Neurosurgical device delivery tool, track forming tool, and neurosurgical device

Abstract

A device delivery tool for inserting a guide tube and cannula into the brain of a mammal, comprising a cannula delivery instrument detachably engageable with a cannula for providing fluid access to the brain, and a guide tube delivery instrument detachably engageable with a guide tube and having a through-bore to receive the cannula delivery instrument. A position of the cannula delivery instrument within the guide tube delivery instrument is adjustable. Also, a track-forming tool for forming a track in brain tissue, comprising an inner probe having a tip configured for dissecting tissue and an outer probe having a through-bore configured to receive the inner probe. A distance by which the tip of the inner probe extends beyond the outer probe is adjustable. Also, a guide tube comprising a through-bore for passage of a fluid transfer tube, an inner layer that is impermeable to fluid, and a resiliently-deformable outer layer having a higher compliance than the inner layer.

Description

[0001] NEUROSURGICAL DEVICE DELIVERY TOOL, TRACK FORMING TOOL, AND

[0002] NEUROSURGICAL DEVICE

[0003] FIELD

[0004] The present invention relates to systems and methods for use in neurosurgery. More particularly, the present invention relates to a neurosurgical device for use in infusing therapies into brain tissue and surgical instruments to prepare and insert the neurosurgical device into the brain.

[0005] BACKGROUND

[0006] Treatment of neurological diseases can be hindered by the presence of the blood-brain barrier. It can be difficult to develop therapeutic agents that can be delivered from the systemic circulation into the brain parenchyma. Therefore, it can be desirable to deliver therapeutic agents directly to specific regions of the brain (‘brain volumes’ or ‘target volumes’). Obtaining an appropriate concentration of the therapeutic agent in a target volume whilst minimising exposure of the rest of the brain to the therapeutic agent is desirable, to reduce undesired side effects.

[0007] Convection Enhanced Delivery (CED) is a method of targeted delivery of therapeutic agents to particular brain volumes by the controlled infusion of the therapeutic agent delivered into the brain parenchyma in a fluid using extremely small cannulas or tubing (often referred to in the art as micro - cannulas). The micro -cannulas have a port or ports at their distal end, allowing an infusate including the therapeutic agent to exit the cannula into the target brain volume. A continuous pressure gradient must be achieved at the port to overcome the ambient pressure of the target brain volume, thereby allowing the infusate to flow effectively into the target brain volume.

[0008] There are challenges in using the CED technique because fluid flowing from a cannula port will follow the path of least resistance. Typically, the path of least resistance will be back along the cannula / tissue interface causing so-called ‘reflux’, instead of driving the fluid into the tissue as desired. To control reflux, so that fluid is driven into the tissue of the target volume, CED cannulas typically have an abrupt change in diameter (a ‘step’) towards their distal end. For example, the distal end of the cannula may be of less than 1mm in diameter for a short length to the extreme end that is placed at the target volume, with a step up to a diameter of 1.5 to 2.5 mm for the remaining, more distal portion of the cannula. The small diameter distal end, if inserted atraumatically, creates a tissue seal around the cannula, minimising reflux along the interface. The change in diameter at the step compresses tissue on insertion into the brain and further resists reflux.

[0009] Careful control of flow rates, typically in the range of 3-5 microlitres per minute, facilitates flow of an infusate into the tissues in preference to reflux. Higher flow rates will tend to increase the degree of reflux and may lead to refluxing infusate flowing past the step and flowing back along the cannula / brain tissue interface, even at the wider diameter portion of the cannula. When the step is overwhelmed in this way, the infusate enters a low resistance pathway through the larger circumferential space around the larger diameter part of the cannula, with a resultant reduction of the intended distribution of infusate within the target volume. The design of the reflux resistant step differs between CED cannulas. The cannulas described in EP 1482851 Bl and US 2010 / 0217228 Al provide a single step. WO 2007 / 024841 A2 provides a cannula with a plurality of steps, and WO 2014 / 016591 Al has a recessed step.

[0010] In addition to the step design, the length that the narrower-diameter part of the cannula extends beyond the step, to its extreme distal end, is an important determinant of both the volume and shape of distribution of infusate into brain tissue. A short-stepped cannula (i.e. a cannula with only a short length of smaller diameter) will have a small volume of distribution (Vd) that is roughly spherical. As the length of the smaller diameter portion increases, the Vd becomes larger and more ovoid, then cylindrical and then pear shaped with a bulbous distal end.

[0011] When the radius of distribution of fluid convected into the brain exceeds that of the region of compressed tissue at the step then the infusate will tend to enter the low resistance pathway along the larger diameter portion of the cannula and reflux away from the target volume. This places a limit on the Vd at the target.

[0012] To deliver therapy to clinically meaningful tissue volumes with a fixed step length arrangement can therefore be problematic. Using a cannula with a short, fixed step-length will require sequential infusions made at different points along a trajectory into the brain in order to fill an elongate volume of tissue. Similarly, multiple passes are required to fill a larger, more spherical structure in the brain. Conversely, filling a smaller target using a cannula with a relatively long ‘step length’ may make it difficult to contain the therapy in the target volume. Therefore, the ability to adjust the step length for each target provides significant advantages.

[0013] The majority of targets for treating central nervous system (CNS) diseases by CED require several cannulas to be implanted to achieve the desired coverage of infusate into brain tissue. When the desired target volume and shape has been defined from MRI images, the number and orientation of cannulas required to fill the volume are determined by understanding the likely distribution shape and volume that can be achieved with the cannulas being deployed. It is also important to confirm that the infused therapy has covered the prescribed treatment volume with MRI imaging either during or immediately following the infusion.

[0014] When rigid cannulas are used, they are fixed in a stereotactic frame whilst the infusion is carried out. In such arrangements the stereotactic frame needs to be MRI-compatible and have a low profile to fit in the imaging coil. Typically, additional cannula placements and infusions are required after completion of the first. Thus, such procedures are relatively lengthy and can expose the patient to increased risks from prolonged anaesthesia and immobilisation.

[0015] Alternative procedures employing multiple cannula trajectories make use of flexible cannulas that are implanted and secured to the skull. The flexible cannula tubing extending out of the skull can be attached to a low-profile skull fixation. This facilitates safe transfer into an MRI scanner where simultaneous infusions can be conducted with the patient awake for neurological evaluation. A stereotactic frame is not required during infusion where flexible cannulas are employed. The flexible cannulas may be removed after the infusions are complete, or in some instances may be left in-situ for repeated infusions days, weeks or months later.

[0016] Uses of flexible cannulas are described in EP 1482851 Bl, EP 2601997 Bl, EP 2819739 Bl, and WO 2014 / 016591 Al. In these arrangements, the distance between the cannula’s distal end and the reflux resistant step can be adjusted. In each case the flexible cannula has a proximal hub and is cut to a desired length for insertion to a target point in the brain. When inserted into an implanted guide tube, also cut to a desired length, the cannula’s hub acts as a stop when it engages with a proximal head on the guide tube that is fixed in the skull. The cannula extends beyond the guide tube and the step thus created by the change in diameter from the cannula to the guide tube provides resistance to reflux of infusate.

[0017] In typical procedures to implant flexible cannulas described in EP 1482851 Bl, EP 2601997 Bl, and EP 2819739 Bl, a profiled hole is made in the skull along the selected trajectory, guided by a stereo-guide or image-guided robot. A probe is then passed through the hole to the planned distal end of the guide tube and then withdrawn, leaving a track in brain tissue. The guide tube, cut to length, is placed over a delivery probe such that the rounded tip of the probe extends just beyond its distal end. The guide tube is inserted down the pre-made track until the head on its proximal end press fits into the formed hole in the skull. The probe is then advanced to the planned position of the cannula target and withdrawn leaving a track through the tissue that is contiguous with the bore of the guide tube.

[0018] The cannula, connected to an infusion pump and delivering infusate at a low flow rate, is inserted down the guide tube and through the pre-formed track in the tissue. The slow infusion through the cannula prevents coring of tissue during its transit. When a therapeutic fluid is delivered through the cannula’s distal port it will follow the path of least resistance and flow back along the cannula-tissue interface before meeting the region of tissue compressed by the distal end of the guide tube. The localised pressure on the interface acts to inhibit reflux and the infusate is then preferentially driven radially into the tissue.

[0019] The devices described above have potential disadvantages. The method of insertion can cause micro trauma to the tissues, creating a low resistance path for infusate which impairs reflux control at the guide tube- tissue interface. As the guide tube is inserted into the pre-made track in the brain, the cut edges of its distal end may shear the tissue, creating a circumferential column of fragmented tissue. The force required to push fit the head of the guide tube into the pre -formed hole in the skull is also transferred to the distal end of the guide tube, which may add to the localised tissue trauma in the region of the step.

[0020] Additionally, as the cannula is inserted down the guide tube it will tend to act as a piston and drive a column of air ahead of it. Even with the application of suction at the proximal end of the guide tube, it is difficult to vent air through the narrow space between the cannula and the guide tube. If air is driven into the brain, it tears the tissue and creates a space -occupying lesion near the reflux controlling step. In the short term this is likely to disrupt the intended pattern of distribution of the infusate, but as the air is absorbed the cavity left can provide a low resistance pathway at the step, which will augment undesired reflux.

[0021] EP 3119310 B1 describes a guide tube with an internal profile configured to provide a fluid return path for carrying any fluid displaced from within the guide tube during insertion of a cannula. Such a path may also conduct and vent air during cannula insertion. However, to create a profile with internal channels of sufficient size to facilitate air venting increases the overall dimensions of the guide tube. A wider-diameter guide tube may cause more trauma on insertion. Narrow channels between the guide tube and cannula may be liable to obstruction of air flow by the presence of liquid, due to surface tension.

[0022] WO 2014 / 016591 Al discloses a recessed step arrangement, wherein the guide tube comprises an internal recess that compresses tissue therein. The internal recess provides a step feature that is intended to provide more effective compression of tissue to limit the flow of infusate along the cannula-tissue interface. However, in such an arrangement the guide tube cores a portion of brain tissue on insertion. The local tissue trauma could result in neurological deficits if in an eloquent part of the brain or may cause haemorrhage.

[0023] A further potential difficulty with known CED devices, particularly those that are chronically implanted, is brain movement. The brain moves within the skull so that fixing of a cannula and / or associated guide tubes to the skull can cause movement of the tubing or cannula relative to brain tissue. This may cause local tissue trauma, particularly at a reflux resistant step, creating local vacuolation and the creation of a low resistance pathway that will tend to augment rather than resist reflux.

[0024] It is an object of the invention to address at least some of the aforementioned difficulties, by providing an improved guide tube and improved tools for delivering the guide tube into the brain.

[0025] SUMMARY

[0026] According to a first aspect of the invention, there is provided a device delivery tool for inserting a guide tube and a fluid transfer tube into the brain of a mammal, the device delivery tool comprising: a cannula delivery instrument having a distal end configured to detachably engage with a proximal end of a fluid transfer tube for providing fluid access to the brain of a mammal; and a guide tube delivery instrument having: a distal end configured to detachably engage with a proximal end of a guide tube configured for insertion into the brain; and a through-bore configured to receive the cannula delivery instrument, wherein a position of the cannula delivery instrument within the through-bore of the guide tube delivery instrument is adjustable, such that a fluid transfer tube engaged with the distal end of the cannula delivery instrument can be advanced into the brain through a guide tube engaged with the distal end of the guide tube delivery instrument.

[0027] As described above, a problem with existing cannula systems is that the insertion of the cannula into the guide tube can drive air into the brain. Inserting the guide tube with the cannula already inside its through -bore can solve this problem. However, this is difficult to achieve with existing tools because of the need to ensure that the distal end of the cannula extends a precise distance beyond the distal end of the guide tube. The present invention provides a novel delivery tool that allows the guide tube and cannula to be delivered together, and for the relative position of the guide tube and cannula to be adjusted in-situ.

[0028] Optionally, the distal end of the guide tube delivery instrument is further configured to engage with a guide hub implanted in an aperture formed in a skull along a trajectory to a target within the brain, the guide hub configured to receive the guide tube along the trajectory; and engagement of the distal end of the guide tube delivery instrument with a guide hub releases a guide tube engaged with the distal end of the guide tube delivery instrument. The guide hub provides a fixed reference point in the skull to retain the guide tube and cannula. This feature allows the guide tube to be precisely positioned in the guide hub.

[0029] Optionally, the distal end of the guide tube delivery instrument comprises one or more retention features configured to prevent proximal movement of a guide tube engaged with the distal end of the guide tube delivery instrument. Optionally, the one or more retention features are configured such that advancement of the distal end of the cannula delivery instrument through the through-bore of the guide tube delivery instrument releases the retention features. The retention features ensure that the guide tube can be predictably and reliably inserted in a controlled manner without its position changing prematurely.

[0030] Optionally, the device delivery tool further comprises a guide tube sheath configured to: engage with the distal end of the guide tube delivery instrument; and enclose a guide tube engaged with the distal end of the guide tube delivery instrument. The guide tube sheath protects the guide tube during preparation of the guide tube for insertion into the brain, for example during the process of cutting the guide tube to length. The sheath can also assist in priming the cannula and guide tube with fluid prior to insertion into the brain.

[0031] Optionally, the guide tube sheath is configured to prevent the release of the one or more retention features when the guide tube sheath is engaged with the distal end of the guide tube delivery instrument. This ensures that the guide tube is not prematurely released from the delivery tool before it is properly positioned in the brain.

[0032] Optionally, one of the guide tube delivery instrument and the cannula delivery instrument comprises a measurement scale; the other of the guide tube delivery instrument and the cannula delivery instrument comprises an indicator feature; the indicator feature and the measurement scale are configured to interact to indicate a distance by which the cannula delivery instrument should be advanced distally relative to the guide tube delivery instrument such that a fluid transfer tube engaged with the distal end of the cannula delivery instrument is fully advanced into a guide tube engaged with the distal end of the guide tube delivery instrument. This assists in the precise and accurate preparation of the guide tube and cannula for insertion into the brain by ensuring the distal end of the cannula extends the correct distance beyond the distal end of the guide tube when fully inserted. Optionally, one or both of: a) a distal region of the guide tube delivery instrument comprises an axially-extending aperture providing access to the through-bore of the guide tube delivery instrument; and b) the cannula delivery instrument comprises a through-bore configured to receive at least a portion of the fluid transfer tube, and a distal region of the cannula delivery instrument comprises an axially-extending aperture providing access to the through-bore of the cannula delivery instrument. Optionally, a distal region of the guide tube delivery instrument comprises an axially -extending slot providing access to the through-bore of the guide tube delivery instrument, the slot extending to the distal end of the guide tube delivery instrument. These apertures allow the fluid transfer tube to have a proximal bubble filter that can be removed from the bore of the delivery tool at the appropriate point in the delivery procedure.

[0033] Optionally, the guide tube delivery instrument and the cannula delivery instrument comprise corresponding alignment features configured such that the guide tube delivery instrument and the cannula delivery instrument adopt a predetermined relative rotational alignment when the cannula delivery instrument is received in the through-bore of the guide tube delivery instrument. This prevents twisting of the fluid transfer tube relative to the guide tube during advancement of the fluid transfer tube.

[0034] According to second aspect, there is provided a kit for use in stereotactic neurosurgery comprising: the device delivery tool of the first aspect; a fluid transfer tube for providing fluid access to the brain of a mammal; and a guide tube configured for insertion into the brain and having a through-bore for passage of the fluid transfer tube. Optionally, the kit further comprises a priming tube configured to connect fluidically to the proximal end of the fluid transfer tube to fill the fluid transfer tube.

[0035] The kit can be provided as a pre-assembled kit, which reduces preparation time for a surgeon because no assembly of the guide tube and cannula is required. It can also improve sterility and reduce the likelihood of surgical complications by reducing handling of the devices prior to insertion into the brain.

[0036] According to a third aspect, there is provided a method for preparing a fluid transfer tube and a guide tube for use in stereotactic neurosurgery using the device delivery tool of the first aspect, wherein the fluid transfer tube is engaged with the distal end of the cannula delivery instrument, and the guide tube is engaged with the distal end of the guide tube delivery instrument, the method comprising: retracting proximally the cannula delivery instrument relative to the guide tube delivery instrument by a first predetermined length from a fully deployed position of the cannula delivery instrument relative to the guide tube delivery instrument, the fully deployed position being a position at which the fluid transfer tube is fully advanced into the guide tube; and cutting the fluid transfer tube and the guide tube together such that the guide tube is cut to a second predetermined length, wherein the sum of the first predetermined length and the second predetermined length is equal to a depth of a surgical target within a skull of a patient. An advantage of being able to handle the guide tube and cannula together is that both can be cut to length in a single operation, rather than needing to be individually cut. This reduces the time taken to prepare the devices, reduces the chance of error in preparation, and reduces handling of the devices.

[0037] According to a fourth aspect, there is provided a track-forming tool for forming a track in brain tissue for insertion of a fluid transfer tube within the through -bore of a guide tube, the track -forming tool comprising: an inner probe having a distal end, the distal end comprising a tip configured for dissecting tissue; an outer probe having a through-bore configured to receive the inner probe, wherein: a distance by which the tip of the inner probe extends beyond a distal end of the outer probe is adjustable; the outer probe is configured for insertion into the brain tissue to form a larger-diameter portion of the track to receive the guide tube; and the inner probe is configured for insertion into the brain tissue to form a smaller-diameter portion of the track extending beyond the end of the larger- diameter portion of the track to receive a portion of the fluid transfer tube extending beyond a distal end of the guide tube.

[0038] The track -forming tool allows for tracks to be formed for both the larger-diameter guide tube and the smaller-diameter fluid transfer tube using a single instrument in a single operation. This reduces the number of steps and the duration of surgical procedures. It also improves the precision and accuracy of the relative placement of the two tracks of different diameters.

[0039] Optionally, the track-forming tool further comprises an outer body having a through-bore configured to receive the outer probe, wherein the outer body is configured to be received in a guide for holding surgical tools in stereotactic surgery. This allows the tool to be easily used with a conventional stereotactic surgical setup.

[0040] Optionally, the distal end of the inner probe is tapered, optionally wherein the distal end of the inner probe tapers from between 0.4mm and 0.6mm to between 0. 1mm and 0.3mm, optionally from 0.5mm to 0.2mm. Optionally, the distal end of the outer probe is tapered, optionally wherein the distal end of the outer probe tapers from between 1mm and 2mm to between 0.5mm and 1mm, optionally from 1 ,4mm to 0.8mm. This allows the tool to form a profded track that leads to compression of brain tissue around the distal end of the fluid transfer tube and the step at the distal end of the guide tube. This inhibits undesirable reflux and promotes correct dispersion of infusate into the brain tissue.

[0041] Optionally, the track-forming tool comprises a cannula track forming instrument, a distal section of the cannula track forming instrument comprising the inner probe and a proximal section of the cannula track forming instrument having a larger diameter than the inner probe, optionally wherein the proximal section and the distal section are integrally formed. Optionally, the track-forming tool comprises a guide tube track forming instrument, a distal section of the guide tube track forming instrument comprising the outer probe and a proximal section of the guide tube track forming instrument having a larger diameter than the outer probe, optionally wherein the proximal section and the distal section are separable. This provides rigidity and ease of handling the probe in the proximal section, which does not enter the brain and so does not need to be sized to match the required track. Optionally, the track-forming tool comprises a cannula track forming instrument, a distal section of the cannula track forming instrument comprising the inner probe; the track -forming tool comprises a guide tube track forming instrument, a distal section of the guide tube track forming instrument comprising the outer probe; one of the cannula track forming instrument and the guide tube track forming instrument comprises a measurement scale; the other of the cannula track forming instrument and the guide tube track forming instrument comprises an indicator feature; the indicator feature and the measurement scale are configured to interact to indicate the distance by which the tip of the inner probe extends beyond the distal end of the outer probe. This allows precise and accurate adjustment to form the two sections of the track.

[0042] Optionally, one or both of a distal end of the outer probe and the distal end of the inner probe comprises a lubricious coating. This reduces trauma to the surrounding tissue when forming the track.

[0043] According to a fifth aspect, there is provided a guide tube for use with a fluid transfer tube for providing fluid access to the brain of a mammal, wherein the guide tube is configured for insertion into the brain, and the guide tube comprises: a through-bore for passage of a fluid transfer tube; an inner layer; and a resiliently-deformable outer layer having a higher compliance than the inner layer, wherein one or both of the inner layer and the outer layer is impermeable to fluid. Optionally, the inner layer defines the through -bore.

[0044] This design of guide tube provides a stiff inner layer that provides column strength to insert the guide tube into the brain, while providing a compliant outer layer. The compliant outer layer helps centre the guide tube in the pre-made track, which may distort after removal of the track -forming tool due to differing density and compressibility of neighbouring brain tissue. The outer layer also minimises tissue trauma, and is compressible to help form a seal to surrounding tissue that prevents or reduces undesirable reflux.

[0045] Optionally, a proximal end of the guide tube has a larger diameter than the distal end of the guide tube, such that the proximal end acts as a stop to limit an insertion depth of the guide tube into the brain, optionally wherein the proximal end is formed integrally with the inner layer. This provides a reliable mechanical stop to insert the guide tube to the correct depth.

[0046] Optionally, one or more of: a) the outer layer comprises a lubricious coating; b) the outer-layer comprises silicone; and c) the outer layer is formed by dip-coating onto the inner layer. These properties help to reduce trauma to surrounding tissue as the guide tube is inserted.

[0047] Optionally, the outer-layer has a hardness of at most 80 measured on the Shore 00 hardness scale, optionally at most 40, optionally at most 20, optionally at most 10. This provides high compliance, with the advantages described above.

[0048] Optionally, a proximal portion of the guide tube is configured to be axially and / or laterally deformable, optionally wherein the proximal portion has a length of between 5mm and 30mm. Optionally, the proximal portion is configured as a spring, optionally by forming a spiral cut through the inner layer in the proximal portion. This prevents localised trauma caused when the brain moves relative to the skull surface to which the guide tube is fixed. Optionally, the proximal portion is configured such that a maximum elastic deformation of the proximal portion under compression is less than a maximum elastic deformation of the proximal portion under extension. This means that the deformability does not adversely affect the insertion procedure, while still providing sufficient flexibility to account for relative movement of the skull and brain.

[0049] Optionally, the inner layer comprises polyether ether ketone, PEEK, or carbon-filled PEEK. These are readily available materials that can provide the required high stiffness at small dimensions.

[0050] Optionally, the through-bore has a diameter of at most 0.7mm, optionally less than 0.6mm. Optionally, wherein an outer diameter of the inner layer is at most 1.5mm, optionally at most 1mm, optionally approximately 0.8mm. Optionally, an outer diameter of the guide tube is at most 1 ,8mm, optionally at most 1.5mm, optionally at most 1.3mm. These dimensions allow for sufficient space to accommodate a fluid transfer tube that can provide suitable flow rate, while minimising the overall size to reduce tissue trauma.

[0051] Optionally, the guide tube has a length of between 25mm and 150mm, optionally between 50mm and 120mm. This allows the guide tube to reach most common targets within the brain of a mammal such as a human.

[0052] According to a sixth aspect, there is provided a kit for use in stereotactic neurosurgery comprising: a fluid transfer tube for providing fluid access to the brain of a mammal; and the guide tube of the fifth aspect. Optionally, the kit further comprises the device delivery tool of the first aspect. The kit allows the components necessary for performing a surgical procedure to be supplied together with compatible sizes and in a sterile package.

[0053] BRIEF DESCRIPTION OF THE DRAWINGS

[0054] The present invention will now be described, by way of non-limitative example only, with reference to the accompanying drawings, in which:

[0055] Fig. 1 is an exploded view of a cannula assembly;

[0056] Fig. 2 is a view of the cannula assembly of Fig. 1 when assembled;

[0057] Fig. 3 shows a guide hub;

[0058] Fig. 4 shows the distal end of a guide tube with indwelling fluid transfer tube;

[0059] Fig. 5 shows detail of the structure of a guide tube;

[0060] Fig. 6 shows the behaviour of a flexible portion of a guide tube;

[0061] Fig. 7 shows detail of the flexible portion of Fig. 6;

[0062] Fig. 8 shows a tool holder and tools for skull preparation;

[0063] Fig. 9 shows a device preparation jig and tools for preparing and inserting a guide tube and fluid transfer tube;

[0064] Fig. 10 shows a cutting jig for cutting a guide tube and fluid transfer tube to length;

[0065] Fig. 11 shows details of the use of cutting jig;

[0066] Fig. 12 shows a cutting tool used with the cutting jig; Fig. 13 shows a track forming tool with probes retracted;

[0067] Fig. 14 shows the track forming tool of Fig. 13 with probes extended;

[0068] Fig. 15 is an exploded view of the track forming tool of Fig. 13;

[0069] Fig. 16 shows detail of the internal structure and distal end of the track forming tool of Fig. 13;

[0070] Fig. 17 shows a device delivery tool;

[0071] Fig. 18 is another view of the device delivery tool of Fig. 17;

[0072] Fig. 19 is an exploded view of the device delivery tool of Fig. 17, with a guide tube and fluid transfer tube for use with the device delivery tool;

[0073] Fig. 20 shows detail of the distal end of the device delivery tool of Fig. 17, with guide tube and fluid transfer tube loaded in the tool;

[0074] Fig. 21 shows the device delivery tool being used to insert a guide tube and fluid transfer tube through a guide hub into a brain; and

[0075] Fig. 22 shows the procedure for securing the guide tube and fluid transfer tube in the guide hub, and removing them from the device delivery tool after insertion.

[0076] DETAILED DESCRIPTION

[0077] The present disclosure addresses at least some of the problems with existing CED systems. The present disclosure provides a fine, flexible CED cannula assembly with an adjustable step length that can be tailored to optimise the shape of the infusion volume to best fill the selected treatment volume in the brain, wherein the cannula assembly can be inserted precisely to deep brain targets with minimal tissue trauma and without the risk of introducing air which can disrupt the distribution of the infiisate in the tissue. In the context of the present disclosure, the terms ‘cannula’ and ‘fluid transfer tube’ may be used interchangeably. The cannula assembly may refer to the cannula (or fluid transfer tube) in combination with a guide tube within which the cannula can be positioned, as will be discussed further below.

[0078] The present disclosure provides cannula assemblies that can be inserted in an operating theatre and that have low profile skull fixations so that the patient can be moved safely and receive simultaneous cannula infusions whilst awake with a minimal risk of cannula dislodgement. The present disclosure also provides surgical devices and methods for inserting the cannula assemblies.

[0079] Fig. 1 and Fig. 2 show a guide hub 50 and a cannula assembly comprising a guide tube 4 and a cannula 6. The guide hub 50 may comprise titanium or a titanium alloy. The guide hub 50 may alternatively comprise PEEK, but in this case pre-tapping of the bone of the skull may be required before the guide hub 50 is inserted. The guide tube 4 and cannula 6 are made of materials that are cuttable with a blade. This means that their skull to target lengths can be individually adjusted and the step-length of the cannula assembly can be tailored to optimise the shape and volume of infiisate distribution to match the target volume.

[0080] Guide hub Fig. 3 shows the guide hub 50 in more detail. The guide hub 50 is inserted in a profded hole made in the skull along a trajectory to a brain target. The guide hub 50 may comprise an open cylinder with through-bore 52 for inserting and securing the guide tube 4 and cannula 6 in the skull along the trajectory to the brain target. The guide hub 50 may comprise threads 53 on its external surface for fixation in the skull. The threads 53 may be self-tapping and have multiple starts, optionally triple starts.

[0081] The guide hub 50 comprises a proximal rim 56 whose distal face acts as a stop on a datum surface made in the skull. A proximal face of the guide hub 50 provides a datum surface for cannula and guide tube insertion tools.

[0082] A proximal end of the guide hub 50 comprises engagement features for a delivery or removal tool that is used to insert or remove the guide hub 50 in the skull. The engagement features may comprise hex-features for engagement with a hex-driver. The hex features may extend above the proximal rim by up to 3mm.

[0083] A distal portion of the guide hub 50 may comprise a stepped reduction in internal diameter. The step provides an engagement surface for a depth -limiting cap on the proximal end of the guide tube 4. The guide hub 50 may comprise a formation in the wall of the through -bore for securing the guide tube 4 and cannula 6, such as an undercut ring. The distal portion of the undercut ring may be tapered. Cannula

[0084] The cannula 6 is preferably narrow and flexible and may be inserted through the bore of the guide hub 50 within the guide tube 4, which is also preferably flexible. The proximal ends of the guide tube 4 and cannula 6 are secured within the hub’s bore 52, creating a fluid seal. The distal end of the guide tube 4 is positioned in a proximal end of a brain target volume and the distal end of the cannula 6 is placed more distally in the target volume. As discussed above, the distal end of the guide tube 4 forms a step to resist the flow of infusate refluxing proximally along the cannula assembly from a port at the distal end of the cannula 6.

[0085] The cannula 6 (which may be interchangeably referred to as a fluid transfer tube) is suitable for insertion into living tissue to deliver an infusate. The fluid transfer tube is preferably made of material that is cuttable with a blade, for example a plastic such as polyether ether ketone (PEEK).

[0086] The fluid transfer tube 6 comprises a proximal end, a distal end for insertion into the tissue and a through-bore configured to allow flow of the infusate from the proximal end to the distal end.

[0087] The fluid transfer tube 6 may comprise a proximal, cylindrical depth-controlling stop 40 that fits within the bore 52 of the guide hub 50. The depth-controlling stop 40 may be configured to engage with a proximal end of the guide tube 4 to form a fluid seal between the fluid transfer tube 6 and the guide tube 4. The stop 40 may have an engagement feature to retain the fluid transfer tube 6 within the bore 52 of the guide hub 50, for example, a feature that snap-fits into a corresponding formation in the wall of the hub’s through bore 52. The depth-controlling stop 40 may engage with a depthlimiting cap at the proximal end of the guide tube 4. Engagement of the distal face of the depth- controlling stop 40 on the fluid transfer tube 6 with the proximal face of an increased diameter portion of the guide tube 4 may form the fluid seal.

[0088] The fluid transfer tube may further comprise a seal element 141 to facilitate the fluid seal, such as an O-ring or washer that is retained on the distal face of the fluid transfer tube’s depth -controlling stop 40. The seal element 141 is compressed against the proximal end of the guide tube’s cap when it is located in the hub 50 and the fluid transfer tube’s engagement feature has been engaged in the hub 50. The seal element 141 forms a fluid seal between the fluid transfer tube’s stop 40 and the bore of the guide tube 4 by linear compression. This creates a fluid seal within the bore of the guide hub 50 preventing leakage of CSF or the ingress of air into the cranial cavity by radial expansion of the seal under compression.

[0089] As shown in Fig. 4, the fluid transfer tube 6 may have a plurality of reflux regions 54 in its outer surface, the reflux regions 54 extending from the distal end 10 of the fluid transfer tube 6 along a length of the fluid transfer tube 6. The reflux regions 54 are configured to allow flow of the infusate from the distal end 10 of the fluid transfer tube 6 towards the proximal end along the reflux regions 54 when the distal end 10 of the fluid transfer tube 6 is inserted into the tissue. The fluid transfer tube 6 may be configured for atraumatic insertion into the tissue.

[0090] The cannula 6 may comprise a proximal fluid connector 174 proximal to the cannula’s depthcontrolling stop 40. The fluid connector 174 may be any suitable connector, such as a female NR-fit or Luer connector. The fluid connector 174 may comprise intrinsic gas and / or bacteria filters. An infused gas bubble will create a brain lesion and may disrupt the distribution of infused liquid through the tissues, so it is desirable to remove such bubbles. The fluid connector may comprise a fluid seal. The fluid seal may be a hydrophilic filter membrane that prevents the passage of gas, for example an acrylic copolymer matrix with a 0.2pm pore size (e.g. S80700 - Pall Supor 200), such that liquid within the primed cannula cannot be displaced except by another liquid. The hydrophilic membrane may also act as a bacteria filter.

[0091] The gas filter may be a hydrophobic filter membrane, for example polyethersulfone (PES) with a 0.2pm pore size (e.g. VRC02S7X10 - Pall Versapor 200 RC). The hydrophobic, gas permeable membrane works in cooperation with the hydrophilic membrane to vent gas from the infusate . The two membranes cooperate to prevent the entrainment of gas into the brain during an infusion.

[0092] By this arrangement the cannula assembly, primed with inert fluid, can be inserted in an operating theatre without exposing theatre staff to potentially biohazardous therapy. In the awake patient an infusion line containing the therapy is connected to the proximal connector 174 and the patient infused whilst awake so that they can be monitored neurologically. This arrangement also facilitates the insertion of multiple cannula assemblies in an operating theatre and simultaneous infusions in awake patients.

[0093] Other examples of suitable fluid transfer tubes that could be used in combination with the other tools and devices disclosed herein are disclosed in PCT / GB2024 / 051228, which is incorporated by reference in its entirety. Guide tube

[0094] The guide tube 4 is configured for use with the fluid transfer tube 6 for providing fluid access to the brain of a mammal. The guide tube 4 is configured for insertion into the brain.

[0095] Fig. 5 show the guide tube 4 in more detail. The guide tube 4 comprises a through -bore 30 for the passage of the fluid transfer tube 6. The through-bore 30 may have a diameter of at most 0.7mm, optionally at most 0.6mm. An outer diameter of the guide tube 4 may be at most 1 ,8mm, optionally at most 1.6mm, optionally at most 1.4mm, optionally approximately 1.3mm. The guide tube 4 may have a length of between 25mm and 150mm, optionally between 50mm and 120mm. This refers to the length of the guide tube as supplied, i.e. prior to being cut to length for insertion to a specific target for a specific patient. The cut length may be significantly shorter. For example, in small children the shortest cut length could be approximately 15mm for some targets. In small animals the shortest cut length may be approximately 10mm.

[0096] The guide tube 4 comprises an inner layer 26 and a resiliently-deformable outer layer 24 having a higher compliance than the inner layer 26. One or both of the inner layer 26 and the outer layer 24 is impermeable to fluid such that fluid (in particular liquid) cannot pass into or out of the through-bore 30 of the guide tube 4 except from one of the ends of the guide tube 4. This impermeability helps to control more precisely the movement of fluid into and out of the guide tube 4 and fluid transfer tube 6 by preventing leakage of fluid through the walls of the guide tube 4.

[0097] The inner layer 26 preferably provides sufficient column stiffness to the guide tube 4 such that it can be inserted unsupported (other than an indwelling fluid transfer tube 6), to a down a pre -made track in brain tissue, for example to a depth of up to 120mm without migrating from the track by more than 3mm.

[0098] The inner layer 26 may be impermeable to fluid, in particular to liquids. This means that fluid cannot pass through the material of the inner layer 26 and the inner layer 26 provides a barrier to the movement of fluid along the entire length of the guide tube 4 over which the inner layer 26 extends. The inner layer 26 may be impermeable to fluid by virtue of one or both of a material of the inner layer 26 and a structure of the inner layer 26. For example, the inner layer 26 may be formed from a material that blocks the passage of fluid, e.g. because it is not porous. The structure of the inner layer 26 may also be such as to prevent fluid passage. The inner layer may form a continuous and / or integral layer, for example without any apertures or perforations that could permit passage of fluid through the inner layer 26 even if the material of the inner layer 26 is fluid impermeable.

[0099] The inner layer 26 may comprise polyether ether ketone, PEEK, or carbon-filled PEEK, for example between 5% and 30% carbon-filled PEEK, optionally 5% carbon-filled PEEK, optionally 10% carbon-filled PEEK. The inner layer 26 may define the through-bore, and thereby have an inner diameter of at most 0.7mm, optionally at most 0.6mm. An outer diameter of the inner layer 26 may be is at most 1.5mm, optionally at most 1mm, optionally approximately 0.8mm.

[0100] The outer layer 24 is resiliently deformable to minimise trauma to the brain upon insertion. The outer layer 24 may be formed by dip-coating onto the inner layer 26. The outer layer 24 may comprise an elastomer such as silicone, natural rubber, or polyurethane. Other possible materials for the outer layer 24 include expanded polytetrafluoroethylene (ePTFE), which may be bonded to the inner layer 26 by thermal welding and compression or adhesive, or another foamed polymer. The outer layer may also comprise electrospun polymer. This provides a compliant and resiliently deformable outer layer with a complex surface that may augment biointegration and reflux resistance for a chronic device.

[0101] Similarly as discussed above for the inner layer 26, the outer layer 24 may be impermeable to fluid. Any of the features discussed above for the inner layer 26 in connection with the impermeability to fluid of the material or structure of the inner layer 26 may equally apply to the outer layer 24.

[0102] The outer-layer 24 is preferably very soft. For example, the outer layer 24 may comprise a material having a hardness of at most 80 measured on the Shore 00 hardness scale, optionally at most 40, optionally at most 20, optionally at most 10. Preferably, the hardness of the outer layer may be approximately 0 measured on the Shore 00 hardness scale. The stiffness of the material of the outer layer 24 may be at most 5 MPa, optionally at most 2MPa, optionally at most IMPa, optionally at most 500kPA, optionally at most 200kPa, optionally at most lOOkPa.

[0103] The outer layer 24 may comprise a material having a high elastic limit and high elongation ratio. For example, the material of the outer layer 24 may be able to elongate elastically by at least 100%, optionally 200%, optionally 500%, optionally 800% without fracturing.

[0104] The outer diameter of the outer layer 24 may define the outer diameter of the guide tube 4. An outer surface of the guide tube 4 may be lubricious, for example provided by the outer layer 24 comprising a lubricious surface treatment or coating such as a hydrophobic or a hydrophilic coating. This reduces sheer stress upon insertion into the brain. The coating may provide the impermeability to fluid of the outer layer 24 where the outer layer 24 is impermeable to fluid. Surface treatments or coatings may include plasma treatment, the application of a PEGylated silicone to make the surface hydrophilic, the application of polydimethylsiloxane, or silane coupling agents. The lubricity of the outer surface may be at most 2N, measured in a IN pinch test, optionally at most IN, optionally at most 0.5N, optionally at most 0.3N.

[0105] The guide tube 4 may have a proximal end with a larger diameter than the distal end of the guide tube 4, which may be referred to as a depth-limiting cap 28. The distal face of the cap 28 provides a depth-limiting stop to limit an insertion depth of the guide tube 4 into the brain when it engages with a step in the bore 52 of the guide hub 50. The proximal face of the cap 28 provides a contact surface for the seal element 141 on the distal end of the cannula’s depth-controlling stop 40, wherein the contact also limits the depth of insertion of the cannula 6. The bore in the proximal end of the cap 28 may be conical for ease of insertion of the cannula 6 into the bore 30. The cap 28 may have a formation in its outer wall such as a circumferential groove to facilitate engagement of the guide tube 4 with a delivery tool, for example features on sprung leaves, as will be discussed further below.

[0106] The cap 28 may be made of the same material as the inner layer 26 of the guide tube 4, for example PEEK. The proximal portion or cap 28 may be bonded to the inner layer 26 using adhesive, or over moulded onto the inner layer 26. Alternatively, the proximal end or cap 28 may be formed integrally with the inner layer 26.

[0107] The compliant and lubricious outer layer 24 and the column stiffness of the inner layer 26 of the guide tube 4 assist in its passage along a track made through the dura and the pia, and along the track through the brain parenchyma which will have closed after removal of the track -forming probes. The outer layer 24 assists in centring the less -compliant inner layer 26 in the pre-made track, thereby preventing the guide tube 4 from cutting through the wall of the track and migrating off trajectory.

[0108] The outer layer 24 is adherent to the inner layer 26 so that as the guide tube 4 is pushed through a tissue track offering resistance, the outer layer 24 will tend to deform proximally so that the guide tube’s outermost edges will tend to become rounded and bullet shaped at the distal end of the guide tube 4. This assists in its insertion and reduces shear forces on the tissue.

[0109] Insertion of the guide tube 4 with minimal tissue trauma is preferable to enable its distal end 20 to create a fluid seal with the tissue. If the tissue is traumatised, then it becomes engorged with fluid (oedema) and this in turn creates a low resistance pathway for infusate delivered by the cannula 6 to reflux around the distal end 20 of the guide tube 4 and away from the target volume.

[0110] Relative flexibility of the cannula assembly is important so that it moves with the brain to minimise brain trauma that could occur with a rigid cannula. The brain cortex can move up to 3mm when moving from a supine to a prone position, the centre of the brain by up to 1mm. The distal end of the cannula 6 could also act as a piston causing local tissue trauma and impairing reflux control at the step between the guide tube 4 and the cannula 6 at the target volume. To mitigate this, the guide tube 4 is preferably stiff in axial compression, but at least in a proximal portion is compliant and elastic in axial extension and lateral bending. This will allow the proximal portion to accommodate relative movement between the skull and the brain and assist in maintaining the distal end 20 of the guide tube 4 at its brain target.

[0111] To this end, as shown in Fig. 6 and Fig. 7, a proximal portion 29 of the guide tube 4 may be configured to be axially and / or laterally deformable. The proximal portion 29 may have a length of between 5mm and 30mm, optionally between 10mm and 15mm. The proximal portion 29 may be configured such that a maximum elastic deformation of the proximal portion 29 under compression is less than a maximum elastic deformation of the proximal portion 29 under extension.

[0112] The deformability of the proximal portion 29 may be achieved by configuring the proximal portion 29 as a spring, for example by forming a spiral cut through the inner layer 26 in the proximal portion 29. The spiral cut may be formed by laser cutting. The laser cut may have a width of 0.025mm. The pitch of the spiral may be 0.2mm.

[0113] As discussed above, the outer layer 24 has very high compliance and is elastic. Preferred materials for the outer layer 24 such as the low-durometer silicone mentioned above can stretch by approximately 800-fold before fracturing. This allows for axial extension and lateral bending of the proximal portion 29 without damaging the outer layer 24. However, the material of the outer layer 24, such as a silicone is relatively incompressible and will be trapped in the cuts of the spiral. Therefore, during insertion with relatively low insertion forces there will be minimal shortening of the guide tube 4 because the outer layer 24 within the spiral cuts prevents axial compression of the proximal portion 29.

[0114] The cannula assembly may have a short, flexible external portion 42, which may be formed as part of the cannula 6 proximal to its depth-controlling stop 40. Flexibility of the external portion of the cannula assembly is important to minimise the risk of displacement of its intracranial portion by being knocked when the patient is moved.

[0115] To deliver therapeutic liquids to the brain parenchyma in humans, the cannula assembly including the guide tube with an indwelling fluid transfer tube may be configured to allow it to be inserted unsupported into a premade track in brain tissue over a distance of at least 50mm, optionally at least 100mm without migrating from the track.

[0116] Preferably, the flexible guide tube 4 is configured to be inserted (supported only by the indwelling cannula) up to 95mm and preferably up to 100mm through the brain parenchyma to a brain target with a 3D Euclidian distance error of no greater than 3mm, preferably no greater than 2mm. Preferably, the flexible cannula 6 is configured to be inserted (supported in its proximal portion by the guide tube 4) through the brain parenchyma up to 100mm, optionally up to 120mm. A 3D Euclidian distance error during the insertion is optionally no greater than 4mm, preferably no greater than 3mm, wherein the maximum length of a distal portion of the cannula 6 that extends beyond the distal end of the guide tube 4, and so is unsupported by the guide tube 4, is no greater than 60mm.

[0117] Preparation for Insertion of the Cannula Assembly

[0118] The procedure for preparing a patient for insertion of a guide hub 50 and cannula assembly such as those described above will now be described.

[0119] 1. Trajectory Planning

[0120] Surgical plans for the placement of one or more cannulas may be carried out in the days or weeks prior to the procedure from a patient’s MRI acquired as an outpatient. From the MRI of the patient’s head, the brain target volume or volumes are segmented and cannula trajectories planned with neurosurgical planning software. Assuming that the infusion profile of the cannula is spherocylindrical, the trajectory is generally positioned along the central axis of the target volume and adjusted to avoid critical brain structures, potential infusate leak paths and blood vessels. The virtual spherocylinder, representing the infusion cloud in the software, is adjusted in length and radius to best fit within the target volume.

[0121] The planned position of the distal end of the guide tube is positioned along the trajectory at the proximal end of the spherocylinder, i.e., closest to the skull entry point. The planned position of the distal end of the cannula is placed at the centre of the distal hemisphere of the spherocylinder, whose spherical boundary is at the distal boundary of the target volume. The distance between the distal end of the guide tube and the distal end of the cannula, known as the cannula step-length, is measured. The skull thickness along the trajectory is also measured. 2. Patient registration to the surgical plan and targeting device

[0122] On the day of surgery, the surgical plan is registered to an image guided targeting device that is fixed with respect to the patient’s head. The targeting device may be a stereotactic instrument, an MRI conditional aiming device, an image guided lockable arm or a surgical robot. Image registration to the targeting device and the patient may be achieved by fixing a head frame to the patient’s skull with pins and attaching fiducial markers to the frame.

[0123] The patient is imaged with MRI or x-ray tomography (CT) and the acquired images of the patient’s head are co-registered with those in the surgical plan. The 3D image coordinates of a brain target are co-registered with the targeting device coordinate system (stereotactic coordinates) with reference to the fiducial markers visible on the images. The fiducials may then be detached from the head frame and the targeting device fixed in a known relationship to the frame and set to the stereotactic target and trajectory coordinates.

[0124] The distance from the targeting device datum (the stereotactic datum) to the distal ends of the guide tube and cannula are established from the surgical plan. However, the distance from the skull surface to the distal ends of the guide tube and cannula, i.e. the lengths of the cannula assembly components to be inserted, cannot be accurately determined from MRI images. This is because bone provides poor MRI signal, has low contrast with surrounding tissue, and magnetic susceptibility artefacts in the vicinity of the skull due to its proximity to the air / tissue interface result in spatial inaccuracies in the image. These inaccuracies, with errors from partial volume effects, are in the order of one to two millimetres.

[0125] The distance from the skull surface to the distal ends of the guide tube and cannula is therefore established by accurately measuring the distance from the stereotactic datum to the skull surface along the planned trajectory. This is done during the first stage of the insertion procedure in which a hub is inserted into the skull that is co-axial with the trajectory.

[0126] 3. Tools for insertion of the huh.

[0127] A Skull Preparation Set is provided for preparing a profiled hole in the skull along a trajectory and inserting the hub. The guide hub 50 provides a datum surface for insertion instruments and provides the means by which the proximal ends of the guide tube 4 and cannula 6 are secured with respect to the skull. More details of an exemplary set of tools that may be included in the skull preparation set are given in GB2406765.4, which is incorporated by reference in its entirety. A specific example set is now described below, but it should be understood that variations in the design of the components of the skull preparation set described below, in particular from the specific dimensions given below, are possible.

[0128] An example of a skull preparation set is shown in Fig. 8. The Skull Preparation Set comprises: i / A Skull Verification Tool 3.

[0129] The Skull Verification Tool 3, also known as a datum tool, is a 7mm OD rod with a pointed distal end that has a handle on its proximal end. The junction between the handle and the rod forms a proximal stop. Just distal to the proximal stop is a threaded section which can be screwed into the proximal bore of a Tool Guide 1. ii / A Tool Guide 1 with a Target Depth Stop 9 and Instrument Guide Stop 5.

[0130] The Tool Guide 1 is a tube configured to receive a series of tools through its bore. A length of the tool guide 1 may be between 100mm and 200mm, optionally approximately 150mm. The Tool Guide 1 has an inner diameter of 7mm and an outer diameter of 18mm. Its proximal end may step up to a larger diameter, for example 22mm. The larger diameter proximal end may then act as a stop. The proximal end of the bore has a threaded inner diameter to receive and retain the Skull Verification Tool 3.

[0131] The Tool Guide 1 may be a stainless steel, titanium or aluminium tube with bushings secured in its proximal and distal bore, wherein the bushings are made of a plastic or a composite plastic material such as carbon filled PEEK. When the Skull Verification Tool 3 is secured in the Tool Guide 1, its distal end projects beyond the distal end of the Tool Guide 1 by about 20 mm. This is the “working distance”.

[0132] The Tool Guide 1 comprises a Target Depth Stop 9 which provides a Tool Guide reference datum that relates to the datum -to-target distance of the stereotactic instrument. The Target Depth Stop 9 may comprise a collar clamp that enables the datum-to-target distance to be adjusted to that of the stereotactic instrument in use. When a Tool Guide 1 is used exclusively with a target centred stereotactic instrument with a known datum to target distance (for example 190mm for the Leksell and Inomed stereotactic instruments, or 160mm for the CRW stereotactic instrument) then a step up in diameter at the proximal end of the Tool Guide, may act as the Target Depth Stop 9 and be positioned at 190mm or 160mm from the distal end of the Skull Verification Tool 3 when it is located in the Tool Guide 1.

[0133] The Tool Guide 1 further comprises an Instrument Guide Stop 5 which is a collar clamp that is fixed around the Tool Guide 1 and whose distal face engages with the datum surface of the stereotactic instrument guide. The Tool Guide 1 with attached Skull Verification Tool 3 and Instrument Guide Stop 5 is passed through the bore of the stereotactic instrument guide so that the distal end of the Skull Verification Tool 3 engages with the skull surface. The Instrument Guide Stop 5 is released and brought into contact with the datum surface on the stereotactic instrument’s guide and then clamped to the Tool Guide 1.

[0134] The Instrument Guide Stop’s datum surface clamped to the Tool Guide 1 acts to provide a fixed measure of the distance from the stereotactic datum to the skull surface and the Target depth Stop 9 datum to the Instrument Guide Stop 5 datum now provides a measure of the distance between the skull surface and the target. The proximal end of the Tool Guide 1 is placed a known distance “d” away from the skull surface, regardless of the position of the stereotactic datum surface.

[0135] When the bore of the stereotactic instrument is greater than 18mm, the Instrument Guide Stop 5 may be provided with a distal hollow cylindrical portion whose outside diameter fits closely within its bore, where it can be detachably retained. When the Instrument Guide of this embodiment is attached to the stereotactic instrument the Tool guide is passed through its bore and clamped as previously described. iii / Bone drills

[0136] Three bone drills are used to form a profiled hole in the skull. Each has a 7mm diameter shaft with a proximal stop. The length between the proximal stop and the distal end of the drill is greater than the predetermined reference length “d” by the length by which it will penetrate the bone surface to form the profiled hole. Preferably the drills have proximal features for attachment to surgical power tools. Each drill may have a replaceable distal tip that performs its bone cutting operation. The drills comprise:

[0137] A Facing Drill 19 used to create a flat area on the generally curved surface of the skull that is orthogonal to the facing drill’s trajectory. Preferably the Facing Drill 19 has stepped bone cutting features that create concentric flat areas on the bone surface that are orthogonal to the drill’s trajectory, wherein the inner flat area has a diameter of about 3mm and is 0.5mm-lmm deep to the outer flat that has a diameter of about 6mm. This helps to ensure that subsequent cutting tools delivered along the same trajectory will engage the bone surface orthogonal to the trajectory, thereby minimising the likelihood of other bone cutting tools skiving off axis, which could result in targeting inaccuracy

[0138] A Pilot Drill 21 used to drill an initial, narrow -diameter hole to guide the core drill. The tool length of the pilot drill 21 distal to its proximal stop may be independently adjusted to be greater than the predetermined reference length d by the distance from the skull surface to the inner table of the skull, or the dura along the planned trajectory. This distance can be determined from radiological images used in the planning process.

[0139] A Core Drill 23 is used to create the profiled hole that will accommodate the hub. Preferably the core drill 23 has a coaxial pin at its distal end that is guided by the pilot hole to maintain its concentricity during bone cutting. The profiled hole may step-down in diameter, to form a proximal datum surface in the bone to control the depth of insertion of devices with a rim. The core drill 23 may have a step in its diameter to create the step-down in diameter of the profiled hole. vi / A Hub Insertion Tool 27.

[0140] The Hub Insertion Tool 27 comprises a 7mm diameter cylindrical shaft with a larger diameter proximal handle and distal engagement features for retaining and driving the hub such as a hexagonal socket with a tapered or interference fit with the hub.

[0141] The proximal handle has a T-bar grip and its junction with the shaft forms a stop surface. The Hub Insertion Tool 27 with the hub 50 attached to its distal end is inserted through the Tool Guide 1 so that threads on the hub’s external surface engage in the profiled hole in the skull. It is then rotated clockwise and the hub’s cutting threads, cutting into the wall of the profiled hole, advance it until the hub’s rim engages with the datum surface created in the skull with the Core Drill 23.

[0142] To prevent over rotation of the Hub Insertion Tool 27, which could result in the threads cutting out of the bone, radial teeth on the stop surface of the Hub Insertion Tool 27 engage with opposing teeth on the proximal end of the Tool Guide 1 stopping rotation when it is fully inserted i.e., when the hub’s rim engages with the skull datum.

[0143] The Skull Preparation Set is provided with the tools located in a Tool Holder 41. This is a rectangular frame which has parallel grooves in the anterior face of its upper and lower cross beams that align the tools required to form the profded hole and insert the hub. The tools are aligned in the Tool Holder 41 in order of use. The Skull Verification Tool 3 may be held in the cranial preparation Tool Holder 41 within the Tool Guide 1. The Tool Guide 1 may have the Target Depth Stop 9 and the Instrument Guide Stop 5 clamped to it. The tools have proximal stops or other features that engage with the top surface of the Tool Holder’s upper cross beam. Grooves on the lower cross beam accommodate the distal ends of the tools and are of different lengths. The length of each tool beyond the length of the Skull Verification Tool 3defmes the length that it will penetrate the skull surface. 4. Workflow for inserting the huh

[0144] The surgeon positions and secures the Instrument Guide Stop 5 in the instrument guide of the surgical targeting device (stereotactic instrument or surgical robot) that has been fixed with respect to the patient’s head frame and aligned with the target trajectory. The Skull Verification Tool 3 and Tool Guide 1 are removed from the Tool Holder 41 with the Target Depth Stop 9 clamped to the Tool Guide 1. The Target Depth Stop 9 is positioned on the Tool Guide 1 at a distance from the distal tip of the Skull Verification Tool 3 that is equal to the stereotactic datum-to-target distance of the stereotactic instrument or robot in use.

[0145] The Skull Verification Tool 3 and Tool Guide 1 are inserted through the Instrument Guide Stop 5 until the distal end touches the scalp to identify the entry point. The scalp is opened with a 2-3cm incision, the wound edges retracted, and the periosteum cleared from the skull entry point. The Skull Verification Tool 3 and attached Tool Guide 1 are advanced through the Instrument Guide Stop 5 until the Skull Verification Tool’s tip engages with the skull surface.

[0146] The Instrument Guide Stop 5 is clamped to the Tool Guide 1 and the Skull Verification Tool 3 unscrewed from the Tool Guide 1 and set aside in the Tool Holder 41. The proximal end of the Tool Guide 1 is now a fixed distance “d” from the skull surface. The distal end of the Tool Guide 1 is positioned approximately 20 mm above the skull surface providing a working distance for the surgeon to visualise the preparation of the profiled hole in the skull with the bone drills, remove fluid and bone debris and visualise the hub insertion.

[0147] A profiled hole is made in the skull that is coaxial with the trajectory to the target using the bone drills. These are passed sequentially through the Tool Guide 1.

[0148] The Facing Drill 19 forms a flat or concentric flats on the curved skull surface. The length of the pilot drill 21 is adjusted using a measurement obtained from the surgical plan so that it then forms a 1 ,8mm diameter hole through the skull and dura along the trajectory. The Core Drill 23 then forms the profiled hole in the skull that will accept the Hub 50. The Core Drill 23 has a distal nib that passes down the pilot hole during the cutting process and maintains its coaxial alignment with the trajectory. The Hub Insertion Tool 27 with the attached hub 50 is inserted through the Tool Guide 1 and screwed into the profiled hole.

[0149] The Tool Guide 1 with attached Target Depth Stop 9 and Instrument Guide Stop 5 is now detached from the targeting device’s instrument guide. The distance between the distal end of the Target Depth Stop 9 and the distal end of the Instrument Guide Stop 5 equals the distance between the skull surface datum and the surgical target.

[0150] The Tool Guide 1 can thus be used as a measuring device to transfer this measurement to a Device Preparation Jig 43, such as that shown in Fig. 9, to set the length of track forming probes and insertable devices without the need to read scales and transfer numbers, thereby reducing the likelihood of human error.

[0151] 5. Tools for preparing and delivering the guide tube and cannula

[0152] To implant the guide tube 4 and cannula 6, they are first primed with liquid, cut to length and then inserted simultaneously through the guide hub 50 and down a pre-made track in the brain tissue with the cannula 6 inside the guide tube 4. When the guide tube 4 has reached its target, the cannula 6 is further advanced to its more distal target and the cannula stop 40 is secured into the hub 50 to secure the cannula assembly in the skull.

[0153] To facilitate the formation of a track in the tissue for both the guide tube 4 and cannula 6, cut them to the required length, and deliver them to target a Device Preparation Set is provided, such as that shown in Fig. 9. The device preparation set comprises a Device Preparation Jig 43, a Device Guide 51, a Track Forming Tool 181 and a Device Delivery Tool 185. i / The Device Preparation Jig 43.

[0154] The Device Preparation Jig 43 is a rectangular frame for setting the depth of insertion of instruments required for inserting devices and setting the length of devices that will be inserted into a patient during surgery. This embodiment may be used with the Tool Guide 1 comprising a Target Depth Stop 9 and an Instrument Guide Stop 5.

[0155] The Device Preparation Jig 43 comprises instrument and device retention and aligning features in a top crossbeam 47 and a moveable horizontal platform 45. The top crossbeam 47 is a fixed horizontal platform with a datum surface representing the skull surface datum (the Skull Surface Datum Platform). The moveable horizontal platform 45 can be moved in parallel with the skull surface datum representing the target datum (the Target Datum Platform) and can be clamped in position.

[0156] The distance between the skull surface datum and the target datum may be set by locating the Target Depth Stop 9 on the Tool Guide 1 in a recess in the Skull Surface Datum Platform and moving the Target Datum Platform to meet the datum surface on the Instrument Guide Stop 5.

[0157] The Skull Surface Datum Platform has receiving features for the distal end of the Track Forming Tool 181 and the Device Delivery Tool 185. The receiving features may be offset from the skull surface datum. For example, when inserted, the proximal end of the hub 50 may be 3mm above the skull surface, wherein the distal face of the Track Forming Tool 181 which contacts the hub surface will engage with the skull surface datum 3mm above its reference datum. Similarly, the distal end of the Device Delivery Tool 185 will contact the proximal end of the hub 50 and its engagement with the Skull Surface Datum Platform will be 3mm above the skull surface datum.

[0158] The Target Datum Platform has receiving features for the distal end of the Guide Tube Track Forming Probe. The distal end of the Guide Tube Track Forming Probe is positioned at the target datum on the Target Datum Platform. The distal end of the Cannula Track Forming Probe may be positioned up to 5mm distal to the distal end of the Guide Tube Track Forming Probe.

[0159] The Target Datum Platform has a cutting jig 302 aligned orthogonal to the Device Delivery Tool, which is shown in more detail in Fig. 10. The cutting jig 302 comprises a vertical receiving slot in the Target Datum Platform for the guide tube 4 and cannula 6 in its packaging sleeve. Either side of the slot are guide channels for a cutting tool 304. The cutting jig 302 cuts the guide tube 4 and indwelling cannula 6, as well as a protective packaging sleeve, to adjust the insertion lengths of the guide tube 4 and the cannula 6, as shown in Fig. 11.

[0160] The cutting tool 304 is shown in more detail in Fig. 12, and comprises a mounted blade and parallel rods positioned on each side that are inserted into the guide channels. As the cutting tool 304 is advanced the blade will pass orthogonally through the guide tube 4 and cannula 6 in its packaging located in the vertical slot. This ensures that the end of the guide tube 4 and cannula 6 are cut cleanly and truly orthogonal to their longitudinal axis at the level of the target datum. ii / The Device Guide 51.

[0161] The Device Guide 51 is a tube with a through-bore that is configured to receive the Track Forming Tool 181 and the Device Delivery Tool 185 in the through bore. In use it is fixed in the bore of the Instrument Guide Stop 5 that is secured in instrument guide of the surgical targeting device, aligned with the target trajectory. The proximal end of the Device Guide 51 is positioned at a fixed distance above the skull datum “h”. The distal end of the Device Guide 51 is positioned above the skull surface datum by at least 10mm, at most 50mm, and optionally about 30mm to provide a working distance for the operator to visualise the insertion site and manipulate tools or devices.

[0162] The through -bore of the Device Guide 51 may have a diameter of at least 10mm, optionally approximately 14mm. The outer diameter of the Device Guide 51 may be at most 20mm, optionally approximately 18mm.

[0163] A distal region of the Device Guide 51 may comprise an aperture providing access to the through-bore of the device guide 51. For example, the distal end of the Device Guide 51 may have opposing sections of its wall removed to facilitate access to the through -bore. This can be useful if access is required to a device delivered using the Device Guide 51 at the skull surface during the implantation / insertion procedure.

[0164] The distal end of the Device Guide 51 may comprise circumferential features for engagement with removable adapters that adapt the distal end of the Device Guide 51 for delivery of specific devices or surgical tools. An example of such a removable adapter is a Conical Guide configured to removably engage with a distal end of the Device Guide 51. The Conical Guide reduces the diameter of a distal end of the through-bore of the Device Guide 51. This may be useful during insertion of narrow devices such as a guide tube 4 and cannula 6 to prevent the narrow device wandering away from the centre of the hub 50 into which it is to be inserted. The Conical Guide may reduce the diameter of the distal end of the through-bore of the Device Guide 51 to at most 2mm, optionally to at most 1.4 mm. The Conical Guide is split across its diameter along its axis. The two halves are held together with a sprung hinge that can be rotated to separate the halves with a finger operated actuator.

[0165] The proximal end of the Device Guide 51 has a clamp to fix the position of the track forming Tool 181 or the Device Delivery tool 185 in its bore. The through-bore of the Device Guide 15 has a channel in its wall that is aligned along the long axis of the Device Guide 51. The Track Forming Tool 181 and the Device Delivery Tool 185 configured for use with the Device Guide 51 , each comprise a rail projecting from one side of its outer diameter that fits in and is guided by the channel in the Device Guide 51. Thereby, the cooperation of the channel and rail, acts to align these cylindrical tools that are passed through the through -bore of the Device Guide 51. The use of a rail is not essential, and other suitable features may be used on the tool. For example, one or more alignment pins may be provided on the outer diameter that fit into the channel. iii / The Track Forming Tool

[0166] Insertion of the flexible guide tube 4 and cannula 6 over their requisite lengths through the brain parenchyma is achievable by forming a profiled track in the parenchyma that approximates their planned insertion profile using an adjustable Track Forming Tool 181 for forming a track in brain tissue for insertion of a fluid transfer tube 6 within the through-bore of a guide tube 4. Fig. 13 shows the track forming tool 181 with its probes retracted. Fig. 14 shows the track forming tool 181 with its probes advanced.

[0167] The Track Forming Tool 181 is used to make a track through the brain tissue to assist in the subsequent delivery of the guide tube 4 and the cannula 6. The depth of insertion of the guide tube 4 and cannula 6 are variable. The cannula 6 is inserted deeper than the guide tube 4 by a length established in the surgical planning (the step-length). Therefore, the Track Forming Tool 181 facilitates the depth adjustment of a Guide Tube Track Forming Probe and an indwelling Cannula Track Forming Probe that can be independently extended distally by a set step-length to form tracks for both the guide tube 4 and the portion of the cannula 6 that extends beyond the distal end of the guide tube 4.

[0168] An exploded view of the track forming tool 181 is shown in Fig. 15. The Track Forming Tool 181 comprises an inner probe 190 and an outer probe 192 having a through-bore configured to receive the inner probe 190. A distance by which the tip of the inner probe 190 extends beyond a distal end of the outer probe 192 is adjustable. One or both of a distal end of the outer probe 192 and the distal end of the inner probe 192 may comprise a lubricious coating to reduce trauma when inserting the probes into brain tissue.

[0169] The outer probe 192 is configured for insertion into the brain tissue to form a larger-diameter portion of the track to receive the guide tube 4. The inner probe 190 is configured for insertion into the brain tissue to form a smaller-diameter portion of the track extending beyond the end of the larger- diameter portion of the track to receive a portion of the fluid transfer tube 6 extending beyond a distal end of the guide tube 4.

[0170] The track -forming tool 181 may comprise a cannula track forming instrument 198, where a distal section of the cannula track forming instrument 198 comprises the inner probe 190. The trackforming tool 181 may further comprise a guide tube track forming instrument 196, where a distal section of the guide tube track forming instrument 196 comprises the outer probe 192. The guide tube track forming instrument 196 comprises a through -bore configured to receive the cannula track forming instrument 198. The Cannula Track Forming Instrument 198 can be moved along the axis of the Guide Tube Track Forming Instrument 196 and their relative position fixed.

[0171] The Track Forming Tool 181 may further comprise an outer body 194. The outer body 194 may be a 14mm diameter tube and may have a tapered distal end 195. The outer body 194 has a through-bore configured to receive the guide tube track forming instrument 196 with the outer probe 192 and is configured to be received in a guide for holding surgical tools in stereotactic surgery. The Guide Tube Track Forming Instrument 196 can be moved along the axis of the outer body 194 and their relative position fixed. The through-bore may have a 12mm diameter, except for at the tapered distal end 195, which reduces to about 1.4mm in diameter. The proximal end of the outer body 194 of the Track Forming Tool 181 may have a clamp for clamping the Guide Tube Track Forming Instrument 196 within its bore. The outer body 194 may further have alignment features projecting from one side of its circumference that engage with the guide for holding surgical tools in stereotactic surgery.

[0172] The Guide Tube Track Forming Instrument 196 may comprise a proximal section comprising a tube, for example a stainless-steel tube, with a 10mm outer diameter and a 6mm internal diameter with a thread at its most distal end. The proximal end of the Guide Tube Track Forming Instrument 196 may have a finger operable clamp to clamp on to the indwelling Cannula Track Forming Instrument 198. The proximal section of the guide tube track forming instrument 196 may have a larger diameter than the outer probe 192. The proximal section and the distal section of the Guide Tube Track Forming Instrument 196 may be separable.

[0173] The outer probe 192, also referred to as the Guide Tube Track Forming Probe, may be a tube with a 1.4mm outer diameter. The Guide Tube Track Forming Probe may comprise stainless steel. The outer probe 192 preferably has an outside diameter that is approximately 0.2mm or 0.1mm larger than the outside diameter of the Guide Tube 4. The proximal end of the outer probe 192 may comprise an attachment feature, such as a male thread, to attach it coaxially to the distal end of the proximal section of the Guide Tube Track Forming Instrument 196. The outer probe 192 may have a lubricious coating such as DLC or PTFE. The coating increases the lubricity of the surface, reducing sheer forces on the tissue thereby reducing tissue trauma and improving the accuracy of delivery.

[0174] As shown in Fig. 16, the distal end of the outer probe 192 may be tapered. The tapering further reduces tissue trauma as the outer probe 192 is advanced through brain tissue. For example, the distal end of the outer probe 192 may taper from between 1mm and 2mm to between 0.5mm and 1mm, optionally from 1 ,4mm to 0.8mm. The distal end of the outer probe 192 may taper over a distance of at most 30mm, optionally 20mm, optionally 15mm, optionally 10mm. Preferably, the distal end of the outer probe 192 tapers to 0.8mm diameter over its distal 15mm. The length of the outer probe 192 may be approximately 145mm, with a through-bore of 0.55mm.

[0175] The Cannula Track Forming Instrument 198 may comprise a proximal section comprising an approximately 6mm diameter rod, for example. The proximal section of the cannula track forming instrument 198 may have a larger diameter than the inner probe 190. The proximal section and the distal section may be integrally formed.

[0176] The inner probe 190, also referred to as the Cannula Track Forming Probe, may be approximately 200mm long with a diameter of 0.5mm. The Cannula Track Forming Probe may be a stainless-steel rod with a DLC, PTFE, or similar coating. The coating increases the lubricity of the surface, reducing sheer forces on the tissue thereby reducing tissue trauma and improving the accuracy of delivery. The coating also reduces the tendency for blood clots to adhere to the surface. Such adherence, in an uncoated surface, could result in the Cannula Track Forming Probe becoming jammed in the bore of the Guide Tube Track Forming Probe due to the tight interface between the two probes.

[0177] As shown in Fig. 16, the distal end of the inner probe 190 may be tapered. The distal end of the inner probe 190 may taper from between 0.4mm and 0.6mm to between 0. 1mm and 0.3mm, optionally from 0.5mm to 0.2mm. The distal end of the inner probe 190 may taper over a distance of at most 10mm, optionally 5mm, optionally 2mm. Preferably, the inner probe 190 tapers to form a distal diameter of approximately 0.2mm over its distal 2mm. A distal end of the inner probe 190 comprises a tip configured for dissecting tissue, for example having a rounded tip.

[0178] One of the cannula track forming instrument 196 and the guide tube track forming instrument 198 may comprise a measurement scale, and the other of the cannula track forming instrument 196 and the guide tube track forming instrument 198 may comprise an indicator feature. For example, the proximal section of the Cannula Track Forming Instrument 198 may have the measurement scale. The measurement scale is used to set the length by which the Cannula Track Forming Probe extends beyond the distal end of the Guide Tube Track Forming Probe. The indicator feature and the measurement scale are configured to interact to indicate the distance by which the tip of the inner probe 190 extends beyond the distal end of the outer probe 192. This distance is the step-length and may be set with a collar clamp applied to the shaft of the Cannula Track Forming Instrument 198.

[0179] The track formed by the Track Forming Tool 181 enables the flexible Guide Tube 4 with its indwelling Cannula 6 to pass relatively freely down the track with minimal resistance. The smaller- diameter distal section of the track formed by the portion of the inner probe 190 that extends beyond the distal end of the outer probe 192 means that the distal end of the Guide Tube 4 compresses the surrounding tissue and forms a fluid seal, iv / The Device Delivery Tool 185. The guide tube 4 and fluid transfer tube 6 are inserted with a Device Delivery Tool 185 such as that shown in Fig. 17 and Fig. 18. The device delivery tool 185 is for inserting a guide tube and a fluid transfer tube into the brain of a mammal. The device delivery tool 185 comprises features that hold the proximal ends of the guide tube 4 and fluid transfer tube 6, allowing the cannula 6 to be moved independently of the guide tube 4 and detach the guide tube 4 from the holding features.

[0180] The device delivery tool 185 comprises a guide tube delivery instrument 204 having a distal end configured to detachably engage with a proximal end of the guide tube 4 to hold the guide tube 4 coaxially with the guide tube delivery instrument 204. The Device Delivery Tool 185 further comprises a cannula delivery instrument 202 having a distal end configured to detachably engage with a proximal end of the fluid transfer tube 6. The cannula delivery instrument 202 holds the proximal end of the cannula 6 within its body and locates the distal end of the cannula 6 in the guide tube 4. The fluid transfer tube 6 and the guide tube 4 may have increased diameter portions at their proximal ends which provide insertion depth stops and engage with holding features of the device delivery tool 185.

[0181] The guide tube delivery instrument 204 comprises a through -bore configured to receive the cannula delivery instrument 202. A position of the cannula delivery instrument 202 within the through-bore of the guide tube delivery instrument 204 is adjustable. This means that a fluid transfer tube 6 engaged with the distal end of the cannula delivery instrument 202 can be advanced into the brain through a guide tube 4 engaged with the distal end of the guide tube delivery instrument 202.

[0182] The Device Delivery Tool 185 may be provided in the form of two or more concentric tubes, where the Guide Tube Delivery Instrument 204 forms the outer tube and the Cannula Delivery Instrument 202 is an inner tube within the Guide Tube Delivery Instrument 204.

[0183] One of the guide tube delivery instrument 204 and the cannula delivery instrument 202 may comprises a measurement scale, and the other of the guide tube delivery instrument 204 and the cannula delivery instrument 202 may comprise a corresponding indicator feature. For example, as shown in Fig. 18, the guide tube delivery instrument 204 may comprise a measurement slot 210 through its wall on one side that is aligned along its long axis and extends from its proximal end but does not extend fully to its distal end. The measurement scale may be provided along a distal portion of the measurement slot 210. The cannula delivery instrument 202 comprises a corresponding indicator feature that fits into the measurement slot 210 to indicate the position of the cannula delivery instrument 202. The indicator feature and the measurement scale are configured to interact to indicate a distance by which the cannula delivery instrument 202 should be advanced distally relative to the guide tube delivery instrument 204 such that a fluid transfer tube 6 engaged with the distal end of the cannula delivery instrument 202 is fully advanced into a guide tube 4 engaged with the distal end of the guide tube delivery instrument 204. Thereby, the measurement scale and indicator feature can be used to set the step-length of the cannula 6.

[0184] Fig. 19 shows an exploded view of the Device Delivery Tool 185. The Guide Tube Delivery Instrument 204 may comprise a tube having an outer diameter chosen to engage with the device guide 51 and an inner diameter chosen to receive the cannula delivery instrument 202. For example, the guide tube delivery instrument 204 may have a 14mm outer diameter and a 10mm inner diameter defining the through bore. The guide tube delivery instrument 204 may be approximately 200mm long. The through bore of the guide tube delivery instrument 204 may reduce at its distal end to become contiguous with the bore of the guide tube 4.

[0185] A distal region of the guide tube delivery instrument 204 may comprise an axially-extending aperture 212 providing access to the through-bore of the guide tube delivery instrument 204. The aperture 212 may be provided on the opposing wall of the guide tube delivery instrument 204 to the measurement slot 210, if present. The aperture 212 does not reach the most distal portion of the guide tube delivery instrument 204. However, the distal region of the guide tube delivery instrument 204 may comprise an axially -extending access slot 214 providing access to the through -bore of the guide tube delivery instrument 204. The access slot 214 extends to the distal end of the guide tube delivery instrument 204, and may be contiguous with the aperture 212. The aperture 212 and access 214 permit access to the cannula’s proximal connector 174 so that the cannula 6 can be ejected from the Device Delivery Tool 185 following delivery of the cannula 6 into the guide hub 50.

[0186] The Guide Tube Delivery Instrument 204 may comprise a locking feature 216 configured to reversibly fix a position of the cannula delivery instrument 202 within the through-bore of the guide tube delivery instrument 204. For example, the locking feature 216 may comprise a locking collar that can clamp the Cannula Delivery Instrument 202 as shown in Fig. 19, optionally having a larger diameter such as approximately 18mm outside diameter and 10mm bore. The locking feature 216 may comprise a finger-operable actuator at the proximal end of the Guide Tube Delivery Instrument 204 for ease of operation during surgical procedures. In the example of Fig. 19, there is a channel in the internal wall of the locking collarthat is contiguous with the measurement slot 210 along the long axis of the Guide Tube Delivery Instrument 204.

[0187] As shown in more detail in Fig. 20, to engage the distal end of the guide tube delivery instrument 204 with the guide tube 4, the distal end of the Guide Tube Delivery Instrument 204 may comprise a cone having at least two, optionally exactly two, optionally three or four, sprung leaves, the distal ends of which grip the guide tube cap 28. The distal ends of the leaves form sections of the wall of a hollow cylinder which engage with the cylindrical guide tube cap 28. The gap between two of the leaves is contiguous with the access slot 214 distal to the aperture 212. This facilitates removal of the cannula 6 from the device. Circumferential teeth on the inner diameter of each of these cylindrical sections may engage in a circumferential groove in the outer wall of the guide tube cap 28 to hold its coaxial alignment and prevent displacement when axially loaded with a distal to proximal vector.

[0188] The distal end of the guide tube delivery instrument 204 is configured to engage with the guide hub 50, which is configured to receive the guide tube 4 along the trajectory to the target volume. Engagement of the distal end of the guide tube delivery instrument 204 with the guide hub 50 releases the guide tube 4 engaged with the distal end of the guide tube delivery instrument 204. In the example of Fig. 20, loading the guide tube cap 28 with a proximal to distal vector will displace the sprung leaves radially and release the guide tube cap 28 from the distal end of the guide tube delivery instrument 204.

[0189] Alternatively, the distal end of the Guide Tube Delivery Instrument 204 may form a cylindrical feature where the bore makes a tight fit with the guide tube cap 28 to retain the guide tube 4 and provide coaxial alignment. The bore has an access slot 214 which is contiguous to the aperture 212 in the wall of the Guide Tube Delivery Instrument 204 and facilitates removal of the cannula 6 from the device.

[0190] The distal end of the guide tube delivery instrument 204 may comprise one or more retention features 218 configured to prevent proximal movement of the guide tube 4 engaged with the distal end of the guide tube delivery instrument 204. The retention features 218 may be provided by one or more sprung leaves that form a surface immediately proximal to the guide tube cap 28. The leaves may also provide a surface that engages in a groove in the outer surface of the guide tube cap 28. These prevent axial displacement of the guide tube 4 in a proximal direction within the cylindrical feature. The one or more retention features 218 may be configured such that advancement of the distal end of the cannula delivery instrument 202 through the through-bore of the guide tube delivery instrument 204 releases the retention features. The leave(s) are displaced by the proximal end of the Cannula Delivery Instrument 202 to allow the cannula stop 40 to pass through the distal end of the Guide Tube Delivery Instrument 204.

[0191] The Cannula Delivery Instrument 202 may comprise a tubular shaft comprising a through -bore configured to receive at least a portion of the fluid transfer tube 6. The Cannula Delivery Instrument 202 has an outer diameter chosen to engage with the Guide Tube Delivery Instrument 204 and an inner diameter chosen to receive the cannula 6 and its proximal connector 174. For example, the cannula delivery instrument 202 may have a 10mm outer diameter and an 8mm inner diameter. The Cannula Delivery Instrument 202 may comprise a housing for the cannula’s proximal connector 174 at its distal end. The housing may be a cylindrical unit with a conical distal end that is fixed to the distal end of the shaft of the cannula delivery instrument 202 with a bonded or interference fit. The cylindrical part of the housing may have an outside diameter of 10mm.

[0192] A distal region of the cannula delivery instrument 202 may comprise an axially -extending access aperture 220 providing access to the through-bore of the cannula delivery instrument 202 for the insertion or removal of the cannula’s proximal connector 174. The access aperture 220 may be provided on one side of the cylindrical part of the housing. A smaller window on the opposite side of the cannula delivery instrument 202 and facing the access aperture 220 may be provided to assist in ejecting the proximal connector 174 from the housing.

[0193] Further detail of the cannula delivery instrument 202 and its interaction with the guide tube delivery instrument 204 are visible in Fig. 21. The housing’s conical distal portion may have a narrow cylindrical end with a flat base which engages with the proximal face of the cannula’s stop 40. The conical portion with its narrow cylindrical end has a narrow bore, with a side-slot that is in continuity with the access aperture 220 and houses the cannula’s external portion between the stop 40 and the proximal connector 174. The cannula stop 40 is held in place by keeping the short external portion of the cannula 6 taught when inserting the proximal connector 174 into the distal end of the cannula delivery instrument 202 in the factory. A series of features, for example co-axial rings or teeth, in the bore of the housing interlock with corresponding features on the outer diameter of the cannula’s proximal connector 174 and the external portion of the cannula 6 allowing for micro-positional adjustments to set the tension and hold the position of the proximal connector 174 in the cannula delivery instrument 202.

[0194] The guide tube delivery instrument 204 and the cannula delivery instrument 202 may comprise corresponding alignment features configured such that the guide tube delivery instrument 204 and the cannula delivery instrument 202 adopt a predetermined relative rotational alignment when the cannula delivery instrument 202 is received in the through-bore of the guide tube delivery instrument 204. For example, at the proximal end of the cannula delivery instrument 202 on the opposite side to the access aperture 220, an alignment pin or rail may project radially from the outside diameter of the cannula delivery instrument 202. When the Cannula Delivery Instrument 202 is inserted into the Guide Tube Delivery Instrument 204, the alignment pin or rail is aligned with and enters a corresponding channel in the wall of the locking collar’s bore and then into the measurement slot 210 along the long axis of the Guide Tube Delivery Instrument 204. The alignment pin or rail may provide the indicator feature, moving against the measurement scale along the measurement slot 210 in the Guide Tube Delivery Instrument 204 to register the relationship between the distal face of the cannula stop 40 and the proximal face of the guide tube cap 28 when these components are located in their respective instruments.

[0195] The device delivery tool 185 may further comprise a third, innermost priming tube 206. The Priming Tube 206 is configured to connect fluidically to the proximal end of the fluid transfer tube 6 to fill the fluid transfer tube 6. The Priming Tube 206 may be a tube with an outside diameter of less than 8mm with a bore of less than 2mm diameter. The priming tube 206 comprises a connector compatible with the proximal connector 174 of the cannula 6 at its distal end, for example a NR-fit Luer, and a connector at its proximal end for connection to an infusion pump, for example a Luer connector.

[0196] The priming tube is inserted into the bore of the Cannula Delivery Instrument 202 from the proximal end of the cannula delivery instrument 202 until the connector on the distal end of the priming tube 206 engages with the cannula’s proximal connector 174. When inserted, the connector at the proximal end of the Priming Tube 206 projects from the proximal end of the cannula delivery instrument 202 for connection to a priming syringe.

[0197] The device delivery tool 185 may further comprise a guide tube sheath 208 configured to engage with the distal end of the guide tube delivery instrument 204 and enclose a guide tube 4 engaged with the distal end of the guide tube delivery instrument 204. The guide tube sheath 208 may also be referred to as the Guide Tube Packaging Sleeve. The guide tube sheath 208 forms a packaging sleeve. When assembled, the guide tube sheath 208 is positioned over the guide tube 4 to protect it prior to insertion into the brain.

[0198] The guide tube sheath 208 may be a plastic tube with a sealed distal end, having a sleeve portion with a bore that is a close fit to the outside diameter of the Guide Tube, which it accommodates. The proximal end of the Guide Tube Packaging Sleeve has a larger bore than the distal end and may have a close or interference fit over the distal end of the Guide Tube Delivery Instrument 204 that accommodates the guide tube cap 28. The guide tube sheath 208 may have features on its proximal end that mechanically lock into corresponding receiving features on the distal end of the Guide Tube Delivery Instrument 204, such as snap fit features or a screw fit over threads on the distal end of the Guide Tube Delivery Instrument 204.

[0199] The guide tube sheath 208 may be configured to prevent the release of the one or more retention features 218 when the guide tube sheath 208 is engaged with the distal end of the guide tube delivery instrument 204. For example, the proximal end of the guide tube sheath 208, when positioned over the distal end of the Guide Tube Delivery Instrument 204, may prevent actuation of the sprung leave(s) that facilitate the release of the guide tube cap 28. This prevents an operator from prematurely displacing the guide tube 4 from the Guide Tube Delivery Instrument 204 when handling the Device Delivery tool 185 until the Guide Tube Packaging Sleeve is removed and the Cannula Delivery instrument 202 is advanced.

[0200] The step created by the acute transition in the outer diameter of the Guide Tube Packaging Sleeve 208 from its sleeve portion to the proximal portion that fits onto the distal end of the Guide Tube Delivery Instrument 204, provides a datum surface. The datum surface is used to position the distal end of the Device Delivery Tool 185 on the Skull Surface Datum Platform in the Device Preparation Jig. This in turn positions the distal Guide Tube 4 precisely in the cutting jig’s vertical slot in the Target Datum Platform.

[0201] The Device Delivery Tool 185 may be provided in a sterile pack with the guide tube 4 and cannula 6 ready for use in a surgical procedure. In the sterile pack, the cannula’s proximal connector 174 is located in its housing in the Cannula Delivery Instrument 202 with the cannula stop 40 positioned at the distal end of the Cannula Delivery Instrument 202. The guide tube cap 28 is located in the distal end of the Guide Tube Delivery Instrument 204. The Guide Tube 4 in the sterile pack may be longer than any insertion depth that is likely to be required, for example 125mm long, and its distal end may be sealed. The Cannula Delivery Instrument 202 is inserted in the Guide Tube Delivery Instrument 204 and the cannula 6 is within the bore of the guide tube 4 with the cannula distal end approximately 5mm from the occluded distal end of the guide tube 4. The locking feature 216 on the proximal end of the Guide Tube Delivery Instrument 204 is clamped onto the Cannula Delivery Instrument 202 fixing their relationship prior to use. The Priming Tube 206 is in the bore of the Cannula Delivery Instrument 202 with its distal connector inserted connected to the cannula’s proximal connector 174. Workflow for preparing and inserting the guide tube and cannula

[0202] 1. Setting the skull surface datum to surgical target distance in the Device Preparation Jig

[0203] The Tool Guide 1 with attached Target Depth Stop 9 and Instrument Guide Stop 5 is detached from the targeting device’s instrument guide after the Skull Verification Tool 3 has been used to set the relationship between the proximal end of the Tool Guide 1 and the skull surface. The Tool Guide 1 is transferred to the Device Preparation Jig 43 so that the distal end of the Target Depth Stop 9 engages with a datum surface on the Skull Surface Datum Platform and the Target Datum Platform is moved up to engage with the distal end of the Instrument Guide Stop 5. The distance between the datum surfaces on Skull Surface Datum Platform and the Target Datum Platform now the equals the distance between the skull surface datum and the surgical target. This relationship is fixed in the Device Preparation Jig 43 by locking the position of the Target Datum Platform with a clamp. The Tool Guide 1 with attached Target Depth Stop 9 and Instrument Guide Stop 5 can then be transferred back to the targeting device’s instrument guide for the surgeon to prepare the entry site and insert the Guide Hub 50.

[0204] 2. Setting the Track Forming Tool

[0205] The Cannula Track Forming Probe 190 is withdrawn into the Guide Tube Track Forming Probe 192 so that their distal ends are flush. Their relative positions are indicated on a measurement scale on the proximal shaft of the Cannula Tube Track Forming Instrument 198 which is zeroed and fixed with a finger tightened clamp on the Guide Tube Track Forming Instrument 196. The Guide Tube Track Forming Instrument 196 is withdrawn into the Track Forming Tool’s outer body 194 so that their distal ends are flush, and their relationship is fixed with a clamp, which may be finger operated, on the Track Forming Tool’s outer body 194. The Track Forming Tool 181 is positioned in the Device Guide 51 so that its stop abuts the proximal end of the Device Guide 51. The two are clamped together with a finger tightened clamp on the Device Guide 51.

[0206] The Track Forming Tool 181 with attached Device Guide 51 are positioned in the Device Preparation Jig 43 with the proximal end of the Track Forming Tool 181 located in retention and aligning features in its top crossbeam. The distal end of the Track Forming Tool 18 is positioned on the receiving features of the Skull Surface Datum Platform. The clamp on the Track Forming Tool’s outer body 194, which may be finger operated, is released and the Guide Tube Track Forming Instrument 196 is lowered until the distal end of the Guide Tube Track Forming Probe 192 engages the datum surface of the Target Datum Platform. The finger operated clamp on the Track Forming Tool’s outer body 194 is now tightened.

[0207] A collar clamp on the shaft of the Guide Tube Track Forming Instrument 196 is released, for example using a hex-driver, and moved along the shaft of the Guide Tube Track Forming Instrument 196 until its distal surface engages with the proximal face of the outer body 194 and clamped. This sets the depth of insertion of the Guide Tube Track Forming Probe 192.

[0208] A collar clamp on the shaft of the Cannula Track Forming Instrument 198 is and moved relative to the measurement scale along the shaft of the Cannula Track Forming Instrument 198 until its distal surface is aligned with the required step-length. The clamp is then secured to the shaft of the Cannula Track Forming Instrument 198. This sets the length by which the Cannula Track Forming Probe 190 will extend beyond the distal end of the Guide Tube Track Forming Probe 192.

[0209] The clamp on the outer body 194 of the Track Forming Tool 181 is released and the Guide Tube Track Forming Instrument 196 withdrawn until the distal end of the Guide Tube Track Forming Probe 192 is flush with the distal end of the Track Forming Tool 181. The clamp is then tightened.

[0210] 3. Inserting the Track Forming Tool 181

[0211] The Track Forming Tool 181 with attached Device Guide 51 are transferred to the targeting device and inserted down the Instrument Guide Stop 5 which has had the Tool Guide 1 removed from its bore . When the distal end of the Track Forming Tool 181 engages with the datum surface of the Guide Hub 5 the collar clamp on the Instrument Guide Stop 5 is locked with a Hex-screwdriver. This fixes the position of the proximal end of the Device Guide 51 which is now distance h from the skull surface datum.

[0212] The Cannula Track Forming Instrument 198 is now advanced by a predetermined distance smaller than the step length, for example 5mm, with reference to the measurement scale on its shaft. The Cannula Track Forming Probe 190 now projects a small distance beyond the distal end of the Guide Tube Track Forming Probe 192. This provides a fine tapered profile for dissection through the brain tissue and the lubricious coating on the probe surfaces, such as PTFE, reduces sheer forces on the tissue thereby minimising tissue trauma and tissue displacement, assisting in the accuracy of targeting deep subcortical structures.

[0213] The clamp on the outer body 194 of the Track Forming Tool 181 is released and the Guide Tube Track Forming Instrument 196 advanced until its stop engages with the proximal end of the outer body 194. The clamp is then tightened. With this manoeuvre the track forming probes have passed through the bore of the guide hub 50, through the dura (which had been pierced by the pilot drill), through the pia (which is pierced by the conical tip of the Cannula Track Forming Probe 190), and through the brain tissue. This positions the distal end of the Guide Tube Track Forming Probe 192 in the proximal part of the target volume.

[0214] The clamp on the Guide Tube Track Forming Instrument 196 is released and the Cannula Track Forming Instrument 198 is advanced until its stop engages with the proximal end of the Guide Tube Track Forming Instrument 196. This advances the Cannula Track Forming Probe 190 beyond the distal end of the Guide Tube Track Forming Tool 196 by the step-length.

[0215] The Cannula Track Forming Probe 190 is withdrawn into the Guide Tube Track Forming Probe 192 and clamped. The Guide Tube Track Forming Probe 192 is withdrawn into the body of the Track Forming Tool 181 and clamped. The Track Forming Tool 181 is now withdrawn from the Device Guide 51 and returned to the Device Preparation Jig 43.

[0216] 4. Preparing the Device Delivery Tool 185

[0217] The Device Delivery Tool 185 is removed from its sterile pack and transferred to the Device Preparation Jig 43 with the Guide Tube Packaging Sleeve 208 retained on the distal end of the Delivery Tool 185 protecting the Guide tube 4 and the indwelling cannula 6. A method is now carried out for preparing the fluid transfer tube 6 and guide tube 4 for use in stereotactic neurosurgery using the device delivery tool 185.

[0218] The fluid transfer tube 6 is engaged with the distal end of the cannula delivery instrument 202, and the guide tube 4 is engaged with the distal end of the guide tube delivery instrument 204. The proximal clamp on the Guide Tube Delivery Instrument 204 is positioned in the retention and aligning features in the Device Preparation Jig’s top crossbeam. The stepped datum on the Guide Tube Packaging Sleeve 208 on the distal end of the Guide Tube Delivery Instrument 204 is positioned in the receiving features in the Skull Surface Datum Platform, which positions its distal length containing the guide tube 4 and indwelling cannula 6 in the Cutting Jig slot in the Target Datum Platform. The position of the Target Datum Platform relative to the Skull Surface Platform has been set, as described previously and equals the planned guide tube length.

[0219] The step-length of the cannula 6 is now set by releasing the finger operable clamp on the proximal Guide Tube Delivery Instrument 204 and retracting proximally the cannula delivery instrument 202 relative to the guide tube delivery instrument 204 by a first predetermined length from a fully deployed position of the cannula delivery instrument 202 relative to the guide tube delivery instrument 204. The fully deployed position is a position at which the fluid transfer tube 6 is fully advanced into the guide tube 4, and the first predetermined length is equal to the prescribed steplength. The retraction is carried out with reference to the measurement scale and indicator on the Device Delivery Tool 185. The finger operable clamp is then tightened.

[0220] The cannula 6 is then primed with liquid prior to its insertion using the priming tube 206. This is preferably with a biologically inert liquid such as artificial cerebrospinal fluid (aCSF), or the diluent for the therapy to be infused, including phosphate buffered saline (PBS). An example procedure for the priming is as follows. A syringe containing the liquid is connected to an in-line T-pressure relief valve (Halkey / Roberts®) via its Luer connector and in turn the T- pressure relief valve is connected via its distal male Luer connector to the female Luer on the proximal end of the Priming Tube 206. The T-pressure relief valve is activated by pressure above 1.2 bar which prevents excessive pressure build up during the priming process thereby protecting the filter membranes in the cannula’s proximal connector 174 from fracturing. Having displaced air from the bore of the cannula 6 the priming liquid now enters the interface between the cannula 6 and guide tube bore and displaces air from it. The syringe and in-line T-pressure relief valve are removed from the Priming Tube 206 and the Priming Tube 206 is detached from the Device Delivery Tool 185.

[0221] The fluid transfer tube 6 and the guide tube 4 are then cut together such that the guide tube 4 is cut to a second predetermined length. The Cutting Tool 304 is used to transversely cut through the Guide Tube Packaging Sleeve 206 and indwelling guide tube 4 and cannula 6. The cutting tool’s rods are inserted into the guide channels, one on each side of the cutting jig slot in the Target Datum Platform in which the guide tube 4 and cannula 6 in their packaging sleeve 206 are positioned. The sum of the first predetermined length and the second predetermined length is equal to a depth of a surgical target within a skull of a patient.

[0222] The Device Delivery Tool 185 is removed from the Device Preparation Jig 43 and the Guide Tube Packaging Sleeve 206 is detached from the Device Delivery Tool 185.

[0223] 5. Insertion of the Cannula 6 and Guide Tube 4.

[0224] Prior to inserting the cannula 6 and guide tube 4, the Conical Guide is attached to the distal end of the Device Guide 51 in the Stereotactic Instrument. The Device Delivery Tool 185 with the Guide tube 4 and indwelling cannula 6 attached at its distal end is inserted through the Device Guide 51 until the guide tube 4 passes through the Conical Guide and enters the bore of the guide hub 50 and advances into the pre-made track in the brain tissue. The Conical Guide is removed from the Device Guide 51 to allow the Device Delivery Tool 185 to advance until its distal end engages with the proximal face of the hub 50. This advances the guide tube 4 with the primed cannula 6 in its bore to the first target position, i.e. the planned position of the distal end of the guide tube 4.

[0225] The shaft of the Cannula Delivery Instrument 202 is then advanced after releasing the locking collar on the proximal shaft of the Guide Tube Delivery Instrument 185. This independently advances the cannula 6 by the step-length to the second target position. This two-stage advancement of the guide tube 4 and cannula 6 ensures that only the step -length of the fine flexible cannula 6 passes through the tissue track unsupported and typically the greater portion is supported and guided to its target by the guide tube 4. Importantly, this method of cannula insertion avoids the risk of displacing air into the brain with a piston-like effect that may occur with other guide tube and cannula arrangements as described in the introduction. Air inadvertently driven into the brain creates a cavity in the tissue that can disrupt the distribution of infused therapy.

[0226] The final stages of the insertion are illustrated in Fig. 22. As the seal on the distal end of the cannula stop 40 engages with the proximal face of the guide tube cap 28 as shown in Fig. 22A, the cap 28 is disengaged from its retention features in the distal end of the Guide Tube Delivery Instrument 204, as shown in Fig. 22B. Both the guide tube 4 and cannula 6 then move simultaneously until the distal end of the guide tube cap 28 engages with the stepped reduction in the internal diameter of the guide hub 50, as shown in Fig. 22C. Further advancement of the shaft of the Cannula Delivery Instrument 202 axially compresses the compliant seal between the cannula stop 40 and the guide tube cap 28 facilitating sufficient displacement of the cannula stop 40 to actuate its snap fit into the formation in the wall of the hub’s through bore. This secures the cannula 6 and guide tube 4 in the hub 50 and therefore to the skull. Radial compression of the seal creates a proximal fluid seal between the cannula 6, the guide tube 4, and the hub 50.

[0227] Finally, as shown in Fig. 22D, the cannula’s proximal connector 174 is extracted through the distal side apertures 212, 220 in the Cannula Delivery Instrument 202, the Guide Tube Delivery Instrument 204 and the Device Guide 51, which are now aligned. The Device Delivery Tool 185 and the device guide 51 are removed from the Stereotactic Instrument and the scalp incision is temporarily closed with sutures around the cannula’s short external portion between its stop and proximal connector 174.

Claims

1. CLAIMS1. A device delivery tool for inserting a guide tube and a fluid transfer tube into the brain of a mammal, the device delivery tool comprising: a cannula delivery instrument having a distal end configured to detachably engage with a proximal end of a fluid transfer tube for providing fluid access to the brain of a mammal; and a guide tube delivery instrument having: a distal end configured to detachably engage with a proximal end of a guide tube configured for insertion into the brain; and a through-bore configured to receive the cannula delivery instrument, wherein a position of the cannula delivery instrument within the through-bore of the guide tube delivery instrument is adjustable, such that a fluid transfer tube engaged with the distal end of the cannula delivery instrument can be advanced into the brain through a guide tube engaged with the distal end of the guide tube delivery instrument.

2. The device delivery tool of claim 1, wherein: the distal end of the guide tube delivery instrument is further configured to engage with a guide hub implanted in an aperture formed in a skull along a trajectory to a target within the brain, the guide hub configured to receive the guide tube along the trajectory; and engagement of the distal end of the guide tube delivery instrument with a guide hub releases a guide tube engaged with the distal end of the guide tube delivery instrument.

3. The device delivery tool of claim 1 or 2, wherein the distal end of the guide tube delivery instrument comprises one or more retention features configured to prevent proximal movement of a guide tube engaged with the distal end of the guide tube delivery instrument.

4. The device delivery tool of claim 3, wherein the one or more retention features are configured such that advancement of the distal end of the cannula delivery instrument through the through-bore of the guide tube delivery instrument releases the retention features.

5. The device delivery tool of any of claims 1 to 4, wherein the device delivery tool further comprises a guide tube sheath configured to: engage with the distal end of the guide tube delivery instrument; and enclose a guide tube engaged with the distal end of the guide tube delivery instrument.

6. The device delivery tool of claims 5 when dependent on claim 3 or 4, wherein the guide tube sheath is configured to prevent the release of the one or more retention features when the guide tube sheath is engaged with the distal end of the guide tube delivery instrument.

367. The device delivery tool of any of claims 1 to 6, wherein: one of the guide tube delivery instrument and the cannula delivery instrument comprises a measurement scale; the other of the guide tube delivery instrument and the cannula delivery instrument comprises an indicator feature; the indicator feature and the measurement scale are configured to interact to indicate a distance by which the cannula delivery instrument should be advanced distally relative to the guide tube delivery instrument such that a fluid transfer tube engaged with the distal end of the cannula delivery instrument is fully advanced into a guide tube engaged with the distal end of the guide tube delivery instrument.

8. The device delivery tool of any of claims 1 to 4, wherein one or both of: a) a distal region of the guide tube delivery instrument comprises an axially-extending aperture providing access to the through-bore of the guide tube delivery instrument; and b) the cannula delivery instrument comprises a through-bore configured to receive at least a portion of the fluid transfer tube, and a distal region of the cannula delivery instrument comprises an axially-extending aperture providing access to the through-bore of the cannula delivery instrument.

9. The device delivery tool of any of claims 1 to 8, wherein a distal region of the guide tube delivery instrument comprises an axially-extending slot providing access to the through-bore of the guide tube delivery instrument, the slot extending to the distal end of the guide tube delivery instrument.

10. The device delivery tool of any of claims 1 to 9, wherein the guide tube delivery instrument and the cannula delivery instrument comprise corresponding alignment features configured such that the guide tube delivery instrument and the cannula delivery instrument adopt a predetermined relative rotational alignment when the cannula delivery instrument is received in the through-bore of the guide tube delivery instrument.

11. The device delivery tool of any of claims 1 to 10, wherein the guide tube delivery instrument comprise a locking feature configured to fix a position of the cannula delivery instrument within the through-bore of the guide tube delivery instrument.

12. A kit for use in stereotactic neurosurgery comprising: the device delivery tool of any of claims 1 to 11; a fluid transfer tube for providing fluid access to the brain of a mammal; and a guide tube configured for insertion into the brain and having a through-bore for passage of the fluid transfer tube.3713. The kit of claim 12, wherein the kit further comprises a priming tube configured to connect fluidically to the proximal end of the fluid transfer tube to fill the fluid transfer tube.

14. A method for preparing a fluid transfer tube and a guide tube for use in stereotactic neurosurgery using the device delivery tool of any of claims 1 to 11, wherein the fluid transfer tube is engaged with the distal end of the cannula delivery instrument, and the guide tube is engaged with the distal end of the guide tube delivery instrument, the method comprising: retracting proximally the cannula delivery instrument relative to the guide tube delivery instrument by a first predetermined length from a fully deployed position of the cannula delivery instrument relative to the guide tube delivery instrument, the fully deployed position being a position at which the fluid transfer tube is fully advanced into the guide tube; and cutting the fluid transfer tube and the guide tube together such that the guide tube is cut to a second predetermined length, wherein the sum of the first predetermined length and the second predetermined length is equal to a depth of a surgical target within a skull of a patient.

15. A track-forming tool for forming a track in brain tissue for insertion of a fluid transfer tube within the through-bore of a guide tube, the track-forming tool comprising: an inner probe having a distal end, the distal end comprising a tip configured for dissecting tissue; an outer probe having a through-bore configured to receive the inner probe, wherein: a distance by which the tip of the inner probe extends beyond a distal end of the outer probe is adjustable; the outer probe is configured for insertion into the brain tissue to form a larger-diameter portion of the track to receive the guide tube; and the inner probe is configured for insertion into the brain tissue to form a smaller-diameter portion of the track extending beyond the end of the larger-diameter portion of the track to receive a portion of the fluid transfer tube extending beyond a distal end of the guide tube.

16. The track -forming tool of claim 15, wherein the track-forming tool further comprises an outer body having a through-bore configured to receive the outer probe, wherein the outer body is configured to be received in a guide for holding surgical tools in stereotactic surgery.

17. The track -forming tool of claim 15 or 16, wherein the distal end of the inner probe is tapered, optionally wherein the distal end of the inner probe tapers from between 0.4mm and 0.6mm tobetween 0.1mm and 0.3mm, optionally from 0.5mm to 0.2mm.

18. The track -forming tool of any of claims 15 to 17, wherein the distal end of the outer probe is tapered, optionally wherein the distal end of the outer probe tapers from between 1mm and 2mm to between 0.5mm and 1mm, optionally from 1.4mm to 0.8mm.

19. The track -forming tool of any of claims 15 to 18, wherein the track-forming tool comprises a cannula track forming instrument, a distal section of the cannula track forming instrument comprising the inner probe and a proximal section of the cannula track forming instrument having a larger diameter than the inner probe, optionally wherein the proximal section and the distal section are integrally formed.

20. The track -forming tool of any of claims 15 to 19, wherein the track-forming tool comprises a guide tube track forming instrument, a distal section of the guide tube track forming instrument comprising the outer probe and a proximal section of the guide tube track forming instrument having a larger diameter than the outer probe, optionally wherein the proximal section and the distal section are separable.

21. The track -forming tool of any of claims 15 to 20, wherein: the track-forming tool comprises a cannula track forming instrument, a distal section of the cannula track forming instrument comprising the inner probe; the track-forming tool comprises a guide tube track forming instrument, a distal section of the guide tube track forming instrument comprising the outer probe; one of the cannula track forming instrument and the guide tube track forming instrument comprises a measurement scale; the other of the cannula track forming instrument and the guide tube track forming instrument comprises an indicator feature; the indicator feature and the measurement scale are configured to interact to indicate the distance by which the tip of the inner probe extends beyond the distal end of the outer probe.

22. The track -forming tool of any of claims 15 to 21, wherein one or both of a distal end of the outer probe and the distal end of the inner probe comprises a lubricious coating.

23. A guide tube for use with a fluid transfer tube for providing fluid access to the brain of a mammal, wherein the guide tube is configured for insertion into the brain, and the guide tube comprises: a through-bore for passage of a fluid transfer tube; an inner layer; anda resiliently-deformable outer layer having a higher compliance than the inner layer, wherein one or both of the inner layer and the outer layer is impermeable to fluid.

24. The guide tube of claim 23, wherein a proximal end of the guide tube has a larger diameter than the distal end of the guide tube, such that the proximal end acts as a stop to limit an insertion depth of the guide tube into the brain, optionally wherein the proximal end is formed integrally with the inner layer.

25. The guide tube of claim 23 or 24, wherein one or more of: a) the outer layer comprises a lubricious coating; b) the outer-layer comprises silicone; and c) the outer layer is formed by dip-coating onto the inner layer.

26. The guide tube of any of claims 23 to C253, wherein the outer-layer has a hardness of at most 80 measured on the Shore 00 hardness scale, optionally at most 40, optionally at most 20, optionally at most 10.

27. The guide tube of any of claims 23 to 26, wherein a proximal portion of the guide tube is configured to be axially and / or laterally deformable, optionally wherein the proximal portion has a length of between 5mm and 30mm.

28. The guide tube of claim 27, wherein the proximal portion is configured such that a maximum elastic deformation of the proximal portion under compression is less than a maximum elastic deformation of the proximal portion under extension.

29. The guide tube of claim 27 or 28, wherein the proximal portion is configured as a spring, optionally by forming a spiral cut through the inner layer in the proximal portion.

30. The guide tube of any of claims 15 to 29, wherein the inner layer comprises polyether ether ketone, PEEK, or carbon-filled PEEK.

31. The guide tube of any of claims 15 to 30, wherein the inner layer defines the through -bore.

32. The guide tube of any of claims 15 to 31, wherein the through-bore has a diameter of at most 0.7mm, optionally less than 0.6mm.

33. The guide tube of any of claims 15 to 32, wherein an outer diameter of the inner layer is at most 1.5mm, optionally at most 1mm, optionally approximately 0.8mm.

34. The guide tube of any of claims 15 to 33, wherein an outer diameter of the guide tube is at most 1.8mm, optionally at most 1.5mm, optionally at most 1.3mm.

35. The guide tube of any of claims 15 to 34, wherein the guide tube has a length of between 25mm and 150mm, optionally between 50mm and 120mm.

36. A kit for use in stereotactic neurosurgery comprising: a fluid transfer tube for providing fluid access to the brain of a mammal; and the guide tube of any of claims 15 to 35.

37. The kit of claim 36, further comprising the device delivery tool of any of claims 1 to 11.

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