset curved shape 16.

[0067] In conjunction with the above discussions of FIGs. 3 to 6, it is beneficial that marker 28A is positioned proximate to the proximal end of the distal region 14 formed by the curved distal portion 22. In the illustrated form, marker 28A is positioned on the generally straight portion 20 of the catheter shaft 12, rather than on the distal region 14 formed by the curved distal portion 22. Marker 28 and its artifact 28A remain aligned with the axis of the generally straight portion 20 (as may of course be modified by contact with patient vessel walls). The position of artifact 28A can therefore be used as a reference point to observe or track the movement of artifact 30A and / or artifact 32A. It is also preferred that the position of marker 28A on the catheter shaft is within about 2 cm, or about 1 cm, of the proximal end of the distal region 14 (i.e. from the proximal start of the curved distal portion 22). For these purposes, marker 28A can be positioned on the generally straight portion 20 proximal of the distal region 14, as shown; or in other forms can be positioned on the distal region 14, but preferably at a location at which marker 28A is not laterally offset from the axis of the straight portion 20 by more than about 1 cm, or more than about 0.5 cm. The marker 28A can thus demark the transition between the straight portion 20 and the distal region 14. As well, the relative changes in the spacing between and movement of the artifact 30A and the artifact 32A, on the distal region 14, relative to the artifact 28, can thereby be more readily observed or tracked.

[0068] In this regard, in certain forms, the distance D2 between the markers 28 and 32 with the distal region 14 in the preset curve shape 16 (see FIG. 6) is no more than 90% of the distance D1 between the markers 28 and 32 with the distal region 14 in the straight configuration (see FIG. 3), or no more than about 80% of the distance D1 , or no more than about 70% of the distance D1 , or no more than about 60% of the distance D1 , or no more than about 50% of the distance D1 , and in some forms is in the range of about 1% to about 90%, or about 1% to about 50%, of the distance DI. In addition or alternatively, in certain forms, the preset curve shape 16 can have a maximum dimension 16D, considered in a direction perpendicular to the axis of the straight proximal shaft portion 20, in the range of about 0.5 cm to about 15 cm, typically about 1 cm to about 10 cm, and more typically about 1 cm to about 5 cm. It will be understood that the maximum dimension 16D will be selected based on the intended application and function for the catheter.

[0069] In some forms, the marker 32 will be positioned proximate to the distal end 18 of catheter 10, for example within about 2 cm, or within about 1 cm, of the distal end 18. In addition or alternatively, in some forms, the marker 30 will occur on the catheter shaft 12 at a position where the preset curve shape 16 has turned between about 65 degrees and about 115 degrees, or between about 75 degrees and about 105 degrees; and / or the marker 30 will occur on the catheter shaft 12 at a position that marks a distal-most position of the preset curve shape 16 and / or a lateral-most position of the preset curve shape 16 relative to the axis of straight portion 20. Where such distal-most and lateral-most positions of the preset curve shape 16 differ, in some forms, the distal region 14 will have a passive MRI marker at longitudinal position therealong that marks a distal-most position of the preset curve shape 16 and another passive MRI marker at a longitudinal position therealong that marks the lateral-most position of the preset curve shape relative to the axis of the straight portion 20.

[0070] In some forms, at least one of the markers 28, 30 and 32 is configured to generate a visible artifact having a size, such as a maximum dimension, that differs from that generated by at least one other of the markers 28, 30, and 32. Such differences can further aid in observation or tracking of the shape of the distal region 14 of the catheter 10. For example, provided in FIGs. 7A to 7D are various exemplary catheter embodiments herein, where the respective illustrated catheters 7A to 7D can be the same as catheters 10 or 10' herein except as otherwise described. In catheter 7A of FIG. 7A, the passive MRI marker 28 is configured to generate a visible artifact 28A, the passive MRI marker 30 is configured to generate a visible artifact 30A, and the passive MRI marker 32 is configured to generate an artifact 32A, where artifact 28A is larger than (e.g. has a greater maximum dimension than) the artifact 30A, and the artifact 30A is larger than (e.g. has a greater maximum dimension than) the artifact 32A. In catheter 7B of FIG. 7B, the passive MRI marker 28 is configured to generate a visible artifact 28A, the passive MRI marker 30 is configured to generate a visible artifact 30A, and the passive MRI marker 32 is configured to generate an artifact 32 A, where artifact 32A is larger than (e.g. has a greater maximum dimension than) the artifact 30A and the artifact 28A, and the artifacts 30A and 28A can have the same size (e.g. maximum dimension) as each other. In catheter 7C of FIG. 7C, the passive MRI marker 28 is configured to generate a visible artifact 28A, the passive MRI marker 30 is configured to generate a visible artifact 30A, and the passive MRI marker 32 is configured to generate an artifact 32A, where artifact 30A is larger than (e.g. has a greater maximum dimension than) the artifact 28A and the artifact 32A, and the artifacts 28A and 32A can have the same size (e.g. maximum dimension) as each other. In catheter 7D of FIG. 7D, the passive MRI marker 28 is configured to generate a visible artifact 28A, the passive MRI marker 30 is configured to generate a visible artifact 30A, and the passive MRI marker 32 is configured to generate an artifact 32A, where artifact 28A is larger than (e.g. has a greater maximum dimension than) the artifact 30A and the artifact 32A, and the artifacts 30A and 32A can have the same size (e.g. maximum dimension) as each other.

[0071] The size, such as maximum dimension, of a visible artifact generated by a passive MRI marker can be controlled in any suitable fashion. Varying the volume of and / or the composition of the passive MRI marker-forming material of respective passive MRI markers can be used for these purposes. For example, in some forms, a passive MRI marker that generates a larger size (e.g. greater maximum dimension) artifact than another can include a greater volume of the same MRI marker-forming material. In other forms, a passive MRI marker that generates a larger size artifact than another can include a different passive MRI marker-forming material than the other. In such forms, the larger artifact-generating passive MRI marker can have the same volume or a lesser volume of a passive MRI marker-forming material having a higher magnetic susceptibility than that of the other passive MRI marker; or, a greater volume of a passive MRI marker-forming material that has a lower magnetic susceptibility than that of the other passive MRI marker. It will be understood that these passive MRI marker configurations apply to markers 28, 30, 32 and 33 of catheter 10 and other catheters herein, as well as to passive MRI markers of differing sizes on other devices as disclosed herein, including wire guides.

[0072] Beneficial embodiments are provided wherein the markers 28, 30 and 32, with the distal region 14 in the preset curve shape 16, provide a pattern unique to the preset curve shape 16 that can be visually observed by a user and / or detected by the MRI system to confirm deployment of the distal region 14 to the preset curve shape 16. For example, in some embodiments, markers 28, 30 and 32 can be positioned to form a linear pattern extending in a direction offset from the axis of proximal shaft portion 20 of catheter 10, for example wherein the markers 28, 30, and 32 and their respective artifacts 28A, 30A and 32A are linearly positioned but spaced more closely to one another as compared to when the distal region 14 is in a straight condition. Other positional patterns may for example include polygonal patterns. These or other positional patterns can also be benefitted by different size(s) among the artifacts 28A, 30A and 32A generated by the passive MRI markers 28, 30 and 32, for example as discussed above. The MRI system can be configured to detect such positional and / or artifact size patterns using a computer processor, for example having been trained using artificial intelligence (Al) to recognize such patterns, and to execute a function controlled by the computer processor based on that detection. For example, the MRI system can provide a signal, such as an audible signal through a speaker or a visible graphic on an electronic display such as the display showing the MRI image(s), with the graphic potentially provided as an overlay of the MRI image(s). Such a graphic overlay may, for example, estimate a shape and / or size of the distal region 14, and / or provide an indicator of the distal-most position and / or lateral-most position of the preset curve shape 16. A user input device such as a keyboard of the system may be used as a control to display or not display the graphic, as desired.

[0073] The above discussions include reference to deployment of the distal region 14 from a straight condition to the preset curve shape 16, and relative movements of the markers 28, 30 and 32 and their respective artifacts 28A, 30A and 32A during such deployment. It will of course be understood that in practical uses of catheter 10, as deployment begins, the distal region 14 may not be in a straight condition, but rather may be in a curved state, but not the preset curve shape 16, due to conditions at the treatment site and / or constraint by a guidewire or other associated interventional device. Nonetheless, the relative movements of the artifacts 28A, 30A, and 32A may be usefully observed or tracked to determine deployment and / or estimate a position of the preset curve shape 16.

[0074] Turning now to some more particular features of illustrative embodiments of catheter 10, the elongate catheter shaft 12 in preferred forms has a generally circular outer profile in cross section. The catheter shaft 12 can include a proximal shaft portion 34 and a distal shaft portion 36 fixedly attached thereto at bond 38, which can for example be a thermal bond. The distal shaft portion 36 can be, or in some forms is not, a radiopaque and / or MRI visible tubular member portion. Distal shaft portion 36 can be formed from a flexible polymeric material, for example comprising a thermoplastic elastomer. In some forms, the shaft portion 36 can comprise a uniformly dispersed composition of a thermoplastic elastomer material and a radiopacifying and / or passive MRI artifact-generating material. In other forms, the shaft portion 36 can be free from any radiopacifying material and free from any passive MRI-artifact generating material.

[0075] Catheter 10 further includes proximal end 40 with connector cap 42 and a female Luer lock connector 44 positioned thereabout for grasping by the physician or other user and manipulation of the catheter 10. Catheter 10 also includes lumen 24 extending longitudinally therein between proximal opening 46 and distal opening 26. The illustrated catheter 10 of FIG. 1 also includes sideports 48 in communication with the lumen 24, which as illustrated are formed in the proximal shaft portion 20 of the catheter 10 but in other forms may also, or instead only, occur in the distal region 14 of the catheter 10. As well, in some forms, the catheter 10 may have a closed distal tip 18 (instead of having opening 26), and one or more sideports in the proximal portion and / or the distal region 14.

[0076] Proximal shaft portion 34 of catheter 10 can have a length, for example, of about 50 to about 150 cm. The flexible polymeric material forming proximal shaft portion 34 can comprise a thermoplastic elastomer material. The thermoplastic elastomer material can comprise a polyamide elastomer such as a commercially available elastomeric nylon-12 material. Alternative thermoplastic elastomer materials that may be used include polyester elastomers, polyurethanes, and polyether block amides. In some forms, the proximal shaft portion 34 can include a radiopaque material and / or an MRI-artifact-generating material dispersed through the thermoplastic elastomer or other polymeric material forming portion 34. Potential radiopaque materials include as examples particulate materials such as bismuth oxychloride, bismuth subcarbonate, bismuth trioxide, and barium sulfate. If present, the radiopaque agent preferably has a magnetic susceptibility of less than about 500 ppm. Potential MRI-artifact-generating materials include as examples particles of a material that has a magnetic susceptibility greater than about 500 ppm, and preferably greater than about 2000 ppm. Examples of MRI-artifact-generating particles include particles of nickel, a nickel alloy, iron, an iron alloy, or titanium. The incorporation of a radiopaque material along with the discrete passive MRI markers (e.g. markers 28, 30, 32) can provide a catheter that can be beneficially used in both X-ray guided and MRI-guided interventional procedures. The incorporation of MRI-artifact-generating materials dispersed in the polymeric material of catheter shaft 12 along with the discrete passive MRI markers (e.g. markers 28, 30, 32) can provide a catheter that both generates an elongate, continuous visible artifact longitudinally along the shaft 12 as well as discrete artifacts (e.g. artifacts 28A, 30A, 32A), preferably having a larger maximum dimension than the continuous artifact in a direction perpendicular to the longitudinal axis of shaft 12, that further aid in tracking and / or identifying a position of the catheter.

[0077] Distal shaft portion 36 of catheter 10 can for example be a 5 cm to 20 cm length of flexible polymeric material, which can be softer and more flexible and / or have a durometer lower than that of the proximal shaft portion 34. The flexible polymeric material of distal shaft portion 34 can comprise a thermoplastic elastomer material. The thermoplastic elastomer material can comprise a polyether block amide. Alternative thermoplastic elastomer materials that may be used include polyester elastomers, polyurethanes, and polyamide elastomers such as elastomeric nylon-12 material. As with proximal shaft portion 34, in some forms, the distal shaft portion 36 can include a radiopaque material and / or an MRI-artifact- generating material dispersed through the thermoplastic elastomer or other polymeric material forming portion 36. Potential radiopaque materials and potential MRI-artifact generating materials include as examples those discussed above for proximal shaft portion 34. In some forms, the polymeric material forming both the proximal and distal shaft portions 34 and 36 may include a radiopaque material and / or an MRI-artifact-generating material dispersed within it. In other forms, the polymeric material forming one or the other of portions 34 and 36 will include a radiopaque material and / or an MRI-artifact-generating material dispersed within it. In still other forms, the polymeric material forming portion 36 will include a radiopaque material and / or an MRI-artifact-generating material dispersed within it, and the polymeric material forming portion 34 will include a radiopaque material dispersed within it, but portion 34 will be less radiopaque than portion 36, for example due to differing concentrations of the radiopaque material and / or differing radiopaque materials within portions 34 and 36.

[0078] Also, while a shaft 12 with attached portions 34 and 36 has been discussed in connection with the embodiments above, it will be understood that the shaft 12 may also be formed of a single, continuous polymeric material in other embodiments, for example any of the thermoplastic elastomers discussed herein. As well, the inclusion of radiopaque materials and / or MRI-artifact-generating materials dispersed in the polymeric material, as discussed above, can be incorporated in such other embodiments.

[0079] In some forms, the distal region 14 of the catheter shaft 12, or the distal portion 36 of the catheter shaft when proximal and distal shaft portions 34 and 36 are both included, or the catheter shaft 12 as a whole, is free from any metal reinforcing member, such as a metal wire coil or metal wire braid. Accordingly, in some embodiments, the proximal portion 34 of the catheter shaft 12 includes a metal reinforcing member such as a metal wire coil or metal wire braid, and the distal portion 36 of the catheter shaft 12 does not. In still further forms, the catheter shaft 12, or at least the distal portion 36 when attached shaft portions 34 and 36 are present, is free of any metal other than that incorporated in passive MRI markers, such as markers 28, 30, 32 and / or 33, included in the catheter 10.

[0080] In certain embodiments, the catheter shaft 12 can be free of any discrete MRI markers between passive MRI markers 28 and 30 when they are present, or free of any discrete MRI markers between passive MRI markers 30 and 32 when they are present, or free of any discrete MRI markers between passive MRI markers 28 and 32 when they are present. In some forms, when passive MRI markers 28, 30 and 32 are present, the length of the catheter shaft including markers 28, 30 and 32 can be free of any other discrete MRI markers. Additionally, in embodiments where passive MRI marker 33 is present, the catheter shaft 12 can be free of any discrete MRI markers between passive MRI marker 33 and passive MRI marker 28 when present or between passive MRI marker 33 and passive MRI marker 30 when passive MRI marker 28 is not present.

[0081] Reference will now be made to FIGs. 8A-12B to describe various beneficial embodiments for passive MRI markers. While the discussions refer specifically to passive marker 28, it will be understood that passive markers 30 and 32, and / or other passive MRI markers discussed herein, can have the discussed features.

[0082] Shown in FIGs. 8A and 8B are views depicting one illustrative structure for passive MRI marker 28. In this form, the marker 28 is a plug 50 embedded within the polymeric material of the wall of the catheter shaft 12. Plug 50 includes a material having a magnetic susceptibility suitable for generating the visible artifact under MRI as discussed herein (herein sometimes called a "passive MRI marker-forming material"). It has been found that relatively small amounts of suitable materials can be used for these markers. Preferred materials for these purposes will have a magnetic susceptibility of at least about 500 ppm, or at least about 2000 ppm, and typically in the range of about 500 ppm to about 1 ,000,000 and more preferably in the range of about 7000 ppm to about 100,000. In some forms, the marker-forming material will have a volume not exceeding 5 mm3, or not exceeding 3 mm3, or not exceeding 1 mm3, or not exceeding 0.1 mm3; in each of these aspects, the volume may be at least 0.00005 mm3, or at least about 0.0001 mm3. In more preferred forms where a relatively high magnetic susceptibility material is used, for example a magnetic susceptibility of at least about 1 (nickel, for example, as a magnetic susceptibility of about 1 .1 ), a volume of the passive MRI markerforming material not exceeding 0.1 mm3, for example in the range of 0.00001 mm3to 0.1 mm3, or in the range of 0.00005 mm3to 0.02 mm3, can be used in forming the passive MRI marker. Particular materials that may be used are discussed hereinbelow. It will be understood that generally the higher the magnetic susceptibility exhibited by an MRI marker-forming material, the lower the volume of that material that will be needed to form a visible artifact of a given size. These aspects can be selected and controlled by persons of skill in the art to provide passive MRI markers configured to generate visible artifacts of a size, or relative size, as discussed herein.

[0083] The ability to utilize relatively small volumes of passive MRI marker-forming material and yet generate beneficially sized visible artifacts is advantageous, as it enables the incorporation of a marker while minimizing disturbance of the physical performance properties of the catheter shaft, which are often carefully engineered with polymeric materials that are relatively soft and flexible. In the illustrated embodiment, the plug 50 is positioned fully within the tubular wall of the catheter shaft 12, having a first volume 52 of the polymeric material from which the catheter shaft is formed occurring radially outward of the plug 50 and extending to the outer surface of the shaft 12, and a second volume 54 of such polymeric material occurring radially inward of the plug 50 and extending to the surface of the catheter lumen 24. Such an arrangement can for example be accomplished by a preparative method embodiment herein that includes inserting the plug 50 into an opening in the wall of the shaft 12 extending from its outer surface and only partly through its thickness, and causing molten volumes of the polymeric material from which the shaft 12 is made to fill the opening and form a new outer surface portion of the shaft 12 over the plug 50. For these purposes, the polymeric material can be heated before, during and / or after insertion of the plug 50, for example ultrasonically or otherwise, to cause it to melt, flow and fill the opening and surround the plug 50, and then cooled (e.g. passively or actively) to solidify. Plug 50 can be mounted to the heated tip of a probe, for example with an ultrasonically heated tip, for insertion into the wall of shaft 12. The probe can heat the plug 50 and the polymeric material during the insertion and can also heat the polymeric material after deposit of the plug 50 in the shaft wall and during its withdrawal from the polymeric material. This can aid in causing the polymeric material to flow and surround the plug and fill in the first volume 52 of polymeric material overtop the plug. Such a technique can aid in achieving a self-healing of the polymeric material in forming a new outer surface of the shaft 12 over the plug 50. Shown in FIGs. 9A and 9B are views depicting another illustrative structure for passive MRI marker 28. In this form, the marker 28 is a plug 60 embedded within the wall of the catheter shaft 12. A solid fill material 62, different from the polymeric material from which the wall of shaft 12 is formed, occurs radially outward of plug 60 and provides an overlying surface 64 of the fill material that in some forms can be substantially flush with the adjacent surfaces of the catheter shaft 12. Fill material 62 may, for example, be an adhesive, such as a polymeric adhesive. Plug 60, like plug 50 discussed above, includes a material having a magnetic susceptibility suitable for generating the visible artifact under MRI as discussed herein.

[0084] FIGs. 10A and 10B provide views depicting another illustrative structure for passive MRI marker 28. In this form, the marker 28 is a plug 70 within the wall of the catheter shaft 12. Plug 70 is formed of a particulate material 72 having a magnetic susceptibility suitable for generating the visible artifact under MRI as discussed herein, dispersed within a matrix material 74, such as a polymeric matrix material (which may be the same as or different from the polymeric material forming the shaft 12) and / or adhesive matrix material. Plug 70 provides a surface 76 that can be flush with adjacent surfaces of the shaft 12. This arrangement for marker 28 form can be created by filling an opening created in the wall of catheter shaft 12 with a flowable material including the particulate material 72 and a precursor to the matrix material 74, for example an adhesive, and curing the precursor material to form the matrix material 74.

[0085] As discussed herein, the flexible distal region 14 of the catheter 10 has a preset curve shape 16. The catheter shaft portion 22 in the preset curve shape 16 can have an innermost portion 16', or "inner spine", that extends upon a line extending in a first curve, and an outermost portion 16", or "outer spine", that extends upon a line extending in a second curve that is opposite the first curve on the shaft portion 22. As also discussed herein, in some forms, the MRI marker can be a plug of MRI marker-forming material embedded in a wall of the catheter. In certain preferred forms, such plug-form marker(s), when present in the flexible distal region 14 of the catheter having the preset curve shape 16, will be positioned on the circumference of the catheter shaft 12 so as not to overlap the innermost portion 16' and / or the outermost portion 16", for example in some forms so as to be circumferentially spaced from the innermost portion 16' and / or the outermost portion 16" by at least about 15 degrees around the catheter shaft 12 outer circumference, or at least about 30 degrees around the catheter shaft 12 outer circumference. Such locations for the plug-form passive MRI marker(s) can be selected to provide embodiments that impart relatively low stresses on the marker(s) during movement of the distal region 14 between the preset curve shape 16 and a straightened condition, e.g. where the marker(s) do not overlap either the inner spine or the outer spine of the preset curve shape 16. As well, such locations for the plugform MRI marker can in some catheter configurations facilitate preservation of the bend properties of the preset curve shape 16 provided by the polymeric material from which it is formed, for example when the outermost portion 16" of the preset curve shape 16 is pressed against anatomical surfaces of a patient during navigation or placement of the catheter while the flexible distal region 14 is in the preset curve shape 16.

[0086] FIGs. 11 A and 11 B provide views depicting another illustrative structure for passive MRI marker 28. In this form, the marker 28 is a band 80 of the MRI markerforming material extending around the outer circumference of the shaft 12 and providing an outer band surface 82 over the shaft 12. Band 80 can include a matrix material 84 in which particles 86 of the MRI marker-forming material are dispersed. Band 80 can in some aspects be formed by curing a flowable material applied to the shaft including a precursor to the matrix material 84 and the particles 86, for example where the flowable material is in the nature of a MRI marker-forming ink that may also include a colorant selected to provide contrast between the band 80 and adjacent surfaces of the shaft 12.

[0087] FIGs. 11 A and 11 B provide views depicting another illustrative structure for passive MRI marker 28. In this form, the marker 28 is a band 80 of the MRI markerforming material extending around the circumference of the shaft 12 and providing an outer band surface 82 over the shaft 12. Band 80 can include a matrix material 84 in which particles 86 of the MRI marker-forming material are dispersed. Band 80 can in some aspects be formed by curing a flowable material applied to the shaft including a precursor to the matrix material 84 and the particles 86, for example where the flowable material is in the nature of a MRI marker-forming ink that may also include a colorant selected to provide contrast between the band 80 and adjacent surfaces of the shaft 12.

[0088] FIGs. 12A and 12B provide views depicting another illustrative structure for passive MRI marker 28. In this form, the marker 28 is a band 90 of the MRI markerforming material captured between an inner tubular shaft layer 12A and an outer tubular shaft layer 12B that are attached (e.g. bonded) to one another to form catheter shaft 12. The respective polymeric materials forming layers 12A and 12B can be the same as or different from each other, and can in some aspects be selected from any of the polymeric materials disclosed herein. In making this depicted arrangement for marker 28, in some forms, the band 90 can be provided by applying a flowable material such as that discussed above for band 80 to the outer surface of tubular shaft layer 12A, and then attaching the shaft layers 12A and 12B to one another to form shaft 12. In other forms, the band 90 can be a solid film or ring positioned over the outer surface of tubular shaft layer 12A and then attaching the shaft layers 12A and 12B to one another to form shaft 12.

[0089] Advantageously, the markers discussed above in conjunction with FIGs. 8A to 12B, or other markers herein, can occur within a relatively small region of the shaft 12. For example, such markers can occur within a longitudinal length not exceeding 10 mm, or not exceeding 5 mm, and typically in the range of 0.2 to 5 mm; and / or, in the case of plug-form markers or some non-circumferential layer markers, can have a width perpendicular to the axis of the shaft 12 that does not exceed about 90%, or about 80%, or about 70%, of the corresponding width of the shaft 12, or that is in the range of about 10% to about 100%, or about 10% to about 70%, of the corresponding width of the shaft 12. Markers that include plugs as discussed above are particularly beneficial in applying a marker within such recited widths as well as such recited longitudinal lengths. Passive MRI markers provided in such limited regions can facilitate avoidance or minimization of any impact of the marker(s) on physical performance properties of the shaft 12, for example bend or resilient properties, by the passive MRI marker-forming material, any other materials (e.g. adhesives) associated therewith, or any disruption of the polymeric material forming the shaft during incorporation of the passive MRI marker-forming material.

[0090] Particular passive MRI marker-forming materials that can be used herein include, for example, nickel, alloys of nickel, iron, alloys of iron, cobalt, alloys of cobalt, or other suitable metals. These may be selected to have magnetic susceptibility values as discussed herein and / or in some forms may be paramagnetic or ferromagnetic materials. In certain advantageous forms, the passive MRI markerforming material will be incorporated as a continuous volume of the passive MRI marker-forming material, for example as a plug or layer (e.g. plated layer), within a length of the catheter shaft 12 or another elongate member of a medical device herein. Such continuous volume-forms of passive MRI markers herein can facilitate minimizing the volume of material needed to be added to and / or to replace a volume of the material forming the catheter shaft 12 or other medical device elongate member herein, for example as compared to forms of passive MRI markers that include particles of the passive MRI marker-forming material dispersed in a volume of another material providing a solid matrix.

[0091] FIG. 13 depicts a longitudinal view of another illustrative flexible catheter 10'. Catheter 10' can have the same features as catheter 10 discussed above, except as otherwise described herein. Catheter 10' has sideport features that differ from catheter 10. In particular, catheter 10' is free of any sideports that occur proximal of marker 28 and includes one or more sideports 48A distal of marker 28. In this fashion, marker 28 provides indication to a physician or other user of catheter 10' that all sideports 48A of catheter 10' are distal of the artifact 28A generated by marker 28. This can be useful for example when delivering a flowable diagnostic or therapeutic material through lumen 24 to a selected target region in which the sideport(s) 48A are located and / or when positioning the sideport(s) 48A within a given region of a patient's vascular such as within the heart to measure the pressure within the region. These and other variations within the structures of catheters 10 and 10', benefiting from the present of the passive MRI markers and their functions, will be apparent to those skilled in the field from the descriptions herein.

[0092] In this regard, FIGs. 1 A, 1 B, and 1C depict additional embodiments of catheters 10A, 10B and 10C, having distal regions with a preset curve shape. Catheters 10A, 10B and 10C can have features that are the same as those for catheter 10 or 10', except as otherwise described herein. Catheter 10A in FIG. 1 A has a preset curve shape 16A that turns continuously for about 180 degrees. The markers 28, 30, 32, and 33 can correspond in function to those on catheters 10 and 10' discussed hereinabove. Catheter 10B in FIG. 10B has a preset curve shape 16B with multiple curves, and in particular a reverse-curve shape. Preset curve shape 16B includes a proximal curve portion 22A of the distal region 14 that curves in a first direction lateral of the longitudinal axis of the straight portion 20 of the catheter shaft 12, and a distal curve portion 22B of the distal region 14 adjoins the proximal curve portion and extends in a second direction lateral of the longitudinal axis of the straight portion 20 and opposite to the first direction of proximal curve portion 22A. The preset curve shape 16B represents a "shepherd hook" preset curve shape, as known in the art. Catheter 16B also includes a further passive MRI marker 28'. Catheter 16B exemplifies embodiments herein having a passive MRI marker 30 positioned on the preset curve shape 16B to provide a visible artifact to mark a distal-most position of the preset curve shape 16B and a further passive MRI marker 28' positioned on the preset curve shape 16B to provide a visible artifact to mark a lateral-most position of the preset curve shape 16B. As well, for observation or tracking of the deployment of the preset curve shape 16B, and in particular its distal curve portion 22B, the passive MRI marker 28' can function similarly to passive MRI marker 28 in regard to movements and relative positions with respect to passive MRI markers 30 and 32. Catheter 10C of FIG. 1 C shows a catheter with another preset curve shape 16C. Preset curve shape 16C turns through less than 180 degrees, and in particular in the illustrated form turns through about 85 degrees, having a smaller radius curved portion near the proximal end of distal region 14 extending distally to a larger radius curved portion and / or straight portion of the preset curve shape 16C. As will be understood, in the case of preset curve shape 16C the passive MRI marker 32 will remain distal of the passive MRI marker 30 during deployment of the preset curve shape 16C and in the deployed preset curve shape 16C, rather than moving proximal of passive MRI marker 30 as in the case of other catheters discussed above (e.g. catheters 10, 10', 10A and 10B). Nonetheless, the relative positions and movements of the markers 28, 30 and 32 of catheter 10C and their respective visible artifacts can be observed or tracked to determine deployment of the preset curve shape 16C. Catheters 10A, 10B, and 10C can have one or more sideports at location(s) as disclosed for catheter 10 or catheter 10', or in other forms can be free of any sideports along the shaft 12, having only end opening 26 to be positioned for fluid communication of the lumen 24 within T1 the patient, for example to receive a patient bodily fluid such as blood and / or to infuse a liquid agent into the patient.

[0093] The passive MRI marker(s) on the flexible distal region 14 of the catheter 10 can in certain preferred manufacturing methods be incorporated before setting the distal region 14 to the preset curve shape 16. Setting the distal region 14 to the preset curve shape 16 can include forcing and holding the polymeric material of the catheter shaft 12 in a desired shape corresponding to the preset curve shape, heating the polymeric material of the catheter shaft 12 while in such desired shape, and then cooling the polymeric material of the catheter shaft while in the desired shape, to provide the preset curve shape 16. In such forms, the shape of the polymeric material of the catheter shaft 12 can be reset in the presence of the volume of passive MRI marker-forming material of the passive MRI marker(s) to be located on the distal region 14 of the shaft 12. In other manufacturing methods, the passive MRI marker(s) on the flexible distal region 14 can be incorporated after setting the flexible distal region 14 to the preset curve shape 16. Also, where the catheter shaft 12 includes a proximal shaft portion 34 attached to a distal shaft portion 36 that includes the distal region 14, the passive MRI marker(s) on the distal region 14 can be incorporated before or after attaching the distal shaft portion 36 to the proximal shaft portion 34. As well, during incorporation of the passive MRI markers on the catheter shaft 12, a mandrel can be positioned through the lumen 24 of the shaft 12 to coincide with a position or positions at which the MRI marker(s) are to be incorporated. Where the passive MRI marker(s) are incorporated on the distal region 14 after it has been set to the preset curve shape 16, in some aspects, a straight mandrel can be inserted into the distal region 14 to force it to a straight condition during incorporation of the passive MRI marker(s) thereon.

[0094] In other embodiments herein, the interventional medical device can be a wire guide. FIG. 14 illustrates an example wire guide 100 useful in interventional procedures performed under MRI. FIG. 14 provides a longitudinal view in which portions of a jacket of the wire guide have been removed to illustrate a core member therein. The wire guide 100 includes a core member 102 and a jacket 104 disposed on the core member 102. The core member 102 in some preferred forms is a continuous elongate member having a proximal end 106, a distal end 108. The core member 102 can have a generally circular outer profile in cross section. The core member 102 is preferably fully encapsulated by the jacket 104, such that no portion of the core member 102 is exposed to the external environment surrounding the wire guide 100. The jacket 104 can have a generally circular outer profile in cross section. The jacket 104 includes a proximal surface 110 that is proximal of the proximal end 106 of the core member 102, and a distal surface 112 that is distal of the distal end 108 of the core member 102. In some forms, the jacket 104 can also include sidewall surface portions 111 adjoining proximal surface 110 and occurring proximal of the proximal end 106 of the core member 102 and / or sidewall surface portions 113 adjoining distal surface 112 and occurring distal of the distal end 108 of the core member 102.

[0095] The core member 102 can be formed of any suitable material, and in typical forms comprises a metallic material, such as a metal alloy. Examples of metallic materials considered suitable for forming the core member 102 include, but are not limited to, superelastic metal alloys, including nickel-titanium alloys such as Nitinol, Superelastic Nitinol SE508 straight with black oxide, matte finished Nitinol, polished Nitinol, nickel chromium, nickel cobalt, titanium, nickel oxide, cobalt chromium nickel molybdenum alloys, such as the alloy available under the trade name Elgiloy from Elgiloy Specialty Metals (Elgin, IL), combinations of those described herein, and any other metallic materials considered suitable for a particular embodiment. In other forms, the core member 102, or at least a longitudinal portion thereof defining the preset curve shape 115 as discussed below, can be formed of non-metallic material (e.g. a fiber-reinforced polymer material) or formed of multiple shorter segments of a metallic material, such as those materials listed above, attached with connectors so as to be electrically insulated from one another, for example as described in U.S. Patent No. 11 ,724,073 issued August 15, 2023, which is hereby incorporated herein by reference.

[0096] In the illustrated example, the core member 102 is a continuous length of wire having a taper along a tapered segment at its distal end. The core member 102 can have any suitable longitudinal length and a skilled artisan will be able to select a suitable length for a core member in a wire guide according to a particular embodiment based on various considerations, including the intended use of the wire guide and the nature of any body vessel within which the wire guide is intended to be placed. Examples of lengths considered suitable for a core member 102 in a wire guide include, but are not limited to, lengths equal to, greater than, less than, or about 100 centimeters, 110 centimeters, 120 centimeters, 130 centimeters, 140 centimeters, 150 centimeters, 240 centimeters, 250 centimeters, 260 centimeters, 270 centimeters, 280 centimeters, between about 50 centimeters and about 350 centimeters, between about 100 centimeters and about 280 centimeters, and between about 120 centimeters and about 260 centimeters.

[0097] The jacket 104 jacket can be formed of one or more dielectric materials, and will typically be formed of a dielectric polymeric material. Examples of suitable dielectric polymeric materials include, but are not limited to, heat-formable polymeric materials, such as polyamide materials, including Nylon materials. These polymeric materials are considered desirable at least because of their ability to melt and flow between and around elements during a heat forming or heat shrinking process. Fluoropolymers, such as polytetrafluoroethylene, polyurethanes, and other polymeric materials can also be used. Additional jackets or other materials can be applied to the jacket 104 if desired. For example, a lubricious material can be applied as a topcoat on the jacket 104. The jacket 104 can have varying composition along the longitudinal length of the wire guide 100. For example, a different polymer composition can be used at one or both ends relative to a polymer composition present in the jacket disposed over the longitudinal midpoint of the wire guide. Polymer compositions that provide a more rigid, durable, or both jacket can be used at one or both ends to provide resistance to tearing or other disruptions in the continuous nature of the jacket 104.

[0098] The wire guide 100 includes a flexible distal region 114 having a preset curve shape 115. Preset curve shape 115 can, in some forms, be or include a curve shape that curves continuously around a point (an in-plane preset curve shape) or an axis (a preset curve shape that extends out of plane). The preset curve shape can be a pigtail shape, as illustrated. In some forms, the preset curve shape 115 can facilitate atraumatic positioning of the catheter past and / or within anatomical structures such as a chamber (e.g. left ventricle) of the heart or its associated valve structures. While in the illustrated embodiment the preset curve shape 115 turns through approximately 540 degrees, it will be understood that in other forms the preset curve shape can turn to a lesser or greater extent, for example including through at least 45 degrees, through at least 90 degrees, through at least 180 degrees, through at least 270 degrees, or through at least 360 degrees. In some typical forms, the preset curve shape 115 will turn through about 270 degrees to about 720 degrees. The flexible distal region 114 defines a distal end 103 of the wire guide 100 that occurs opposite a proximal end 101 of the wire guide 100. The wire guide 100 has a generally straight proximal portion 105 attached to a curved distal portion 107 defining the preset curve shape 115. The longitudinal length of the wire guide 100 that defines the curved distal portion 107 is typically in the range of about 1 cm to about 20 cm, more typically about 5 cm to about 15 cm. In addition or alternatively, in certain forms, the preset curve shape 115 can have a maximum dimension 115D, considered in a direction perpendicular to the axis of the straight proximal portion 105 of the wire guide 100, in the range of about 0.25 cm to about 8 cm, more typically about 0.5 to about 3 cm.

[0099] The wire guide 100 includes a first passive MRI marker 116, a second passive MRI marker 117, and a third passive MRI marker 118, longitudinally spaced from one another along the wire guide 100. The illustrative wire guide 100 also includes a fourth passive MRI marker 119 positioned on the straight portion 105 a relatively large longitudinal distance proximally of the next-occurring passive MRI marker of the wire guide 100 distal of the passive MRI marker 119 (providing a proximal reference marker), for example where such longitudinal distance is at least about two times, or at least about 3 times, the longitudinal distance between any two adjacent passive MRI markers of a plurality of passive MRI markers located distal of the passive MRI marker 119 on the wire guide 100. For example, such adjacent passive MRI markers can be passive markers 116 and 117 as well as passive markers 117 and 118 in some forms, or can be passive MRI markers 116 and 117 in some forms (where passive MRI marker 118 is not included in the wire guide), or can be passive MRI markers 116 and 118 in some forms (where passive marker 117 is not included in the wire guide), or can be passive MRI markers 117 and 118 in some forms (where passive marker 116 is not included in the catheter). The length of the wire guide 100 between passive MRI marker 119 and the next-occurring passive MRI marker distal of the passive MRI marker 119, can be free from any discrete MRI marker, whether passive or active. In this manner, under MRI, the relatively large spacing between respective visible artifacts generated by passive MRI marker 119 and the next-occurring discrete MRI marker distal of the passive MRI marker 119 (e.g. passive MRI marker 1 16) can be observed or tracked, rendering marker 119 and its corresponding visible artifact a beneficial positional reference for the wire guide 100 when used under MRI. In addition or alternatively, the passive MRI marker 119 can in some forms be configured to generate under MRI a visible artifact that differs from, for example has a maximum dimension larger than (e.g. at least 1 .25 times that of) or instead that is smaller than, the visible artifact generated by at least the next-occurring discrete MRI marker distal of the passive MRI marker 119 (e.g. passive MRI marker 116) and in some forms the respective visible artifacts generated by each of a plurality of passive MRI markers occurring distal of the passive MRI marker 119, e.g. passive MRI markers 116, 117 and 118. This can also aid in the function of passive MRI marker 119 as a positional reference for wire guide 100 and its distal region.

[0100] While four passive MRI markers are shown in the illustrated embodiment, any suitable number of passive MRI markers can be included on wire guides as disclosed herein, including fewer, or more, passive MRI markers than four. In the illustrated form, the wire guide 100 includes passive MRI markers 116 and 119 located on the straight portion 105 of the wire guide 100, proximate to the distal region 114, and the MRI markers 117 and 188 located on the distal region 114 of the wire guide. Other arrangements are contemplated for other embodiments herein, including in some forms arrangements in which at least one passive MRI marker is located on the straight portion 105 (e.g. at least marker 116 or at least marker 119) and at least one passive MRI marker (e.g. at least marker 117 or at least marker 118) or at least two passive MRI markers (e.g. both of markers 117 and 118) is / are located on the distal region 114; or, arrangements in which at least two passive MRI markers (e.g. both of markers 116 and 119) are located on the straight portion 105 and at least one passive marker (e.g. at least marker 117 or at least marker 118) or at least two passive MRI markers (e.g. both of markers 117 and 118) are located on the distal region 114.

[0101] The distal region 114 can be deployed from a generally straight configuration in which it is held (e.g. constrained within a lumen of a catheter) to resiliently move to the preset curve shape 115, in a fashion analogous to the deployment of the generally straight configuration of the distal region 14 of catheter 10 to the preset curve shape 16 as discussed in conjunction with FIGs. 3 to 6 above. During such deployment of the distal region 114, the relative movements and positions of the passives MRI markers 116, 117, and 118 will correspond at deployment stages to those of passive MRI markers 28, 30 and 32, respectively, of catheter 10 (see e.g. FIGs. 3-6 and discussions related thereto), which positions and movements need not be repeated here but are fully contemplated for wire guide 100 and other wire guide embodiments herein. Additionally, in the exemplary wire guide 100, from a stage corresponding to that illustrated in FIG. 6, the passive MRI marker 118 and its respective visible artifact with move distally and laterally relative to marker 116 and its visible artifact, and upon reaching the preset curve shape 115 will be positioned closer to passive MRI marker 117 and its visible artifact than to passive MRI marker 116 and its visible artifact.

[0102] Additionally, in some forms, at least one of the markers 116, 117 and 118 is configured to generate a visible artifact having a size, such as a maximum dimension, that differs from that generated by at least one other of the markers 116, 117, and 118. Such differences can further aid in observation or tracking of the shape of the distal region 114 of the wire guide 100. For example, in certain wire guide embodiments herein, the passive MRI markers 116, 117, and 118 are be configured to generate visible artifacts of sizes (e.g. maximum dimensions) that correspond, respectively, to those generated by passive MRI markers 28, 30 and 32 discussed in conjunction with FIGs. 7A-7D above.

[0103] In certain embodiments, the wire guide 100 can be free of any discrete MRI markers between passive MRI markers 116 and 117 when they are present, or free of any discrete MRI markers between passive MRI markers 117 and 118 when they are present, or free of any discrete MRI markers between passive MRI markers 116 and 118 when they are present. In some forms, when passive MRI markers 116, 117 and 118 are all present, the length of the wire guide 100 including markers 116, 117 and 118 can be free of any other discrete MRI markers. Additionally, in embodiments where passive MRI marker 119 is present, the wire guide 100 can be free of any discrete MRI markers between passive MRI marker 119 and passive MRI marker 116 when present or between passive MRI marker 119 and passive MRI marker 117 when passive MRI marker 116 is not present.

[0104] FIG. 15 provides a cross-sectional view taken along line 14X-14X illustrating the core member 102 surrounded by the jacket 104, in a region of the wire guide 100 that does not include a passive MRI marker. FIGs. 16A, 17A and 18A provide cross-sectional views taken along line 14Y-14Y of various embodiments of wire guide 100 having differing passive MRI marker configurations for passive MRI marker 116. FIGs. 16B, 17B and 18B show corresponding longitudinal views of a segment of the wire guide 100 in the region of line 14Y-14Y. Shown in FIGs. 16A and 16B are views depicting one illustrative structure for passive MRI marker 116. The marker 116 is a plug 120 embedded within the polymeric material of the jacket 104. Plug 120 includes an MRI marker-forming material as discussed herein. It has been found that relatively small amounts of suitable materials can be used for these markers. Preferred materials for these purposes are those discussed hereinabove for the catheter 10. In the illustrated embodiment, the plug 120 is positioned fully within the tubular wall of the jacket 104, having a first volume 122 of the polymeric material from which the jacket 104 is formed occurring radially outward of the plug 120 and extending to the outer surface of the jacket 104, and a second volume 124 of such polymeric material occurring radially inward of the plug 120 and extending to the surface of the core member 102. Such an arrangement can for example be accomplished by a preparative method embodiment herein that includes inserting the plug 120 into an opening in the wall of the jacket 104 extending from its outer surface and only partly through its thickness, and causing molten volumes of the polymeric material from which the jacket 104 is made to fill the opening and form a new outer surface portion of the jacket 104 over the plug 120. For these purposes, the polymeric material can be heated before, during and / or after insertion of the plug 120, for example ultrasonically or otherwise, to cause it to melt, flow and fill the opening and surround the plug 120, and then cooled (e.g. passively or actively) to solidify. Plug 120 can be mounted to the heated tip of a probe, for example with an ultrasonically heated tip, for insertion into the wall of jacket 104. The probe can heat the plug 120 and the polymeric material during the insertion and can also heat the polymeric material after deposit of the plug 120 in the jacket 104 wall and during its withdrawal from the polymeric material. This can aid in causing the polymeric material to flow and surround the plug 120 and fill in the first volume 122 of polymeric material overtop the plug 120. Such a technique can aid in achieving a self-healing of the polymeric material in forming a new outer surface of the jacket over the plug 120. The plug 120 is embedded in the jacket 104, and the jacket 104 encapsulates the core member 102 as discussed hereinabove. While in the illustrated embodiment the plug 120 is positioned only partly through the wall thickness of the jacket 104, in other forms the plug 120 can be inserted completely through the wall thickness of the jacket 104 and contact the core member 102, and the volume 122 of polymeric material can nonetheless extend between the plug 120 and the outer surface of the jacket 104.

[0105] Shown in FIGs. 17A and 17B are views depicting another illustrative structure for passive MRI marker 116. In this form, the marker 116 is a plug 130 embedded within the wall of the jacket 104. A solid fill material 132, different from the polymeric material from which the wall of jacket 104 is formed, occurs radially outward of plug 130 and provides an overlying surface 134 of the fill material that in some forms can be substantially flush with the adjacent surfaces of the jacket 104. Fill material 132 may, for example, be an adhesive, such as a polymeric adhesive. Plug 130, like plug 120 discussed above, includes an MRI marker-forming material as discussed herein.

[0106] FIGs. 18A and 18B provide views depicting another illustrative structure for passive MRI marker 116. In this form, the marker 116 is a band 140 of the MRI marker-forming material captured between the outer surface of the core member 102 and the inner surface of the jacket 104. The band 140 preferably has a thickness not exceeding about 0.1 mm, and typically being in the range of about 0.01 mm to about 0.05 mm, or about 0.01 mm to about 0.03 mm, or about 0.01 to about 0.02 mm. In some forms, the band 140 of MRI marker-forming material is adherent at least to the outer surface of the core member 102. In some forms, the band 140 can include a matrix material in which particles of the MRI marker-forming material are dispersed. In making such an arrangement for marker 116, in some forms, the band 140 can be formed by curing a flowable material applied to the outer surface of the core member. The flowable material includes a precursor to the matrix material and the particles, and upon curing solidifies to form the band 140. The jacket 104 can then be applied over the core member 102. In other forms, the band 140 can include a metal plated, for example electroplated, onto the outer surface of the core member 102, e.g. prior to applying the jacket 104 to the core member 102. Plated nickel is particularly preferred for these purposes. In still other forms, the band 90 can be formed from a solid layer material, for example a metal foil such as a nickel foil, placed over and potentially adhered (e.g. with an adhesive) to the outer surface of the core member 102 prior to applying the jacket 104 to the core member 102.

[0107] FIGs. 19A and 19B provide views depicting another illustrative structure for passive MRI marker 116. In this form, the marker 116 is a plug 150 within the wall of the jacket 104. Plug 150 is formed of a particulate MRI marker-forming material 152 dispersed within a matrix material 154, such as a polymeric matrix material (which may be the same as or different from the polymeric material forming the jacket 104). Plug 150 provides a surface 156 that can be flush with adjacent surfaces of the jacket 104. This arrangement for marker 116 form can be created by filling an opening created in the wall of jacket 104 with a flowable material including the particulate material 152 and a precursor to the matrix material 154, e.g. an adhesive, and curing the precursor material to form the matrix material 154.

[0108] FIGs. 20A and 20B provide views depicting another illustrative structure for passive MRI marker 116. In this form, the marker 116 is a band 160 of the MRI marker-forming material extending around the outer circumference of the jacket 104 and providing an outer band surface 162 over the jacket 104. Band 160 can include a matrix material 164 in which particles 166 of the MRI marker-forming material are dispersed. Band 160 can in some aspects be formed by curing a flowable material applied to the shaft including a precursor to the matrix material 164, for example an adhesive, and the particles 166, for example where the flowable material is in the nature of a MRI marker-forming ink that may also include a colorant selected to provide contrast between the band 160 and adjacent surfaces of the jacket 104.

[0109] While the above discussions regarding passive MRI marker configurations refer particularly to passive MRI marker 116 of wire guide 100, it will understood that the other passive MRI markers of the wire guide 100, for example passive markers 117, 118, and 119, can have the same features. As well, it will be understood that different passive MRI markers on the wire guide 100 may have different configurations, e.g. including a combination of any of those discussed herein.

[0110] As well, while some of the discussions above refer to MRI-marker-forming material occurring in a band extending circumferentially around the core member 102 or the jacket 104 of the wire guide 100, it will be understood that in other embodiments the discussed MRI marker-forming material could be or occur in a layer that does not extend completely around the circumference of the core member 102 or the jacket 104. These and other variations are contemplated within the scope of the present disclosure.

[0111] As discussed herein, the distal region 114 the wire guide 100 has a preset curve shape 115. The polymer jacket 104 in the preset curve shape 115 can have an innermost portion 115', or "inner spine", that extends upon a line extending in a first curve, and an outermost portion 115", or "outer spine", that extends upon a line extending in a second curve that is opposite the first curve on the jacket 104. As also discussed herein, in some forms, the MRI marker can be a plug of MRI markerforming material embedded in a wall of a polymeric jacket 104 of the wire guide 100. In certain preferred forms, such plug-form marker(s), when present in the distal region of the wire guide 100 having the preset curve shape 115, will be positioned on the circumference of the jacket 104 so as not to overlap the innermost portion 115' and / or the outermost portion 115", for example in some forms so as to be circumferentially spaced from the innermost portion 115' and / or the outermost portion 115" by at least about 15 degrees around the jacket 104 outer circumference, or at least about 30 degrees around the jacket 104 outer circumference. Such locations for the plug-form passive MRI marker(s) can be selected to provide embodiments that impart relatively low stresses on the marker(s) during movement of the distal region 114 between the preset curve shape 115 and a straightened condition, e.g. where the marker(s) do not overlap either the inner spine or the outer spine of the preset curve shape 115. Such locations for the plug-form MRI marker can in some wire guide 100 configurations facilitate preservation of the bend properties of the preset shape 1 15, for example when the outermost portion 115" of the preset shape 1 15 is pressed against anatomical surfaces of a patient during navigation or placement of the wire guide 100 while the distal region 114 is in the preset curve shape 115.

[0112] Advantageously, the marker configurations discussed above in conjunction with FIGs. 16A to 20B, or other markers herein, can occur within a relatively small region of the wire guide 100. For example, such markers can occur within a longitudinal length not exceeding 10 mm, or not exceeding 5 mm, and typically in the range of 0.2 to 5 mm; and / or, in the case of plug-form markers or some non- circumferential material layer markers, can have a width perpendicular to the axis of the jacket 104 that does not exceed about 90%, or about 80%, or about 70%, of the corresponding width of the jacket 104, or that is in the range of about 10% to about 100%, or about 10% to about 70%, of the corresponding width of the jacket 104. Markers that include plugs of MRI marker-forming material as discussed above are particularly beneficial in applying a marker within such recited widths as well as such recited longitudinal lengths.

[0113] In some embodiments, core member 102 can include features that aid in the detection of disruptions in the continuous nature of the jacket 104, which may aid in assuring use of wire guides having a truly continuous jacket 104. For example, core member 102 can include a high contrast color jacket on its surface, disposed under jacket 104. The high contrast color of this underlayment jacket is relative to any color of jacket 104. For example, if jacket 104 is a dark color, such as a black or grey, a bright color underlayment jacket, such as a yellow jacket, provides a high contrast color that, if visible upon inspection prior to use of a wire guide, can alert a user to a disruption in the continuous nature of jacket 104, allowing the user to assess whether the wire guide should be used in a contemplated procedure. Also, the core member 102 can include a coating that is responsive to exposure to an external substance other than the jacket 104, such as water. For example, the core member 102 can include a coating that changes color if it contacts an external substance, such as water. The color change can be visible under ambient light or another wavelength, such as under ultraviolet or another wavelength. Inspecting a wire guide or plurality of wire guides for suitable color changes, under appropriate light wavelengths, can be incorporated into methods of making a wire guide or a plurality of wire guide when the core member includes such a coating.

[0114] Additional embodiments herein relate to interventional medical systems that include a catheter and a wire guide extendable through a lumen of the catheter to position a distal region of the wire guide beyond a distal end of the catheter, and to wire guides and catheters that can be used in such systems. The distal region of the wire guide has at least a first wire guide-positioned passive MRI marker configured to generate a first wire guide-positioned visible artifact having a maximum dimension. The catheter has at least a first catheter-positioned passive MRI marker configured to generate a first catheter-positioned visible artifact having a maximum dimension. The maximum dimension of the first wire guide-positioned visible artifact is greater than the maximum dimension of the first catheter-positioned visible artifact, and in particularly advantageous forms substantially greater as discussed hereinbelow.

[0115] Referring now to FIGs. 21 and 22, shown in FIG. 21 is a partial cutaway side view of one illustrative embodiment of an interventional system 170 herein, and shown in FIG. 22 is a corresponding view also graphically depicting visible artifacts generated by incorporated passive MRI markers under MRI. System 170 includes a catheter 172 and a wire guide 174 extendable through a lumen of the catheter to position a distal region 176 of the wire guide 174 beyond a distal end 178 of the catheter 172. Distal region 176 includes a distal end 180 of the wire guide 174. The distal region 176 may in some forms have a longitudinal length of at least about 5 cm, or at least about 7 cm, or at least about 10 cm, or in the range of about 5 to about 30 cm, or in the range of about 7 cm to 20 cm. The distal region 176 of the wire guide 174 includes a first wire guide-positioned passive MRI marker 182. The catheter 172 includes a first catheter-positioned passive MRI discrete marker 184. As can be seen in FIG. 22, under MRI, the first wire guide-positioned passive MRI marker 182 is configured to generate a first wire guide-positioned discrete visible artifact 182A, and the first catheter-positioned passive MRI marker 184 is configured to generate a first catheter-positioned discrete visible artifact 184A, where the visible artifact 182A has a maximum dimension that is greater than that of the visible artifact 184A. In preferred forms, the maximum dimension of the first wire guide-positioned discrete artifact 182A will be at least about 1 .3 times, or at least about 2 times, that of the first catheter-positioned discrete artifact 184A, and in some aspects in the range of about 1 .3 times to about 3 times, or about 1 .5 times to about 3 times, that of the first catheter-positioned discrete artifact 184A. In certain embodiments, the first catheter-positioned passive MRI marker 184 can be the distal-most discrete MRI marker on the catheter 172, and / or the passive MRI marker 182 can be the proximal-most discrete MRI marker on the distal region 176 of the wire guide 174, and in some variants the proximal-most discrete MRI marker on the wire guide 174. As well, in some forms, the first wire guide-positioned artifact 182A may have a larger maximum dimension than that generated by any discrete MRI marker on the catheter 172 within 5 cm, or within 10cm, from its distal end 178, or in some forms on the catheter 172 as a whole. In some forms in which the first wire guide-positioned marker 182 is the proximal-most discrete MRI marker on the wire guide 174, the system 170 is positionable to a first configuration in which the marker 182 is longitudinally spaced distally of the distal end 178 of the catheter 172 a longitudinal distance D3 of at least about 5 cm, or at least about 7 cm, or at least about 10 cm, or in the range of about 5 to about 30 cm, or in the range of about 7 cm to 20 cm, along the system 170. Additionally or alternatively, where the first catheter-positioned passive MRI marker 184 is the distal-most discrete MRI marker on catheter 172 and the first wire guide-positioned passive MRI marker is the proximal-most discrete MRI marker on the wire guide 174, the passive MRI marker 184 is spaced from the passive MRI marker 182 a longitudinal distance D4 that is no more than about 1 .5 times the longitudinal distance D3, or no more than about 1 .25 times, or no more than 1 .1 times, along the system 170. It will be understood that such arrangements include embodiments in which longitudinal distances D3 and D4 are the same (where MRI marker 184 can be positioned at the distal end 178 of catheter 172).

[0116] The catheter 172 and / or the wire guide 174 can have one or more additional passive MRI markers in certain embodiments. For example, the wire guide 174 may have a second wire guide-positioned passive MRI marker 186 positioned distal of MRI marker 182 and configured to generate a discrete visible artifact 186A, which with distal region 126 in a straight configuration may be spaced from visible artifact 182A or may partially overlap visible artifact 182A as illustrated; and / or, the catheter 172 may have a second catheter-positioned passive MRI marker 188 positioned proximal of MRI marker 184 and configured to generate a discrete visible artifact 186A, which with catheter 172 in a straight configuration is preferably, but not in all embodiments necessarily, spaced from visible artifact 184A. The passive MRI markers on the catheter 172, e.g. markers 184 and 188, can in some aspects have the features shown and discussed in conjunction with any one of FIGs. 8A-12B for marker 28, and / or the passive MRI markers on the wire guide 174, e.g. markers 182 and 186, can in some aspects have the features shown and discussed in conjunction with any one of FIGs. 16A to 20B for the marker 116.

[0117] In use, the wire guide-positioned passive MRI marker(s) 182 and / or 186 can provide a distally-located positional reference during a procedure in which catheter 172 is moved proximally and / or distally along the wire guide 174 while the wire guide 174 remains in a fixed position within the patient. For example, the procedure may be conducted to treat the patient, e.g. diagnostically and / or therapeutically, within a target region 190, which in some forms is within the vasculature of the patient. For example, the treatment may include the deployment of an implant carried by the catheter, such as a stent or stent valve, into the target region, and / or the inflation of a balloon mounted on the catheter 172 within the target region, e.g. to expand a stenosed vessel segment in the target region. The wire guide 174 can be percutaneously introduced into the patient and guided through and past the target region 190 to position marker(s) 182 and / or 186 beyond the target region 190. The catheter 172 can be percutaneously introduced over the wire guide 174 (with the wire guide extending through a lumen of catheter 172) and advanced along the wire guide 174 and into the target region 190. With the wire guide 174 remaining in a fixed position in the patient, the catheter 172 can be used to treat the patient within the target region 190. During the treatment, MRI image data can be acquired and used to generate and visually display (e.g. on an electronic display monitor other electronic display) real-time or near real-time MRI images, such as two-dimensional MRI image slices, that include both the target region 190 with the catheter 172 therein and the position of the wire guide-positioned marker(s) 182 and / or 184. The image data can represent and the images can display the artifacts 182A and / or 184A generated by the wire guide-positioned marker(s) 182 and / or 184 and the artifacts 184A and / or 188A generated by the catheter-positioned MRI marker(s) 184 and / or 188. The continued visual observation, or tracking, of the wire guide- positioned artifacts 182A and / or 186A in their fixed position in the patient can provide a reference for determining that the catheter 172, and its visually observed / tracked catheter-positioned artifacts 184A and / or 188A, remain within the target region 190 (e.g. providing an indication that the system 170 as a whole has not shifted in the patient). During a given procedure on a patient, image data and displayed images may represent various regions, such as tissue planes, within the target region 190, and may be taken at various angles through or heights / depths within the volume of the target region 190. This can provide improved determinations of patient anatomical features of interest and the relative position of the catheter 172, e.g. by visual observation / tracking of the catheter-positioned artifact(s) 184A and / or 188A. As well, the patient anatomy in the target region and surrounding regions may well orient the distal region 176 of the wire guide 174 to extend in a deflected direction relative to the distal region of the catheter 172 involved in the treatment. The relatively large size(s) of the artifact(s) 182A and / or 186A can facilitate assuring that MRI image data and MRI images (e.g. two dimensional image slices) acquired to represent or show various tissue planes or other segments within the volume of target region 190 will include the artifact(s) 182A and / or 186A. In this manner, the MRI marker(s) 182 and / or 186 and their large artifacts 182A and / or 186A can serve as a highly advantageous positional reference, located outside the target region 190, during the procedure. At the same time, the relatively smaller catheter-positioned artifacts 184A and / or 188A, within the target region 190, can minimize any extent to which patient anatomical features of interest within the target region 190 are obscured.

[0118] LISTING OF SELECTED EMBODIMENTS

[0119] The following clauses provide a non-limiting enumerated listing of some of the embodiments disclosed herein. It will be understood that one, two, or more features disclosed hereinabove can be combined with the enumerated embodiments below to provide still further specific embodiments disclosed herein and that where alternative ranges or other alternative features are expressed within an enumerated embodiment each alternative range or other feature is considered to be an individually disclosed embodiment.

[0120] Embodiment 1 . An interventional medical device useful in a procedure guided under magnetic resonance imaging (MRI), comprising: an elongate member configured for insertion in a patient and having a flexible distal region, the flexible distal region having a preset curve shape in a relaxed condition but being resiliently configurable by the application of force to a second shape that differs from the preset curve shape; a first passive MRI marker at a first position along the elongate member, the first passive MRI marker configured to generate a first artifact under the MRI; a second passive MRI marker at a second position distal of the first position and along the flexible distal region, the second passive MRI marker configured to generate a second artifact under the MRI; wherein a change in relative position of the first passive MRI marker with respect to the second passive MRI marker is visibly detectable under the MRI when the flexible distal region is moved from the second shape to the preset curve shape. Embodiment 2. The interventional medical device of Embodiment 1 , wherein in the preset curve shape the flexible distal region has a longitudinal axis extending in a flat plane.

[0121] Embodiment 3. The interventional medical device of Embodiment 1 or 2, wherein the first artifact has a first maximum dimension that is about 1 .5 to about 50 times a first outer diameter of a first longitudinal segment of the catheter shaft on which the first passive MRI marker occurs, and the second artifact has a second maximum dimension that is about 1 .5 to about 50 times a second outer diameter of a second longitudinal segment of the catheter shaft on which the second passive MRI marker occurs; and, optionally wherein the first artifact has a maximum dimension that is about 2 to about 20 times the first outer diameter and the second artifact has a second maximum dimension that is about 2 to about 20 times the second outer diameter.

[0122] Embodiment 4. The interventional medical device of any one of Embodiments 1 to 3, wherein the first and second artifacts have a minimum dimension that is at least about 2 times, or at least about 3 times, greater than a maximum diameter of the flexible distal region of the elongate body.

[0123] Embodiment 5. The interventional medical device of any one of Embodiments 1 to 4, wherein as the flexible distal region moves between the second shape and the preset curved shape the second passive MRI marker moves laterally with respect to the first passive MRI marker.

[0124] Embodiment 6. The interventional medical device of any one of Embodiments 1 to 5, wherein as the flexible distal region moves between the second shape and the preset curved shape the second passive MRI marker moves closer to the first passive MRI marker, optionally wherein the second shape is a straight condition of the flexible distal region and a distance between the first and second passive MRI markers when the distal region is in the preset curve shape is no more than about 90% of a distance between the first and second passive MRI markers when the distal region is in the straight condition and preferably no more than about 50% of a distance between the first and second passive MRI markers when the distal region is in the straight condition.

[0125] Embodiment 7. The interventional medical device of any one of Embodiments 1 to 6, also comprising a third passive MRI marker, wherein the third passive MRI marker is proximal of the second passive MRI marker longitudinally along the distal region.

[0126] Embodiment 8. The interventional medical device of Embodiment 7, wherein with the flexible distal region in the second shape the second passive MRI marker is distal of the third passive MRI marker, and wherein with the flexible distal region in the preset curve shape the second passive MRI marker is proximal of the third passive MRI marker.

[0127] Embodiment 9. The interventional medical device of any one of Embodiments 1 to 8, wherein the first passive MRI marker is on the elongate member at a position proximal of the flexible distal region.

[0128] Embodiment 10. The interventional medical device of Embodiment 9, wherein the first passive MRI marker is positioned within about 2 cm of a proximal end of the distal region.

[0129] Embodiment 11 . The interventional medical device of any of Embodiments 1 to 8, wherein the first passive MRI marker is on the flexible distal region at a position proximal of the second passive MRI marker.

[0130] Embodiment 12. The interventional medical device of Embodiment 11 , wherein with the flexible distal region in the second shape the second passive MRI marker is distal of the first passive MRI marker, and wherein with the flexible distal region in the preset curve shape the second passive MRI marker is proximal of the first passive MRI marker.

[0131] Embodiment 13. The interventional medical device of any one of Embodiments 1 to 12, wherein the device is a catheter.

[0132] Embodiment 14. The interventional medical device of Embodiment 13, wherein the catheter has at least one sideport. Embodiment 15. The interventional medical device of Embodiment 14, wherein the at least one sideport is distal of the first passive MRI marker and the elongate member is free of any sideports proximal of the first passive MRI marker.

[0133] Embodiment 16. The interventional medical device of any one of Embodiments 13 to 15, wherein the first passive MRI marker and the second passive MRI marker each comprise a passive MRI marker-forming material embedded in a wall of the catheter.

[0134] Embodiment 17. The interventional medical device of Embodiment 16, wherein the wall of the catheter includes a first volume of a polymeric material forming the wall positioned radially inward of the passive MRI marker-forming material and between the passive MRI marker forming material and a catheter lumen surface defined by the first volume of polymeric material.

[0135] Embodiment 18. The interventional medical device of any one of Embodiments 13 to 17, wherein the flexible distal region is formed of a thermoplastic elastomer material.

[0136] Embodiment 19. The interventional medical device of any one of Embodiments 1 to 12, wherein the device is a wire guide.

[0137] Embodiment 20. The interventional medical device of Embodiment 19, wherein the wire guide comprises a core member and a polymeric jacket encapsulating the core member.

[0138] Embodiment 21 . The interventional medical device of Embodiment 20, wherein the core member is a single, continuous length of wire.

[0139] Embodiment 22. The interventional medical device of Embodiment 21 , wherein the wire is formed of a superelastic metal alloy.

[0140] Embodiment 23. The interventional medical device of Embodiment 22, wherein the superelastic metal alloy is nitinol.

[0141] Embodiment 24. The interventional medical device of any one of Embodiments 20 to 23, wherein the polymeric jacket is formed of a polyamide polymer.

[0142] Embodiment 25. The interventional medical device of any one of Embodiments 20 to 24, wherein the first and second passive MRI markers each comprise a passive MRI marker-forming material between the polymeric jacket and the core member. Embodiment 26. The interventional medical device of Embodiment 25, wherein the passive MRI marker-forming material is a metal layer plated onto an outer surface of the core member, optionally wherein the metal layer is a nickel layer. Embodiment 27. The interventional medical device of any one of Embodiments 20 to 24, wherein the first passive MRI marker and the second passive MRI marker each comprise a passive MRI marker-forming material embedded in a wall of the polymeric jacket.

[0143] Embodiment 28. The interventional medical device of any one of Embodiments 1 to 27, wherein the preset curve shape turns through at least about 90 degrees, at least through about 180 degrees, or at least through about 360 degrees.

[0144] Embodiment 29. The interventional medical device of Embodiment 28, wherein the preset curve shape turns through no more than about 720 degrees.

[0145] Embodiment 30. The interventional medical device of Embodiment 28 or 29, wherein the second passive MRI marker occurs at a position where the preset curve shape has turned between about 65 degrees and about 115 degrees.

[0146] Embodiment 31 . The interventional medical device of any one of Embodiments 1 to 30, wherein the first passive MRI marker and the second passive MRI each occur within a longitudinal length of the elongate member not exceeding about 10 mm, or not exceeding about 5 mm, or in the range of about 0.2 to about 5 mm.

[0147] Embodiment 32. The interventional medical device of Embodiment 31 , wherein the first passive MRI marker and the second passive MRI marker each include a layer of a passive MRI marker-forming material, optionally wherein the layer in the form of a circumferential band.

[0148] Embodiment 33. The interventional medical device of Embodiment 32, wherein the first passive MRI marker and the second passive marker each include a plug of a passive MRI marker-forming material, optionally wherein the plug does not overlap an innermost portion of the elongate member that, with the distal region in the preset curve shape, extends upon a line extending in a first curve of the preset curve shape and also does not overlap an outermost portion of the elongate member that, with the distal region in the preset curve shape, extends upon a line extending in a second curve that is opposite the first curve.

[0149] Embodiment 34. The interventional medical device of any one of Embodiments 1 to 32, wherein the first passive MRI marker and the second passive MRI marker occur within a width across the elongate member not exceeding about 70% of an outer width of the elongate member at a respective position of the first passive MRI marker and the second passive MRI marker.

[0150] Embodiment 35. The interventional medical device of any one of Embodiments 1 to 34, wherein the first passive MRI marker and the second passive MRI marker each include (i) an MRI marker-forming material having a volume not exceeding 5 mm3, or not exceeding 3 mm3, or not exceeding 1 mm3, or not exceeding 0.1 mm3in each of these aspects, the volume may be at least 0.00005 mm3, or at least about 0.0001 mm3; or (i) an MRI marker-forming material having a magnetic susceptibility of at least about 1 and having a volume not exceeding 0.1 mm3, or in the range of 0.00001 mm3to 0.1 mm3, or in the range of 0.00005 mm3to 0.02 mm3.

[0151] Embodiment 36. The interventional medical device of any one of Embodiments 1 to 35, wherein the first passive MRI marker and the second passive MRI marker each include an MRI-marking forming material having a magnetic susceptibility of at least about 500 ppm, or at least about 2000 ppm, or in the range of about 500 ppm to about 1000, or in the range of about 7000 ppm to about 1000.

[0152] Embodiment 37. The interventional medical device of any one of Embodiments 1 to 36, wherein the first passive MRI marker and the second passive MRI marker each include an MRI marker-forming material selected from nickel, nickel alloys, cobalt, cobalt alloys, iron, and iron alloys.

[0153] Embodiment 38. The interventional medical device of any one of Embodiments 1 to 37, also comprising a proximal reference passive MRI marker on the elongate member at a position proximal of the first passive MRI marker, optionally wherein the proximal reference passive MRI marker is configured to generate an artifact (i) having a maximum dimension greater than that of the first passive MRI marker and that of the second passive MRI marker, or (ii) having a maximum dimension greater than that of any discrete MRI marker distal of the proximal reference passive MRI marker.

[0154] Embodiment 39. The interventional medical device of Embodiment 38, wherein: the first passive MRI marker is longitudinally adjacent to the second passive MRI marker and positioned a first longitudinal distance from the second passive marker, wherein the proximal reference passive MRI marker is positioned a second longitudinal distance from the first passive MRI marker, and wherein the second longitudinal distance is at least two times the first longitudinal distance; and / or the proximal reference passive MRI marker is configured to generate an artifact having a maximum dimension that is at least about 1 .25 times that of the first passive MRI marker and that of the second passive MRI marker.

[0155] Embodiment 40. The interventional medical device of any one of Embodiments 1 to 39, wherein: the first passive MRI marker and the second passive MRI markers are configured to generate artifacts that differ in size from each other; or the first passive MRI marker and the second passive MRI marker are formed from the same passive MRI maker-forming material but have differing volumes of the passive MRI marker-forming material; or the first passive MRI marker is formed of a first passive MRI markerforming material and the second passive MRI marker is formed of a second passive MRI marker-forming material, wherein the first passive MRI marker-forming material has a magnetic susceptibility that differs from that of the second passive MRI marker-forming material.

[0156] Embodiment 41 . An interventional system useful in medical procedures guided under magnetic resonance imaging (MRI) at a primary magnetic field strength, comprising: a first elongate medical device for treating a target region of a patient with a distal region of the medical device, the first elongate medical device having a distal end, the first elongate medical device including a first passive MRI marker; and a second elongate medical device positionable through a lumen of the first elongate medical device so as to locate a distal region of the second elongate of the medical device distal of the distal end of the first elongate medical device, the distal region including a first passive MRI marker; wherein the first passive MRI marker of the first elongate medical device is configured to generate a first medical device-positioned artifact under the MRI having a maximum dimension; wherein the first passive MRI marker of the second elongate medical device is configured to generate a second medical device-positioned artifact under the MRI having a maximum dimension; and wherein the maximum dimension of the second medical device-positioned artifact is greater than the maximum dimension of the first medical device-positioned artifact.

[0157] Embodiment 42. The interventional system of Embodiment 41 , wherein the first elongate medical device is a catheter.

[0158] Embodiment 43. The interventional system of Embodiment 41 or 42, wherein the second elongate medical device is a wire guide.

[0159] Embodiment 44. The interventional system of Embodiment 43, wherein the wire guide comprises a core member and a polymeric jacket encapsulating the core member.

[0160] Embodiment 45. The interventional system of Embodiment 44, wherein the core member is a single, continuous length of wire.

[0161] Embodiment 46. The interventional system of Embodiment 45, wherein the wire is formed of a superelastic metal alloy.

[0162] Embodiment 47. The interventional system of Embodiment 46, wherein the superelastic metal alloy is nitinol.

[0163] Embodiment 48. The interventional system of any one of Embodiments 44 to 47, wherein the polymeric jacket is formed of a polyamide polymer.

[0164] Embodiment 49. The interventional system of any one of Embodiments 44 to 48, wherein the first and second passive MRI markers each comprise a passive MRI marker-forming material between the polymeric jacket and the core member. Embodiment 50. The interventional system of Embodiment 49, wherein the passive MRI marker-forming material is a metal layer plated onto an outer surface of the core member, optionally wherein the metal layer is a nickel layer.

[0165] Embodiment 51 . The interventional system of any one of Embodiments 44 to 48, wherein the first passive MRI marker and the second passive MRI marker each comprise a passive MRI marker-forming material embedded in a wall of the polymeric jacket.

[0166] Embodiment 52. The interventional system of any one of Embodiments 41 to 51 , wherein the distal region of the second elongate medical device has a longitudinal length of at least about 5 cm, or at least about 7 cm, or at least about 10 cm, or in the range of about 5 to about 30 cm, or in the range of about 7 cm to 20 cm. Embodiment 53. The interventional system of any one of Embodiments 41 to 52, wherein the first passive MRI marker of the second elongate medical device is a proximal-most discrete MRI marker in the distal region of the second elongate medical device, and wherein the system is positionable to a first configuration in which the first passive MRI marker of the second elongate medical device is longitudinally spaced a first distance distally of the distal end of the first elongate medical device, wherein the first distance is at least about 7 cm, or at least about 10 cm, or in the range of 7 to 30 cm.

[0167] Embodiment 54. The interventional system of Embodiment 53, wherein the first passive MRI marker of the first elongate medical device is a distal-most discrete MRI marker of the first elongate medical device, and wherein in the first configuration the first passive MRI marker of the second medical device is longitudinally spaced a second distance distally of the first passive MRI marker of the first elongate medical device, wherein the second distance is no more than about 1 .25 times the first distance.

[0168] Embodiment 55. The interventional system of any one of Embodiments 41 to 54, wherein the first medical device is a catheter, and wherein the first passive MRI marker comprises a passive MRI marker-forming material embedded in a wall of the catheter.

[0169] Embodiment 56. The interventional system of Embodiment 55, wherein the wall of the catheter includes a first volume of a polymeric material forming the wall positioned radially inward of the passive MRI marker-forming material and between the passive MRI marker forming material and a catheter lumen surface defined by the first volume of polymeric material.

[0170] Embodiment 57. The interventional system of Embodiment 56, wherein the polymeric material comprises a thermoplastic elastomer material.

[0171] Embodiment 58. The interventional system of any one of Embodiments 41 to 57, wherein the first passive MRI marker and the second passive MRI marker each include (i) an MRI marker-forming material having a volume not exceeding 5 mm3, or not exceeding 3 mm3, or not exceeding 1 mm3, or not exceeding 0.1 mm3in each of these aspects, the volume may be at least 0.00005 mm3, or at least about 0.0001 mm3; or (i) an MRI marker-forming material having a magnetic susceptibility of at least about 1 and having a volume not exceeding 0.1 mm3, or in the range of 0.00001 mm3to 0.1 mm3, or in the range of 0.00005 mm3to 0.02 mm3.

[0172] Embodiment 59. The interventional system of any one of Embodiments 41 to

[0173] 58, wherein the first passive MRI marker and the second passive MRI marker each include an MRI-marking forming material having a magnetic susceptibility of at least about 500 ppm, or at least about 2000 ppm, or in the range of about 500 ppm to about 1000, or in the range of about 7000 ppm to about 1000.

[0174] Embodiment 60. The interventional system of any one of Embodiments 41 to

[0175] 59, wherein: the first passive MRI marker and the second passive MRI marker each include an MRI marker-forming material selected from nickel, nickel alloys, cobalt, cobalt alloys, iron, and iron alloys; or the first passive MRI marker and the second passive MRI marker are configured to generate visible artifacts that differ in size from each other; or the first passive MRI marker and the second passive MRI marker are formed from the same passive MRI maker-forming material but have differing volumes of the passive MRI marker-forming material; or the first passive MRI marker is formed of a first passive MRI markerforming material and the second passive MRI marker is formed of a second passive MRI marker-forming material, wherein the first passive MRI marker-forming material has a magnetic susceptibility that differs from that of the second passive MRI marker-forming material.

[0176] Embodiment 61 . An interventional medical device useful under magnetic resonance imaging (MRI), comprising: an elongate member configured for insertion in a patient and having a flexible distal region, the flexible distal region having a preset curve shape in a relaxed condition but being resiliently configurable upon the application of force to a straight condition; a first passive MRI marker at a first position along the elongate member; a second passive MRI marker at a second position along the elongate member, the second position longitudinally spaced from the first position; and wherein: (i) the first passive MRI marker is proximate to a proximal end of the flexible distal region having the preset curve shape and the second passive MRI marker is longitudinally distal of the first passive MRI marker and on the flexible distal region having the preset curve shape, and wherein the second passive MRI marker is closer to the first passive marker when the distal region is in the preset curve shape than when the distal region is in the straight condition; or

[0177] (ii) the first passive MRI marker and the second passive MRI marker are both on the flexible distal region having the preset curve shape, and are configured to generate respective, discretely visible artifacts under MRI at a primary magnetic field strength of at least one of 0.55T, 1 ,5T and 3T, both when the flexible distal region is in the straight condition and in the preset curve shape; or

[0178] (iii) one of the first passive MRI marker or the second passive MRI marker is positioned on the distal region so as to mark a distal-most position of the preset curve shape.

[0179] Embodiment 62. The interventional medical device of Embodiment 61 , wherein the first passive MRI marker is proximal of the flexible distal region having a preset curve shape and the second passive MRI marker is on the flexible distal region having a preset curve shape, wherein the second passive MRI marker is closer to the first passive marker when the distal region is in the preset curve shape than when the distal region is in the straight condition.

[0180] Embodiment 63. The interventional medical device of Embodiment 62, wherein a distance between the first and second passive MRI markers when the distal region is in the preset curve shape is no more than about 90% of a distance between the first and second passive MRI markers when the distal region is in the straight condition, and optionally wherein the first passive MRI marker is positioned longitudinally within 2 cm of the flexible distal region.

[0181] Embodiment 64. The interventional medical device of any one of Embodiments 61 to 63, also comprising a third passive MRI marker; and, optionally wherein at least one of the first, second, and third passive MRI markers is configured to generate a visible artifact having a size that differs from at least one other of the first, second, and third passive MRI markers.

[0182] Embodiment 65. The interventional medical device of Embodiment 64, wherein the third passive MRI marker is positioned on the distal region and is longitudinally between the first the first passive MRI marker and the second passive MRI marker along the elongate member.

[0183] Embodiment 66. The interventional medical device of Embodiment 65, wherein with the flexible distal region in the straight condition the second passive MRI marker is distal of the third passive MRI marker, and wherein with the flexible distal region in the preset curve shape the second passive MRI marker is proximal of the third passive MRI marker.

[0184] Embodiment 67. The interventional medical device of Embodiment 65 or 66, wherein the second passive MRI marker is closer to the first passive marker when the distal region is in the preset curve shape than when the distal region is in the straight condition.

[0185] Embodiment 68. The interventional medical device of Embodiment 62, wherein the first passive MRI marker and the second passive MRI marker are both on the flexible distal region having the preset curve shape, and are longitudinally spaced from one another and configured to generate respective, discretely visible artifacts under MRI at a primary magnetic field strength of at least one of 0.55T, 1 ,5T and 3T, both when the flexible distal region is in the straight condition and in the preset curve shape.

[0186] Embodiment 69. The interventional medical device of Embodiment 68, wherein the second passive MRI marker is longitudinally proximal of the first passive MRI marker on the flexible distal region, and wherein with the flexible distal region in the straight condition the first passive MRI marker is distal of the second passive MRI marker, and with the flexible distal region in the preset curve shape the first passive MRI marker is proximal of the second passive MRI marker.

[0187] Embodiment 70. The interventional medical device of Embodiment 68 or 69, also comprising a third passive MRI marker; and, optionally wherein at least one of the first, second, and third passive MRI markers is configured to generate a visible artifact having a size that differs from at least one other of the first, second, and third passive MRI markers.

[0188] Embodiment 71 . The interventional medical device of Embodiment 70, wherein the third passive MRI marker is positioned longitudinally within about 2 cm of a proximal end of the flexible distal region. Embodiment 72. The interventional medical device of any one of Embodiments 69 to 71 , wherein a distance between the first and third passive MRI markers when the flexible distal region is in the preset curve shape is no more than about 90% of a distance between the first and third passive MRI markers when the flexible distal region is in the straight condition; and, optionally wherein a distance between the first and third passive MRI markers when the flexible distal region is in the preset curve shape is no more than about 50% of a distance between the first and third passive MRI markers when the flexible distal region is in the straight condition. Embodiment 73. The interventional medical device of any one of Embodiments 61 to 72, wherein the second passive MRI marker is positioned on the distal region so as to mark a distal-most position of the preset curve shape.

[0189] Embodiment 74. The interventional medical device of any one of Embodiments 61 to 73, which is a wire guide, optionally wherein the wire guide comprises a core member and a polymeric jacket encapsulating the core member.

[0190] Embodiment 75. The interventional medical device of Embodiment 74, wherein the wire guide comprises a core member and a polymeric jacket encapsulating the core member, and wherein the core member is a single, continuous length of wire. Embodiment 76. The interventional medical device of Embodiment 75, wherein the wire is formed of a superelastic metal alloy.

[0191] Embodiment 77. The interventional medical device of Embodiment 76, wherein the superelastic metal alloy is nitinol.

[0192] Embodiment 78. The interventional medical device of any one of Embodiments 74 to 77, wherein the polymeric jacket is formed of a polyamide polymer.

[0193] Embodiment 79. The interventional medical device of any one of Embodiments

[0194] 73 to 78, wherein the first and second passive MRI markers each comprise a passive MRI marker-forming material between the polymeric jacket and the core member.

[0195] Embodiment 80. The interventional medical device of Embodiment 79, wherein the passive MRI marker-forming material is a metal layer plated onto an outer surface of the core member, optionally wherein the metal layer is a nickel layer. Embodiment 81 . The interventional medical device of any one of Embodiments

[0196] 74 to 78, wherein the first passive MRI marker and the second passive MRI marker each comprise a passive MRI marker-forming material embedded in a wall of the polymeric jacket.

[0197] Embodiment 82. The interventional medical device of any one of Embodiments 61 to 72, which is a catheter.

[0198] Embodiment 83. The interventional medical device of Embodiment 82, wherein the catheter has at least one sideport.

[0199] Embodiment 84. The interventional medical device of Embodiment 83, wherein the at least one sideport is distal of the first passive MRI marker and the elongate member is free of any sideports proximal of the first passive MRI marker.

[0200] Embodiment 85. The interventional medical device of any one of Embodiments 82 to 84, wherein the first passive MRI marker and the second passive MRI marker each comprise a passive MRI marker-forming material embedded in a wall of the catheter.

[0201] Embodiment 86. The interventional medical device of Embodiment 85, wherein the wall of the catheter includes a first volume of a polymeric material forming the wall positioned radially inward of the passive MRI marker-forming material and between the passive MRI marker forming material and a catheter lumen surface defined by the first volume of polymeric material.

[0202] Embodiment 87. The interventional medical device of any one of Embodiments 82 to 86, wherein the flexible distal region is formed of a thermoplastic elastomer material.

[0203] Embodiment 88. The interventional medical device of any one of Embodiments 61 to 87, wherein the preset curve shape turns through at least about 90 degrees, at least through about 180 degrees, or at least through about 360 degrees.

[0204] Embodiment 89. The interventional medical device of Embodiment 88, wherein the preset curve shape turns through no more than about 720 degrees.

[0205] Embodiment 90. The interventional medical device of any one of Embodiments 61 to 89, wherein the second passive MRI marker occurs at a position where the preset curve shape has turned between about 65 degrees and about 115 degrees. Embodiment 91 . The interventional medical device of any one of Embodiments 61 to 90, wherein the first passive MRI marker and the second passive MRI each occur within a longitudinal length of the elongate member not exceeding about 10 mm, or not exceeding about 5 mm, or in the range of about 0.2 to about 5 mm. Embodiment 92. The interventional medical device of any one of Embodiments 61 to 91 , wherein the first passive MRI marker and the second passive MRI marker occur within a width across the elongate member not exceeding about 70% of an outer width of the elongate member at a respective position of the first passive MRI marker and the second passive MRI marker.

[0206] Embodiment 93. The interventional medical device of any one of Embodiments 61 to 92, wherein the first passive MRI marker and the second passive MRI marker each include (i) an MRI marker-forming material having a volume not exceeding 5 mm3, or not exceeding 3 mm3, or not exceeding 1 mm3, or not exceeding 0.1 mm3in each of these aspects, the volume may be at least 0.00005 mm3, or at least about 0.0001 mm3; or (i) an MRI marker-forming material having a magnetic susceptibility of at least about 1 and having a volume not exceeding 0.1 mm3, or in the range of 0.00001 mm3to 0.1 mm3, or in the range of 0.00005 mm3to 0.02 mm3.

[0207] Embodiment 94. The interventional medical device of any one of Embodiments 61 to 93, wherein the first passive MRI marker and the second passive MRI marker each include an MRI-marking forming material having a magnetic susceptibility of at least about 500 ppm, or at least about 2000 ppm, or in the range of about 500 ppm to about 1000, or in the range of about 7000 ppm to about 1000.

[0208] Embodiment 95. The interventional medical device of any one of Embodiments 61 to 94, wherein the first passive MRI marker and the second passive MRI marker each include an MRI marker-forming material selected from nickel, nickel alloys, cobalt, cobalt alloys, iron, and iron alloys.

[0209] Embodiment 96. The interventional medical device of any one of Embodiments 61 to 95, wherein: the first passive MRI marker and the second passive MRI markers are configured to generate artifacts that differ in size from each other; or the first passive MRI marker and the second passive MRI marker are formed from the same passive MRI maker-forming material but have differing volumes of the passive MRI marker-forming material; or the first passive MRI marker is formed of a first passive MRI marker-forming material and the second passive MRI marker is formed of a second passive MRI marker-forming material, wherein the first passive MRI marker-forming material has a magnetic susceptibility that differs from that of the second passive MRI markerforming material.

[0210] Embodiment 97. The interventional medical device of Embodiment any one of Embodiments 61 to 96, wherein the first passive MRI marker and the second passive MRI marker each include a layer of a passive MRI marker-forming material, optionally wherein the layer in the form of a circumferential band.

[0211] Embodiment 98. The interventional medical device of any one of Embodiments 61 to 96, wherein the first passive MRI marker and the second passive marker each include a plug of a passive MRI marker-forming material, optionally wherein the plug does not overlap an innermost portion of the elongate member that, with the distal region in the preset curve shape, extends upon a line extending in a first curve of the preset curve shape and also does not overlap an outermost portion of the elongate member that, with the distal region in the preset curve shape, extends upon a line extending in a second curve that is opposite the first curve.

[0212] Embodiment 99. A method for making an interventional medical device useful in a procedure guided under magnetic resonance imaging (MRI), comprising: providing an elongate member configured for insertion in a patient and having a flexible distal region, the flexible distal region having a preset curve shape in a relaxed condition but being resiliently configurable by the application of force to a second shape that differs from the preset curve shape; providing a first passive MRI marker at a first position along the elongate member, the first passive MRI marker configured to generate a first artifact under the MRI; and providing a second passive MRI marker at a second position distal of the first position and along the flexible distal region, the second passive MRI marker configured to generate a second artifact under the MRI.

[0213] Embodiment 100. The method of Embodiment 99, wherein: said providing an elongate member includes treating the elongate member to introduce the preset curve shape; and wherein said providing a second passive MRI marker is conducted before said treating.

[0214] Embodiment 101 . The method of Embodiment 100, wherein: said providing a passive marker includes embedding a volume of a passive MRI marker-forming material in a polymeric material of the elongate member; and said treating includes heating the polymeric material to reset its shape in the presence of the volume of passive MRI marker-forming material.

[0215] Embodiment 102. The method of any one of Embodiments 99 to 101 , wherein the interventional medical device is a catheter and the elongate member is a catheter shaft.

[0216] Embodiment 103. The method of any one of Embodiments 99 to 102, wherein the first passive MRI marker is also along the flexible distal region.

[0217] Embodiment 104. The method of any one of Embodiments 99 to 103, wherein: said interventional medical device is a catheter according to any one of Embodiments 1 -18, 28-40, 61-72 or 82-98.

[0218] While embodiments of the disclosure have been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only some embodiments have been shown and described and that all changes and modifications that come within the spirit of the disclosures herein are desired to be protected. As examples, it will be understood that individual features or combinations of features (e.g. 2, 3 or 4 features) as described in the Detailed Description above can be combined with the features of the Claims below to provide additional embodiments herein.

[0219] The uses of the terms "a" and "an" and "the" and similar references herein (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as") provided herein, is intended merely to better illuminate embodiments of the disclosure and does not pose a limitation on the scope of the disclosure unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the products or methods defined by the claims.

[0220] All references cited herein are indicative of the level of skill in the art and are hereby incorporated by reference in their entirety.

Claims

CLAIMS1 . An interventional medical device useful in a procedure guided under magnetic resonance imaging (MRI), comprising: an elongate member configured for insertion in a patient and having a flexible distal region, the flexible distal region having a preset curve shape in a relaxed condition but being resiliently configurable by the application of force to a second shape that differs from the preset curve shape; a first passive MRI marker at a first position along the elongate member, the first passive MRI marker configured to generate a first artifact under the MRI; a second passive MRI marker at a second position distal of the first position and along the flexible distal region, the second passive MRI marker configured to generate a second artifact under the MRI; wherein a change in relative position of the first passive MRI marker with respect to the second passive MRI marker is visibly detectable under the MRI when the flexible distal region is moved from the second shape to the preset curve shape.

2. The interventional medical device of claim 1 , wherein in the preset curve shape the flexible distal region has a longitudinal axis extending in a flat plane.

3. The interventional medical device of claim 1 or 2, wherein the first artifact has a first maximum dimension that is about 1 .5 to about 50 times a first outer diameter of a first longitudinal segment of the catheter shaft on which the first passive MRI marker occurs, and the second artifact has a second maximum dimension that is about 1 .5 to about 50 times a second outer diameter of a second longitudinal segment of the catheter shaft on which the second passive MRI marker occurs; and, optionally wherein the first artifact has a maximum dimension that is about 2 to about 20 times the first outer diameter and the second artifact has a second maximum dimension that is about 2 to about 20 times the second outer diameter.

4. The interventional medical device of any one of claims 1 to 3, wherein the first and second artifacts have a minimum dimension that is at least about 2 times, or at least about 3 times, greater than a maximum diameter of the flexible distal region of the elongate body.

5. The interventional medical device of any one of claims 1 to 4, wherein as the flexible distal region moves between the second shape and the preset curved shapethe second passive MRI marker moves laterally with respect to the first passive MRI marker.

6. The interventional medical device of any one of claims 1 to 5, wherein as the flexible distal region moves between the second shape and the preset curved shape the second passive MRI marker moves closer to the first passive MRI marker, optionally wherein the second shape is a straight condition of the flexible distal region and a distance between the first and second passive MRI markers when the distal region is in the preset curve shape is no more than about 90% of a distance between the first and second passive MRI markers when the distal region is in the straight condition and preferably no more than about 50% of a distance between the first and second passive MRI markers when the distal region is in the straight condition.

7. The interventional medical device of any one of claims 1 to 6, also comprising a third passive MRI marker, wherein the third passive MRI marker is proximal of the second passive MRI marker longitudinally along the distal region.

8. The interventional medical device of claim 7, wherein with the flexible distal region in the second shape the second passive MRI marker is distal of the third passive MRI marker, and wherein with the flexible distal region in the preset curve shape the second passive MRI marker is proximal of the third passive MRI marker.

9. The interventional medical device of any one of claims 1 to 8, wherein the first passive MRI marker is on the elongate member at a position proximal of the flexible distal region.

10. The interventional medical device of claim 9, wherein the first passive MRI marker is positioned within about 2 cm of a proximal end of the distal region.11 . The interventional medical device of any of claims 1 to 8, wherein the first passive MRI marker is on the flexible distal region at a position proximal of the second passive MRI marker.

12. The interventional medical device of claim 11 , wherein with the flexible distal region in the second shape the second passive MRI marker is distal of the first passive MRI marker, and wherein with the flexible distal region in the preset curve shape the second passive MRI marker is proximal of the first passive MRI marker.

13. The interventional medical device of any one of claims 1 to 12, wherein the device is a catheter.

14. The interventional medical device of claim 13, wherein the catheter has at least one sideport.

15. The interventional medical device of claim 14, wherein the at least one sideport is distal of the first passive MRI marker and the elongate member is free of any sideports proximal of the first passive MRI marker.

16. The interventional medical device of any one of claims 13 to 15, wherein the first passive MRI marker and the second passive MRI marker each comprise a passive MRI marker-forming material embedded in a wall of the catheter.

17. The interventional medical device of claim 16, wherein the wall of the catheter includes a first volume of a polymeric material forming the wall positioned radially inward of the passive MRI marker-forming material and between the passive MRI marker forming material and a catheter lumen surface defined by the first volume of polymeric material.

18. The interventional medical device of any one of claims 13 to 17, wherein the flexible distal region is formed of a thermoplastic elastomer material.

19. The interventional medical device of any one of claims 1 to 12, wherein the device is a wire guide.

20. The interventional medical device of claim 19, wherein the wire guide comprises a core member and a polymeric jacket encapsulating the core member.21 . The interventional medical device of claim 20, wherein the core member is a single, continuous length of wire.

22. The interventional medical device of claim 21 , wherein the wire is formed of a superelastic metal alloy.

23. The interventional medical device of claim 22, wherein the superelastic metal alloy is nitinol.

24. The interventional medical device of any one of claims 20 to 23, wherein the polymeric jacket is formed of a polyamide polymer.

25. The interventional medical device of any one of claims 20 to 24, wherein the first and second passive MRI markers each comprise a passive MRI marker-forming material between the polymeric jacket and the core member.

26. The interventional medical device of claim 25, wherein the passive MRI marker-forming material is a metal layer plated onto an outer surface of the core member, optionally wherein the metal layer is a nickel layer.

27. The interventional medical device of any one of claims 20 to 24, wherein the first passive MRI marker and the second passive MRI marker each comprise a passive MRI marker-forming material embedded in a wall of the polymeric jacket.

28. The interventional medical device of any one of claims 1 to 27, wherein the preset curve shape turns through at least about 90 degrees, at least through about 180 degrees, or at least through about 360 degrees.

29. The interventional medical device of claim 28, wherein the preset curve shape turns through no more than about 720 degrees.

30. The interventional medical device of claim 28 or 29, wherein the second passive MRI marker occurs at a position where the preset curve shape has turned between about 65 degrees and about 115 degrees.31 . The interventional medical device of any one of claims 1 to 30, wherein the first passive MRI marker and the second passive MRI each occur within a longitudinal length of the elongate member not exceeding about 10 mm, or not exceeding about 5 mm, or in the range of about 0.2 to about 5 mm.

32. The interventional medical device of claim 31 , wherein the first passive MRI marker and the second passive MRI marker each include a layer of a passive MRI marker-forming material, optionally wherein the layer in the form of a circumferential band.

33. The interventional medical device of claim 32, wherein the first passive MRI marker and the second passive marker each include a plug of a passive MRI marker-forming material, optionally wherein the plug does not overlap an innermost portion of the elongate member that, with the distal region in the preset curve shape, extends upon a line extending in a first curve of the preset curve shape and also does not overlap an outermost portion of the elongate member that, with the distal region in the preset curve shape, extends upon a line extending in a second curve that is opposite the first curve.

34. The interventional medical device of any one of claims 1 to 32, wherein the first passive MRI marker and the second passive MRI marker occur within a width across the elongate member not exceeding about 70% of an outer width of the elongate member at a respective position of the first passive MRI marker and the second passive MRI marker.

35. The interventional medical device of any one of claims 1 to 34, wherein the first passive MRI marker and the second passive MRI marker each include (i) an MRI marker-forming material having a volume not exceeding 5 mm3, or not exceeding 3 mm3, or not exceeding 1 mm3, or not exceeding 0.1 mm3in each of these aspects, the volume may be at least 0.00005 mm3, or at least about 0.0001 mm3; or (i) an MRI marker-forming material having a magnetic susceptibility of at least about 1 and having a volume not exceeding 0.1 mm3, or in the range of 0.00001 mm3to 0.1 mm3, or in the range of 0.00005 mm3to 0.02 mm3.

36. The interventional medical device of any one of claims 1 to 35, wherein the first passive MRI marker and the second passive MRI marker each include an MRI- marking forming material having a magnetic susceptibility of at least about 500 ppm, or at least about 2000 ppm, or in the range of about 500 ppm to about 1000, or in the range of about 7000 ppm to about 1000.

37. The interventional medical device of any one of claims 1 to 36, wherein the first passive MRI marker and the second passive MRI marker each include an MRI marker-forming material selected from nickel, nickel alloys, cobalt, cobalt alloys, iron, and iron alloys.

38. The interventional medical device of any one of claims 1 to 37, also comprising a proximal reference passive MRI marker on the elongate member at a position proximal of the first passive MRI marker, optionally wherein the proximal reference passive MRI marker is configured to generate an artifact (i) having a maximum dimension greater than that of the first passive MRI marker and that of the second passive MRI marker, or (ii) having a maximum dimension greater than that of any discrete MRI marker distal of the proximal reference passive MRI marker.

39. The interventional medical device of claim 38, wherein: the first passive MRI marker is longitudinally adjacent to the second passive MRI marker and positioned a first longitudinal distance from the second passive marker, wherein the proximal reference passive MRI marker is positioned a second longitudinal distance from the first passive MRI marker, and wherein the second longitudinal distance is at least two times the first longitudinal distance; and / orthe proximal reference passive MRI marker is configured to generate an artifact having a maximum dimension that is at least about 1 .25 times that of the first passive MRI marker and that of the second passive MRI marker.

40. The interventional medical device of any one of claims 1 to 39, wherein: the first passive MRI marker and the second passive MRI markers are configured to generate artifacts that differ in size from each other; or the first passive MRI marker and the second passive MRI marker are formed from the same passive MRI maker-forming material but have differing volumes of the passive MRI marker-forming material; or the first passive MRI marker is formed of a first passive MRI markerforming material and the second passive MRI marker is formed of a second passive MRI marker-forming material, wherein the first passive MRI marker-forming material has a magnetic susceptibility that differs from that of the second passive MRI marker-forming material.41 . An interventional system useful in medical procedures guided under magnetic resonance imaging (MRI) at a primary magnetic field strength, comprising: a first elongate medical device for treating a target region of a patient with a distal region of the medical device, the first elongate medical device having a distal end, the first elongate medical device including a first passive MRI marker; and a second elongate medical device positionable through a lumen of the first elongate medical device so as to locate a distal region of the second elongate of the medical device distal of the distal end of the first elongate medical device, the distal region including a first passive MRI marker; wherein the first passive MRI marker of the first elongate medical device is configured to generate a first medical device-positioned artifact under the MRI having a maximum dimension; wherein the first passive MRI marker of the second elongate medical device is configured to generate a second medical device-positioned artifact under the MRI having a maximum dimension; and wherein the maximum dimension of the second medical device-positioned artifact is greater than the maximum dimension of the first medical device-positioned artifact.

42. The interventional system of claim 41 , wherein the first elongate medical device is a catheter.

43. The interventional system of claim 41 or 42, wherein the second elongate medical device is a wire guide.

44. The interventional system of claim 43, wherein the wire guide comprises a core member and a polymeric jacket encapsulating the core member.

45. The interventional system of claim 44, wherein the core member is a single, continuous length of wire.

46. The interventional system of claim 45, wherein the wire is formed of a superelastic metal alloy.

47. The interventional system of claim 46, wherein the superelastic metal alloy is nitinol.

48. The interventional system of any one of claims 44 to 47, wherein the polymeric jacket is formed of a polyamide polymer.

49. The interventional system of any one of claims 44 to 48, wherein the first and second passive MRI markers each comprise a passive MRI marker-forming material between the polymeric jacket and the core member.

50. The interventional system of claim 49, wherein the passive MRI markerforming material is a metal layer plated onto an outer surface of the core member, optionally wherein the metal layer is a nickel layer.51 . The interventional system of any one of claims 44 to 48, wherein the first passive MRI marker and the second passive MRI marker each comprise a passive MRI marker-forming material embedded in a wall of the polymeric jacket.

52. The interventional system of any one of claims 41 to 51 , wherein the distal region of the second elongate medical device has a longitudinal length of at least about 5 cm, or at least about 7 cm, or at least about 10 cm, or in the range of about 5 to about 30 cm, or in the range of about 7 cm to 20 cm.

53. The interventional system of any one of claims 41 to 52, wherein the first passive MRI marker of the second elongate medical device is a proximal-most discrete MRI marker in the distal region of the second elongate medical device, and wherein the system is positionable to a first configuration in which the first passive MRI marker of the second elongate medical device is longitudinally spaced a first distance distally of the distal end of the first elongate medical device, wherein thefirst distance is at least about 7 cm, or at least about 10 cm, or in the range of 7 to 30 cm.

54. The interventional system of claim 53, wherein the first passive MRI marker of the first elongate medical device is a distal-most discrete MRI marker of the first elongate medical device, and wherein in the first configuration the first passive MRI marker of the second medical device is longitudinally spaced a second distance distally of the first passive MRI marker of the first elongate medical device, wherein the second distance is no more than about 1 .25 times the first distance.

55. The interventional system of any one of claims 41 to 54, wherein the first medical device is a catheter, and wherein the first passive MRI marker comprises a passive MRI marker-forming material embedded in a wall of the catheter.

56. The interventional system of claim 55, wherein the wall of the catheter includes a first volume of a polymeric material forming the wall positioned radially inward of the passive MRI marker-forming material and between the passive MRI marker forming material and a catheter lumen surface defined by the first volume of polymeric material.

57. The interventional system of claim 56, wherein the polymeric material comprises a thermoplastic elastomer material.

58. The interventional system of any one of claims 41 to 57, wherein the first passive MRI marker and the second passive MRI marker each include (i) an MRI marker-forming material having a volume not exceeding 5 mm3, or not exceeding 3 mm3, or not exceeding 1 mm3, or not exceeding 0.1 mm3in each of these aspects, the volume may be at least 0.00005 mm3, or at least about 0.0001 mm3; or (i) an MRI marker-forming material having a magnetic susceptibility of at least about 1 and having a volume not exceeding 0.1 mm3, or in the range of 0.00001 mm3to 0.1 mm3, or in the range of 0.00005 mm3to 0.02 mm3.

59. The interventional system of any one of claims 41 to 58, wherein the first passive MRI marker and the second passive MRI marker each include an MRI- marking forming material having a magnetic susceptibility of at least about 500 ppm, or at least about 2000 ppm, or in the range of about 500 ppm to about 1000, or in the range of about 7000 ppm to about 1000.

60. The interventional system of any one of claims 41 to 59, wherein:the first passive MRI marker and the second passive MRI marker each include an MRI marker-forming material selected from nickel, nickel alloys, cobalt, cobalt alloys, iron, and iron alloys; or the first passive MRI marker and the second passive MRI marker are configured to generate visible artifacts that differ in size from each other; or the first passive MRI marker and the second passive MRI marker are formed from the same passive MRI maker-forming material but have differing volumes of the passive MRI marker-forming material; or the first passive MRI marker is formed of a first passive MRI markerforming material and the second passive MRI marker is formed of a second passive MRI marker-forming material, wherein the first passive MRI marker-forming material has a magnetic susceptibility that differs from that of the second passive MRI marker-forming material.

61. An interventional medical device useful under magnetic resonance imaging (MRI), comprising: an elongate member configured for insertion in a patient and having a flexible distal region, the flexible distal region having a preset curve shape in a relaxed condition but being resiliently configurable upon the application of force to a straight condition; a first passive MRI marker at a first position along the elongate member; a second passive MRI marker at a second position along the elongate member, the second position longitudinally spaced from the first position; and wherein:(i) the first passive MRI marker is proximate to a proximal end of the flexible distal region having the preset curve shape and the second passive MRI marker is longitudinally distal of the first passive MRI marker and on the flexible distal region having the preset curve shape, and wherein the second passive MRI marker is closer to the first passive marker when the distal region is in the preset curve shape than when the distal region is in the straight condition; or(ii) the first passive MRI marker and the second passive MRI marker are both on the flexible distal region having the preset curve shape, and are configured to generate respective, discretely visible artifacts under MRI at a primary magneticfield strength of at least one of 0.55T, 1 ,5T and 3T, both when the flexible distal region is in the straight condition and in the preset curve shape; or(iii) one of the first passive MRI marker or the second passive MRI marker is positioned on the distal region so as to mark a distal-most position of the preset curve shape.

62. The interventional medical device of claim 61 , wherein the first passive MRI marker is proximal of the flexible distal region having a preset curve shape and the second passive MRI marker is on the flexible distal region having a preset curve shape, wherein the second passive MRI marker is closer to the first passive marker when the distal region is in the preset curve shape than when the distal region is in the straight condition.

63. The interventional medical device of claim 62, wherein a distance between the first and second passive MRI markers when the distal region is in the preset curve shape is no more than about 90% of a distance between the first and second passive MRI markers when the distal region is in the straight condition, and optionally wherein the first passive MRI marker is positioned longitudinally within 2 cm of the flexible distal region.

64. The interventional medical device of any one of claims 61 to 63, also comprising a third passive MRI marker; and, optionally wherein at least one of the first, second, and third passive MRI markers is configured to generate a visible artifact having a size that differs from at least one other of the first, second, and third passive MRI markers.

65. The interventional medical device of claim 64, wherein the third passive MRI marker is positioned on the distal region and is longitudinally between the first the first passive MRI marker and the second passive MRI marker along the elongate member.

66. The interventional medical device of claim 65, wherein with the flexible distal region in the straight condition the second passive MRI marker is distal of the third passive MRI marker, and wherein with the flexible distal region in the preset curve shape the second passive MRI marker is proximal of the third passive MRI marker.

67. The interventional medical device of claim 65 or 66, wherein the second passive MRI marker is closer to the first passive marker when the distal region is in the preset curve shape than when the distal region is in the straight condition.

68. The interventional medical device of claim 62, wherein the first passive MRI marker and the second passive MRI marker are both on the flexible distal region having the preset curve shape, and are longitudinally spaced from one another and configured to generate respective, discretely visible artifacts under MRI at a primary magnetic field strength of at least one of 0.55T, 1 ,5T and 3T, both when the flexible distal region is in the straight condition and in the preset curve shape.

69. The interventional medical device of claim 68, wherein the second passive MRI marker is longitudinally proximal of the first passive MRI marker on the flexible distal region, and wherein with the flexible distal region in the straight condition the first passive MRI marker is distal of the second passive MRI marker, and with the flexible distal region in the preset curve shape the first passive MRI marker is proximal of the second passive MRI marker.

70. The interventional medical device of claim 68 or 69, also comprising a third passive MRI marker; and, optionally wherein at least one of the first, second, and third passive MRI markers is configured to generate a visible artifact having a size that differs from at least one other of the first, second, and third passive MRI markers.71 . The interventional medical device of claim 70, wherein the third passive MRI marker is positioned longitudinally within about 2 cm of a proximal end of the flexible distal region.

72. The interventional medical device of any one of claims 69 to 71 , wherein a distance between the first and third passive MRI markers when the flexible distal region is in the preset curve shape is no more than about 90% of a distance between the first and third passive MRI markers when the flexible distal region is in the straight condition; and, optionally wherein a distance between the first and third passive MRI markers when the flexible distal region is in the preset curve shape is no more than about 50% of a distance between the first and third passive MRI markers when the flexible distal region is in the straight condition.

73. The interventional medical device of any one of claims 61 to 72, wherein the second passive MRI marker is positioned on the distal region so as to mark a distal- most position of the preset curve shape.

74. The interventional medical device of any one of claims 61 to 73, which is a wire guide, optionally wherein the wire guide comprises a core member and a polymeric jacket encapsulating the core member.

75. The interventional medical device of claim 74, wherein the wire guide comprises a core member and a polymeric jacket encapsulating the core member, and wherein the core member is a single, continuous length of wire.

76. The interventional medical device of claim 75, wherein the wire is formed of a superelastic metal alloy.

77. The interventional medical device of claim 76, wherein the superelastic metal alloy is nitinol.

78. The interventional medical device of any one of claims 74 to 77, wherein the polymeric jacket is formed of a polyamide polymer.

79. The interventional medical device of any one of claims 73 to 78, wherein the first and second passive MRI markers each comprise a passive MRI marker-forming material between the polymeric jacket and the core member.

80. The interventional medical device of claim 79, wherein the passive MRI marker-forming material is a metal layer plated onto an outer surface of the core member, optionally wherein the metal layer is a nickel layer.81 . The interventional medical device of any one of claims 74 to 78, wherein the first passive MRI marker and the second passive MRI marker each comprise a passive MRI marker-forming material embedded in a wall of the polymeric jacket.

82. The interventional medical device of any one of claims 61 to 72, which is a catheter.

83. The interventional medical device of claim 82, wherein the catheter has at least one sideport.

84. The interventional medical device of claim 83, wherein the at least one sideport is distal of the first passive MRI marker and the elongate member is free of any sideports proximal of the first passive MRI marker.

85. The interventional medical device of any one of claims 82 to 84, wherein the first passive MRI marker and the second passive MRI marker each comprise a passive MRI marker-forming material embedded in a wall of the catheter.

86. The interventional medical device of claim 85, wherein the wall of the catheter includes a first volume of a polymeric material forming the wall positioned radially inward of the passive MRI marker-forming material and between the passive MRI marker forming material and a catheter lumen surface defined by the first volume of polymeric material.

87. The interventional medical device of any one of claims 82 to 86, wherein the flexible distal region is formed of a thermoplastic elastomer material.

88. The interventional medical device of any one of claims 61 to 87, wherein the preset curve shape turns through at least about 90 degrees, at least through about 180 degrees, or at least through about 360 degrees.

89. The interventional medical device of claim 88, wherein the preset curve shape turns through no more than about 720 degrees.

90. The interventional medical device of any one of claims 61 to 89, wherein the second passive MRI marker occurs at a position where the preset curve shape has turned between about 65 degrees and about 115 degrees.91 . The interventional medical device of any one of claims 61 to 90, wherein the first passive MRI marker and the second passive MRI each occur within a longitudinal length of the elongate member not exceeding about 10 mm, or not exceeding about 5 mm, or in the range of about 0.2 to about 5 mm.

92. The interventional medical device of any one of claims 61 to 91 , wherein the first passive MRI marker and the second passive MRI marker occur within a width across the elongate member not exceeding about 70% of an outer width of the elongate member at a respective position of the first passive MRI marker and the second passive MRI marker.

93. The interventional medical device of any one of claims 61 to 92, wherein the first passive MRI marker and the second passive MRI marker each include (i) an MRI marker-forming material having a volume not exceeding 5 mm3, or not exceeding 3 mm3, or not exceeding 1 mm3, or not exceeding 0.1 mm3in each of these aspects, the volume may be at least 0.00005 mm3, or at least about 0.0001 mm3; or (i) an MRI marker-forming material having a magnetic susceptibility of at least about 1 and having a volume not exceeding 0.1 mm3, or in the range of 0.00001 mm3to 0.1 mm3, or in the range of 0.00005 mm3to 0.02 mm3.

94. The interventional medical device of any one of claims 61 to 93, wherein the first passive MRI marker and the second passive MRI marker each include an MRI-marking forming material having a magnetic susceptibility of at least about 500 ppm, or at least about 2000 ppm, or in the range of about 500 ppm to about1000, or in the range of about 7000 ppm to about 1000.

95. The interventional medical device of any one of claims 61 to 94, wherein the first passive MRI marker and the second passive MRI marker each include an MRI marker-forming material selected from nickel, nickel alloys, cobalt, cobalt alloys, iron, and iron alloys.

96. The interventional medical device of any one of claims 61 to 95, wherein: the first passive MRI marker and the second passive MRI markers are configured to generate artifacts that differ in size from each other; or the first passive MRI marker and the second passive MRI marker are formed from the same passive MRI maker-forming material but have differing volumes of the passive MRI marker-forming material; or the first passive MRI marker is formed of a first passive MRI marker-forming material and the second passive MRI marker is formed of a second passive MRI marker-forming material, wherein the first passive MRI marker-forming material has a magnetic susceptibility that differs from that of the second passive MRI markerforming material.

97. The interventional medical device of claim any one of claims 61 to 96, wherein the first passive MRI marker and the second passive MRI marker each include a layer of a passive MRI marker-forming material, optionally wherein the layer in the form of a circumferential band.

98. The interventional medical device of any one of claims 61 to 96, wherein the first passive MRI marker and the second passive marker each include a plug of a passive MRI marker-forming material, optionally wherein the plug does not overlap an innermost portion of the elongate member that, with the distal region in the preset curve shape, extends upon a line extending in a first curve of the preset curve shape and also does not overlap an outermost portion of the elongate member that, with the distal region in the preset curve shape, extends upon a line extending in a second curve that is opposite the first curve.

99. A method for making an interventional medical device useful in a procedure guided under magnetic resonance imaging (MRI), comprising: providing an elongate member configured for insertion in a patient and having a flexible distal region, the flexible distal region having a preset curve shape in a relaxed condition but being resiliently configurable by the application of force to a second shape that differs from the preset curve shape; providing a first passive MRI marker at a first position along the elongate member, the first passive MRI marker configured to generate a first artifact under the MRI; and providing a second passive MRI marker at a second position distal of the first position and along the flexible distal region, the second passive MRI marker configured to generate a second artifact under the MRI.

100. The method of claim 99, wherein: said providing an elongate member includes treating the elongate member to introduce the preset curve shape; and wherein said providing a second passive MRI marker is conducted before said treating.101 . The method of claim 100, wherein: said providing a passive marker includes embedding a volume of a passive MRI marker-forming material in a polymeric material of the elongate member; and said treating includes heating the polymeric material to reset its shape in the presence of the volume of passive MRI marker-forming material.

102. The method of any one of claims 99 to 101 , wherein the interventional medical device is a catheter and the elongate member is a catheter shaft.

103. The method of any one of claims 99 to 102, wherein the first passive MRI marker is also along the flexible distal region.

104. The method of any one of claims 99 to 103, wherein: said interventional medical device is a catheter according to any one of claims 1 -18, 28-40, 61 -72 or 82-98.

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