Patent ID: 12208134

FIG.1shows an intervention device for high-precision image guided interventions targeting cranial autonomic ganglia. The device can also be used wherever applicable for injections, core needle biopsy, fine needle biopsy, puncture, aspiration, ablation, and for the positioning of electrodes, radioactive seeds, catheters or implants.

The device consists of a proximal piece2, body4and an end piece6with a tip8. It is made of a rigid material to avoid navigation inaccuracy. This is of paramount importance since there is no way for the interventionist to be aware of deformations of an instrument as soon as skin or mucosa is punctured and the instrument is within the body.

The end piece6comprises a rigid lumen through which an object such as a needle10can pass. The lumen can be of any suitable diameter, length and form, provided that it has sufficient length to penetrate to the injection site. In this example embodiment it is sized for use in a lateral or transnasal medial approach to the SPG and hence the end piece6extends away from the body4by about 12 cm allowing for sufficient length to penetrate the skin and reach the SPG, which can be perhaps 6 to 9 cm from the skin as noted above. The lumen of the end piece6is made of a rigid material to avoid navigation inaccuracy and it should be rigid enough to permit placement of the tip8with millimetre accuracy without deformation as the lumen penetrates the intervening body tissues and whilst being subject to bending moments that might arise as it is manoeuvred along the selected approach toward the SPG (which may be transnasal or lateral). The lumen of this example has a diameter just big enough fit a 25 G needle with appropriate clearance.

The end piece6has centimetre marks to provide an indication of the depth of insertion beneath the skin. The end piece6extends through the body4and is attached to proximal piece2to allow for the needle10to extend along the proximal piece as described below. The lumen is open at the proximal end to provide access for the needle10. The tip8can be sharp as shown or rounded to minimize tissue damage. Potential adaptations to the design of the tip8are discussed below in relation toFIG.3. The outer diameter of the end piece6may taper off from the proximal end to the distal end of the end piece6. The very distal end of the end piece may be approximately 20-22 G. The inner diameter will typically be just big enough to carry the preferred 25 G needle.

The body4is connected to and holds the end piece6and proximal piece2. The body4includes an ergonomic shaped handle12that allows for one-handed use. The body4also holds an array14with reflector balls for an optical guidance system mounted on a suitable anchor point16. This optical guidance array14can be used in conjunction with further reflector balls18mounted on the proximal piece for best accuracy and to permit the navigation system to also monitor the position of the needle10within the end piece6. The body4in this example also has a universal clamp anchor point20, which is formed to fit universal clamps as provided by manufacturers, and also an electromagnetic anchor22. The various anchor points16,20,22allow for alternative guidance systems to be used for the needle guide. For electromagnetic navigations system any connection point provided by the manufacturer could be embedded.

The body4optionally includes a mounting point (for example, as described below in relation toFIGS.5to7) for a handheld device replacing the traditional computer platform, such as a tablet, smart phone, iPod™ or the like. The display screen of the handheld device can be used during navigation to show the operator what movement of the end piece is required or to show images from an endoscope attached to the intervention device. Such a handheld device can include software that by animation (e.g. three-dimensional) of the medical image with targets and bars, will provide guidance to the operator in relation to the puncture site, alignment of the end piece and distance to the target along with warnings if the device is off track. The software may display a magnified view of a region of interest in the navigation image on the screen of the handheld device. Appropriate software could also be integrated into the software of the computer platform provided by the manufacturers of navigation systems either in addition to software on a handheld device and capable of interacting with the handheld device or as an alternative allowing the use of a separate computer platform without a handheld device. This can make the intervention procedure safer and more precise. Furthermore, it can make the procedure available not only for specialized surgeons but also to surgeons with less experience in this field as well as potentially to other medical professionals such as neurologists and anaesthesiologists. This is of importance since the ease of performing a procedure and hence its availability to patients is as important as the existence of such procedure. The handheld device can communicate with a computer platform through Wi-Fi, Bluetooth or the like. The computer platform can be integrated in a tracking rack, making it convenient for storage and transport, and therefore for outpatient use or the like. The device may include a sensor in the body of the device connected to the handheld device that registers movements of the needle and/or of the proximal piece, this is done with or without usage of the possibility of tracking movements by markers on the proximal piece.

The proximal piece2is attached to the end piece6and the body4. The proximal piece comprises two clamps24for attachment of the needle10. These clamps24are used to fix the needle10in place relative to the tip8. With appropriate guidance from an optical navigation system or similar, the needle guide can be pushed forward using the tip8and end piece6to penetrate the skin and body tissue. When the tip8is at a suitable distance from the target site the distal end of the needle10can be extended from the tip8by manipulation of the proximal end of the needle10at the proximal piece. A scale provided on the proximal piece shows how far the needle has been inserted. In this way the device avoids the risk tissue damage that might otherwise be caused by the larger end piece of the device approaching close to the target site. Extending and then retracting the needle10can also be used to avoid backflow of a pharmacological substance as one retracts the device.

Another way to measure the distance that the needle10has been moved is the use of positional markers, e.g. in the case of an optical system, reflectors, for calculating the distance. In the embodiment shown one of the reflector balls18could slide along the proximal piece2connected to an associated clamp24and hence provide an indication of the distance that the needle10has moved. In such cases, with appropriate software, the position of the needle can be seen on a navigation screen or other computer device.

The device will be made of a rigid material to avoid IGS inaccuracies. Any instrument guided by the device can be semi-rigid, in this case the needle10, as the device in itself provides the requisite stiffness to ensure that the intervention is accurate.

The needle10in this example is a 25 G needle that is provided with a specially designed needle tip26, which is shown inFIG.2. The tip26has a slightly rounded end to minimise the risk of damage to the target site (the SPG in one example) and there are openings on each side of the tip26so that tissue on either side is infiltrated by the pharmacological substance.FIG.2also shows detail of the proximal end of the needle10, which is provided with a luer lock device for connection to an appropriate source of the pharmacological substance, for example a syringe.

FIG.3shows potential alternative designs for the tip8of the lumen, with adaptations to bend the needle10as it is pushed out of the tip8and to thereby direct it away from the line of the end piece6. This allows for targeting of injection sites that are not in a location than can be easily accessed in a straight line from an appropriate puncture site. Since the effect of the shaped tip8on the final position of the needle10as it is extended will be known then the angled path of the needle10can be taken into account when the desired path for insertion of the end piece6into the body is determined.FIG.3shows three possible arrangements, including an angled tip8, and two systems using internal contours within the tip8to angulate the needle10either as it exits a hole at the very end of the tip8or as it exits a hole in the side of the tip. One advantageous use for an angled tip8is shown inFIG.11, where the SPG is targeted using a transnasal approach.

Another exemplary intervention device is shown inFIGS.4and5. This device has generally similar features to the device described in relation toFIG.1and comprises the same main parts, with a proximal piece2, body section4and end piece6. With the perspective views ofFIGS.4and5the arrangement of the array14of reflector balls can be more clearly seen, in particular the spacing of the front and rear pairs of balls14. This arrangement is also found in the device ofFIG.1.

The example device ofFIGS.4and5includes various additional or alternative features compared to the device ofFIG.1. The differences are in the proximal piece2and body section4, and also in the supply of fluid to the needle. If not described otherwise then the remaining features can be taken to be similar or identical to the features described above forFIG.1. The proximal piece2includes a handle in the form of a ring30for enabling the user to push or pull the instrument with the thumb or a finger. In this way the needle can be moved in a one-handed operation whilst the handle12of the body section is held by the same hand. A reflector18is attached to the ring30to permit the navigation system to determine the position of the needle as it moves with movement of the ring30. To supply fluid to the needle the device of this second example includes an ampule32attached to the needle within the body section4. There are also further features for actuating the device in the form of two trigger levers34,36. The body section4incorporates a locking mechanism to lock needle in place and prevent further movement of the proximal piece, and this is actuated using a first, shorter, lever34. A second, longer, lever36is provided for actuating a mechanism that aspirates and then injects a substance from the ampule32.

It will be seen thatFIG.5includes an additional feature of a handheld device38, which is not inFIG.4. The handheld device38is mounted to the body section4and can operate as discussed above in order to assist the user with navigation.

FIGS.6and7show a similar device to that shown inFIG.5, but with an additional feature of a cheek-stopper40. The other features are as inFIG.5, although for this example the ring30is omitted.FIG.6is a side view andFIG.7is an end view looking along the line of the end piece6from the tip8toward the body section4. It should also be noted that whilstFIGS.4and5show the needle10in a retracted position, withdrawn within the end piece6and hence not visible,FIG.6shows the needle10extended out of the tip8of the end piece6. The reflector18clamped to the needle10at the proximal piece2is hence moved forward by the same distance that the needle10has moved.

A further example of an intervention device is shown inFIGS.8and9. The device is broadly similar to the other examples herein, but the design of the handle12is changed and a three reflector navigation array14is used in place of the four reflector navigation array14of the above devices. In addition, in place of the luer lock28or ampule32, the device ofFIGS.8and9includes a core biopsy instrument42to take core needle biopsy. An example of a suitable instrument for the core biopsy instrument42is the BARD MONOPTY® Disposable Core Biopsy Instrument, as manufactured by Bard Peripheral Vascular Inc., of Tempe, AZ, USA. See www.bardbiopsy.com. Another possible biopsy instrument is the BARD MAGNUM® Resuable Core Biopsy Instrument, from the same manufacturer. The core biopsy device42is connected to a slide at the proximal piece2and can be moved by way of a ring30that is operable via a finger or thumb.FIG.8shows the needle10withdrawn inside the end piece6andFIG.9shows the core biopsy instrument42slid forward and the needle10therefore extending from the tip8of the end piece6.

FIGS.10aand10bshow another example device, which once again is broadly similar to the other examples described herein. In these Figures the reference numbers show similar features to those described above, including the proximal piece2, body section4, end piece6and tip8. The navigation array14has three reflectors similar to the example ofFIGS.8and9. The device ofFIGS.10aandbhas a syringe44connected to the needle10via the proximal piece2. The syringe44can be coupled to the needle10using any suitable coupling mechanism, for example a three-way stop cock. The device further includes a cradle48for a handheld device38. The handheld device38can be used as described above to assist in the intervention procedure. A cheek stopper40is also present. It will be appreciated that the device ofFIGS.10aandbcould be used without the cradle48and cheek stopper40, if required.

The device ofFIGS.10aand10bfurther includes a track46on the body section4, in which the navigation array14is mounted. The track46allows the navigation array14to slide along the body section, although in the arrangement of the Figures this feature is not in use and the navigation array would instead be fixed in place. When the sliding connection is used the instrument (the needle10in this example) would be connected to the navigation array14via a coupling between the proximal piece2and the array14. This is to allow the array14to be rigidly connected to the instrument and to hence reflect the location of the instrument within the body.

Another example device is shown inFIGS.11aand11b. The main features are similar to the example ofFIGS.10aand10b, but the syringe is not present and instead an endoscope52is mounted on the body section4. Advantageously, the endoscope52can be linked to the display of a smart phone38mounted in smartphone cradle48so that the smart phone38shows the endoscope52image feed. This allows the view from the endoscope52to be easily seen by the user and also to be aligned with the orientation of the device/end piece6. As noted above, fitting the device with an endoscope52enables convenient combined use of the endoscope52with other instruments, such as a needle10, without risk of collision of the two instruments.

The further example ofFIG.12is similar to that ofFIGS.10aand10b, but the cradle48and cheek stopper40have been removed and the syringe44is replaced with a core biopsy instrument42, similar to that discussed above. Once again the body section4has a track46that the navigation array14is mounted in for sliding movement. The movable proximal piece2is connected to the navigation array14by a coupling so that when the biopsy instrument42is moved then the navigation array14also moves.FIG.11also shows a handle12made of a transparent material, which is an optional feature. The internal mechanism of the device can be seen. In this example a trigger is provided to actuate the device and cause the biopsy instrument and the needle to advance.

It should be noted that the features of the needle tip described in relation toFIG.2and the various alternative embodiments of the tip8of the end piece6shown inFIG.3can also be utilised in the devices shown inFIGS.4to12. Similarly, the additional features ofFIGS.4to12relating to the handheld device38/cradle48, ring30, ampule32and lever system, sliding track46, syringe44, cheek stopper40, core biopsy instrument42, endoscope52and so on can also be used with the device ofFIG.1or as optional features for any of the other devices ofFIGS.2to12.

The devices described above makes it safe to use the lateral approach targeting the SPG, significantly lowering the risk of complications such as tissue destruction of adjacent structures by the very instrument at use or adverse events due to misjudged placement of the needle while injecting the pharmacological substance. At the same time the positioning of the injection will be highly accurate, making it feasible to use small volumes with minimal possibilities of diffusion into adjacent structures. Such a precision also ensures optimal delivery of the pharmacological substances and therefore optimal treatment effect.

In further alternative embodiments the end piece6and tip8can be designed for implantation of neuromodulators where, for example, the very end of the neuromodulator can be pointed and pushed out of the device to be installed at the target site as applicable. The distal end can alternatively, be formed to carry an implant, for example a steroid releasing implant to be installed in sinuses. The device may also be adapted for other procedures such as those listed below.

The end piece6can also be adjusted in design by providing it with anchor points for flexible or rigid endoscopes. An endoscope may alternatively be mounted on the body section of the device, as in the example ofFIGS.11aand11b. Use of an endoscope would ease the localisation of the best entry point on the lateral wall of the nasal cavity using the transnasal route, making this procedure more user friendly and more accessible as procedure performed under local anaesthesia. An endoscope can also assist with other procedures using the device.

In the case of electromagnetic navigation, which can be used as an alternative or in addition to optical navigation, a coil can be embedded in the tip8and/or the end piece6.

Example dimensions for the end piece are set out in the table below. The example end pieces are manufactured of beta titanium and available from Futaku Precision Machinery Industry Company of Kyoto, Japan. Alternative sizes could of course be used, provided that they have sufficient rigidity.

LengthTo the angledOuter diameterStraight/segmentTotalProximalDistalInnerangled tip(cm)(cm)(mm)(mm)diameter (mm)Straight143.048/1.6511.100.945 degrees14163.0481.2701.1Straight163.0481.401.120 degrees14163.0481.6511.340 degrees14163.0481.701.6Straight163.0481.2700.920 degrees14163.0481.2701.140 degrees14163.0481.451.3Straight183.0482.101.6

A possible advantageous use of the device is the injection of neuroinhibitory substances such as botulinum toxin in close proximity to the SPG or OG. Note that the injection device should not penetrate the SPG or OG. The injection is achieved in order to treat or prevent headache and may be achieved without damage to surrounding critical structures within the head. A neuroinhibitor is defined as any substance that affects transmission in a neural structure, resulting in any change of transmission, which may decrease or increase the neural activity. The neuroinhibitory substance is preferably a neurotoxin.

By delivery of the active substance in close proximity (proximally) to the sphenopalatine ganglion or otic ganglion means that the botulinum toxin or other neuroinhibitory substance in question is delivered so that it causes the desired technical effect, e.g. the prevention of treatment of headache etc. Ideally therefore the neuroinhibitory substance is injected to within 5 mm of the SPG or OG, preferably within 4 mm, such as within 3 mm, especially within 2 mm. Ideally injection of the active ingredient takes place 2 mm or less form the target SPG or OG. This can be measured using the device and associated computer technology which is described in detail below.

The injection of the neuroinhibitor occurs infrazygomatically or transnasally in order to ensure that a safe, close injection of the neuroinhibitor is achieved. The terms infrazygomatic or transnasally are terms of this art.

The term infrazygomatic therefore requires that the injection takes place inferior to the zygomatic arch on either side of the mandibula, typically anterior or through the mandibular notch.

The term transnasally defines an injection route which involves advancing the needle through the nasal cavity. Targeting the SPG this route will further violate the lateroposterior boundary of the nasal cavity, constituting the medial boundary of the SF.

Targeting the OG involves advancing through the maxillary ostium and the maxillary sinus, violating the back wall of the maxillary sinus, advancing on the lateral aspect of the lateral pterygoid plate. The OG is located in the infratemporal fossa, the SPG in the sphenopalatine fossa.

It is preferably the case that access to the SPG or OG from the outside of the body is achieved infrazygomatically or transnasally by insertion of the injection device such that the device defines a straight line between SPG or OG (or more specifically the point proximal to the SPG and OG where active substance release will occur) and the point at which the external skin or mucosa is penetrated. This is illustrated inFIGS.13,15and16.FIG.14shows an alternative preferred approach where the end piece of the device has a curved tip enabling the needle to be directed toward the SPG or OG at an angle from the main axis of the lumen. The device punctures the wall of the nasal cavity at puncture site50and the angled tip directs the needle toward the target site.

The infrazygomatic approach therefore allows the injection device to pass through the skin and then soft tissue to the SPG or OG. That can be achieved in a straight line and hence with a straight injection device. That means that the injection can be targeted very accurately in close proximity to the SPG or OG. This method of administration allows application under local anaesthetic.

Where the injection takes place transnasally the route involves passing through the nasal mucosa and the sphenopalatine foramen or the perpendicular plate of the palatine bone to reach the SPG. Injection is not therefore lateral (via the cheek) but preferably involves a straight line from the injection point to the SPG. Transnasal route to reach the OG involves advancing through the maxillary ostium and the maxillary sinus, violating the back wall of the maxillary sinus, advancing on the lateral aspect of the lateral pterygoid plate. This involves a straight line from the injection site to the OG. These methods may require general anaesthesia.

The injection described above can be used in the treatment or prevention of headaches, in particular any kind of primary headache or secondary headache. The treatment or prevention may relate therefore to cluster headaches, migraine, tension-type headache, short lasting unilateral neuralgiform headache with conjunctival injection and tearing/cranial autonomic features (SUNCT/SUNA), hemicrania continua or paroxysmal hemicrania.

Paroxysmal hemicrania is a primary headache disorder involving frequent attacks of unilateral, pen-orbital and temporal pain typically lasting less than 30 minutes. The pain can be associated with conjunctival injection, lacrimation, nasal congestion, rhinorrhea, ptosis and eyelid edema.

SUNCT/SUNA is a primary headache disorder characterized by multiple attacks of unilateral, pen-orbital and temporal pain typically lasting less than 2 minutes. The pain is associated with conjunctival injection, lacrimation, nasal congestion, rhinorrhea, and eyelid edema. This headache may be associated with trigeminal neuralgia.

Hemicrania continua is a primary headache disorder characterized by a strictly unilateral headache responsive to Indomethacin. The pain is associated with conjunctival injection, lacrimation, nasal congestion, rhinorrhea, ptosis, and eyelid edema.

It will be appreciated that the term treatment here refers to reduction in pain experienced by a patient and/or a reduction in the frequency in which headache occurs. The term prevention means preventing headaches occurring, e.g. as frequently as before.

The neuroinhibitory substance is one which is capable of preventing or treating headache when administered in close proximity to the SPG or OG. Suitable inhibitors include Botulinum toxin, Tetanus neurotoxin, (which is produced byClostridium tetani), Staphylococcal alpha-toxin, and acylpolyamine toxins (e.g. AR636 and AG489).

In general the therapeutic modality used to treat and/or prevent headache is a presynaptic neurotoxin. “Presynaptic neurotoxin” as used herein refers to those neurotoxins and their derivatives which are known to produce localized, reversible flaccid paralysis of musculature in mammals which does not result in degeneration of muscle or nervous tissue.

It is preferred however if the inhibitor is botulinum toxin. This is a protein and neurotoxin produced by the bacteriumClostridium botulinumand is commercially available. It is preferred if the botulinum toxin is of types A, B, C, D, E, F or G, such as Botulinum toxin type A. Botulinum toxin may for example be administered in the manner and form described in U.S. Pat. No. 7,981,433

The frequency of the injections needed may be every 3 to 8 months but will be patient dependent.

Whilst the method described above is in relation to the administration of neuroinhibitory substances such as botulinium toxin, the method of injection and device discussed here can be used for the injection of other active substances such as local anaesthetics (e.g. lidocaine or marcain) and corticosteroids (e.g. triamcinolone). The method and device may be used to inject a local anaesthetic or corticosteroid for use in a method for treating or preventing headache, rhinitis, rhinosinusitis, Frey syndrome or hypersecretion of tears/lacrimation comprising injecting said substance in close proximity to the sphenopalatine ganglion or otic ganglion wherein an injection device comprising said substance is brought into close proximity to the sphenopalatine ganglion or otic ganglion by inserting said injection device into the patient transnasally or infrazygomatically and the substance injected in close proximity to the SPG or OG.

Various example procedures using the device described above are set out below andFIGS.13athrough16illustrate the locations of the SPG and OG along with possible approaches for interventions on the SPG or OG as discussed above.

Example 1

A female patient with refractory hemicrania continua was treated via injection of Botox around the SPG. Due to an occipital neurostimulator MRI was contraindicated and identification of SPG on MRI was not possible. Preoperatively the calculated position of the SPG was marked on a CT scan with 1 mm slides. On the navigation planning system a preplanned puncture site and trajectory was made. On the symptomatic side a navigable needle guide was advanced through the sphenopalatine foramen and towards the SPG. The needle was passed through the guide and the tip of the needle was confirmed to be 1 mm from the SPG by the navigation system while 75 IU botulinum toxin type A was injected.

Over a period of two months prior to the treatment the patient had an average headache intensity of 8.1 (scale 1-10) and normally experienced from one to four headache attacks daily. From 4 to 10 weeks after the treatment the patient had not a single attack during the whole period and the average headache intensity was 6.3. The patient also did not experience any complication during 4 months follow-up.

Example 2

The patient was a male that presented with a prevertebral mass close to the atlas (C1) seen on MRI. He had formerly been treated for pulmonary cancer histologically classified as adenocarcinoma. After a clinical assessment it was concluded that the tumor was not available for conventional procedures for a histological diagnosis. Using a navigable guide with an optical navigation system and a transoral approach it was possible to do a fine needle biopsy of the tumor deep in the neck to confirm the suspicion of a pulmonary metastasis.

Example 3

A female patient with refractory chronic cluster headache was treated via injection of lidocaine around the OG. Preoperatively the calculated position of the SPG was marked on a CT scan with 1 mm slides. On the navigation planning system a pre-planned puncture site and trajectory was made. On the symptomatic side a navigable needle guide was advanced through the maxillary ostium and the back wall of the maxillary sinus, and then at the lateral aspects of the lateral pterygoid plate to the OG. 5 ml of lidocaine 20 mg/ml was injected. The patient had a short relief of the headache as expected using short-acting local anaesthetic.

Example Applications

The advantages for interventions targeting the SPG will also arise when using the device for IGS in the rest of the body for indications such as injections, biopsies, punctures, aspiration, ablation therapy, and for positioning of electrodes, catheters, radioactive seeds and implants. The same device can be used or it may be advantageous to use a similar device with an alternative tip design or a different length of end piece, depending on the characteristics of the target site, the approach available and the procedure that is to be carried out. The needle guide device may thus be utilised for procedures to address numerous medical conditions. Procedures that the device can be used for include:InjectionsAny pharmacological substanceNeuroexcitatory agentNeuroinhibitory agentsBotulinum toxin, any typeStaphylococcal alpha-toxinTetanus neurotoxinAcylpolyamine toxinsCore needle biopsy and fine needle biopsyHead/neck areaIntracraniallyExtracraniallyRetropharyngeal spaceParapharyngeal spaceSkull baseDeep regions of the face/neckAny region of the face/neckIn the vicinity of the columnaIn the vicinity of bone in any region of the bodyAny region of the bodyPuncture and aspirationEvacuation of cystic structures and fluidic compartment for diagnosis and therapyAny part of the bodyAblation therapyAny nerve or neural structure, intracranially and extracraniallyAblation of normal tissue to reduce volume and/or increase stiffness in any region of the bodyAblation of tumour tissue in any region of the bodyPositioning of electrodes, catheters, implants, electrophysiological measurements, radioactive seedsAny structure or organ of the body including nerve, neural structure, blood vessel.Endoscopy and/or pointer proceduresFlexible or rigid endoscope may be attached to the deviceAny procedure in an open cavity that requires endoscope or pointerParanasal sinusisNasal cavityFarynxLarynx

The device can be used in the treatment of conditions including:HeadacheMigraineCluster headacheTension-type headacheTrigeminal Autonomic HeadacheSUNCTHemicrania ContinuaParoxysmal hemicraniaAny kind of primary headacheAny kind of secondary headacheRhinitisAllergic rhinitisVasomotor rhinitisRhinitis medicamentosaPolypous rhinitisAny kind of non-structural rhinitisRhinosinusitisWithout polypsWith polypsAny kind of rhinosinusitisHypersecretion of tears/excessive lacrimationAny disease with hypersecretion of tearsFrey syndrome/auriculotemporal syndrome/gustatory sweatingTinnitusObjective tinnitusSubjective tinnitus

Whilst the indications and examples above primarily relate to conditions of the human body the device can of course also be utilised for interventions on the animal body.