Ultrasound-guided delivery of a therapy delivery device to a nerve target

[0001] This application claims priority from U.S. Provisional Patent Application Ser. No. 61/150,804, filed Feb. 9, 2009, the subject matter of which is incorporated hereby incorporated by reference in its entirety.

[0002] The present invention relates generally to neuromodulatory methods, and more particularly to an ultrasound-guided approach for modulating the activity of a sympathetic nerve chain target.

[0003] Surgical procedures are often performed by skilled individuals, such as surgeons. Surgeons can perform various surgical procedures based upon their training and past experience, augmented by study of a particular patient. Nevertheless, various portions of a particular patient may be difficult to examine or identify depending upon the area of the anatomy to be examined and the positioning of the patient.

[0004] The anatomical structures surrounding the cervical and thoracic ganglia, for example, comprise various critical structures in close proximity to the ganglia. The anatomy surrounding the cervical and thoracic ganglia presents a number of complications potentially associated with access to the ganglia, some of which can be life threatening.

[0005] Surgical techniques used to access and treat the cervical and thoracic ganglia (e.g., nerve blockade) have evolved from the use of the standard blind technique to computerized tomography (CT), magnetic resonance imaging (MRI), and radionuclide tracers. These techniques are not practical in clinical practice, however, as they are time consuming, cost-ineffective, and involve radiation exposure. Newer approaches, such as fluoroscopy present a reliable technique for identifying bony structures during surgical access to the cervical and thoracic ganglia. Fluoroscopy cannot, however, identify soft tissue anatomical structures adjacent to bony structures. Consequently, inadvertent needle placement into the vertebral artery, thyroid, thyroid vessels, neural tissues, pleura/lung, or esophagus can occur when using fluoroscopy to access the cervical and/or thoracic ganglia.

[0006] According to one aspect of the present invention, a method is provided for guiding a therapy delivery device to a sympathetic nerve chain target of a subject. One step of the method includes selecting a sympathetic nerve chain (SNC) target. A second step of the method includes using ultrasound imaging to obtain an ultrasound image of anatomical structures relevant to the SNC target. A third step of the method includes determining an implantation pathway based on the ultrasound image. The implantation pathway defines a trajectory that avoids the relevant anatomical structures and extends between an insertion point on the skin of the subject and a bony spinous target. A fourth step of the method includes inserting an introducer into the insertion point. The introducer includes a bevel located at a distal end thereof. A fifth step of the method includes navigating the introducer through the implantation pathway until the distal tip is positioned adjacent or proximate to the bony spinous target. A sixth step of the method includes advancing the therapy delivery device through the introducer to the SNC target. The fourth, fifth, and sixth step of the method are performed using real-time ultrasound imaging.

[0007] According to another aspect of the present invention, a method is provided for treating a medical condition in subject. One step of the method includes selecting a SNC target. A second step of the method includes using ultrasound imaging to obtain an ultrasound image of anatomical structures relevant to the SNC target. A third step of the method includes determining an implantation pathway based on the ultrasound image. The implantation pathway defines a trajectory that avoids the relevant anatomical structures and extends between an insertion point on the skin of the subject and a bony spinous target. A fourth step of the method includes inserting an introducer into the insertion point. The introducer includes a bevel located at a distal end thereof. A fifth step of the method includes navigating the introducer through the implantation pathway until the distal tip is positioned adjacent or proximate to the bony spinous target. A sixth step of the method includes advancing the therapy delivery device through the introducer to the SNC target. A seventh step of the method includes applying an electrical current to the SNC target. The fourth, fifth, and sixth step of the method are performed using real-time ultrasound imaging.

[0016] The present invention relates generally to neuromodulatory methods, and more particularly to an ultrasound-guided approach for modulating the activity of a sympathetic nerve chain (SNC) target. As representative of the present invention, FIGS. 1 and 6 illustrate ultrasound-guided methods for delivering a therapy delivery device to a SNC target for treatment of a medical condition in a subject. Unlike prior art methods used to guide therapy delivery devices to SNC targets, which require open surgical dissection and/or inadequate imaging techniques, the present invention takes advantages of ultrasound imaging technology to provide a percutaneous approach for guiding a therapy delivery device to a SNC target. By using ultrasound technology to guide therapy delivery devices, the present invention provides a surgical technique that substantially reduces the risk of damaging critical anatomical structures during placement of a therapy delivery device at a SNC target.

[0017] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention pertains.

[0018] In the context of the present invention, the term “medical condition” can refer to any vascular disorder (e.g., stroke) or sympathetically-mediated pain in the upper extremity, head, and/or neck. The term can also refer to movement disorders, epilepsy, cerebrovascular diseases, autoimmune diseases, sleep disorders, autonomic disorders, urinary bladder disorders, abnormal metabolic states, disorders of the muscular system, infectious and parasitic diseases (as provided in ICD-9 codes 1-139), neoplasms (as provided in ICD-9 codes 140-239), endocrine diseases, nutritional and metabolic diseases, immunological diseases (as provided in ICD-9 codes 240-279), diseases of the blood and blood-forming organs (as provided in ICD-9 codes 280-289), mental disorders (as provided in ICD-9 codes 290-319), diseases of the nervous system (as provided in ICD-9 codes 320-359), diseases of the sense organs (as provided in ICD-9 codes 360-389), diseases of the circulatory system (as provided in ICD-9 codes 390-459), diseases of the respiratory system (as provided in ICD-9 codes 460-519), diseases of the digestive system (as provided in ICD-9 codes 520-579), diseases of the genitourinary system (as provided in ICD-9 codes 580-629), diseases of the skin and subcutaneous tissue (as provided in ICD-9 codes 680-709), diseases of the musculoskeletal system and connective tissue (as provided in ICD-9 codes 710-739), congenital anomalies (as provided in ICD-9 codes 740-759), certain conditions originating in the perinatal period (as provided in ICD-9 codes 760-779), and symptoms, signs, and ill-defined conditions (as provided in ICD-9 codes 780-799).

[0019] Pain treatable by the present invention can be caused by conditions including, but not limited to, migraine headaches, including migraine headaches with aura, migraine headaches without aura, menstrual migraines, migraine variants, atypical migraines, complicated migraines, hemiplegic migraines, transformed migraines, and chronic daily migraines, episodic tension headaches, chronic tension headaches, analgesic rebound headaches, episodic cluster headaches, chronic cluster headaches, cluster variants, chronic paroxysmal hemicranias, hemicrania continua, post-traumatic headache, post-traumatic neck pain, post-herpetic neuralgia involving the head or face, pain from spine fracture secondary to osteoporosis, arthritis pain in the spine, headache related to cerebrovascular disease and stroke, headache due to vascular disorder, reflex sympathetic dystrophy, cervicalgia (which may be due to various causes, including, but not limited to, muscular, discogenic, or degenerative, including arthritic, posturally related, or metastatic), glossodynia, carotidynia, cricoidynia, otalgia due to middle ear lesion, gastric pain, sciatica, maxillary neuralgia, laryngeal pain, myalgia of neck muscles, trigeminal neuralgia (sometimes also termed tic douloureux), post-lumbar puncture headache, low cerebro-spinal fluid pressure headache, temporomandibular joint disorder, atypical facial pain, ciliary neuralgia, paratrigeminal neuralgia (sometimes also termed Raeder's syndrome); petrosal neuralgia, Eagle's syndrome, idiopathic intracranial hypertension, orofacial pain, myofascial pain syndrome involving the head, neck, and shoulder, chronic migraneous neuralgia, cervical headache, paratrigeminal paralysis, SPG neuralgia (sometimes also termed lower-half headache, lower facial neuralgia syndrome, Sluder's neuralgia, and Sluder's syndrome), carotidynia, vidian neuralgia, causalgia, and/or a combination of the above.

[0020] Movement disorders treatable by the present invention may be caused by conditions including, but not limited to, Parkinson's disease, cerebropalsy, dystonia, essential tremor, and hemifacial spasms.

[0021] Epilepsy treatable by the present invention may be, for example, generalized or partial.

[0022] Cerebrovascular disease treatable by the present invention may be caused by conditions including, but not limited to, aneurysms, strokes, and cerebral hemorrhage.

[0023] Autoimmune diseases treatable by the present invention include, but are not limited to, multiple sclerosis.

[0024] Sleep disorders treatable by the present invention may be caused by conditions including, but not limited to, sleep apnea and parasomnias.

[0025] Autonomic disorders treatable by the present invention may be caused by conditions including, but not limited to, gastrointestinal disorders, including but not limited to gastrointestinal motility disorders, nausea, vomiting, diarrhea, chronic hiccups, gastroesphageal reflux disease, and hypersecretion of gastric acid, autonomic insufficiency; excessive epiphoresis, excessive rhinorrhea; and cardiovascular disorders including, but not limited, to cardiac dysrythmias and arrythmias, hypertension, and carotid sinus disease.

[0026] Urinary bladder disorders treatable by the present invention may be caused by conditions including, but not limited to, spastic or flaccid bladder.

[0027] Abnormal metabolic states treatable by the present invention may be caused by conditions including, but not limited to, hyperthyroidism or hypothyroidism.

[0028] Disorders of the muscular system treatable by the present invention can include, but are not limited to, muscular dystrophy, and spasms of the upper respiratory tract and face.

[0029] Neuropsychiatric or mental disorders treatable by the present invention may be caused by conditions including, but not limited to, depression, schizophrenia, bipolar disorder, and obsessive-compulsive disorder.

[0030] As used herein, the term “headache” can refer to migraines, tension headaches, cluster headaches, trigeminal neuralgia, secondary headaches, tension-type headaches, chronic and epsisodic headaches, medication overuse/rebound headaches, chronic paroxysmal hemicrinia headaches, hemicranias continua headaches, post-traumatic headaches, post-herpetic headaches, vascular headaches, reflex sympathetic dystrophy-related headaches, crvicalgia headaches, caroidynia headaches, sciatica headaches, trigeminal headaches, occipital headaches, maxillary headaches, cliary headaches, paratrigeminal headaches, petrosal headaches, Sluder's headache, vidian headaches, low CSF pressure headaches, TMJ headaches, causalgia headaches, myofascial headaches, all primary headaches (e.g., primary stabbing headache, primary cough headache, primary exertional headache, primary headache associated with sexual activity, hypnic headache, and new daily persistent headache), all trigeminal autonomic cephalagias (e.g., episodic paroxysmal hemicranias, SUNCT, all probable TACs, and SUNA), chronic daily headaches, occipital neuralgia, atypical facial pain, neuropathic trigeminal pain, and miscellaneous-type headaches.

[0031] As used herein, the terms “modulate” or “modulating” can refer to causing a change in neuronal activity, chemistry and/or metabolism. The change can refer to an increase, decrease, or even a change in a pattern of neuronal activity. The terms may refer to either excitatory or inhibitory stimulation, or a combination thereof, and may be at least electrical, biological, magnetic, optical or chemical, or a combination of two or more of these. The terms can also be used to refer to a masking, altering, overriding, or restoring of neuronal activity.

[0032] As used herein, the term “subject” can refer to any warm-blooded organism including, but not limited to, human beings, pigs, rats, mice, dogs, goats, sheep, horses, monkeys, apes, rabbits, cattle, etc.

[0033] As used herein, the terms “treat” or “treating” shall have their plain and ordinary meaning to one skilled in the art of pharmaceutical or medical sciences. For example, “treat” or “treating” can mean to prevent or reduce a pain in a subject.

[0034] FIG. 1 is a process flow diagram illustrating one aspect of the present invention. In FIG. 1, a method 10 is provided for guiding a therapy delivery device 24 (FIGS. 5A-B) to a SNC target (FIG. 2) of a subject. The SNC 27 (FIG. 5B) is part of the sympathetic nervous system and comprises a plurality of interconnected ganglia. The SNC 27 is organized into different sections relative to the cervical, thoracic, lumbar, and sacral sections of the spinal column. The SNC target of the present invention can include any section of the cervical, thoracic, lumbar, or sacral SNC. For example, the SNC target can comprise a cervical ganglion (i.e., superior ganglion, middle ganglion, intermediate ganglion, or inferior ganglion) (not shown), a stellate ganglion 26 (FIG. 2), a T1 ganglion (not shown), a T2 ganglion (not shown), or a T3 ganglion (not shown).

[0035] At Step 12 of the method 10 (FIG. 1), a SNC target is selected. The SNC target can be chosen based on a variety of factors, including a particular medical condition or location of the SNC target relative to surrounding anatomical structures. For example, some SNC targets may be appropriate targets for a particular disease, but situated so that they cannot be readily accessed because of tortuous or precarious anatomical structures surrounding (or en route to) the SNC target. Thus, some other SNC target that is more readily accessible may have to be chosen. As described in more detail below, one example of a SNC target can include the stellate ganglion 26 (FIG. 2).

[0036] After selecting a SNC target, an ultrasound image of the anatomical structures relevant to the SNC target is obtained using ultrasound imaging at Step 14. Ultrasound apparatus and related methods for obtaining ultrasound images are known in the art and can include linear or curved array transducers capable of producing, two-, three-, or four-dimensional images. One example of such an apparatus is the Sonosite 180 PLUS ultrasound system (not shown) with an 11-mm broadband (4-7 MHz) tightly curved array transducer (SONOSITE, Bothell, Wash.). Before obtaining the ultrasound image, the subject can be positioned in a supine position with his or her neck extended by placing a pillow under the subject's shoulder to stretch the esophagus 28 so that the esophagus moves medially under the trachea 30. Using aseptic technique, an ultrasound transducer 32 (FIG. 3) is then used to obtain a short axis image of the root of the subject's neck to identify relevant anatomical structures.

[0037] Unlike imaging modalities of the prior art used to identify anatomical structures (e.g., fluoroscopy, MRI, CT, etc.), the ultrasound image generated at Step 14 clearly displays important anatomical structures, such as soft tissues, nerves, and vessels. Where the SNC target comprises the stellate ganglion 26, for example, the ultrasound image can identify important anatomical structures including, but not limited to, the trachea 30, the esophagus 28, the recurrent laryngeal nerve 34, the thyroid gland (not shown), the carotid artery 36, the internal jugular vein 38, the vagus nerve 40, the longus coli muscle 42, the inferior thyroid vessels 44, and the vertebral vessels 46.

[0038] At Step 16, an implantation pathway is determined based on the ultrasound image obtained at Step 14. The implantation pathway defines a trajectory that avoids the relevant anatomical structures, and extends between an insertion point on the skin of the subject and a bony spinous target. Where the SNC target comprises the stellate ganglion 26, for example, the implantation pathway can be determined by first identifying a bony spinous target, such as C7 48. The level of C7 48 can be identified by the characteristic shape of the transverse process and the position of C7 relative to the vertebral artery 46. After identifying C7 48, a trajectory can be identified that: (1) avoids the relevant anatomical structures along the anterior aspect of the longus coli muscle 42; and (2) extends between an insertion point at the root of the subject's neck and C7.

[0039] Using real-time ultrasound imaging, an introducer 50 (FIG. 4) is inserted into the insertion point at Step 18. The introducer 50 can comprise any device that is capable of tunneling to, and then delivering, a therapy delivery device 24 (FIG. 6) to a SNC target. For example, the introducer 50 (FIG. 4) can comprise a needle having a beveled distal tip (not shown in detail). As shown in FIG. 4, the introducer 50 is inserted into the insertion point using an in-plane or out-of-plane approach to target the anterior aspect of the longus coli muscle 42 where the SNC extends. Navigation of the introducer 50 through the implantation pathway can be stabilized using a securing mechanism (not shown), such as a guide catheter or adhesive tape. At Step 20, the introducer 50 is then navigated through the implantation pathway (e.g., using tactile force) using real-time ultrasound until the distal tip is positioned adjacent or proximate to the bony spinous target (e.g., C7 48). After negative aspiration, placement of the introducer 50 can be checked using real-time fluoroscopy and about 1 ml of contrast agent.

[0040] At Step 22, a therapy delivery device 24 (FIG. 5A) is delivered to the SNC target. The therapy delivery device 24 can include any medical device or apparatus capable of delivering an electrical current to a SNC target. As shown in FIG. 5A, the therapy delivery device 24 can comprise an electrical lead 52 including at least one electrode 54 and being connected to a power source 56. Although the therapy delivery device 24 is shown as being directly connected to the power source 56, it will be appreciated that wireless power sources may also be used to deliver an electric current to the therapy delivery device.

[0041] The orientation of the introducer 50 can be adjusted depending upon the location of the SNC target. Where the SNC target comprises a middle or superior cervical ganglion, for example, the distal tip of the introducer 50 can be rotated so that the bevel is oriented in a cephalad direction. Alternatively, where the SNC target comprises an inferior cervical ganglion or thoracic ganglion, the distal tip of the introducer 50 can be rotated so that the bevel is oriented in a caudal direction (FIG. 5B). As the therapy delivery device 24 is advanced through the introducer 50, the ultrasound transducer 32 is moved to obtain a longitudinal image and thereby precisely follow advancement of the therapy delivery device in real time.

[0042] The present invention take advantage of real-time ultrasound to facilitate placement of therapy delivery devices 24 at SNC targets and thereby minimize the risk of damaging critical anatomical structures when doing so. When delivering a therapy delivery device 24 to the stellate ganglion 24, for example, it is known that the vertebral artery 46 runs anterior to the stellate ganglion at the level of C7 48 before it enters the foramen (not shown) of the C6 transverse process (not shown) in about 90% of cases. In the remaining cases, however, the vertebral artery 46 enters at C5 (not shown) or higher. This makes the vertebral artery 46 vulnerable to injury at the level of both C6 and C7 48. Using ultrasound, however, can mitigate this possibility by enabling visualization of both bony structures (i.e., C6 and C7 48) and vascular structures (i.e., the vertebral artery 46) during placement of therapy delivery devices 24. Similarly, the inferior thyroid vessels 44 run ventrally at the level of C6 and C7 48. The inferior thyroid vessels 44, together with the thyroid gland, have been reported to be a source of retropharyngeal hematoma with stellate ganglion block. Using fluoroscopic guidance, for example, the thyroid gland and inferior thyroid vessels 44 can be easily injured in the path of the introducer 50. Using ultrasound, however, can mitigate this possibility by enabling visualization of vascular structures (i.e., the inferior thyroid vessels 44) during placement of therapy delivery devices 24.

[0043] FIG. 6 is a process flow diagram illustrating another aspect of the present invention. In FIG. 6, a method 60 is provided for treating a subject with a medical condition. Although the method 60 will be described below in terms of treating a subject with complex regional pain syndrome (CRPS), it will be appreciated that the method can be used to treat any one or combination of medical conditions described herein.

[0044] The steps of the method 60 are substantially identical to Steps 12-22 of the method 10 (FIG. 1) above, except where described below. For example, the method 60 (FIG. 6) can begin by selecting an SNC target at Step 12. To treat a subject suffering from CRPS, the stellate ganglion 24 can be selected for neuromodulation. After selecting the stellate ganglion 24 as the SNC target, an ultrasound image of the anatomical structures relevant to the stellate ganglion can be obtained at Step 14. For example, an ultrasound transducer 32 can be used to obtain a short axis image of the root of the subject's neck. The ultrasound image can then be used to identify critical anatomical structures, such as the trachea 30, esophagus 28, recurrent laryngeal nerve 34, thyroid gland, carotid artery 36, internal jugular vein 38, vagus nerve 40, longus coli muscle 42, inferior thyroid vessels 44, the vertebral vessels 46, nerve roots, and spinal cord.

[0045] At Step 16 of the method 60, an implantation pathway can be determined based on the ultrasound image. Where the SNC target comprises the stellate ganglion 24, the implantation pathway can be determined by first identifying a bony spinous target, such as C7 48. The level of C7 48 can be identified by the characteristic shape of the transverse process and the position of C7 relative to the vertebral artery 46. After identifying C7 48, a trajectory can be identified that: (1) avoids the relevant anatomical structures along the anterior aspect of the longus coli muscle 42; and (2) extends between an insertion point at the root of the subject's neck and C7 48.

[0046] Using real-time ultrasound, an introducer 50 can be inserted into the insertion point at Step 18. The introducer 50 can comprise a needle having a beveled distal tip, for example. The introducer 50 can be inserted at the insertion point using an in-plane or out-of-plane approach to target the anterior aspect of the longus coli muscle 42 where the SNC extends. Navigation of the introducer 50 through the implantation pathway can be stabilized using a securing mechanism (not shown), such as a guide catheter or adhesive tape. At Step 20, the introducer 50 can be navigated through the implantation pathway (e.g., using tactile force) using real-time ultrasound until the distal tip is positioned adjacent or proximate to the bony spinous target (e.g., C7 48). After negative aspiration, placement of the introducer 50 can be checked using real-time fluoroscopy and about 1 ml of contrast agent.

[0047] At Step 22, a therapy delivery device 24 can be delivered to the SNC target (FIGS. 5A-B). As shown in FIG. 5A, the therapy delivery device 24 can comprise an electrical lead 52 including at least one electrode 54 and being connected to a power source 56. The distal tip of the introducer 50 can then be rotated so that the bevel is oriented towards the SNC target. With the bevel appropriately positioned, the electrical lead 52 can then be advanced through the introducer 50 (indicated by arrow) under real-time ultrasound until at least one electrode 54 of the electrical lead is positioned adjacent or proximate to the stellate ganglion 24.

[0048] At Step 62, the power source 56 can be activated so that an electrical current is passed through the electrical lead 52 and into the stellate ganglion 24. The electrical current may be episodic, continuous, phasic, in clusters, intermittent, upon demand by the subject or medical personnel, or pre-programmed to respond to a sensor (not shown) (e.g., a closed-loop system). The electrical current can be operated at a constant voltage (e.g., at about 0.1 v to about 25 v), at a constant current (e.g., at about 25 microampes to about 50 milliamps), at a constant frequency (e.g., at about 5 Hz to about 10,000 Hz), and at a constant pulse-width (e.g., at about 50 μsec to about 10,000 μsec). Application of the electrical current can be monopolar, bipolar, or multipolar, depending upon the polarity of the electrical lead 52. The waveform may be, for example, biphasic, square wave, sine wave, or other electrically safe and feasible combinations. Additionally, the electrical current may be applied to the SNC target (i.e., the stellate ganglion) simultaneously or sequentially.

[0049] Delivery of electrical current to the stellate ganglion 24 can suppress the pain experienced by the subject by “blocking” nerve impulse transmission through the stellate ganglion. As unregulated and increased nerve transmission is essential for the body to propagate and recognize pain, blocking nerve impulse transmissions through the stellate ganglion 24 can diminish the pain experienced by the subject. Upon delivery of the electrical current to the electrical lead 52, the subject may be asked to report any pain sensation. The position of the electrical lead 52, or frequency of electrical current being delivered to the electrical lead, may then be adjusted until the subject reports experiencing diminished pain sensation and/or autonomic changes in the head and/or upper extremities, lungs, and heart are observed. Once satisfactory, the electrical lead 52 can be self-anchored or anchored to the deep tissues and then tunneled to an infraclavicular area (not shown) where an IPG (not shown) can be implanted.

[0050] From the above description of the invention, those skilled in the art will perceive improvements, changes and modifications. For example, it will be appreciated that the therapy delivery device 24 can comprise a drug infusion catheter (not shown) or a drug infusion system (not shown), examples of which are known in the art. Such improvements, changes, and modifications are within the skill of the art and are intended to be covered by the appended claims.