WO2012176050A1

WO2012176050A1 - Cranial anchor

Info

Publication number: WO2012176050A1
Application number: PCT/IB2012/001234
Authority: WO
Inventors: Eric Marty; Serge Mordon; Denise BECHET; Muriel-Agnès BARBERI-HEYOB
Original assignee: Universite De Lorraine; Centre Alexis Vautrin (Etablissement Prive)
Priority date: 2011-06-24
Filing date: 2012-06-21
Publication date: 2012-12-27
Also published as: FR2976813A1; FR2976813B1

Abstract

The invention relates to a cranial anchor comprising a plate (100) with a plurality of fixation holes (131, 132, 133), a cannula (110) protruding from an upper face of the plate, and a clip (115) for preliminary positioning that protrudes from a bottom face of the plate, with a hollow guide tube (120) being drilled through the cannula and the plate in order to permit the passage of a probe. Application to the field of the neurosciences, for example to the measurement of intracranial physiological parameters, to intracranial treatment by therapy, etc.

Description

Cranial anchor

Technical field and state of the art

The invention relates to a cranial anchor for precise insertion of a probe (microdialysis probe or the like) through a drill bit hole. The invention is advantageously applied in the medical field, more specifically in the field of the measurement of intracerebral physiological parameters of a person or an animal, or in the field of therapeutic treatment of diseases of the brain. The invention also finds application in the field of research, in particular for measurements or tests carried out on animals whose skull dimensions are very small, of the order of 10 to 30 mm in diameter and less than 1 mm thick for example. In particular, a cranial anchor is known from document D I (EP 2,070,561). It keeps a catheter or an electrical probe in position for the duration (several days) of the treatment of a patient. The anchor has a funnel shape, and the electric probe is wound on an outer edge of the funnel. Thanks to this particular shape, involuntary pulling on the free end of the probe can not cause tearing of the probe or the catheter. The outer edge of the anchor must necessarily have a diameter greater than the minimum radius of curvature of the probes or catheter associated therewith. It follows that the anchor is necessarily large, of the order of 20 to 40 mm. An anchor of this size may be attached to an adult human skull, but it can not be attached to a small skull, such as that of an animal commonly used in the laboratory such as a rat. Also, such an anchor can not, under any circumstances, be used with measuring tools such as optical fibers because their radius of curvature is too large and the dimensions of such an anchor adapted for holding in position a fiber optical would be disproportionate compared to the size of a human skull, even adult.

In the document D2 (Optogenic interrogation of neural circuits: technology for probing mammalian brain structures, Nature protocols, vol.5 No. 3, 2010, pp439-456), a technique is described p 455, figure a to maintain an optical fiber. The fiber is inserted into a cannula of the same internal diameter, and the cannula is attached to the skull of a rat by dental cement. This technique does not allow accurate positioning because it is difficult to measure the angle between the cannula and the skull, and especially to maintain this constant angle throughout the drying time of the cement.

In practice, there is no commercially available cranial anchor to date allowing precise positioning of the probe, adapted for use with a fiber optic type probe and / or adapted for attachment to a small skull. cut.

Description of the invention

The invention proposes a new cranial anchor not having all or some of the disadvantages of known anchors. More specifically, the invention provides a cranial anchor comprising a plate having a plurality of fixing holes, a cannula projecting from an upper face of the plate and a pre-positioning clip. protruding from an underside of the plate, the cannula and the plate being pierced with a hollow guide tube for the passage of a probe.

The anchor according to the invention, comprising the plate, the cannula and the clip, is preferably made in one piece, in the form of a single piece, for example machined using a lathe adapted to the dimensions of the anchor to cut. Alternatively, the plate and the cannula are made in one piece, and the clip is an ankle positioned in a recess of the plate opening on the underside of the plate. The fixing holes are preferably opening to allow the passage of fastening screws for securing the anchor on the bones of a skull. The guide tube preferably has an axis substantially perpendicular to the plate to facilitate the identification in space during the introduction of a probe in the hollow guide tube. The clip is used to preposition the anchor in a hole of bit of the same diameter, before fixing the anchor; the clip can be located in the center of the board, but not necessarily. The height of the clip (along a longitudinal axis of the clip) is preferably less than or equal to the thickness of a cranial bone, so that the clip does not penetrate inside the skull. The outer dimensions of the clip (in a transverse direction) are limited to the maximum, so as to minimize the intrusive effect of the anchor. The anchor may also include a positioning mark, for example drawn, cut or engraved, on a visible part of the anchor, for example on a top face of the plate. The marker facilitates positioning of the anchor: the clip of the anchor is positioned at a reference point, for example at the so-called bregma point of the skull, and the positioning mark is then oriented in a desired direction, for example according to a sagittal suture of the skull. Thus, it is no longer necessary to use a stereotaxis apparatus to set up the anchor, all the information necessary for the positioning being predefined on the anchor.

The tray can have a solid disc shape. It can also have any other form, as will be seen better later in examples, to adapt to the shape and dimensions of the skull on which the anchor must be fixed. The fixing holes are preferably positioned near the periphery of the plate, and distributed around the guide hole, depending on the shape and dimensions of the skull on which the anchor is to be fixed. If the tray has a disc shape, the holes may for example be positioned on shelf spokes at about 120 degrees from each other. The anchor is fixed by screws of length less than or equal to the thickness of the plate plus the thickness of the bones of the skull.

The anchor is first positioned accurately on the skull of an individual, or using a stereotaxic device, along an anteroposterior axis, a lateral axis and a dorso-ventral axis, from of a precise atlas of the brain, either by using the anchor positioning mark. The anchor is then attached to the bones of the skull with the smallest screws possible depending on the size of the holes and the thickness of the skull. If a stereotactic camera has been used, it is then removed. Thanks to its particular form and its particular mode of attachment, the anchor according to the invention can remain in position several days, several weeks, without discomfort for the subject; it thus allows a treatment continued over several days, several weeks. Once fixed, the anchor can be used at any time, without recourse to the frame of stereotaxis, to insert a probe along a perfectly identified axis, thanks to the cannula arranged above the plate. The fixed plate imposes a precise positioning along the anteroposterior axis and the lateral axis perpendicular to the axis of the cannula, the anchor forms thus a means of positioning the probe particularly accurate in two dimensions. A depression of the probe of a precise height (determined for example by MRI measurements) in the guide hole of the cannula then allows a micrometric positioning, in the cranial volume, according to the three dimensions orthogonal to each other. The anchor is made of non-magnetic material; It does not interfere with imaging devices such as Magnetic Resonance Imaging (MRI) devices or X-ray scanners. This improves the accuracy in positioning the anchor, then in the introduction of the machine. probe inside the skull via the guide tube of the anchor, then in any measurements made by the probe held in position by the anchor.

Preferably, a thickness of the anchor plate is less than 1 mm. Thus, the plate is sufficiently conformable, flexible to adapt to the shape of the skull, which is not quite flat. This is particularly useful if the anchor is positioned on the skull of a young animal such as a rat whose skull is physiologically concave or curved, of the order of 10 to 20 mm wide and of the order from 20 to 30 mm.

In addition, after fixing the anchor on the bones of the skull, and thanks to the thin thickness of the anchor plate, all of the soft tissues that cover the skull of the individual can cover the plate of the anchor and heal around the cannula so that only the cannula of the anchor remains accessible. This eliminates any discomfort for the individual, and also greatly limits the risk of infection or the risk of tearing.

More preferably, the fixing holes on the anchor plate have an oblong shape. The oblong shape of the holes allows the screws to move along the hole when the bones of the skull grow. As the bones of the cranial box all grow simultaneously and in the same proportions, the axes of positioning in the three directions are preserved in time. Thus, the anchor can be installed on the skull of a young and still growing individual. It can even be installed on the skull of a young rat whose dimensions can grow by about 10% in 2 to 3 weeks.

More preferably, the dimensions of the guide hole of the cannula and the clip are equal to or slightly greater than the dimensions of the probe. The probe can thus be inserted into the skull in the most perfect direction possible. The depth of the probe is adjustable.

The anchor may also include a locking means for locking the probe when the probe is in position at a predetermined depth within the guide hole. Thus, once locked in position, the probe can be used without time limit, without risk of being misplaced. In one exemplary embodiment, the locking means is a small hollow plastic sheath about 5 mm long and having an internal recess of identical section to the section of the probe. The sheath is accurately positioned on the probe using a micrometer caliper at a distance from the end of the probe depending on the desired depression of the probe in the brain. The probe is then inserted into the guide hole until contact of the locking sheath on the free end of the cannula.

According to another variant, the cannula and the anchor plate, or the cannula, the plate and the clip of the anchor are pierced with several guide tubes, to allow the simultaneous insertion of several probes, measuring instruments or Therapy instruments at specific locations inside the brain. In a cannula according to the invention, the cannula and the plate are pierced with a guide tube, or several. In a variant, the guide tube or tubes pass through not only the cannula and the plate but also the clip of the anchor. This variant is well suited to an anchor of very small size (for example a centimeter or less) and / or comprising a small number of guide tubes to allow the introduction of a small number of probes, for example one or two probes; the transverse dimensions of the clip must indeed be sufficient to allow drilling the clip to form the guide tube or tubes. In another variant, the guide tube or tubes pass through the cannula, the plate, but not the clip of the anchor. This variant is particularly suitable for an anchor larger and / or allowing the establishment of several probes (via several guide tubes as will be seen better later) more or less spaced apart from each other; it makes it possible to limit the external dimensions of the clip to minimum dimensions imposed by machining constraints or mechanical rigidity constraints of the clip, much lower than those imposed for the drilling of a guide tube. This greatly improves accuracy when positioning and placing the anchor, and also limits the intrusive appearance of the clip.

The guide tube or tubes, passing through the cannula, the plate and possibly the clip may or may have an axis substantially perpendicular to the plate, each axis at a predetermined distance from a longitudinal axis of the clip and each axis forming with the positioning mark a predefined angle measured with respect to the longitudinal axis of the clip, the predefined distance and the predefined angle being a function of an area of a brain to be treated. Thus, by using the clip as a reference center and using the positioning mark for setting up the anchor, the guide tube or tubes are immediately at the desired radial position. In other words, all the three-dimensional information necessary for the positioning of the probes is predefined on the anchor. No apparatus, no mapping is no longer necessary for the installation of the anchor.

The anchor may also comprise a closure means (for example a stopper) comprising a gripping portion extended by a wire of length equal to the height of the cannula plus the height of the plate plus the height of the clip, the wire having by moreover a section of shapes and dimensions similar to those of the guide hole. The sealing means thus fits perfectly to the guide hole to completely obstruct it. The closure means wire is inserted into the cannula, preventing infection and allowing the bit hole to remain accessible at all times without the risk of resealing.

The anchor may further comprise a gripping means for fixing it with a rack in a stereotactic frame for precise positioning. According to a variant, the gripping means is the gripping part of the plug. The anchor according to the invention and the fixing screws are made of a material compatible with the magnetic fields used in non-invasive imaging (MRI) techniques, such as X-ray tomographic techniques (scanner, etc.); it is for example made of polyvinyl chloride (PVC), or polyoxymetylene (POM), such as Delrin (r), or in a microporous biocompatible material that can be recolonized by bone cells. The anchor is thus viewable but does not disturb the acquisition of images and measurements. Also preferably, the material chosen is thermoformable. The shape of the plate can thus, if necessary, be adjusted to the shape of the skull by thermoforming before setting it in position. The invention also relates to a method of placing a cranial anchor as described above, the method comprising in particular the following steps:

• position the pre-positioning clip of the anchor in a bit hole made in a cranial box,

• Orient the anchor using a stereotaxic frame and from anatomical landmarks of the cranial box, • Fix the anchor on the cranial box with screws.

The main advantages of the anchor according to the invention are its simplicity of realization by machining, and especially its particularly small dimensions, which makes it very little intrusive and allow to use it even in very small subjects.

The anchor according to the invention was developed for stereotaxic interstitial photodynamic therapy in small animals guided by microIRM; placed on the skull of a young rat in full growth, it was used to inoculate tumor cells at a specific point in the brain using a micro-needle, then treat this tumor for several weeks by therapy Interstitial photodynamics using an optical fiber diameter 272 micrometers.

The anchor can be used more widely in all areas of neuroscience, and for larger individuals, including humans. For example, in stereotactic neurosurgery, the anchor can be used for different interventions:

• for the removal of tissue metabolites and / or dialysate, biopsies or removal of an area ^'interest, instillation or injection of different principles (drugs, contrast agents, chemicals or cells, etc.)

· For the positioning of objects: optical fiber for treatment or fluorescence detection, microdialysis probe, intracranial pressure probe, thermal probe, blood flow probe, external derivation of cerebrospinal fluid, etc.,

For the positioning of electrodes (electrophysiology) or for the realization of optogenetic protocol (injection of cells or viruses and excitation at a wavelength of interest),

· For measuring a physiological parameter or taking an image at a predefined point inside the cranial box of an individual.

Brief description of the figures

The invention will be better understood, and other features and advantages of the invention will become apparent in the light of the following description of examples of embodiments of anchors according to the invention. These examples are given in a non-limiting manner. The description is to be read in conjunction with the accompanying drawings in which

FIGS. 1, 3 and 5 and 6 are respectively a view from above and three sections A-A of an anchor according to a first embodiment of the invention, and

FIGS. 2 and 4 are respectively a top view and a B-B section of an anchor according to a second embodiment of the invention,

FIG. 7 is a sectional view of an anchor held by a clamp of a stereotactic apparatus,

FIG. 8 is a sectional view of an anchor holding a syringe in position, and FIGS. 9, 10 and 11 are respectively a view from above, a section BB and a section AA of an anchor according to a third embodiment.

DESCRIPTION OF AN EMBODIMENT OF THE INVENTION Specific prototypes of an anchor according to the invention have been developed to optimize the interstitial treatment of brain tumors in the rat for stereotaxic interstitial therapy guided by non-invasive imaging using, inter alia things, light brought by an optical fiber. The tests were particularly conclusive. The prototypes made correspond to the different variants represented.

The cranial anchors shown in the figures essentially comprise a plate 100, a cannula 1 10 and a pre-positioning clip 1 15. The cannula 1 10 projects from a top face of the plate 100 in a direction perpendicular to the plate. The clip 1 15 projects from a bottom face of the plate 100.

In the example of Figures 1, 3 the cannula 1 10, the plate 100 and the clip 115 are pierced with a hollow cylindrical tube 120 for guiding a wire probe, for example an optical fiber 154, along a perpendicular axis on the plateau. In the example of Figures 2, 4, the plate 100, the cannula 1 10 and the clip 1 15 are pierced with a hollow cylindrical tube 120a, and a hollow tube 120b having an oblong section on a first portion 120c and a circular section on a second part 120d. Such a tube 120b is adapted for passage, positioning and maintenance of a microdialysis probe commonly used in the field of neuroscience. In the example of Figures 9-1 1, the clip 1 15 is not pierced, it is full, and of much smaller dimensions than the clips of Figures 1 to 4. The plate 100 and the cannula 110 are as to they pierced with three guide tubes: a tube 120a of circular section, and two tubes 120b having an oblong section on a first portion and a circular section on a second portion.

The outer shape of the cannula 1 10, above the plate, is selected firstly according to the number, position and shape of the guide tubes, and then to facilitate its implementation. Thus, in the example of Figures 1, 3, 5-8, the cannula has a cylindrical outer shape, of circular section a little larger than the tube 120 from which it is pierced. In the example of Figures 2, 4, the cannula has a cylindrical outer shape but of oblong section, allowing the presence of the two guide tubes 120a, 120b. In the example of FIGS. 9, 10 and 11, the cannula has a substantially parallelepipedal external shape, extending over the entire dimension of the plate along the axis BB, and the cannula comprises two transverse grooves along the axis AA bottom of which are drilled three guide tubes 120a, 120b.

The plate has several holes 131, 132, 133 oblong fixing. The longitudinal axis of each fixing hole passes substantially through the axis of the hollow tube. If the anchor is positioned on an area of the flat skull, two holes and two fixing screws 134 are sufficient to ensure perfect immobilization of the plate on the skull 140. If the anchor is positioned on an area of the skull not all-to- made plane (the most common), three holes and three screws 134 fixing at least are necessary to ensure perfect immobilization of the anchor plate on the skull 140. Once the anchor is positioned and fixed, the stereotactic reference frame is fixed: the dorso-ventral axis corresponds to the axis of the guide hole, the anteroposterior axis and the lateral axis are in a plane perpendicular to the axis of the guide hole, plane which corresponds to the plane of the plate at least in the vicinity of the cannula and the clip.

In the example of Figures 1, 3, the plate 100 is a disk. The fixing holes 131, 132, 133 are distributed on shelf spokes spaced about 90 ° relative to one another and have a circular shape. In another example not shown, the holes may be distributed on shelf spokes spaced about 120 ° relative to each other. In another example not shown, the plate has substantially the shape of a disk portion. In the example of Figures 2, 4, and 9, the plate has substantially the shape of a multi-sided polygon. The fixing holes 131, 132, 133 are distributed in the vicinity of the periphery of the plate so that the entire surface of the plate matches the surface of the skull after fixation. The fixing holes are also positioned on the one hand so as not to risk damaging the brain when they are put in place, on the other hand so as not to hinder the insertion of a probe into the guide holes 120, 120a, 120b and do not interfere with the operation of a probe after its introduction. The fixing holes have an oblong shape and open to allow the passage of screws. In a variant of the anchor, adapted to be fixed on the skull of a small animal such as a rat, the plate has a thickness of about 1 mm, its largest dimension is of the order of 6 mm and its smallest dimension is of the order of 4 mm. The smallest dimension of the oblong fixing holes is of the order of 1 mm, to allow the passage of diameter fixing screws of the order of 1 mm. The largest dimension of the fixing holes is of the order of 2 mm; it allows the growth of a rat's skull by about 10%. The anchor can thus be fixed for example on the skull of a rat of about 10 days, and can remain in position for 2 to 4 weeks without disturbing the animal or the growth of bones of the skull.

In a variant of the anchor, adapted to be fixed on the skull of an adult human, the plate has a thickness of about 5 mm, its largest dimension is of the order of 10 to 15 mm and its smaller dimension is of the order of 5 mm to 10 mm. The fixing holes are circular and have a diameter of the order of 1 to 2 mm, to allow the passage of diameter fixing screws of the order of 1 to 2 mm. In an example of an anchor adapted for the passage of an optical fiber of diameter 0.272 mm and having a radius of curvature of the order of 120 °, the internal diameter of the cannula and the clip is of the order of 0 , 3 mm. The cannula has for example an outer diameter of about 1 mm, and a height of about 4 to 5 mm. The clip has an outer diameter of the order of 0.8 mm. The clip has a height of the order of 0.5 mm, substantially equal to a bone thickness 140 of the skull of a small animal. In an example of an anchor adapted for the passage of a microdialysis probe, the hollow tube 120b has, in a first portion 120c, an oblong section of which a large dimension is of the order of 2 mm and of which a small dimension is of the order of 1 mm and in a second section 120d, a circular section of diameter of the order of 2 mm.

The anchor according to the invention is preferably made in the form of a single machined piece, monobloc therefore, using a lathe adapted to the dimensions of the anchor to be cut. In the example of Figures 1 to 8, the clip, the cannula and the plate are monobloc, made in a single machined part. In the example of Figures 9 to 11, the plate and the cannula are monobloc, and the clip 1 15 is a tubular pin, for example plastic or stainless steel, positioned inside a recess of the plate opening on the underside of the board. Figure 5 shows the anchor of Figures 1, 3 and its shutter means in position on the cannula. The closure means here is a plug 150 comprising a gripping portion 151 extended by a wire 152. The wire 152 has a length equal to the height of the cannula plus the height of the plate plus the height of the clip; the wire 152 has a section of shapes and dimensions similar to those of the guide tube. The plug wire fits perfectly to the guide hole to completely block it.

Figure 6 shows the anchor of Figures 1, 3 in which a probe is immobilized at a desired depth in the guide hole by the locking means of the anchor. The locking means 153 of the anchor is in the example shown a small hollow plastic sheath about 5 mm in length and having an inner recess of identical section to the section of the probe. The sheath is accurately positioned on the probe using a micrometer caliper at a distance from the end of the probe depending on the desired depression of the probe in the brain. The probe is then inserted into the guide hole until contact of the locking sheath on the free end of the cannula.

Figure 7 shows the anchor mounted on a stereotactic frame for accurate positioning. A clip 155 of the stereotactic frame is positioned within the guide hole of the anchor to hold it and one end of the clip is attached to a rigid guide 156 attached to the stereotactic frame. The clip and the guide are abutted against the anchor so as to lock the anchor against the cranial box. In this example, the guide hole serves as a gripping means for fixing the anchor in the stereotactic apparatus. In a variant not shown, the gripping means is the gripping portion of the plug.

FIG. 8 is a sectional view of an anchor holding a micrometer syringe 157 in position, a silica needle 10 of a diameter of 1 micron extending in the volume of the cranial box.

In the example of Figure 9, a notch 160 at the edge of the plate forms a positioning mark to allow the establishment of the anchor without the use of stereotactic apparatus.

In all the examples shown, the guide tubes 120, 120a, 120b have longitudinal axes perpendicular to the plate. In the examples of Figures 1, 2, the tubes 120, 120a, 120b pass through the cannula, the tray and the clip. In the example of Figure 9, the tubes 120a, 120b through the cannula and the tray, but not the clip. In the example of FIG. 9, the tube 120b is positioned at a predefined distance from the longitudinal axis of the clip, and forms with the positioning mark 160 a predefined angle alpha measured with respect to the longitudinal axis of the clip. The predefined distance and the predefined angle are chosen according to an area of a brain to be treated. NOMENCLATURE plateau

cannula

clip

, 120a, 120b hollow tubes

c, 120d first part and second part of the hollow tube 120b, 132, 133 fixing holes

screw

skull

plug

grasping part of the stopper

plug wire

blocking means

optical fiber

rigid guide of the stereotactic frame

stereotactic frame clip

syringe

syringe needle

positioning marker

Claims

1. Cranial anchor comprising a tray (100) having a plurality of attachment holes (131, 132, 133), a cannula (1 10) projecting from an upper face of the tray and a protruding pre-positioning clip (1 15) from a bottom face of the tray, the cannula and the plate being pierced with a hollow guide tube (120) allowing the passage of a probe.

2. Anchor according to claim 1, also comprising a positioning mark (160), for example drawn, cut or engraved, on a visible part of the anchor, for example on a top face of the plate (100).

3. Anchor according to one of the preceding claims, wherein a thickness of the plate (100) is less than 1 mm.

4. Anchor according to one of the preceding claims, wherein internal dimensions of the guide tube (120) are equal to or greater than the corresponding dimensions of the probe.

5. Anchor according to one of the preceding claims, further comprising a locking means (153) in position of a probe inside the guide hole.

6. Anchor according to one of the preceding claims, wherein the cannula (1 10), the plate (100) and the clip (115) are pierced with the guide tube.

7. Anchor according to one of the preceding claims, wherein the cannula (1 10) and the plate (100) or the cannula (1 10), the plate (100) and the clip (1 15) are pierced with several tubes. (120a, 120b) guide.

8. Anchor according to one of claims 2 to 7, wherein the or the guide tubes (120, 120a, 120b) has or have an axis substantially perpendicular to the plate (100), each at a predetermined distance from an axis longitudinal axis of the clip (1 15) and each forming with the positioning mark (160) a predefined angle measured with respect to the longitudinal axis of the clip, the predefined distance and the predefined angle being a function of an area of a brain treat.

9. Anchor according to one of the preceding claims, wherein the fixing holes (131, 132, 133) have an oblong shape.

10. Anchor according to one of the preceding claims, further comprising a closure means (150) comprising a gripping portion (151) extended by a wire (152) of length equal to the height of the cannula plus the height of the tray the height of the clip, the wire also having a section of shapes and dimensions similar to those of the guide tube.

1. An anchor according to one of the preceding claims, further comprising an anchor gripping means for fixing the anchor in a stereotaxis apparatus for accurate positioning of the anchor.

12 Method for placing a cranial anchor according to one of the preceding claims, comprising the following steps, consisting of:

• position the pre-positioning clip of the anchor in a bit hole made in a cranial box, • orienting the anchor using a stereotaxic frame and brain mapping contained in the cranial box, or using the positioning marker, and

• fix the anchor on the cranial box with screws.

13. Use of an anchor according to one of claims 1 to 1 1, for measuring a physiological parameter or taking an image at a predefined point inside the cranial box of an individual.