Patent Publication Number: US-2021177265-A1

Title: Systems and methods for imaging and therapy suitable for use in the cardiovascular system

Description:
CROSS-REFERENCES TO RELATED APPLICATIONS 
     This application is based on, claims the benefit of, and claims priority to U.S. Provisional Application No. 62/577,042, filed Oct. 25, 2017, which is hereby incorporated herein by reference in its entirety for all purposes. 
    
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH 
     Not Applicable. 
     BACKGROUND 
     The present disclosure relates to imaging and therapy methods, apparatuses, and devices, and more particularly to exemplary aspects of imaging and/or therapy methods and systems which can be suitable for use in visualizing and conducting therapy on a heart, valves, or blood vessels to obtain a diagnosis, acquire tissue, treat via the removal of pathology, or assist in the deployment of other devices. 
     Direct visualization of structures is often very useful for diagnosis and therapeutic interventions in medicine and surgery. However, physicians currently do not have a reliable means to directly visualize structures inside the beating heart and its chambers, or inside the major blood vessels. This is due to light being attenuated by blood. 
     Fluoroscopy and echocardiography are currently available modalities for real-time imaging of cardiovascular structures. While these techniques can be used to guide certain minimally invasive intracardiac procedures, but both are indirect and imprecise. This tends to make such procedures time and resource consuming. In addition to significantly prolonged procedural times, fluoroscopy is associated with risks. For example, fluoroscopy exposes patients and the clinical team to significant ionizing radiation. As another example, transesophageal echocardiography (TEE) is associated with a risk of esophageal injury. As yet another example, there is a risk of an inadvertent tissue injury or perforation by a device or a catheter that is guided by fluoroscopy or TEE during indirect visual navigation through the heart chambers or great vessels that is exacerbated by the relatively poor quality of the visualization. 
     Only a few methods have been attempted to directly visualize structures inside the heart, but none have found a widespread acceptance in clinical practice. For example, direct contact between an endoscope and cardiac tissue can provide a visualization, but such a visualization shows only an extremely small field. As another example, use of a transparent toroidal balloon chamber that displaces blood between the lens and the object could facilitate visualization, but does not allow any instrumentation through the balloon itself. As yet another example, displacement of blood with pressurized transparent fluid boluses is not capable of maintain imaging for sustained periods of time, and can cause hemodynamic instability. Finally, a complete replacement of intracardiac blood with a transparent nourishing perfusate can facilitate imaging, but also requires utilization of peripheral cardiopulmonary bypass and comes with substantial cost in addition to being a substantially more invasive procedure than fluoroscopy. 
     Therefore, the current unmet need lies in the absence of a method and apparatus for a direct imaging of the endocardial surface of the heart and blood vessels, also known herein as cardioscopy. In addition to diagnostic direct visualization, physicians also need a means for obtaining tissue, biopsy, and/or tissue removal of any pathology on a beating heart and blood vessels. Further therapeutic applications arise from a unique benefit of direct visualization of the intracardiac or intravascular structures in either energy delivery during ablative procedures or during delivery and deployment of various medical devices inside the heart or great vessels. All current diagnostic and therapeutic interventions on the heart and great vessels would potentially benefit from a radically new and direct imaging modality. 
     There are numerous examples of limitations of current imaging modalities in clinical practice. In case of massive or sub-massive pulmonary embolism (PE), currently available options (e.g., systemic thrombolysis, catheter-based direct thrombosis, and angiovac aspiration) have various drawings. For example, system thrombosis is very non-specific and frequently ineffective. As another example, catheter-based direct thrombolysis does not physically remove a large burden of the remaining clot. As yet another example, angiovac aspiration systems generally lack direct visualization of the thrombus, and procedures using such systems often rely instead on fluoroscopy, resulting in a very imprecise aspiration of the clot, in addition to requiring an invasive veno-venous bypass circuit. Ultimately, currently employed surgical embolectomy via sternotomy on a heart-lung machine is extremely invasive and requires substantial postoperative recovery. PE is very common and a massive or sub-massive PE is very morbid and frequently fatal. It is not surprising, therefore, that virtually all currently available therapeutic interventions targeted at PE are associated with substantial periprocedural morbidity and mortality either due to its significant ineffectiveness or a very radical invasiveness. 
     Further limitations include lack of direct visualization of the endocardial surface during ablative procedures for various arrhythmias, such as atrial fibrillation, supraventricular tachycardia, or ventricular tachycardia. Currently available options include employment of the catheter systems that deliver energy to create a tissue scar, thus interrupting micro or macro-reentrant circuits. The procedures tend to be long and frustrating because of lack of direct visualization of the catheter in relation to the endocardial surface and anatomical structures. Frequently fluoroscopy, transesophageal echocardiography, and/or intracardiac echocardiography are employed to get the task accomplished. However, despite all currently available indirect imaging modalities, most ablation procedures are frequently ineffective and require repeat interventions. The task would be much easier accomplished with a direct visualization of the catheter in the intracardiac chamber. 
     Another example is how heart transplant patients currently undergo multiple myocardial biopsies as part of their organ rejection surveillance regimen. Currently, a bioptome is advanced blindly under fluoroscopy guidance through the tricuspid valve. Not surprisingly, as the result of multiple biopsy sessions and blind passages across the tricuspid valve, the leaflets of the tricuspid valve are frequently injured and destroyed leading to a subsequent severe tricuspid regurgitation. Sometimes these very sick patients have to undergo either a heart re-transplant or a very high-risk tricuspid valve replacement via open heart surgery due to potentially avoidable injury of the tricuspid valve. Direct visualization of the bioptome passing across the tricuspid valve would ensure less injury to the tricuspid valve and make biopsy procedure more effective and less time consuming. The same can be said about guidance of the bioptome for biopsy of other intracardiac or intravascular pathologies. 
     However, perhaps most clinically relevant and time-pressing is the current suboptimal visualization modality in deployment of various currently available intracardiac or intravascular devices and related procedures, including, but not limited to, transcatheter aortic valve replacement, left atrial appendage occlusion, chronic total occlusion, transcatheter mitral valve repair, patent foramen ovale closure, transcatheter pulmonary valve replacement, paravalvular leak closure, and percutaneous transluminal coronary angioplasty. One example of percutaneous tricuspid or mitral annuloplasty devices, the currently available strategy employs both, fluoroscopy and echocardiography guidance to deploy and secure these devices around the valve hopefully well in the annular tissue. However, the platform is quite risky because of the neighboring coronary arteries, conduction system, and other anatomical structures. Due to the indirect imaging provided by fluoroscopy and echocardiography, the deployment is imprecise, time-consuming, and carries a high risk of injuring a neighboring anatomical structure, such as a coronary artery, conduction system, valve itself, or other anatomical structure. Further, the annulus of the valve, tricuspid or mitral, is a very thin structure and is best identified by its whitish colored line between atrial wall and actual valve leaflet tissue. The precision that is required to place an annuloplasty device into the annular tissue of the valve can be best achieved only by a direct visualization of the anatomical structure and not so much by a current guesswork-based on indirect and imprecise fluoroscopy and echocardiography. The current platform of indirect guidance by fluoroscopy or echocardiography is a far cry from what a proceduralist would prefer in terms of image quality to deploy a needed device. 
     Direct visualization and guidance in the delivery and deployment of various medical devices in the field of heart and vascular disease would provide a more successful, more durable, more precise, less time-consuming, and less complications-prone platform. It would literally revolutionize the way the numerous devices are placed in the heart and/or in the great vessels. 
     BRIEF SUMMARY 
     In an aspect, the present disclosure provides a probe. The probe includes a proximal portion and a distal portion. The probe includes a channel, an optical waveguide, and a ferrofluid attractor. The channel has a proximal port, a distal port, and an interior surface. The proximal port is positioned at the proximal end of the probe. The distal port is positioned at the distal portion of the probe. The interior surface is composed of a material that is chemically and magnetically inert to a ferrofluid. The channel, the proximal port, and the distal port have size dimensions that allow the ferrofluid to enter the channel via the proximal port, move along the channel, and exit the channel via the distal port when the ferrofluid is introduced at a predefined pressure. The optical waveguide has a proximal waveguide end and a distal waveguide end. The proximal waveguide end is positioned at the proximal portion of the probe. The distal waveguide end is positioned at the distal portion of the probe. The ferrofluid attractor is coupled to the distal end of the probe. The ferrofluid attractor has magnetic properties and positioning relative to the distal port to magnetically attract the ferrofluid when exiting the distal port. 
     In another aspect, the present disclosure provides a catheter. The catheter includes a probe as described herein and a sheath configured to receive the probe. 
     In a further aspect, the present disclosure provides an optical imaging system. The optical imaging system includes an optical imaging light source, an optical imaging detector, a probe as described herein, a circulator, and an optical imaging controller. The circulator is coupled to the optical imaging light source, the optical imaging detector, and the optical waveguide. The circulator is configured to direct light from the optical imaging light source to the optical waveguide and from the optical waveguide to the optical imaging detector. The optical imaging controller is coupled to the optical imaging detector and configured to provide an optical imaging signal output representative of an optical signal measured at the optical imaging detector. 
     In yet another aspect, the present disclosure provides an optical coherence tomography (OCT) system. The OCT system includes an OCT light source, an OCT detector, a probe as described herein, a circulator, and an OCT controller. The circulator is coupled to the OCT light source, the OCT detector, and the optical waveguide. The circulator is configured to direct light from the OCT light source to optical waveguide and from the optical waveguide to the OCT spectrometer. The OCT controller is coupled to the OCT spectrometer and configured to provide an OCT signal output representative of an OCT signal measured at the OCT spectrometer. 
     In yet a further aspect, the present disclosure provides a ferrofluid for use in direct visualization medical imaging of an internal structure. The ferrofluid includes ferromagnetic particles and a biologically inert solvent. The ferromagnetic particles are present in an amount by weight of between 0.1 milligrams of iron per milliliter and 100 milligrams of iron per milliliter. 
     In another aspect, the present disclosure provides a method of acquiring a direct visualization medical image of an internal structure. The method includes: a) introducing a ferrofluid into an area near the internal structure, thereby displacing a biological fluid within the area, the ferrofluid retained in the area using a magnetic effect; and b) acquiring the direct visualization medical image of the internal structure through the ferrofluid. 
     The foregoing and other aspects and advantages of the invention will appear from the following description. In the description, reference is made to the accompanying drawings which form a part hereof, and in which there is shown by way of illustration a preferred embodiment of the invention. Such embodiment does not necessarily represent the full scope of the invention, however, and reference is made therefore to the claims and herein for interpreting the scope of the invention. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
       The invention will be better understood and features, aspects and advantages other than those set forth above will become apparent when consideration is given to the following detailed description thereof. Such detailed description makes reference to the following drawings. 
         FIG. 1  is a schematic of a probe, in accordance with an aspect of the present disclosure. 
         FIG. 2  is another schematic of a probe, in accordance with an aspect of the present disclosure. 
         FIG. 3  is a schematic of a use of a probe, in accordance with an aspect of the present disclosure. 
         FIG. 4  is another schematic of a use of a probe, in accordance with an aspect of the present disclosure. 
         FIG. 5  is an absorbance spectrum of the ferrofluid prepared in Example 1. 
         FIG. 6  is an image of a ferrofluid cloud formed in a buffer solution, as described in Example 2. 
         FIG. 7  is an image of a ferrofluid cloud formed in whole blood, as described in Example 3. 
         FIGS. 8A to 8C  are various images taken with and without a ferrofluid cloud, as described in Example 4. 
         FIG. 9A  is yet another schematic of a probe, in accordance with an aspect of the present disclosure. 
         FIG. 9B  is still another schematic of a probe, in accordance with an aspect of the present disclosure. 
       FIGS.  10 A 1  to  10 B 3  are various schematics of probes, in accordance with aspects of the present disclosure. 
         FIGS. 11A and 11B  are additional schematics of probes, in accordance with aspects of the present disclosure. 
         FIG. 12  is a cross-section schematic of a probe, in accordance with an aspect of the present disclosure. 
         FIG. 13  is a photograph of a probe, in accordance with an aspect of the present disclosure. 
         FIGS. 14A to 14I  are cross-sections of various magnet configurations in accordance with aspects of the present disclosure. 
         FIGS. 15A to 15E  are additional magnet configurations in accordance with aspects of the present disclosure. 
         FIG. 16A  is various magnet configurations and corresponding magnetic flux models in accordance with aspects of the present disclosure. 
         FIG. 16B  is a depiction of flux density for magnet configurations of  FIG. 16A  in accordance with aspects of the present disclosure. 
         FIG. 17  is a magnetic flux model corresponding to a particular magnet configuration of  FIG. 16A  in accordance with an aspect of the present disclosure. 
         FIG. 18  is an absorbance spectrum of Feraheme at various concentrations. 
         FIG. 19  is an absorbance spectrum of two different ferrofluids at various concentrations. 
         FIG. 20  is a depiction of wavelength spectra for different filters and corresponding ferrofluid guided images. 
         FIGS. 21A to 21D  is a series of images taken with and without ferrofluid guided imaging in a pulsatile pump system, as described in Example 9. 
         FIGS. 22A and 22B  are a series of images taken using ferrofluid guided imaging in a sheep heart, as described in Example 10. 
         FIG. 23  is a series of images showing the use of a bioptome by ferrofluid guided imaging, as described in Example 11. 
         FIG. 24  is a photograph of a pulsatile pump system used for testing, as described in Example 12. 
         FIG. 25  is a photograph of a probe implemented in accordance with an aspect of the present disclosure, as described in Example 13. 
         FIG. 26  is a photograph of a probe implemented in accordance with an aspect of the present disclosure, as described in Example 14. 
         FIGS. 27A to 27E  is a series of images taken using ferrofluid guided imaging in a narrow tube simulating a coronary artery in accordance with an aspect of the present disclosure, as described in Example 15. 
     
    
    
     DETAILED DESCRIPTION 
     Before the present invention is described in further detail, it is to be understood that the invention is not limited to the particular embodiments described. 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. The scope of the present invention will be limited only by the claims. As used herein, the singular forms “a”, “an”, and “the” include plural embodiments unless the context clearly dictates otherwise. 
     It should be apparent to those skilled in the art that many additional modifications beside those already described are possible without departing from the inventive concepts. In interpreting this disclosure, all terms should be interpreted in the broadest possible manner consistent with the context. Variations of the term “comprising”, “including”, or “having” should be interpreted as referring to elements, components, or steps in a non-exclusive manner, so the referenced elements, components, or steps may be combined with other elements, components, or steps that are not expressly referenced. Embodiments referenced as “comprising”, “including”, or “having” certain elements are also contemplated as “consisting essentially of” and “consisting of” those elements, unless the context clearly dictates otherwise. It should be appreciated that aspects of the disclosure that are described with respect to a system are applicable to the methods, and vice versa, unless the context explicitly dictates otherwise. 
     Numeric ranges disclosed herein are inclusive of their endpoints. For example, a numeric range of between 1 and 10 includes the values 1 and 10. When a series of numeric ranges are disclosed for a given value, the present disclosure expressly contemplates ranges including all combinations of the upper and lower bounds of those ranges. For example, a numeric range of between 1 and 10 or between 2 and 9 is intended to include the numeric ranges of between 1 and 9 and between 2 and 10. 
     Lengths and distances described herein are described in terms of optical path length lengths and distances, unless the context clearly dictates otherwise. Accordingly, light traveling along a coiled optical fiber travels a distance that is equal to the uncoiled length of the optical fiber, not the physical distance between the input and output of the optical fiber. 
     As used herein, the term “substantially-transparent” refers to the ability to successfully transmit light through a medium. “Substantially” referring to the fact that the medium is neither optically transparent nor completely absorbent. For example, a medium that is substantially transparent would allow visualization of a target image with a light based imaging device at a resolution that allows desired structures to be discernable. It is assumed that a substantially transparent medium will have an absorbance at minimum less than blood, allowing light transmittance at a depth and resolution necessary for the specific application. The present disclosure provides systems and methods that have a variety of advantages relative to those available in the art. The following description of these advantages is not intended to be limiting, nor is it intended to imply that the systems and methods can only be used to achieve these advantages. 
     For example, the present disclosure provides examples of probes, catheters, optical systems, OCT systems, ferrofluids, and processes as described herein. Features described in connection with one or more of aspects of these examples are generally applicable to the others. For example, features described in connection with probes are generally applicable to OCT systems, and features described in connection with ferrofluids are generally applicable to the processes. 
     In some aspects, mechanisms described herein can be used (e.g., by physicians) to directly image and conduct minimally-invasive therapy on cardiovascular structures in the presence of flowing blood. For example, a device for directly imaging cardiovascular structures can include a flexible cardioscope (e.g., an endoscope used in the cardiovascular system) that includes a magnetic tip. In such an example, a liquid that becomes magnetized when placed in the presence of a magnetic field (sometimes referred to herein as a ferrofluid), is injected through a working channel to the tip of the cardioscope. The magnetic field produced by the magnetic tip of the cardioscope in such an example can cause the ferrofluid to localize near the tip of the cardioscope scope, which can form a ferrofluid cloud that displaces blood. In such an example, light can more easily penetrate through the ferrofluid cloud than through blood, which can facilitate direct visualization of a target. Additionally, a minimally-invasive surgical procedure can be conducted through the ferrofluid cloud, while the target is continuously visualized. After such a procedure is over, suction through the working channel can be used to remove the ferrofluid from the tip of the cardioscope. 
     As described above, one solution for direct cardioscopy entails a substantially transparent ferrofluid that displaces blood while staying around a magnetized tip of a flexible probe or cardioscope (see, e.g.,  FIG. 1 ). Ferrofluids are conventionally a colloidal liquid made of ferromagnetic particles in a carrier fluid that become magnetized in the presence of a magnetic field. An aspect of this disclosure is a substantially transparent ferrofluid that can displace blood and through which an optical spectroscopic measurement or image can be acquired. In one exemplary aspect of this disclosure, a cardioscope can be advanced into the heart or into the pulmonary artery in cases of pulmonary embolism using any suitable technique or combination of techniques (e.g., transaortic, transapical, transfemoral, transeptal, transradial, transfemoral, transsubclavian, transjugular, etc.). The substantially transparent ferrofluid would then emanate from the tip of the endoscope via a separate lumen within the probe and remain at least partially adjacent to the probe as a spherical “cloud” around the tip of the probe, while displacing the blood in between the cardiovascular anatomical structure and the imaging arrangement within the cardioscope. For cases where a direct biopsy is required, bioptome forceps may be advanced via a lumen within the cardioscope probe and the structure of interest is biopsied under direct visualization through the ferrofluid cloud. In cases of the need to aspirate (e.g., clot or vegetation, etc.), the tip of the cardioscope is pushed against the clot or vegetation, the ferrofluid is aspirated back, and then the clot or vegetation is aspirated via a lumen within the cardioscope. A basket can be deployed through the ferrofluid behind the clot to assist in clot removal. 
     The systems and methods described herein can be utilized in multiple clinical applications in cardiology, and can facilitate expansion of the field of minimally-invasive cardiovascular surgery. For example, the mechanisms described herein can be used in connection with diagnosis and/or treatment of atrial fibrillation, pulmonary embolism, heart valve disease, heart failure, coronary artery disease, conduction disorders, vascular disease, etc. As another example, the mechanisms described herein can facilitate direct imaging of the heart and endovascular structures, which can be used by a healthcare provider (e.g., a physician) during various procedures. For example, the physician can use the mechanisms described herein to perform directly visualized biopsy and tissue removal procedures. As another example, the physician can use the mechanisms described herein to more effectively extract and/or aspirate clots. As yet another example, the physician can use the mechanisms described herein to more efficiently perform ablation procedures. As still another example, the physician can use the mechanisms described herein to provide visual guidance during deployment of various intracardiac and endovascular devices. As a further example, the physician can use the mechanisms described herein to directly identify perivalvular leaks. As another further example, the physician can use the mechanisms described herein to perform numerous directly visualized intracardiac procedures such as atrial septectomy, stitch placement, and others. The mechanisms described herein can be used by various types of healthcare providers in a variety of settings. For example, the mechanisms described herein can be used by interventional cardiologists and cardiac surgeons performing procedures in hybrid operating rooms or cardiac catheterization labs. 
     In a more particular example, applications of this disclosure can include aspiration of blood clots from the pulmonary arteries in cases of pulmonary embolism. With the direct cardioscopy of this disclosure, the clot is identified in the pulmonary artery and then directly aspirated via a main lumen. This would allow a much more elegant, less expensive, less invasive, more expedited, and more thorough treatment of pulmonary embolism. Another application of the cardioscopy would include direct visualization of the endocardial surface during catheter ablation of either atrial fibrillation or ventricular tachycardia. Direct visualization would reduce risk of spontaneous and potentially very hazardous perforations that still occur during current fluoroscopic and echocardiographic guidance. It would also potentially improve the actual effectiveness of the ablation procedure due to a better and more precise localization of the catheter on the endocardial surface. Another application would include cardioscopic ferrofluid-guidance during placement of the miniaturized leadless pacemaker, which is currently placed under fluoroscopic guidance. Ferrofluid-guided cardioscopy would assist in a more precise and a less traumatic placement of the pacemaker device and potentially would reduce its future dislodgement or interaction with intracardiac structures such as valve or chordal tissue. 
     Other potential applications lie in the directly visualized endomyocardial biopsy of the right ventricle in the heart transplant patients. Having the means of directly visualized biopsies via this disclosure would obviate tricuspid valve injury. 
     Further applications include directly visualized biopsy capabilities of the entire spectrum of the right sided and left sided cardiac lesions—whether those are endocarditis vegetations or cardiac tumors. Also, ferrofluid cardioscopy would allow one to assist an interventionalist in deployment of numerous intracardiac devices, such as an Amplatzer device for ASD closure, Watchman device for the left atrial appendage occlusion, annuloplasty device on the tricuspid valve, MitraClip deployment on the mitral leaflets or Neochord placement on a flail mitral leaflet, as well as stent graft placement in the aorta, and so on. A robust ferrofluid cardioscopy device would enable numerous further developments of intracardiac interventions on a beating heart and blood vessels. The field of ferrofluid cardioscopy, in and of itself, is a completely unchartered territory with a practically unlimited spectrum of clinical applications. 
     In case of MitraClip deployment, one would have a much easier and quicker way to perform the transseptal puncture and to position the clip on the mitral leaflets. With the help of spherical fluid around the tip of the catheter providing direct visualization one would identify foramen ovale anatomy much more precise and quicker. One would assess the anatomy of anterior and posterior leaflets directly, one would identify the ruptured chords or other pathology, and one would much better identify the best location for the most successful placement of the MitraClip. This would obviate the need for a lengthy and frustrating guidance by the TEE and fluoroscopy and would significantly shorten procedural time while allowing a much easier and more satisfying placement of the device on the leaflets resulting in a much more durable and effective treatment. 
     A direct cardioscopy platform such as the one described herein would allow a much more precise placement of the annuloplasty ring and would ensure a higher success, shorter procedure time, and less injury of the neighboring structures. Overall, the benefit of a direct visualization during deployment of the intracardiac or intravascular devices is multifaceted and difficult to quantify. 
     With the present disclosure, the patient benefit lies in the less invasive approach, since open heart surgery is very invasive and carries significant associated morbidity and mortality. If there is a way to remove a clot from the pulmonary artery without opening the sternum and being placed on the heart lung machine, every patient would sign up for it. The clinician benefit lies in a more expedited, less invasive aspiration of the clot. Potentially, with the established technology, the ferrofluid cardioscopy procedure could be performed at the bedside, just like bronchoscopy or some other endoscopic procedure. The payer benefit of this disclosure lies in the less expensive treatment (both surgery and catheter-based thrombolysis or Vortex procedure need to be done in either an operating room or in an angio suite) and shorter hospital stay. With the direct ferrofluid cardioscopic aspiration of the clot, the procedure could potentially be done at the bedside and would involve only a percutaneous access via the femoral vein. Overall, percutaneous embolectomy by means of ferrofluid cardioscopy would be a significantly more elegant solution than currently existing alternatives. 
     Referring to  FIG. 1 , an exemplary schematic of a probe  100  is illustrated. The probe  100  of  FIG. 1  is illustrated in a configuration that is optimized for use in imaging from an end surface of the probe. The probe  100  includes a channel  110 . The probe  100  can be flexible. A container  105  contains a ferrofluid to be introduced and removed via the channel  110 . The probe  100  includes a ferrofluid attractor  120  at a distal portion of the probe  100 . The ferrofluid emerges from a distal port  130  or distal opening  130  located at a distal portion of the probe  100 . When introduced via the channel  110  and the distal port  130 , the ferrofluid forms a ferrofluidic cloud  140  due to being attracted by the ferrofluid attractor  120 . The probe  100  is illustrated engaging a target  150  that will be imaged. The probe  100  includes an optional working channel  170 , through which a medical device and/or apparatus can be introduced to the target  150 . The probe  100  includes an optical waveguide  160  for coupling light to and from the target  150 . In use, the ferrofluidic cloud  140  displaces surrounding biological fluid  180 , thereby providing a medium of generally known optical properties (i.e., the ferrofluid) between the optical waveguide  160  and the target  150 . A spectroscopic imaging device  190  is optically coupled to the optical waveguide  160  and is configured to acquire a spectroscopic image of the target  150  through the ferrofluidic cloud  140 . 
     The channel  110  can have a proximal port (not illustrated) positioned at a proximal portion of the probe. The channel  110 , the proximal port, and the distal port  130  can have size dimensions that allow the ferrofluid to enter the channel via the proximal port, move along the channel  110 , and exit the channel  110  via the distal port  130  when the ferrofluid is introduced at a predefined pressure. The size dimensions also allow the opposite motion when suction is introduced to the proximal port at a predefined negative pressure. The channel  110  has an interior surface that can be a material that is chemically and magnetically inert to the ferrofluid. 
     The ferrofluid attractor  120  can attract the ferrofluid based on magnetic properties of the ferrofluidic attractor  120  and the ferrofluid, and can be implemented using various different materials that have various different magnetic properties. For example, the ferrofluid attractor  120  can include a permanent magnet component. In a more particular example, the ferrofluid attractor  120  can be a neodymium iron boron permanent magnet, a samarium cobalt permanent magnet, an alnico permanent magnet, a ceramic permanent magnet, and/or a ferrite permanent magnet. The ferrofluid attractor  120  can be a printed 3D magnet that is printed by a magnet 3D printer to more precisely control the position of the dipoles. As another example, the ferrofluid attractor  120  can include an electromagnet component. As yet another example, the ferrofluid attractor  120  can include a ferromagnetic (which may be generally unmagnetized), that has a magnetic susceptibility sufficient to magnetically attract a ferrofluid having a persisting ferromagnetism. A variety of different coatings can be used in connection with the ferrofluidic attractor  120 , such as nickel, gold, chrome, copper, epoxy resin, zinc, Teflon, silver, etc., to prevent undesirable chemical interactions between the ferrofluidic attractor  120  and biological fluid  180  (or other components of the probe  100 ). The ferrofluid attractor  120  can be a single component (e.g., a single permanent magnet, a single electromagnet, a single ferromagnetic (but unmagnetized) component, etc.). In such an example, the ferrofluid attractor  120  can be monolithic. Alternatively, the ferrofluid attractor  120  can include multiple attractor components. For example, the ferrofluid attractor  120  can include a permanent magnet, and an electromagnet. As another example, the ferrofluid attractor  120  can include multiple permanent magnets that are arranged to provide a particular magnetic field strength and/or shape. 
     One or more magnetic properties of the ferrofluid attractor  120  can be tuned to be control how strongly the ferrofluid is magnetically attracted to the ferrofluid attractor  120 . For example, the magnetism can be tuned to be strong enough to retain the ferrofluidic cloud  140  in a stable orientation despite the movement of surrounding fluid, such as the pumping of blood through a blood vessel. In a more particular example, the ferrofluid attractor  120  can be configured to transition between a state of relatively high magnetism and a state of low relatively low (or no) magnetism. For example, a magnet of the ferrofluid attractor  120  can be coupled to an actuator that is configured to move the magnet closer to, and farther from, the distal port(s)  130  and/or a surface of the probe  100 , altering the magnetic field strength outside of probe  100 . As another example, a magnetic component of the ferrofluid attractor  120  can be configured to have an adjustable magnetic field strength. In a more particular example, when a component of the ferrofluid attractor  120  is implemented as an electromagnet, a magnetic field strength can be controlled based on the amount of current passed through the electromagnet, based on a position of a core material (e.g., a ferromagnetic core) within a coil of the electromagnet, etc. Additionally or alternatively, 
     The ferrofluid attractor  120  can be modified to alter a shape of the magnetic field. For example, in the case of a toroidal-shaped magnet, the corners of the top of the magnet (i.e., the portion of the magnet closest to the distal port  130  can be covered by a material that reduces the magnetic attraction in that region, forcing the ferrofluid cloud toward the center axis of the probe  100  in a region of relatively less dense magnetic field lines. This is merely an example, and a similar technique can be utilized with differently shaped and sized magnets to alter the shape of the magnetic field of the ferrofluid attractor  120  and influencing the shape of the ferrofluidic cloud  140 . Additionally, cohesion of the ferrofluidic cloud  140  with the surrounding biological fluid  180  can be used to collect the ferrofluid cloud  140  more densely at the center axis of the probe  100 . The ferrofluid attractor  120  can extend beyond the probe  100  circumferentially to stabilize and concentrate the ferrofluidic cloud  140 , while leaving an opening that still maintains the ability to direct light forward and/or to the side and utilize tools or suction. The ferrofluid attractor  120  can have an oscillating magnetic field direction, which can control a net movement of the ferrofluid in a manner that resists dissipation into flowing of the biological fluid  180  (e.g., blood and/or other solutions around the ferrofluid cloud  140 ). For example, a permanent magnet can be physically rotated to cause net movement of the ferrofluid cloud  140  which can be controlled based on the rotation of the permanent magnet. As another example, oscillation of the current through an electromagnet can cause net movement of the ferrofluid cloud  140  which can be controlled based on the frequency, amplitude, and/or magnitude of the current signal. 
     The target  150  can be an intracardiac structure, a blood vessel wall, cardiovascular tissue, skin, gastrointestinal tissue, lung tissue, brain tissue, urologic tissue, gynecologic tissue, a thrombus, cardiac vegetation, a certain pathology of interest, a foreign body, a medical device, or the like. 
     The working channel  170  can be configured to receive a medical instrument or other device for delivery to the distal portion of the probe  100 . The medical instrument or other device can be a suction catheter, biopsy forceps, a clip, a stent, a blood clot retrieval basket, a tissue ablator, a hook, an ablation catheter, a retrieval basket, a brush, a fixation device (e.g., a screw), an annuloplasty device or the like, a small leadless catheter, or a combination thereof. 
     The present disclosure also provides catheters. The catheter can include a probe (e.g., the probe  100 ) as described herein and a sheath configured to receive the probe. The catheter can be of various diameters for different applications. The catheter can be an angioscope, cardioscope, endoscope, cardioscopic catheter, nasogastric tube, any laparoscopic imaging device, etc. 
     The present disclosure also provides optical imaging systems. The optical imaging systems can include an optical imaging light source, an optical imaging detector, a probe (e.g., the probe  100 ) as described herein, an optical circulator, and an optical imaging controller. The optical circulator is coupled to the optical imaging light source, the optical imaging detector, and an optical waveguide (e.g., the optical waveguide  160 ). The optical circulator can be configured to direct light from the optical imaging light source to the optical waveguide and from the optical waveguide to the optical imaging detector. The optical imaging controller can be coupled to the optical imaging detector and configured to provide an optical imaging signal output representative of an optical signal measured at the optical imaging detector. The optical imaging system can be a fluorescence, autofluorescence, Raman, OCT, SECM, or other spectroscopic imaging system. The optical light source and optical detector can be chosen for the appropriate type of spectroscopic imaging. 
     The present disclosure also provides OCT systems. The OCT systems includes an OCT light source, an OCT detector, a probe (e.g., the probe  100 ) as described herein, an optical circulator, and an OCT controller. The circulator is coupled to the OCT light source, the OCT detector, and an optical waveguide (e.g., the optical waveguide  160 ). The optical circulator can be configured to direct light from the OCT light source to the optical waveguide and from the optical waveguide to the OCT detector. The OCT controller can be coupled to the OCT detector and configured to provide an OCT signal output representative of an optical signal measured at the OCT detector. The OCT light source can be a broadband light source. 
     The present disclosure also provides ferrofluids for use in connection with the probes and systems described herein. The ferrofluids can be used for direct visualization medical imaging of an internal structure. The ferrofluids can include ferromagnetic particles (e.g., iron particles) and a biologically inert carrier fluid. Ferromagnetic particles present in an amount of 0.1 mg Fe/ml or less to as high as 100 mg Fe/ml is conceivable. Also, dosages ranging from less than 0.2 mg Fe/kg to as high as a single dose of 1000 mg Fe is conceivable. Specific dosage and concentration may vary based on the desired application and imaging device. Also, the ferromagnetic particle content (e.g., iron content) may be able to be higher, as limited by toxicity of the specific ferrofluid in the human body. 
     The ferromagnetic particles can include a coating. There are a wide range of conceivable coatings, and the specific coating may vary based on the specific application and imaging device. Possible carbohydrate coatings include dextran, galactose, mannose, glucose, ethylene glycol, citrate, fucose, carboxymaltose, carboxydextran, polyethylene glycol, carboxy-methyldextran, arabinogalactan, and poly-styrene, and the like. Other coatings include hydroxyphosphonate, folate, sodium ferric gluconate, silica, carboxylates, polyamidoamine, lipid bilayers, curcumin, hydrophilic polymers, hydrophobic polymers, polymers that are neither hydrophobic nor hydrophilic, amphiphilic ligands, and additional bound proteins that can be single amino acids or chains of amino acids, etc. Coatings with a range in weight from 1 kilodalton (kD) to 2000 kD are conceivable. Dextran, which is often used as a ferromagnetic nanoparticle coating, ranges from 3 to 2000 kD. 
     The ferromagnetic particles can be of a size that substantially reduces the amount of light that is scattered by the ferromagnetic particles. The ideal ferromagnetic particle size will differ on the application and the light based imaging device. For example, depending on the resolution or wavelength utilized in the light-based imaging device, different particles sizes will scatter more or less light. Particle coatings ranging from 6 to 100,000 nm is conceivable. Further, the use of superparamagnetic iron oxide particles (SPIO) which range from 100 to 200 nm, ultrasmall superparamagnetic iron oxide particles (USPIO) which are less than 50 nm, and micron sized particles of iron oxide (MPIO) which are greater than 1000 nm, are all conceivable. 
     The ferrofluid can include a viscosity enhancing agent. The viscosity enhancing agent can be present in as little as 1% or less of the solution, or as much as the saturation point of the solution. For example, for dextran the saturation point occurs roughly when the ratio of dextran to water is 2:1. Besides dextran, other viscosity enhancing agents can include any agent that is both water-soluble and non-toxic. Examples of which can include other polysaccharides or oligosaccharides, such as starch, glycogen, callose, chyrsolaminarin, xylan, arabinoxylan, mannan, fucoidan, hydroxyethyl cellulose, and galactomannan. In addition, biocompatible oils can be used as a viscosity enhancing agent for some clinical applications. 
     Ferrofluid with a viscosity between 0.089 centipoise (cP) to 10,000 cP is conceivable. In certain applications, the viscosity can be between 3 to 10 cP, which is near the viscosity of blood. 
     The ferrofluid can be substantially transparent. The ferrofluid can have an average optical absorbance greater than water and less than blood for at least one wavelength between 400 and 1400 nm. The specific wavelength and transparency can vary based on the clinical application and imaging device, and can be related to the concentration and type of ferrofluid used. 
     The biologically inert carrier fluid can be water, which can act as a solvent for the ferromagnetic particles and/or viscosity enhancing agent. Alternatively, the biologically inert carrier fluid can be a buffer solution, such as a phosphate buffered saline (PBS) buffer, which can act as a solvent for the ferromagnetic particles and/or viscosity enhancing agent. 
     The present disclosure also provides a method of acquiring a direct visualization medical image of an internal structure. The method includes: a) introducing a ferrofluid into an area near the internal structure, thereby displacing a biological fluid within the area; b) acquiring the direct visualization medical image of the internal structure through the ferrofluid. The method can also include, prior to the acquiring of step b), contacting the internal structure with the ferrofluid. The internal structure can be any of the targets  150  described above. The introducing of step a) can be done via the channel  110  of the probe  100 . The acquiring of step b) can be done via the optical waveguide  160  of the probe  100  and/or using the optical imaging system or OCT imaging system described herein. The contacting the internal structure with the ferrofluid can be achieved by moving the ferrofluid attractor  120  or by moving a distal tip or distal portion of the probe  100 . 
     The systems, probes  100 , and methods described herein can be used for any processes utilizing catheters, including flexible catheters. Such processes include in vivo imaging, such as in vivo cardiology or gastrointestinal tract imaging. 
     Referring to  FIG. 2 , an exemplary schematic of a probe  100  is illustrated. The probe  100  of  FIG. 2  is illustrated in a configuration that is optimized for use in imaging circumferentially relative to the probe  100 . The probe  100  includes a channel  110 . The probe  100  includes a ferrofluid attractor  120  at a distal portion of the probe  100 . The ferrofluid attractor  120  is arranged circumferentially relative to the distal portion of the probe  100  in order to retain the ferrofluid in a suitable location for circumferential imaging. Note that the configuration of the ferrofluid attractor  120  is merely an example, and the ferrofluid attractor  120  can be configured to have various other forms (e.g., as described below in connection with  FIGS. 14A to 141, 15A to 15E, and 16A ). The probe  100  includes two or more distal ports  130  in fluid communication with the channel  110 . When introduced via the channel  110  and the two or more distal ports  130 , the ferrofluid forms a ferrofluidic cloud  140  or multiple ferrofluidic clouds  140  due to being attracted by the ferrofluid attractor  120 . The probe  100  is illustrated within a target  150  that is tubular in shape, such as a blood vessel. The probe  100  includes an optical waveguide  160  and an optional imaging optic  175  for coupling light  185  to the target  150 . The light  185  is transmitted through the ferrofluidic cloud  140  to irradiate the target  150 . Light returning from the target  150  traversed the ferrofluidic cloud  140  and is collected by the optical waveguide  160  or the optional imaging optic  175 . The probe  100  can include a driveshaft  195  that is used to rotate the optical waveguide  160  and/or the optional imaging optic  175  to rotate the light  185  to provide circumferential irradiation to a substantially tubular target  150  and to acquire light returning in the same fashion. In some cases, the driveshaft  195  is excluded and the optional imaging optic  175  rotates via a motor located adjacent to the optional imaging optic  175 . 
     The optical waveguide  160  can be an optical fiber, for example coupled to a laser emitting diode or other light source. The optical fiber can be a single-mode fiber. The optical fiber can be a double clad optical fiber. The optical waveguide  160  can serve as a sample arm for an OCT system. 
     The imaging optic  175  can be a lens, a reflector, other optics known to those having ordinary skill in the art to be useful for coupling light for the purposes of imaging, or combinations thereof. In some cases, the lens can be a ball lens, a spherical lens, an aspherical lens, a graded index (GRIN) fiber lens, an axicon, a diffractive lens, a meta lens, lensing with phase manipulation, or the like. 
     The driveshaft  195  can be coupled to the optical waveguide  160 , the imaging optic  175 , including a lens and/or a reflector, or a combination thereof. 
     The probe  100  can include a pump (not illustrated) for providing positive pressure to the ferrofluid when introducing the ferrofluid to the target and/or for providing negative pressure to remove the ferrofluid from the target. 
     Referring to  FIG. 3 , one specific use of the probe  100  described above is illustrated. Specifically, the probe  100  is illustrated as being used to extract a blood clot from the pulmonary artery. As shown in  FIG. 3 , a flexible probe cardioscope  210  is inserted through the heart  200  into the pulmonary artery  220 . The ferrofluid  230  (the extent of which is indicated by a dashed line) is transmitted at the tip of the cardioscope  210  and held into place by a magnet at the tip of the cardioscope  210  in a position where blood is displaced from the field of view of the imaging apparatus of the cardioscope  210 . In the illustrated case, the cardioscope  210  is directed to a blood clot  240  within the pulmonary artery  220 . An instrument such as a retrieval basket or a suction catheter can be inserted via the optional working channel  170  described above and can be used to remove the blood clot  240 . 
     Referring to  FIG. 4 , another specific use of the probe  100  described above is illustrated. Specifically, the probe  100  is illustrated as being used to visualize and biopsy an endocardial surface. Referring to  FIG. 4 , a flexible probe cardioscope  310  is inserted through a tricuspid valve  320  of the heart  400 . The tip of the cardioscope  310  is inserted into the right ventricle  330  in order to visualize the endocardial surface  340  for biopsy. The ferrofluid  350  is introduced from the tip of the cardioscope  310  and forms a cloud between the catheter and the cardiovascular structure, thereby displacing blood between the cardioscope  310  and the endocardial surface  340 . Once a visual image is established, biopsy forceps  360  are introduced via the working channel  170  of the catheter  310  and are used to collect the tissue of the right ventricular wall  340  under direct visualization. 
     Referring to  FIG. 9A , yet another schematic of a probe is shown. The probe of  FIG. 9A  is configured for circumferential imaging. An optical fiber  901  is housed in a drive shaft  904  which emits a beam  903  that rotates to acquire circumferential images. The beam  903  is emitted through a transmission gap  907  that lies between two magnets  906 . The ferrofluid can be injected through a channel  905 . Once injected, the ferrofluid would concentrate around the magnets  906  to displace surrounding fluid (e.g., blood). In the probe of  FIG. 9A , a housing  902  can enclose magnets  906 , and at least a portion of driveshaft  904 . For example, housing  902  can be a catheter, or a capsule. 
     Referring to  FIG. 9B , still another schematic of a probe is shown. The probe of  FIG. 9B  is configured for circumferential imaging, and is similar in some aspects to the probe of  FIG. 9A  in that the optical fiber  901  is housed in the drive shaft  904  which emits a beam  903  that rotates to acquire circumferential images, and the beam  903  is emitted through a transmission gap  907  that lies between two magnets  906 . However, in the probe of  FIG. 9B , the ferrofluid can be injected through a sheath  908  surrounding housing  902 , and can flow out of sheath  908  via one or more openings  909 . Once injected, the ferrofluid can concentrate around the magnets  906  to displace surrounding fluid (e.g., blood). 
     Referring to FIGS.  10 A 1  to  10 B 3 , various schematics of probes are shown. FIG.  10 A 1  shows a catheter  1000  with an uninflated balloon  1010  at a distal end and forward-facing imaging tip  1020 . FIG.  10 A 2  shows the balloon  110  inflated with iron particles  1030  in order to create a magnetic field at the tip of the catheter. For example, iron particles  1030  can be included in a ferrofluid, which can be the same ferrofluid that is used to produce a ferrofluid cloud, or a ferrofluid having different properties (e.g., a different concentration of particles, a different solvent, etc.). FIG.  10 A 3  shows a ferrofluid cloud  1040  that is injected outside of the catheter  1000  so that the particles concentrate around the magnetized balloon  1010 . The ferrofluid cloud  1040  displaces surrounding biological fluid (e.g., blood) allowing light  1050  to be transmitted more easily toward a sample. FIG.  10 B 1  shows another catheter  1001  which includes two uninflated balloons  1060  on either side of a side viewing imaging tip  1070 . FIG.  10 B 2  shows the balloons  1060  inflated with iron particles  1080  to create and/or augment a magnetic field at the tip of the catheter. FIG.  10 B 3  shows a ferrofluid cloud  1090  surrounding the magnetized balloons  1060 . The ferrofluid cloud  1090  displaces surrounding biological fluid (e.g., blood) allowing light  1091  to be transmitted more easily toward a sample. The probe of FIGS.  10 B 1  to  10 B 3  can, for example, be used in connection with transcatheter procedures that involve navigation of the catheter through smaller vessels to reach a desired region in the heart. 
     Referring to  FIGS. 11A and 11B , additional schematics of probe are shown.  FIG. 11A  shows a catheter  1100  which includes a transparent outer sheath  1110  that extends beyond an imaging tip  1120  to allow for displacement of biological fluid (e.g. blood) and visualization.  FIG. 11B  shows the sheath  1110  being retracted from the tip. A ferrofluid cloud  1150  is shown concentrated around a magnetic tip  1170  of the catheter  1100 . The ferrofluid cloud  1150  is able to displace the biological fluid (e.g., blood) previously displaced by the transparent sheath  1110 . A bioptome  1160  is shown extending within the ferrofluid cloud  1150 . The probe of  FIGS. 11A and 11B  can, for example, be used in connection with applications that involve navigating through regions of the heart with higher flow rates, as the probe of  FIGS. 11A and 11B  can facilitate direct visualization and the ability to work through the ferrofluid cloud in such an environment. Sheath  1110  can be deaired and/or flushed (e.g., with saline) prior to being inserted into a subject&#39;s cardiovascular system. 
     Referring to  FIG. 12  a cross-section of a probe.  FIG. 12  shows a probe  1200  that includes a ring magnet  1260  which can be magnetized through the diameter or thickness, or can include multiple arc segments (e.g., as described below in connection with  FIGS. 14A to 14G ) or multiple concentric rings (e.g., as described below in connection with  FIGS. 14H and 14I ). In the center of the magnets are three channels  1210 ,  1220 , and  1230 . The smaller channel  1210  can allow for ferrofluid injection, while channel  1220  can be a working channel that allows for insertion of instrumentation. The channel  1230  can include imaging components, which can include, for example, four multimode fiber bundles  1240  that can be used to illuminate a target and an optical sensor  1250 . Note that this is merely an example, and other combination of optics can be used, such as optics described above in connection with  FIGS. 1 and 2 . 
     Referring to  FIGS. 14A to 14I , cross-sections of various magnet configurations are shown.  FIG. 14A  shows a radial ring magnet that includes four arc magnets where north is on the outside and south is on the inside of each arc magnet.  FIG. 14B  shows four arc magnets where two are magnets are magnetized through the diameter and two are magnetized through the thickness (i.e., the two arc magnets shown as having the south pole exposed are magnetized through the thickness, such that the poles are aligned with the axial direction).  FIG. 14C  shows two arc magnets magnetized through the diameter with two rod magnets between them with south on the tip that is shown (i.e., the poles are aligned with the axial direction).  FIGS. 14D, 14E, and 14F  each show four arc magnets magnetized through the diameter with rod magnets (in  14 D), rectangular magnets (in  14 E), and pyramid magnets (in  14 F) disposed between the ends of the arc magnets.  FIG. 14G  shows 8 arc magnets where four are magnetized through the diameter and four are magnetized through the thickness.  FIG. 14H  shows a radial ring inside a ring magnet that is magnetized through the thickness (i.e., the outer ring is magnetized such that the poles are aligned with the axial direction).  FIG. 14I  shows a ring magnet magnetized through the thickness with a radial ring magnet on the outside. 
     Referring to  FIGS. 15A to 15E  are additional examples of magnet configurations.  FIG. 15A  shows two ring magnets stacked, in which an imaging device can be inserted through the center of the ring magnets. For  FIG. 15A , one magnet is magnetized radially while one magnet is magnetized through the thickness. For example, the radially magnetized ring magnet can be closer to the distal end of the probe (e.g., probe  100 ), while the axially magnetized ring magnet is farther from the distal end of the probe.  FIG. 15B  shows a similar configuration to  FIG. 15A  with the magnet order is reversed.  FIG. 15C  shows a funnel shaped configuration that includes two magnets, with an inner magnet radially magnetized, and an outer magnet axially magnetized through the thickness. In the configuration shown in  FIG. 15C  an imaging device can be inserted so that either the larger diameter end or the shorter diameter end of the funnel-shaped magnet can be closer to the distal end of the probe. FIG.  15 D 1  shows another magnet variation where radially magnetized magnets and magnets magnetized through the thickness are stacked along a length of the imaging device to increase the strength of the magnetic field at the tip of the device (e.g., the tip of the probe  100 ). Note that in addition to the configuration shown in FIG.  15 D 1  the magnets can be configured with various magnetizations. For example, all of the magnets in FIG.  15 D 1  can be radially magnetized or all the magnets can be magnetized through the thickness. FIG.  15 D 2  shows the magnet configuration in FIG.  15 D 1  arranged in a manner that facilitates bending of the imaging device (e.g., a catheter) along the length of the stacked the magnets, which can allow the number of magnets surrounding the tip of the probe to be increased, which can increase the magnetic field strength, while still allowing the device to bend. Configurations show in  FIGS. 15A to 15E  can augment the shape of the ferrofluid cloud to cause the cloud to extend more from the tip of the probe, rather than forming a sphere centered on the ferrofluidic attractor. 
     Referring to  FIG. 16A , various magnet configurations and magnetic flux models are shown demonstrating a variety of potential magnet orientations, and  FIG. 16B  shows a depiction of flux density for each of the configurations in  FIG. 16B  as a function of distance from a tip of the probe extending toward a target. Configuration  1610  includes a radially polarized ring magnet with the north pole facing the inner diameter, and generates moderate magnetic flux (i.e., about 0.3 tesla (T) at the tip) that falls as the distance from the probe increases. Configuration  1620  includes four arcs polarized diametrically and encased by a stainless steel ring (note that this is a similar configuration to that depicted in  FIG. 13 ), and generates less flux density at the tip (i.e. about 0.2 T at the tip). Configuration  1630  includes a cone magnet polarized axially, and generates even less flux density at the tip (i.e., less than 0.1 T). Configuration  1640  includes four axially polarized ring magnets and six arc magnets that are polarized diametrically and encased by a brass ring (e.g., note that this is a similar configuration to that depicted in  FIG. 24 ), and generates higher flux close to the probe (i.e., about 0.36 T) that drops off relatively quickly. Configuration  1650  includes an axially polarized ring and a similarly-sized radially polarized ring nearer the distal end, and generates slightly denser flux along the entire profile than the configuration  1610  despite having similar radial dimensions and being shorter in the axial direction. Configuration  1670  includes an axially polarized ring magnet, and a radially polarized ring magnet nearer the distal end with both having a smaller inner diameter than the magnets shown in configurations  1610  and  1650 . The configuration  1660  generates relatively higher density flux at the distal tip of the probe (i.e., about 0.59 T) and along the entire profile. The configuration  1670  is similar to the configuration  1660 , but the axially polarized ring magnet is longer along the axial direction, and generates higher flux density near the tip (i.e., about 0.61 T) and along the entire profile than the configuration  1660 . As shown in  FIGS. 16A and 16B , combinations of axially and radially magnetized magnets can generate higher flux both close to and farther away from the probe than magnets having a single magnetization direction. 
     Referring to  FIG. 17 , a magnetic flux model corresponding to the configuration  1670  is shown. As described above, in the configuration  1670  two ring magnets are stacked, and a probe that includes channels for imaging, instrumentation, and/or in administration of ferrofluid can be inserted through the middle of the magnets. The distal magnet (the top magnet in  FIG. 17 ) is magnetized radially with the north pole facing the inner diameter while the bottom magnet is magnetized axially through the thickness of the magnet with the north pole facing the distal tip and the radially magnetized ring magnet. The flux model shown in  FIG. 17  is based on configuration  1670  with both magnets having an inner diameters of 4 mm and an outer diameters of 8 mm, the top magnet having an axial length of 4 mm, and the bottom magnet having an axial length of 8 mm. The flux density model shows a cross sectional cut through the center and gives indications of the shape and extent of ferrofluid cloud. Note that this is merely a particular example, and magnets having other dimensions can be used. For example, the magnet dimensions can be configured based on constraints on the probe, such as size and materials. 
     EXAMPLES 
     The following examples set forth, in detail, ways in which the optical systems and/or the probes (e.g., the probe  100 , the probes depicted in  FIGS. 9A, 9B ,  10 A 1  to  10 B 1 ,  11 A,  11 B,  12 ,  13 , etc.), and/or the ferrofluid can be used or implemented, and will enable one of skill in the art to more readily understand the principles thereof. The following examples are presented by way of illustration and are not meant to be limiting in any way. Among other things, example 1 demonstrates that light can be transmitted through the ferrofluid; example 2 demonstrates that the ferrofluid can be concentrated using a magnetic field to form a ferrofluid cloud; example 3 demonstrates that the ferrofluid can displace blood; example 4 demonstrates that a ferrofluid cloud can displace blood and facilitate imaging (e.g., OCT imaging) of a target previously at least partially occluded by the blood; example 5 demonstrates an implementation of a scope that can be used in connection with ferrofluid imaging; example 6 demonstrates that light with a peak at about 775 nm can be transmitted through a ferrofluid that includes Feraheme; example 7 demonstrates that modifications of ferrofluid properties can impact how the ferrofluid affects light transmitted through the ferrofluid; example 8 demonstrates images captured using 400-1000 nm light and a Feraheme-based ferrofluid cloud in a blood-filled cavity; example 9 demonstrates images captured with and without a Feraheme-based ferrofluid cloud in an environment that simulates conditions in the right side of the heart using a pulsatile pump; example 10 demonstrates ferrofluid guided imaging used to directly visualization structures inside the right side of a blood-filled (non-beating) sheep heart; example 11 demonstrates of an instrument inserted through a ferrofluid cloud to biopsy tissue being imaged; example 12 demonstrates a probe inserted into a environment used to simulate conditions in the right side of the heart; example 13 demonstrates an example of a cardioscope that can be used for forward-facing ferrofluid imaging; example 14 demonstrates an example of an OCT probe that can be used for circumferential ferrofluid imaging; and example 15 demonstrates images captured through a Feraheme-based ferrofluid using OCT imaging techniques in a simulated coronary artery with constant blood flow. 
     Example 1 
     An exemplary ferrofluid for cardioscopy was prepared by mixing dextran-coated ferromagnetic particles having a mean diameter of 9 nm into PBS to provide a suspension. The average molecular weight of the dextran coating on the ferromagnetic particles was 40 kD.  FIG. 5  shows the optical absorbance spectrum of this ferrofluid acquired using a 1-cm path length cuvette against an aqueous reference. The concentration of ferromagnetic nanoparticles in the solution was 0.8 mg/mL. The spectrum indicates a strong optical absorption below 600 nm due to the large absorption coefficient of the ferromagnetic nanoparticles. The spectrum also shows high optical transmission from 650 nm to 1400 nm, which can be used as an optical window to visualize an internal structure, as described elsewhere herein. 
     Example 2 
     The ferrofluid of Example 1 was introduced via an optical probe having features described elsewhere herein into a PBS solution. Referring to  FIG. 6 , a photograph of a stable ferrofluid cloud  500  (the extent of which is indicated with a dashed line) formed around the base of an optical probe  510  placed in a PBS solution  520  is shown. A toroidal-shaped neodymium magnet  530 , also referred to as a NdFeB magnet, was positioned at the base of the probe to generate the magnetic field that confines the ferromagnetic nanoparticles producing a roughly spherical cloud  500  having an approximate viewing depth of 3 mm beneath the optical probe. The magnet had an outer diameter of 4.67 mm and a length of 4.63 mm, thus providing the viewing depth of 3 mm. 
     Example 3 
     A ferrofluid having 40 kD dextran coated ferromagnetic nanoparticles in an amount of 0.4% (w/w) suspended in a 5% aqueous dextran solution was prepared and introduced into a blood sample via an optical probe having features described elsewhere herein. Referring to  FIG. 7 , a photograph shows a stable ferrofluid cloud  600  formed around an optical probe  610  in a whole blood  620  sample. At the distal tip of the optical probe  610 , a toroidal NdFeB magnet  630  was positioned to generate the magnetic field. As the ferrofluid solution was delivered to the base of the magnet  630 , the ferromagnetic particles were trapped by the strong magnetic field and displaced the surrounding whole blood  620 , thereby creating an optical window  600  around the probe  610 . The ferrofluid window  600  appears as a dark ring next to the probe  610  and NdFeB magnet  630 . The addition of dextran assisted in the ability of the ferrofluid cloud  600  to displace the whole blood  620  and persist for several minutes. 
     Example 4 
     Referring to  FIGS. 8A to 8C , a series of OCT images were collected from a probe, such as the probe  100  described above. OCT was conducted using light centered at 1310 nm with a 100 nm bandwidth. The OCT probe was fixed in space and did not scan. The vertical axis represents optical depth from the probe and the horizontal axis represents the time in which successive acquisitions of the OCT signal were recorded and processed into depth-resolved reflectivity profiles. Short horizontal lines in the images indicate particles that diffused into and out of the OCT beam while long horizontal lines indicate reflections from stationary structures. Referring to  FIG. 8A , an image of a stationary nylon target  700  imaged through saline  710  is shown. The presence of inclusions within the nylon target  700  is shown below a target interface  720  between the saline  710  and the nylon target  700 . Referring to  FIG. 8B , an image of the same stationary nylon target is shown imaged through heparinized whole blood  730  without a ferrofluid cloud. Strong scattering from the red blood cells and hematocrit in the whole blood obscure the target interface and significantly limit visibility. Referring to  FIG. 8C , an image of the same stationary nylon target in whole blood is shown imaged through a ferrofluid cloud  750  introduced into the whole blood. The target interface  720  is much more clearly visible when the ferrofluid cloud  750  is used. The ferrofluid cloud  750  remained stable for several minutes. The ferrofluid used in  FIG. 8C  is the ferrofluid of Example 3. 
     Example 5 
     Referring to  FIG. 13 , a photograph of a magnet on an Olympus GIF type XP160 Evis Exera Gastrointestinal videoscope  1300 . Surrounding the magnet is a thin stainless steel casing  1310 . There are four arc magnets  1320  which are radially magnetized through the diameter with south on the inner diameter allowing the field lines to congregate at the center. There is a thin layer of epoxy  1360  coating the lip between the stainless steel casing  1310  and the magnets  1320 . The scope includes a working channel  1330 , sensor  1340 , and light source  1350 . 
     Example 6 
     Referring to  FIG. 18 , optical absorbance spectra of Feraheme, a clinically approved ferrofluid, acquired using a 1-cm path length cuvette against an aqueous reference is shown. The absorbance of Feraheme at a clinical concentration of 30 mg Fe/mL, and diluted to 15, 7.5, and 3.75 mg Fe/mL is shown for light from 700 to 1350 nm. The results indicate that the absorbance has a minimum at around 775 nm in the range of wavelengths shown. This suggests that using a light source that extends beyond visible spectrum (400-750 nm) into the near-infrared may improve visualization through Feraheme. 
     Example 7 
     Referring to  FIG. 19 , the optical absorbance of Feraheme at 800 nm is shown with optical absorbance of a different non-clinical ferrofluid from Ferrotec. Absorbance is shown for the two ferrofluids at multiple iron concentrations. The results indicate that the non-clinical ferrofluid has a higher absorbance at 800 nm than Feraheme. When comparing the two ferrofluids, the size of the nanoparticles for the non-clinical ferrofluid were smaller than for the Feraheme. Also, the carbohydrate coating on the nanoparticles differed. Both ferrofluids were tested in a pulsatile pump, and the non-clinical ferrofluid maintained a shape of the ferrofluid cloud at larger flow rates and larger pressure than Feraheme at the same iron concentration. These result demonstrate that various properties of the ferrofluid affect the ability of the ferrofluid to transmit light and withstand flow (e.g., of blood). This also suggests that different ferrofluids can be used for different clinical applications when certain properties are desired. 
     Example 8 
     Referring to  FIG. 20A , a light spectrum is shown. The dashed line corresponds to conventional white light imaging (e.g., 400-750 nm light), and the solid line corresponds to the usage of a filter in the light source that results in imaging that incorporates the near-infrared in addition to visible light (e.g., 400-1000 nm). An image  2010  was acquired using 400-750 nm light to image sheep heart issue in a blood-filled cavity, while an image  2020  was acquired using 400-1000 nm light to image the sheep heart tissue at the same position. Image  2020  demonstrates that by incorporating near-infrared light, increased detail of the sheep heart tissue is discerned. Image  2020  demonstrates that different wavelengths of light can be used for different clinical applications through specific ferrofluids. 
     Example 9 
     Referring to  FIGS. 21A to 21D , a series of images recorded using the Olympus GIF type XP160 Evis Exera Gastrointestinal videoscope is shown (note that this corresponds to the probe described above in connection with  FIG. 13 ). The images were recorded in a pulsatile pump (e.g., as described below in connection with Example 12 and  FIG. 24 ) simulating the flow rates, pressure, and temperature of the right side of the heart at distance from the target of about 4 mm. Referring to  FIG. 21A , an image of a USAF Field target is shown through water. Referring to  FIG. 21B , an image of the same USAF Field Target is shown covered by blood in the absence of a ferrofluid cloud disallowing visualization by the videoscope. Referring to  FIG. 21C , an image of the same USAF Field target is shown in blood in the presence of a Feraheme cloud as described herein displacing the surrounding blood and allowing visualization of the target. The image in  FIG. 21C  was recorded using conventional white light imaging. Referring to  FIG. 21D , the same target is shown in blood displaced by Feraheme using white light and near-infrared imaging (400-1000 nm). The ferrofluid attractor was a radial ring magnet (e.g., as shown in  FIG. 13 ). These images demonstrate the ability of the clinically approved ferrofluid to displace blood in a pulsatile pump while allowing imaging through the ferrofluid cloud. 
     Example 10 
     Referring to  FIG. 22A and 22B , various still shots are shown of Feraheme imaging inside of a blood-filled sheep heart. The imaging demonstrates the ability of the ferrofluid guided imaging to allow for direct visualization of significant structures inside the major chambers of the heart. The same imaging system as described in Example 9 was used to capture the images. 
     Example 11 
     Referring to  FIG. 23 , a sequence of still shots are shown of Feraheme imaging inside a blood-filled sheep heart. A bioptome  2300  is shown protruding through the ferrofluid cloud and successfully collecting a tissue sample from within the heart guided by direct visualization. The images demonstrate the ability of the ferrofluid guided imaging to allow instrumentation through the cloud during direct visualization. The same imaging system as described in Example 9 was used. 
     Example 12 
     Referring to  FIG. 24 , a photograph demonstrating a pulsatile pump used to generate the images in  FIGS. 21A to 21D  is shown. The pulsatile pump simulates the flow rate, pressure, and temperature of the heart. The photograph shows the endoscope  2440  with a radial ring magnet  2400  attached. The ferrofluid cloud  2410  can be seen protruding past the endoscope and the light transmitting through the ferrofluid cloud  2410  can be identified. Below the scope is the USAF target  2420 . The photograph shows the flask  2450  filled with saline. The pump was filled with blood in order to test the ability of the ferrofluid to withstand various flow rates and pressure while still allowing visualization through blood. Images acquired when the pump was filled with blood and saline are described above in connection with  FIGS. 21A to 21D . 
     Example 13 
     Referring to  FIG. 25 , a photograph of a smaller probe using an Enable Imaging minnieScope-XS miniature videoscope  2500  is shown. The scope can be inserted through a polymer tubing with two channels. One channel includes the scope and the second channel  2540  allows ferrofluid injection or instrumentation. A combination of magnets surrounds the polymer tubing, and includes four ring magnets  2510  magnetized through the thickness with north on the distal end and six arc magnets  2520  which are magnetized through the diameter with north on the inner diameter. Surrounding the arc magnets is a thin brass encasing  2530 . This configuration can cause the magnetic field lines to aggregate near the center of the probe, and can cause the magnetic field lines to project forward. The scope  2500  itself includes optical fiber bundle waveguides  2550  for target illumination and a sensor  2560 . The outer diameter of the scope is 1.7 mm while the total diameter of the probe is 7 mm, which allows for navigation into smaller areas of inside the heart. 
     Example 14 
     Referring to  FIG. 26 , a photograph of a probe configured for circumferential imaging is shown. A drive shaft  2620  houses an optical fiber that emits a beam from a ball lens and through the two ring magnets  2610 . The drive shaft can be connected to a rotary junction using a connection  2640 . Together, the drive shaft  2620 , optical fiber, and ball lens can rotate 360 degrees to acquire circumferential images. Ferrofluid can be injected through an injection site  2630  to concentrate around the ring magnets  2610  and displace blood. 
     Example 15 
     Referring to  FIGS. 27A to 27E , a series of images recorded using an OCT probe for circumferential imaging (i.e., the system described above in connection with  FIG. 26 ) is shown. Circumferential OCT imaging was conducted using light centered at 1310 nm with a 100 nm bandwidth. The images were recorded with the probe inserted into a nylon tube to simulate a coronary artery and allowed for flow of various liquids. The nylon tube was imaged as the target at 1.5 mm and had a thickness of 0.7 mm. Referring to  FIG. 27A , a clear OCT image of the cross section of the nylon tube is shown through water. Referring to  FIG. 27B , the nylon tube was filled with blood at static conditions which disallowed visualization by the OCT probe. Referring to  FIG. 27C , an image of the nylon tube with blood at static conditions is shown with a Feraheme cloud displacing the surrounding blood and allowing clear visualization of the entire thickness of the target. Referring to  FIG. 27D , an image of the nylon tube is shown with continuous Feraheme injection and blood flow through the nylon tube simulating flow in the coronary artery. These images demonstrate the ability of clinically approved ferrofluid to displace blood in a stimulated artery with constant flow to allow circumferential imaging through the ferrofluid cloud. 
     Thus, while the invention has been described above in connection with particular embodiments and examples, the invention is not necessarily so limited, and that numerous other embodiments, examples, uses, modifications and departures from the embodiments, examples and uses are intended to be encompassed by the claims attached hereto. Indeed, the arrangements, systems, and methods according to the exemplary embodiments of the present disclosure can be used with and/or implemented any OCT system, OFDI system, SD-OCT system or other imaging systems capable of imaging in vivo or fresh tissues, and for example with those described in International Patent Application PCT/US2004/029148, filed Sep. 8, 2004 which published as International Patent Publication No. WO 2005/047813 on May 26, 2005, U.S. patent application Ser. No. 11/266,779, filed Nov. 2, 2005 which published as U.S. Patent Publication No. 2006/0093276 on May 4, 2006, and U.S. patent application Ser. No. 10/501,276, filed Jul. 9, 2004 which published as U.S. Patent Publication No. 2005/0018201 on Jan. 27, 2005, U.S. Patent Publication No. 2002/0122246, published on May 9, 2002, U.S. Patent Application 61/649,546, U.S. patent application Ser. No. 11/625,135, and U.S. Patent Application 61/589,083, the disclosures of which are incorporated by reference herein in their entireties. The entire disclosure of each patent and publication cited herein is incorporated by reference, as if each such patent or publication were individually incorporated by reference herein.