Microcatheter systems and methods for crossing total occlusions

Abstract

Microcatheter systems for crossing total occlusions are provided. Aspects of the systems include: a microcatheter with proximal and distal regions, the distal region comprising a fixed, sealed end, wherein the microcatheter comprises a lumen that receives liquid and gas, a fluid introduction module for introducing liquid and gas into the microcatheter lumen and an actuator that repeatedly pressurizes a liquid and gas mixture present within the microcatheter lumen such that the distal region of the microcatheter vibrates, moving the microcatheter across a total occlusion. Also provided are methods for modulating a total occlusion, e.g., by crossing a total occlusion or modifying a proximal cap thereof, e.g., by producing a divot or hole in the proximal cap. The systems and methods find use in a variety of different applications, including balloon angioplasty applications or other catheter-based therapies or treatments, such as conditions in which a total occlusion may be present in a vessel, including, for example, cardiovascular disease.

Description

Cross-Reference to Related Applications Pursuant to 35 U.S.C. § 119(e), this application claims priority to the filing date of United States provisional patent application serial no. 63 / 552,936 filed February 13, 2024, the disclosure of which application is incorporated herein by reference in its entirety. Introduction Chronic total occlusions (CTOs) are complete or nearly complete atherosclerotic vessel occlusions that occur in the human vasculature such as cardiovascular arteries. A chronic total occlusion is typically defined in a blockage lasting for more than three months. CTOs are present in approximately 20-25% of all patients with coronary artery disease. The morphology of the CTO, including the proximal cap, occlusion length, location and size of the compromised vessel, the tortuosity of the compromised vessel, and level of calcification, creates unique technical challenges to successful treatment. One common open surgical approach to address such conditions is coronary artery bypass graft (CABG), an open-heart procedure in which the clinician removes a segment of a vein or artery from another location in the anatomy and uses the segment to create a detour around the CTO to restore healthy blood flow. More recently endovascular approaches to the treatment of CTOs have been developed. One such endovascular approach is the use of conventional guidewires, which are usually 0.22-0.40 mm in diameter, to cross the CTO lesion and then to guide other endovascular instruments across the lesion. Conventional guidewires usually consist of an inner core and outer spring-coil or polymer jacket. Issues with conventional guidewires cause difficulty in their use, including, for example, guidewire buckling at the CTO proximal cap and difficulty ensuring that the guidewire remains within the true lumen of the luminal tissue. In addition to the conventional guidewire, specialty crossing techniques and devices exist that aid the interventionalist in crossing CTOs. For example, guidewires can be used to cross in anterograde (crossing through the proximal cap), retrograde (crossing through the distal cap), and / or sub-intimally (i.e., through the subintimal space). Past proposed solutions have included devices with a special support balloon that engages the proximal vessel wall and lengthens during cyclical pulsatile pressure waves to push an inner guidewire through the CTO. Such devices attempt to localize the force required to push the guidewire through the proximal cap to the wall area just proximal to the CTO lesion. However, issues with these devices include potential damage to the healthy vessel wall proximal to the CTO, poor trackability, inability to steer the guidewire, and buckling. Therefore, there remains a need for improved systems and methods for successfully penetrating the proximal cap of a total occlusion while minimizing the forces on the surrounding vessel wall and successfully navigating the length of the CTO. As described herein, the invention relates to CTO crossing systems and methods. Summary Microcatheter systems for crossing total occlusions are provided. Aspects of the systems include a microcatheter with proximal and distal regions, the distal region comprising a fixed, sealed end, wherein the microcatheter comprises a lumen that receives liquid and gas, a fluid introduction module for introducing liquid and gas into the microcatheter lumen; and an actuator that repeatedly pressurizes a liquid and gas mixture present within the microcatheter lumen such that the distal region of the microcatheter vibrates, moving the microcatheter across an a total occlusion. In some cases, the fluid introduction module is configured for separately introducing liquid and gas into the microcatheter lumen. In other cases, the fluid introduction module is configured for introducing liquid and gas together into the microcatheter lumen. In embodiments, repeatedly pressurizing the liquid and gas mixture present within the microcatheter lumen causes the gas to form a plurality of bubbles. In embodiments, repeatedly pressurizing the liquid and gas mixture present within the microcatheter lumen forces at least some of the plurality of gas bubbles towards the distal region of the microcatheter. In some cases, repeatedly pressurizing the liquid and gas mixture present within the microcatheter lumen agitates the gas bubbles in the distal region of the microcatheter. In some cases, agitating the gas bubbles in the distal region of the microcatheter causes the distal region of the microcatheter to vibrate. In embodiments, the vibration of the distal region of the microcatheter causes the distal region of the microcatheter to advance across the total occlusion. In some embodiments, the vibration of the distal region of the microcatheter causes cracks in calcified plaque present in the total occlusion. In certain cases, the liquid and gas present in the microcatheter lumen propagate pressure along the lumen from the proximal to distal region of the microcatheter. In other cases, the liquid comprises a saline solution or a contrast fluid. In embodiments, the total occlusion is a chronic total occlusion. In embodiments, the total occlusion comprises calcified plaque. Methods of crossing a total occlusion are also provided. Embodiments of methods comprise: deploying a microcatheter system comprising a microcatheter with proximal and distal regions, the distal region comprising a fixed, sealed end, wherein the microcatheter comprises a lumen that receives liquid and gas, so that the distal region of the microcatheter is adjacent to a proximal end of atotal occlusion, the microcatheter system further comprising: afluid introduction module an interface for introducing liquid and gas into the microcatheter lumen; and an actuator that repeatedly pressurizes a liquid and gas bubble mixture present within the microcatheter lumen; and engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen such that the distal region of the microcatheter vibrates, moving the microcatheter across the total occlusion. Certain embodiments further comprise separately introducing liquid and gas into the microcatheter lumen. Other embodiments further comprise introducing liquid and gas together into the microcatheter lumen. In embodiments, engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen comprises repeatedly applying a relatively high pressure to the microcatheter lumen followed by applying a relatively low pressure to the microcatheter lumen. In embodiments, the total occlusion comprises calcified plaque. Embodiments of the invention further comprise applying an axial force to the microcatheter while the distal region of the microcatheter vibrates. Embodiments of the present invention further comprise engaging the system to crack calcified plaque in the total occlusion. Brief Description of the Figures The invention may be best understood from the following detailed description when read in conjunction with the accompanying drawings. Included in the drawings are the following figures: FIGS. 1A and 1B provide a schematic diagrams of a microcatheter system for crossing total occlusions according to an embodiment of the invention. FIGS. 2A, 2B, and 2C provide schematic diagram of aspects of microcatheter systems in accordance with embodiments of the invention. FIG. 3 provides a cutaway side illustration of an embodiment of a proximal connector or amplifier or actuator of the invention. FIG. 4 depicts aspects of an embodiment of a microcatheter system of the invention. FIG. 5 depicts aspects of an embodiment of a connector of a microcatheter system of the invention. FIGS. 6A, 6B, and 60 depict aspects of an embodiment of a method of crossing total occlusions of the present invention. FIGS. 7A and 7B show an application of applying pressure oscillations to aspects of a microcatheter system of the invention in contact with a CTO. Detailed Description Microcatheter systems for crossing total occlusions will now be described with reference to the accompanying figures. Aspects of the systems include: a microcatheter with proximal and distal regions, the distal region comprising a fixed, sealed end, wherein the microcatheter comprises a lumen that receives liquid and gas, an interface for separately introducing liquid and gas into the microcatheter lumen and an actuator, also referred to as an amplifier or proximal connector or connector, that repeatedly pressurizes a liquid and gas mixture present within the microcatheter lumen such that the distal region of the microcatheter vibrates, moving the microcatheter across a total occlusion. Also provided are methods for modulating a total occlusion, e.g., by crossing a total occlusion or modifying a proximal cap thereof, e.g., by producing a divot or hole in the proximal cap. The systems and methods find use in a variety of different applications, including balloon angioplasty applications or other catheter-based therapies or treatments, such as conditions in which a total occlusion may be present in a vessel, including, for example, cardiovascular disease. By “total occlusion,” it is meant a lesion, such as an occluded lesion, a chronic total occlusion or other calcified plaque (CP) deposit. In embodiments of the present invention, the vibration of a distal region of the microcatheter is a mechanism of action for causing cracks in calcified plaque (CP) present in luminal tissue (e.g., vessel walls, arterial walls, etc.) and for moving the distal end of the microcatheter into and across a lesion, such as an occluded lesion, chronic total occlusion or other calcified plaque (CP) deposit. That is, in embodiments, repeatedly pressurizing a liquid-gas mixture present the distal region of the microcatheter causes a distal region of the microcatheter to vibrate. For example, such repeated pressurization may cause intense movement of a plurality of bubbles present in a distal region of the microcatheter, and the bubbles’ interactions with each other and with the interior surfaces of the microcatheter lumen causes a distal region of the microcatheter to vibrate. Such vibration of a distal region of the microcatheter, when brought into contact with a lesion comprising calcified plaque, such as an occluded lesion, chronic total occlusion or other calcified plaque (CP) deposit, causes cracks in the calcified plaque present in such lesion. Such cracking, in conjunction with applying an axial force to the microcatheter (e.g., a force urging the distal end of the microcatheter in a distal direction), allows the distal end of the microcatheter to create a channel into and across such lesion. Microcatheter Systems For Crossing Total Occlusions As summarized above, microcatheter systems for crossing total occlusions are provided. Microcatheter systems of embodiments of the invention are configured to enable movement of a microcatheter across a total occlusion or severe stricture in a vessel structure or the like by repeatedly pressurizing a liquid and gas mixture present in the microcatheter causing bubbles to form near a distal region of the microcatheter. Continuing to repeatedly pressurize the liquid and gas mixture present in the microcatheter causes the bubble and liquid mixture near the distal region of the microcatheter to vibrate which vibrations are transmitted to the tissue of the total occlusion, in some cases causing cracking of calcified plaque, and thereby moving the microcatheter across the total occlusion and, in some cases, disrupting the total occlusion. For example, when a distal region, such as the distal end, of the microcatheter is brought into contact with a CTO, such as a proximal face of the CTO, the vibrations of the distal end of the microcatheter are transmitted to the proximal face of the CTO. Such transmitted vibrations cause the CTO to vibrate, thereby disrupting the CTO or the proximal cap of the CTO, e.g., by causing cracking of calcium present therein, such as calcified plaque, and allowing the microcatheter to move across the CTO. In embodiments, the amplitude, frequency and duty cycle of repeatedly pressurizing the liquid and gas mixture in the microcatheter affects the amplitude, frequency and duty cycle of vibrations transmitted from the distal region of the microcatheter to the total occlusion. In some cases, the proximal cap of a CTO is the most difficult aspect of the CTO to disrupt or modify or break up, depending, at least in part, on the calcification patterns and degree of calcification of the CTO. Embodiments of the present invention may find use creating a lumen in a CTO, by, for example, disrupting the proximal cap of the CTO, which can then be used to pass a guidewire through the lumen. Embodiments of the present invention find use clearing space within a CTO for subsequently performing a pulsatile intravascular lithotripsy procedure. That is, the vibration of the microcatheter of the present invention disrupts the CTO, e.g., by cracking calcified plaque, creating space within the lesion such that a pulsatile intravascular lithotripsy balloon can be inserted and a pulsatile intravascular lithotripsy treatment applied. In embodiments, the outside diameter of the microcatheter and / or the outside diameter of a distal tip of the microcatheter may be configured to be greater than the outside diameter of a pulsatile intravascular lithotripsy catheter assembly, e.g., a folded balloon of a pulsatile intravascular lithotripsy catheter assembly. In other cases, embodiments of the present invention find use clearing space within a CTO for subsequently performing a secondary intervention, such as interventions well-known in the art, including, for example, inserting a drug coated balloon into the CTO. In embodiments, any convenient technique may be utilized to bring a distal region, such as the distal end, of the microcatheter into contact with a proximal face of the CTO. In some cases, an operator may guide a distal region, including the distal end, into contact with a proximal face of the CTO. In other cases, microcatheter systems of the invention comprise a linear stage, such a motor configured to control the lateral position of the microcatheter, which is used to bring a distal region, such as the distal end of the microcatheter into contact with a proximal face of the CTO. In some cases, a distal region, such as the distal end, of the microcatheter is repeatedly brought into contact with a proximal face of the CTO, i.e., such that the vibrating distal end of the microcatheter pecks at the proximal face of the CTO. Such gross lateral motion of the microcatheter in conjunction with the vibrations caused by applying pressure oscillations to the microcatheter together cause movement of the microcatheter across the CTO. Systems of the invention find use in a variety of applications. In some instances, the systems find use in treating chronic total occlusions. Specifically, systems of the invention find use in treating chronic total occlusions including (1) passing a microcatheter across a chronic total occlusion’s proximal cap, potentially in connection with passing a guidewire across a chronic total occlusion’s proximal cap, (2) navigating through long, tortuous chronic total occlusion lesions, (3) guiding the microcatheter through or around varying tissue densities and (4) remaining within and reaching the distal “true lumen” of the chronic total occlusion. For embodiments presented herein, the present disclosure describes applications related to treating chronic total occlusions related to atherosclerotic calcifications within an arterial conduit, such as a coronary or peripheral artery. However, the present system and teachings are not solely limited to chronic total occlusions related to atherosclerotic calcifications nor arterial conduits and may be generally applied to other applications as determined by those skilled in the art. A microcatheter system in accordance with an embodiment of the invention is schematically illustrated in FIGS. 1A-B. FIG. 1A shows an embodiment of a microcatheter system of the invention with the right-hand side of the figure being relatively distal (i.e., towards the total occlusion) and the left-hand side of the figure being relatively proximal (i.e., away from the total occlusion). Shown in FIG. 1A is microcatheter system 100 comprising microcatheter 150 extending from actuator 110 to distal region of microcatheter 160, ultimately to distal end of microcatheter 170. The relative longitudinal length of microcatheter 150 is not depicted, as indicated by the cut-through line showing where an arbitrary length of microcatheter 150 is shown for purposes of illustration only. Microcatheter system 100 further comprises interface 120 with gas port 130, i.e., for introducing gas into microcatheter lumen 180, and liquid port 140, i.e., for introducing liquid into microcatheter lumen 180. Interface 120, through separate gas port 130 and liquid port 140, enables control of separate introduction of gas and liquid into microcatheter lumen 180. Distal region of microcatheter 160 includes a region, in which bubbles of the liquid-gas mixture present within microcatheter lumen 180 are caused to congregate by application of pressure oscillations created by actuator 110 to the liquid-gas mixture present in microcatheter lumen 180. Bubbles present in distal region of microcatheter 160 are agitated by such pressure oscillations and such resulting turbulence causes distal region of microcatheter 160 to vibrate. These vibrations cause disruption at the proximal end of the CTO causing movement of microcatheter 150 across a total occlusion. Application of pressure oscillations, created by actuator 110, to fluid present in microcatheter 150 cause the fluid column extending from actuator 110 to distal end 170 of microcatheter 150 to be pulsed via hydraulic or differential shock or a water hammer effect, in which the fluid transmits a pressure wave from actuator 110, ultimately, to distal end 170 of microcatheter 150. As described herein, actuator 110 receives output potential energy from switch 111 and converts that energy to a hydraulic or differential shock and guides that shock to microcatheter 150 and ultimately to distal end 170 of microcatheter 150. Distal end 170 of microcatheter 150 is a fixed, sealed end of microcatheter 150. That is, distal end 170 does not change shape (e.g., inflate or deform under pressure) or allow fluid, such as a liquid-gas mixture to flow out of microcatheter lumen 180. Microcatheters employed in embodiments of systems according to the present invention comprise proximal and distal regions, the distal region 160 comprising a fixed, sealed distal end 170, wherein the microcatheter comprises a lumen 180 that receives liquid (via liquid port 140) and gas (via gas port 130). By proximal region, it is meant a region of the catheter relatively closer to an operator of the microcatheter system and relatively further away from the CTO or other lesion of a subject, on whom the microcatheter system is employed. By distal region, it is meant a region of the catheter relatively closer to the CTO or other lesion of a subject, on whom the microcatheter system is employed and relatively further away from an operator of the microcatheter system. By fixed, sealed distal end (e.g., fixed, sealed distal end 170), it is meant that the distal end of the microcatheter may include a covering or a cap or a closed end that is configured to seal fluid within the microcatheter lumen 180. Microcatheters employed in systems of the invention may be configured to be reusable or single use, as desired. The microcatheter according to the present invention may vary. Microcatheters of the invention are capable of structurally withstanding high-frequency, high-amplitude vibrations over a period of time. Additionally, microcatheters of this invention are capable of receiving fluids, including pressurized fluids without being deformed or damaged. Suitable materials for microcatheters of this invention include any biocompatible polymer materials well known in the art, such as, for example, rubber, silicone, latex, polyvinyl chloride (PVC), polyurethane and the like. In some embodiments, microcatheters may be reinforced along a portion of, or the entire length of, the microcatheter. Such reinforcement materials may include braided, co-extruded, or discrete layers. Examples include polyimide braids or a thermoplastic jacket, for example, a polyimide. Materials utilized for such reinforcement layers include stainless steel, nitinol, polymeric fibers, or any combination thereof. In some embodiments, the microcatheter may further comprise an external coating selected based on the application of the microcatheter system. For example, in some cases, embodiments of the microcatheter may further comprise a lubricious exterior coating. Any convenient coating that reduces friction related to the interaction of the microcatheter and the internal luminal tissue to which the microcatheter is applied may be used. In some cases, such an exterior coating may comprise polytetrafluoroethylene (i.e., PTFE). In embodiments, the microcatheter may comprise an elongate microcatheter with a length ranging from approximately 50 cm to 500 cm, such as 200 cm, 300 cm or 400 cm. In embodiments, the microcatheter may have an outer diameter ranging from between 0.2 mm to 3.0 mm, such as 0.7 mm or 1.0 mm or 2.0 mm. In embodiments, the outer diameter of the microcatheter may vary as needed depending upon, among other things, characteristics of the tissue the distal crasser unit is applied to, including the diameter of the internal luminal tissue, such as an artery or vein. In other instances, the outer diameter of the microcatheter may vary depending on characteristics of the total occlusion, such as the diameter of the total occlusion. The outer diameter of the microcatheter may vary across different regions of the elongate microcatheter. In some instances, the microcatheter may be tapered. In such instances, the microcatheter may comprise a taper ranging from 0.01e to 5e, such as 1e or 2e or 3B or 4e, over a region of the microcatheter. In some instances, different regions of the microcatheter may comprise different amounts of tapering, including in some instances, no tapering. The amount of tapering may vary depending on, among other things, different applications of the distal crasser unit and different characteristics of the total occlusion. FIG. 1B provides another view of microcatheter system 100. Microcatheter system 100 includes a console 112 and potential source 1113 that is set to provide an output 112a of potential energy, which output may vary, such as a pre-determined output, user-set output, or feedback / feedforward-controlled output. The potential source 113 can vary, where examples of potential sources include, but are not limited to, electromagnetic, such as electrical voltage or current, potential sources or a high- pressure gas, such as nitrogen, carbon dioxide, compressed air or mixtures of gases, etc. The potential source output 113 can be set to a certain potential output such as voltage or pressure or another output such as current or flow rate. This output can be adjusted, e.g., via a regulator, between a minimum and maximum level (e.g., pressure or voltage or current), which may or may not exceed the level of the input potential source 113. In some cases, multiple potential sources may be used at once or at separate times (e.g., via a single console or multiple consoles and / or a single handle or multiple handles). As illustrated, the potential output 112a of console 112 is output (i.e., transmitted) to a switch 111, for example an electronic and or mechanical switch, solenoid or the like. Switch 111 may be located within a handle. Switch 111 and / or a handle may comprise multiple output connections such as an output to proximal connector 110. Switch 111 and / or handle is operably connected to proximal connector 110. However, proximal connector 110 and switch 111 and / or handle are each configured such that proximal connector 110 can be releasably engaged (i.e. capable of being operably connected and then disengaged) from switch 111 and / or handle. In certain cases, the switch 111 and / or handle are reusable, whereas the proximal connector 110 is disposable, such that the switch 111 and / or handle can be disengaged from, for example, proximal connector 110 in order to operably connect switch 111 and / or handle to another proximal connector (itself connected to another microcatheter and interface). Where desired, the microcatheter system may include one or more sensors, e.g., configured to provide data regarding one or more aspects of the system. Any convenient type of sensor may be included in the microcatheter, where sensors of interest include, but are not limited to: force sensors, pressure sensors, positional sensors, displacement sensors, proximity sensors, flow sensors, temperature sensors, vibration sensors and the like. In some instances, the microcatheter lumen includes a pressure sensor present in a distal region of the microcatheter. In such instances, the pressure sensor may detect pressure and changes thereof in the fluid, such as a liquid or a liquid-gas mixture, present at such distal region of the microcatheter lumen. When included, any convenient type of pressure sensor may be present, where examples of pressure sensors that may be present include, but are not limited to: resistive, capacitive, piezoelectric, optical, and MEMS-based pressure sensors, and the like. Pressure sensors of interest include pressure sensors capable of measuring pressure applied to a mixture of liquid and gas. Further, any combination of sensors may be used to gather positional data of a distal region of the microcatheter. In cases in which a combination of positional sensors is employed, e.g., to ensure sensors provide correct data across a variety of conditions, such as frequencies, sensor data may be combined through “sensor fusion” techniques, such as those known in the art. Fabrication methods of sensors of interest may include, but are not limited to: adhesives, direct printing, welding, embedding and the like. In FIG. 1B, console assembly 112 is associated with controller 130 configured to receive input (comprising, e.g., control and / or data input signals, e.g., sensor data signals) from at least one of console assembly 112, potential source 113, switch 112or other aspects of system 100. In the depicted embodiment, controller 130 receives input from sensors 152, 153 via electrical connector 155. Sensors 152, 153 may comprise any sensor configured to sense any relevant characteristic of microcatheter system 100 capable of detection. For example, sensor 152 may comprise a pressure transducer configured to measure a pressure within microcatheter 150, and sensor 153 may comprise a volume sensor (i.e., a displacement sensor, such as a Hall sensor, integrated into proximal connector 110, for example), configured to measure a volume of fluid present in, i.e., displaced into, for example, microcatheter 150 (i.e., where operation of connector 110 displaces fluid, e.g., liquid or a liquid-gas mixture, into microcatheter 150). Embodiments of the microcatheter system may further comprise catheter marker bands. In embodiments, catheter marker bands may be affixed to different components of the microcatheter system, such as, for example, to various locations on the microcatheter such as a distal region of the microcatheter or the distal tip of the microcatheter. For example, one or more marker bands may be located at a distal region or at the distal tip of the microcatheter to visualize progress of the advancement of the microcatheter across the lesion, i.e., CTO. Catheter marker bands may be used to visualize the position of the microcatheter system, or components thereof, when applied to a subject. Catheter marker bands may be placed on the microcatheter such that they may be used to visualize a relative position of different regions of the microcatheter. Marker bands used in embodiments may be any convenient, readily available, off the shelf catheter marker band capable of being affixed, for example, crimped or heat bonded or welded or adhered, to components of the microcatheter system. Marker bands of interest may be polymer bands laden with gold or platinum or tungsten or another material that facilitates visualization, such as visualization via fluoroscopy. Catheter bands may be visualized via fluoroscopic or radiologic visualization techniques. Embodiments of the microcatheter system may further comprise a guiding sheath (or centering balloon) used to align a distal region, including, in some cases, the distal end, of the microcatheter with the proximal cap of the CTO. Such an embodiment is depicted in FIGS. 7A-B, described in detail herein. In general, the guiding sheath itself does not traverse the CTO. That is, the guiding sheath holds the microcatheter in a fixed position relative to the cross section of the luminal tissue surrounding the CTO while the microcatheter interfaces with the CTO. The guiding sheath may be a sheath comprising a microcatheter lumen, i.e., a lumen in which the microcatheter of the microcatheter system is present. The guiding sheath may be made of a material that offers greater stiffness or ability to be steered so that the sheath can be manipulated to align the microcatheter with the proximal cap of the CTO. The interior diameter of the guiding sheath may be configured to substantially conform to the diameter of the microcatheter so that there is minimal space between the outer diameter of the microcatheter and the inner diameter of the sheath. The outer diameter of the sheath may vary based on the diameter of the luminal tissue into which it is introduced. A guiding sheath according to the present invention may comprise one or more balloons configured for aligning the sheath with the proximal cap of the CTO. A balloon may be mounted on the exterior of the guiding sheath at the distal end of the guiding sheath. The balloon may be mounted such that when inflated, the balloon engages the luminal tissue, thereby holding the guiding sheath in a fixed position relative to the CTO. In some cases, the guiding sheath may comprise more than one balloon mounted on the exterior surface used to offset the center of the guiding sheath in the event an opening on the proximal cap of the CTO is off center with respect to the surrounding luminal tissue. When present, any convenient technique may be applied with respect to inflating such one or more balloons attached to an external region of the sheath. For example, the sheath may comprise one or more lumens for supplying fluid to such centering balloon or balloons, e.g., such that the sheath is a dual lumen catheter, or a separate fluid channel, such as a microcatheter that is separate from the sheath, may be provided for inflating such centering balloon on the sheath. Microcatheter systems of embodiments of the invention may be configured to determine the distance the microcatheter travels given an amount pressure and a frequency of pressure oscillations applied to the microcatheter over a period of time. That is, embodiments of microcatheter systems are configured to measure the longitudinal distance the distal tip travels into the CTO given a specified number of pressure oscillations at a specific frequency and amplitude applied to the microcatheter, i.e., applied to the plurality of bubbles of the liquid-gas mixture present in a distal region of the microcatheter. Microcatheter systems may comprise one or more controllers, or other microprocessor devices, configured to receive sensor data, including, for example, imaging data, which may be utilized to measure the longitudinal distance the distal tip travels into the CTO. Microcatheter systems may comprise a linear stage configured to advance the distal end of the microcatheter, i.e., in a lateral direction, where such linear stage may be further configured to output one or more electronic signals utilized by a controller to determine the distance travelled by the distal end of the microcatheter into the CTO. Embodiments may comprise a visual indication of lateral movement for a user to manually observe while urging the microcatheter in a linear direction. Embodiments may comprise an electronic assembly configured to precisely measure linear movement of the microcatheter, such as an optical encoder or other positional sensor or the like. Readings from measurements of linear movement of the microcatheter (i.e., in a distal direction) may be compared (i.e., compared in real time during a procedure) against imaging results indicative of a thickness of a lesion such as a CTO. Such comparison may be used to indicate when the microcatheter has traveled any desired distance, such as completely across, a CTO. Microcatheters may further be configured to measure changes in distance traveled, given a specified amplitude and / or frequency of pressure oscillations applied to the microcatheter over a period of time. Embodiments may be further configured to determine, for example, when a distal region of the microcatheter has reached a region of a CTO where the distance the distal tip moves begins to diminish notwithstanding that the same pressure oscillations are applied to the microcatheter. Such change may be due, for example, to changed characteristics of the CTO or even malfunctioning of the microcatheter system. Such embodiments may be used to understand the pathology, stiffness or other characteristics of the CTO and / or to determine a current location of a distal region of the microcatheter in the vessel. For example, embodiments capable of providing this information (e.g., distance traveled by the distal tip for fixed pressure oscillations applied to the microcatheter) may be used to understand when the distal region of the microcatheter hits soft healthy tissue, such as a vessel or vessel wall. Such information can be used to help minimize the possibility of puncturing healthy tissue, such as a vessel or vessel wall. Embodiments may be configured to utilize such collected data, such as distance traveled by the distal tip, to control, for example, characteristics of the pressure applied to the microcatheter (e.g., frequency of pressure pulses, maximum or minimum pressures applied, magnitude of a differential between maximum and minimum pressures applied or the like). Such embodiments may be configured to comprise a feedback control system based on such collected data. Embodiments of microcatheters of the invention comprise lumens capable of receiving fluids, including pressurized fluids, i.e., without deforming or damaging the microcatheter. Any convenient fluid may be applied, and such may vary. Microcatheter lumens of interest are capable of receiving fluids undergoing pressure oscillations, such as high-frequency, high-amplitude pressure oscillations, without being deformed or damaged. In instances, applying pressure to the fluid present in the microcatheter lumen enables propagation of pressure along the microcatheter lumen, e.g., to propagate pressure along the microcatheter lumen from a proximal region of the microcatheter to a distal region of the microcatheter. The microcatheter lumen may have any convenient diameter to suit the desired volume of fluid present therein and in general may range from 0.15 mm to 2.9 mm, such as 0.45 mm. In embodiments, the distal region of the microcatheter comprises a fixed, sealed end. That is, the distal region of the microcatheter substantially maintains its shape without deformation upon pressurizing fluid present in the microcatheter lumen. Further, the distal region of the microcatheter substantially maintains its shape without deformation upon repeated, high frequency pressure oscillations applied to fluid present in the microcatheter lumen causing such distal end to vibrate. In embodiments, the distal region of the microcatheter does not comprise a balloon, such as a pulsatile intravascular lithotripsy balloon, or other device or tooling configured to deform upon application of pressure pulses to fluid present in the microcatheter. In embodiments, pressure is applied to fluid present in the microcatheter lumen from a relatively proximal location on the length of the microcatheter, e.g., a location that remains ex vivo when the microcatheter system is in use. In certain embodiments, the distal region of the microcatheter comprises a passive feature for holding the microcatheter in a fixed position relative to the CTO. For example, the outer diameter or exterior surface of a distal region of the microcatheter (e.g., a surface of the microcatheter that may interface with the interior lumen surface or the CTO) may be rough, or otherwise comprise features configured to diminish the smoothness and / or lubricity of the surface, in order to facilitate having the surface of the microcatheter catching and holding onto, instead of sliding against, the internal lumen surface or CTO surface. In some cases, the passive feature comprises a rough exterior surface or a serrated surface or a rough edge or a serrated edge, or any combination thereof that restricts backward movement (i.e., movement of the distal end in a proximal direction). That is, a distal region of the microcatheter may comprise features that help to hold the microcatheter in a position relative to the CTO or help urge the microcatheter to move in only one direction, i.e., across the CTO, or to otherwise help the vibration of the microcatheter to disrupt the CTO. In other cases, the distal region of the microcatheter comprises a taper. Any convenient taper shape may be applied. Such shape may facilitate advancing the microcatheter across a CTO, e.g., such that the distal end of the microcatheter wedges itself into and across the CTO. By tapered, it is meant that a distal region of the microcatheter has a different (i.e., larger) cross-sectional diameter than the diameter of the distal end of the microcatheter. Such configurations may facilitate maneuvering the microcatheter across certain CTOs, allowing the distal end of the microcatheter to fit through even narrower spaces, such as narrow spaces in a CTO. In certain cases, the distal region of the microcatheter has a high circumferential stiffness; i.e., the circumferential stiffness may have sufficient stiffness that the microcatheter lumen does not collapse or deform when subjected to pressure oscillations within the microcatheter lumen and / or external pressure applied by the tissue of the CTO to the microcatheter; i.e., a distal region of the microcatheter maintains largely the same shape, including the same diameter, regardless of the pressure applied to such distal region of the microcatheter. That is, in embodiments, the microcatheter, in particular a distal region of the microcatheter, is configured such that it vibrates when pressure oscillations are applied to a gas-liquid mixture present therein and not to dampen or absorb such pressure oscillations. In embodiments, a distal region of the microcatheter may comprise one or more materials selected to provide such stiffness; i.e., such material maybe selected to provide a sufficiently high durometer or Shore durometer such that the distal region of the microcatheter can withstand pressure oscillations and interfacing with the CTO, as described herein. In some cases, a distal region of the microcatheter may be reinforced with a distal tip, as described herein, where such distal tip comprises material with a sufficiently high durometer or Shore durometer to provide a sufficiently rigid distal tip and / or distal region of the microcatheter. In embodiments, the microcatheter system further comprises a distal tip. In some cases, the distal end of the microcatheter is tapered to form a tapered microcatheter core, upon which a distal tip is mounted. The distal tip of the microcatheter may comprise a coil located at the distal end of the microcatheter and attached to the tapered microcatheter core. In embodiments, the distal tip may be shaped based on how the coil is wrapped or coiled. Because the distal tip is shaped based on the configuration of the coil forming the distal tip, the distal tip can be shaped in any number of ways. The length and material of the tapered microcatheter core and the coil are related to the stiffness of the distal tip and the load that the distal tip is designed to bear. The stiffness and distal tip load may be varied based on the application and underlying pathologies, i.e., of the CTO. The distal tip may have the same, or substantially the same, diameter as the microcatheter (i.e., the diameter of the microcatheter at a region other than the region of the tapered microcatheter core) and may be made from the same or different material as that of the microcatheter. In some cases, the distal tip may have a larger diameter than the microcatheter, such as a diameter that is 0.1% or more greater than the diameter of the microcatheter, such as 1% greater, 2% greater, 5% greater or 10% or more greater. In other cases, the distal tip may have a smaller diameter than the microcatheter, such as a diameter than is 0.1% or more smaller than the diameter of the microcatheter, such as 1% smaller, 2% smaller, 5% smaller or 10% or more smaller. The longitudinal length of the distal tip may range from about 1 mm to 50 mm, such as 2 mm or 5 mm or 15 mm or 40 mm. In some cases, the coil of the distal tip may be configured to form a blunt tip. By blunt tip, it is meant that the coil of the distal tip is coiled so that a surface of, and not a single point of, the distal tip comes into contact with the proximal face of the CTO when the microcatheter system is engaged. For example, the blunt tip of the microcatheter may comprise a rounded or substantially hemispherical shape. In general, a blunt tip refers to a shape designed to spread longitudinal force of the microcatheter over a relatively greater cross-sectional surface area of the CTO. In other cases, the distal tip may be shaped so that it forms a sharp tip. By sharp tip, it is meant that the coil of the distal tip is coiled so that the distal end of the distal tip substantially comes to a point. For example, the sharp tip of the distal tip may be substantially conical. In other cases, the sharp tip of the distal tip may be a nib at the end of a rounded or substantially hemispherical shaped tip. In general, a sharp tip refers to a shape designed to focus longitudinal force of the microcatheter over a relatively smaller cross-sectional surface area. In such embodiments, the coil of the distal tip may be configured to form an atraumatic tip. By atraumatic tip, it is meant that the distal tip is shaped to minimize or eliminate tissue damage or trauma to the total occlusion or the luminal tissue (e.g., vessel wall) when the microcatheter is applied to the CTO. In other words, the distal tip may be shaped so that it reduces or eliminates the likelihood that the distal tip will puncture or lacerate tissue of the CTO or tissue proximal thereto during use of the microcatheter. In still other cases, the distal tip may be configured into a shape that is based on a pathology of the CTO. That is, the distal tip may be configured to conform to the shape or other characteristics, such as density or stiffness, of the CTO. In some cases, the distal tip may be configured in a bespoke or nonlinear or nonregular shape that complements the shape of the CTO. For example, the shape of the distal tip may be configured to complement the shape of the proximal face of the CTO. In some cases, the distal tip may be configured so that its shape offers the greatest structural support for the microcatheter system, i.e., a distal region, including the distal end, of the microcatheter, as it progresses across the CTO. In other cases, the distal tip is configured so that its shape offers the greatest likelihood of enabling the microcatheter, i.e., a distal region of the microcatheter, to cross the CTO. Aspects of microcatheter systems in accordance with embodiments of the invention are illustrated in FIGS. 2A-C. FIG. 2A shows an embodiment of distal tip 210 of an embodiment of microcatheter 250a. Distal tip 210 comprises wire coil 230 that is present at a distal region, including the distal end, of microcatheter 250a. Distal tip 210 culminates in atraumatic tip 220 present at the distal end of distal tip 210 of microcatheter 250a. Atraumatic tip 220 comprises a substantially rounded shape intended to reduce the likelihood that distal tip 210 will puncture or lacerate tissue of a CTO or tissue proximal thereto during use of microcatheter 250a and distal tip 210. FIG. 2B shows an embodiment of inner core 240 of an embodiment of microcatheter 250b. Inner core 240 illustrates how a distal region of microcatheter 250b may comprise a smaller diameter and may be tapered. Such shape may allow for a coil, such as coil 230, to surround inner core 240. That is, inner core 240 may comprise a shape that allows a coil, such as coil 230, to be mounted thereon. FIG. 2C shows an embodiment of a distal region of microcatheter 250c. In contrast to atraumatic tip 220, distal region of microcatheter 250c comprises sharp tip 260. Sharp tip 240 substantially comes to a point at the distal end of distal region of microcatheter 250c. Sharp tip 240 focuses any longitudinal force that is a component of the vibration of distal region of microcatheter 250c (i.e., when the microcatheter system is in use) over a relatively smaller crosssectional surface area (i.e., the point at the very distal end, i.e., the sharp tip 240, of distal region of microcatheter 250c). Microcatheters, in particular, a distal region of the microcatheter, including, in some cases, the distal end of the microcatheter, according to the present invention, may be configured so that they are capable of being steered, i.e., directed within a vessel or luminal tissue towards a desired direction, i.e., forward direction, or angle. Steering a distal region of the microcatheter may facilitate aligning the microcatheter with the CTO; or may facilitate guiding the microcatheter through luminal tissue such as a vein or artery to arrive at a CTO; or may facilitate efficiently crossing the CTO. By steering, it is meant that a distal region, including, in some cases, the distal end or a distal tip, of the microcatheter is oriented towards a new direction such that subsequent forward movement of the microcatheter is urged in a new direction. In some cases, a distal region, including, in some cases, the distal end or a distal tip, of a microcatheter is configured so that it can be steered by rotating the microcatheter. In such cases, the microcatheter may be configured so that it has a bias towards one direction, such as a bias to rotate or turn in a specific direction. When the microcatheter is so configured, a distal region, including, in some cases, the distal end, of the microcatheter may be steered by rotating the microcatheter. Rotating the microcatheter enables steering because rotating the microcatheter rotates the side to which the microcatheter is biased. In some cases, a region of the microcatheter is relatively stiff compared with other regions of the microcatheter where such stiff region of the microcatheter biases the microcatheter to turn in a specific direction. For example, on radial section or arc of the microcatheter may comprise a differential radial stiffness. In other embodiments, steering a distal region, including, in some cases, the distal end, of the microcatheter is accomplished through steering springs. That is, in such embodiments, a distal region of the microcatheter comprises steering springs configured to steer the microcatheter. Such springs may be mounted on, or incorporated into, the microcatheter in a manner that biases the microcatheter in a specific direction. In still other embodiments, a distal region of the microcatheter comprises one or more steering cables. For example, one or more steering cables may be attached to distal regions of the microcatheter. The steering cable may be configured such that retracting the steering cable (i.e., applying pressure to the cable in a proximal direction), urges a distal region of the microcatheter to turn or otherwise change direction. Turning now to interface 120 of microcatheter system 100 of FIG. 1, interface 120 further comprises liquid port 140 and gas port 130. Interface 120, through separate gas port 130 and liquid port 140, enables control of the separate introduction of gas and liquid into microcatheter lumen 180. Various configurations of interfaces are of interest in connection with embodiments of the present invention. Embodiments of the present invention comprise a fluid connection module. In some embodiments, the fluid connection module comprises an interface, such as, for example, interface 120. In some cases, interfaces comprise one or more injection-molded elements, with, for example, one or more ports, such as two, ports, configured to receive gas and liquid into the microcatheter. In other embodiments, the fluid connection module comprises one or more Luer locks, such as a three-way Luer lock or a plurality of Luer locks, such as two Luer locks, such that the plurality of Luer locks comprise at least two ports, one for receiving gas into the microcatheter and one for receiving liquid into the microcatheter. In still other embodiments, the microcatheter may be prefilled with a liquid and gas mixture. Such embodiments may comprise a fluid connection module that is sealed; i.e., since liquid and gas are pre-filled in microcatheter, such fluid connection module remains sealed during and after the microcatheter is inserted into a vessel. In embodiments, a liquid-gas mixture is introduced into the microcatheter lumen 180 such that, repeatedly pressurizing the microcatheter lumen 180 causes a plurality of bubbles to form and further causes such bubbles to be urged toward a distal region 160 of the microcatheter lumen 180. When present in a distal region 160 of the microcatheter lumen 180, such plurality of bubbles responds to continued pressure oscillations by increasing the vibration of a distal region 160 of the microcatheter 150 (e.g., increasing the magnitude of vibration of a distal region 160 of the microcatheter 150 as compared with vibrations that occur when only a liquid is present in such distal region 160 of the microcatheter 150). In embodiments, an operator may utilize the fluid connection module, e.g., an interface, such as interface 120, or one or more Luer locks, adjust the total volume of liquid, the total volume or gas or the ratio between the two that is present within the microcatheter. An operator may do so in order that application of pressure oscillations via the connector (and potential energy source connected thereto) generate adequate pulse force to disrupt the CTO. For example, the operator may consider adding additional gas in order that additional bubbles are formed within the catheter in order to increase the pulse force of the microcatheter (i.e., the force applied at the distal end of the microcatheter when pulse oscillations are applied to fluid in the microcatheter). In still other embodiments, fluid introduction module may comprise a mechanism used to produce or generate bubbles within the microcatheter. For example, the fluid introduction mechanism may comprise electrodes configured to expose fluid present within the microcatheter to current. In such cases, passing current through a fluid, e.g., a liquid, produces bubbles within the microcatheter. In such cases, the fluid introduction module may not comprise an external connection to gas (i.e., may not comprise a delivery mechanism for delivering gas to the microcatheter). Other techniques, such as other electricity-based techniques, plasma-based techniques, thermal-based techniques, light-based techniques or the like may be utilized to generate bubbles in fluid present within the microcatheter. In certain cases, the fluid introduction module may comprise a tube operably connected to a distal region of the microcatheter, e.g., the distal end of the microcatheter, and may be configured for porting bubbles directly into the distal end of the microcatheter. Fluid delivery mechanisms, such as interfaces, of interest, such as interface 120 shown in FIG. 1 A, allow for controllable fluidic communication between a source of liquid and a source of gas and the microcatheter lumen, such as microcatheter lumen 180 shown in FIG. 1A. By controllable fluidic communication, it is meant that the interface separately allows a specified amount of liquid from a liquid source to enter the microcatheter lumen and a specified amount of gas from a gas source to enter the microcatheter lumen. In embodiments, the interface allows liquid and gas to enter the microcatheter lumen sequentially. That is, the interface allows the microcatheter lumen to first be substantially filled with liquid, followed by the introduction, via the interface, of gas into the microcatheter lumen. In embodiments, the interface may comprise one or more ports, such as two or more ports or valves configured to allow access from a liquid source and a gas source to the microcatheter lumen. In some cases, the interface may comprise fittings, such as threaded fittings enabling a liquid or gas source to be attached to the microcatheter. The interface, in embodiments, is made of a stiff material such as polyvinyl chloride (PVC) or polycarbonate (PC) or polyimide or the like and may be reinforced with a braid of nitinol or steel or fibrous wire or the like. In embodiments, the interface, such as the ports or valves thereof, may comprise one or more control mechanisms, such as a pin valve or chamber valve or an equivalent thereof, in each case attached to a control, such as a screw mechanism, for opening such ports or valves thereby allowing liquid or gas, as the case may be, to enter the microcatheter lumen. In embodiments, the microcatheter lumen may be depressurized to substantially form a vacuum in the microcatheter lumen, after which liquid followed by gas are introduced into the microcatheter lumen. In certain embodiments, the interface may be configured to allow the introduction of liquid or gas into the microcatheter lumen at any convenient rate, and such may vary. In other embodiments, the liquid source and / or the gas source are controlled (e.g., pressurized) in order to control the rate that liquid and / or gas are introduced into the microcatheter lumen. In embodiments, liquid may be introduced through the interface into the microcatheter lumen at any convenient rate, and such may vary, depending, for example on the liquid and the gas that comprise the liquid-gas mixture present in the microcatheter lumen. In embodiments, a plunger mechanism, such as a syringe, may be attached to the interface be used to introduce liquid into the microcatheter lumen. In some embodiments, gas is bubbled into the liquid present in the microcatheter lumen via the interface. In embodiments, gas may be introduced through the interface into the microcatheter lumen at any convenient rate. More specifically, in some cases, gas may be introduced into the microcatheter lumen at a rate that facilitates the formation of a plurality of gas bubbles with desired shapes or sizes or other characteristics, such as, for example, a preferred dispersion (i.e., spacing) of bubbles throughout a volume of the microcatheter lumen. In embodiments of microcatheter systems of the present invention, the interface is present in a proximal region of the microcatheter. In some cases, the interface comprises a single fluid introduction port for introducing liquid and gas into the microcatheter lumen, where the fluid introduction port comprises a valve mechanism and / or threading for attaching a source of liquid and / or gas. In some cases, the interface comprises: a first fluid introduction port and a second fluid introduction port. In certain instances, the first fluid introduction port comprises a first valve mechanism, and the second fluid introduction port comprises a second valve mechanism. Such first and second valve mechanisms may be controllable, i.e., manipulated to allow greater or lesser liquid or gas, as the case may be, to enter the microcatheter lumen. In embodiments, the first fluid introduction port is connected to a liquid source, and the second fluid introduction port is connected to a gas source. In some embodiments, the interface comprises a control mechanism that separately controls the flow of liquid and gas introduced into the microcatheter lumen. In such embodiments, the control mechanism comprises at least two valves with separate controls. In embodiments, such valves may comprise one-way valves. In other embodiments, such valves may comprise two-way valves. In some cases, an alternative mechanism is used to generate gas bubbles within the microcatheter lumen in addition to or separate from bubbling gas into the liquid of the microcatheter lumen. For example, gas bubbles may be generated using a pair of electrodes disposed within the microcatheter lumen, where the electrodes are spaced apart (i.e., there is a gap between the electrodes) at a sufficient distance such that when a high voltage pulse of electrical potential is applied between the electrodes, a steam bubble is formed in the microcatheter lumen, as a result. In embodiments, each pulse of high voltage is applied to the electrodes and forms an electrical arc across the electrodes that imparts sufficient energy to the liquid present in the microcatheter lumen to generate a bubble. In some cases, the energy imparted to the fluid by the electrical potential applied to the electrodes is sufficient to create plasma in the fluid which causes a bubble to form in the fluid. Any convenient voltage source and controller may be operably connected to the electrodes to provide electrical potential across the electrodes for a specified duration of time such that the electrodes impart sufficient energy to the liquid to generate a bubble. Any convenient duration of an electrical pulse at any convenient voltage may be applied that results in the generation of one or more bubbles of a desired volume and shape, where high electrical voltage potentials and longer duration pulses result in larger bubbles being formed. In other examples, gas bubbles may be generated by directing light energy from a light source to liquid present in the microcatheter such that sufficient energy is imparted to the liquid to generate bubbles. In such embodiments, light energy from a light source may be directed to liquid present in the microcatheter with sufficient energy that plasma formation is initiated within the liquid of the microcatheter causing bubbles to form therein. In embodiments, light energy is transmitted or guided from the light source to the liquid present in the microcatheter via any convenient means of directing light, such as via an optical fiber. Optical fibers, or other suitable mechanisms for transmitting light energy, comprise a proximal end operably connected to the light source and a distal end located within the microcatheter lumen, i.e., proximal to or operably connected to the liquid present in the microcatheter lumen. Embodiments may comprise any convenient number of optical fibers, or other suitable mechanisms for transmitting light energy, for transmitting light from one or more light source to one or more locations within the microcatheter lumen. One or more optical fibers, or other suitable mechanisms for transmitting light energy, may be located within the microcatheter or along an external surface of the microcatheter. Light sources of interest comprise a laser source or another suitable energy source, capable of providing energy that is guided to the liquid present within the microcatheter in sufficient magnitude to generate gas bubbles. Some embodiments of systems may comprise still other mechanisms for generating bubbles or for generating bubbles of a desired size or other characteristics in fluid present within microcatheter. In some cases, a fluid pathway of the system, such as, for example, the microcatheter lumen or an interface or other connector to the microcatheter through which fluid flows towards the distal end of the microcatheter, comprises a grate or a screen or another obstacle designed to generate turbulent flow of fluid within the fluid pathway of the system. Such turbulent flow is introduced in order to break up larger gas bubbles into smaller gas bubbles. That is, embodiments of the system may be configured such that the fluid pathway of the system comprises an obstruction, such as a grate or a screen or the like, that, when relatively larger bubbles are urged to pass through such obstacle, such larger bubbles are broken up into a plurality of smaller bubbles. The resulting smaller bubbles may be desirable in embodiments in connection with generating vibrations of the distal end of the microcatheter when fluid, including such resulting smaller bubbles, is subjected to pressure oscillations by operation of the actuator of the system. In embodiments, such grate or screen or other obstruction may be positioned at any convenient location within the fluid pathway, such as within the catheter lumen, or within a connector or other element of the microcatheter that fluid must pass through as it is urged towards a distal region of the microcatheter. For example, a grate or screen or other obstruction may be located within a specified distance from the distal end of the microcatheter. In some cases, a plurality of grates or screens or other obstructions may be present within a fluid pathway of the system, e.g., within the microcatheter lumen. In some cases, a grate or screen or other obstruction may be positioned such that gas bubbles are urged through it each time the actuator applies a pressure oscillation. Other techniques for creating turbulent flow within the fluid pathway of the microcatheter may also be employed, such as, for example, changes in volume or changes in direction or the introduction of particles such as beads, etc. may be employed to break up gas bubbles into smaller gas bubbles as desired for effective vibration of the distal end of the microcatheter. As described herein, microcatheter systems of the present invention are capable of receiving fluid, in particular fluid that is subjected to pressure oscillations during use. In embodiments, both a liquid as well as gas are introduced into the microcatheter system, i.e., a lumen of the microcatheter, and such combination of liquid and gas is subjected to pressure oscillations. Any convenient liquid and gas may be applied, and such may vary. Liquids of interest comprise water or a saline solution with or without a contrast or other radiopaque liquid or fluorocarbons or perfluorocarbons, where, in each case, the liquid may be sterile. Gases of interest comprise air or another gas that is capable of dissolving into the bloodstream, such as CO2, where, in each case, the gas may be sterile. In embodiments, any convenient volume of total fluid may be introduced into the catheter, and such may vary. For example, in some cases, between 0.5 mL and 50.0 mL of fluid may be introduced, such as 0.5 mL, 0.6 mL, 0.7 mL, 0.8 mL, 0.9 mL, 1 mL, 2 mL, 3 mL, 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 20 mL, 30 mL, 40 mL or 50 mL of fluid. In some embodiments, about 3 mL of fluid is introduced. In embodiments, any convenient ratio of liquid and gas may be introduced, and such may vary. For example, in some cases, between 0.5% and 30% of the volume of fluid introduced may be gas at standard temperature and pressure (STP), such as 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20% or 30% of the volume of fluid introduced may be gas at STP. In addition, such liquid-gas mixture may comprise gas bubbles in the liquid present within the microcatheter lumen. A plurality of gas bubbles may be formed (i.e., the number of separate gas bubbles may be increased) when the liquid-gas mixture is subjected to pressure oscillations. In embodiments, during use, the gas typically forms bubbles substantially spherical or bubbles that are substantially elliptical. In embodiments, during use, the gas typically forms a plurality of bubbles such as ten or more bubbles, including 100 or 1,000, or 5,000 or 10,000 or more bubbles. Further, the liquid-gas mixture may be selected based on how the liquid-gas mixture is expected to respond to pressure oscillations applied to the microcatheter lumen (i.e., that the plurality of bubbles are urged toward a distal region of the microcatheter and that the presence of the bubbles has the effect of amplifying the vibration of a distal region of the microcatheter). In embodiments, higher amplitude and / or higher frequency pressure oscillations applied to the microcatheter, in particular the plurality of bubbles present in a distal region of the microcatheter, also equate to a stronger force, including longitudinal force, for driving the microcatheter into and across the CTO. That is, applying higher amplitude and / or higher frequency pressure oscillations to the microcatheter, in particular the plurality of bubbles present in a distal region of the microcatheter, may cause the microcatheter to apply greater force to the CTO, such as, may cause the distal tip, as described herein, to apply greater force to the CTO. As described above, in embodiments, repeatedly pressurizing the liquid and gas mixture present within the microcatheter lumen causes the gas to form a plurality of bubbles. In some embodiments, repeatedly pressurizing the liquid and gas mixture present within the microcatheter lumen forces at least some of the plurality of gas bubbles towards the distal region of the microcatheter. In other embodiments, repeatedly pressurizing the liquid and gas mixture present within the microcatheter lumen agitates the gas bubbles in the distal region of the microcatheter. In such embodiments, agitating the gas bubbles in the distal region of the microcatheter may cause the distal region of the microcatheter to vibrate. In embodiments, the vibration of the distal region of the microcatheter causes the distal region of the microcatheter to advance across the CTO. In some cases, the rate of advancing the distal region of the microcatheter across the CTO is configured based at least in part on an amplitude and frequency of the pressure applied to the liquid and gas mixture present within the microcatheter lumen. In embodiments, the vibration of the distal region of the microcatheter in conjunction with applying a lateral force to the microcatheter (e.g., a force urging the microcatheter in a relatively distal direction) causes the distal region of the microcatheter to advance across the CTO. In embodiments, the system further comprises a linear stage to advance the microcatheter in a lateral directly (e.g., a force urging the catheter in a relatively distal direction). In embodiments, the liquid and gas present in the microcatheter lumen propagate pressure along the lumen from a relatively proximal region to a relatively distal region of the microcatheter. In some embodiments, the liquid comprises a saline solution or a contrast fluid. In some cases, the gas comprises carbon dioxide. In other embodiments, the microcatheter and the microcatheter lumen are coaxial. Referring to Figures 1,3, and 5, further details regarding actuators of the present invention are shown. The actuator 110 is configured to repeatedly pressurize a liquid and gas mixture present within the microcatheter lumen 180 such that the distal region 160 of the microcatheter vibrates, causing disruption at the proximal end of the CTO and creating the ability for the microcatheter to move across a CTO. As described herein, fluid present within the microcatheter lumen comprises, for example, a liquid-gas mixture, such that applying pressure oscillations thereto causes a plurality of bubbles to form within the microcatheter lumen. Upon pressurizing such microcatheter lumen, bubbles are urged to a distal region of the microcatheter. Bubbles present in a distal region of the microcatheter, when subjected to further pressure oscillations, become agitated causing additional turbulence that works to vibrate a distal region of the microcatheter. Such vibration, alone or in conjunction with application of a lateral force to the microcatheter (e.g., urging the distal end of the microcatheter towards or into the CTO) causes the microcatheter to move across the CTO. In systems of the invention, any convenient actuator capable of applying desired pressure oscillations to fluid present within the microcatheter lumen may be applied. That is, any convenient actuator capable of applying pressure oscillations of sufficient amplitude and / or frequency over a desired period of time may be applied. In embodiments, one or both of the amplitude and frequency of pressure oscillations applied to the microcatheter may vary over a period of time to generate desired vibrations that move a distal region of the microcatheter across the CTO. In embodiments, the actuator may be configured to apply such pressure oscillations and desired amplitudes and frequencies over any convenient period of time or duty cycle. As described herein, embodiments of amplifiers of the invention comprise diaphragms configured such that longitudinal motion of the diaphragm causes the application of a “water hammer” effect of pulsatile energy to be applied to fluid present in a distal region of the amplifier as well as to the microcatheter operably connected to the amplifier, including, ultimately, to the distal end of the microcatheter assembly, i.e., to the mixture of liquid and gas present within the distal end of the microcatheter. In some instances, such longitudinal motion of the diaphragm causes an effect involving the super-propulsion of bubbles, e.g., wherein gas bubbles present within the microcatheter to compress or expand in a manner that is propagated to other bubbles within the microcatheter, causing the distal end of the microcatheter to vibrate. Actuators employed in systems of the invention may be configured to be reusable or single use, as desired. Actuators employed in systems of the invention may be configured to receive a sterile sleeve such that the actuator may be used while not contaminating the sterile field of the operating room. In some embodiments, an actuator may comprise a source of potential energy configured to provide energy which may be regulated as desired by a regulator and an oscillator to provide for applying pressure oscillations to fluid present in the microcatheter lumen. Any convenient potential energy source may be employed, where examples include voltage sources, pressure sources, electromagnetic sources, electric field sources, chemical sources and the like. In some embodiments, the potential energy source is a pressure source, where examples of suitable pressure sources include, but are not limited to: compressed gas cylinders, compressors, and the like. Where desired, the potential energy source may be operably coupled to a regulator, which serves to modulate energy to a suitable form so that it may be further acted upon by the oscillator. For example, where the potential source is a high-pressure gas source, e.g., as may be employed in a pneumatic actuator, the regulator may serve to regulate the pressure of the gas to a suitable value that can be input to the oscillator. In addition to the potential energy source and regulator, the actuator may include an oscillator. In such instances, the oscillator is used to modulate the magnitude and timing of the potential energy from the potential energy source to provide for the desired energy for use in applying pressure oscillations to the microcatheter lumen. In embodiments, an actuator may comprise a pressure source and an operable connection between such pressure source and, ultimately, a distal region of the microcatheter lumen, where the actuator is configured to transmit pressure to such distal region of the microcatheter, i.e., a distal region in which bubbles of the liquid-gas mixture are present. In embodiments, the actuator is configured to transmit pressure to such distal region of the microcatheter, via the microcatheter lumen, via fluid present in the microcatheter lumen, such as a liquid-gas mixture, such as a saline solution-CO2 mixture, present in the system. In some cases, the actuator converts pressure from a pressure source in one form to pressure in another form for applying pressure oscillations to the microcatheter. For example, the actuator may convert pneumatic pressure from a gas pressure source to bubbles present at a distal region of the microcatheter via the liquid-gas mixture. The actuator may be configured to receive pressure from a single pressure source and use exclusively that pressure source to generate pressure oscillations or may receive pressure from more than one pressure source and sequentially transmit pressure from the different pressure sources to generate pressure oscillations. For example, in some embodiments, the actuator comprises a manifold configured to generate multiple oscillating outputs from a single pressure source. In other embodiments, the actuator may comprise two or more pressure sources that may alternate to repeatedly apply pressure to a distal region of the microcatheter. Further details regarding potential energy sources, oscillators, regulators, etc., and components thereof, that may be employed in embodiments of the present invention are provided in United States Published Patent Application Publication No. 20200046949 as well as pending PCT Application Serial No. PCT / US2020 / 055458 as well as United States Application No. 63238381; the disclosures of which are herein incorporated in their entireties by reference. Embodiments of actuators of the present invention comprise a proximal connector operably connected to the microcatheter. In embodiments, a proximal connector is a component of the microcatheter system located proximally in the assembled system, e.g., at the proximal end or near the proximal end, e.g., within 1 m or closer to the proximal end. The proximal connector may be configured to operably connect the microcatheter to a potential energy source, such as a pressure source. In such embodiments, the proximal connector is configured to transduce energy derived from, for example, the pressure source to energy transmitted along the microcatheter for applying pressure to a liquid-gas mixture present in a distal region of the microcatheter; i.e., to agitate bubbles present at a distal region of the microcatheter. In embodiments, the proximal connector comprises a proximal chamber and a distal chamber separated by a membrane. The volume of each of the proximal and distal chambers may vary, ranging in some instances from 0.1 mL to 100 mL, such as 1 mL to 4 mL, where in some instances the proximal chamber is occupied by a fluid only, such as a liquid, and the distal chamber is occupied by a fluid, such as the liquid-gas mixture present in the microcatheter, or in other cases, in which the actuator and / or microcatheter is configured to segregate gas bubbles within a designated region of the microcatheter, by a liquid only. In each case, the proximal chamber is operably connected to a potential energy source, such as, for example, a pressure source and configured to transduce energy (i.e., pressure) to the distal chamber, via the membrane. While the form of the proximal connectors of embodiments may vary, in some instances the proximal chamber is defined by a proximal flange and the distal chamber is defined by a distal flange, where the proximal and distal flanges are positioned on either side of the membrane to define the proximal and distal chambers, which may be hermetically sealed from each other by the separating membrane. The membrane is configured to move in response to pressure applied to the proximal chamber and, based on such movement, produce pressure in the distal chamber of the connector. The dimensions of the membrane may vary, where in some instances the membrane has an area ranging from 100 mm2 to 5,000 mm2, such as 500 mm2 to 2,000 mm2. The membrane may be fabricated from any convenient elastic (e.g., pliant) material, where in some instances the material has a hardness ranging from Shore 10A to Shore 90A, such as Shore 50A, and a thickness between 0.5 mm to 5 mm, such as 1.0 mm to 2.5 mm. Examples of suitable membrane materials include, but are not limited to: silicone, rubber, and the like and in some cases may be strengthened by adding a reinforcing component, such as a braid. Where desired, a biasing component, such as a spring, may be provided to provide for a default or baseline membrane position. For example, a spring may be provided on the distal chamber side of the membrane which urges the membrane back to an initial position when force is removed from the proximal chamber side of the membrane. In embodiments, the proximal chamber of the proximal connector comprises a port operably connecting the proximal chamber with, ultimately, a pressure source. Similarly, in embodiments, the distal chamber of the proximal connector comprises a port operably connecting the distal chamber with, ultimately, a fluidic passage of the microcatheter. Where desired, the proximal connector may include one or more sensors, e.g., configured to provide data regarding one or more components of the system. Any convenient type of sensor may be included in the proximal connector, where sensors of interest include, but are not limited to: pressure sensors, positional sensors, displacement sensors, proximity sensors, flow sensors, temperature sensors and the like. In some instances, the proximal connector includes a pressure sensor operably coupled to the distal chamber. In such instances, the pressure sensor may detect pressure and changes thereof in the fluid, such as a liquid or a liquid-gas mixture, in the distal chamber. When included, any convenient type of pressure sensor may be present, where examples of pressure sensors that may be present include, but are not limited to: resistive, capacitive, piezoelectric, optical, and MEMS-based pressure sensors, and the like. In some instances, the proximal connector includes a membrane positional sensor configured to provide spatial data regarding the position of the membrane at a given time, e.g., during use of the system. When present, any convenient membrane position sensor may be employed. In some instances, the membrane positional sensor is a Hall sensor, e.g., which may be employed in conjunction with a magnet (e.g., permanent magnet or electromagnet) present at a fixed location relative to the membrane, such as a fixed location of the proximal connector or the pulse generator (e.g., hand-held actuator), etc., such that the fixed magnet is positioned to modulate voltage of the Hall Sensor upon membrane movement. In other instances, the membrane positional sensor may be an optical sensor, electric field potential sensor, resistive sensor, magnetic sensor, angle sensor, or acceleration sensor. Further, any combination of these sensors may be used to gather positional data of the membrane or diaphragm. In cases in which a combination of membrane positional sensors is employed, e.g., to ensure sensors provide correct data across a variety of conditions, such as frequencies, sensor data may be combined through “sensor fusion” techniques, such as those known in the art. Fabrication methods of the membrane sensor may include, but are not limited to: adhesives, direct printing, welding, embedding and the like. Further details regarding embodiments of proximal connectors which may be employed in connection with the systems described herein are provided in U.S. Application No. 63145641, the disclosure of which is hereby incorporated herein by reference. Referring now to FIG. 3, this figure shows an internal view, i.e., cutaway view, of amplifier assembly 300 (i.e., proximal connector or actuator assembly) according to an embodiment of the invention. Amplifier assembly 300 may comprise, for example, amplifier assembly 110 seen in FIGS. 1A-B or amplifier 310 of FIG. 3 or amplifier 610 of FIGS. 6A-C, in each case, as described in detail herein. In FIG. 3, elements having the same or similar reference numerals have the same or similar features as corresponding elements in FIGS. 1-2, unless explicitly stated otherwise. In amplifier assembly 300, diaphragm 370 is held in place within amplifier assembly 300 by being compressed between proximal nose 310 and distal waveguide 360. Metal pins 367 , i.e., retaining pins, present within amplifier assembly are used to hold diaphragm 370 in place, i.e., by compressing distal waveguide 360 against proximal nose 310. Metal pins 367 may be inserted into holes in, or molded into, e.g., proximal nose 310, such that they contact and abut a distal surface of distal waveguide 360. Other techniques, including, e.g., the use of adhesives or welds, for holding distal waveguide 360 against proximal nose 310 with diaphragm 370 therebetween may also be employed. Diaphragm 370 is compressed between proximal nose 310 and distal waveguide 360 such that proximal chamber 312 is sealed off on the relatively proximal side of diaphragm 370 and distal chamber 362 is sealed off on the relatively distal side of diaphragm 370. Diaphragm 370 is configured to translate back and forth (i.e., relatively proximally and relatively distally) within proximal chamber 312 and distal chamber 362. More specifically, diaphragm 370 is configured to translate back and forth (i.e., relatively proximally and relatively distally) between distal face 311 (of proximal nose 310) and proximal face 361 (of distal waveguide 360). Diaphragm 370 is configured to do so without producing strain on diaphragm 370; i.e., substantial strain. That is, diaphragm 370 is configured to do so without producing tension on diaphragm 370 or without stretching the material of diaphragm 370 or without resistance from the material of diaphragm 370 or without applying stress to the material of diaphragm 370. Diaphragm 370 is depicted in a neutral state, i.e., a relaxed state, i.e., located approximately in the middle between distal face 311 and proximal face 361. Such state corresponds to there being relatively equal pressures within proximal chamber 312 and distal chamber 362. In amplifier assembly 300, diaphragm 370 comprises pleats 273 that are shaped to allow diaphragm 370 to translate between distal face 311 of proximal nose 310 and proximal face 362 the distal waveguide 360 without producing strain on diaphragm 370. That is, depending on the distance diaphragm 370 translates away from a neutral position, diaphragm 370 is urged to unfold pleats 373 thereby taking on a new shape allowing diaphragm 370 to occupy a new position without producing strain on diaphragm 370. For example, pleats 373 of diaphragm 370 are positioned and shaped such that when diaphragm 370 is translated fully into distal face 311, such pleats unfold and substantially seamlessly contact or envelop distal face 311. Similarly, pleats 373 of diaphragm 370 are positioned and shaped such that when diaphragm 370 is translated fully into proximal face 361, such pleats unfold and substantially seamlessly contact or envelop proximal face 361. Diaphragm 370 comprises pleats 373 that are shaped and positioned such that diaphragm 370 can fit within the indentations or curvatures of distal face 311 as well as the indentations or curvatures of proximal face 361, when translated to fully proximal and distal positions, respectively. As described herein, proximal nose 310 comprises distal face 311 present on an internal distal surface of proximal nose 310. The volume between distal face 311 of proximal nose 310 and diaphragm 370 forms proximal chamber 312. Proximal chamber 312 receives energy, e.g., pressure such as pressure pulses or static pressure, from, e.g., fluid such as CO2, entering amplifier assembly 300 via high pressure connector 323 of proximal interface 320. Such energy, e.g., pressure such as pressure pulses or static pressure, from, e.g., fluid such as CO2, entering amplifier assembly 300 via high pressure connector 323, is sealed within high pressure connector 323 and proximal chamber 312 by an O-ring present in O-ring groove 325 of high-pressure connector 323. Distal face 311 of proximal nose 310 is shaped so that diaphragm 370, when translated in a fully proximal position, seats itself on distal face 311 of proximal nose 310, i.e., pleats 373 or diaphragm 370 unfold or unfurl to follow the shape of distal face 311 such that diaphragm 370 translates without producing strain on diaphragm 370. As described above, distal waveguide 360 comprises proximal face 361 present on an internal proximal surface of distal waveguide 360. The volume between proximal face 361 of distal waveguide 360 and diaphragm 370 forms distal chamber 362. Proximal face 361 of distal waveguide 360 is shaped so that diaphragm 370, when translated in a fully distal position, seats itself on proximal face 361 of distal waveguide 360, i.e., pleats 373 of diaphragm 370 unfold or unfurl to follow the shape of proximal face 361 such that diaphragm 370 translates without producing strain on diaphragm 370. Distal chamber 362 receives energy, e.g., pressure such as pressure pulses or static pressure, as diaphragm 370 is translated as a result of energy, e.g., pressure such as pressure pulses or static pressure, applied to proximal chamber 312. Such energy, e.g., pressure such as pressure pulses or static pressure, is transmitted along distal waveguide 360 and ultimately output to catheter assembly 365 fluidically connected to an output of distal waveguide 360 via catheter interface 364, e.g., a threaded connector or a Luer lock mechanism, such as a Luer lock or floating Luer lock, or another operable connector, as desired. Such catheter interface 364 is in fluidic communication with distal chamber 362 of distal waveguide 360. Such catheter interface 364 receives high-pressure fluid, i.e., pulses of high-pressure and / or static pressure, in each case from distal chamber 362. Such pressure may be transmitted via fluid in distal chamber 362, such as, e.g., saline. In part, in order to seal proximal chamber 312 and distal chamber 362 (i.e., fluidically seal such chambers), diaphragm 370 comprises substantially T-shaped protrusion 375 at the outer circumference of diaphragm 370. Such protrusion is shaped to seal off a connection between proximal nose 310 and distal waveguide 360 such that fluid does not escape between these elements even when relatively high pressures, including high pressure pulses, are applied to fluid present in either chamber and / or even when diaphragm 370 is translated fully in the proximal or distal directions. As described above, proximal nose 310 comprises proximal interface 320 for interfacing with a handle assembly. Proximal interface 320 comprises high pressure connector 323 for receiving energy, e.g., fluid such as fluid pressure pulses or static fluid pressure, where such fluid may be, for example, a gas, such as CO2 or air. Such high-pressure connector 323 is in fluidic communication with proximal chamber 312. That is, high-pressure connector 323 is configured to receive high pressure fluid, i.e., from a handle assembly, and transmit such pressure to proximal chamber 312. High-pressure connector 323 may be made of metal and / or may be molded into the material of proximal nose 310, e.g., molded into plastic of proximal nose 310. High-pressure connector 323 comprises O-ring groove 325 configured to receive an O-ring. Also as described herein, proximal interface 320 comprises alignment elements 327, i.e., keying elements such as a keyway, such as a grove or plurality of groves, configured to align amplifier assembly 300 with a handle assembly. Electrical connectors 330 of electrical assembly 335 are shown at a relatively upper position of proximal nose 310. Electrical assembly 335 comprises a flexible printed circuit board electrically connected to electrical connectors 330 as well as outputs of various sensors described herein. Distal waveguide 360 is shaped to allow access to a distal region of distal chamber 362 such that pressure sensor 369 can be located on distal waveguide 360 allowing pressure readings of fluid, e.g., saline, present in distal chamber 362. Any convenient pressure sensor 369 capable of measuring fluid and generating electrical signals based on such readings may be employed. Pressure sensor 369 is integrated into distal waveguide 360 in any convenient manner, e.g., via a threaded interface or the like. Pressure sensor 369 is used to sense pressure, including pressure changes, i.e., caused by pressure pulses, within distal chamber 362 and therefore transmitted through catheter interface 364 and through catheter assembly 365, ultimately to a distal region, e.g., the distal end, of a microcatheter operably connected to amplifier assembly 300. That is, pressure readings obtained by pressure sensor 369 reflect pressure applied by amplifier assembly 300 to, e.g., a distal region or the distal end of a microcatheter. The output of pressure sensor 369 is electrically connected to electrical assembly 335, such that pressure sensor 369 readings may be processed, stored and / or transmitted (e.g., via electrical connectors 330) by electrical assembly 335. Readings from pressure sensor 369 may be electronically transmitted to a remote display for review by a user. Amplifier assembly 300 further comprises one or more sensors for sensing a position of diaphragm 370, i.e., to what extent diaphragm 370 has translated between distal face 311 and proximal face 361. In amplifier 300, a Hall sensor is used for such a positional sensor, i.e., to sense a position of diaphragm 370. Such Hall sensor comprises first magnet 376 integrated into proximal nose 310 and second magnet 366 integrated into distal waveguide 360. Such magnets are positioned such that they remain a fixed distance away from each other and in a fixed position of proximal nose 310 and distal waveguide 360, as applicable. Such magnets may be oriented in any convenient orientation with respect to magnetic polarities. The Hall sensor further comprises electrical probe 375a present in a central region of diaphragm 370. Electrical probe 375a is electrically connected to electronics assembly 335 via a “pigtail” connector, i.e., a connector with enough slack built into the length of the connector such that it can follow diaphragm’s 370 movement back and forth towards proximal face 361 and distal face 311. Such electrical probe may be fastened to diaphragm 370 using any convenient means such as a bonding technique or glue, such as epoxy, or adhesive, so long as electrical probe 370 moves with and to the same extent that diaphragm 370 moves as a result of applying pressure, e.g., pressure pulses or static pressure to amplifier assembly 300. The position of diaphragm 370 corresponds to a volume of (or changes in volume of) distal chamber 362. Proximal nose 310 comprises a first receptacle to hold the first magnet in a fixed position. Distal waveguide 360 comprises a second receptacle to hold the second magnet in a fixed position. Such receptacles may comprise any convenient technique or mechanism for holding magnets in fixed positions, such as bonding, adhesives, glue, mechanical configurations or the like. For example, first and second receptacles comprise crush ribs, meaning protrusions (i.e., ribs) around an outer circumference of a receptacle between which a magnet is positioned, thereby compressing (i.e., crushing) such ribs such that the magnet is held in tension between such ribs. In other embodiments, a positional sensor may be configured such that a magnet may be present on a central region of diaphragm 370 and one or more electrical probes may be located on a fixed position of distal waveguide 360 and / or proximal nose 310. Such configuration may represent easier manufacturing aspects or longer useful life of amplifier assembly 300 insofar as the magnet present on diaphragm 370 does not require an electrical connection to electronics assembly 335. Housing 390 is present around the exterior of proximal nose 310, distal waveguide 360 and diaphragm 370, such that such elements are substantially enclosed by housing 390. Housing 390 is shaped to expose proximal interface 320 for interfacing with a handle assembly and to expose the output of catheter interface 364, such that output of amplifier assembly 300 is transmitted to catheter assembly 365. In certain embodiments of the present invention, the actuator (i.e., actuator assembly or amplifier or proximal connector) further comprises a microcatheter shaft connecting the proximal connector to a microcatheter inflation lumen configured to propagate pressure from the first proximal connector along the microcatheter shaft to the microcatheter inflation lumen. FIG. 4 depicts an embodiment of a microcatheter shaft 451 connecting proximal connector 410 and microcatheter inflation lumen 453, according to embodiments of the present invention. In embodiments, the microcatheter shaft may include tubing connecting the distal chamber of the proximal connector (i.e., attaching to a distal chamber port) to a microcatheter inflation lumen. A microcatheter inflation lumen may comprise a chamber in which a proximal region of the microcatheter is exposed to fluid contained in the inflation lumen, such that pressure applied to fluid in the microcatheter shaft is transmitted to the fluid of the microcatheter lumen, via the microcatheter inflation lumen. Such pressure applied to the microcatheter inflation lumen is ultimately transmitted to a distal region of the microcatheter to create and agitate bubbles present in such region. The microcatheter shaft and inflation lumen may take any convenient configuration and may vary. In some cases, the microcatheter shaft is a tube-like cylinder and, in some cases, may be tapered. Similarly, in some cases, the microcatheter inflation lumen is a tube-like cylinder and, in some cases, may be tapered. In some cases, the microcatheter shaft comprises a stopcock or valve or port by which a fluid, such as a saline solution, may be injected. In some cases, the microcatheter shaft may comprise one or more ports or valves configured to allow access to fluid in the microcatheter shaft and / or microcatheter inflation lumen. In embodiments, such ports or valves may comprise an interface, as described here, with ports or valves for controllably injecting fluid (e.g., a first port for liquid and a second port for gas) into the microcatheter lumen. In other embodiments, the microcatheter system may comprise a separate interface with ports in addition to ports on the microcatheter shaft. In some cases, the microcatheter shaft may comprise fittings, such as threaded fittings enabling the microcatheter shaft to be replaced or swapped out of the system. The microcatheter shaft, in embodiments, is made of a stiff material such as polyvinyl chloride (PVC) or polycarbonate (PC) or polyimide or the like and may be reinforced with a braid of nitinol or steel or fibrous wire or the like. The microcatheter shaft may have a length between 100 cm and 300 cm, such as 200 cm or 300 cm or 400 cm. In embodiments, the microcatheter inflation lumen may comprise tubing configured such that the microcatheter is longitudinally aligned within the microcatheter inflation lumen. That is, the microcatheter may be fitted within the microcatheter inflation lumen in a coaxial configuration. In embodiments, such microcatheter inflation lumen may comprise a segment of the microcatheter or may comprise a fitting configured to interface with a segment of the microcatheter, in either case, as may be configured to facilitate filling the microcatheter lumen with fluid. The microcatheter inflation lumen may take any convenient shape and may vary, such as a substantially cylindrical shape with or without a taper. The microcatheter inflation lumen, in embodiments, is made of a stiff material such as polyvinyl chloride (PVC) or polycarbonate (PC) or the like. The microcatheter inflation lumen may have a length between 1 and 1,000 mm, such as 1 mm or 10 mm or 100 mm, and may have a diameter between 0.2 mm and 10 mm, such as 1 mm or 3 mm. An actuator in accordance with an embodiment of the invention is schematically illustrated in FIG. 4. FIG. 4 shows a proximal region of aspects of a microcatheter system, i.e., components of an embodiment of an actuator, with the right-hand side of the figure being relatively distal (i.e., towards the CTO) and the left-hand side of the figure being relatively proximal (i.e., away from the CTO). Referring now to FIG. 4, this figure depicts actuator 400 comprising proximal connector 410, in each case according to an embodiment of the present invention. Proximal connector 410 is operably connected to microcatheter 450. The figure depicts a region of microcatheter 450. Certain regions of microcatheter 450 are present within actuator 400 and certain regions extend in a distal direction from actuator 400, where ultimately a distal region, including the distal end, is present (such as distal region 160 of microcatheter depicted in FIG. 1). Proximal connector 410 is configured to transduce input pressure 411 received from a pressure source to microcatheter 450 via microcatheter shaft 451, ultimately to a distal region of microcatheter 450 (such as distal region 160 of microcatheter depicted in FIG. 1). As described in detail herein, proximal connector 410 comprises proximal and distal chambers separated by a membrane. The proximal chamber is operably connected to a source of pressure that provides pressure 411 to proximal connector 410, and the distal chamber of proximal connector 410 is operably connected to microcatheter 450 via microcatheter shaft 451. Microcatheter shaft 451 is located in a distal direction relative to proximal connector 410. Microcatheter shaft 451 is configured as tubing where the distal end of microcatheter shaft 451 is connected to connector 420. In the embodiment shown, connector 420 comprises an interface with fluid port 435, where such port 435 is configured to facilitate filling the microcatheter with fluid, such as liquid and / or gas and / or a liquid-gas combination. In embodiments, connector 420, i.e., an interface, of microcatheter system, may comprise any convenient number of ports (such as one or more fluid ports, such as two fluid ports), where such ports are configured to controllably fill microcatheter 450 with fluid. Microcatheter inflation lumen 453, by which the microcatheter is pressurized, is operably connected to connector 420. Microcatheter 450 is pressurized with a liquid-gas mixture, including, for example, a saline solution and CO2. In some cases, liquid only, e.g., saline only, is present in the distal chamber of proximal connector 410, microcatheter shaft 451 and microcatheter inflation lumen 453. In other cases, a liquid-gas mixture is present in the distal chamber of proximal connector 410, microcatheter shaft 451 and microcatheter inflation lumen 453. The liquid-gas mixture is pressurized due to pressure applied by proximal connector 410 such that a plurality of bubbles are formed in the liquid-gas mixture, which are urged toward a distal region of microcatheter 450 where such bubbles cause such distal region to vibrate (such as distal region 160 of microcatheter 150 shown in FIG. 1). The microcatheter 450 distal to connector 420 comprises strain relief 452 to support manipulating the direction of microcatheter 450 without folds or kinks or other deformations or obstructions to transmitting fluid and pressure pulses. That is, microcatheter 450 on the distal side of connector 420 is connected to strain relief tubing 452 allowing for flexibility with respect to the direction of microcatheter 450 as it exits connector 450. In embodiments, the microcatheter inflation lumen may be operably connected to a connector, e.g., an interface, comprising ports configured to allow passage of fluid to the microcatheter. One of the ports of the connector is operably connected to the microcatheter inflation lumen. The microcatheter is operably connected to the microcatheter inflation lumen, and the microcatheter is connected to the microcatheter inflation lumen such that the microcatheter can extend, for example, with luminal tissue towards a CTO. The connector and microcatheter inflation lumen may be formed from any convenient material, such as polyvinyl chloride (PVC) or polycarbonate (PC) or the like, and may comprise strain relief elements, such as, for example, flexible tubing, providing flexibility in the positioning of the connector with respect to the microcatheter shaft. Referring now to FIG. 5, this figure depicts a close-up, cutaway view of connector 520, microcatheter inflation lumen 553, strain relief 552 and microcatheter 550. Connector 520 comprises first port 521, to which microcatheter shaft 551 is connected. The distal end of microcatheter shaft 551 is threaded and interfaces with a threaded fitting of first port 521. Connector 520 comprises second port 522, to which microcatheter inflation lumen 553 is connected. Microcatheter inflation lumen 553 is configured to transmit pressurized fluid (e.g., a pressurized liquid or pressurized gas or a pressurized liquid-gas mixture) to a lumen of microcatheter 550. That is, microcatheter inflation lumen 553 receives pressurized fluid (e.g., a pressurized liquid or pressurized gas or a pressurized liquid-gas mixture) from microcatheter shaft 551 via connector 520 and enables fluidic communication of microcatheter shaft 551 with the lumen of microcatheter 550. Such application of pressurized fluid to the lumen, i.e., fluidic passage, of microcatheter 550, in the form of pressure oscillations over a period of time, ultimately is responsible for causing vibrations at a distal region of microcatheter (such as distal region 160 of microcatheter 150 shown in FIG. 1). Strain relief tubing 552 is present on microcatheter 550 and microcatheter inflation lumen 552 allowing for flexibility with respect to the direction of microcatheter 550 with respect to its connection to connector 520. Connector 520 further comprise fluid port 535 configured for controllably introducing fluid, such as liquid or gas or a liquid-gas combination into microcatheter 550. Embodiments of systems of the invention may further comprise a guidewire. In some cases, the microcatheter may be configured to interface with a guidewire. For example, the microcatheter may be configured such that a guidewire can be used in connection with deploying the microcatheter towards the CTO. In particular, the microcatheter may be configured such that a guidewire can be used in connection with guiding a distal region, such as the distal end, of the microcatheter to the CTO, e.g., such that the distal end abuts the CTO. In embodiments, the microcatheter may be configured with a lumen dedicated for use with a guidewire. In some cases, the microcatheter may be configured such that the guidewire shares a lumen with fluid (e.g., a gas-liquid mixture) present within the microcatheter. In other cases, the microcatheter is configured such that a separate, guidewire-dedicated lumen is present, in addition to a lumen with fluid (e.g., a gas-liquid mixture). In certain cases, the system is configured to utilize a rapid exchange (RX) delivery technique. Some embodiments of systems comprise a rapid exchange (RX) delivery system. Some embodiments of systems are rapid exchange (RX) systems. In some cases, the microcatheter of the embodiment of the system comprises a rapid exchange port in a distal region for use with a guidewire for a rapid exchange delivery technique. For example, an embodiment of a microcatheter may comprise a rapid exchange port at or near the distal end of the microcatheter for use with rapid exchange over a guidewire. In some cases, a distal region of the microcatheter comprises a guidewire port for use with a rapid exchange technique. In some embodiments, such guidewire port is located between 5.0 mm and 100.0 mm from the distal end of the microcatheter. In some cases, such guidewire port comprises an opening configured to receive a guidewire at or near the distal end of the microcatheter. In some cases, the microcatheter system comprises a rapid exchange mechanism comprising a single guidewire port located at a distal region of the microcatheter, such as at or near the distal end of the microcatheter. In other cases, the system is configured to utilize an over-the-wire (OTW) delivery technique. Some embodiments of systems comprise an over-the-wire (OTW) delivery system. Some embodiments of systems are over-the-wire (OTW) systems. In still other cases, the system is configured to utilize a monorail delivery technique. Some embodiments of systems comprise monorail delivery system. Some embodiments of systems are monorail systems. Further details regarding aspects of embodiments of microcatheter systems of the invention, including further details regarding microcatheters, amplifiers, handles, consoles, etc. are found in United States Patent No. 11,464,949; United States Published Patent Application Publication No. 20200046949; United States Application Serial No. 17897604; pending PCT Application Serial No. PCT / US2019 / 027139; pending PCT Application Serial No. PCT / US2020 / 055458; United States Application Serial No. 63274832; United States Application Serial No. 17827169; pending PCT Application Serial No. PCT / US2022 / 014785; United States Application Serial No. 63238381; pending PCT Application Serial No. PCT / US2022 / 040586; United States Application Serial No. 63346703; pending PCT Application Serial No. PCT / US23 / 23533; United States Application Serial No. 63346704; pending PCT Application Serial No. PCT / US23 / 22685; United States Application Serial No. 63444414; and United States Application Serial No. 63545060; the disclosures of each of which are herein incorporated by reference. Methods Methods of crossing a total occlusion are also provided and similarly find benefit in the applications described above. Methods according to the present invention comprise deploying a microcatheter system comprising a microcatheter with proximal and distal regions, the distal region comprising a fixed, sealed end, wherein the microcatheter comprises a lumen that receives liquid and gas, so that the distal region of the microcatheter is adjacent to a proximal end of a total occlusion. Such microcatheter system further comprises: an interface for separately introducing liquid and gas bubbles into the microcatheter lumen, and an actuator that repeatedly pressurizes a liquid and gas bubble mixture present within the microcatheter lumen. Such components of microcatheter systems are described in detail above. Methods according to the present invention further comprise engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen such that the distal region of the microcatheter vibrates, moving the microcatheter across the total occlusion. By repeatedly pressurize, it is meant that a distal region of the microcatheter is repeatedly subjected to pressure oscillations, at any convenient amplitude, frequency, duty cycle and duration. Such pressure oscillations originate from the actuator, as described in detail above in connection with embodiments of systems. Any suitable amplitude, frequency, duty cycle and duration of pressure oscillations may be used, and such may vary. It is preferable that such characteristics of such pressure oscillations cause the liquid-gas mixture present in the microcatheter lumen to form bubbles; for such bubbles to be urged toward a distal region of the microcatheter; and for such bubbles to congregate with sufficient density that the vibration of the distal region of the microcatheter is significantly increased (thereby increasing vibration transmitted to a total occlusion). By moving the microcatheter across the total occlusion, it is meant that upon applying pressure oscillations to vibrate a distal region of the microcatheter, such vibration causes the microcatheter to move relative to the proximal face of the CTO (as well as potentially disrupts aspects of the total occlusion) such that continued vibration of the distal region of the microcatheter progressively moves the microcatheter across the total occlusion. In embodiments, engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen comprises repeatedly applying a relatively high pressure to the microcatheter lumen followed by applying a relatively low pressure to the microcatheter lumen. That is, in embodiments, pressure oscillations that include large swings in amplitude are applied to cause a distal region of the microcatheter to vibrate. In some embodiments, engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen comprises repeatedly applying a pressure at a specified amplitude or a specified frequency. In other embodiments, repeatedly pressurizing the liquid and gas mixture present within the microcatheter lumen further comprises allowing the distal region of the microcatheter to engage with a proximal cap of the total occlusion. By engage with the proximal cap of the total occlusion, it is meant, in some cases, that a distal region of the microcatheter physically contacts, at one or more locations, the proximal cap of the total occlusion. In such embodiments, allowing the distal region of the microcatheter to engage with a proximal cap of the total occlusion may comprise allowing the distal region of the microcatheter to vibrate against the proximal cap of the total occlusion. In certain cases, allowing the distal region of the microcatheter to vibrate against the proximal cap of the total occlusion may cause a transmission of vibration from the distal region of the microcatheter to the proximal cap of the total occlusion. In embodiments, an amplitude or frequency of the vibration transmitted to the proximal cap of the total occlusion is configured based at least in part on an amplitude or frequency of vibration of the distal region of the microcatheter. In some embodiments, the amplitude and frequency of vibration of the distal region of the microcatheter is configured based at least in part on an amplitude or frequency at which the actuator repeatedly pressurizes the liquid and gas mixture present within the microcatheter lumen. In embodiments, engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen comprises applying pressure at an amplitude or frequency sufficient that the gas present in the microcatheter lumen forms a plurality of gas bubbles. In some cases, engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen further comprises applying pressure at an amplitude or frequency sufficient that at least some of the plurality of gas bubbles move to a distal region of the microcatheter. In other cases, engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen further comprises applying pressure at an amplitude or frequency sufficient to agitate the gas bubbles present in a distal region of the microcatheter. Embodiments of methods of the invention further comprise applying an axial force to the microcatheter. In such embodiments, the axial force in conjunction with the vibration of a distal region of the microcatheter causes the microcatheter to create a channel in a lesion, such as an occlusion, a total occlusion, a chronic total occlusion or other calcified plaque deposit. By axial force, it is meant a force substantially parallel with the long axis of the microcatheter, i.e., urging a distal region of the microcatheter in a distal direction. Such force may be applied manually, e.g., by an operator of a system of the invention, or automatically, e.g., by a linear stage actuated by a motor and / or controlled by a controller, attached to a relatively proximal region of the microcatheter. In embodiments, the axial force, in conjunction with the vibration of the distal region of the microcatheter causes cracking in calcified plaque and enables the creation of a channel, through which a distal region of the microcatheter can advance. Visualization-. Embodiments of the present invention further comprise using an imaging technique to align the distal region of the microcatheter with a proximal cap of the CTO. Any convenient imaging technique capable of visualizing aspects of a catheter present in a lumen, such as a microcatheter system according to the invention, may be applied. Imaging techniques may comprise, for example, ultrasound imaging, such as intravascular ultrasound technique, a lightbased imaging technique, an angioplasty-based imaging technique or an optical coherence tomography-based technique or the like. In some cases, diagnostic X-ray imaging may be applied. In embodiments, a clinician may use imaging techniques that are well known in the art to determine the position of the microcatheter with respect to the CTO. Guiding sheath-. As described above, in some cases, a guiding sheath may be applied within luminal tissue to orient and align a distal region, including, in some cases, the distal end, of the microcatheter with a total occlusion. For example, in some cases, methods of crossing a total occlusion of the invention further comprise using a guiding sheath having a lumen, in which the microcatheter is present to align a distal region of the microcatheter with a proximal cap of the total occlusion. In embodiments, the guiding sheath comprises a balloon located in an exterior distal region of the guiding sheath. For example, the guiding sheath may comprise a wraparound balloon present near the distal end of the guiding sheath. Embodiments may further comprise inflating the guiding sheath balloon in a manner sufficient to align the distal crosser unit with a proximal cap of the total occlusion. By inflating the guiding sheath balloon, it is meant applying pressure to the interior of the balloon typically through a catheter system where fluid is applied under pressure. Any convenient fluid may be used for inflating a guiding sheath, such as, for example, a saline solution. In some cases, the microcatheter system further comprises a balloon present in the distal region of the microcatheter. In such cases, methods of the present invention may further comprise inflating the balloon such that the balloon engages with a luminal wall, holding the microcatheter in a fixed position relative to the total occlusion. Embodiments of a method of crossing a total occlusion of the invention may further comprise an additional intervention. Additional interventions of interest may comprise performing a procedure related to angioplasty, stenting, or any other secondary treatment known in the art. For example, embodiments may comprise an additional intervention that utilizes a location of the microcatheter extending across a distal end of the total occlusion, or a portion thereof. In other words, the additional invention may leverage the location of the microcatheter of the microcatheter system when the microcatheter has been moved a distance across the total occlusion, such as when the microcatheter has been moved distal to the total occlusion such as to a position on the distal end of the total occlusion. In embodiments, the additional intervention may comprise applying a balloon-based catheter system to a region of the total occlusion. In such cases, the method may further comprise using the microcatheter to position the balloon-based catheter system at a treatment region of the total occlusion. In some embodiments, the additional intervention comprises enlarging a region of the total occlusion with balloon angioplasty. In other embodiments, the additional intervention comprises inserting a stent into a region of the total occlusion. In still other embodiments, the additional intervention comprises using the microcatheter to transport an object across the total occlusion. For example, embodiments could be used to pull large caliber devices along without causing damage to the rest of the arterial system. In some cases, large caliber devices may comprise a proximal tool such as a balloon or a percutaneously-inserted heart valve. Modifying a proximal cap of a total occlusion-. In addition to the methods of crossing a total occlusion described above, also provided are methods of modifying a proximal cap of a total occlusion to receive a guidewire. Such methods comprise deploying a microcatheter system comprising a microcatheter with proximal and distal regions, the distal region comprising a fixed, sealed end, wherein the microcatheter comprises a lumen that receives liquid and gas, so that the distal region of the microcatheter is adjacent to a proximal end of a total occlusion, the microcatheter system further comprising: an interface for separately introducing liquid and gas bubbles into the microcatheter lumen, and an actuator that repeatedly pressurizes a liquid and gas bubble mixture present within the microcatheter lumen. Such components are described in detail above. The method further comprises engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen such that the distal region of the microcatheter vibrates, modifying the proximal cap of the total occlusion to receive a guidewire. In some cases, modifying the proximal cap of the total occlusion comprises creating a divot in the proximal cap of the total occlusion. In other cases, modifying the proximal cap of the total occlusion comprises producing a hole in the proximal cap of the total occlusion. Modifying a proximal cap of a CTO may further comprise an additional intervention, where additional interventions of interest may comprise performing a procedure related to angioplasty, stenting, or any other secondary treatment known in the art. Embodiments of methods of modifying a proximal cap of a total occlusion to receive a guidewire of the invention may further comprise an additional intervention applied to a region of the total occlusion comprising the divot or the hole in the proximal cap of the total occlusion. In some cases, the additional intervention comprises passing a guidewire, e.g., a conventional guidewire, through the divot or the hole in the proximal cap of the total occlusion. By conventional guidewire, it is meant, for example, a guidewire configured for use in the context of treatment of total occlusions or arteriosclerosis or the like. Such conventional guidewires include those known in the art. Guide wire and Delivery Techniques'. Some embodiments of the invention utilize a guidewire in connection with delivering a microcatheter of the present invention to a CTO, e.g., a region near a proximal face of a CTO, e.g., such that the distal end of the microcatheter abuts the proximal face of the CTO. In some cases, systems of the invention are configured to utilize a rapid exchange (RX) delivery technique. In such cases, a guidewire may be first inserted into a vessel and utilized to guide a microcatheter of the present invention (e.g., a microcatheter comprising a sealed, distal end) to the proximal face of the CTO. When the distal end of the microcatheter is positioned with respect to CTO, e.g., such that the distal end of the microcatheter abuts, or nearly abuts, the CTO, the microcatheter is repeatedly pressurized, as described herein, such that the distal end of the microcatheter vibrates, and an axial force (i.e., along the longitudinal axis of the microcatheter) is applied to the vibrating microcatheter to cause the microcatheter to disrupt the CTO and / or advance in a relatively distal direction within the CTO. Once the microcatheter has advanced across the CTO or across a portion of the CTO, the microcatheter may be removed, via a rapid exchange (RX) delivery technique, and another catheter assembly (e.g., a pulsatile intravascular lithotripsy catheter assembly) inserted, using the same guidewire. In some cases, the CTO is sufficiently disrupted such that a balloon of a balloon catheter assembly, such as pulsatile intravascular lithotripsy catheter assembly, can be positioned within the CTO. In such cases, the outside diameter of the microcatheter is larger than the outside diameter of the balloon catheter assembly when the balloon is in a wrapped configuration; i.e., the microcatheter is shaped with a sufficient outside diameter that advancing the microcatheter across the CTO creates a space sufficiently large that a balloon catheter assembly can be inserted therein to allow, for example, a pulsatile intravascular lithotripsy treatment to proceed to further disrupt the lesion. Embodiments of methods of the invention further comprise utilizing a guidewire for positioning the microcatheter (i.e., a distal region of the microcatheter) with respect to the CTO, e.g., a proximal face of the CTO. Embodiments of methods of the invention further comprise utilizing a rapid exchange (RX) mechanism of the microcatheter system in order to position the microcatheter (i.e., a distal region of the microcatheter) with respect to the CTO, e.g., a proximal face of the CTO. Embodiments of methods of the invention further comprise removing the microcatheter from the luminal space, e.g., vessel, e.g., CTO, via a rapid exchange (RX) mechanism. Embodiments of methods of the invention further comprise utilizing a rapid exchange (RX) mechanism of the microcatheter system in order to exchange the microcatheter with tooling relevant for a secondary treatment. Further details regarding methods in which embodiments of the invention may be used, including further details regarding applying pressure oscillations using an actuator, etc., are found in United States Patent No. 11,464,949; United States Published Patent Application Publication No. 20200046949; United States Application Serial No. 17897604; pending PCT Application Serial No. PCT / US2019 / 027139; pending PCT Application Serial No. PCT / US2020 / 055458; United States Application Serial No. 63274832; United States Application Serial No. 17827169; pending PCT Application Serial No. PCT / US2022 / 014785; United States Application Serial No. 63238381; pending PCT Application Serial No. PCT / US2022 / 040586; United States Application Serial No. 63346703; pending PCT Application Serial No. PCT / US23 / 23533; United States Application Serial No. 63346704; pending PCT Application Serial No. PCT / US23 / 22685; United States Application Serial No. 63444414; and United States Application Serial No. 63545060; the disclosures of each of which are herein incorporated by reference. Various aspects of the methods of the invention being generally described above, elements of the method are now further reviewed in the context of specific embodiments. Specific Embodiment - Method of Crossing Total Occlusion FIGS. 6A-C depict aspects of an embodiment of a method of crossing total occlusions of the present invention. FIGS. 6A-C depict microcatheter system 600 with actuator 610, microcatheter 650 with distal region of microcatheter 660 and distal end of microcatheter 670, as well as the interface comprising fluid input port 640 and gas input port 630. FIGS. 6A-C show the repeated application of this embodiment of the method 600, in particular applying pressure oscillations to a liquid-gas mixture in present in the microcatheter lumen, illustrating how the continued application of such pressure oscillations works to move microcatheter 650, in particular distal region of microcatheter 660, further and further across a total occlusion. FIG. 6A shows microcatheter system 600 shortly after gas bubbles 685 have been introduced, via gas input port 640 of the interface, into liquid present in the microcatheter lumen (the liquid having already been introduced into the microcatheter lumen via liquid input port 640). In FIG. 6A, gas bubbles 685 are present in an area near the gas input port 630 of the interface, and have not dispersed through microcatheter 650, nor especially congregated in any particular region of microcatheter 650. Gas bubbles 685 are not present, for example, within actuator 610, which, as a result, comprises a liquid only zone. In FIG. 6A, pressure oscillations have not yet been applied to the liquid-gas mixture within microcatheter 650 and therefore the distal region of microcatheter, including distal end of microcatheter 670 are capable of no, or only very small, distal tip vibration as indicated by the very small width of arrow 680. FIG. 6B shows microcatheter system 600 shortly after pressure oscillations 690 have begun to be applied to microcatheter 650 via actuator 610. In FIG. 6B, as a result of initiating pressure oscillations 690, bubbles 685 present in microcatheter 650 have begun to translate distally, and bubbles 685 have begun to congregate at distal region of microcatheter 660, including near distal end of microcatheter 670. In addition, the liquid only zone 650 (i.e., a region of microcatheter 650 that is substantially free of bubbles) has expanded distally, as compared to liquid only zone 650 of FIG. 6A. In addition, as a result of initiating pressure oscillations 690 and the resulting translation of bubbles 685 towards, and congregation of bubbles 685 in, distal region of microcatheter 660, vibration 680 of distal region of microcatheter 660 has become more significant. That is, the magnitude of vibrations 680 of distal region of microcatheter 660 has increased, as compared with vibrations 680 shown in FIG. 6A, as indicated by the increased width of arrow 680. As a result, vibrations 680 transmitted to surrounding tissue, such as CTOs have increased in magnitude. FIG. 6C shows microcatheter system 600 when pressure oscillations 690 have continued to be applied to microcatheter 650 via actuator 610. In FIG. 6C, as a result of continued pressure oscillations 690, bubbles 685 present in microcatheter 650 have translated further distally and a higher proportion of bubbles 685 have translated distally, such that bubbles 685 are substantially congregated at distal region of microcatheter 660, including near distal end of microcatheter 670. In addition, the liquid only zone 650 (i.e., a region of microcatheter 650 substantially free of bubbles) has expanded further distally. In addition, as a result of continued pressure oscillations 690 and the resulting congregation of bubbles 685 in distal region of microcatheter 660, vibration 680 of distal region of microcatheter 660 has become still more significant. That is, the magnitude of vibrations 680 of distal region of microcatheter 660 has further increased, as compared with vibrations 680 shown in FIG. 6B, as indicated by the increased width of arrow 680. As a result, vibrations 680 transmitted to surrounding tissue, such as CTOs have further increased in magnitude. FIGS. 7A-7B show an application of continually applying pressure oscillations to microcatheter lumen 755 of microcatheter 750 such that distal region of microcatheter 785 moves distally across total occlusion 710. FIG. 7A shows how pressure oscillations cause bubbles of liquid-gas mixture present within microcatheter lumen 755 to congregate near the distal end of distal region of microcatheter 760. Such congregation of bubbles 785 in conjunction with continued application of pressure oscillations causes distal region of microcatheter 785 to vibrate and move across total occlusion 710. Shown in FIGS. 7A-B is CTO 710 with proximal cap 715 (proximal face) present within internal luminal tissue 720 seen as a luminal wall. FIGS. 7A-7B depict only certain aspects of a microcatheter system of the invention. Microcatheter 750 with microcatheter lumen 755 and distal region of microcatheter 760 are shown with a liquid-gas mixture, including bubbles 785, present in microcatheter lumen 755. The distal end of microcatheter 750 is a fixed, sealed end, such that such distal end vibrates and does not otherwise absorb pressure oscillations, e.g., via changes in shape or the like. Microcatheter 750 is present in guiding sheath 790 with centering balloon 795. In FIG. 7A, the balloon 795 is inflated thereby aligning distal region of microcatheter 760, including the distal end thereof, with proximal cap 715 of total occlusion 710. In FIG. 7A, as distal region of microcatheter 760 is initially aligned with CTO 710, vibration of distal region of microcatheter 760 may be continued or increased (e.g., increased in frequency and / or amplitude or otherwise adjusted such that proximal cap 715 of total occlusion 710 is vibrated to a greater degree as a result of vibration transmitted from distal region of microcatheter 760). Vibration transmitted from distal region of microcatheter 760 to total occlusion 710 is represented by arrow 795. FIG. 7B shows the movement of distal region of microcatheter 760 across total occlusion 710 as a result of continued operation of the microcatheter system to cause vibration of distal region of microcatheter 760. In particular, FIG. 7B illustrates how distal region of microcatheter 760 has progressed distally across total chronic occlusion 710, relative to the position of distal region of microcatheter 760 depicted in FIG. 7A. Vibration of distal region of microcatheter 760 may be caused by applying constant pressure oscillations or variations of different pressure oscillations, as desired, depending on, for example, characteristics of the tissue of CTO 710. Vibration of distal region of microcatheter 760 urges distal region of microcatheter 760 distally into CTO 710. Vibration transmitted from distal region of microcatheter 760 to total occlusion 710 is represented by arrow 795. Features present on the outside surface of microcatheter at distal region of microcatheter 760, such as a rough or serrated texture, may help distal region of microcatheter 760 to translate in only one direction, i.e., distally through total occlusion 710, as vibrations 795 continue. In FIG. 7B, centering balloon 795 continues to remain inflated and as a result sheath 790 continues to align microcatheter 750 with proximal cap 715 of total occlusion 710. The methods may be used for crossing total occlusions or CTOs or accessing total occlusion or CTOs or strictures or otherwise restricted luminal tissue in tissue locations of any number of different subjects. In some instances, the subjects are “mammals” or "mammalian," where these terms are used broadly to describe organisms which are within the class mammalia, including the orders carnivore (e.g., dogs and cats), rodentia (e.g., mice, guinea pigs, and rats), and primates (e.g., humans, chimpanzees, and monkeys). In some instances, the subjects are humans. Notwithstanding the appended claims, the disclosure is also defined by the following clauses: 1. A microcatheter system for crossing total occlusions, the system comprising: a microcatheter with proximal and distal regions, the distal region comprising a fixed, sealed end, wherein the microcatheter comprises a lumen that receives liquid and gas; a fluid introduction module for introducing liquid and gas into the microcatheter lumen; and an actuator that repeatedly pressurizes a liquid and gas mixture present within the microcatheter lumen such that the distal region of the microcatheter vibrates, moving the microcatheter across a total occlusion. 2. The microcatheter system of clause 1, wherein the fluid introduction module is configured for separately introducing liquid and gas into the microcatheter lumen. 3. The microcatheter system of clause 1, wherein the fluid introduction module is configured for introducing liquid and gas together into the microcatheter lumen. 4. The microcatheter system of any of the previous clauses, wherein the fluid introduction module comprises an interface. 5. The microcatheter system of any of the previous clauses, wherein the fluid introduction module comprises a connector. 6. The microcatheter system of any of the previous clauses, wherein repeatedly pressurizing the liquid and gas mixture present within the microcatheter lumen causes the gas to form a plurality of bubbles. 7. The microcatheter system of any of the previous clauses, wherein repeatedly pressurizing the liquid and gas mixture present within the microcatheter lumen forces at least some of the plurality of gas bubbles towards the distal region of the microcatheter. 8. The microcatheter system of any of the previous clauses, wherein repeatedly pressurizing the liquid and gas mixture present within the microcatheter lumen agitates the gas bubbles in the distal region of the microcatheter. 9. The microcatheter system of clause 8, wherein agitating the gas bubbles in the distal region of the microcatheter causes the distal region of the microcatheter to vibrate. 10. The microcatheter system of any of the preceding clauses, wherein the vibration of the distal region of the microcatheter causes the distal region of the microcatheter to advance across the total occlusion. 11. The microcatheter system of any of the preceding clauses, wherein the vibration of the distal region of the microcatheter causes cracks in calcified plaque present in the total occlusion. 12. The microcatheter system of any of clauses 10 to 11, wherein the rate of advancing the distal region of the microcatheter across the total occlusion is configured based at least in part on an amplitude and frequency of the pressure applied to the liquid and gas mixture present within the microcatheter lumen. 13. The microcatheter system of any of the preceding clauses, wherein the distal region of the microcatheter comprises a passive feature for holding the microcatheter in a fixed position relative to the total occlusion. 14. The microcatheter system of clause 13, wherein the passive feature comprises a rough exterior surface or a serrated surface or a rough edge or a serrated edge. 15. The microcatheter system of any of the preceding clauses, wherein the distal region of the microcatheter comprises a taper. 16. The microcatheter system of any of the preceding clauses, wherein the distal region of the microcatheter has a high circumferential stiffness. 17. The microcatheter system of any of the preceding clauses, wherein the liquid and gas present in the microcatheter lumen propagate pressure along the lumen from the proximal to distal region of the microcatheter. 18. The microcatheter system of any of the preceding clauses, wherein the liquid comprises a saline solution or a contrast fluid. 19. The microcatheter system of any of the preceding clauses, wherein the gas comprises carbon dioxide. 20. The microcatheter system of any of the preceding clauses, wherein the microcatheter and the microcatheter lumen are coaxial. 21. The microcatheter system of any of the preceding clauses, wherein the microcatheter system further comprises a distal tip. 22. The microcatheter system of clause 21, wherein the distal tip comprises a coil attached to the distal region of the microcatheter. 23. The microcatheter system of any of clauses 21 to 22, wherein the distal tip is a blunt tip or a sharp tip. 24. The microcatheter system of any of clauses 21 to 22, wherein the distal tip is an atraumatic tip. 25. The microcatheter system of any of clauses 21 to 24, wherein the distal tip is shaped based on a pathology of the total occlusion. 26. The microcatheter system of any of the preceding clauses, further comprising a guiding sheath having a lumen that aligns the distal region of the microcatheter with a proximal cap of the total occlusion. 27. The microcatheter system of clause 26, wherein the guiding sheath comprises a balloon located in an exterior distal region of the guiding sheath. 28. The microcatheter system of any of the preceding clauses, wherein the distal region of the microcatheter can be steered by rotating the microcatheter. 29. The microcatheter system of any of the preceding clauses, wherein the microcatheter comprises a region where the microcatheter is relatively stiff. 30. The microcatheter system of any of the preceding clauses, wherein the distal region of the microcatheter comprises a steering spring configured to steer the microcatheter. 31. The microcatheter system of any of the preceding clauses, wherein the distal region of the microcatheter comprises a steering cable configured such that retracting the steering cable causes the distal region of the microcatheter to change direction. 32. The microcatheter system of any of the preceding clauses, wherein the actuator comprises a proximal connector operably connected to the microcatheter. 33. The microcatheter system of clause 32, wherein the actuator further comprises a microcatheter shaft connecting the proximal connector to a microcatheter inflation lumen configured to propagate pressure from the proximal connector along the microcatheter shaft to the microcatheter inflation lumen. 34. The microcatheter system of any of the preceding clauses, wherein the proximal connector comprises a proximal chamber and a distal chamber separated by a membrane. 35. The microcatheter system of any of the preceding clauses, wherein the actuator comprises a first pressure source. 36. The microcatheter system of clause 35, wherein the first pressure source is a single pressure source, and the actuator comprises a manifold configured to generate a plurality of pressure oscillations. 37. The microcatheter system of any of clauses 35 to 36, further comprising flexible tubing operably connected to the distal end of the first pressure source. 38. The microcatheter system of any of the preceding clauses, wherein the actuator comprises a second pressure source. 39. The microcatheter system of clause 38, wherein the first pressure source and the second pressure source are configured to generate a plurality of pressure oscillations. 40. The microcatheter system of any of the preceding clauses, further comprising a force sensor present on the distal region of the microcatheter. 41. The microcatheter system of any of the preceding clauses, further comprising a pressure sensor present within microcatheter lumen at the distal region of the microcatheter. 42. The microcatheter system of any of the preceding clauses, wherein the fluid introduction module is present in the proximal region of the microcatheter. 43. The microcatheter system of any of the preceding clauses, wherein the interface is present in the proximal region of the microcatheter. 44. The microcatheter system of any of the preceding clauses, wherein the interface comprises: a first fluid introduction port and a second fluid introduction port. 45. The microcatheter system of any of the preceding clauses, wherein, the first fluid introduction port comprises a first valve mechanism, and the second fluid introduction port comprises a second valve mechanism. 46. The microcatheter system of any of clauses 44 to 45, wherein the first fluid introduction port is connected to a liquid source, and the second fluid introduction port is connected to a gas source. 47. The microcatheter system of any of the preceding clauses, wherein the interface comprises a control mechanism that separately controls the flow of liquid and gas introduced into the microcatheter lumen. 48. The microcatheter system of clause 47, wherein the control mechanism comprises at least two valves with separate controls. 49. The microcatheter system of any of the preceding clauses, wherein the fluid introduction module generates bubbles in the microcatheter. 50. The microcatheter system of any of the preceding clauses, wherein the fluid introduction module comprises two electrodes separated from each other. 51. The microcatheter system of any of the preceding clauses, wherein the fluid introduction module is configured to utilize electricity to generate bubbles in the microcatheter. 52. The microcatheter system of any of the preceding clauses, wherein vibration of the distal region of the microcatheter comprises vibration along the longitudinal axis of the microcatheter. 53. The microcatheter system of any of the preceding clauses, further comprising a balloon present in the distal region of the microcatheter such that, in an inflated state, the balloon engages with a luminal wall. 54. The microcatheter system of any of the preceding clauses, wherein the total occlusion is a chronic total occlusion. 55. The microcatheter system of any of the preceding clauses, wherein the total occlusion comprises calcified plaque. 56. The microcatheter system of any of the preceding clauses, further comprising a bubble generator configured to generate gas bubbles in liquid present in the microcatheter lumen. 57. The microcatheter system of clause 55, wherein the bubble generator comprises: two electrodes spaced apart within the microcatheter lumen; and an electrical pulse generator operably connected to the electrodes. 58. The microcatheter system of clause 57, wherein the electrical pulse generator comprises: an electrical potential source; and a controller configured to apply electrical potential from the potential source across the electrodes. 59. The microcatheter system of clause 58, wherein the magnitude of the electrical potential and the duration of time the electrical potential is applied across the electrodes imparts sufficient energy to liquid present in the microcatheter lumen to generate a bubble. 60. The microcatheter system of any of clauses 56 to 59, wherein the bubble generator comprises: a light transmitting element, with a proximal end and a distal end, wherein the distal end is present within the microcatheter lumen; and a light energy pulse generator, operably connected the proximal end of the light transmitting element. 61. The microcatheter system of clause 60, wherein the light energy pulse generator comprises: a source of light energy; and a controller configured to cause light energy from the source of light energy to be transmitted via the light transmitting element. 62. The microcatheter system of clause 61, wherein the magnitude of the light energy and the duration of time the light energy is transmitted to fluid in the microcatheter imparts sufficient energy to liquid present in the microcatheter lumen to generate a bubble. 63. The microcatheter system of any of the preceding clauses, wherein the distal region of the microcatheter is configured such that it maintains its shape upon pressurizing fluid present therein. 64. The microcatheter system of any of the preceding clauses, wherein the fluid introduction module is integrated into a region of the microcatheter. 65. The microcatheter system of any of the preceding clauses, wherein the fluid introduction module comprises a separate element from the microcatheter. 66. The microcatheter system of any of the preceding clauses, wherein the fluid introduction module is operably connected to the microcatheter. 67. The microcatheter system of any of the preceding clauses, wherein the fluid introduction module is located in a relatively proximal region of the microcatheter. 68. A microcatheter system for crossing total occlusions, the system comprising: a microcatheter with proximal and distal regions, the distal region comprising a fixed, sealed end, wherein the microcatheter comprises a lumen that receives liquid and gas; a fluid introduction module for introducing liquid into the microcatheter lumen; a bubble generator configured to generate gas bubbles in liquid present in the microcatheter lumen; and an actuator that repeatedly pressurizes the liquid and gas mixture present within the microcatheter lumen such that the distal region of the microcatheter vibrates, moving the microcatheter across a total occlusion. 69. A microcatheter system for crossing total occlusions, the system comprising: a microcatheter with proximal and distal regions, the distal region comprising a fixed, sealed end, wherein the microcatheter comprises a lumen that receives liquid and gas; a fluid introduction module for introducing liquid and gas together into the microcatheter lumen; a bubble generator configured to generate gas bubbles in liquid present in the microcatheter lumen; and an actuator that repeatedly pressurizes the liquid and gas mixture present within the microcatheter lumen such that the distal region of the microcatheter vibrates, moving the microcatheter across a total occlusion. 70. The microcatheter system of any of clauses 68 to 69, wherein the bubble generator comprises: two electrodes spaced apart within the microcatheter lumen; and an electrical pulse generator operably connected to the electrodes. 71. The microcatheter system of clause 70, wherein the electrical pulse generator comprises: an electrical potential source; and a controller configured to apply electrical potential from the potential source across the electrodes. 72. The microcatheter system of clause 71, wherein the magnitude of the electrical potential and the duration of time the electrical potential is applied across the electrodes imparts sufficient energy to liquid present in the microcatheter lumen to generate a bubble. 73. The microcatheter system of clause 72, wherein the bubble generator comprises: a light transmitting element, with a proximal end and a distal end, wherein the distal end is present within the microcatheter lumen; and a light energy pulse generator, operably connected the proximal end of the light transmitting element. 74. The microcatheter system of clause 73, wherein the light energy pulse generator comprises: a source of light energy; and a controller configured to cause light energy from the source of light energy to be transmitted via the light transmitting element. 75. The microcatheter system of clause 74, wherein the magnitude of the light energy and the duration of time the light energy is transmitted to fluid in the microcatheter imparts sufficient energy to liquid present in the microcatheter lumen to generate a bubble. 76. A method of crossing a total occlusion, the method comprising: deploying a microcatheter system comprising a microcatheter with proximal and distal regions, the distal region comprising a fixed, sealed end, wherein the microcatheter comprises a lumen that receives liquid and gas, so that the distal region of the microcatheter is adjacent to a proximal end of a total occlusion, the microcatheter system further comprising: a fluid introduction module for introducing liquid and gas into the microcatheter lumen; and an actuator that repeatedly pressurizes a liquid and gas bubble mixture present within the microcatheter lumen; and engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen such that the distal region of the microcatheter vibrates, moving the microcatheter across the total occlusion. 77. The method of crossing a total occlusion of clause 76, further comprising: separately introducing liquid and gas into the microcatheter lumen. 78. The method of crossing a total occlusion of clause 76, further comprising: introducing liquid and gas together into the microcatheter lumen. 79. The method of crossing a total occlusion of any of clauses 76 to 78, wherein engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen comprises repeatedly applying a relatively high pressure to the microcatheter lumen followed by applying a relatively low pressure to the microcatheter lumen. 80. The method of crossing a total occlusion of any of clauses 76 to 79, wherein engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen comprises repeatedly applying a pressure at a specified amplitude or a specified frequency. 81. The method of crossing a total occlusion of any of clauses 76 to 80, wherein repeatedly pressurizing the liquid and gas mixture present within the microcatheter lumen further comprises allowing the distal region of the microcatheter to engage with a proximal cap of the total occlusion. 82. The method of crossing a total occlusion of clause 81, wherein allowing the distal region of the microcatheter to engage with a proximal cap of the total occlusion comprises allowing the distal region of the microcatheter to vibrate against the proximal cap of the total occlusion. 83. The method of crossing a total occlusion of clause 82, wherein allowing the distal region of the microcatheter to vibrate against the proximal cap of the total occlusion causes a transmission of vibration from the distal region of the microcatheter to the proximal cap of the total occlusion. 84. The method of crossing a total occlusion of clause 83, wherein an amplitude or frequency of the vibration transmitted to the proximal cap of the total occlusion is configured based at least in part on an amplitude or frequency of vibration of the distal region of the microcatheter. 85. The method of crossing a total occlusion of clause 84, wherein the amplitude and frequency of vibration of the distal region of the microcatheter is configured based at least in part on an amplitude or frequency at which the actuator repeatedly pressurizes the liquid and gas mixture present within the microcatheter lumen. 86. The method of crossing a total occlusion of any of clauses 76 to 85, wherein engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen comprises applying pressure at an amplitude or frequency sufficient that the gas present in the microcatheter lumen forms a plurality of gas bubbles. 87. The method of crossing a total occlusion of any of clauses 76 to 86, wherein engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen further comprises applying pressure at an amplitude or frequency sufficient that at least some of the plurality of gas bubbles move to the distal region of the microcatheter. 88. The method of crossing a total occlusion of any of clauses 76 to 87, wherein engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen further comprises applying pressure at an amplitude or frequency sufficient to agitate the gas bubbles present in the distal region of the microcatheter. 89. The method of crossing a total occlusion of any of clauses 76 to 88, further comprising: engaging the microcatheter to transfer the vibration of the microcatheter to the total occlusion such that calcified plaque present in the total occlusion is cracked. 90. The method of crossing a total occlusion of any of clauses 76 to 89, further comprising using an imaging technique to align the distal region of the microcatheter with a proximal cap of the total occlusion. 91. The method of crossing a total occlusion of clause 90, wherein the imaging technique comprises an intravascular ultrasound technique, a light-based imaging technique, an angioplasty-based imaging technique or an optical coherence tomography-based technique. 92. The method of crossing a total occlusion of any of clauses 76 to 91, wherein the microcatheter system further comprises a balloon present in the distal region of the microcatheter. 93. The method of crossing a total occlusion of clause 92, further comprising inflating the balloon such that the balloon engages with a luminal wall, holding the microcatheter in a fixed position relative to the total occlusion. 94. The method of crossing a total occlusion of any of clauses 76 to 93, further comprising using a guiding sheath having a lumen to align the distal region of the microcatheter with a proximal cap of the total occlusion. 95. The method of crossing a total occlusion of clause 94, wherein the guiding sheath comprises a balloon located in an exterior distal region of the guiding sheath. 96. The method of crossing a total occlusion of clause 95, further comprising inflating the guiding sheath balloon in a manner sufficient to align the distal region of the microcatheter with a proximal cap of the total occlusion. 97. The method of crossing a total occlusion of any of clauses 76 to 96, wherein the method is a method for treating cardiovascular disease. 98. The method of crossing a total occlusion of clause 97, wherein the method is a method for treating arteriosclerosis. 99. The method of crossing a total occlusion of any of clauses 76 to 98, wherein the method further comprises an additional intervention. 100. The method of crossing a total occlusion of clause 99, wherein the additional intervention comprises drawing a guidewire across a distal end of the total occlusion. 101. The method of crossing a total occlusion of clause 100, wherein the additional intervention comprises applying a balloon-based catheter system to a region of the total occlusion. 102. The method of crossing a total occlusion of clause 101, further comprising using the guidewire to position the balloon-based catheter system at a treatment region of the total occlusion. 103. The method of crossing a total occlusion of any of clauses 99 to 102, wherein the additional intervention further comprises enlarging a channel of the total occlusion with balloon angioplasty. 104. The method of crossing a total occlusion of any of clauses 99 to 103, wherein the additional intervention comprises inserting a stent into a region of the total occlusion. 105. The method of crossing a total occlusion of any of clauses 99 to 104, wherein the additional intervention comprises using the guidewire to transport an object across the total occlusion. 106. The method of crossing a total occlusion of any of clauses 76 to 105, wherein the method is a method for crossing the total occlusion of a subject. 107. The method of crossing a total occlusion of clause 106, wherein the subject is mammalian. 108.   The method of crossing a total occlusion of clause 107, wherein the subject is human. 109.   The method of crossing a total occlusion of any of clauses 76 to 108, wherein the total occlusion is a chronic total occlusion, optionally comprising calcified plaque. 110. The method of crossing a total occlusion of any of clauses 76 to 109, wherein the total occlusion comprises calcified plaque. 111. The method of crossing a total occlusion of any of clauses 76 to 110, further comprising de-bubbling the microcatheter lumen. 112. The method of crossing a total occlusion of any of clauses 76 to 111, further comprising introducing liquid into the microcatheter lumen via the interface. 113. The method of crossing a total occlusion of any of clauses 76 to 112, further comprising introducing gas into the microcatheter lumen via the fluid introduction module. 114. The method of crossing a total occlusion of any of clauses 76 to 113, wherein the microcatheter system further comprises a bubble generator configured to generate gas bubbles in the liquid present in the microcatheter lumen. 115. The method of crossing a total occlusion of clause 114, further comprising engaging the bubble generator to generate gas bubbles in the liquid present in the microcatheter lumen. 116. The method of crossing a total occlusion of any of clauses 114 to 115, wherein the bubble generator comprises: two electrodes spaced apart within the microcatheter lumen; and an electrical pulse generator operably connected to the electrodes. 117. The method of crossing a total occlusion of clause 116, wherein the electrical pulse generator comprises: an electrical potential source; and a controller configured to apply electrical potential from the potential source across the electrodes. 118. The method of crossing a total occlusion of clause 117, wherein the magnitude of the electrical potential and the duration of time the electrical potential is applied across the electrodes imparts sufficient energy to the liquid present in the microcatheter lumen to generate a gas bubble. 119. The method of crossing a total occlusion of any of clauses 114 to 118, further comprising engaging the bubble generator to transmit a plurality of pulses of electrical potential to the electrodes present in the microcatheter lumen to generate gas bubbles in the liquid present in the microcatheter lumen. 120. The method of crossing a total occlusion of any of clauses 114 to 119, wherein the bubble generator comprises: a light transmitting element, with a proximal end and a distal end, wherein the distal end is present within the microcatheter lumen; and a light energy pulse generator, operably connected to the proximal end of the light transmitting element. 121. The method of crossing a total occlusion of clause 120, wherein the light energy pulse generator comprises: a source of light energy; and a controller configured to cause light energy from the source of light energy to be transmitted via the light transmitting element. 122. The method of crossing a total occlusion of clause 121, wherein the magnitude of the light energy and the duration of time the light energy is transmitted to the liquid in the microcatheter lumen imparts sufficient energy to generate a gas bubble. 123. The method of crossing a total occlusion of any of clauses 114 to 122, further comprising engaging the bubble generator to transmit a plurality of pulses of light energy to the distal end of the light transmitting element present in the microcatheter lumen to generate gas bubbles in the liquid present in the microcatheter lumen. 124. A method of crossing a total occlusion, the method comprising: deploying a microcatheter system comprising a microcatheter with proximal and distal regions, the distal region comprising a fixed, sealed end, wherein the microcatheter comprises a lumen that receives liquid and gas, so that the distal region of the microcatheter is adjacent to a proximal end of a total occlusion, the microcatheter system further comprising: a fluid introduction module for introducing liquid into the microcatheter lumen; a bubble generator configured to generate gas bubbles in liquid present in the microcatheter lumen; and an actuator that repeatedly pressurizes a liquid and gas bubble mixture present within the microcatheter lumen; and engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen such that the distal region of the microcatheter vibrates, moving the microcatheter across the total occlusion. 125. The method of crossing a total occlusion of clause 124, further comprising engaging the bubble generator to generate gas bubbles in the liquid present in the microcatheter lumen. 126. The method of crossing a total occlusion of any of clauses 124 to 125, wherein the bubble generator comprises: two electrodes spaced apart within the microcatheter lumen; and an electrical pulse generator operably connected to the electrodes. 127. The method of crossing a total occlusion of any of clauses 124 to 126, wherein the electrical pulse generator comprises: an electrical potential source; and a controller configured to apply electrical potential from the potential source across the electrodes. 128. The method of crossing a total occlusion of clause 127, wherein the magnitude of the electrical potential and the duration of time the electrical potential is applied across the electrodes imparts sufficient energy to the liquid present in the microcatheter lumen to generate a gas bubble. 129. The method of crossing a total occlusion of any of clauses 124 to 128, further comprising engaging the bubble generator to transmit a plurality of pulses of electrical potential to the electrodes present in the microcatheter lumen to generate gas bubbles in the liquid present in the microcatheter lumen. 130. The method of crossing a total occlusion of any of clauses 124 to 129, wherein the bubble generator comprises: a light transmitting element, with a proximal end and a distal end, wherein the distal end is present within the microcatheter lumen; and a light energy pulse generator, operably connected the proximal end of the light transmitting element. 131. The method of crossing a total occlusion of clause 130, wherein the light energy pulse generator comprises: a source of light energy; and a controller configured to cause light energy from the source of light energy to be transmitted via the light transmitting element. 132. The method of crossing a total occlusion of any of clause 131, wherein the magnitude of the light energy and the duration of time the light energy is transmitted to liquid present in the microcatheter lumen imparts sufficient energy to generate a gas bubble. 133. The method of crossing a total occlusion of any of clauses 124 to 132, further comprising engaging the bubble generator to transmit a plurality of pulses of light energy to the distal end of the light transmitting element present in the microcatheter lumen to generate gas bubbles in the liquid present in the microcatheter lumen. 134. A method of modifying a proximal cap of a total occlusion to receive a guidewire, the method comprising: deploying a microcatheter system comprising a microcatheter with proximal and distal regions, the distal region comprising a fixed, sealed end, wherein the microcatheter comprises a lumen that receives liquid and gas, so that the distal region of the microcatheter is adjacent to a proximal end of a total occlusion, the microcatheter system further comprising: a fluid introduction module for introducing liquid and gas into the microcatheter lumen; and an actuator that repeatedly pressurizes a liquid and gas bubble mixture present within the microcatheter lumen; and engaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen such that the distal region of the microcatheter vibrates, modifying the proximal cap of the total occlusion to receive a guidewire. 135. The method of modifying a proximal cap of a total occlusion to receive a guidewire of clause 134, further comprising: separately introducing liquid and gas into the microcatheter lumen. 136. The method of any of clauses 134 to 135, wherein modifying a proximal cap of a total occlusion to receive a guidewire comprises creating a divot in the proximal cap of the total occlusion. 137. The method according to any of clauses 134 to 136, wherein the method further comprises an additional intervention applied to a region of the total occlusion comprising the divot in the proximal cap of the total occlusion. 138. The method according to clause 137, wherein the additional intervention comprises passing a guidewire through the divot in the proximal cap of the total occlusion. 139. The method of any of clauses 134 to 138, wherein modifying the proximal cap of the total occlusion to receive a guidewire comprises creating a hole in the proximal cap of the total occlusion. 140. The method according to any of clauses 134 to 139, wherein the method further comprises an additional intervention applied to a region of the total occlusion comprising the hole in the proximal cap of the total occlusion. 141. The method according to clause 140, wherein the additional intervention comprises passing a conventional guidewire through the hole in the proximal cap of the total occlusion. 142. The method according to any of clauses 134 to 141, wherein the total occlusion is a chronic total occlusion. 143. The method according to any of clauses 134 to 142, wherein the total occlusion comprises calcified plaque. 144. The method according to any of clauses 76 to 143, further comprising applying an axial force to the microcatheter while the distal region of the microcatheter vibrates. 145. The method according to any of clauses 76 to 144, wherein the microcatheter system is a system according to any of clauses 1 to 75. 146. A kit comprising: a microcatheter according to any of clauses 1 to 75; and packaging for the microcatheter. 147. The kit according to clause 146, further comprising: an interface as clauseed in any of clauses 1 to 75; and packaging for the interface. 148. The kit according to any of clauses 146 to 147, further comprising: an actuator as clauseed in any of clauses 1 to 75; and packaging for the actuator. 149. The kit according to any of clauses 146 to 148, further comprising: a first pressure source. 150. The kit according to clause 149, further comprising: a second pressure source. 151. The kit according to any of clauses 146 to 150, further comprising: a liquid source. 152. The kit according to any of clauses 146 to 151, further comprising: a gas source. 153. The kit according to any of clauses 146 to 152, wherein one or more components of the kit are sterile. 154. The kit according to any of clauses 146 to 153, wherein one or more components of the kit are re-usable. 155. The kit according to any of clauses 146 to 154, wherein one or more components of the kit are disposable. It is to be understood that this invention is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims. In at least some of the described embodiments, one or more elements used in an embodiment can interchangeably be used in another embodiment unless such a replacement is not technically feasible. It will be appreciated by those skilled in the art that various other omissions, additions and modifications may be made to the methods and structures described herein without departing from the scope of the claimed subject matter. All such modifications and changes are intended to fall within the scope of the subject matter, as defined by the appended claims. Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention. Certain ranges are presented herein with numerical values being preceded by the term "about." The term "about" is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number may be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number. As will be understood by one skilled in the art, for any and all purposes, such as in terms of providing a written description, all ranges disclosed herein also encompass any and all possible sub-ranges and combinations of sub-ranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art all language such as “up to,” “at least,” “greater than,” “less than,” and the like include the number recited and refer to ranges which can be subsequently broken down into sub-ranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1-3 articles refers to groups having 1, 2, or 3 articles. Similarly, a group having 1-5 articles refers to groups having 1,2, 3, 4, or 5 articles, and so forth. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, representative illustrative methods and materials are now described. All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference and are incorporated herein by reference, including, but not limited to, disclosing and describing the methods and / or materials in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed. It is noted that, as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation. As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention. Any recited method can be carried out in the order of events recited or in any other order which is logically possible. It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (e.g., bodies of the appended claims) are generally intended as “open” terms (e.g., the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases “at least one” and “one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (e.g., “a” and / or “an” should be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (e.g., the bare recitation of “two recitations,” without other modifiers, means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to “at least one of A, B, and C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “ a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C together, etc.). In those instances where a convention analogous to “at least one of A, B, or C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “ a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C together, etc.). It will be further understood by those within the art that virtually any disjunctive word and / or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B.” In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group. Although the invention is described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims. Accordingly, the disclosure hereof merely illustrates the principles of the invention. It will be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly described or shown herein, embody the principles of the invention and are included within its spirit and scope. Furthermore, all examples and conditional language recited herein are principally intended to aid the reader in understanding the principles of the invention and the concepts contributed by the inventors to furthering the art, and are to be construed as being without limitation to such specifically recited examples and conditions. Moreover, all 5 statements herein reciting principles, aspects, and embodiments of the invention as well as specific examples thereof, are intended to encompass both structural and functional equivalents thereof. Additionally, it is intended that such equivalents include both currently known equivalents and equivalents developed in the future, i.e., any elements developed that perform the same function, regardless of structure. Moreover, nothing disclosed herein is intended to be dedicated 10 to the public regardless of whether such disclosure is explicitly recited in the claims. While the systems, devices and methods have or will be described for the sake of grammatical fluidity with functional explanations, it is to be expressly understood that the claims, unless expressly formulated under 35 U.S.C. § 112, are not to be construed as necessarily limited in any way by the construction of “means” or “steps” limitations, but are to be accorded the full 15 scope of the meaning and equivalents of the definition provided by the claims under the judicial doctrine of equivalents, and in the case where the claims are expressly formulated under 35 ll.S.C. § 112 are to be accorded full statutory equivalents under 35 U.S.C. § 112.

Claims

1. A microcatheter system for crossing total occlusions, the system comprising: a microcatheter with proximal and distal regions, the distal region comprising a fixed, sealed end, wherein the microcatheter comprises a lumen that receives liquid and gas;a fluid introduction module for introducing liquid and gas into the microcatheter lumen; andan actuator that repeatedly pressurizes a liquid and gas mixture present within the microcatheter lumen such that the distal region of the microcatheter vibrates, moving the microcatheter across a total occlusion.

2. The microcatheter system of Claim 1, wherein repeatedly pressurizing the liquid and gas mixture present within the microcatheter lumen causes the gas to form a plurality of bubbles.

3. The microcatheter system of any of the previous claims, wherein repeatedly pressurizing the liquid and gas mixture present within the microcatheter lumen forces at least some of the plurality of gas bubbles towards the distal region of the microcatheter.

4. The microcatheter system of any of the previous claims, wherein repeatedly pressurizing the liquid and gas mixture present within the microcatheter lumen agitates the gas bubbles in the distal region of the microcatheter.

5. The microcatheter system of any of the preceding claims, wherein the vibration of the distal region of the microcatheter causes the distal region of the microcatheter to advance across the total occlusion.

6. The microcatheter system of any of the preceding claims, wherein the vibration of the distal region of the microcatheter causes cracks in calcified plaque present in the total occlusion.

7. The microcatheter system of any of the preceding claims, wherein the distal region of the microcatheter comprises a passive feature for holding the microcatheter in a fixed position relative to the total occlusion.

8. The microcatheter system of any of the preceding claims, wherein the liquid comprises a saline solution or a contrast fluid and the gas comprises carbon dioxide.

9. The microcatheter system of any of the preceding claims, wherein the microcatheter and the microcatheter lumen are coaxial.

10. The microcatheter system of any of the preceding claims, wherein the microcatheter system further comprises a distal tip that comprises a coil attached to the distal region of the microcatheter.

11. The microcatheter system of any of the preceding claims, further comprising a guiding sheath having a lumen that aligns the distal region of the microcatheter with a proximal cap of the total occlusion.

12. The microcatheter system of any of the preceding claims, wherein the distal region of the microcatheter can be steered by rotating the microcatheter.

13. The microcatheter system of any of the preceding claims, wherein the proximal connector comprises a proximal chamber and a distal chamber separated by a membrane.

14. The microcatheter system of any of the preceding claims, further comprising a bubble generator configured to generate gas bubbles in liquid present in the microcatheter lumen.

15. A method of crossing a total occlusion, the method comprising:deploying a microcatheter system comprising a microcatheter with proximal and distal regions, the distal region comprising a fixed, sealed end, wherein the microcatheter comprises a lumen that receives liquid and gas, so that the distal region of the microcatheter is adjacent to a proximal end of a total occlusion, the microcatheter system further comprising:a fluid introduction module for introducing liquid and gas into the microcatheter lumen; andan actuator that repeatedly pressurizes a liquid and gas bubble mixture present within the microcatheter lumen; andengaging the actuator in a manner sufficient to repeatedly pressurize the liquid and gas mixture present within the microcatheter lumen such that the distal region of the microcatheter vibrates, moving the microcatheter across the total occlusion.

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