Magnetic resonance guided focused ultrasound system for treatment of neck and head pain

Abstract

A magnetic resonance guided focused ultrasound (MRgFUS) system for treatment of neck pain of a patient can include a head support brace, an ultrasound transducer assembly, an acoustic coupling assembly, and a positioning gantry. The head support brace includes a conformal neck cradle having an ultrasound access opening. At least one imaging MRI coil can be oriented to allow imaging of a target tissue volume. The ultrasound transducer assembly includes a focused ultrasound transducer capable of producing a focused ultrasound and oriented to direct the focused ultrasound through the ultrasound access opening. The acoustic coupling assembly includes a conformable fluid enclosure housing a volume of ultrasound transparent liquid and adapted to transmit the focused ultrasound from the focused ultrasound transducer to skin of the patient. The positioning gantry is operatively connected to the ultrasound transducer assembly and adapted to translate the ultrasound assembly in at least one direction relative to the patient.

Description

[0001] M GNETIC RESONANCE GUIDED FOCUSED UETRASOUND SYSTEM FOR TREATMENT OF NECK AND HEAD PAIN

[0002] CROSS REFERENCE TO RELATED APPLICATIONS

[0003] This application claims priority to U.S. Provisional Application No. 63 / 696,527, filed on September 19, 2024, which is hereby incorporated herein by reference.

[0004] STATEMENT REGARDING FEDERALLY SPONSORED

[0005] RESEARCH OR DEVELOPMENT

[0006] This invention was made with government support under U18 EB030607 awarded by the National Institutes of Health. The government has certain rights in the invention.

[0007] BACKGROUND

[0008] Neck pain is the fourth leading cause of disability, with an annual prevalence of 12% to 71%, and is also a significant cause of cervicogenic headaches. Nearly 50% of patients continue to have symptoms after an initial episode despite conservative measures. Although a myriad of etiologies can cause neck pain, the facet joints (FJs) are implicated in up to 60% of patients with chronic neck pain and 70% of cervicogenic headaches, which can result from C2-C3 FJ arthropathy. Conservative treatments with systemic analgesic drugs, such as opioids, often fail due to their off-target toxicity, development of tolerance, and abuse potential. Highly invasive surgery has inherent procedural and long-term risks, which may limit applicability in many chronic neck pain patients. Interventional pain procedures, such as radiofrequency ablation (RFA), provide some target specificity to frequent paingenerating FJs.

[0009] RFA of FJs may help neuropathic spinal pain, with pain relief lasting longer than 12 months in 58%-74% of correctly selected patients, with some reporting decreased refilling of opioid prescriptions. Systematic reviews of cervical facet RFA efficacy for neck pain demonstrate evidence for long-term effectiveness. Notably, one-third of patients undergo repeat RFA within 3 years, which should be considered as RFA is invasive and associated with risks of radiation exposure, infection / hematoma, and long-term damage to paraspinal muscles. Interventionalists use fluoroscopic osseous landmarks most often; however, neck Attorney Ref. No. 00846-U8616.PCT percutaneous procedures pose even greater risks of complications compared to those in the lumbar spine given the close proximity of critical vascular and neural structures to the osseous spine such that off-target trajectory can be catastrophic.

[0010] While RFA has good clinical outcomes when rigorous patient selection criteria are applied and specific procedural techniques are used, pain relief procedures, overall, have surged by 228% from 2000 to 2011.

[0011] SUMMARY

[0012] A magnetic resonance guided focused ultrasound (MRgFUS) system for treatment of neck pain of a patient can include a head support brace, at least one imaging MRI coil, an ultrasound transducer assembly, an acoustic coupling assembly, and a positioning gantry. The head support brace includes a conformal neck cradle having an ultrasound access opening. The ultrasound transducer assembly includes a focused ultrasound transducer capable of producing a focused ultrasound and oriented to direct the focused ultrasound through the ultrasound access opening. The acoustic coupling assembly includes a conformable fluid enclosure housing a volume of ultrasound transparent liquid and adapted to transmit the focused ultrasound from the focused ultrasound transducer to skin of the patient. The positioning gantry is operatively connected to the ultrasound transducer assembly and adapted to translate the ultrasound assembly in at least one direction relative to the patient.

[0013] An example method of making a magnetic resonance guided focused ultrasound system for treatment of neck pain of a patient can include measuring a neck shape of the patient and providing a head support brace which includes a conformal neck cradle having an ultrasound access opening. The shape of the conformal neck cradle can be selected based on the measured neck shape of the patient. Providing at least one imaging MRI coil to allow imaging the target tissue at the transducer focus (e.g. embedded in the neck cradle, the ultrasound transducer, or other adjacent location). An ultrasound transducer assembly can include a focused ultrasound transducer capable of producing a focused ultrasound. The ultrasound transducer assembly can be oriented to direct the focused ultrasound through the ultrasound access opening. The ultrasound transducer assembly can be coupled to an acoustic coupling assembly including a conformable fluid enclosure housing a volume of ultrasound Attorney Ref. No. 00846-U8616.PCT transparent liquid and adapted to transmit the focused ultrasound from the focused ultrasound transducer to the skin of the patient. A positioning gantry can be connected to the ultrasound transducer assembly. The positioning gantry can be adapted to translate the ultrasound assembly in at least one direction relative to the patient.

[0014] An example method of treating neck pain in a patient can include positioning the patient in a head support brace that includes a conformal neck cradle conforming to a neck of the patient. The conformal neck cradle can have an ultrasound access opening. At least one imaging MRI coil can be oriented to allow imaging the target tissue at the transducer focus (e.g. embedded in the neck cradle, coupled to the ultrasound transducer, or oriented at a suitable adjacent location). An ultrasound transducer assembly can include a focused ultrasound transducer capable of producing acoustic waves and an acoustic coupling assembly can include a conformable fluid enclosure housing a volume of ultrasound transparent liquid. The ultrasound transducer assembly and the acoustic coupling assembly can be positioned such that the ultrasound transparent liquid transmits the focused ultrasound from the focused ultrasound transducer, through the ultrasound access opening, to skin of the patient. The ultrasound transducer assembly can be positioned using a positioning gantry that is operatively connected to the ultrasound transducer assembly and adapted to translate the ultrasound transducer assembly in at least one direction relative to the patient. A target tissue can be located near the focal spot of the focused ultrasound transducer within the neck of the patient using MRI scanning. The target tissue can be acoustically exposed using the focused ultrasound transducer.

[0015] There has thus been outlined, rather broadly, the more important features of the invention so that the detailed description thereof that follows may be better understood, and so that the present contribution to the art may be better appreciated. Other features of the present invention will become clearer from the following detailed description of the invention, taken with the accompanying drawings and claims, or may be learned by the practice of the invention. Attorney Ref. No. 00846-U8616.PCT

[0016] BRIEF DESCRIPTION OF THE DRAWINGS

[0017] FIG. 1A shows a perspective view of an example MRgFUS system in accordance with the present technology.

[0018] FIG. IB shows an exploded view of the example system of FIG. 1A.

[0019] FIG. 2 shows a perspective view of an example MRI sled with an example MRgFUS system and a patient in accordance with the present technology.

[0020] FIG. 3A shows a perspective view of an example MRI sled with an example MRgFUS system in accordance with the present technology.

[0021] FIG. 3B is a side view of the example system shown in FIG. 3A.

[0022] FIG. 3C is a top view of the example system shown in FIG. 3A.

[0023] FIG. 3D is an end view of the example system shown in FIG. 3A.

[0024] FIG. 4A is a perspective view of an example MRgFUS system in accordance with the present technology.

[0025] FIG. 4B is a cross-sectional view of an example MRgFUS system in accordance with the present technology.

[0026] FIG. 4C is an end view of an example MRgFUS system configured for bilateral treatment in accordance with the present technology.

[0027] FIG. 5A is an end view of an example MRgFUS system in accordance with the present technology.

[0028] FIG. 5B is a side view of the example system shown in FIG. 5A.

[0029] FIG. 5C is an end view of the example system shown in FIG. 5A viewed from the opposite end.

[0030] FIG. 5D is a top view of the example system shown in FIG. 5A.

[0031] FIG. 6A is a perspective view of an example head support brace in accordance with the present technology.

[0032] FIG. 6B is a top view of the example head support shown in FIG. 6A.

[0033] FIG. 6C is an end view of the example head support shown in FIG. 6A.

[0034] FIG. 6D is a front view of an anterior coil having a single loop in accordance with one example of the present technology.

[0035] FIG. 6E is a front view of an anterior coil having two loops in accordance with another example of the present technology. Attorney Ref. No. 00846-U8616.PCT

[0036] FIG. 6F is a front view of an anterior coil having a series of five loops in accordance with an example of the present technology.

[0037] FIG. 7A is a schematic perspective view of an example ultrasound transducer assembly in accordance with the present technology.

[0038] FIG. 7B is a partially exploded view of the ultrasound transducer assembly of FIG. 7 A.

[0039] FIG. 7C is a top cross-section view of the ultrasound transducer assembly of FIG. 7A taken through the three positioning coils.

[0040] FIG. 8A is a side cross-section view of an example positioning coil in accordance with the present technology.

[0041] FIG. 8B is an exploded side view of the positioning coil of FIG. 8 A.

[0042] FIG. 9 is a perspective view of another example MRgFUS system in accordance with the present technology.

[0043] FIG. 10 is a perspective view of another example MRgFUS system in accordance with the present technology.

[0044] FIGs. 11A-11D show results from swine MRgFUS ablation in accordance with an example. (A) Coronal oblique 3D segmented EPI image with real-time MR temperature monitoring shows focal ablation of medial branch (MB) nerve at L2 level (yellow arrow). (B) Temperature rise as a function of time with a peak temperature rise of ~33 °C above body temperature. (C) Swine positioned in oblique supine position above the FUS transducer. White volume overlay on (C) T2w MRI and (D) T2 map (black arrow) shows lethal thermal dose volume along MB nerve course.

[0045] FIGs. 1 IE-1 IF are performance characterization of the ultrasound transducer used in an example of the presented cervical MRgFUS system where a 2D hydrophone scan (Onda HNA-0400) of the (E) transverse and (F) longitudinal patterns are shown, obtained at a transducer output of 20 acoustic W under free-field conditions. In (b) the transducer is located to the left of the image.

[0046] FIGs. 11G-11H show ultrasound transducer pressure over a range of therapeutic power output levels. (G) The measured pressure wave over two acquired cycles and (H) the measured peak positive (red x) and peak negative pressure (black x) as a function of acoustic power. Attorney Ref. No. 00846-U8616.PCT

[0047] FIG. 12A is a graph showing a comparison of the positioning coil prediction accuracy and measured focal point position of the transducer. The predicted and measured position is shown individually for all three MRI coordinate directions. The Euclidean distance error for all measured points was found to be 2.22 ± 0.74 mm.

[0048] FIGs. 12B-12C are imaged SNR of the cervical neck system using the dual coil system.

[0049] FIG. 12D: The magnetic resonance temperature measurement precision during one sonication at level C3-4 in a goat.

[0050] FIGs. 12E-12H: Demonstration of MR-ARFI and MRTI utilized for MRgFUS in the cervical spine of the goat model.

[0051] FIGs. 12I-12K: Example of MRgFUS heating at a C2-3 level which shows the peak heating rise in °C for two individual sonications that were performed (I and J) with the cumulative thermal dose in cumulative equivalent minutes at 43 °C for all sonications (K) which shows the T1 -weighted contrast-enhanced image at that treated level.

[0052] FIG. 12M shows an image including a liquid filled bellows and coupling membrane with ultrasound rays overlaid to show a FUS focal spot within a target volume.

[0053] FIG. 13 shows (left) an example of 3D Tlw pig image above a MRgFUS transducer, and (right) a semi-automatic segmentation of the anatomy, creating a numerical model for acoustic modeling.

[0054] FIGs. 14A-14D are composite display images including MRI images with overlaid volumetric temperatures.

[0055] These drawings are provided to illustrate various aspects of the invention and are not intended to be limiting of the scope in terms of dimensions, materials, configurations, arrangements or proportions unless otherwise limited by the claims.

[0056] DETAILED DESCRIPTION

[0057] While these exemplary embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, it should be understood that other embodiments may be realized and that various changes to the invention may be made without departing from the spirit and scope of the present invention. Thus, the following more detailed description of the embodiments of the present invention is not intended to limit the scope of Attorney Ref. No. 00846-U8616.PCT the invention, as claimed, but is presented for purposes of illustration only and not limitation to describe the features and characteristics of the present invention, to set forth the best mode of operation of the invention, and to sufficiently enable one skilled in the art to practice the invention. Accordingly, the scope of the present invention is to be defined solely by the appended claims.

[0058] Definitions

[0059] In describing and claiming the present invention, the following terminology will be used.

[0060] The singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a membrane” includes reference to one or more of such materials and reference to “the transducer” refers to one or more of such devices.

[0061] As used herein with respect to an identified property or circumstance, “substantially” refers to a degree of deviation that is sufficiently small so as to not measurably detract from the identified property or circumstance. The exact degree of deviation allowable may in some cases depend on the specific context.

[0062] As used herein, “adjacent” refers to the proximity of two structures or elements. Particularly, elements that are identified as being “adjacent” may be either abutting or connected. Such elements may also be near or close to each other without necessarily contacting each other. The exact degree of proximity may in some cases depend on the specific context.

[0063] As used herein, the term “about” is used to provide flexibility and imprecision associated with a given term, metric or value. The degree of flexibility for a particular variable can be readily determined by one skilled in the art. However, unless otherwise enunciated, the term “about” generally connotes flexibility of less than 2%, and most often less than 1%, and in some cases less than 0.01%.

[0064] As used herein, a plurality of items, structural elements, compositional elements, and / or materials may be presented in a common list for convenience. However, these lists should be construed as though each member of the list is individually identified as a separate and unique member. Thus, no individual member of such list should be construed as a de Attorney Ref. No. 00846-U8616.PCT facto equivalent of any other member of the same list solely based on their presentation in a common group without indications to the contrary.

[0065] As used herein, the term “at least one of’ is intended to be synonymous with “one or more of.” For example, “at least one of A, B and C” explicitly includes only A, only B, only C, or combinations of each.

[0066] Numerical data may be presented herein in a range format. It is to be understood that such range format is used merely for convenience and brevity and should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a numerical range of about 1 to about 4.5 should be interpreted to include not only the explicitly recited limits of 1 to about 4.5, but also to include individual numerals such as 2, 3, 4, and subranges such as 1 to 3, 2 to 4, etc. The same principle applies to ranges reciting only one numerical value, such as “less than about 4.5,” which should be interpreted to include all of the above-recited values and ranges. Further, such an interpretation should apply regardless of the breadth of the range or the characteristic being described.

[0067] Any steps recited in any method or process claims may be executed in any order and are not limited to the order presented in the claims. Means-plus-function or step-plus- function limitations will only be employed where for a specific claim limitation all of the following conditions are present in that limitation: a) “means for” or “step for” is expressly recited; and b) a corresponding function is expressly recited. The structure, material or acts that support the means-plus function are expressly recited in the description herein. Accordingly, the scope of the invention should be determined solely by the appended claims and their legal equivalents, rather than by the descriptions and examples given herein.

[0068] Example Embodiments

[0069] The technology described herein involves magnetic resonance guided focused ultrasound systems (MRgFUS) and methods that can be used to treat various conditions related to the neck. In certain examples, the systems and methods can be used to treat pain, such as pain from facetogenic or occipital neuralgic pain, or pain due to osteoid osteoma or vertebral body metastases in the cervical spine, or other sources of neck pain. The systems Attorney Ref. No. 00846-U8616.PCT and methods can also be used to treat soft tissue of the head and neck, such as head and neck tumors. These treatments can include applying focused ultrasound energy to tissue within the neck or head of a patient. Depending on the strength of the power of the focused ultrasound, the target tissue can be ablated, heated, or otherwise stimulated.

[0070] As mentioned above, some previous treatments for neck pain have involved RFA of cervical facet joints. The cervical facet joints are innervated by medial branches of the dorsal rami from the same level and the level above and are RFA targets, as in the lumbar spine. However, neck percutaneous procedures pose even greater risks of complications compared to lumbar RFAs given the close proximity of critical vascular and neural structures to the osseous spine and the cervical spinal cord such that off target trajectory can be catastrophic. Major complications, such as stroke and carotid blowout, have been reported with percutaneous RFA procedures because of the proximity of RFA electrodes to the carotid artery. For cervicogenic headache, the targets for RFA can include the third occipital nerve and an articular branch of the C3 posterior ramus, which innervate the C2-3 facet joint. These targets are precariously close to the vertebral arteries and neural structures such as the spinal cord. Procedures at these higher levels have adverse event rate of 18.5%. Interventionalists most often use fluoroscopic osseous landmarks for facet RFAs, aiming for the articular pillar. The inability to visualize the intervening structures increases the risk of complications due to imprecise targeting, which can be solved with high resolution MR imaging. MR-guidance provides superior contrast and resolution, which is advantageous in avoiding inadvertent vessel or nerve injury.

[0071] Focused ultrasound (FUS) has been shown to decrease the functionality of targeted neurons, which may be helpful to treat chronic pain, including chronic migraines. MRgFUS allows for non-invasive and precise ablation of targets in the spine. In addition to ablative procedures, FUS has the potential to treat pain by neuromodulation of the spinal pain generators without surrounding tissue damage. The biological effects of FUS are dependent on the specific tissue being treated and the FUS parameters used, including the FUS intensity and the sonication duration. FUS has been shown to stimulate neuronal activity at low exposures or inhibit it at higher exposures in both the central nervous system and peripheral nervous system. Attorney Ref. No. 00846-U8616.PCT

[0072] FUS performed under non-ionizing MR-guidance offers many benefits including better treatment visualization, excellent soft tissue characterization, three-dimensional imaging, and real-time treatment feedback and monitoring. These factors allow for accurate and precise targeting while avoiding injury to adjacent structures in an anatomic landscape of closely apposed critical structures.

[0073] A cervical spine-specific MRgFUS device for ablation can provide a non-invasive alternative to the current invasive or systemically detrimental treatment modalities to treat neck pain. The safety and efficacy for cervical FJ and third occipital nerve (TON) ablation can be provided. There is a broad patient population who can benefit from this treatment, in part because neck pain affects all ages: those patients with chronic neck pain not ameliorated by conventional methods (i.e., medical management, physical therapy, and percutaneous treatments), and those patients who are not candidates for surgery or invasive spinal stimulators. This contribution is significant because it can offer MRgFUS as a non-invasive treatment option for neck pain and potentially decrease the detrimental effect of dependence on oral analgesic medications.

[0074] This system incorporates a focused ultrasound system that is MRI compatible, integrating all features used to generate high resolution magnetic resonance images to accurately and safely deliver and monitor focused ultrasound energy. This can include a patient-specific neck cradle support that is focused ultrasound and MRI compatible, integrated MRI receiving and positioning coils and an acoustic coupling device. In certain examples, a cervical spine specific magnetic resonance guided focused ultrasound system for the treatment of neck pain can provide a non-invasive alternative to the current invasive and systemically detrimental treatment modalities to treat neck pain. It will also potentially decrease the detrimental effect of dependence on oral analgesic medications.

[0075] In one example of the present technology, a magnetic resonance guided focused ultrasound (MRgFUS) system for treatment of neck pain of a patient can include a head support brace, an ultrasound transducer assembly, an acoustic coupling assembly, and a positioning gantry. The head support brace includes a conformal neck cradle having an ultrasound access opening. The at least one imaging MRI coil can be oriented at any location which allows imaging the target tissue at the transducer focus. As non-limiting examples of suitable locations the imaging MRI coil(s) can be embedded in the neck cradle, coupled to Attorney Ref. No. 00846-U8616.PCT the transducer, attached to the patient, other structure, or combinations of these locations. The ultrasound transducer assembly includes a focused ultrasound transducer capable of producing a focused ultrasound and oriented to direct the focused ultrasound through the ultrasound access opening. The acoustic coupling assembly includes a conformable fluid enclosure housing a volume of ultrasound transparent liquid and adapted to transmit the focused ultrasound from the focused ultrasound transducer to skin of the patient. The positioning gantry is operatively connected to the ultrasound transducer assembly and adapted to translate the ultrasound assembly in at least one direction relative to the patient.

[0076] FIG. 1A shows a perspective view of an example MRgFUS system 100. This system includes a head support brace 110 that includes a conformal neck cradle 120. The conformal neck cradle includes an imaging MRI coil 122 embedded in the neck cradle. The neck cradle also includes an ultrasound access opening 124 which can allow ultrasound to reach the neck of the patient. A ultrasound transducer assembly 130 includes a focused ultrasound transducer 132 that can produce focused ultrasound. This ultrasound transducer assembly is oriented so that the focused ultrasound is directed through the ultrasound access opening. The system also includes an acoustic coupling assembly 140 that includes a conformable fluid enclosure 142 housing a volume of ultrasound transparent liquid. The acoustic coupling assembly is between the ultrasound transducer and the neck of the patient, which allows the focused ultrasound to be transmitted through the ultrasound transparent liquid to the skin of the patient. The system also includes a positioning gantry 150 operatively connected to the ultrasound transducer assembly. The positioning gantry can translate the ultrasound transducer assembly in at least one direction with respect to the patient. In this particular example, the positioning gantry allows the ultrasound transducer assembly to be moved with multiple degrees of freedom. This allows the ultrasound transducer to be moved so that the focal point of the focused ultrasound can be at a variety of different locations within the neck of the patient.

[0077] An exploded view of the example system 100 is shown in FIG. IB. The head support brace 110 is not directly connected to the positioning gantry 150 or the ultrasound transducer assembly 130 or the acoustic coupling assembly 140. In this particular example, the head support brace includes attachment rods 112 that can be attached to another structure, such as an MRI sled (not shown) which can include a patient support bed, orientation gantry, or any Attorney Ref. No. 00846-U8616.PCT other patient support device that carries a patient in an MRI device. The head support brace also includes articulated supports 114 connecting the neck cradle 120 to the attachment rods. In some cases, the articulated supports and / or the attachment rods can be moveable to allow for positioning of the patient. For example, the attachment rods can be moveable by sliding at a connection point with an MRI sled or other patient support. The articulated supports can be moveable at hinge joints. Together, these can provide the head support brace with multiple degrees of freedom of motion to position the head and neck of the patient. In certain examples, the head support brace can allow translational motion of the patient head and neck along a superior-inferior axis (i.e., in the direction of the head or in the direction of the feet of the patient) and / or along an anterior-posterior axis (i.e., in the direction of the front of the patient or in the direction of the back of the patient). In further examples, the head support brace can allow rotational motion of the patient head and neck about an axis of rotation that extends in the lateral direction (i.e., from side to side of the patient) and / or about an axis of rotation that extends in the superior-inferior direction and / or about an axis of rotation that extends in the anterior-posterior direction. In some examples, the head support brace can be movable with 1-5 degrees of freedom. In further examples, any moveable joints in the head support brace can be locked in place to prevent motion of the patient head and neck during a treatment.

[0078] The positioning gantry 150 can also provide multiple degrees of freedom for moving the ultrasound transducer assembly 130 and the acoustic coupling assembly 140. Because the positioning gantry allows the ultrasound transducer assembly to be moved to various different positions and angles with respect to the patient, and because the head support brace 110 allows the patient neck and head to be positioned in various positions, the system as a whole can be highly adaptable to position the ultrasound transducer to target a desired target tissue in the neck or head of the patient. The positioning gantry in this example includes a base 152 that can be attached to a patient support, such as an MRI sled. The base includes an arcuate track 154 that forms an arc around the patient neck. The positioning gantry also includes a shuttle 156 with articulated supports 158 that connect the shuttle to the ultrasound transducer assembly. The shuttle can move along the arcuate track, and the articulated supports can allow the transducer assembly to be moved with one or more degrees of freedom with respect to the shuttle. In some examples, the articulated supports can provide translation Attorney Ref. No. 00846-U8616.PCT and / or rotational motion to the ultrasound transducer assembly. Together, the motion of the shuttle along the arcuate track and the motion of the articulated supports can allow the ultrasound transducer assembly to be positioned at a wide variety of locations about the neck or head of the patient and the ultrasound transducer assembly can be angled at a variety of angles to focus the ultrasound on target tissues in the neck or head of the patient. In some examples, the articulated supports can move the ultrasound transducer assembly with 1-3 translational degrees of freedom and 1-3 rotational degrees of freedom with respect to the shuttle. The motion of the shuttle along the arcuate track provides an additional degree of freedom that is both translational and rotational. In certain examples, the positioning gantry as a whole can move the ultrasound transducer assembly with 1-8 total degrees of freedom.

[0079] The ultrasound transducer assembly 130 is depicted with a focus cone 134 emitted from the ultrasound transducer. The focus cone is not a physical part of the ultrasound transducer, but rather represents the ultrasound being focused to a focal point 136. When the MRgFUS system 100 is used to treat a patient, the focal point can be positioned at a target tissue in the head or neck of the patient. The acoustic coupling assembly 140 is placed over the ultrasound transducer. The acoustic coupling assembly contains an ultrasound- transparent liquid that conducts ultrasound from the transducer to the skin of the patient.

[0080] The MRgFUS system can be compatible with MRI scanners, so that the MRgFUS system, together with a patient whose head is supported by the head support brace, can be placed in an MRI scanner. The MRI scanner can be used to generate images of tissue structures in the neck of the patient, including vertebrae, nerves, and others. These images can be used to aim the focused ultrasound transducer at a target tissue to be treated. As mentioned above, the MRgFUS system can include a neck cradle and at least one radio frequency imaging MRI coil which can be embedded in the neck cradle or associated with the ultrasound transducer assembly. This imaging MRI coil can be used together with the MRI scanner to generate very clear images of the neck of the patient. In particular, the images can be clearer than images generated with a generic MRI scanner due to the imaging MRI coils in the neck cradle. The imaging MRI coils can be positioned as close as possible to the neck of the patient. The neck cradle can be a particularly effective location since it can be in direct contact with the neck and can be shaped to conform to the neck of the patient. This allows the imaging MRI coils to be closer to the target tissue, resulting in clearer MRI images Attorney Ref. No. 00846-U8616.PCT generated by the MRI scanner. These MRI coils are shape and size dependent based on the shape of the anatomy and skin surface and the depth of the imaging volume. Although MRI imaging coils are typically round in shape, these coils can be made to have any shape that forms a loop and can be positioned near the skin surface in order to be closer to the volume of tissue being imaged. The imaging coils can be made to conform to the head and neck support if needed or can be mounted on the surface of the coupling fluid membrane but can be near the surface of the skin for improved signal acquisition. Imaging coil signal sensitivity profdes are such that the highest signal is achieved near the axis of the coil and that this signal decreases as the source of the signal gets further away from the coil. In order to achieve the highest signal-to-noise ratio (SNR) from these imaging coils they can have a radius that is about the same distance as the depth of the imaging volume being imaged. If the coils are smaller than this, the imaging region does not penetrate deep enough to image target tissue, and if they are too large, they pick up additional unnecessary noise from surrounding tissue that is not required for imaging the target volume. The imaging MRI coils can be tuned in their environment using distributed capacitors in or around the circumference of the loop. The values of the tuning capacitors of the imaging coils is dependent on the inductance of the coil loop and the patient resistive load, which is generally patient specific. The frequency the coils need to be tuned to is also dependent on the frequency of the rotating hydrogen spins of the molecules in the given MRI scanner. This frequency is generally set by the magnetic field strength of the scanner. In addition to being tuned to the correct frequency, the coils can be power matched to the cables for maximum power transfer between the coil and the preamp and provide a noise optimized impedance to the preamp for improved SNR of the acquired images. This tuning and matching of the imaging coils can usually be done in the same environment as the actual imaging and treatment studies, therefore, the transducer, coupling fluid, support hardware and patient can all be present in order for the imaging coil to have the correct inductance and resistive load for optimal imaging in that complicated environment. Because of the complexity of the tune and matching process, the imaging coils can employ a remote tune and match circuit for the coils that allows the user to position the hardware and patient on the MRI table and then do the bulk of the tuning and matching remotely, so as to avoid the need to repeatedly move the patient and or hardware to reach the capacitor components on the coil loops for tuning and Attorney Ref. No. 00846-U8616.PCT matching. These remote tune and match circuits can allow the users to use cable lengths of various lengths between the coil and the preamplifiers with little SNR loss.

[0081] Additional MRI coils can also be located in the ultrasound transducer assembly. In certain examples, at least one positioning MRI coil can be coupled to the focused ultrasound transducer. In further examples, at least three positioning MRI coils can be coupled to the focused ultrasound transducer. These coils can allow the position of the ultrasound transducer to be tracked in MRI space. The position of the focal point relative to the ultrasound transducer can be known. Therefore, the positioning MRI coils can allow the position of the focal point to be tracked in MRI space. In some examples, a target tissue can be located using MRI imagery, and the location of the focal point of the ultrasound transducer can also be located using MRI imagery. The ultrasound transducer assembly can be moved using the positioning gantry until the focal point overlaps with the target tissue. When the ultrasound transducer has been aimed in this way, the ultrasound transducer can be activated to sonicate the target tissue with a desired amount of focused ultrasound energy to ablate the tissue or to heat the tissue or to otherwise stimulate the tissue. As a guideline, RF imaging coils can be generally circular in shape, made of copper wire or foil, and placed near the anatomy of interest. Although not always achieved depending on anatomy and device limitations, the ideal imaging depth (location of highest SNR) is along the normal axis of the coil, one coil radius deep (away from the plane of the coil). Thus, as anatomy depth increases, the size of the coil can also be increased to achieve strong SNR.

[0082] In some examples, the positioning gantry can be attached to or integrated in a patient support such as an MRI sled that can support the patient in the MRI scanner. FIG. 2 shows an example MRI sled 200 with an example MRgFUS system 100 attached to the sled. A patient 202 rests on the sled. The head of the patient is supported by the head support brace 110 of the system. The position of the head and neck of the patient can be adjusted by moving the head support brace. The position and angle of the ultrasound transducer assembly 130 can also be adjusted using the positioning gantry 150. In some examples, these mechanical adjustments can be made to get the focal point of the ultrasound as close as possible to the target position. Additional fine adjustments to the position of the focal point can be made using electronic steering of the ultrasound beam in the ultrasound transducer itself. Attorney Ref. No. 00846-U8616.PCT

[0083] Further, in some cases, the MRI sled 200 can include a base portion 204 and an assembly deck 206 where the MRI sled and assembly deck can slide along a z-axis with respect to one another. More specifically, the base portion can be used for sliding the patient, positioning gantry, and MRgFUS system into an MRI device. The assembly deck can support the positioning gantry and patient support while also allowing minor adjustments along the z-axis. The base portion and assembly deck can be slidably connected via linear tracks 208 and relative motion controlled via a MR-safe piezoelectric driver motor 210. See FIG. 4B for further details.

[0084] As a general guideline, the focused ultrasound focal point can be adjusted with the phased array ultrasound transducer within a smaller region of interest than can be achieved with mechanical motion of the entire ultrasound transducer assembly via the positioning gantry. For example, the electronic steering achieved by the transducer can allow tuning of the position of the beam once the transducer is mechanically moved to a target level or location. In one example, the mechanical motion of the gantry can move up to 50 cm, while electronic steering can move the focal point by around 15 mm. In further examples, the mechanical adjustments of the gantry can be accurate to within about 1 cm to about 2 cm, while the electronic steering of the focal point can be accurate to within less than 1 mm.

[0085] Additional views of the MRI sled 200 with the attached MRgFUS system 100 are shown in FIGs. 3A-3D. FIG. 3A shows a perspective view of the system without the patient. FIG. 3B shows a side view of the system. This view shows how the head support brace 110 includes attachment rods 112 that are attached to a patient positioning chair 250 that can be fixed to the MRI sled. The head support brace can be supported by these attachment rods, which allows the head support brace to be adjusted independent of the positioning gantry. In some examples, the head support brace can be supported by the attachment rods alone, and the head support brace may not be physically connected to the positioning gantry 150 or the ultrasound transducer assembly 130 or the acoustic coupling assembly 140. In other examples, the head support brace can be connected to the positioning support gantry for additional support.

[0086] FIG. 3C shows a top down view of the MRgFUS system 100 and MRI sled 200 and the patient positioning chair 250. In this view it is clearly visible that the neck cradle 120 has two ultrasound access openings 124, one on each side of the neck cradle. The acoustic Attorney Ref. No. 00846-U8616.PCT coupling assembly and the ultrasound transducer assembly can be moved to either of these openings so that the ultrasound used to treat the patient passes through either of these openings. Alternatively, a system can include two ultrasound transducer assemblies and two acoustic assemblies, one on each side. This can allow ultrasound to be transmitted through both of the ultrasound access openings for bilateral treatment. In other examples, the neck cradle can have ultrasound access openings of any other suitable shape or size or number. For example, a neck cradle can have a single larger ultrasound access opening. The single opening can allow access to both sides of the neck of the patient. This can allow a single ultrasound transducer assembly to be moved to either side of the neck, or for two ultrasound transducer assemblies to be used for bilateral treatment. In further examples, the neck cradle can have three ultrasound access openings, or four ultrasound access openings, or more.

[0087] FIG. 3D shows an end view of the MRgFUS system 100 and MRI sled 200. This view shows the acoustic coupling assembly 140 protruding through one of the ultrasound access openings 124 of the neck cradle 120. The acoustic coupling assembly includes a conformable fluid enclosure 142, which can be a flexible membrane or balloon filled with an ultrasound-transparent liquid. When the patient is not present, the conformable fluid enclosure can have a rounded dome shape as shown in FIG. 3D. When the patient is present, the conformable fluid enclosure can deform and conform to the neck of the patient. Therefore, when the neck of the patient is present in the neck cradle, the conformable fluid enclosure may not protrude through the ultrasound access openings as shown in FIG. 3D. This figure also shows the focal point 136 of the ultrasound transducer assembly 130. As explained above, this is not a physical part of the ultrasound transducer assembly, but rather the focal point represents the location where ultrasound energy will be focused. When a patient is present, the focal point will be located inside the head or neck of the patient to focus the ultrasound energy on a target tissue.

[0088] FIG. 4A shows a perspective view of an example MRgFUS system 100 without the head support, to clearly display that other components of the system. This figure shows a positioning gantry 150 that supports an ultrasound transducer assembly 130 with an acoustic coupling assembly 140 positioned to transmit focused ultrasound from the ultrasound transducer assembly to the skin of a patient. In this example, the positioning gantry includes a base 152 having an arcuate track 154 that forms an arc about the neck of the patient. A Attorney Ref. No. 00846-U8616.PCT shuttle 156 is associated with the arcuate track to move along the arcuate track to various different positions relative to the patient. The shuttle also includes articulated supports 158 that connect the shuttle to the ultrasound transducer assembly. The articulated supports allow the ultrasound transducer assembly to be translated and / or rotated in multiple directions, which can be used to aim the focused ultrasound at a target tissue of the patient.

[0089] FIG. 4B shows a cross-sectional view of the system 100 when the shuttle 156 is positioned in the center of the arcuate track 154 of the positioning gantry 150. In this view, some of the articulated supports 158 are visible and some of the internal features are visible. For example, the ultrasound transducer assembly 130 includes a focused ultrasound transducer 132. In this cross-sectional view, the concave shape of the focused ultrasound transducer can be seen, which helps provide focusing of the ultrasound energy. The crosssection of the acoustic coupling assembly 140 shows that the acoustic couple assembly fits over the top of the ultrasound transducer assembly and includes a conformable fluid enclosure 142. This figure also shows part of an MRI sled 200 attached to the base 152 of the positioning gantry. As described previously, the MRI sled can include a base portion 204 and an assembly deck 206 having a linear track 208 which allows the assembly deck to slide along a z-axis with respect to the base portion via a driver motor 210.

[0090] FIG. 4C shows another similar example system 100 that is configured for bilateral treatment. This example includes a positioning gantry 150 that has two shuttles 156. Each of the shuttles supports its own ultrasound transducer assembly 130 and acoustic coupling assembly 140. The two shuttles can be independently moveable along the arcuate track 154 to the extent that there is space with both shuttles and ultrasound transducer assemblies and acoustic coupling assemblies present. This arrangement can allow for treating patient with focused ultrasound from two different directions at once.

[0091] FIGs. 5A-5D show additional views of the MRgFUS system 100. FIG. 5 A shows a view in an inferior to superior direction, as if viewing from the feet of a patient toward the head of the patient. This view shows the arcuate shape of the arcuate track 154 that is part of the positioning gantry 150. The arcuate track allows the shuttle 156 supporting the ultrasound transducer assembly 130 and the acoustic coupling assembly 140 to move around the neck, while keeping the ultrasound transducer pointed toward the neck. The shuttle and / or track can include a lock that allows the shuttle to be locked in place at different positions along the Attorney Ref. No. 00846-U8616.PCT track. In this figure, the head support brace 110 appears to be suspended above the other components of the system. As explained above, the head support brace can be connected to a patient support, such as a patient support chair fixed to an MRI sled, through the attachment rods 112. This figure also shows the acoustic coupling assembly protruding through an ultrasound access opening 124 of the neck cradle 120. The focal point 136 of the ultrasound transducer assembly is located at a point where the head or neck of the patient will be when a patient is present. The focal point can be located on an opposite side of the ultrasound access opening from the ultrasound transducer.

[0092] FIG. 5B shows a side view of the MRgFUS system 100. This view clearly shows some of the articulated supports 158 of the positioning gantry 150. The articulated supports can be connected to the shuttle 156 and to the ultrasound transducer assembly 130 to allow the ultrasound transducer assembly to be moved with respect to the shuttle. As explained above, in some examples, the articulated supports can provide multiple degrees of freedom for moving the ultrasound transducer assembly with respect to the shuttle. For example, the articulated supports can allow the ultrasound transducer assembly to be translated along up to three different axes and rotated about up to three different axes. The shuttle itself can provide additional degrees of freedom as the shuttle allows the ultrasound transducer assembly to move along the arcuate track. FIG. 5C shows another end view in a superior to inferior direction, as if looking at the top of the head of the patient. This view also shows the arcuate track 154. FIG. 5D shows a top down view of the system. This view shows how the neck cradle 120 is positioned over the arcuate track so that the ultrasound transducer assembly can move along the arcuate track and point the focused ultrasound toward any desired target location in the neck of the patient. The target location can also be in certain portions of the head of the patient that are accessible to the ultrasound.

[0093] Referring to the head support brace in more detail, FIGs. 6A-6C show several views of an example head support brace 110 on its own. The head support brace can be configured to hold the head and neck of the patient above the ultrasound transducer assembly, allowing the ultrasound transducer assembly to be moved to a desired location to target tissue in the head or neck of the patient. FIG. 6A shows a perspective view of the example head support brace. This example includes a neck cradle 120 supported by articulated supports 114. The articulated supports are connected to attachment rods 112, which can be attached to a patient Attorney Ref. No. 00846-U8616.PCT support (not shown). In this example, the neck cradle is a single piece designed to support both the neck and head of the patient. In other examples, the head support brace can include a neck cradle designed to support the neck, and a separate head cradle designed to support the head of the patient.

[0094] FIG. 6B shows a top-down view of the example head support brace 110. The neck cradle 120 can be designed to conform to the neck shape of the patient. In this example, the neck cradle includes a narrowed portion 126 that can conform to a narrowest part of the neck of the patient. The neck cradle also include flared portions 128 below and above the narrowed portion. The flared portions can be designed to conform to the shoulders and upper back of the patient or the head of the patient. FIG. 6C shows an end view in an inferior to superior direction, as if looking up from the feet of the patient toward the head of the patient. This view shows the lower flared portion that is shaped to conform to the shoulders and upper back of the patient.

[0095] FIGs. 6A-6C also show the ultrasound access openings 124 in the neck cradle 120, which provide space for the acoustic coupling assembly to transmit focused ultrasound from the ultrasound transducer to the skin of the patient. The ultrasound access openings can have any desired shape and size. It can be useful to make the ultrasound access openings sufficiently large to allow the acoustic coupling assembly to be move to a variety of positions in contact with the neck or head of the patient. In some examples, the ultrasound access openings can have a dimension (i.e., length or width or diameter of the opening) that is from about 5 cm to about 30 cm, or from about 5 cm to about 20 cm, or from about 5 cm to about 15 cm. In certain examples, the neck cradle can include two ultrasound access openings of similar size and shape, with one opening on each side of the neck cradle. In further examples, the neck cradle can include a single ultrasound access opening that extends on both sides of the neck cradle. The ultrasound access opening can allow the acoustic coupling assembly to be placed in contact with the skin of the patient through the opening. The opening or openings can allow the acoustic coupling assembly to be positioned on either side of the neck of the neck of the patient in some examples. In other examples, the opening can allow two acoustic assemblies to be positioned simultaneously on both sides of the neck, and two ultrasound transducers can be used to provide bilateral ultrasound treatment to the neck. Attorney Ref. No. 00846-U8616.PCT

[0096] FIGs. 6A-6C also show imaging MRI coils 122 embedded in the neck cradle 120, although these imaging coils may be eternally attached to the neck cradle or oriented adjacent (e.g. the transducer assembly) or other location. The imaging MRI coils are radio frequency (RF) coils that are used to generate MRI images when the system and patient are placed in an MRI scanner. These integrated RF coils can provide superior imaging capabilities to visualize the targets and vascular and neural structures in the neck and to increase treatment targeting accuracy. Some existing MRI systems use the body coil or large flex coils wrapped around the patient and transducer. However, these coils are not purpose-built and hence suffer from low SNR at the target tissue. For ablation of targets in the neck and visualization of critical vascular and neural structures, high resolution imaging with dedicated coils can be very beneficial. Therefore, the systems described herein can include neck-specific integrated MRI coils. To image pathologies in the neck, high resolution imaging is desirable. Unlike the head, the neck is more difficult to image because of the different shapes and sizes present in the population. In some examples, an interchangeable neck shape-specific coil can be prepared for clinical anterior neck imaging, that result in 3-4 times SNR improvements compared to the commercial head / neck coils. In the example shown in the figures, the imaging MRI coils are located around the perimeter of the ultrasound access openings 124. In some examples, the neck cradle can include one imaging MRI coil surrounding the perimeter of each of the two ultrasound access openings. In further examples, there can be two or more imaging MRI coils around each ultrasound access opening. The imaging MRI coils can also have other configurations. In some examples, the imaging MRI coils can be located on a side of the ultrasound access opening, or around a perimeter of the neck cradle as a whole. In further examples, the imaging MRI coils can be positioned on an interior surface of the neck cradle, so that, including a thin layer of comfort padding, the coils are near the 5 mm safety limit for proximity to the skin of the patient. In other examples, the coils can be positioned on an exterior surface of the neck cradle, or in a middle volume of the neck cradle between the exterior surface and the interior surface.

[0097] In other examples, one or more imaging MRI coils can be attached to the conformable fluid enclosure 142 so that the coil translates with the transducer during treatments. In this case, the imaging MRI coil can be positioned so that when the enclosure is compressed against the skin, the coil is very near the surface of the skin. Attorney Ref. No. 00846-U8616.PCT

[0098] In further examples, the MRI coils can be positioned on the side and anterior surfaces of the neck to achieve high SNR in the target volume. In other examples, coils can be positioned on the anterior of the neck that work in conjunction with the coils on the posterior of the neck to enhance the MRI signal at the focal point of the transducer and of the target tissue. Anterior neck coils may can have a variety of different shapes to conform to the anterior neck anatomy of any given patient. These coils may be standard coils with cables and their own preamps, or may be wireless coils that just provide magnetic field shaping for the coils on the back of the neck. For any given patient scenario, coils can be placed at any position around the surface of the neck that will provide adequate SNR for focused ultrasound treatment of the target anatomy. As an example of anterior MRI coils, FIG. 6D-F illustrate several non-limiting variations of anterior coils which can be used. FIG. 6D shows an anterior coil 602 having a single loop. FIG. 6E shows an anterior coil 604 having a pair of adjacent loops which are equal in size. FIG. 6F shows an anterior coil 606 having five loops which are distributed across the anterior coil. These three examples represent any number of loops that can be used to form the anterior coil.

[0099] In additional examples, the MRI coils can be positioned near the back of the neck and the sides and anterior surfaces of the neck to completely surround the volume of the neck and provide for volumetric imaging of the target tissue. In some cases, the imaging MRI coils can be flexible. In some cases, the number of imaging coils can range from 1 to 3 or from 1 to 12 or more MRI coils. In some cases, some of the imaging coils can be connected to preamplifiers with cables to create an independent receiver channel of the MRI system, while other MRI coil elements can be wirelessly or magnetically coupled to nearby coil elements without having their own cable, preamplifier and receiver channel. In other cases, the imaging coils may include local shim capability to homogenize the magnetic fields in the volume of the neck. In other cases, dielectric pads and or metamaterials can be used near the surface of the skin to homogenize the signal received from the MRI coils. In other cases, any combination of size, shape and placement of any number of receiver coils, pads and materials can be used to obtain the SNR required for clinically effective visualization and treatment of the target tissue.

[0100] In certain examples, the imaging MRI coils can be positioned so that the focal point of the ultrasound transducer is within about 1 cm to about 10 cm from at least one imaging Attorney Ref. No. 00846-U8616.PCT

[0101] MRI coil, or within about 1 cm to about 8 cm, or within about 1 cm to about 5 cm from at least one imaging MRI coil.

[0102] In some examples, the conformal neck cradle can have a patient-specific shape which is created based on measurements of the patient. Such measurements can be taken via MRI, optical images, 3D scanning, or the like. In other examples, a cast of the patient neck can be made and the cast can be used to make a neck cradle having a shape conforming to the cast. In further examples, the neck cradle can be made using additive manufacturing methods such as 3D printing based on the measurements or 3D scan of the patient. Thus, the neck cradle can be custom made for an individual patient. Furthermore, design of the neck cradle can be a function of headrest angle, head clearance with respect to the MRI scanner bore, degree of spine arching, and transducer clearance against patient, etc. As a general guideline, a headrest angle of about 15° with respect to a chest support portion of the patient support can be used, although angles of 0° to 30° may be used. In addition, contours of the neck cradle can be adjusted to provide for a gap distance of 5 mm or less between the cradle surface and patient skin across the neck cradle surface. In some cases, the acquired 3D scan of a patient can include wrinkles or other artifacts which, if reproduced exactly, can create uncomfortable spots for a patient. Accordingly, an optional smoothing algorithm can be applied to the acquired 3D scan in order to reduce or eliminate such wrinkles and artifacts. Alternatively, or in addition, a thin compressed foam layer or other pad can be fitted along an inside surface of the conformal neck cradle to provide additional patient comfort.

[0103] In other examples, it may be more cost effective and faster to use a pre-made neck cradle instead of creating a new neck cradle for a specific patient. However, the shape of the neck cradle can still be selected to fit the neck shape of the patient. For example, a set of several neck cradles can be prepared ahead of time, where the neck cradles can have several different sizes and shapes to match common neck sizes and shapes in a patient population. One of these pre-made neck cradles can provide the best fit to conform to the neck shape of the patient. The neck cradle with the closest fit can be used, allowing the treatment to be performed without waiting for a custom neck cradle to be made. In further examples, the neck cradles can be reusable so that the same neck cradle can be used again with a different patient in the future. In various examples, the system can include any suitable number of neck cradles having different sizes and shapes, such as from 3 to 12 neck cradles, or from 3 Attorney Ref. No. 00846-U8616.PCT to 9 neck cradles, or from 3 to 6 neck cradles. The neck cradles can have integrated imaging MRI coils or removable coils. Additional neck cradles with different sizes and shapes and integrated imaging coils can be made fairly inexpensively. The imaging coils can be inexpensive, while the more expensive RF preamplifier (‘preamp’) box used with the coils can be a separate component that can be connected to the coils of any of the neck cradles, and thus shared between the different neck cradles. The RF coils can allow for high SNR images to be obtained of the targeted anatomy during all phases of treatment. The multichannel coil can be mechanically compatible with the focused ultrasound transducer and provide parallel imaging capabilities. This system can maintain acoustic transparency and not transfer heat to the skin of the patient. In further examples, an additional anterior coil can be added to the setup for more homogenous SNR throughout the neck if desired.

[0104] In another example, the conformal neck cradle can be further secured to the positioning gantry sufficient to reduce or eliminate relative movement between the patient, the focused ultrasound transducer, and the MRI coils.

[0105] In some examples, the movement of the positioning gantry can be performed by manual adjustment. The ultrasound transducer assembly can be manually moved to a desired location and orientation, facilitated by the positioning gantry. In certain examples, the positioning gantry can include one or more locks to lock the positioning gantry in place once the ultrasound transducer assembly has been moved to its desired location and orientation. For example, in the systems shown in the figures above, the shuttle can be moved to a desired position on the arcuate track, and then the shuttle can be locked in the desired position. The ultrasound transducer assembly can be further moved and / or rotated using the articulated supports attached to the shuttle. The shuttle can include one or more locks to lock the ultrasound transducer in place after it has been move to the desired location and orientation.

[0106] In alternative examples, the movement of the positioning gantry can be performed by motors that may be controlled electronically. For example, motors can be connected to the arcuate track, the shuttle, the articulated supports, or any combination of these to provide motorized movement of the positioning gantry. In some examples, precision motors such as stepper motors can be used to provide fine control over the movement of the positioning gantry. In further examples, a combination of manual adjustment and motorized movement can be used. In such examples, some portions of the positioning gantry can be motorized Attorney Ref. No. 00846-U8616.PCT while other portions can be moved manually. As mentioned above, the ultrasound transducer itself can provide electronic control to steer the focused ultrasound within a certain distance, so that fine adjustments to the location of the focal point can be made electronically using the ultrasound transducer.

[0107] It is noted that the system shown in the figures above is merely one example of the systems described herein. In various other examples, the positioning gantry can have a different design than the design shown in the above figures. In certain examples, the positioning gantry can include an articulated arm that can provide multiple degrees of freedom to translate and / or rotate the ultrasound transducer assembly. In further examples, the positioning gantry can include one or more rails operable to move the ultrasound transducer assembly in one or more directions by linear motion. For example, the positioning gantry can include rails to move the ultrasound transducer along any of the x, y, or z axes.

[0108] The systems described herein can be used to allow treatment of multiple different target tissues without moving the patient. In some examples, the positioning gantry and the electronic steering provided by the ultrasound transducer can be used to target a certain tissue for treatment. After treating this target tissue, and the positioning gantry and / or the electronic steering of the ultrasound transducer can be used to target a different tissue, and then treatment can be performed and that tissue. This can be repeated any number of times as desired to treat multiple target tissues in a patient without moving the patient. In certain examples, multiple vertebral levels can be treated without moving the patient. In further examples, bilateral treatment can be performed either by moving the ultrasound transducer from one side of the neck to the other or by using two ultrasound transducers positioned on either side of the neck.

[0109] Regarding the ultrasound transducer assembly, in some examples the ultrasound transducer assembly can include at least one positioning MRI coil coupled to the focused ultrasound transducer. FIG. 7 A shows a perspective view of an example ultrasound transducer assembly 730. The assembly includes a focused ultrasound transducer held within a frame assembly 732 and three positioning MRI coils 738 arranged in a triangle pattern around the focused ultrasound transducer. The focused ultrasound transducer can produce a focused ultrasound 740 (partially shown). The focused ultrasound transducer assembly can also include a flexible bellows 742. In some cases, the flexible bellows can include a flexible Attorney Ref. No. 00846-U8616.PCT imaging coil 754 (e.g. a dedicated RF receive coil) oriented against the anatomy around the coupling membrane as described below.

[0110] FIG. 7B shows a partially disassembled view of the ultrasound transducer assembly 730. In this view, the flexible bellows 742 is removed to expose a conformable fluid enclosure 746. The conformable fluid enclosure can be retained in place via a securing collar 748. In this example, the securing collar is a two-piece segmented collar which can be attached at a hinge 750. The conformable fluid enclosure can be in contact with the skin of the patient. The conformable fluid enclosure (e.g. flexible bellows) can be filled with a liquid that transmits ultrasound from the transducer to the skin. In some examples, the liquid can include water, a water-based gel, glycerin, propylene glycol, mineral oil, or combinations of these. The conformable fluid enclosure can include a balloon, a membrane, a flexible accordion member, or other conformable enclosure. In a particular example, the conformable fluid enclosure can include a liquid fdled balloon oriented adjacent to and between the focused ultrasound transducer and a neck of the patient at the ultrasound access opening. As a specific example, the conformable fluid enclosure can further comprise a liquid source fluidly connected to the liquid filled balloon, and a control valve which allows selective addition or removal of liquid from the liquid filled balloon via fluid lines 752. This can be useful for changing the volume of the balloon. For example, if the ultrasound transducer assembly is moved closer to the skin of the patient, then some liquid can be removed from the balloon to make the balloon fit in the smaller space. If the ultrasound transducer assembly is moved farther away from the skin of the patient, then more liquid can be introduced into the balloon to expand the balloon to fill the larger space.

[0111] Other arrangements of positioning MRI coils can also be used. These coils can be used to pinpoint the position and orientation of the ultrasound transducer assembly in MRI space using an MRI scanner. The position of the focal point of the ultrasound can then be determined based on the position and orientation of the ultrasound transducer assembly. In certain examples, three positioning coils can be placed circumferentially around the transducer assembly. These coils can be used in conjunction with a simple MRI pulse sequence that has a ID readout gradient applied in all three directions. As illustrated in FIG. 7C, the positions of the three coils can form a triangle with unique side length (i.e. non- symmetrically distributed) which allow the transducer position and focal spot location to be Attorney Ref. No. 00846-U8616.PCT determined automatically in the ultrasound control software environment. For example, software such as ThermoGuide™ Image Guided Therapy, from Pessac, France, can be used.

[0112] Although other positioning coil designs can be used, FIG. 8A-8B illustrate one example positioning coil 800. FIG. 8A shows a positioning coil which can include a primary coil 802 wrapped around a small MR signal producing bead 804. One example may include a benzonatate bead which will produce signal during an MR scan (and also act as an MRI compatible form to wrap wire). The signal produced by the bead 804 is received by the positioning coil (primary coil 802). These positioning coils can be encased in waterproof housings 806 to protect them from any leaking acoustic coupling fluid. In this case, the waterproof housing can be provided as a two-piece assembly which includes a base portion and a cap portion (shown removed in FIG. 7B). The positioning coil can also include a secondary coil 812 which is electrically connected to the primary coil 802. The primary coil can be electrically connected via a primary electrical connection 814 and the secondary coil can be electrically connected via a secondary electrical connection 816 which in this example are isolated from one another via an electrically insulated conduit 818. A cable assembly 810 of the primary electrical connection 814, secondary electrical connection 816, and insulated conduit 818 can optionally be secured using a clasp 820 (e.g. cable tie). To improve treatment workflow and ensure positioning accuracy, three RF positioning coils can be mounted on the rear of the transducer mount to allow for automatic location of the focal spot in MRI coordinates. Alternatively, or in addition, other US focal point tracking techniques can be used such as, but not limited to, MR-ARFI.

[0113] The focused ultrasound transducer can emit focused ultrasound with sufficient power so that the ultrasound energy concentrated at the focal point can heat tissue, ablate tissue, or otherwise treat tissue such as nerves, vertebrae, and so on. Ultrasound-induced bioeffects can depend on the parameters applied: continuous-wave ultrasound primarily causes thermal effects, utilized for hyperthermia and ablative procedures, while pulsed ultrasound can be used for mechanical destruction, vasodilation, and neurostimulation.

[0114] MRgFUS enables ablation of targeted tissue by inducing localized heating, and provides real-time MRI monitoring of temperature and high-quality anatomical images of the internal organs of the patient. This allows for treatment adjustments based on ongoing Attorney Ref. No. 00846-U8616.PCT monitoring of the therapeutic effect on the tissue and also assures maximum effectiveness and safety.

[0115] The MRgFUS system can be capable of determining the amount of energy delivered by the ultrasound sonication as well as ensuring precise targeting without damaging adjacent or intervening tissue. Quantitative MR temperature imaging (MRTI), which is based on the temperature dependence of the water proton resonance frequency shift, enables calculation of thermal dose and superimposes a representation of the regions in which the thermal dose has achieved cytotoxic levels on an anatomic MR image. MRgFUS thermometry is independent of tissue type (apart from cortical bone and fat tissue) and thermally induced tissue changes; therefore, it can be used at all stages of the procedure, from tissue targeting with low-energy sonications, to treatment guidance with high-energy sonications, to prediction of thermal damage. During a MRgFUS procedure, in one example, the temperature-sensitive MR sequence provides a closed-loop control of energy deposition, with temperature accuracy of 1°C, spatial resolution of 1 mm, and temporal resolution of 3 seconds. MR acoustic radiation force imaging (MR-ARFI) allows precise localization of the ultrasound focus with negligible heating to the tissue.

[0116] In one example, the focused ultrasound transducer in the MRgFUS system can be a 256-element phased array transducer. This particular transducer can have an aperture of 12.3 cm with an 11 cm focal length. The 256 transmit elements can each be 5 mm in diameter. Other types of ultrasound transducers can also be used, and may have different numbers of transducer elements, and may have a different aperture and focal length and element size. In some examples, the focal length can be from about 1 cm to about 30 cm, or from about 1 cm to about 20 cm, or from about 5 cm to about 15 cm.

[0117] In one example, a 128 element transducer can have a frequency range of 0.8 to 1.2 MHz and a central frequency of 1 MHz, allowing further patient-specific tailoring of the ultrasound sonications. The transducer can be driven with a MR-compatible multi -channels signal generator such as a generator from Image Guided Therapy in Pessac, France having 0.3-5 MHz bandwidth, 4W / channel, allowing for independent control of the frequency, amplitude and phase of each of the phased-array channels, enabling both electronic beam steering and phase aberration correction. Bandwidth and power per channel can vary considerably depending on the specific signal generator and device configuration. Attorney Ref. No. 00846-U8616.PCT

[0118] A variety of other designs can be used for the components in the MRgFUS system. As an example, FIG. 9 shows another example MRgFUS system 900. This system includes a head support brace 910 that is shaped like the back half of a helmet to support the patient head. This example also includes a conformal neck cradle 920 that has two ultrasound access openings 924 and two MRI coils 922 around the ultrasound access openings. This example includes a positioning gantry 950 with a different design than the examples shown above. The positioning gantry includes an arcuate track 954 formed as a slot in a side of the base 952. An ultrasound transducer assembly 930 is operatively connected to the positioning gantry such that the ultrasound transducer assembly can slide along the arcuate track. The ultrasound transducer assembly includes a focused ultrasound transducer that emits focused ultrasound focusing on a focal point 936. This figure does not show an acoustic coupling assembly, but an acoustic coupling assembly with a conformable fluid enclosure can be added to transmit ultrasound from the ultrasound transducer to the skin of the patient.

[0119] FIG. 10 shows another example system 1000. This system includes an ultrasound transducer assembly 1030 with an accordion shaped acoustic coupling assembly 1040 on the ultrasound transducer assembly. The ultrasound transducer assembly includes a focused ultrasound transducer that focuses ultrasound on a focal point 1036. A conformal neck cradle 1020 is positioned above the ultrasound transducer assembly. The conformal neck cradle includes a single ultrasound access opening 1024 that allows the acoustic coupling assembly to contact the skin of the patient through the opening. In this example, the single ultrasound access opening is large enough that ultrasound can be applied to either side of the neck or bilaterally to both sides of the neck. This figure does not show a positioning gantry, but any type of positioning gantry described above can be used to position the ultrasound transducer assembly.

[0120] The present disclosure also describes methods of making the systems described herein. The various components of the systems described above can be assembled such that the system is highly adjustable and customizable for various patients. As explained above, in some examples the conformal neck cradle can be custom made for each individual patient based on the neck size and shape of the individual patient. In other examples, a number of differently sized and shaped conformal neck cradles can be pre-made, and one of these premade neck cradles can be selected to provide the best fit possible for an individual patient. Attorney Ref. No. 00846-U8616.PCT

[0121] Methods of treatment are also described using the systems described herein. In one example, a method of treatment can include positioning the patient in a head support brace including a conformal neck cradle. The neck cradle can conform to the shape of the neck of the patient, and the neck cradle can include at least one imaging MRI coil embedded in the neck cradle. An ultrasound transducer assembly can be positioned with an acoustic coupling assembly to transmit ultrasound from the ultrasound transducer assembly to the skin of the patient through an ultrasound access opening in the neck cradle. The positioning can be facilitated by a positioning gantry. A target tissue can be located at a focal spot of the focused ultrasound transducer within the neck of the patient. MRI scanning can be used to image the tissue to facilitate locating the target tissue. The target tissue can then be sonicated using the focused ultrasound transducer.

[0122] In some examples, the method of treatment can include locating the focal spot of the focused ultrasound transducer using at least one positioning MRI coil coupled to the focused ultrasound transducer. The position of the focal spot can also be checked by monitoring temperature of tissues shown in MRI images. For example, thermal MRI scanning can monitor the temperature of tissues while an ultrasound pulse is used to heat the tissue at the focal point of the ultrasound transducer. If the temperature rises in the desired target tissue, then this can confirm that the focal point is located at the target tissue. Otherwise, the position of the ultrasound transducer can be adjusted. Thermal MRI scanning can also be used during treatment to ensure that tissue surrounding the target tissue does not heat up to a dangerous temperature. In a certain example, the system can be programmed to automatically discontinue sonication if a nearby or surrounding tissue heats up above a predetermined threshold temperature. In some examples, the ultrasound can provide sufficient energy to the target tissue to ablate the target tissue. In further examples, the target tissue can be a cervical facet joint, a third occipital nerve, an articular branch of the C3 posterior ramus, a medial branch nerve, or a combination thereof.

[0123] Examples

[0124] In one example, a cervical spine MRgFUS system was designed and constructed to be used with a goat test patient. The system included a positioning gantry, head support frame and transducer adjustment and coupling system. The system was installed in a wide bore 3T scanner integrated into the existing MR exam table. Attorney Ref. No. 00846-U8616.PCT

[0125] In this example, the system had a total of 6 independent degrees of freedom. All motion was achieved manually with visual gauges provided for accurate positioning.

[0126] In this example, the cervical spine MRgFUS system consisted of four main components: (1) positioning gantry, (2) head support frame, (3) transducer adjustment and coupling system, and (4) imaging MRI coil(s) and positioning coils. The positioning gantry was constructed of extruded fiberglass components and linear guide bearings that suspend the goat head and neck above the transducer system. Head position adjustments were available in the scanner Z and Y directions, and transducer adjustments were possible along the scanner Z direction. The head support frame can be specifically designed for patient anatomy. In another example for a goat patient, the frame can be a clamping mechanism consisting of a bite bar on one side and a padded bar that fits behind the horns. The frame securely mounts to the positioning gantry with an optional chin tilt adjustment. The frame can be attached to the goat during prep and allows for animal to be positioned in the supine position for posterior targeting. The transducer assembly and acoustic coupling system can contain the phased array ultrasound transducer, three positioning coils for automatically determining transducer and focal spot position in the ultrasound control software environment, supporting electronics for radiofrequency receive coils, and adjustment hardware for radial positioning of the transducer’s focal spot. The transducer can be secured within a water-tight housing with an expanding Tegaderm™ film (3M, St. Paul, Minnesota, USA) coupling membrane that is filled with degassed water until it is acoustically coupled to the skin of the animal. A flexible rubber bellows holds a dedicated RF receive coil against the animal around the coupling membrane. The system is designed to allow for bilateral treatment; however, this present configuration requires that the bellows and coil to be repositioned on the opposite side of the neck for bilateral access. This can involve removal and repositioning of the animal.

[0127] This system can non-invasively treat both neck pain and cervicogenic headache with MRI guided focused ultrasound. This can provide a safer and more effective solution to the existing clinical options.

[0128] This system can provide a safe and efficacious ablation of cervical spine targets via MRgFUS. The system can include design innovations including (1) a novel transducer positioning system allowing bilateral treatment of multiple vertebral levels without moving Attorney Ref. No. 00846-U8616.PCT the patient with (2) a sophisticated neck positioning system and acoustic coupling apparatus accommodating a large range of patient neck sizes, and (3) integrated RF coils to provide superior imaging capabilities necessary to visualize the targets and vascular and neural structures in the neck and to increase treatment targeting accuracy. Procedural innovations include integrated software for accurate treatment planning and monitoring of (1) cervical facet joint and (2) third occipital nerve ablation. Successful translation of this innovative cervical spine-specific MRgFUS system offers a new option for clinical practice and will address a significant unmet clinical need by providing a non-invasive treatment option providing precise targeting and avoiding damage to vital structures in the neck.

[0129] RF can be applied to the medial branches of the dorsal ramus as heat destructive continuous radiofrequency, performed between 60°C and 80°C to destroy the afferents’ soma; or pulsed radiofrequency, in which the RF current is applied in a pulsed fashion to achieve a temperature increase up to 42°C. Pulsed radiofrequency at a 42°C increase for 120 seconds was shown to be less destructive (only transient endoneurial edema) than continuous radiofrequency at a 67°C increase for 60 seconds when applied to rabbit dorsal root ganglion, though both RF techniques disrupt cell substructures. Variables important in determining the extent and permanency of the effective lesion include the ratio of small unmyelinated C fiber afferents to large afferent input to the dorsal horn, the size of the root and ganglia, the presence of CSF acting as an insulator or heat dissipator, the presence of the dural sheath, and the duration of the lesion. Focused ultrasound (FUS) is a totally non-invasive therapeutic technology that uses ultrasonic energy to precisely target tissue deep in the body, and MRL guidance can be used to guide and control treatment in real time and confirm the effectiveness of the treatment.

[0130] In one example, the ultrasound transducer in the cervical neck MRgFUS system is a 256-element phased array transducer. Briefly, this particular transducer has an aperture of 12.3 cm with an 11 cm focal length. The 256 transmit elements are 5 mm in diameter. There are an additional 4 ultrasound receiver elements with more broadband characteristics that can be used to detect any cavitation activity. Radiation force balance measurements were obtained to calibrate the acoustic output of the transducer. Scanning hydrophone measurements were obtained with a calibrated hydrophone (HNA-0400, Onda) under free field conditions. Briefly, the hydrophone is mounted on a gantry with x and y stepper motors Attorney Ref. No. 00846-U8616.PCT to allow a 2D scan to be acquired with 0.25 mm isotropic resolution over a 1 .0 x 1 .0 cm area center at the focal point of the ultrasound beam. The measured 2D complex pressure pattern was then propagated into a 3D volume matching the relevant portion of the simulated model size using the angular spectrum approach.

[0131] Three positioning coils are placed circumferentially around the transducer assembly. These coils are used in conjunction with a simple MRI pulse sequence that has a ID readout gradient applied in all three directions. The positions of the three coils form a triangle with unique side lengths which allow the transducer position and focal spot location to be determined automatically in the ultrasound control software environment (ThermoGuideT™, Image Guided Therapy, Pessac, France). These three coils are encased in waterproof housings to protect them from any leaking acoustic coupling fluid. The accuracy of the positioning coils was assessed by replacing the coupling bellows with a cone that contained a fiducial bead (benzonatate) fixed at the geometric focus of the transducer, allowing an accurate, manual assessment of the true position of the transducer’s focal spot. The positioning coil accuracy was assessed through moving the transducer to eight distinct positions, exploring the full range of movement. The measured positioned (the location of the benzonatate bead) was compared to the prediction provided by the positioning coils.

[0132] Imaging coils can also be integrated into the cervical neck MRgFUS system to both allow adequate SNR in the targeting region for treatment planning and assessment and to ensure that adequate temperature precision can be achieved for the MR temperature imaging. Two prototype coaxial cable RF coils were designed to be positioned on either side of the subject’s neck. One loop was placed around the rubber bellows with an equivalent coil placed on the opposite side of the subject’s neck. Coil SNR was evaluated using a homogeneous CU2SO4 phantom that was positioned in the cervical neck MRgFUS system. SNR was measured using a 2D gradient echo sequence (TR / TE = 500 / 100 ms, flip angle = 90°, resolution = 1 x 1 x 5 mm, FOV = 256 x 256 mm). SNR and noise correlation were calculated for three individual coil configurations: body coil, one coil around the bellows only and two coils placed around the bellows and opposite on the subject’s neck. SNR measurements were quantitatively compared along the approximate ultrasound propagation direction.

[0133] Magnetic resonance temperature imaging precision of the MRgFUS cervical neck system can be determined by calculating the standard deviation of the temperature Attorney Ref. No. 00846-U8616.PCT measurement through time on a voxel wise basis. Mean precision values were calculated on a per animal basis in regions of interest defined in the areas adjacent to the targeted focused ultrasound heating that did not experience heating.

[0134] A transducer positioning protocol was used to position the system. The appropriate model can effectively recapitulate the spectrum of spine degeneration, including reproducible structural, compositional and biomechanical changes. Several studies have demonstrated the usefulness of the animal models (e.g. pig) as an accurate model for facet and SI joints treatment in humans. A goat model increases the feasibility for evaluating FUS application to the central and peripheral nervous system in the neck region because relative larger size compared to that of rodents and relatively similar size to humans as compared to pigs. Specifically, the C2-C4 vertebrae are the best segments for obtaining biomechanical data comparable to the human cervical spine. MRgFUS ablation was compared to RFA of lumbar facet joints in swine. Multiparametric MR imaging can be correlated to histopathological data. Preliminary data demonstrated that MRgFUS applied to the lumbar spine facet joints and medial branch nerves was superior to RFA in precision, measurable ablation effectiveness, and reduction of peripheral tissue damage.

[0135] FIG. 1 IE-1 IF shows performance characterization of the ultrasound transducer used in the presented cervical MRgFUS system. A 2D hydrophone scan (Onda HNA-0400) of the (a) transverse and (b) longitudinal patterns are shown, obtained at a transducer output of 20 acoustic W under free-field conditions. In (b) the transducer is located to the left of the image.

[0136] FIG. 11G-11H shows ultrasound transducer pressure over a range of therapeutic power output levels. (G) The measured pressure wave over two acquired cycles and (H) the measured peak positive (red x) and peak negative pressure (black x) as a function of acoustic power.

[0137] FIG. 12A shows comparison of the positioning coil prediction accuracy and measured focal point position of the transducer. The predicted and measured position is shown individually for all three MRI coordinate directions. The Euclidean distance error for all measured points was found to be 2.22 ± 0.74 mm.

[0138] FIGs. 12B and 12C show image SNR of the cervical neck system using the dual coil system. The two coil conditions were evaluated with a cylindrical Cu2SO4 phantom. Axial images showing the dual coil (top) and body coil (bottom) conditions. Quantitative Attorney Ref. No. 00846-U8616.PCT measurements along the approximate ultrasound propagation direction (white dashed line) are shown. The dual coil condition provides an approximate 5 fold increase in SNR compared to the body coil only condition at the lowest signal position at the center of the phantom.

[0139] FIG. 12D shows the magnetic resonance temperature measurement precision during one sonication at level C3-4 in goat 4 (G23-004, the most ‘precise’ goat). The precision in the defined square ROI (25 x 25 voxels) is 0.45°C. The area indicated by the lower arrow is where the heating occurred during the sonication. The area at the top of the image indicated by the upper arrow has a decreased measurement precision due to lower SNR and the motion artifacts of the esophagus, trachea and large veins and arteries in the region.

[0140] FIGs. 12E-12H show a demonstration of MR-ARFI and MRTI utilized for MRgFUS in the cervical spine of the goat model. FIGs. 12E and 12G show the MR-ARFI displacement measured at a location in the muscle in micrometers, proximal to the intended target to verify focused ultrasound accuracy. FIGs. 12F and 12H show the MRTI at the peak temperature rise in °C during a focused ultrasound sonication at the intended level. FIGs. 12E and 12F are for level C4-5 in goat G22-004 slice 170, and FIGs. 12G and 12H are for level C2-3 in goat G23-001.

[0141] FIGs. 12I-12L show an example of MRgFUS heating at a C2-3 level. FIG. 121 shows the peak heating time for three individual sonications performed and FIG. 12J shows the cumulative thermal dose for all sonications. FIG. 12K shows the Tl-weighted contrast- enhanced image at that treated level. FIG. 12L shows H&E histology.

[0142] FIG. 12M shows an MRI image including a bellows and coupling membrane with ultrasound rays overlaid to show a FUS focal spot within a target volume. In this case, an expandable membrane (e.g. balloon) is filled with an ultrasound coupling liquid (e.g. water) to allow conformal coupling with skin of the patient. An optional bellows and support structure can be used to house the expandable membrane during inflation and storage.

[0143] In one example, the system design can be constructed with three main components: (1) an integrated focused ultrasound applicator and power generator, (2) mechanical positioning system and (3) neck holder with integrated RF coils. Software for positioning and monitoring can be used. The patient can be treated in a supine position and the FUS applicator can be embedded into the treatment table. The supine orientation will allow comfortable positioning of the patient and bilateral treatment access without moving the Attorney Ref. No. 00846-U8616.PCT patient. In one example, an ultrasound transducer is oriented to direct focused ultrasound through an ultrasound opening which allows for the ultrasound transducer to access the patient from multiple angles. Replaceable neck cradles with integrated MRI RF coils can be designed for different neck shapes, determined using rendered anatomized MR or CT datasets. Generally, 3-4 different size cradles with RF coils can accommodate the various patient sizes, but additional sizes can be manufactured fairly inexpensively as the expensive component (RF preamp box) can be shared among coils. The RF coils can allow for high SNR images to be obtained of the targeted anatomy during all phases of treatment. This multi-channel coil can be mechanically compatible with the focused ultrasound applicator and provide parallel imaging capabilities. This system can maintain acoustic transparency and not transfer heat to the skin of the patient. If needed an additional anterior coil can be added to the setup for more homogenous SNR throughout the neck. To improve treatment workflow and ensure positioning accuracy, three RF positioning coils can be mounted on the transducer mount to allow for automatic location of the focal spot in MRI coordinates. In one example, the 128 element transducer can have a frequency range of 0.8 to 1.2 MHz and a central frequency of 1 MHz, allowing further patient-specific tailoring of the ultrasound sonications. Individual and composite system components can be designed, allowing the effects of different patient sizes on the FUS applicator design to be simulated, minimizing required hardware iterations. The transducer can be driven with a MR-compatible multichannels signal generator (Image Guided Therapy, Pessac, France, 0.3-5 MHz bandwidth, 4W / channel), allowing for independent control of the frequency, amplitude and phase of each of the phased-array channels, enabling both electronic beam steering and phase aberration correction.

[0144] Ultrasound fields using the parameters identified through patient-specific spine models can produce efficacious ablation with minimal damage to adjacent areas. Hydrophone measurements can be used where the focused ultrasound transducer of the prototype system is positioned in a large cylinder with a fiberoptic hydrophone (Onda Corp., 10 kPa to 15 MPa range) that can be scanned with two stepper motors in a transverse plane near the geometric focus. Using the angular spectrum method, the 2D complex pressure pattern can be mapped to characterize the full volumetric beam pressure pattern. To determine the in situ pressure required to achieve efficacious ablation, a 3D T1 -weighted Attorney Ref. No. 00846-U8616.PCT planning images can be used to create segmented models of the animal anatomy. FIG. 13 shows an example segmented model of animal anatomy. Using the Hybrid Angular Spectrum acoustic modeling method, the in situ pressure achieved can be estimated at the targeted cervical facet joints and TON sites in the animal model. Using similarly generated human numerical models derived from clinical imaging studies, acoustic and thermal modeling can be used to determine the transducer output parameters to achieve efficacious in situ pressure in a human patient. This can be evaluated on a range of patient sizes to obtain the required transducer power output and to evaluate the effect of neck and spinal anatomy on potential phase aberration.

[0145] The RF coil design may not provide sufficient SNR to adequately visualize the targeted nerves. In some cases, one or more of additional coil geometries, more averaging, and lower spatial resolution can be used to increase the measurement SNR. Further, in some cases, the RF coil is not acoustically transparent. In such cases, RF coils can be positioned away from ultrasound pathways and alternative material can allow placement of coils in the FUS beam path.

[0146] A treatment planning and monitoring software can be used for the cervical spine, including (a) a treatment planning module for rapid trajectory planning and transducer positioning / adjustment of targets and surrounding complex anatomy (e.g. vessels, nerves) and (b) a monitoring module based on real-time MR thermometry and validate the accuracy of the software and hardware integration in vivo. Such treatment planning and treatment monitoring modules can allow visualization and reformatting in 3D.

[0147] Efficient treatment planning can involve ultrasound beam models that account for heterogeneity and patient-specific neck and cervical spine anatomy in a clinically relevant time. With the patient positioned in the device, 3D treatment planning images can be acquired, which also visualize whether acoustic coupling from transducer to patient is achieved. Using the RF positioning coils built onto the transducer mount allows acquisition of the transducer position and its focal spot in MR image space, which can be overlaid onto the planning images. The treatment planning module can show an overlay of the transducer and its beam path to the focus in the whole 3D dataset, which can be manipulated by the operator to focus on the target and avoid bone and other sensitive areas, while restricting it to the physically possible transducer positions of the mounting system and calculating the Attorney Ref. No. 00846-U8616.PCT necessary transducer motion. Once the transducer / beam path overlay is in the desired position, the transducer can be moved based on the calculated translation / rotation (all moving axes are indexed and can be precisely dialed in, but the actual manipulation is manual, i.e., not motorized) and a tracking scan can confirm the new transducer position and focal spot. In the case where the transducer is a phased array, the focal spot can be electronically steered to within 15 mm in-plane and 20 mm along the beam direction after the mechanical positioning.

[0148] The system also has the capability to deactivate individual elements of the phased array transducer, allowing to shape the beam path to avoid obstructions, which can be outlined on the images by the user and automatically deactivated. Ultrasound and thermal predictions can be displayed in the user interface, allowing comparison to any experimental MRTI (see treatment monitoring module).

[0149] A monitoring module can be incorporated into Thermoguide allowing the display of 3D MRTI data overlaid onto high quality planning images. While volumetric MRTI and thermal dose data can currently be displayed in Thermoguide, images are displayed slice-by- slice making it difficult for the treating physician to interpret both the accuracy and efficacy. Software modules can be incorporated into Thermoguide to create a composite display showing the volumetric temperatures as a real-time color overlay onto the high resolution planning images. Examples of such a display are shown in FIG. 14A-D, which are currently implemented for off-line viewing outside of Thermoguide. The module can also allow the user to mark structures near the treatment area or in the near field, which will be continuously monitored and can automatically stop the sonication if it reaches a certain temperature threshold. The images shown in FIGs. 14A-14D are a temperature image display being developed for real-time visualization of the 3D temperature of the sonication, which can make it easier for the physician to visualize the ablation in familiar anatomical orientation. FIGs. 14A-14C show axial, coronal and sagittal reformats of the temperature distribution. The images can be easier to interpret for the physician. As temperature volumes are often prescribed parallel or perpendicular to the ultrasound propagation direction and centered around the focal spot, resulting 2D images can be difficult to interpret. FIG. 14D shows the reformatted temperature overlay from a patient breast treatment overlaid in familiar Attorney Ref. No. 00846-U8616.PCT orientation. Please note, that noise thresholding has not been implemented to demonstrate future capabilities.

[0150] For temperature monitoring, various 3D MRI pulse sequences, can be used for robust, real-time, volumetric MRTI with pulse sequence parameters optimized to imaging in the neck. In addition, real-time motion detection can be added as a safety feature. Previous experience with the MRgFUS treatment of painful bone metastases has shown that pain during sonication (the nerve endings in the periosteum are ablated) can cause the patient to move if the anesthesia levels are not sufficient. As the patient motion causes artifacts in the temperature images, it allows the attentive physician to press the stop-sonication-button and avoid off-target ablation.

[0151] However, as images are only updated every 3-4 seconds and the physician needs to react and actively stop the sonication, such a delay could have negative effects in the neck. For cervical MRgFUS, the patient can be under moderate anesthesia, similar to what is currently used in RFA. Therefore, a navigator echo can be added to the pulse sequence to detect potential motion, which automatically triggers the sonication to stop. Due to the design of the neck holder motion can be mainly restricted to the anterior / posterior direction and will start with implementing a ID navigator in that direction.

[0152] If using a simple homogeneous model for thermal predictions is not sufficient for treatment planning, patient specific models can be used (e.g., a semi-automatic segmentation module for subcutaneous fat layers that uses MR fat / water images). Methods to non- invasively estimate patient-specific thermal properties can include perfusion, increasing the accuracy of temperature predictions. If flow artifacts obscuring the target area become an issue, a sat band (already implemented in the pulse sequence) can be added to kill inflowing blood into the imaging volume. If there is fluctuations in the MR temperature images due to susceptibility effects from breathing (lung filling), phase navigators can be added.

[0153] MR neurography sequences (such as T1 -weighted and T2-SPAIR TSE [Spectral Adiabatic Inversion Recovery Turbo Spin Echo]) can be used for detection, characterization, and accurate targeting of cervical facet joints and safely avoid the various vascular and neural structures in close proximity. MR-acoustic radiation force imaging (2D or 3D) can be used to verify focal spot location in expected region of each medial branch nerve. Attorney Ref. No. 00846-U8616.PCT

[0154] During all FUS treatments, the temperature increase can be monitored with MRI using standard proton resonance frequency (PRF) methods with volumetric 3D echo planar imaging-based MR thermometry (MRTI). As the cortical bone of the incoming US beam absorbs most of the energy, this is the area that will experience the highest temperature, although the actual focus of the sonication may be positioned deeper in the bone or bone marrow (depending on the desired ablation area). In fact, the peak temperature in some cases can occur 10-15 secs after the FUS beam was switched off.

[0155] Therefore, using 3D MRTI temperature imaging together with accurate treatment planning can allow predictions of the actual temperature within structures and subsequent damage to nerves to enhance the safety and efficacy of the procedure. When the temperature is measured in real-time using MR thermometry within the expected region of each medial branch nerve near the facet joint during each sonication, temperature and targeting can be adjusted to avoid damage to surrounding critical structures.

[0156] In one example, ablation of each medial branch nerve can be performed using continuous wave sonication (e.g. an in situ acoustic intensity 500 W / cm2for 20 s, based on results of medial branch nerve ablation in a 20-25 kg goat, with exact intensities being determined in simulation and experiments) with real-time temperature imaging feedback and thermal dose measurement.

[0157] Monitoring the procedure with MRTI will offer the advantage of thermal dose calculation and can be used for tissue targeting and prediction of any thermal damage. Additionally, the safety and efficacy of FUS to the medial branch of the dorsal ramus in the in vivo goat cervical spine model up to 6 weeks can be shown.

[0158] Given the close proximity of vascular and the spinal cord in the neck, the target of facet joint denervation can be shifted towards the joint capsule instead of the conventionally- employed medial dorsal branch as it can provide a technically easier target and may extend the duration of the therapeutic response owing to attacking the usually non-regenerating nerve receptors impeded in the joint capsule. The cervical spine system is designed for supine positioning which may be most comfortable for the patient, but other alternatives are possible. In one alternative, a holder can be used that allows the whole system to be mounted at a 90° angle. Such an alternative would not change MR imaging (as RF coils can be rotated Attorney Ref. No. 00846-U8616.PCT around the magnetic field). To assess if there is thermal damage to adjacent bone with MRgFUS, the follow-up period can be extended before euthanasia and histologic analysis.

[0159] By addressing technical issues in a large animal model with similar cervical spine biomechanics and morphology, the technology can be translated to humans.

[0160] Enumerated Examples

[0161] The technology described herein can also include the following enumerated examples:

[0162] Example 1 : A magnetic resonance guided focused ultrasound system for treatment of neck pain of a patient, comprising: a head support brace which includes a conformal neck cradle having an ultrasound access opening; at least one imaging MRI coil; an ultrasound transducer assembly including a focused ultrasound transducer capable of producing a focused ultrasound and oriented to direct the focused ultrasound through the ultrasound access opening; an acoustic coupling assembly including a conformable fluid enclosure housing a volume of ultrasound transparent liquid and adapted to transmit the focused ultrasound from the focused ultrasound transducer to skin of the patient; and a positioning gantry operatively connected to the ultrasound transducer assembly and adapted to translate the ultrasound transducer assembly in at least one direction relative to the patient.

[0163] Example 2: A system as in any of examples 1-12, or a method as in any of examples 13-22, wherein the at least one imaging MRI coil includes at least two imaging MRI coils.

[0164] Example 3: A system as in any of examples 1-12, or a method as in any of examples 13-22, wherein the at least one imaging MRI coil is embedded in the neck cradle, coupled to the ultrasound transducer assembly, or both.

[0165] Example 4: A system as in any of examples 1-12, or a method as in any of examples 13-22, wherein the ultrasound transducer assembly includes at least three positioning MRI coils coupled to the focused ultrasound transducer. Attorney Ref. No. 00846-U8616.PCT

[0166] Example 5: A system as in any of examples 1 -12, or a method as in any of examples 13-22, wherein the conformal neck cradle has a patient-specific shape which is created based on measurements of the patient.

[0167] Example 6: A system as in any of examples 1-12, or a method as in any of examples 13-22, wherein the conformal neck cradle is selected, based on measurements of the patient, from a set of premade neck cradles having different shapes.

[0168] Example 7: A system as in any of examples 1-12, or a method as in any of examples 13-22, wherein the at least one imaging MRI coil is flexible.

[0169] Example 8: A system as in any of examples 1-12, or a method as in any of examples 13-22, wherein the ultrasound access opening is bilateral across the neck.

[0170] Example 9: A system as in any of examples 1-12, or a method as in any of examples 13-22, wherein the conformable fluid enclosure includes a liquid filled balloon oriented adjacent to and between the focused ultrasound transducer and a neck of the patient at the ultrasound access opening.

[0171] Example 10: A system as in any of examples 1-12, or a method as in any of examples 13-22, wherein the conformable fluid enclosure further comprises a liquid source fluidly connected to the liquid filled balloon, and a control valve which allows selective addition or removal of liquid from the liquid filled balloon.

[0172] Example 11 : A system as in any of examples 1-12, or a method as in any of examples 13-22, wherein the conformal neck cradle is further secured to the positioning gantry sufficient to reduce or eliminate relative movement between the patient, the focused ultrasound transducer, and the at least one imaging MRI coil.

[0173] Example 12: A system as in any of examples 1-12, or a method as in any of examples 13-22, further comprising an MRI scanner electronically connected to the at least one imaging MRI coil and adapted to provide an MRI image of a target tissue within the neck of the patient.

[0174] Example 13: A method of making a magnetic resonance guided focused ultrasound system for treatment of neck pain of a patient, comprising: measuring a neck shape of the patient; providing a head support brace which includes a conformal neck cradle having an ultrasound access opening; Attorney Ref. No. 00846-U8616.PCT providing at least one imaging MRI coil; selecting a shape of the conformal neck cradle based on the measured neck shape of the patient; orienting an ultrasound transducer assembly including a focused ultrasound transducer capable of producing a focused ultrasound to direct the focused ultrasound through the ultrasound access opening; coupling the ultrasound transducer assembly to an acoustic coupling assembly including a conformable fluid enclosure housing a volume of ultrasound transparent liquid and adapted to transmit the focused ultrasound from the focused ultrasound transducer to the skin of the patient; and connecting a positioning gantry to the ultrasound transducer assembly, wherein the positioning gantry is adapted to translate the ultrasound transducer assembly in at least one direction relative to the patient.

[0175] Example 14: A system as in any of examples 1-12, or a method as in any of examples 13-22, wherein selecting the shape of the conformal neck cradle comprises custom fabricating the conformal neck cradle to fit the measured neck shape of the individual patient.

[0176] Example 15: A system as in any of examples 1-12, or a method as in any of examples 13-22, wherein selecting the shape of the conformal neck cradle comprises selecting the conformal neck cradle, based on the measured neck shape of the patient, from a set of premade neck cradles having different shapes.

[0177] Example 16: A method of treating neck pain in a patient, comprising: positioning the patient in a head support brace including a conformal neck cradle conforming to a neck of the patient, wherein the conformal neck cradle has an ultrasound access opening; positioning an ultrasound transducer assembly including a focused ultrasound transducer capable of producing a focused ultrasound and an acoustic coupling assembly including a conformable fluid enclosure housing a volume of ultrasound transparent liquid such that the ultrasound transparent liquid transmits the focused ultrasound from the focused ultrasound transducer, through the ultrasound access opening, to skin of the patient, wherein the Attorney Ref. No. 00846-U8616.PCT ultrasound transducer assembly is positioned using a positioning gantry operatively connected to the ultrasound transducer assembly and adapted to translate the ultrasound transducer assembly in at least one direction relative to the patient; locating a target tissue at a focal spot of the focused ultrasound transducer within the neck of the patient using MRI scanning; orienting at least one imaging MRI coil adjacent the target tissue; and sonicating the target tissue using the focused ultrasound transducer.

[0178] Example 17: A system as in any of examples 1-12, or a method as in any of examples 13-22, further comprising locating the focal spot in MRI space using at least one positioning MRI coil coupled to the focused ultrasound transducer.

[0179] Example 18: A system as in any of examples 1-12, or a method as in any of examples 13-22, further comprising monitoring a temperature of the target tissue using MRI scanning.

[0180] Example 19: A system as in any of examples 1-12, or a method as in any of examples 13-22, further comprising applying low-energy sonication to the target tissue to verify the location of the target tissue based on an increase in temperature measured by the MRI scanning.

[0181] Example 20: A system as in any of examples 1-12, or a method as in any of examples 13-22, further comprising monitoring a temperature of an additional tissue structure proximate to the target tissue, and automatically discontinuing sonication if the additional tissue structure reaches a predetermined temperature threshold.

[0182] Example 21 : A system as in any of examples 1-12, or a method as in any of examples 13-22, wherein the sonication provides sufficient ultrasound energy to ablate the target tissue.

[0183] Example 22: A system as in any of examples 1-12, or a method as in any of examples 13-22, wherein the target tissue comprises a cervical facet joint, a third occipital nerve, an articular branch of the C3 posterior ramus, a medial branch nerve, or a combination thereof.

[0184] Reference was made to the examples illustrated in the drawings and specific language was used herein to describe the same. It will nevertheless be understood that no limitation of the scope of the technology is thereby intended. Alterations and further modifications of Attorney Ref. No. 00846-U8616.PCT the features illustrated herein and additional applications of the examples as illustrated herein are to be considered within the scope of the description.

[0185] Furthermore, the described features, structures, or characteristics may be combined in any suitable manner in one or more examples. In the preceding description, numerous specific details were provided, such as examples of various configurations to provide a thorough understanding of examples of the described technology. It will be recognized, however, that the technology may be practiced without one or more of the specific details, or with other methods, components, devices, etc. In other instances, well-known structures or operations are not shown or described in detail to avoid obscuring aspects of the technology.

[0186] Although the subject matter has been described in language specific to structural features and / or operations, it is to be understood that the subject matter defined in the appended claims is not necessarily limited to the specific features and operations described above. Rather, the specific features and acts described above are disclosed as example forms of implementing the claims. Numerous modifications and alternative arrangements may be devised without departing from the spirit and scope of the described technology.

Claims

Attorney Ref. No. 00846-U8616.PCTCL IMSWhat is claimed is:

1. A magnetic resonance guided focused ultrasound system for treatment of neck pain of a patient, comprising: a head support brace which includes a conformal neck cradle having an ultrasound access opening; at least one imaging MRI coil; an ultrasound transducer assembly including a focused ultrasound transducer capable of producing a focused ultrasound and oriented to direct the focused ultrasound through the ultrasound access opening; an acoustic coupling assembly including a conformable fluid enclosure housing a volume of ultrasound transparent liquid and adapted to transmit the focused ultrasound from the focused ultrasound transducer to skin of the patient; and a positioning gantry operatively connected to the ultrasound transducer assembly and adapted to translate the ultrasound transducer assembly in at least one direction relative to the patient.

2. The system of claim 1, wherein the at least one imaging coil includes at least two imaging MRI coils.

3. The system of claim 1, wherein the at least one imaging MRI coil is embedded in the neck cradle, coupled to the focused ultrasound transducer, or both.

4. The system of claim 1, wherein the ultrasound transducer assembly includes at least three positioning MRI coils coupled to the focused ultrasound transducer.

5. The system of claim 1, wherein the conformal neck cradle has a patient-specific shape which is created based on measurements of the patient.

6. The system of claim 1, wherein the conformal neck cradle is selected, based on measurements of the patient, from a set of premade neck cradles having different shapes.Attorney Ref. No. 00846-U8616.PCT7. The system of claim 1, wherein the at least one imaging MRI coil is flexible.

8. The system of claim 1, wherein the ultrasound access opening is bilateral across the neck.

9. The system of claim 1, wherein the conformable fluid enclosure includes a liquid filled balloon oriented adjacent to and between the focused ultrasound transducer and a neck of the patient at the ultrasound access opening.

10. The system of claim 9, wherein the conformable fluid enclosure further comprises a liquid source fluidly connected to the liquid filled balloon, and a control valve which allows selective addition or removal of liquid from the liquid filled balloon.

11. The system of claim 1, wherein the conformal neck cradle is further secured to the positioning gantry sufficient to reduce or eliminate relative movement between the patient, the focused ultrasound transducer, and the at least one imaging MRI coil.

12. The system of claim 1, further comprising an MRI scanner electronically connected to the at least one imaging MRI coil and adapted to provide an MRI image of a target tissue within the neck of the patient.

13. A method of making a magnetic resonance guided focused ultrasound system for treatment of neck pain of a patient, comprising: measuring a neck shape of the patient; providing a head support brace which includes a conformal neck cradle having an ultrasound access opening; providing at least one imaging MRI coil; selecting a shape of the conformal neck cradle based on the measured neck shape of the patient; orienting an ultrasound transducer assembly including a focused ultrasound transducer capable of producing a focused ultrasound to direct the focused ultrasound through the ultrasound access opening;Attorney Ref. No. 00846-U8616.PCT coupling the ultrasound transducer assembly to an acoustic coupling assembly including a conformable fluid enclosure housing a volume of ultrasound transparent liquid and adapted to transmit the focused ultrasound from the focused ultrasound transducer to the skin of the patient; and connecting a positioning gantry to the ultrasound transducer assembly, wherein the positioning gantry is adapted to translate the ultrasound transducer assembly in at least one direction relative to the patient.

14. The method of claim 13, wherein selecting the shape of the conformal neck cradle comprises custom fabricating the conformal neck cradle to fit the measured neck shape of the individual patient.

15. The method of claim 13, wherein selecting the shape of the conformal neck cradle comprises selecting the conformal neck cradle, based on the measured neck shape of the patient, from a set of premade neck cradles having different shapes.

16. A method of treating neck pain in a patient, comprising: positioning the patient in a head support brace including a conformal neck cradle conforming to a neck of the patient, wherein the conformal neck cradle has an ultrasound access opening; positioning an ultrasound transducer assembly including a focused ultrasound transducer capable of producing a focused ultrasound and an acoustic coupling assembly including a conformable fluid enclosure housing a volume of ultrasound transparent liquid such that the ultrasound transparent liquid transmits the focused ultrasound from the focused ultrasound transducer, through the ultrasound access opening, to skin of the patient, wherein the ultrasound transducer assembly is positioned using a positioning gantry operatively connected to the ultrasound transducer assembly and adapted to translate the ultrasound transducer assembly in at least one direction relative to the patient; locating a target tissue at a focal spot of the focused ultrasound transducer within the neck of the patient using MRI scanning;Attorney Ref. No. 00846-U8616.PCT orienting at least one imaging MRI coil adjacent the target tissue; and sonicating the target tissue using the focused ultrasound transducer.

17. The method of claim 16, further comprising locating the focal spot in MRI space using at least one positioning MRI coil coupled to the focused ultrasound transducer.

18. The method of claim 16, further comprising monitoring a temperature of the target tissue using MRI scanning.

19. The method of claim 18, further comprising applying low-energy sonication to the target tissue to verify the location of the target tissue based on an increase in temperature measured by the MRI scanning.

20. The method of claim 18, further comprising monitoring a temperature of an additional tissue structure proximate to the target tissue, and automatically discontinuing sonication if the additional tissue structure reaches a predetermined temperature threshold.

21. The method of claim 16, wherein the sonication provides sufficient ultrasound energy to ablate the target tissue.

22. The method of claim 16, wherein the target tissue comprises a cervical facet joint, a third occipital nerve, an articular branch of the C3 posterior ramus, a medial branch nerve, or a combination thereof.

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