Patent ID: 12226167

DETAILED DESCRIPTION

Example embodiments are described and illustrated herein. These illustrated examples are not intended as limitations on the systems and methods described herein. For example, one or more aspects of the system can be utilized in other embodiments and other types of instruments. Such systems may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Like, but not necessarily the same, elements in the various figures are denoted by like reference numerals for consistency. Terms such as “first,” “second,” “front,” “rear,” “inner,” and “outer” are used merely to distinguish one component (or part of a component or state of a component) from another. Such terms are not necessarily intended to denote a preference or a particular orientation.

Under most circumstances, extravascular blood that pools in the brain converts into a gel with maximum viscosity in several minutes. The viscosity is near enough to the surrounding brain viscosity that increasing the intensity of an aspiration catheter may pose local injury when small bore catheters are used. Additionally, negative pressure applied through a small tube is not able to overcome the shear stress of the blood clot in the acute phase. Hematoma evacuation therefore requires an open or mini-open approach for direct visualization to manipulate the clot for safe aspiration. Eventually the clot will liquefy and could be easily drained but the delay in treatment, assuming survival, elevates the risk. The delay may lead to irreversible injury if not decompressed promptly.

In the case of superficial (e.g. subdural) brain hematomas, treatment of a clotted hematoma is possible and widely practiced because the brain itself is not violated as the clot is ‘extra-axial’. Open craniotomy is thus the standard of care. However, in case of deep-brain hematomas surgical excision may not be possible or may be associated with a higher likelihood or degree of morbidity as discussed above, depending on location.

The precision, accuracy and control of an MRgFUS device is within millimeters, which renders such device suitable to identify and triangulate a deep brain clotted hematoma, and to focus ultrasound radiation on the triangulated clot to liquefy the hematoma. Once liquefied, it is necessary to drain the liquefied material in order to effectively treat the hematoma to improve recovery by restoring the brain back to a normal configuration. One example of an MRgFUS device that can be used with the present system is the EXABLATE NEURO™ device provided by Insightec™ in Israel. This device is currently marketed for treating essential tremor and Parkinson's disease. The device is docked to an MRI machine and can deliver up to 1,024 ultrasound waves across the skull of a patient to precisely ablate a target deep in the brain.

Referring initially toFIG.1, a schematic, cross-sectional illustration of a conventional MRgFUS device is depicted. The device includes a focused ultrasound transducer assembly10, a cranial diaphragm20and a skull fixture30. Briefly, the transducer assembly10comprises an array of ultrasonic transducers distributed over a substantially hemispherical frame and is configured to deliver ultrasonic energy to the cranium of a patient under treatment. By separately controlling the individual transducers within the array, a targeted and precisely controlled dose of ultrasonic waves can be delivered to a triangulated position within the patient's cranium. The cranial diaphragm20is composed of a diaphragm membrane22extending radially inward from a rigid circular frame24. The diaphragm membrane22has an opening23at its center, which is cut and sized to elastically stretch over and provide a conformal circumferential seal against the patient's shaved scalp. The circular frame24is sealingly mated to the rim of the transducer assembly10(e.g. via an intermediate O-ring gasket) to provide a watertight seal therebetween. When positioned on a patient, the dome of the patient's head penetrates the hemispherical space defined within the transducer assembly10. This space defines a jacket bounded by an interior surface12of the transducer assembly10and the cranial diaphragm20that caps its opening. The jacket is filled with chilled water or other fluid, which acts as a medium to conduct ultrasound waves between the transducer array on the transducer assembly10and the patient's head. The patient's head is held stationary via the skull fixture30, which can include a series of fixturing pins34extending radially inward from a perimeter frame32. The pins can be driven into the patient's skull via local anesthetic to ensure the head remains fixed during the procedure.

The MRgFUS device is configured to be docked to a conventional MRI machine so that ultrasound energy can be delivered to triangulated locations within the patient's brain identified via MRI image guidance. As noted, use of the conventional MRgFUS system is indicated for treatment of essential tremor and Parkinson's disease, where it is used to triangulate a discrete thalamic nucleus via MRI imaging followed by ultrasonically lesioning the brain at that location. MRI imaging is used throughout the procedure, intermittently with successive doses of ultrasound energy, to image and track a forming lesion and help guide successive ultrasound doses in order to achieve a lesion of desired geometry, location and size. While a frame is used to hold the head, the procedure does not use any incisions. The ultrasound waves are focused on the target through the transducers mounted in a helmet apparatus. The energy from the summation of the waves heats the tissue enough to denature the protein (typically >55 C). This selectively ‘lesions’ the brain. Disclosed here is a suite of tools that could be integrated with the existing MRgFUS device and used in real time to guide treatment.

Turning now to the present embodiment, a system and method are provided in which a body within the brain (or other organ) can be located and accessed for treatment. An MRgFUS device can be used not to lesion thalamic nuclei, but rather to triangulate and liquefy thrombotic material deep within the brain. The liquified material then can be suction aspirated via an emplaced catheter.FIG.2illustrates a system100for magnetic resonance-guided focused ultrasound aspiration in accordance with an example embodiment. The system100includes a conventional MRI environment110, which generally comprises a bed or patient support120, an MRI scanner, and an MRI workstation130. The MRI environment110can be provided as an MRI suite having a control room for the MRI workstation130and a separate magnet room that houses the MRI scanner, or any other suitable environment. An MRgFUS device is provided which comprises a transducer assembly140coupled to a cranial diaphragm150. The transducer assembly140includes a plurality of transducers arranged in an array and mounted in a helmet apparatus or in a substantially hemispherical manner and configured to surround a portion of a patient's head. The cranial diaphragm150is configured to surround another portion of the patient's head and comprises a membrane that can function as a cooling system. For instance, the membrane can be configured to retain a liquid therein, such as degassed water, which is coupled to a liquid circulation, cooling, and degassing system160so that an appropriate and comfortable temperature of the patient's head can be maintained during treatment. A mechanical positioning system170can also be provided to suitably position the transducer assembly140with respect to the patient and the MRI scanner. A stereotactic frame180can be secured to the patient's head to provide reference points for targeting and to hold the head secure during treatment, thereby preventing unwanted motion.

A device190for access to and treatment of a deep-seated body200, such as a blood clot, or tumor is provided, which will be described in greater detail below. A focused ultrasound workstation210includes a processor configured for treatment planning, thermometry, and dosimetry and is in communication with a driving system220. The driving system220receives signals from the processor and in turn, directs the transducer assembly140to generate ultrasound energy. The MRI scanner is used to guide the application of ultrasound energy to the body200.

FIG.3illustrates an example method for aspirating and/or treating a body that employs magnetic resonance-guided focused ultrasound. The body is described herein as a hematoma or blood clot; however, it is to be appreciated that any other suitable body, such as a tumor, can be treated with the described system and method. To carry out this procedure, a catheter or tool is placed at the body, and the surgeon is given cranial access to reposition the device based on image guidance during the procedure. Accordingly, at the start of the example method, an image of the hematoma is acquired. For instance, at300, stereotactic computed tomography (CT) is used to precisely locate the hematoma within the brain. Alternatively, magnetic resonance imaging (MRI) can be used to image the hematoma. Once the hematoma is located, a trajectory for a catheter is planned to minimize tissue injury and maximize clot evacuation at310.FIG.4illustrates an example of a CT image370with a planned trajectory for placement of a device380used to access the hematoma390. At320, a channel is defined along the planned trajectory to provide communication from an opening in the skull to the hematoma. The channel can be defined by the insertion of a thin guide tube, which is configured to accommodate one or more catheters or other tools therethrough for treatment of the hematoma.

An example of how a guide tube can be inserted is illustrated inFIGS.5A through5C. A small incision is first made in the patient's scalp to define an entry point. Then, as shown inFIG.5A, an opening510is made in the skull500. A guide tube520is then inserted through the skull500and guided into an appropriate position, such as until a distal end of the guide tube520is disposed proximate or within the hematoma. Localization imaging such as a CT scan can be used to stereotactically insert the guide tube520using commercially available navigation software and hardware such those available from BrainLab™ or Medtronic™. Alternatively, MRI can be used to position the guide tube520into place. It is to be appreciated that the guide tube520could be initially inserted more superficially and then advanced as necessary. A portion of the guide tube520, where it emerges from the skull, could be secured to the bone. Alternatively, the guide tube can include a balloon portion540used to hold the guide tube520in place relative to the skull. The balloon portion540can be formed as a materially integral component of the guide tube520. With this configuration, the guide tube520is inserted into skull until the balloon portion540is aligned with the opening510in the skull500, as shown. The balloon portion540is then inflated to hold the assembly in place using the skull500as a support (FIG.5B). The guide tube520can include a first end port550through which one or more instruments570used to remove the clot and/or administer agents are passed through the guide tube520. The guide tube520can also include a second end port560used for inflating and deflating the balloon portion540.

Turning back toFIG.3, once the guide tube has been placed, the patient's head is immobilized and positioned within the MRgFUS device, as illustrated inFIG.2. At330, an aspiration catheter can be provided through the guide tube such that a distal end of the catheter is positioned within the hematoma. Then, at340, ultrasound energy is delivered via MRI image guidance to the hematoma. The ultrasonic energy can be directed and focused on the hematoma to liquefy it without damaging the tissue around it. Once liquified, the hematoma is evacuated via the catheter at350. During evacuation, the distal end of the catheter may need to be repositioned as the shape of the hematoma changes. Real-time MRI imaging can be used to guide this repositioning of the catheter. By ensuring that the distal end remains or is repositioned at the base of pooling liquid, the hematoma can be entirely or substantially removed. Image guidance also can be used to refocus delivery of the ultrasound energy in conformity with the evolution of the hematoma as it is sonicated and evacuated, to ensure it is fully liquefied for removal. Once the hematoma has been partially or fully removed, which can be verified via MRI, the patient can be removed from the MRgFUS system and the catheter and guide tube withdrawn (360). If a balloon was used to secure the guide tube, once the aforementioned procedure is complete, the balloon is deflated and the guide tube can be removed from the patient without opening up the skin again, as will be described in more detail below.

The guide tube, catheter, and any other tools or instruments used with the MRgFUS system are of relatively small diameter and made of a non-ferromagnetic material, such as plastic or a silicone-based material. By using a suitable non-ferromagnetic material, none of the guide tube, catheter, or other tools will be moved by the magnetic fields, induce unwanted heating, or cause confounding imaging artifacts during the procedure. The small diameter renders the guide tube substantially insignificant within the jacket defined at the interior of the transducer assembly. The guide tube may emerge from the patient's scalp at a position within the jacket. The guide tube can be 7 gauge or smaller, and more preferably 14 gauge or smaller. At least one catheter and/or tool that is advanced through the guide tube has a diameter that is smaller than the diameter of the guide tube and where appropriate, up to 34 gauge. To access the guide tube with the catheter and/or tool, the guide tube penetrates the MRgFUS device to reach the external environment via an access port, as described further below. The catheter or other surgical implement to treat and/or drain clot material or other target can be inserted from the external environment via the guide tube and manipulated and/or repositioned by a surgeon for treatment. A proximal end of the catheter can extend beyond a proximal end of the guide tube. In the case of aspirating a hematoma, a suction apparatus can be coupled to the proximal end of the catheter. The suction may be manual or automated. A negative pressure setting for the suction apparatus can be adjustable.

FIG.6illustrates an example of another mechanism for holding a guide tube in position in the skull of a patient. The mechanism includes a cylindrical insert580having an outer diameter that corresponds with an opening (such as opening510) made in the skull. The outer diameter is provided with threads585that allow the insert580to be threaded and securely positioned in place in the bone. An inner diameter of the insert580corresponds with an outer diameter of a guide tube590such that the guide tube590is securely held by the insert580. The guide tube590can be a one-piece tube that fits through the inner diameter of the insert580, or it may include a top tube portion and a separate bottom tube portion, each of which can be secured within the insert, such as through threaded connections.

FIG.7illustrates an example of an inflatable member750or balloon that can be used to hold a guide tube in position within the skull. The inflatable member750includes a substantially flexible inner surface (not shown), which defines an opening755therethrough for insertion of the guide tube. The outer wall760of the insert is also made of a flexible material and a space between the inner and outer walls is confined but for a small sealable opening. Thus, upon receiving an air or gas in the space, both the inner and outer walls of the insert can expand radially, thereby inflating the inflatable member750. In its non-expanded or uninflated state, the outer diameter of the inflatable member750is smaller than an opening provided in the skull such that the inflatable member750can be placed within the opening. Once positioned, a liquid, such as saline, or a pressurized air or gas is provided through a thin communication tube765and into the insert space to expand the outer walls of the inflatable member750against the opening, thereby securing the inflatable member750in place. As the inner wall also expands, a guide tube positioned through the opening755will also be securely held in place when the inflatable member750is inflated. When secured within the opening, a first end cap770is positioned at an inside surface of the skull bone and a second end cap775is positioned at an outside surface of the skull, which mitigates the inflatable member750from being pushed or pulled out of the skull opening. While the inflatable member750can secured against an opening in the skull similar to the balloon portion540described with respect toFIGS.5A-5C, because the inflatable member750is not materially integral with the guide tube as inFIGS.5A-5C, the inflatable member750can be moved longitudinally along the guide tube, which facilitates adjustability and placement of the distal end of the guide tube proximate the body to be treated.

FIGS.8A and8Billustrate another example of an inflatable member780or balloon that can be used to hold a guide tube in position within the skull.FIGS.9A and9Billustrate the inflatable member780slidably engaged with a guide tube785in accordance with an embodiment. The inflatable member780comprises a substantially torus-shaped body. An outer diameter of the body is sized to correspond with an opening made within a skull. An inner diameter of the body corresponds with an outer diameter of the guide tube785. Thus, the guide tube785is sized to fit through a central opening790in the inflatable member780. A collar795can extend upwardly from the torus-shaped body and provides an interference fit between an inner diameter of the collar795and an outer diameter of the guide tube785. The collar795includes a sealable opening in communication with an inner portion of the body to facilitate inflation and deflation thereof. A communication channel805is secured within the opening in the collar795through which a gas and/or liquid can travel to provide the inflation and deflation of the inflatable member780. The communication channel805extends alongside an outer surface of the guide tube785and can be coupled thereto. When in a deflated state, the fit between the inflatable member780and the guide tube785is tight but still allows for movement or adjustability of the inflatable member780along the length of the guide tube785.

Similar to the method described above, to place the guide tube785, an incision is first made in a patient's scalp and then an opening is made in the skull. The guide tube785can then be placed along the planned trajectory until a distal end is positioned proximate a target body to be treated. The inflatable member780can then be slidably moved along a length of the guide tube785until the inflatable member780is positioned within the skull opening. Alternatively, the inflatable member780can be pre-positioned at a distance from the distal end of the guide tube785, as determined during the trajectory planning stage, and held in place via the interference fit between the collar795and the guide tube785. Once in place, the member780is inflated via the communication channel805. The torus-shaped body allows for inflation at both the inner and outer diameter of the inflatable member780thereby securing the member780in place against both the guide tube785and the skull, which in turn, secures the guide tube785in position with respect to the skull. The incision made in the patient's scalp is closed and the guide tube785and communication channel805can then be tunneled beneath the scalp to exit the scalp at a position away from the incision site. During removal of the guide tube785, the inflatable member780is deflated via the communication channel805and the entire guide tube785and inflatable member780assembly can be pulled from the skull without reopening the initial incision site. A stopper815can be secured to or materially integral near a distal end of the guide tube785. The stopper815has an outer diameter that is larger than the central opening790of the inflatable member780. Thus, the stopper815mitigates separation, of sliding off, of the inflatable member780from the guide tube785during removal of the assembly from the patient.

The inflatable member780, and the other inflatable members described herein, can be made from a semi-compliant and/or compliant yet puncture resistant material. For example, the body can include a polyurethane material coated with silicone. It is to be appreciated that any other suitable material can be used that allows inflation of the body to securely hold the inflatable member780against the skull opening while being puncture resistant against any sharp edges of the skull bone. The guide tube785can also be made from a flexible polymer material, such as silicone, to allow for sharp bends, such as 90-degrees, during tunneling.

FIG.10illustrates an example guide tube assembly860having an adjustable balloon component or inflatable member865, as described above. The balloon component865is provided around a guide tube870and adjusted to a desired location along the guide tube870based on a depth of a clot or body to be treated. For instance, the guide tube870is generally positioned such that the distal end is proximate a top portion of the clot. Thus, the distance between the top portion of the clot and the skull along the planned trajectory corresponds to a distance between the desired location of the balloon865and the distal end of the guide tube870. A numbered depth gauge875can be provided on the tube to facilitate positioning of the balloon865.

Because the guide tube870is made of flexible materials to accommodate sharp turns, the guide tube870may be too flexible to push through to the target location. Thus, the guide tube assembly860can also include a navigation tool, such as a stylet,880to assist in navigation of the guide tube870during placement. Because the navigation tool880is only needed temporarily, it can be positioned through a tube or channel885secured to a side of the guide tube870, thereby simplifying insertion and removal of the navigation tool880. It is also not necessary for the stylet to be made from an MRI-compatible material and thus, can be made from a stainless steel or other stiff wire material. The navigation tool880can be a Medtronic or Brainlab stylet, or any other suitable tool to facilitate accurate guidance and placement of the guide tube870proximate the clot.FIG.11illustrates an example of a guide tube905configured with a low-profile secondary channel, such as a Y-channel,915that can branch off the guide tube905. This secondary channel915allows for insertion of a navigation tool925through the guide tube905and to its distal end. A cap935can be tethered to the secondary channel915to close off the channel when not in use. A Luer lock mechanism or other suitable mechanism can also be provided at an opening of the secondary channel915to allow for easy and secure insertion and removal of the navigation tool925. After insertion, a dial lock, such as a Tuohy Borst adapter, can be provided to secure the navigation tool925in place during use. Once the guide tube905is positioned, the navigation tool925is removed.

Turning back toFIG.10, at a proximal end of the guide tube870, a dial lock mechanism890, such as a Tuohy Borst adapter, is provided. Once the guide tube870has been placed and the patient is moved to and positioned within the MRgFUS system, a catheter895can be threaded through the guide tube870. In the case of aspirating a blood clot, the catheter895is positioned such that its distal end extends past the distal end of the guide tube870and into the clot. Once in position, the dial lock mechanism890is used to secure the catheter895. The catheter895is configured to bend around sharp turns, such as a 90-degree angle at the skull entrance, be suitable kink resistant, and of a material that is MM-compatible. One example is a plastic coil reinforced tube suitable for aspirating a liquified body. Various other tools and catheters can be provided through the guide tube870for treatment of a target body.

FIGS.12A,12B, and13illustrate another mechanism of securing a guide tube assembly in accordance with an embodiment. A first balloon component1020can be secured to an outer wall of a guide tube1025and a second balloon component1030can be secured to an inner wall of the guide tube1025.FIG.12Aillustrates the first and second balloon components1020,1030in deflated states. When in the deflated states, the guide tube1025is inserted into an opening1035made in the skull1040. Once aligned, the first balloon component1020can be inflated such that the first balloon component1020can anchor the guide tube1025to the skull bone1040(FIG.12B). Once a catheter1045, or other instrument, is inserted through the guide tube1025, the second balloon component1030can be inflated to hold the catheter1045in position. It is to be appreciated that the dial lock mechanism890described inFIG.10can be used in place of the second balloon component1030, if desired. Locking the catheter1045, or other instrument, in place prevents migration during the procedure. As shown inFIG.13, first and second inflation/deflation tubes1050,1060can be provided to facilitate inflation and deflation of the first and second balloon components1020,1030, respectively. For instance, saline/air can be injected into or suctioned from the inflation tubes1050,1055via syringes positioned outside of the MRgFUS device.

FIG.14illustrates an example MRgFUS device600that can be used with the systems and methods described herein. The MRgFUS device600includes a focused ultrasound transducer assembly610having an array of ultrasonic transducers distributed over a substantially hemispherical frame. For instance, the transducer assembly610can include an array of1024individual ultrasound transmitting elements. The individual elements can be controlled separately, thereby providing a targeted and precisely controlled dose of ultrasonic waves that can be delivered to a triangulated position within the patient's cranium. The MRgFUS device600also includes a cranial diaphragm620, which includes a diaphragm membrane630extending radially inward from a rigid circular frame640. The diaphragm membrane630has an opening650at its center. The opening650is sized to elastically stretch over and provide a conformal circumferential seal against the patient's scalp660. The circular frame640is sealingly mated to the rim of the transducer assembly610, such as via an intermediate O-ring gasket (not shown), to provide a watertight seal therebetween. When positioned on a patient, the dome of the patient's head penetrates the hemispherical space defined within the transducer assembly610. This space defines a jacket670bounded by an interior surface of the transducer assembly610and the cranial diaphragm620that caps its opening. The jacket670is filled with chilled water or other fluid, which acts as a medium to conduct ultrasound waves between the transducer array on the transducer assembly610and the patient's head660.

An access ring680can be interposed between the transducer assembly610and the cranial diaphragm620. The access ring680includes a substantially circular frame having one or a plurality of access ports690distributed about its circumference. The access ports690are configured to provide access from the external environment into the MRgFUS device600through the access ring680. The frame of the access ring680can be secured between the transducer assembly610and the frame640of the cranial diaphragm620using any suitable fastener while maintaining a substantially water-tight seal within the jacket670. For example, the access ring680can be fitted with complementary hardware and structure at a first side so that the cranial diaphragm620will mate with and be secured thereto in the same manner as it otherwise would mate to the transducer assembly610. Likewise, the access ring680can be fitted with complementary hardware and structure at a second, opposing side so that the transducer assembly610will mate and be secured thereto in the same manner as it otherwise would mate to the cranial diaphragm620. Thus, the access ring680becomes integrated with the MRgFUS device600to help define the water-tight jacket670that holds circulating ultrasound medium (preferably chilled water) when used in the disclosed methods to aspirate liquefied thrombotic material. A first seal can be provided between an end surface of the transducer assembly610and the second side of the access ring680and a second seal can be provided between the first side of the access ring680and a corresponding side of the frame640of the cranial diaphragm620to provide a watertight structure. The first and second seals can be O-ring gaskets or any other suitable gasket. Alternatively, or additionally, machined mating surfaces opposing one another may be compressed together to form the first and second seals.

Procedurally, a guide tube700is first placed in the patient's cranium660as described above. The guide tube700is then threaded through an available access port690in the access ring680so that a proximal end of the guide tube700emerges from the access ring680to the exterior environment. Then, the patient is fitted within the MRgFUS device600with its head conformally and water-tightly received through the opening650at the center of the diaphragm membrane630, and within the jacket670defined at the center of the transducer assembly610. With the access ring680in-place and secured to the both the transducer assembly610and the cranial diaphragm620as described, the ultrasound medium (e.g., chilled water) can be filled and circulated through the jacket670to complete the assembly prior to an MM-guided ultrasound treatment to liquefy a target body, such as a hematoma, deliver a therapeutic agent, and/or treat the target body via one or more other tools. Ideally, any slack is removed from the guide tube700within the assembled MRgFUS device600, such as during assembly, so that the guide tube700remains unbunched within the jacket670between the scalp660and the transducer assembly610, on its way to the access port690where it exits the assembled MRgFUS device600. Alternatively, the guide tube700may be tunneled beneath the scalp a short distance and then perforate the scalp to minimize interference with the transducer ultrasound waves. The guide tube700may also need to be affixed via adhesives or anchors resting on top of the scalp.

The access ports690can be provided with self-healing silicone diaphragms to ensure maintenance of a water-tight seal at each of the ports690. For example, the self-healing diaphragms can be needle-punctured to provide a passage through which the guide tube700may be threaded. Once threaded, the diaphragm will compress (i.e. ‘heal’) radially inward against the guide tube700passing therethrough, essentially closing the diaphragm (and the associated port690) about the guide tube700.

FIG.15illustrates a portion of an MRgFUS device710in accordance with another example embodiment. In this embodiment, the MRgFUS device710includes a hemispherical transducer assembly and a cranial diaphragm, as described above. However, rather than an access ring positioned between the transducer assembly and the cranial diaphragm, access ports800are provided directly in the diaphragm membrane730of the cranial diaphragm740. The diaphragm membrane730includes one or more discrete access ports800disposed therein, preferably a plurality of access ports distributed about a circular path around the diaphragm membrane730. As with the aforementioned access ring680, distributing the access ports800around the diaphragm membrane730provides access at a multitude of different locations. This helps avoid the need to ensure a specific angular alignment of the cranial diaphragm740(or of the access ring680in the earlier embodiment) so that an access port800will be positioned in a desired location. It also can be desirable if multiple access ports are useful or necessary for a single procedure. Tunneling the guide tube beneath the scalp or anchoring on the surface may be needed with this approach. By tunneling the guide tube, the opening in the scalp can be moved to an area outside the chilled water bath. This configuration is also beneficial to mitigate contamination of the water with blood and/or potential contamination with instruments provided through the guide tube.

FIGS.16A and16Billustrate an example access port800that can be secured directly to the diaphragm membrane730. The access port800includes a first body portion810and a first gasket820and an opposing second body portion830and a second gasket840. The first body portion810includes a substantially planar surface that is secured to a first surface of the first gasket820. Similarly, the second body portion830includes a substantially planar surface that is secured to a first surface of the second gasket840. The first and second body portions810,830include an aperture sized to receive a cylindrical sleeve850therethrough. The cylindrical sleeve850is sized to receive a guide tube and/or at least one catheter or instrument therethrough. The cylindrical sleeve850is optional and alternatively, the guide tube can extend directly through the aperture provided in the access port800.

As shown inFIG.17, when coupling the access port800to the diaphragm membrane730, a second surface of the first gasket820is secured to an outer surface (a side facing the external environment, or the surgeon) of the diaphragm membrane730. Then, the sleeve850, which can have the second body portion830and second gasket840positioned thereon, is pushed through an aperture or small perforation in the diaphragm membrane730and through the first gasket and aperture in the first body portion810. A second surface of the second gasket840is then secured to an inner surface (a side facing the patient) of the diaphragm membrane730. Each of the first and second gaskets820,840are configured to seal against the diaphragm membrane in a liquid-tight manner. For instance, the first and second gaskets820,840can be formed or provided with self-healing portions through which the sleeve850is pushed. If not positioned during assembly of the access port800body to the diaphragm membrane730, the sleeve850may be fed from an inner portion of the MRgFUS device through the second body portion830and second gasket840, through the diaphragm membrane, and then through the first gasket820and first body portion810to the external environment. The first and gaskets820,840provide the required liquid-tight seal so that the diaphragm membrane730can hold a cooling agent, such as water, while permitting a guide tube, catheter, lead, or the like to pass through the sleeve850and to the outside environment where its proximal end may be accessed to insert one or more catheters and/or other tools.

As shown inFIGS.17through20, the access ports secured to the diaphragm membrane can be of any suitable size. For instance, a smaller configuration of the access port, as shown inFIG.18, can be used to tunnel out EEG leads.FIG.19illustrates a syringe coupled to an access port to instill an amount of medication. A plurality of access ports may be secured to any suitable position on the diaphragm membrane, as desired. For instance, a group of access ports may be secured proximate each other as inFIG.18or a plurality of access ports can be spaced radially around the cranial diaphragm, as shown inFIG.20. The relatively simple configuration of the access ports allows positioning of the access ports anywhere along the diaphragm membrane, as needed. Moreover, it is to be appreciated that the access port configuration shown herein is merely an example configuration and any suitable structure, device, or system can be used as an access port so long as the configuration provides liquid tight access for a guide tube through a diaphragm membrane. In each of the systems disclosed herein, once a guide tube has been placed and the patient introduced into an MRgFUS device, the guide tube is pushed through an access port to the external environment. A surgeon can then insert a treatment catheter, such as a suction catheter, or other tool for treatment of the target body (e.g., hematoma) via the guide tube to deliver its distal end proximate the target body. Insertion and positioning of the catheter and/or tool is carried out via MRI guidance as desired relative to the body. At the same time, it is possible to re-confirm proper placement of the distal end of the guide tube. If adjustments to the guide tube or to the catheter fed therethrough are appropriate to reposition either, such adjustments can be made by the surgeon under real-time MRI guidance as is conventional, but now within the MRgFUS device. Once hematoma triangulation and catheter placement have been established/confirmed, the transducer assembly can be actuated to deliver a targeted dose of ultrasound energy to the body in order to liquefy it. Liquefied material then is aspirated via the emplaced catheter, which is fed via the guide tube, and confirmed via MRI periodically or in real-time. As liquefied thrombotic material is drained, adjustments in position of the distal end of the catheter can be made, as well as additional targeted doses of ultrasound energy delivered, based on MRI imaging as it evolves through liquefaction and drainage.

In addition to lateral repositioning, the depth of the catheter also may be adjusted based on MRI image guidance; for example, by advancing and/or withdrawing the catheter via the guide tube along its insertion axis as needed. Withdrawal to reposition the distal end of the catheter at a shallower location might be achieved simply by mechanically pulling the catheter from outside the MRgFUS device, which will result in it being withdrawn along its insertion pathway through the guide tube and from the patient's cranium. Regarding advancement, similar adjustment can be achieved by physically pushing the catheter through the guide tube along its insertion axis.

There are two imaging activities that are essential for the success of this program: (1) where is the location of the catheter (and its tip) in relation to the hematoma; and (2) what portions of the clot have become liquid and which remain solid. As catheters are generally MRI-black on all sequences (contains no mobile protons), alternative ways need to be optimized to reliably identify their location, which we will undertake. This might also entail conducting a scan with contrast agents within the middle of the catheter. Imaging characteristics of liquid blood vs clotted blood can be strikingly different on various sequences, and we will optimize scan parameters to accentuate this difference. This imaging may also entail a thermography sequence to identify the temperature of the clot during sonication. Ideally these sequences could be run in real time during sonication, and thereby provide real-time feedback about efficacy, and positioning. If optimized, after one sonication the catheter could be repositioned from a liquefied clot into a non-liquefied portion, and the process repeated. The images might be rendered into a 3D model that is displayed on the console or even in a VR space to help guide the treatment. It may be desirable to have a coordinate-based system that directs the position or suggests manual adjustments for the position of the catheter in space.

Guide tubes can be placed and left in position for extended periods of time. The use of a guide tube allows for easy replacement of catheters that may become clogged and use of various tools during treatment.FIG.21illustrates an example of tunneling a guide tube1090beneath a patient's scalp1075. As discussed above, an incision is made in the scalp and then an opening is provided through the skull. The guide tube1090is provided through the opening to a desired depth and then secured to the skull bone, such as via a balloon member. A proximal end of the guide tube1090can then be tunneled under the scalp to exit at a remote location (e.g., location1080) so that the initial incision site1070can be closed. By closing the initial incision site, infection at the site is mitigated and contamination of the cooling liquid used in the MRgFUS system is prevented. The exit location1080for the guide tube1090can be positioned at a location within the jacket defined by a transducer assembly, in which case the guide tube1090is passed through an access port. However, the guide tube1090may also be tunneled to an exit location outside of the MRgFUS system, or in other words, outside of the cooling liquid bath. In both cases, a liquid tight anchor or sealing device1085can be provided at the exit location1080to support the guide tube1090and seal the opening from the liquid bath or the environment.

It is to be appreciated that various tools and/or instruments can be used in connection with the guide tube assembly described herein. For instance, as illustrated inFIG.22, a syringe1100can be used to dispense an agent, such as flowseel or definity, preloaded at a tip portion1110. The syringe1100can actuate a plunger and/or wires extending through the guide tube1115to release the agent.FIG.23illustrates another example in which a balloon1130is positioned through and extends past a distal end of the guide tube1115. A syringe1120or other actuation device can be coupled to the balloon1130to inject a fluid and/or air to inflate the balloon1130. This can be employed as a tamponade if active bleeding is encountered.FIG.24illustrates an intracranial pressure monitor transducer1140or other pressure monitor that can be provided through the guide tube1115and used as an early warning of increasing pressure. Moreover, any suitable catheter configuration can be used with the guide tube assembly disclosed herein. For instance, a telescoping catheter, such as the catheter developed by Route 92 Medical of San Mateo, California, can be used.

As previously described, one or more guidewires or navigation tools can be employed for assisting in the positioning and/or repositioning of the distal end of the catheter. The guidewires, if used during MRI imaging, must be suitable to mitigate imaging artifacts that could obscure the surgical field or create magnetic interactions resulting from ferromagnetic materials, which could damage both the patient and the MRI machine. Accordingly, the wires used to guide the catheter may be composed of nitinol, a nickel-titanium alloy that has been shown to be generally safe and not disruptive under MRI. However, depending on the strength of the MRI device (i.e. the magnetic field that it generates), it is possible that nitinol components or guidewires of a catheter may produce undesirable imaging artifacts. In that case, it may be appropriate to utilize instead rigid or semi-rigid plastic or fiberglass strands as guidewires to manipulate the distal end of a repositionable catheter to direct it to desired locations. These guidewires may be curved to improve steerability.

FIGS.25through31illustrate the use of smaller aspiration catheters that can be used to reach a hematoma.FIG.25illustrates a cross sectional schematic diagram of a catheter900according to one example. The catheter900is positioned through a guide tube910, as described herein. A smaller aspiration catheter920extends through the catheter900to facilitate positioning of a distal end930of the catheter900proximate a hematoma940. A tip portion950of the aspiration catheter920can include a J-shaped curve or any other desired shape to improve reachability of the aspiration catheter920within the hematoma. In addition, it may be necessary to insert catheters with small distal balloons attached to create a cavity in the clot and then deliver an agent such as Definity or tPA through the same catheter via a side channel.

FIGS.26and27illustrate an example of a multi-chambered catheter that can be employed.FIG.26illustrates a longitudinal cross section of a catheter960having four chambers; andFIG.27illustrates a distal end view of the same catheter960. The chambers are formed by two intersecting longitudinal walls or dividers970,980extending the length of the catheter960and thereby dividing the catheter960into four substantially equal chambers. Smaller aspiration catheters1000can be provided through the chambers for facilitating aspiration of the liquified hematoma. In order to facilitate aspiration of a larger area of the hematoma, each of the chambers can have a curved base portion990. When the aspiration catheter1000is provided through catheter960, the curved base portion990projects a distal end1010of the aspiration catheter1000along the curve. Thus, by controlling the curve of the base portion990, a larger area of the hematoma can be reached during aspiration. One or more of the chambers can also be used to deliver an agent, as will be discussed in more detail below.

FIGS.28-31illustrate another example of a multi-chambered catheter in accordance with an embodiment.FIG.28illustrates a longitudinal cross section of a catheter1200having two chambers; andFIGS.29A and29Billustrate distal end views of the same catheter1200. The chambers are formed by one longitudinal wall or divider1210extending the length of the catheter1200and thereby dividing the catheter1200into two substantially equal chambers. Smaller aspiration catheters1220,1230can be provided through the chambers for facilitating aspiration of the liquified hematoma. As above, to facilitate aspiration of a larger area of the hematoma, each of the chambers can have a curved base portion1240. When the aspiration catheters1220,1230are provided through catheter1200, the curved base portions1240project distal ends of the aspiration catheters1220,1230along the curves. Thus, by controlling the curves1240, a larger area of the hematoma can be reached during aspiration. Additionally, a larger area can be reached by rotation of the catheter1220.FIG.29Aillustrates the catheter in a first position andFIG.29Billustrates the catheter after a 90-degree counterclockwise rotation. Thus, using a two-chambered catheter and a 90-degree rotation can cover the same area as a four-chambered catheter as described herein. As shown inFIGS.30and31, the curved base portions1240can be provided as an attachment1250that can be threaded or otherwise secured to the end of the catheter1200. One or more of the chambers can also be used to deliver an agent, as will be discussed in more detail below.

A clotted hematoma can be liquefied in at least two ways using ultrasound. Initially, when a patient presents with symptoms indicative of a clot in the brain, such as an acute onset headache and right sided weakness, an image is acquired of the brain. The image can be acquired via CT, MRI, or any other suitable imaging system. Upon finding a deep-seated hemorrhage in the imaging results, a surgeon recommends how to best liquify and aspirate the clot. If the clot is located in a small central location of the brain, the surgeon may decide to use thermal lysis. Here, ultrasound energy delivers sufficient internal energy to the thrombotic material to reach a temperature threshold causing liquefaction; or via cavitation, where sonication delivers sufficient mechanical energy to disrupt the hematoma and mechanically disrupt thrombin to liquefy it. During this process, referred to as High Intensity Focused Ultrasound (HIFU), the ultrasonic energy is delivered at a higher frequency, such as 660 kHz, using low power for a long duration. It may not be desired to deliver any therapeutic agents to the hematoma prior to sonication during thermal lysis.

If the clot is large and/or located in a lateral location in the brain, the surgeon may decide to use mechanical lysis. In this situation, it may be desirable to deliver a cavitation-nucleation agent such as Definity®, which is an FDA-approved contrast agent. This agent has been shown to yield microbubbles that can be agitated via cavitation under ultrasound to deliver mechanical work. It was found that use of such an agent enhances liquification of the clot. A thrombolytic agent such as tPA could be added for synergistic effect. This or another suitable nucleation agent may be delivered via the catheter, previously emplaced with the hematoma. If desired, the catheter can be repositioned to distribute the nucleation agent at locations throughout the hematoma space under MM-image guidance. During this process, referred to as Low Intensity Focused Ultrasound (LIFU), the ultrasonic energy is delivered at lower frequency, such as 220 kHz, using high power for a short duration. In practice, whether via thermal denaturation or mechanical disruption, the hematoma can be liquefied via successive doses of targeted ultrasound radiation, followed by or contemporaneous with suction aspiration via the catheter to evacuate liquefied material. The target focus of sonication as well as the placement of the catheter distal end both can be adjusted in real time, or successively with intermediate MRI imaging, to liquefy and evacuate clot material.

Although embodiments described herein are made with reference to example embodiments, it should be appreciated by those skilled in the art that various modifications are well within the scope and spirit of this disclosure. The foregoing system and methods have been disclosed in the context of liquefying and aspirating a clotted deep-brain hematoma. However, it will be appreciated that other deep-brain interventions may be practiced using the disclosed system and methods. Therefore, the scope of the example embodiments is not limited herein. For example, in certain instances it may be desirable to combine targeted ultrasound therapy with deep-brain electrical stimulation to evaluate and treat epilepsy, or other neurologic disorders. In this scenario, a guide tube may be placed as described above to provide a conduit for delivering a deep-brain electrode to a desired position within the patient, in order to supply targeted electrical stimulation in combination with delivery targeted ultrasound energy. Also, multiple guide tubes as described above can be placed, for example passing through multiple access ports, in order to deliver catheter and/or tool access to different deep-brain positions, or to provide two or more catheters or tools in the same vicinity, e.g. to perform MM-guided microsurgery in conjunction with targeted sonification treatment. In other examples, the blood brain barrier may be opened and chemotherapy, immunotherapy, gene therapies or other therapeutic agents could be delivered to a body or region of interest, such as an abscess, infection, an area damaged by stroke. The disclosure is intended to include all such modifications and alterations disclosed herein or ascertainable herefrom by persons of ordinary skill in the art without undue experimentation.