SUPERHEATING SYSTEM FOR INERTIAL IMPULSE GENERATION TO DISRUPT VASCULAR LESIONS

RELATED APPLICATIONS

This application claims priority on United States Provisional Application Serial No. 62/865,507, filed on June 24, 2019, and entitled“SUPERHEATING SYSTEM FOR INERTIAL IMPULSE GENERATION TO DISRUPT VASCULAR LESIONS”, on United States Provisional Application Serial No. 62/865,524, filed on June 24, 2019, and entitled“RESISTIVE HEATER SUPERHEATING SYSTEM FOR INERTIAL IMPULSE GENERATION TO DISRUPT VASCULAR LESIONS", and on United States Application Serial No. 16/879,635 filed on May 20, 2020, and entitled“SUPERHEATING SYSTEM FOR INERTIAL IMPULSE GENERATION TO DISRUPT VASCULAR LESIONS”. To the extent permitted, the contents of United States Provisional Application Serial Nos. 62/865,507 and 62/865,524, and United States Application Serial No. 16/879,635 are incorporated in their entirety herein by reference.

BACKGROUND

Vascular lesions within vessels in the body can be associated with an increased risk for major adverse events, such as myocardial infarction, embolism, deep vein thrombosis, stroke, and the like. Severe vascular lesions can be difficult to treat and achieve patency for a physician in a clinical setting. Vascular lesions may be treated using interventions such as drug therapy, balloon angioplasty, atherectomy, stent placement, vascular graft bypass, to name a few. Such interventions may not always be ideal or may require subsequent treatment to address the lesion.

SUMMARY

In a first aspect, a catheter system for imparting pressure to induce fractures in a vascular lesion within or adjacent a vessel wall is included. The catheter system includes a catheter configured to advance to the vascular lesion located within a blood vessel. The catheter can include an elongate shaft and a balloon coupled to the elongate shaft. The balloon can include a balloon wall and be configured to expand from a collapsed configuration suitable for advancing the catheter through a patient’s vasculature to a first expanded configuration suitable for anchoring the catheter in position relative to a treatment site. The catheter system can include a superheating system configured to heat a balloon fluid within the balloon rapidly enough to achieve spontaneous vaporization of the balloon fluid and generate inertial bubbles and acoustic pressure waves.

In a second aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, where the superheating system includes a first light guide extending along the elongate shaft and configured to be placed in optical communication with a light source at a proximal portion of the first light guide, the first light guide defining a first light window at a distal portion of the light guide.

In a third aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, where the first light guide is an optical fiber and where the light source is a laser.

In a fourth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, where the catheter system can further include a second light guide coupled to the elongate shaft, where the second light guide is in optical communication with the light source.

In a fifth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, where the first light guide includes a spiral path around a distal portion of the elongate shaft.

In a sixth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, where the distal portion of the light guide includes a diverting feature configured to direct light in the light guide toward a side surface portion of the distal portion of the light guide, and where the diverting feature is selected from a group including of a reflecting element and a refracting element; and a first light window positioned on the side surface portion.

In a seventh aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, where the light guide includes a first fiber diffuser in a distal portion of the light guide, and where the first fiber diffuser directs light from the light guide to exit the light guide at a side surface portion of the light guide, and where the side surface portion is in optical communication with a first light window.

In an eighth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, where the first fiber diffuser is selected from a group including of a machined portion of the light guide, a laser- machined portion of the light guide, fiber Bragg gratings, a fused splicing forming at least one internal mirror, and a splicing of two or more diffuse regions.

In a ninth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, where the catheter system can further include a plurality of light windows including the first light window, and a plurality of fiber diffusers in the distal portion of the light guide including the first fiber diffuser, where each fiber diffuser directs light from the light guide to exit the light guide at a side surface portion of the light guide, and where each side surface portion is in optical communication with one of the plurality of light windows.

In a tenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, where the plurality of light windows is axially spaced apart with at least one intervening non-emitting portion of the light guide disposed between each of the plurality of light windows.

In an eleventh aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, where the side surface portion is a cylindrical side surface portion and the first light window is configured as a cylindrical window.

In a twelfth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, where the first light window is in optical communication with the balloon fluid.

In a thirteenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, where the catheter system can further include a thermally conductive photonic absorption layer disposed on the first light window and configured to be in optical communication with the light source, where the thermally conductive photonic absorption layer is configured to absorb a photonic energy from the light guide and convert the photonic energy into thermal energy to achieve spontaneous vaporization of a balloon fluid within the balloon and to generate inertial bubbles and acoustic pressure waves.

In a fourteenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, where the elongate shaft defines a guidewire lumen.

In a fifteenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, where the elongate shaft defines an inflation lumen surrounding the guidewire lumen, and where the inflation lumen is in fluid communication with the balloon at a distal portion of the elongate shaft.

In a sixteenth aspect, a method for generating pressure to induce fractures in a vascular lesion within or adjacent a vessel wall of a blood vessel is included. The method can include advancing a catheter to a vascular lesion location within the blood vessel, where the catheter can include a balloon coupled to an elongate shaft. The method can include expanding the balloon from a collapsed configuration suitable for advancing the catheter through a patient’s vasculature to a first expanded configuration suitable for anchoring the catheter in position relative to the vascular lesion location. The method can include after expanding the balloon, heating a balloon fluid in contact with a superheating system to achieve spontaneous vaporization of the balloon fluid and generation of inertial bubbles and acoustic pressure waves directed toward a balloon wall, thereby imparting pressure upon the vascular lesion to induce fractures in the vascular lesion.

In a seventeenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, where heating the balloon fluid includes heating the balloon fluid to above its boiling point in more than 1 nanosecond and less than 10 seconds.

In an eighteenth aspect, a catheter system for imparting pressure to induce fractures in a vascular lesion within or adjacent a vessel wall is included. The catheter system can include a catheter configured to advance to the vascular lesion located within a blood vessel, where the catheter can include an elongate shaft and a balloon coupled to the elongate shaft. The balloon includes a balloon wall and is configured to expand from a collapsed configuration suitable for advancing the catheter through a patient’s vasculature to a first expanded configuration suitable for anchoring the catheter in position relative to a treatment site. The catheter system can include a superheating system configured to heat a balloon fluid within the balloon rapidly enough to achieve spontaneous vaporization of the balloon fluid and generate inertial bubbles and acoustic pressure waves, where the superheating system includes a first light guide extending along the elongate shaft and configured to be placed in optical communication with a light source at a proximal portion of the first light guide, and where the first light guide includes at least a first light window in optical communication with a distal portion of the light guide. The first light guide can be an optical fiber and where the light source is a laser.

In a nineteenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the catheter system can further include a thermally conductive photonic absorption layer in optical communication with the first light window and the light source, where the thermally conductive photonic absorption layer is configured to absorb a photonic energy from the light guide and convert the photonic energy into thermal energy to achieve spontaneous vaporization of a balloon fluid within the balloon and to generate inertial bubbles and acoustic pressure waves.

This summary is an overview of some of the teachings of the present application and is not intended to be an exclusive or exhaustive treatment of the present subject matter. Further details are found in the detailed description and appended claims. Other aspects will be apparent to persons skilled in the art upon reading and understanding the following detailed description and viewing the drawings that form a part thereof, each of which is not to be taken in a limiting sense. The scope herein is defined by the appended claims and their legal equivalents.

BRIEF DESCRIPTION OF THE FIGURES

Aspects may be more completely understood in connection with the following figures (FIGS.), in which:

FIG. 1 is a schematic longitudinal cross-sectional view of a catheter in accordance with various embodiments herein.

FIG. 2 is a schematic axial cross-sectional view of an elongate shaft of a catheter along line 2-2’ in FIG. 1 in accordance with various embodiments herein.

FIGS. 3-5 are schematic axial cross-sectional views of additional configurations for an elongate shaft of the catheter along line 2-2’ in FIG. 1 in accordance with various embodiments herein.

FIG. 6 is a schematic longitudinal cross-sectional view of a catheter in accordance with various embodiments herein.

FIG. 7 is a schematic flow diagram of generating an inertial bubble as generated by a catheter in accordance with various embodiments herein.

FIG. 8 is a schematic view of an acoustic pressure wave and inertial impulse generated by a catheter in accordance with various embodiments herein.

FIG. 9 is a schematic cross-sectional view of a distal portion of a light guide in accordance with various embodiments herein.

FIG. 10 is a schematic cross-sectional view of an additional embodiment of a distal portion of a light guide in accordance with various embodiments herein. FIG. 1 1 is a schematic cross-sectional view of a distal portion of a light guide in accordance with various embodiments herein.

FIG. 12 is a schematic cross-sectional view of a distal portion of a light guide in accordance with various embodiments herein.

FIG. 13 is a schematic side view of a light guide disposed about an elongate shaft in accordance with various embodiments herein.

FIG. 14 is a schematic flow diagram for a method in accordance with the various embodiments herein.

FIGS. 15-17 are schematic axial cross-sectional views of various embodiments of a distal portion of a light guide.

FIGS. 18-29 are schematic axial cross-sectional views of additional embodiments of an elongate shaft of a catheter in accordance with various embodiments herein.

FIG. 30 is a schematic view of a thin-film resistive heater in accordance with the various embodiments herein.

FIG. 31 is a schematic view of a wire heater in accordance with the various embodiments herein.

While embodiments are susceptible to various modifications and alternative forms, specifics thereof have been shown by way of example and drawings, and will be described in detail. It should be understood, however, that the scope herein is not limited to the particular aspects described. On the contrary, the intention is to cover modifications, equivalents, and alternatives falling within the spirit and scope herein.

DESCRIPTION

Treatment of vascular lesions can reduce major adverse events or death in affected subjects. A major adverse event is one that can occur anywhere within the body due to the presence of a vascular lesion. Major adverse events can include, but are not limited to major adverse cardiac events, major adverse events in the peripheral or central vasculature, major adverse events in the brain, major adverse events in the musculature, or major adverse events in any of the internal organs.

Various catheter systems for imparting pressure to induce fractures in a vascular lesion within or adjacent a vessel wall are described. The catheter systems can include a catheter configured to advance to the vascular lesion located within a blood vessel, the catheter including an elongate shaft and a balloon coupled to the elongate shaft. The catheter systems can include a balloon that includes a balloon wall and is configured to expand from a collapsed configuration suitable for advancing the catheter through a patient’s vasculature to a first expanded configuration suitable for anchoring the catheter in position relative to a treatment site. The catheter systems herein can include a superheating system configured to heat a balloon fluid within the balloon rapidly enough to achieve spontaneous vaporization of the balloon fluid and generate inertial bubbles and acoustic pressure waves.

It will be appreciated that the catheters herein can include many different forms. Referring now to FIG. 1 , a schematic cross-sectional view of a catheter system 100 is shown in accordance with various embodiments herein. Catheter system 100 is suitable for imparting pressure to induce fractures in a vascular lesion within or adjacent a vessel wall. Catheter system 100 includes a catheter 101 . Catheter 101 can be configured to advance to a vascular lesion location within or adjacent a blood vessel. In some embodiments, the vascular lesion can include a calcified vascular lesion. In some embodiments, the vascular lesion can include a fibrous vascular lesion. The catheter 101 can include an elongate shaft 102 and a balloon 122 coupled to the elongate shaft 102. The elongate shaft 102 can extend from a proximal portion 104 to a distal portion 106, and can also include a lumen 108. In some embodiments, lumen 108 includes a guidewire lumen. The elongate shaft 102 can further include an inflation lumen, as will be discussed in more detail below. In some embodiments, the catheter 101 can have a distal portion opening and can accommodate and be tracked over a guidewire to a treatment location. In some embodiments, the catheter 101 does not include a lumen. In embodiments where the elongate shaft 102 does not include a lumen to be accessed by a caregiver, the elongate shaft 102 can be configured to allow the catheter to be steered through a patient’s vasculature.

The elongate shaft 102 of catheter 101 can be coupled to a first light guide 1 10 in optical communication with a light source 1 16. In some embodiments, the first light guide 1 10 can be an optical fiber and the light source can be a laser. The light source 1 16 can be in optical communication with the first light guide 1 10 at a proximal portion 104 of the elongate shaft 102. In some embodiments, the elongate shaft can be coupled to multiple light guides such as a second light guide 1 12 and a third light guide 1 14. The light source 1 16 can be in optical communication with the second light guide 1 12 and the third light guide 1 14 at a proximal portion 104 of the elongate shaft 102.

It will be appreciated that the catheters herein can include any number of light guides in optical communication with the light source 1 16 at the proximal portion 104 and the balloon fluid 124 at the distal portion 106. For example, in some embodiments, the catheters herein can include from one light guide to five light guides. In other embodiments, the catheters herein can include from five light guides to fifteen light guides. In yet other embodiments, the catheters herein can include from ten light guides to thirty light guides. The catheters herein can include one, two, three, four, five, six, seven, eight, nine, or ten light guides. The catheters can include 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, or 30 light guides. It will be appreciated that catheters herein can include any number of light guides that can fall within a range, wherein any of the forgoing numbers can serve as the lower or upper bound of the range, provided that the lower bound of the range is a value less than the upper bound of the range. In some embodiments, the catheters herein can include more than 30 light guides.

The balloon 122 of catheter 101 can include a balloon wall and can expand from a collapsed configuration suitable for advancing the catheter through a patient’s vasculature to a first expanded configuration suitable for anchoring the catheter in position relative to a treatment site. Expansion of the balloons herein to various expanded configurations will be discussed in more detail below. The catheter system 100 can further include a superheating system configured to heat a balloon fluid 124 within the balloon 122 rapidly enough to achieve spontaneous vaporization of the balloon fluid 124 and generate inertial bubbles 126 and acoustic pressure waves. The superheating system can include a first light guide 1 10 extending along the elongate shaft 102 and configured to be placed in optical communication with a light source 1 16 at a proximal portion 104 of the first light guide 1 10. The first light guide 1 10 can be in optical communication with the balloon fluid 124 at a distal portion 106 of the first light guide 1 10. The first light guide 1 10 can include at least a first light window (not shown) in optical communication with a distal portion 106 of the first light guide 1 10.

The light guides herein can include a plurality of light windows, including a first light window, along the length of a light guide and disposed within the balloon 122. For example, in some embodiments, each light guide herein can include from one light window to five light windows. In other embodiments, each light guide herein can include from five light windows to fifteen light windows. In yet other embodiments, each light guide herein can include from ten light windows to thirty light windows. Each light guide herein can include one, two, three, four, five, six, seven, eight, nine, or ten light windows. Each light guide herein can include 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, or 30 light windows. It will be appreciated that light guides herein can include any number of light windows that can fall within a range, wherein any of the forgoing numbers can serve as the lower or upper bound of the range, provided that the lower bound of the range is a value less than the upper bound of the range. In some embodiments, the light guides herein can include more than 30 light windows.

The light windows can be disposed along the length of each light guide in various configurations and spacings. The light windows can be longitudinally separated from each other along the length of a light guide by a distance of from zero millimeters (mm) to 500 mm. In some embodiments, the light windows can be longitudinally separated from each other along the length of a light guide by a distance of from 0 mm to 300 mm. In some embodiments, the longitudinal separation between the light windows can be greater than or equal to 0 mm, 10 mm, 20 mm, 30 mm, 40 mm, 50 mm, 60 mm, 70 mm, 80 mm, 90 mm, 100 mm, 1 10 mm, 120 mm, 130 mm, 140 mm, 150 mm, 160 mm, 170 mm, 180 mm, 190 mm, 200 mm, 210 mm, 220 mm, 230 mm, 240 mm, 250 mm, 260 mm, 270 mm, 280 mm, 290 mm, or 300 mm, or can be an amount falling within a range between any of the foregoing. The light windows can be staggered along one or more light guides in a proximal to distal fashion and can be staggered both longitudinally and circumferentially. In some embodiments, the light windows can be disposed along a light guide in a spiral path around a distal portion of the elongate shaft.

When multiple light windows are present, the light windows can be radially offset from one another by about at least about or about 45 degrees. In some embodiments, the light windows can be radially offset from one another by at least about or about 60 degrees. In some embodiments, the light windows can be axially offset from one another by about or at least about 90 degrees. In some embodiments, the light windows can be radially offset from one another by at most about or about 180 degrees. In some embodiments, a plurality of light windows will be evenly spaced and radially offset from each other so that where there are n light windows, they are spaced apart by 360 degrees divided by n. In some embodiments, the light windows are not evenly spaced apart but are concentrated in one region of the elongate shaft in an asymmetrical fashion.

Examples of catheters having multiple light guides disposed about an elongate shaft at different positions around the circumference are shown in FIGS. 2-5. Referring now to FIG. 2, a schematic cross-sectional view of a catheter 101 of FIG. 1 along line 2-2’ in FIG. 1 is shown in accordance with various embodiments herein. Catheter 101 includes an elongate shaft 102, a first light guide 1 10, a second light guide 1 12, and a third light guide 1 14 separated by about 120 degrees around the circumference. Referring now to FIGS. 3-5 schematic cross-sectional views of additional configurations for catheters having multiple light guides are shown in accordance with various embodiments herein. The configuration of catheter 300 in FIG. 3 includes an elongate shaft 102, a first light guide 1 10, and a second light guide 1 12 separated by about 180 degrees around the circumference. The configuration of catheter 400 in FIG. 4 includes an elongate shaft 102, a first light guide 1 10, a second light guide 1 12, a third light guide 1 14, and a fourth light guide 1 15 separated by about 90 degrees around the circumference. The configuration of catheter 500 shown in FIG. 5 includes an elongate shaft 102, a first light guide 1 10, a second light guide 1 12, a third light guide 1 14, a fourth light guide 1 15, a fifth light guide 1 18, and a sixth light guide 120 separated by about 60 degrees around the circumference.

When multiple light guides are present, the light guides can be radially offset from one another by at least about or about 45 degrees. In some embodiments, the light guides can be radially offset from one another by at least about or about 60 degrees. In some embodiments, the light guides can be radially offset from one another by about or at least about 90 degrees. In some embodiments, the light guides can be radially offset from one another by at most about or about 180 degrees. In some embodiments, a plurality of light guides will be evenly spaced and radially offset from each other so that where there are n light guides, they are spaced apart by 360 degrees divided by n. In other embodiments, the light guides will be unevenly spaced and radially offset from each other. In some embodiments, each of the light guide locations shown in FIGS. 2-5 or otherwise described herein include two parallel light guides that are touching.

Catheter Embodiments Using Electric Energy Source (FIG. 6)

The catheter systems herein can also include catheters that include electrical leads for powering one or more resistive heaters to cause superheating of the balloon fluid. Referring now to FIG. 6, a schematic cross-sectional view of an additional embodiment of a catheter system 600 is shown in accordance with various embodiments herein. Catheter system 600 is suitable for imparting pressure to induce fractures in a vascular lesion within or adjacent a vessel wall. Catheter system 600 includes a catheter 601 . Catheter 601 can be configured to advance to a vascular lesion location within or adjacent a blood vessel. In some embodiments, the vascular lesion can include a calcified vascular lesion. The catheter 601 can include an elongate shaft 102 and a balloon 122 coupled to the elongate shaft 102. The elongate shaft 102 can extend from a proximal portion 104 to a distal portion 106, and can also include a lumen 108. In some embodiments, lumen 108 is a guidewire lumen. The elongate shaft 102 can further include an inflation lumen, as will be discussed in more detail below. In some embodiments, the catheter 601 can define a distal end opening at its distal end and can accommodate and be tracked over a guidewire to a treatment location. In some embodiments, the catheter 601 does not include a guidewire lumen. In embodiments where the elongate shaft 102 does not include a guidewire lumen, the elongate shaft 102 can be configured to allow the catheter to be steered through a patient’s vasculature, such as by having a tip that aids maneuverability.

The elongate shaft 102 of catheter 601 can enclose or be coupled to a first electrical lead 610 in electrical communication with a generator 616 of a voltage potential. The generator 616 can be in electrically connected to the first electrical lead 610 at a proximal portion 104 of the elongate shaft 102. In some embodiments, the elongate shaft can enclose or be coupled to multiple electrical leads such as a second electrical lead and a third electrical lead (first and second electrical leads are not shown in FIG. 6). The generator 616 can be electrically connected to the second electrical lead and the third electrical lead at a proximal portion 104 of the elongate shaft 102.

It will be appreciated that the catheters herein can include any number of electrical leads in electrical communication with the generator 616 at the proximal portion 104 and the balloon fluid 124 at the distal portion 106. In some embodiments, each electrical lead is connected to a separate resistive heater. For example, in some embodiments, the catheters herein can include from one electrical lead to five electrical leads. In other embodiments, the catheters herein can include from five electrical leads to fifteen electrical leads. In yet other embodiments, the catheters herein can include from ten electrical leads to thirty electrical leads. The catheters herein can include one, two, three, four, five, six, seven, eight, nine, or ten electrical leads. The catheters can include 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, or 30 electrical leads. It will be appreciated that catheters herein can include any number of electrical leads that can fall within a range, wherein any of the forgoing numbers can serve as the lower or upper bound of the range, provided that the lower bound of the range is a value less than the upper bound of the range. In some embodiments, the catheters herein can include more than 30 electrical leads.

The balloon 122 of catheter system 600 can include a balloon wall and can expand from a collapsed configuration suitable for advancing the catheter through a patient’s vasculature to a first expanded configuration suitable for anchoring the catheter in position relative to a treatment site. Expansion of the balloons herein to various expanded configurations will be discussed in more detail below. The catheter system 600 can further include a superheating system configured to heat a balloon fluid 124 within the balloon 122 rapidly enough to achieve spontaneous vaporization of the balloon fluid 124 and generate inertial bubbles 126 and acoustic pressure waves. The superheating system can include a first electrical lead 610 extending along the elongate shaft 102 and configured to be placed in electrical communication with a generator 616 of a voltage potential at a proximal portion 104 of the first electrical lead 610. The first electrical lead 610 can be in electrical communication with the balloon fluid 124 at a distal portion 106 of the first electrical lead 610.

The first electrical lead 610 can include at least a first resistive heating element 612 in electrical communication with a distal portion 106 of the first electrical lead 610. The first resistive heating element 612 can be in thermal communication with the balloon fluid 124 at a distal portion 106 of the first electrical lead 610. In some embodiments, the first electrical lead 610 can include a second resistive heating element 614 at the distal portion of the first electrical lead. The first electrical lead 610 can be in electrical communication with the second resistive heating element 614, where the second resistive heating element 614 is in thermal communication with the balloon fluid 124 at a distal portion 106 of the first electrical lead 610. The first resistive heating element 612 and the second resistive heating element 614 can be axially spaced from each other along the elongate shaft 102. The first electrical lead 610 can be in electrical communication with a third resistive heating element 618, where the third resistive heating element 618 can be in thermal communication with the balloon fluid 124 at a distal portion 106 of the first electrical lead 610. The electrical leads herein can be in electrical communication with a plurality of resistive heating elements, including a first resistive heating element, along the length of an electrical lead and disposed within the balloon 122. For example, in some embodiments, each electrical lead herein can include from one resistive heating element to five resistive heating elements. In other embodiments, each electrical lead herein can include from five resistive heating elements to fifteen resistive heating elements. In yet other embodiments, each electrical lead herein can include from ten resistive heating elements to thirty resistive heating elements. Each electrical lead herein can include one, two, three, four, five, six, seven, eight, nine, or ten resistive heating elements. Each electrical lead herein can include 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, or 30 resistive heating elements. It will be appreciated that electrical leads herein can include any number of resistive heating elements that can fall within a range, wherein any of the forgoing numbers can serve as the lower or upper bound of the range, provided that the lower bound of the range is a value less than the upper bound of the range. In some embodiments, the light guides herein can include more than 30 resistive heating elements. When multiple electrical leads are present, the electrical leads can be disposed about the elongate shaft in various positions. It will be appreciated that while the embodiments shown in FIGS. 2-5 are described as depicting an elongate shaft having one or more light guides disposed about the elongate shaft, the electrical leads described herein can also be disposed about the elongate shaft in the same location configurations as the light guides shown and described with respect to FIGS. 2-5.

The resistive heating elements can be disposed along the length of an electrical lead in various configurations and spacings. The resistive heating elements can be disposed along the length of the elongate shaft and each be connected to separate electrical leads in various configurations and spacings. The resistive heating elements can be longitudinally separated from each other along the length of an electrical lead or the elongate shaft by a distance of from zero millimeters (mm) to 500 mm. In some embodiments, the resistive heating elements can be longitudinally separated from each other along the length of an electrical lead or the elongate shaft by a distance of from 0 mm to 300 mm. In some embodiments, the longitudinal separation between the resistive heating elements can be greater than or equal to 0 mm, 10 mm, 20 mm, 30 mm, 40 mm, 50 mm, 60 mm, 70 mm, 80 mm, 90 mm, 100 mm, 1 10 mm, 120 mm, 130 mm, 140 mm, 150 mm, 160 mm, 170 mm, 180 mm, 190 mm, 200 mm, 210 mm, 220 mm, 230 mm, 240 mm, 250 mm, 260 mm, 270 mm, 280 mm, 290 mm, or 300 mm, or can be an amount falling within a range between any of the foregoing. The resistive heating elements can be staggered along the elongate shaft using one or more electrical leads in a proximal to distal fashion and can be staggered both longitudinally and circumferentially. In some embodiments, the resistive heating elements can be disposed in a spiral path around a distal portion of the elongate shaft.

When multiple resistive heating elements are present, the resistive heating elements can be radially offset from one another by about at least about or about 45 degrees. In some embodiments, the resistive heating elements can be radially offset from one another by at least about or about 60 degrees. In some embodiments, the resistive heating elements can be radially offset from one another by about or at least about 90 degrees. In some embodiments, the resistive heating elements can be radially offset from one another by at most about or about 180 degrees. In some embodiments, a plurality of resistive heating elements will be evenly spaced and radially offset from each other so that where there are n resistive heating elements, they are spaced apart by 360 degrees divided by n. In some embodiments, the resistive heating elements are not evenly spaced apart but are concentrated in one region of the elongate shaft in an asymmetrical fashion.

In some embodiments, catheter system for imparting pressure to induce fractures in a vascular lesion within or adjacent a vessel wall can include a catheter configured to advance to a lesion location within the blood vessel. The catheter can include an elongate shaft and a balloon coupled to the elongate shaft, and a first electrical lead extending along the elongate shaft and configured to be placed in electrical communication with, or electrically connected to, a voltage potential at a proximal portion of the first electrical lead. The first electrical lead can be electrically connected to a resistive heating element at a distal portion of the first electrical lead, where the resistive heating element is in thermal communication with the balloon fluid. The balloon can include a balloon wall and can be configured to expand from a collapsed configuration suitable for advancing the catheter through a patient’s vasculature to a first expanded configuration suitable for anchoring the catheter in position relative to a treatment site. The catheter system can include a superheating system configured to heat a balloon fluid within the balloon rapidly enough to achieve spontaneous vaporization of the balloon fluid and generate inertial bubbles and acoustic pressure waves. The catheter system can be configured to fill the balloon with fluid.

Suitable resistive heating elements can include hot filament elements, such as a low voltage electric heater or microheater elements. In some embodiments, the microheater elements can be a thin microfilm heater. The resistive heating elements described herein can be made from materials that, include, but are not to be limited to those made from tungsten, aluminum, brass, carbon, copper, palladium, titanium, platinum, tantalum, tantalum/aluminum alloys, nickel/chrome alloys (e.g., nichrome), iron/chromium/aluminum alloys (e.g., FeCrAI), copper/nickel alloys, molybdenum alloys, tungsten alloys, graphite, steel, stainless steel, zinc, alloys including at least nickel, chromium, and iron; molybdenum, molybdenum disilicide (M0S12), silicon carbide, barium titanate, and lead titanate composites.

Generation of Inertial Bubbles and Acoustic Pressure Waves (FIGS. 7-12)

The catheter systems including superheating systems described herein can heat a balloon fluid within the balloon rapidly enough to achieve spontaneous vaporization of the balloon fluid and generate inertial bubbles and acoustic pressure waves. Exemplary inertial bubbles are depicted by inertial bubbles 126 in FIGS. 1 and 6. Without wishing to be bound by any particular theory, it is believed that the inertial bubbles are generated by superheating a fluid to the point of a spontaneous vaporization of a volume of the fluid. It is believed that superheating a fluid, such as the balloon fluids disclosed herein, can occur when optical or thermal energy is efficiently absorbed by the fluid to result in superheating of the fluid to temperatures greater than two times, three times, or more, than the boiling temperature of the fluid. The superheating of the fluid to such temperatures results in approaching the spinodal limit of the fluid. The superheated fluid becomes unstable to random density fluctuations and an explosive phase transition from a fluid to a vapor takes place to produce a fast expanding vapor bubble, such as the inertial bubbles described herein.

In the embodiments herein, it is believed that an inertial bubble can form as a result of superheating a volume of the balloon fluid at or near the light windows or resistive heating elements described. The volume of balloon fluid to be superheated at or near the light windows or resistive heating elements has an initial volume prior to being heated. As the volume of balloon fluid at or near the light windows or resistive heating elements is superheated from the light exiting a light window or from the heat generated at a resistive heating element, that volume of the balloon fluid begins to increase temperature and the balloon fluid begins to vaporize and form an inertial bubble during the phase transition from a fluid to a vapor. The inertial bubble continues to form during the superheating process until it has a diameter that is about two times to about ten times the diameter of the initial volume of the balloon fluid prior to heating. In some embodiments, the inertial bubble has a diameter that is greater than ten times the diameter of the initial volume of the balloon fluid prior to heating. It is believed that one or more high- energy inertial acoustic pressure wave fronts will form within a balloon fluid as an inertial bubble expands to its maximum size and then undergoes a cavitation event.

The acoustic pressure waves are generated having pressures in the range of 2 megapascals (MPa) to 25 MPa, as will be discussed in more detail below. The final inertial bubble diameters suitable for use herein can include those from 1 mm to about 25 mm. In some embodiments, the final inertial bubble diameter can be greater than or equal to 0.5 mm 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 1 1 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, 21 mm, 22 mm, 23 mm, 24 mm, or 25 mm, or can be an amount falling within a range between any of the foregoing.

Referring now to FIG. 7, a schematic flow diagram of a spontaneous vaporization process 700 of a balloon fluid and generation of an inertial bubble is shown in accordance with various embodiments herein. The process of superheating begins at 710 where light or thermal energy 706 is supplied to an initial volume of the balloon fluid 124 at or near the light windows or resistive heating elements the light disposed along the light guide or electrical lead 702. The volume of balloon fluid at or near the light windows or resistive heating elements is superheated rapidly enough to lead to the spontaneous vaporization of that initial volume of balloon fluid to generate an inertial bubble 704. The inertial bubble will have an initial diameter at the instant the spontaneous vaporization of that initial volume of balloon fluid occurs. At 712 the inertial bubble 704 continues to expand and the diameter of the inertial bubble 704 continues to expand. At 714 the expansion of the inertial bubble 704 reaches a maximum and begins to collapse, resulting in a cavitation event. The entire spontaneous vaporization process 700 results in the generation of one or more acoustic pressure waves. The spontaneous vaporization process 700 can occur within zero to five seconds. In some embodiments, the spontaneous vaporization process can occur during a time from greater than or equal to 1 nanosecond (ns), 10 ns, 100 ns, 1 microsecond (ps), 10 ps, 100 ps, 200 ps, 300 ps, 400 ps, 500 ps, 600 ps, 700 ps, 800 ps, 900 ps, 1 millisecond (ms), 10 ms, 20 ms, 30 ms, 40 ms, 50 ms, 60 ms, 70 ms, 80 ms, 90 ms, or 100 ms, 250 ms, 500 ms, 1 second (sec), 2 sec, 3 sec, 4 sec, 5 sec, 6 sec, 7 sec, 8 sec, 9 sec, or 10 sec, or can be an amount falling within a range between any of the foregoing.

The acoustic pressure waves generated by the catheter systems described herein can disrupt a vascular lesion within or adjacent to a vessel of a patient. FIGS. 8-12 show examples of catheters using light energy to disrupt a vascular lesion. Catheters using electrical energy sources could also be constructed similar to FIGS. 8-12 with resistive heating elements located where the light diverting elements and light windows are shown in FIGS. 8-12. Referring now to FIG. 8, a schematic depiction 800 of the collapse of an inertial bubble and the subsequent generation of acoustic pressure waves is shown in accordance with various embodiments herein. Light 809 can be directed from light guide 810 by a diverting element (discussed below), to initiate a superheating of the balloon fluid within a balloon to rapidly achieve spontaneous vaporization of the balloon fluid and to generate an inertial bubble, such as inertial bubble 704 in FIG. 7. The rapid spontaneous vaporization and expansion of the inertial bubble and the subsequent inertial bubble collapse 812 (depicted as small bubbles) can result in formation of one or more acoustic pressure waves 802. Acoustic pressure wave 802 can be directed toward the balloon wall 804 to create an inertial impulse in a vessel wall 806 to transfer momentum to the vascular lesion 808 to result in the disruption the vascular lesion 808.

The light guides herein can include various configurations and one or more light windows distributed along the longitudinal axis. The light guides can be in optical communication with a light source at a proximal portion of a catheter system and the light windows at a distal portion of a catheter system and disposed within a balloon. Referring now to FIGS. 9-12, a schematic views of various configurations for the distal tip of a light guide suitable for use in the catheter systems herein are shown in accordance with various embodiments herein. In the configuration shown in FIG. 9, a schematic view of the distal tip of a light guide 902 is shown. Light guide 902 includes a cylindrical end shape. Light guide 902 is configured such that light 904 travels from a light source (not shown) in the direction from the proximal portion 104 of the light guide 902 to a distal portion of the light guide 902, as indicated by the arrows. Light 904 within light guide 902 is directed from the light guide 902 to the distal tip of the light guide 902 where it exits at a first light window 906. Balloon fluid (not shown) at the distal tip of light guide 902 is heated rapidly enough to achieve spontaneous vaporization of the balloon fluid and generate an inertial bubble 908.

In the configuration shown in FIG. 10, a schematic view of a distal tip of a light guide 1002 having multiple fiber diffusers disposed therein. Light guide 1002 includes a cylindrical end shape. Light guide 1002 is configured such that light 1004 travels from a light source (not shown) in the direction from the proximal portion of the light guide 1002 to a distal portion of the light guide 1002, as indicated by the arrows. Light 1004 within light guide 1002 is directed within the light guide 1002 to a first fiber diffuser 1016 and a second fiber diffuser 1018 disposed in the distal tip of the light guide 1002. The first fiber diffuser 1016 and the second fiber diffuser 1018 are configured to direct light 1004 from the light guide 1002 to exit the light guide 1002 at a side surface portion of the light guide 1002. In cases where a light guide 1002 includes a first fiber diffuser 1016 to direct light 1004 from the light guide 1002 to exit the light guide 1002 at a side surface portion of the light guide 1002, the side surface portion of the light guide 1002 is in optical communication with at least a first light window 1006 and the light 1004 exits the first light window 1006. In some embodiments, the first fiber diffuser 1016 can also be in optical communication with a second optical window 1008. In some embodiments, an optical window can span the entire circumference of a light guide. In other embodiments, an optical window can span only a portion of the circumference of a light guide.

The second fiber diffuser 1018 is configured to direct light 1004 from the light guide 1002 to exit the light guide 1002 at a side surface portion of the light guide 1002. The second fiber diffuser 1018 can direct light 1004 from the light guide 1002 to exit the light guide 1002 at a side surface portion of the light guide 1002, the side surface portion of the light guide 1002 is in optical communication with at least a third light window 1010 and the light 1004 exits the third light window 1010. In some embodiments, the second fiber diffuser 1018 can also be in optical communication with a fourth optical window 1012. Balloon fluid (not shown) at the distal tip of light guide 1002 is heated rapidly enough to achieve spontaneous vaporization of the balloon fluid and generate one or more inertial bubbles 1014.

In the configuration shown in FIG. 1 1 , a schematic view of a distal tip of a light guide 1 102 having a single large fiber diffuser disposed therein. Light guide 1 102 includes a single fiber diffuser 1 104 positioned along the elongate shaft of the distal region of the light guide 1 102. The fiber diffuser 1 104 directs light 1 101 to exit the light guide 1 102 at a side surface portion thereof. The side surface portion of the light guide 1 102 is in optical communication with one or more light windows 1 106 and fiber diffuser 1 104, such that the fiber diffuser 1 104 and the one or more light windows 1 106 are in optical communication with one another. Balloon fluid (not shown) at the distal tip of light guide 1 102 is heated rapidly enough to achieve spontaneous vaporization of the balloon fluid and generate one or more inertial bubbles 1 108.

In the configuration shown in FIG. 12, a schematic view of a distal tip of a light guide 1202 having multiple fiber diffusers and multiple light windows having a thermally conductive photonic absorption layer disposed thereon. Light guide 1202 includes a cylindrical end shape. Light guide 1202 is configured such that light 1204 travels from a light source (not shown) in the direction from the proximal portion of the light guide 1202 to a distal portion of the light guide 1202, as indicated by the arrows. Light 1204 within light guide 1202 is directed within the light guide 1202 to a first fiber diffuser 1016 and a second fiber diffuser 1218 disposed in the distal tip of the light guide 1202. The first fiber diffuser 1216 and the second fiber diffuser 1218 are configured to direct light 1204 from the light guide 1202 to exit the light guide 1202 at a side surface portion of the light guide 1202. In cases where a light guide 1202 includes a first fiber diffuser 1216 to direct light 1204 from the light guide 1202 to exit the light guide 1202 at a side surface portion of the light guide 1202, the side surface portion of the light guide 1202 is in optical communication with at least a first light window 1206 and light 1204 exits the first light window 1206. In some embodiments, the first fiber diffuser 1216 can also be in optical communication with a second light window 1208. In some embodiments, an optical window can span the entire circumference of a light guide. In other embodiments, an optical window can span only a portion of the circumference of a light guide.

The second fiber diffuser 1218 is configured to direct light 1204 from the light guide 1202 to exit the light guide 1202 at a side surface portion of the light guide 1202. The second fiber diffuser 1218 can direct light 1204 from the light guide 1202 to exit the light guide 1202 at a side surface portion of the light guide 1202, the side surface portion of the light guide 1202 is in optical communication with at least a third light window 1210 and light 1204 exits the third light window 1210. In some embodiments, the second fiber diffuser 1218 can also be in optical communication with a fourth light window 1212. Balloon fluid (not shown) at the distal tip of light guide 1202 is heated rapidly enough to achieve spontaneous vaporization of the balloon fluid and generate one or more inertial bubbles 1214.

The light guide 1202 further includes a first thermally conductive photonic absorption layer 1220 disposed on the first light window 1206, where the first thermally conductive photonic absorption layer 1220 is configured to absorb photonic energy from the light guide 1202 and convert the photonic energy into thermal energy to achieve spontaneous vaporization of a balloon fluid within the balloon and to generate inertial bubbles and acoustic pressure waves. The light guide can further include a second thermally conductive photonic absorption layer 1222 disposed on second light window 1208; a third thermally conductive photonic absorption layer 1224 disposed on third light window 1210; and a fourth thermally conductive photonic absorption layer 1226 disposed on fourth light window 1212. It will be appreciated that more than four thermally conductive photonic absorption layers can be used when more than four light windows are used.

In some embodiments, the light guides can include a thermally conductive photonic absorption layer disposed on any of the light windows. In some embodiments, the light guides can include a thermally conductive photonic absorption layer disposed on all of the light windows. In some embodiments, the light guides can include a thermally conductive photonic absorption layer disposed on a portion of the light windows. The thermally conductive photonic absorption layer can be completely disposed about the light guide or partially disposed about the light guide. The thermally conductive photonic absorption layer can be disposed on a first light window. The thermally conductive photonic absorption layer can be configured to absorb photonic energy from the light guide and convert the photonic energy into thermal energy, heating the thermally conductive photonic absorption layer, which in turn heats the balloon fluid to achieve spontaneous vaporization of the balloon fluid and to generate inertial bubbles and acoustic pressure waves. The thermally conductive photonic absorption layer can include, but is not to be limited to nanoparticles, carbon nanotubes, carbon black, candle soot, candle soot nanoparticles, a nanotube array, multiwall carbon nanotubes, light absorbing dyes, gold nanoparticles, and the like.

Spiral Path for Energy Source (FIG. 13)

In various embodiments herein, the light guides or the electrical leads can be disposed in a spiral configuration about an elongate shaft of the catheter systems herein. Referring now to FIG. 13, a schematic view of a light guide 1302 disposed in a spiral configuration about an elongate shaft 102 is shown in accordance with various embodiments herein. Light guide 1302 includes a plurality of light windows 1304 disposed about the length of the light guide 1302 and disposed axially about the elongate shaft 102. It will be appreciated that the configuration of light windows in light guide 1302 can allow for the generation of inertial bubbles and acoustic pressure waves that can simultaneously be directed toward a balloon wall adjacent to a vascular lesion, and thereby imparting pressure upon the vascular lesion to induce fractures in a treatment site. It will be appreciated that an electrical lead can be disposed in a spiral configuration about an elongate shaft, where resistive heating elements can be included in the place of the light windows as shown in FIG. 13.

Methods (FIG. 14)

The catheters described herein can be used in one or more methods for inducing fractures in a vascular lesion within or adjacent a vessel wall of a blood vessel. Referring now to FIG. 14, a schematic flow diagram for a method 1400 is shown in accordance with the various embodiments herein. Method 1400 includes advancing a catheter 1410 to a treatment site 1414 within the blood vessel 1412, the catheter 1410 including an elongate shaft 102, and a balloon 122 coupled to the elongate shaft 102 at 1402. In some embodiments, the treatment site 1414 can include a vascular lesion location within a patient’s vasculature. In some embodiments, the vascular lesion can include a calcified lesion. The method 1400 includes expanding the balloon 122 from a collapsed configuration suitable for advancing the catheter 1410 through a patient’s vasculature to a first expanded configuration 1404 suitable for anchoring the catheter in position relative to the treatment site 1414. The method 1400 includes, after expanding the balloon 122, heating a balloon fluid 124 (illustrated in Figure 1 ) in contact with a superheating system to achieve spontaneous vaporization of the balloon fluid 124 and the generation of inertial bubbles 1416 and acoustic pressure waves directed toward a balloon wall, thereby imparting pressure upon the vascular lesion to induce fractures in the treatment site 1414.

In some embodiments, the method 1400 includes a first light guide and a first light window in optical communication with a distal portion of the first light guide and disposed within the balloon. In some embodiments, the method 1400 includes a first electrical lead and a first resistive heating element in electrical communication with a distal portion of the first electrical lead and disposed within balloon 122. The method 1400 can also include, after heating the balloon fluid, further expanding the balloon 122 from the first expanded configuration 1404 to a second further expanded configuration at 1406. The method can include completely removing the catheter 1410 from the patient’s vasculature at 1408.

Heating the balloon fluid, such as in method 1400, can include superheating the balloon fluid to above its boiling point, in less than 10 milliseconds. In some embodiments, heating the balloon fluid, can include superheating the balloon fluid to above its boiling point in more than 1 milliseconds and less than 10 seconds. In some embodiments, heating the balloon fluid, can include superheating the balloon fluid to above its boiling point in more than 1 nanosecond and less than 20 seconds. In some embodiments, heating the balloon fluid can occur during a time from greater than or equal to 1 nanosecond (ns), 10 ns, 100 ns, 1 microsecond (ps), 10 ps, 100 microseconds (ps), 200 ps, 300 ps, 400 ps, 500 ps, 600 ps, 700 ps, 800 ps, 900 ps, 1 millisecond (ms), 10 ms, 20 ms, 30 ms, 40 ms, 50 ms, 60 ms, 70 ms, 80 ms, 90 ms, or 100 ms, 250 ms, 500 ms, 1 second (sec), 2 sec, 3 sec, 4 sec, 5 sec, 6 sec, 7 sec, 8 sec, 9 sec, or 10 sec, 1 1 sec, 12 sec, 13 sec, 14 sec, 15 sec, 16 sec, 17 sec, 18 sec, 19 sec, or 20 sec, or can be an amount falling within a range between any of the foregoing. In some embodiments, heating the balloon fluid can occur during a time from greater than 20 seconds. In some embodiments, heating the balloon fluid can include superheating the balloon fluid in a range of from 100 ^S C to 700 ^S C depending on the composition of the balloon fluid to be used.

The duration of the treatments herein can vary according to the specific treatment site and size of a vascular lesion. In some embodiments, the total treatment time can be from one second to thirty seconds. In some embodiments, the total treatment time can be from five seconds to twenty seconds. In other embodiments, the total treatment time can be from five seconds to ten seconds. The frequency of the superheating process for light pulses or for electric current can be run at a from 1 hertz (Hz) to 100 Hz. In some embodiments, the frequency of the superheating process for light pulses or for electric current can be run at a from 100 Hz to 5000 hertz (Hz).

Balloons

The balloons suitable for use in the catheter systems herein include those that can be passed through the vasculature of a patient when in a collapsed configuration. In some embodiments, the balloons herein are made from silicone. In other embodiments, the balloons herein are made from polydimethylsiloxane (PDMS), polyurethane, polymers such as PEBAX™ material available from Arkema, which has a location at King of Prussia, Pennsylvania, USA, nylon, and the like. In some embodiments, the balloons can include those having diameters ranging from 1 millimeter (mm) to 25 mm in diameter. In some embodiments, the balloons can include those having diameters ranging from 1 .5 mm to 12 mm in diameter. In some embodiments, the balloons can include those having diameters ranging from 1 mm to 5 mm in diameter. In some embodiments, the diameter can be greater than or equal to 0.5 mm, 1 .0 mm, 1 .5 mm, 2.0 mm, 2.5 mm, 3.0 mm,

3.5 mm, 4.0 mm, 4.5 mm, 5.0 mm, 5.5 mm, 6.0 mm, 6.5 mm, 7.0 mm, 7.5 mm, 8.0 mm, 8.5 mm, 9.0 mm, 9.5 mm, 10.0 mm, 10.5 mm, 1 1 .0 mm, 1 1 .5 mm, 12.0 mm,

12.5 mm, 13.0 mm, 13.5 mm, 14.0 mm, 14.5 mm, 15.0 mm, 15.5 mm, 16.0 mm, 16.5 mm, 17.0 mm, 17.5 mm, 18.0 mm, 18.5 mm, 19.0 mm, 19.5 mm, or 20.0 mm, or can be an amount falling within a range between any of the foregoing.

In some embodiments, the balloons herein can include those having a length ranging from 5 mm to 300 mm in length. In some embodiments, the balloons herein can include those having a length ranging from 8 mm to 200 mm in length. In some embodiments, the length of the balloon can be greater than or equal to 5 mm, 10 mm, 20 mm, 30 mm, 40 mm, 50 mm, 60 mm, 70 mm, 80 mm, 90 mm, 100 mm, 1 10 mm, 120 mm, 130 mm, 140 mm, 150 mm, 160 mm, 170 mm, 180 mm, 190 mm, 200 mm, 210 mm, 220 mm, 230 mm, 240 mm, 250 mm, 260 mm, 270 mm, 280 mm, 290 mm, or 300 mm, or can be an amount falling within a range between any of the foregoing.

The balloons herein can be inflated to inflation pressures from 1 atmosphere (atm) to 70 atm. In some embodiments, the balloons herein can be inflated to inflation pressures of from 6 atm to 20 atm. In some embodiments, the balloons herein can be inflated to inflation pressures of from 20 atm to 70 atm. In some embodiments, the balloons herein can be inflated to inflation pressures that can be greater than or equal to 1 atm, 10 atm, 20 atm, 30 atm, 40 atm, 50 atm, 60 atm, or 70 atm, or can be an amount falling within a range between any of the foregoing.

The balloons herein can include those having various shapes, including, but not to be limited to, a conical shape, a square shape, a rectangular shape, a spherical shape, a conical/square shape, a conical/spherical shape, an extended spherical shape, an oval shape, a tapered, shape, a bone shape, a stepped diameter shape, an offset shape, or a conical offset shape.

In some embodiments, the balloons herein can provide a therapeutic agent to a treatment site. In some embodiments, the therapeutic agent can be delivered via a drug eluting coating, a drug eluting stent structure, or by the delivery of a drug composition through one or more lumens of the catheters described herein. The drug elution coating or drug eluting stent structure can include one or more therapeutic agents including anti-inflammatory agents, anti-neoplastic agents, anti- angiogenic agents, and the like. Exemplary agents can include, but is not to be limited to paclitaxel, docetaxel, everolimus, and sirolimus, and analogs thereof. Balloon Fluids

Exemplary balloon fluids suitable for use herein can include, but are not to be limited to one or more of water, saline, contrast agent, fluorocarbons, perfluorocarbons, gases, such as carbon dioxide, and the like. In some embodiments, the balloon inflation fluids include a mixture of saline to contrast agent in a volume ratio of 50:50. In some embodiments, the balloon fluids include a mixture of saline to contrast agent in a volume ratio of 25:75. In some embodiments, the balloon fluids include a mixture of saline to contrast agent in a volume ratio of 75:25. The balloon fluids suitable for use herein can be tailored on the basis of composition, viscosity, and the like in order to manipulate the rate of travel of the acoustic pressure waves therein. The balloon fluids suitable for use herein are biocompatible. A maximum volume of balloon fluid to be subjected to superheating can be tailored by the chosen light source and the type of balloon fluid used.

In some embodiments, the contrast agents used herein can include, but are not to be limited to, iodine-based contrast agents, such as ionic or non-ionic iodine- based contrast agents. Some non-limiting examples of ionic iodine-based contrast agents include diatrizoate, metrizoate, iothalamate, and ioxaglate. Some non limiting examples of non-ionic iodine-based contrast agents include iopamidol, iohexol, ioxilan, iopromide, iodixanol, and ioversol. In other embodiments, non iodine based contrast agents can be used. Suitable non-iodine containing contrast agents can include gadolinium (lll)-based contrast agents. Suitable fluorocarbon and perfluorocarbon agents can include, but are not to be limited to, agents such as the perfluorocarbon dodecafluoropentane (DDFP, C5F12), perfluoro-octane (PFO), perfluoroperhydrophenanthrene, perfluorodecalin (PFD), perfluorotributylamide (PFTB) and perfluorooctylbromide (PFOB), and the like.

The balloon fluids herein can include those that include absorptive agents that can selectively absorb light in the ultraviolet region (e.g., 10 nanometers (nm) to about 400 nm), visible region (e.g., about 400 nm to about 780 nm), and near- infrared region of the electromagnetic spectrum (e.g., about 780 nm to 2.5 pm). Suitable absorptive agents can include those with absorption maxima along the spectrum from 10 nm to 2.5 pm. In some embodiments, the balloon fluids herein can include those that include absorptive agents that have a peak absorption at or near 1 .91 pm. In some embodiments, the absorptive agents used herein can be water soluble. In other embodiments, the absorptive agents used herein are not water soluble. In some embodiments, the absorptive agents used in the balloon fluids herein can be tailored to match the peak emission of the light source. Various light sources having emission wavelengths of about 10 nanometers to 10 millimeters are discussed elsewhere herein.

Light Guides (FIGS. 15-17)

The light guides herein can include an optical fiber or flexible light pipe. The light guides herein can be thin and flexible and can allow light signals to be sent with very little loss of strength. The light guides herein can include a core surrounded by a cladding about its circumference. In some embodiments, the core can be a cylindrical core or a partially cylindrical core. The core and cladding of the light guides can be formed from one or more materials, including but not limited to one or more types of glass, silica, or one or more polymers. The light guides may also include a protective coating, such as a polymer. It will be appreciated that the index of refraction of the core will be greater than the index of refraction of the cladding.

Each light guide can guide light along its length to a distal portion having at least one optical window. The light guides can create a light path as portion of an optical network including a light source. The light path within the optical network allows light to travel from one part of the network to another without being modified. Both the optical fiber or the flexible light pipe can provide a light path within the optical networks herein.

The light guides herein can assume many configurations about the elongate shaft of the catheters described herein. In some embodiments, the light guides can run parallel to the longitudinal axis of the elongate shaft of the catheter. In some embodiments, the light guides can be disposed spirally or helically about the longitudinal axis of the elongate shaft of the catheter. In some embodiments, the light guides can be physically coupled to the elongate shaft. In other embodiments, the light guides can be disposed along the length of the outer diameter of the elongate shaft. In yet other embodiments the light guides herein can be disposed within one or more light guide lumens within the elongate shaft. Various configurations for the elongate shafts and light guide lumens will be discussed below.

The light guides herein can include one or more diverting features configured to direct light within the light guide toward a side surface portion of the distal portion of the light guide. The diverting feature can include a reflecting element, a refracting element, a fiber diffuser, or any combination thereof, and a first light window positioned on the side surface portion. When light guides include a diverting feature configured to direct light within the light guide toward a side surface portion of the distal portion of the light guide, the light guides can also include at least a first light window positioned on a side surface portion of the light guide. In some embodiments the light windows span the entire circumference of the light guides, while in other embodiments the light windows only span a portion of the circumference of the light guides. Other properties of the light guides, including size, spacing, and distribution are described elsewhere herein.

In various embodiments, the light guides herein include one or more fiber diffusers. In some embodiments, a light guide can include a first fiber diffuser in a distal portion of the light guide, where the first fiber diffuser directs light from the light guide to exit the light guide at a side surface portion of the light guide. In cases where a light guide includes a first fiber diffuser to direct light from the light guide to exit the light guide at a side surface portion of the light guide, the side surface portion of the light guide is in optical communication with a first light window. In some embodiments the light windows span the entire circumference of the light guides, while in other embodiments the light windows only span a portion of the circumference of the light guides.

In yet other embodiments, the light guides herein can include a plurality of light windows and a plurality of fiber diffusers in the distal portion of the light guide. The plurality of light windows can include a first light window and the plurality of fiber diffusers can include the first fiber diffuser. Each fiber diffuser can direct light from the light guide to exit the light guide at a side surface portion of the light guide, where each side surface portion is in optical communication with one of the plurality of light windows. The plurality of light windows can be axially spaced apart with at least one intervening non-emitting portion of the light guide disposed between each of the plurality of light windows. The side surface portion can be a cylindrical side surface portion and a first light window can be configured as a cylindrical window.

In some embodiments, the light guides can include a thermally conductive photonic absorption layer disposed on any of the light windows. The thermally conductive photonic absorption layer can be disposed on a first light window. The thermally conductive photonic absorption layer can be configured to absorb photonic energy from the light guide and convert the photonic energy into thermal energy to achieve spontaneous vaporization of a balloon fluid within the balloon and to generate inertial bubbles and acoustic pressure waves.

The light guides herein can include various configurations at a distal portion of the light guide. Referring now to FIGS. 15-17, schematic cross-sectional views of the distal portions of various shaped light guides are shown in accordance with various embodiments herein. In FIG. 15, a schematic cross-sectional view of a light guide 1500 is shown. Light guide 1500 includes a cylindrical end shape. In some embodiments, the end of the light guide can have a tapered shape. By way of example, in FIG. 16 a schematic cross-sectional view of a light guide 1600 having a tapered end shape is shown. In some embodiments, the end of the light guide can have an angled shape. By way of example, in FIG. 17 a schematic cross- sectional view of a light guide 1700 is shown. Light guide 1700 includes an angled end shape. The light guide 1700 also includes a diverting feature 1706 at the distal portion to direct the light 1704 within the light guide toward the side surface portion of the light guide. Light guide 1700 is configured such that light 1704 travels from a light source (not shown) in the direction from the proximal portion 104 of the light guide to the distal portion of the light guide 1700, as indicated by the arrow. Upon contact with the diverting feature 1706, the light 1704 is diverted, or reflected, within the light guide 1700.

In some embodiments, a diverting feature can be included with the light guide to direct light toward a side surface portion of the distal portion of the light guide. A diverting feature can include any feature of the system herein that diverts light from the light guide away from its axial path toward a side surface portion of the light guide. Examples include a reflector, a refracting structure, and a fiber diffuser. Fiber diffusers will be discussed in more detail below.

In other embodiments, the light guides can form a spiral configuration about the longitudinal axis of the elongate shaft of the catheter. In some embodiments, the spiral configuration can run clockwise about the longitudinal axis of the elongate shaft of the catheter, while in other embodiments the spiral configuration can run counter-clockwise about the longitudinal axis of the elongate shaft of the catheter. In some embodiments, the light guides can form a single helix, a double helix, a triple helix, or a quadruple helix about the longitudinal axis of the elongate shaft of the catheter.

The light guides herein can come in various sizes and configurations. The light guides will have a longitudinal axis along the elongate shaft of the light guide and short axis about its circumference. In some embodiments, the light guides can have an outer diameter of about 100 pm, including the cladding and the core. In other embodiments, the light guides can include those that have an outer diameter of from 50 pm to 1000 pm including the cladding and the core. The length of the light guides can include those having a length of from 40 cm to 175 cm. In some embodiments, the length of the light guides can include those having a length of from 50-150 cm. In some embodiments, the length of the light guide can include those having a length of 40 cm, 50 cm, 60 cm, 70 cm, 80 cm, 90 cm, 100 cm, 125 cm, 150 cm, or 175 cm. It will be appreciated that the light guides herein can have a usable length that can fall within a range, wherein any of the forgoing lengths can serve as the lower or upper bound of the range, provided that the lower bound of the range is a value less than the upper bound of the range. It will be appreciated that one or more light guides herein can be adhered to the outer surface of the elongate shaft of a catheter, to create a catheter. However, in other embodiments, one or more light guides can be disposed within a lumen of a catheter. In addition, the catheter may define a lumen for a guidewire having an inner diameter of about 0.014 inch (0.356 mm). In some embodiments, the catheter can include those having an inner diameter of about 0.018 inch (0.457 mm). In yet other embodiments, the catheter can include those having an inner diameter of about 0.035 inch (0.889 mm). In some embodiments the light guides herein can be integrated with a balloon catheter. In some embodiments the light guides herein can be integrated into a guidewire. In embodiments where the light guide is integrated into a guidewire, the resulting catheter can be used independently or can be used with various other balloon catheters.

Leads

The electrical leads convey energy from a generator outside of a patient’s body to one or more resistive heaters inside the catheter inside of a patient’s body. The leads are configured to electrically connect the resistive heater of the catheter to an external generator. The leads can be situated in a number of different configurations, based on the particular implementation of the catheter. For example, a coaxial lead can be provided with an inner conductor and an outer conductor. In alternative examples, a wire positioned within a lumen, on an inner surface, or on an outer surface of the elongate shaft can be used as a lead. In alternative examples, a lead can be a conductive trace within a lumen, on an inner surface, or on an outer surface of the elongate shaft. Each resistive heater is provided with at least one lead. A separate lead can be provided for each resistive heater. One example of a conductor that can be used is stainless steel. One other example of a conductor that can be used is copper.

Lumens of the Elongate Shaft (FIGS. 18-29)

The elongate shafts herein can include one or more lumens that span the length of the elongate shaft. Referring now to FIGS. 18-29, schematic cross- sectional views of various embodiments of an elongate shaft having multiple lumens are shown in accordance with various embodiments herein. In some embodiments, the elongate shaft can define a guidewire lumen. In some embodiments, the elongate shaft defines an inflation lumen surrounding the guidewire lumen, where the inflation lumen is in fluid communication with a balloon at a distal portion of the elongate shaft. In other embodiments, the elongate shaft defines an inflation lumen disposed alongside the guidewire lumen, where the inflation lumen is in fluid communication with a balloon at a distal portion of the elongate shaft. The elongate shaft can further define at least one control lumen, at least one light guide lumen, or at least one electrical lead lumen.

In the configuration in FIG. 18, elongate shaft 1800 includes concentrically disposed guidewire lumen 1802 and an inflation lumen 1804. In the configuration in FIG. 19, elongate shaft 1900 includes guidewire lumen 1902 and an inflation lumen 1904 disposed adjacent to and partially surrounding guidewire lumen 1902. In the configuration in FIG. 20, elongate shaft 2000 includes guidewire lumen 2002 and an inflation lumen 2004 disposed adjacent to guidewire lumen 2002. In the configuration in FIG. 21 , elongate shaft 2100 includes guidewire lumen 2102, inflation lumen 2104, and a control lumen 2106. It will be appreciated that the control lumens herein can be used for many purposes, including, but not to be limited to, blood flow, cooling or heating fluid flow, delivery of a diagnostic or therapeutic agent, a light guide lumen, an electrical lead lumen, an inflation lumen, and the like. In the configuration in FIG. 22, elongate shaft 2200 includes guidewire lumen 2202, inflation lumen 2204, and two control lumens 2206 and 2208. In the configuration in FIG. 23, elongate shaft 2300 includes guidewire lumen 2302, inflation lumen 2304, and control lumens 2306.

The light guides or electrical leads can be disposed within one or more energy source lumens disposed within the elongate shafts symmetrically about the circumference. In the configuration in FIG. 24, elongate shaft 2400 includes guidewire lumen 2402, energy source lumen 2404, and control lumen 2406. One or more of lumens 2402, 2404, and 2406 can serve as an inflation lumen. In the configuration in FIG. 25, elongate shaft 2500 includes guidewire lumen 2502, energy source lumen 2504, and control lumen 2506. Elongate shaft 2500 includes two additional lumens that can both be configured as energy source lumens, control lumens, or both an energy source lumen and control lumen. One or more of lumens 2502, 2504, and 2506 can serve as an inflation lumen. In the configuration in FIG. 26, elongate shaft 2600 includes guidewire lumen 2602, energy source lumen 2604, and control lumen 2606. Elongate shaft 2600 includes six additional lumens that can be configured as inflation lumens, energy source lumens, control lumens, or any combination of inflation lumens, energy source lumens, and control lumens.

The light guides or electrical leads can be disposed within one or more energy source lumens disposed within the elongate shafts asymmetrically about the circumference. In the configuration in FIG. 27, elongate shaft 2700 includes guidewire lumen 2702, energy source lumen 2704, and control lumen 2706. Elongate shaft 2700 includes one additional lumen that can be configured as an inflation lumen, an energy source lumen, or a control lumen. In the configuration in FIG. 28, elongate shaft 2800 includes guidewire lumen 2802, energy source lumen 2804, and control lumen 2806. Elongate shaft 2800 includes three additional lumens that can be configured as inflation lumens, energy source lumens, control lumens, or any combination of energy source lumens and control lumens. In the configuration in FIG. 29, elongate shaft 2900 includes guidewire lumen 2902, energy source lumen 2904, and control lumen 2906. Elongate shaft 2900 includes three additional lumens that can be configured as inflation lumens, energy source lumens, control lumens, or any combination of inflation lumens, energy source lumens and control lumens.

It will be appreciated that the lumens described in FIGS. 18-29 can assume many shapes, including, but not to be limited to, circular shape, square shape, crescent shape, triangular shape, and the like. The lumens of the elongate shafts can by symmetrically disturbed in the elongate shaft, asymmetrically distributed, or concentrically distributed. It will be further appreciated that the light guide lumens herein can be coated along the longitudinal length of the elongate shaft with a reflective material capable of propagating light along the elongate shaft from a distal light source to the proximal portion of the catheter, so that the lumen itself can act as a light guide without a separate fiber optic structure.

Resistive Heaters (FIGS. 30 & 31 )

Suitable resistive heating elements can include hot filament elements, such as a low voltage electric heater or microheater elements. In some embodiments, the heating element can be a thin microfilm heater. In some embodiments, the heating element can be a wire heater on a substrate. The heating elements described herein can be made from materials that, include, but are not to be limited to those made from tungsten, aluminum, brass, carbon, copper, platinum, tantalum, tantalum/aluminum alloys, nickel/chrome alloys (e.g., nichrome), iron/chromium/aluminum alloys (e.g., FeCrAI), copper/nickel alloys, molybdenum alloys, tungsten alloys, graphite, steel, stainless steel, zinc, alloys including at least nickel, chromium, and iron; molybdenum, molybdenum disilicide (M0S12), silicon carbide, barium titanate, and lead titanate composites.

To achieve superheating and spontaneous vaporization, the rate of heating the balloon fluid must be sufficiently high, typically on the order of 10 ⁵ to 10 ⁷ K/s (kelvins per second). Resistive heating elements with small thermal mass can obtain high heating rates. One exemplary structure for obtaining a high heating rate is thin-film resistive heaters of sub-micron thickness deposited on a substrate with low thermal conductivity. Referring now to FIG. 30 a schematic top-down view of a thin-film resistive heater 3000 is shown in accordance with various embodiments herein. Thin-film resistive heater 3000 can be in electrical communication with lead 3002, where a voltage potential exists across the thin- film resistive heater 3000. In FIG. 30, the positive potential exists at a first side 3006 and the negative potential exists at the second side 3008. It will be appreciated that in some embodiments, the first side 3006 having a negative potential can be on a proximal side of the heater and the second side 3008 having a positive potential can be on a distal side of the heater, or the reverse can be true. The thin-film resistive heaters can assume many shapes, including, but not to be limited to squares, circles, rectangles, parallelograms, triangles, and the like. The dimensions of the thin-film resistive heaters can include a height 3010 and a width 3012. The dimensions of the thin-film resistive heaters can further include a film thickness (not shown in FIG. 30). The width of the thin-film resistive heaters can be from 10 miti to 10 millimeters (mm) and the length of the thin-film resistive heaters can be from 10 gm to 10 mm. The thin-film resistive heaters can have a film thickness of from 1 nanometer (nm) to 100 micrometers (miti).

One example is a thin-film resistive heater structured as those contained within a thermal ink jet printhead sold as HP 51604A Ink Cartridge, commercially- available from Hewlett-Packard, as, Zhao et al. ,“Pressure and Power Generation during Explosive Vaporization on a Thin-Film Microheater,” International Journal of Heat and Mass Transfer 43 (2000) 281 -296. Other options for resistive heaters are described in U.S. Patent Nos. 6,460,966 and 8,369,696 and in U.S. Patent Application 2004/0178879, which are hereby incorporated herein in their entireties.

The resistive heaters herein can also include a hot filament resistive heater. In some embodiments, the hot filament resistive heaters herein can include a wire heater. Referring now to FIG. 31 a schematic top-down view of a wire heater 3100 is shown in accordance with various embodiments herein. The wire heater 3100 can be in electrical communication with lead 3102, where a voltage potential exists across a wire 31 18 of the wire heater 3100. In FIG. 31 , the positive potential exists at a first end point 3106 of the wire 31 18 and the negative potential exists at a second end point 3108 of the wire 31 18. It will be appreciated that in some embodiments, the first end point 3106 having a negative potential can be on a proximal side of the heater and the second end point 3108 having a positive potential can be on a distal side of the heater, or the reverse can be true. Alternatively, the first end point 3106 having a negative potential can be on a lateral side of the heater and the second end point 3108 having a positive potential can be on an opposite lateral side of the heater.

The wire 31 18 is on a substrate 31 16. The substrate 31 16 can be made from non-conducting materials such as polymers and ceramics.

The wire heaters can assume many shapes, including, but not to be limited to squares, circles, rectangles, parallelograms, triangles, and the like. In FIG. 31 , the wire includes a first end point, and second end point, and a serpentine portion between the first end point and second end point.

The dimensions of the wire heaters can include a height 31 10 and a width 31 12. The dimensions of the wire heaters can further include a trace, or wire, thickness (not shown in FIG. 31 ). The width of the substrate of the wire heaters 3100 can be from 10 pm to 10 millimeters (mm) and the length of the substrate of the wire heaters 3100 can be from 10 pm to 10 mm. A thickness of the trace or wire 31 18 can be from 1 nanometer (nm) to 100 micrometers (pm).

Fiber Diffusers

A fiber diffuser directs light from within a light guide to exit at a side surface portion of the light guide. The fiber diffusers described herein can be created several ways. In some embodiments, the fiber diffusers can be created by micro machining the surface of the distal portion of a light guide with a CO2 laser. In some embodiments, a fused silica coating can be applied to the distal portion of the light guide. In other embodiments, the fiber diffuser can be formed from a glass, a polymer, or a metal coating on the distal portion of the light guide. In other embodiments, the fiber diffuser can be formed by a fiber Bragg grating on the distal portion of the light guide. In some embodiments, the fiber diffuser can include a machined portion of the light guide, a laser-machined portion of the light guide, fiber Bragg gratings, a fused splicing, a fused splicing forming at least one internal mirror, and a splicing of two or more diffuse regions. Suitable materials for a fiber diffuser can include, but not be limited to, the materials of the core or cladding, ground glass, silver coated glass, gold coated glass, Ti02, and other materials that will scatter and not significantly absorbed the light wavelength of interest. One method that can be used to create a uniform diffuser in a light guide, optical component, or materials is to utilize scattering centers on the order of 50 nanometers to 5 micrometers in size. The scattering centers can have a distribution around 200 nanometers in size.

Light Sources The light sources suitable for use herein can include various types of light sources including lasers and lamps. Suitable lasers can include short pulse lasers on the sub-millisecond timescale. In some embodiments, the light source can include lasers on the nanosecond (ns) timescale. The lasers can also include short pulse lasers on the picosecond (ps), femtosecond (fs), and microsecond (us) timescales. It will be appreciated that there are many combinations of laser wavelengths, pulse widths and energy levels that can be employed to achieve superheating in the balloon fluid of the catheters described herein. In various embodiments, the pulse widths can include those falling within a range including from at least 10 ps to 200 ps. In some embodiments, the pulse widths can include those falling within a range including from at least 20 ps to 100 ps. In other embodiments, the pulse widths can include those falling within a range including from at least 1 ps to 500 ps.

Exemplary microsecond lasers can include those within the UV to IR spectrum, spanning wavelengths of about 10 nanometers to 1 millimeter. In some embodiments, the light sources suitable for use in the catheter systems herein can include those capable of producing light at wavelengths of from at least 750 nm to 2000 nm. In some embodiments, the light sources can include those capable of producing light at wavelengths of from at least 700 nm to 3000 nm. In some embodiments, the light sources can include those capable of producing light at wavelengths of from at least 100 nm to 10 micrometers (pm). Microsecond lasers can include those having repetition rates of up to 200 kHz. In some embodiments, the laser can include a Q-switched thulium:yttrium-aluminum-garnet (Tm:YAG) laser. In some embodiments, the laser can include a neodymium:yttrium- aluminum-garnet (Nd:YAG), holmium:yttrium-aluminum-garnet (Ho:YAG), erbium:yttrium-aluminum-garnet (Er:YAG), excimer laser, helium-neon laser, carbon dioxide laser, as well as doped, pulsed, fiber lasers.

Acoustic Pressure Waves

The catheters herein can generate acoustic pressure waves having pressures in the range of 2 megapascals (MPa) to 25 MPa. The maximum pressure generated by a particular catheter will depend on the light source, the absorbing material, the propagation medium, and other factors. In some embodiments, the catheters herein can generate acoustic pressure waves having peak or maximum pressures in the range of 5 MPa to 20 MPa. In some embodiments, the catheters herein can generate acoustic pressure waves having peak pressures of about 1 MPa, 2 MPa, 3 MPa, 4 MPa, 5 MPa, 6 MPa, 7 MPa, 8 MPa, 9 MPa, 10 MPa, 1 1 MPa, 12 MPa, 13 MPa, 14 MPa, 15 MPa, 16 MPa, 17 MPa, 18 MPa, 19 MPa, 20 MPa, 21 MPa, 22 MPa, 23 MPa, 24 MPa, or 25 MPa. It will be appreciated that catheters herein can generate acoustic pressure waves having operating pressures or peak pressures that can fall within a range, wherein any of the forgoing numbers can serve as the lower or upper bound of the range, provided that the lower bound of the range is a value less than the upper bound of the range.

Therapeutic treatment can act via a fatigue mechanism or a brute force mechanism. For a fatigue mechanism, operating pressures would be about 0.5 MPa to 2 MPa, or about 1 MPa. For a brute force mechanism, operating pressures would be about 20 MPa to 30 MPa, or about 25 MPa. Pressures between the extreme ends of these two ranges may act upon a calcified lesion using a combination of a fatigue mechanism and a brute force mechanism.

It should be noted that, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. It should also be noted that the term“or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise.

It should also be noted that, as used in this specification and the appended claims, the phrase“configured” describes a system, apparatus, or other structure that is constructed or configured to perform a particular task or adopt a particular configuration. The phrase "configured" can be used interchangeably with other similar phrases such as arranged and configured, constructed and arranged, constructed, manufactured and arranged, and the like. All publications and patent applications in this specification are indicative of the level of ordinary skill in the art to which this invention pertains. All publications and patent applications are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated by reference.

As used herein, the recitation of numerical ranges by endpoints shall include all numbers subsumed within that range (e.g., 2 to 8 includes 2.1 , 2.8, 5.3, 7, etc.).

The headings used herein are provided for consistency with suggestions under 37 CFR 1 .77 or otherwise to provide organizational cues. These headings shall not be viewed to limit or characterize the invention(s) set out in any claims that may issue from this disclosure. As an example, although the headings refer to a“Field,” such claims should not be limited by the language chosen under this heading to describe the so-called technical field. Further, a description of a technology in the“Background” is not an admission that technology is prior art to any invention(s) in this disclosure. Neither is the“Summary” to be considered as a characterization of the invention(s) set forth in issued claims.

The embodiments described herein are not intended to be exhaustive or to limit the invention to the precise forms disclosed in the following detailed description. Rather, the embodiments are chosen and described so that others skilled in the art can appreciate and understand the principles and practices. As such, aspects have been described with reference to various specific and preferred embodiments and techniques. Flowever, it should be understood that many variations and modifications may be made while remaining within the spirit and scope herein.