LU101433B1

LU101433B1 - Device and method for introducing and detecting fiducial markers during radiological imaging of the head

Info

Publication number: LU101433B1
Application number: LU101433A
Authority: LU
Inventors: Andreas HUSCH; Frank Hertel; Peter Gemmar
Original assignee: Centre Hospitalier De Luxembourg; Univ Luxembourg
Priority date: 2019-10-11
Filing date: 2019-10-11
Publication date: 2021-04-15
Also published as: WO2021069648A1

Abstract

The proposed device and method allow for the introduction and detection of fiducial markers, which are preferably spherical markers, during radiological imaging of the head. The provision of predetermined positions for each fiducial marker reduces the likelihood of wrongful use of the device by an operator. The proposed device is easier to attach to a patient's head, while providing for automatic fiducial detection and registration.

Description

3. > » 1 LU101433

DEVICE AND METHOD FOR INTRODUCING AND DETECTING FIDUCIAL

MARKERS DURING RADIOLOGICAL IMAGING OF THE HEAD Technical field The invention lies in the field of medical devices and medical imaging. In particular, the invention relates to a stereotactic localizer device for introducing representations of fiducial markers into medical imagery of the human brain, and to a method for detecting such markers in a radiological image.

Background of the invention Stereotactic surgery is a minimally invasive form of surgical intervention that makes use of a three- dimensional coordinate system to locate small targets inside the body and to perform on them some surgical actions. In stereotactic neurosurgery, a surgical instrument has to be precisely navigated to a specific position within the patient's brain using devices attached to the skull of the patient. This process is directly related to preoperative imaging in the sense of image-guided surgery. By merging imaging information, a stereotactic device may be used to precisely access specific structures within the patient's brain. Either a tissue maybe fetched from a specific region of the brain (e.g., stereotactic brain tumor biopsy) or an object may be placed within a specific target region (e.g. catheters or deep brain stimulation electrodes). To allow for the precise placement of the stereotactic device with respect to the available imaging information, the coordinate systems of the image, and of the stereotactic hardware have to be aligned first. This implies image registration in the sense of defining a spatial transformation between imaging space and stereotactic space. To achieve this, it is known to introduce fiducial reference markers into the medical images. Stereotactic localizers are known for their use in determining a registration between the stereotactic space and the image space in stereotactic surgery. Probably the most wide-spread localizer design is the N-bar localizer by Brown. The Brown-Roberts-Wells stereotactic frame incorporates this N- localizer, see for example Brown RA, Roberts TS, Osborn AE: “Stereotaxic frame and computer software for CT-directed neurosurgical localization.” Invest Radiol. 1980, 15:308-312. Typically, three such N-shaped localizers are arranged at 120 degree steps on a stereotactic head- frame. Thus, the three localizers uniformly cover the stereotactic space. Tomographic 2D images or slices of the head to which this localizer is attached show sections of the vertical bars, and an elliptical section of the diagonal bar. The distance of the latter to the sections of the two vertical bars allows to determine the distance or depth of the imaged slice with respect to the boundaries of the localizer device. Another known design is based on a configuration of four V-shaped localizers, where the V-shape is divided by a vertical line. This configuration was originally developed for polar coordinates based Riechert-Mundinger type, RM, frames, and later adopted for the center-of- arc based Zamorano-Dujovny type, ZD, systems, which shared the head ring geometry with the RM system. These known localizers are integrated into four localizer plates, which are arranged in 90 degree steps on the stereotactic head frame. The known N-bar based and V-shape localizers feature several disadvantages. A large and psychologically frightening “cage” system accommodating the localizers has to be mounted to the patient's head for image acquisition. In several known implementations, the usable diameter of the stereotactic system is restricted to 22 cm, which is problematic and very uncomfortable for patients having a large head geometry. All fiducial markers in such known systems have a “bar” or rod/line form. No closed error theory exists for line fiducials. These known systems are only suited for 3D- to-3D registration, e.g., referencing stereotactic space coordinates with a computer tomographic (CT), image. They are not suited for 2D-to-3D registration, for example for additional registration of a two-dimensional X-Ray image. Due to the bar-shaped fiducials, automatic registration using computer-run algorithms is problematic, so that the accuracy of the systems is limited by the manual registration procedures and the shape of the fiducial markers. Some of the systems comprise several individual plates, each bearing a localizer device. All or at least three plates have to be mounted to the patient's head for registration. No registration is possible with fewer mounted plates, not even a registration having diminished accuracy. It has been proposed to use spherical or cylindrically shaped liquid-filled containers as fiducial markers in a stereotactic localizer device, wherein a configurable number of fiducial markers in a corresponding CT image may be detected by imaging software. Manipulation of a configurable number of fiducial markers by an operator or hospital staff represents a potential source of error which may lead to incorrect detection and registration, and ultimately to erroneous navigation of a surgical tool in the stereotactic space.

Technical problem to be solved It is an objective of the present invention to provide a device and method that overcome at least some of the disadvantages of the prior art.

Summary of the invention In accordance with a first aspect of the invention, a head-mountable device for introducing fiducial markers during radiological imaging of the head is provided. The device comprises head fixing means and a circumferential frame. The device is remarkable in that the frame comprises at least one pair of circumferentially spaced and mutually facing regions, wherein each region comprises receiving means for receiving a set of fiducial markers in predetermined positions, and wherein the arrangement of the predetermined positions is different within each region.

Preferably, the mutually facing regions within a pair may orthogonally project at least partially onto each other. Preferably, the frame may comprise at least one pair of opposing regions, which may preferably orthogonally project at least partially onto each other.

The frame may preferably comprise two pairs of opposing regions. The two opposing pairs of regions may preferably be arranged orthogonally with respect to each other along said circumferential frame.

Preferably, the arrangement of the predetermined positions in each region may be such that they do not orthogonally project onto the predetermined positions of a different region. Preferably, the arrangement of the predetermined positions in a first region of a pair is such that they do not orthogonally project onto the predetermined positions of the second region of said pair.

Preferably, the device may comprise a total of at least four predetermined positions for holding fiducial markers, wherein the arrangement of the predetermined positions is such that the respective orthogonal projections of fiducial markers held at these positions onto any imaging plane yields at least three distinct projection images.

Preferably, the receiving means may comprise a cavity in each of said predetermined positions. The geometry of the cavity may preferably be adapted for a corresponding fiducial marker to fit inside. Each region may preferably be defined by a fiducial marker holder that is removably coupled to said frame.

Further preferably, each region may be defined by a support that is integrally formed with said frame. According to another aspect of the invention, a set comprising at least one pair of fiducial marker holders adapted for being mounted to a head-mountable device is provided. Each fiducial marker holder defines a region having receiving means for receiving a set of fiducial markers in predetermined positions, wherein the arrangement of the predetermined positions is different for each fiducial marker holder.

The device may preferably comprise a set of fiducial markers for the receiving means of each region, wherein the fiducial markers of a set of fiducial markers are held in the predetermined positions of the respective receiving means.

Preferably, each set may comprise a plurality of fiducial markers.

Preferably, the fiducial markers comprise spherical fiducial markers.

Preferably, all fiducial markers may have the same dimensions, and a diameter comprised between 4 and 8 mm. Preferably, the diameter may be substantially equal to 6 mm.

The fiducial markers may preferably comprise titanium.

Preferably, the fiducial markers may be solid fiducial markers.

The head fixing means may preferably comprise a plurality of mounting screws.

In accordance with another aspect of the invention, a stereotactic frame is proposed, which comprises a localizer device. The stereotactic frame is characterized in that the localizer device conforms to aspects of the invention.

In accordance with a further aspect of the invention, a method for determining the spatial position of an imaged brain area with respect to a stereotactic localizer device is provide. The method comprises the following steps: i) providing a three-dimensional representation of at least part of a brain, wherein a device in accordance with aspects of the invention was attached to the corresponding head when the representation was acquired, so that said fiducial markers are included in said representation;

| LU101433 ii) using image processing means, detecting the positions of said fiducial markers in said representation; iii) using computing means, determining a position of said imaged brain area with respect to the pre-determined positions of said fiducial markers. 5 Preferably, the imaging processing and computing means may comprise a data processor configured for realizing the corresponding method steps. Preferably, said data processor may be configured by appropriately formulated software code. The first step i) may preferably further comprise: - attaching a device in accordance with aspects of the invention to a subject's head; - acquiring a three-dimensional radiological representation of said head including said device.

The method may further preferably comprise the preliminary step of providing a head-mountable frame and a set of fiducial marker holders in accordance with an aspect of the invention, attaching a set of fiducial markers to the receiving means of each fiducial marker holder, and attaching the latter to the head-mountable frame so that pairs of fiducial marker holders are circumferentially spaced and mutually facing.

The method may further preferably comprise the preliminary step of providing a head-mountable device in accordance with the first aspect of the invention, and attaching a set of fiducial markers to each of the device's receiving means at their respective predetermined positions.

The second step ii) may preferably comprise determining the position of the center of gravity of each fiducial marker.

Said representation may preferably be a three-dimensional computer-tomography image.

In accordance with yet another aspect of the invention, a computer program is provided. The computer program comprises computer readable code means, which, when run on a computer, causes the computer to carry out the method according to aspects of the invention.

In accordance with another aspect of the invention, a computer program product comprising a computer readable medium is provided, on which the computer program according to aspects of the invention is stored.

In accordance with a final aspect of the invention, a computing device comprising a memory element and a data processor is provided. The data processor is configured for carrying out the method according to aspects of the invention. The data processor preferably implements said image processing means and said computing means.

The proposed device allows for the introduction of fiducial markers, which are preferably spherical markers, during radiological imaging of the head. The provision of predetermined positions for all fiducial markers reduces the likelihood of wrongful use of the device by an operator. Indeed, fiducial markers may only be attached to predetermined positions in predetermined regions along the circumference of a stereotactic frame. These positions are known in advance, which facilitates registration of radiological images that are taken of a head to which the device is attached. By using fiducial markers that can be assimilated to a point, for example to their center of gravity, highly accurate automatic detection algorithms may be used, and both 2D and 3D image registration is enabled. Automatic detection of the fiducial markers increases the detection and registration accuracy as compared to known stereotactic N-localizer devices. At the same time, the suggested setup is considerably smaller than N-localizer based devices, thereby providing potentially better comfort and lower psychological stress to the patient who is to be imaged. Due to the large number of (point) fiducials, the provided design provides extremely low expected Target Registration Errors magnitude across the whole stereotactic space even when using only two localizer plates or regions supporting fiducial markers. The proposed device may for example accommodate a head having a diameter of up to 24 cm. The provision of removably coupled supports for the fiducial marker, or equivalently fiducial marker holders, allows for easy manipulation and mounting of the localizer device to a stereotactic base frame, which also decrease the risk of wrongful operation and the introduction of errors into the system.

Brief description of the drawings Several embodiments of the present invention are illustrated by way of figures, which do not limit the scope of the invention, wherein: - Fig. lis a schematic illustration of a top view on a transverse section of a device according to a preferred embodiment of the invention; - Fig. 2 is a schematic illustration of a top view on a transverse section of a device according to a preferred embodiment of the invention, including fiducial markers; - Fig. 3 is a perspective view of device according to a preferred embodiment of the invention; - Fig. 4 is a perspective view of a set of fiducial marker holders, including fiducial markers, in accordance with a preferred embodiment of the invention.

- Fig. Sa illustrates an arrangement of predetermined positions for fiducial markers of an anterior support region in accordance with a preferred embodiment of the invention; - Fig. 5b illustrates an arrangement of predetermined positions for fiducial markers of a posterior support region in accordance with a preferred embodiment of the invention; - Fig. Sc illustrates an arrangement of predetermined positions for fiducial markers of a left support region in accordance with a preferred embodiment of the invention; - Fig. 5d illustrates an arrangement of predetermined positions for fiducial markers of a right support region in accordance with a preferred embodiment of the invention; - Fig. 5e illustrates the mutual orthogonal projections of the arrangements of predetermined positions for fiducial markers on the facing support regions as shown in Figs. 5a and 5b respectively, in accordance with a preferred embodiment of the invention; - Fig. Sf illustrates the mutual orthogonal projections of the arrangements of predetermined positions for fiducial markers on the facing support regions as shown in Figs. 5¢ and 5d respectively, in accordance with a preferred embodiment of the invention; - Fig. 6 illustrates a workflow indicating the main method steps in accordance with a preferred embodiment of the invention.

Detailed description of the invention This section describes features of the invention in further detail based on preferred embodiments and on the figures, without limiting the invention to the described embodiments. Unless otherwise stated, features described in the context of a specific embodiment may be combined with additional features of other described embodiments. Throughout the description, similar reference numerals will be used for similar concepts or for the same concept across different embodiments of the invention. For example, reference numerals 100 and 200 both refer to a device in accordance with the invention.

In accordance with aspects of the invention, a head-mountable device is provided that allows to introduce a set of fiducial markers into a radiological image of a patient's head, wherein the image, for example a 3D computer tomographic image, is taken while the device including the fiducial markers is attached to the patient's head. The fiducial markers may have a variety of shapes, for as long as they may be approximated by a point. Preferably, all the fiducial markers are therefore ball shaped or substantially spherical, with a diameter of about 4 to 8, preferably of 6 mm. Tetrahedral or cube shaped fiducial markers, or a combination of shapes, may provide alternatives. The fiducial markers are made of a material that is well imaged in a computer tomographic image. While other materials may be used, the fiducial markers are preferably made of solid titanium.

A substantially ring-shaped frame, mountable around the patient's head, is made of a material that is transparent to radiological imaging.

The frame supports the fiducial markers in predetermined positions.

Providing predetermined positions facilitates the correct placement of the frame, and of the fiducial markers, relative to the patient's head.

This in turn facilitates the automatic detection of the fiducial markers and the computation of an accurate mapping between the reference coordinate system defined by the fiducial markers and the coordinate system of the stereotactic space.

Fig. 1 illustrates a preferred embodiment of device 100 in accordance with the invention, without limiting the invention to this embodiment.

A transverse section along a plane in which the device's elliptic frame 110 extends is shown.

The depicted frame comprises a pair 120 of mutually facing regions 130, 140, having receiving means 132, 142. As shown by the dashed lines rising up from section 140, the orthogonal projections of regions 130 and 140 overlap at least partially.

The receiving means in this embodiment are oriented inward towards the center of the frame 110, but other arrangements, for example outward facing receiving means, may also be considered without departing from the scope of the invention.

In the illustrated section, the receiving means 132 of the first region 130 are complementary shaped to accommodate a spherical and a cube-shaped fiducial marker.

The receiving means comprise for example a hollow having an at least partially surrounding lip on its inward face, which allows for click-inserting and retaining a fiducial marker therein.

As an alternative, the receiving means may comprise a seat or a chamber for accommodating fiducial markers, preferably closable by a closing mechanism, such as a door.

The receiving means are located at predetermined positions, in each of which a fiducial marker should be placed while imaging of the patient's head together with the device 100 is undertaken.

The arrangement of the predetermined positions in each region 130, 140 of the pair is different.

This allows an operator to quickly find the correct orientation of the device with respect to the patient's head.

The first region 130 may for example correspond to an anterior region of the head, while the second region 140 may correspond to a posterior region of the head.

Similarly, the differing arrangements of the predetermined positions of both regions allow a software implemented image processing algorithm to rapidly and reliably detect the orientation of the device's frame 110. While a total of four predetermined positions, shared among regions 130 and 140 are shown in Fig. 1,

this number of predetermined positions is not limiting of the invention.

A minimum of three predetermined positions should be provided by the device 100, while larger aggregate numbers of predetermined positions, and therefore fiducial markers, are also possible.

In Fig. 2, the same device 100 is shown, in which the set of fiducial markers 10, 11 have been attached to the receiving means 132 of the first region 130, and in which the set of fiducial markers 12, 13 have been attached to the corresponding receiving means 142 of the second region 140 of the mutually facing region pair 120.

Fig. 3 illustrates another preferred embodiment of a device 200 in accordance with the invention, without limiting the invention to this embodiment. A perspective view is shown. The depicted circular frame 210 comprises a first pair 220 of mutually facing regions 230, 240, having receiving means 232, 242. The receiving means define predetermined positions for receiving fiducial markers, which are shown as equally sized spherical fiducials 10. The frame 210 further comprises a second pair 250 of mutually facing regions 260, 270, having corresponding receiving means 262, 272 respectively. All regions 230, 240, 260, 270 are circumferentially spaced along the frame 210, while the pairs 220, 250 of mutually facing regions are arranged orthogonally with respect to each other. In this embodiment, the regions 230, 240, 260, 270 are defined by respective supporting plates, which are also referred to as fiducial marker holders. Each supporting plate extends in a plane that is orthogonal to the ring’s 210 plane. The supporting plates are each provided with a foot that is shaped so that it allows them to be fastened on the frame 210 by non-depicted fastening means such as screws or equivalent mechanical arrangements. By providing support regions 230, 250, 260, 270 that may be fitted with fiducial markers first, before being fitted themselves to the frame 210, and before the latter is finally fitted to the patient's head, accurate and less error-prone handling by an operator of the device 200 is facilitated. By way of example, the depicted receiving means comprise cylindrical hollows having a diameter that allows the insertion of the fiducial markers 10 therein. The receiving means are located at predetermined positions, in each of which a fiducial marker should be placed while imaging of the patient's head together with the attached device 200 is undertaken. The arrangement of the predetermined positions in each region within a pair of regions 220, 250 is different. This allows an operator to quickly find the correct orientation of the device with respect to the patient's head. The first region 230 of the first pair 220 may for example correspond to a right region of the head, while the second region 240 may correspond to a left region of the head. The first region 260 of the second pair 250 may for example correspond to an anterior region of the head, while the second region 270 may correspond to a posterior region of the head. Similarly, the differing arrangements of the predetermined positions of the regions allows a software implemented image processing algorithm to rapidly and reliably detect the orientation of the device's frame 210.

Fig. 4 illustrates another preferred embodiment of a set of fiducial marker holders in accordance with the invention, without limiting the invention to this embodiment. While the depicted set comprises two pairs of fiducial markers, this is not a limitation of the invention, and the use of different numbers of pairs of fiducial marker holders is in line with the present invention. A perspective view is shown. A first pair 320 of mutually facing fiducial marker holders defines regions 330, 340, having receiving means 332, 342. The receiving means define predetermined positions for receiving fiducial markers, which are shown as equally sized spherical fiducials 10. A second pair 350 of mutually facing fiducial marker holder defines regions 360, 370, having corresponding receiving means 362, 372 respectively. When mounted to a circumferential head- mountable frame, the regions defined by all holders 330, 340, 360, 370 are circumferentially spaced along the frame, while the pairs 320, 350 of mutually facing fiducial marker holders are arranged orthogonally with respect to each other. In this embodiment, the regions defined by the fiducial marker holders 330, 340, 360, 370 each comprise a respective supporting plate. Each supporting plate extends in a plane. The supporting plates are each provided with a foot that is shaped so that it allows them to be fastened on a circumferential head-mountable frame which is not shown in Fig. 4, using non-depicted fastening means such as screws or equivalent mechanical arrangements. When mounted to a circumferential head-mountable frame, each supporting plate extends orthogonally to the plane in which said frame extends. By way of example, the depicted fiducial marker holders comprise cylindrical hollows having a diameter that allows the insertion of the fiducial markers 10 therein. The receiving means are located at predetermined positions, in each of which a fiducial marker should be placed while imaging of the patient's head together with the attached circumferential frame is undertaken. The arrangement of the predetermined positions in each region within a pair of fiducial marker holders 320, 350 is different. This allows an operator to quickly find the correct orientation of the device with respect to the patient's head. The first region 330 of the first pair 320 may for example correspond to a right region of the head, while the second region 340 may correspond to a left region of the head. The first region 360 of the second pair 350 may for example correspond to an anterior region of the head, while the second region 370 may correspond to a posterior region of the head. Similarly, the differing arrangements of the predetermined positions of the regions allows a software implemented image processing algorithm to rapidly and reliably detect the orientation of the head-mountable device's frame. In order to avoid that one or more fiducial markers are eclipsed by the representations of another fiducial markers during imaging of the device, a particular arrangement of the predetermined positions should preferably be respected. As provided by the embodiment of Fig. 3, the arrangement of the predetermined positions in a first region 230, 260 of a pair 220, 250 is such that they do not overlap with, or orthogonally project onto the predetermined positions of the second region 240, 270 of the same pair. Further, the predetermined positions of different regions do preferably not involve symmetries, while the distances between predetermined positions within a region should be maximized. While a plurality of arrangements of the predetermined positions for the fiducial markers respect these conditions, and are equivalently applicable in the context of the invention, Figs. 5a to Sf illustrate a particular instance of such an arrangement in further detail, without limiting the invention to this example.

Fig. 5a shows the arrangement of predetermined positions of an anterior head region of a device in accordance with an embodiment of the invention, corresponding for example to the support 260 shown in Fig. 3. The support plate may correspondingly be optically marked with the letter “A”, as shown in dashed lines, so that an operator may identify the corresponding region quickly. The predetermined positions within a region are spaced far apart from each other. This facilitates their respective unique detection by automated detection means. Fig. 5b shows the arrangement of predetermined positions of a posterior head region of a device in accordance with the invention, corresponding for example to the support 270 shown in Fig. 3. The support may correspondingly be optically marked with the letter "P”, as shown in dashed lines, so that an operator may identify the corresponding region quickly. Fig. 5e is a representation of the respective orthogonal projections of the mutually facing regions shown in Figs. Sa and 5b respectively, onto each other.

The arrangement of the predetermined positions of the receiving means of these regions are clearly such that their projections do not overlap or eclipse each other. Fig. Sc shows the arrangement of predetermined positions of a left head region of a device in accordance with the invention, corresponding for example to the support 240 shown in Fig. 3. The support may correspondingly be optically marked with the letter “L”, as shown in dashed lines, so that an operator may identify the corresponding region quickly. This facilitates their respective unique detection by automated detection means. Fig. 5d shows the arrangement of predetermined positions of a right head region of a device in accordance with the invention, corresponding for example to the support 230 shown in Fig. 3. The support may correspondingly be optically marked with the letter "R”, as shown in dashed lines, so that an operator may identify the corresponding region quickly. Fig. 5fis a representation of the respective orthogonal projections of the mutually facing regions shown in Figs. 5c and 5d respectively, onto each other. The arrangement of the predetermined positions of the receiving means of these regions are clearly such that their projections do not overlap, and so that representation of fiducial markers held in these predetermined positions, do not eclipse each other. Of course, other arrangements of predetermined positions for the fiducial markers, representing other letters reminiscing similar concepts, may equally be used without departing from the scope of the invention. The easily discernible arrangements may for example reflect other linguistic cues or letter from different alphabets.

In all of the above embodiments, the device may further comprise non-illustrated head-mounting means which are known in the art, such as mounting screws that are adapted to attach the frame rigidly to the patient's skull.

Fig. 6 shows the main method steps in accordance with a preferred embodiment of the invention.

For determining the spatial position of an imaged brain area with respect to a stereotactic localizer device in accordance with aspects of the invention an as described here above, the method comprises the following steps:

i) providing a three-dimensional representation, for example a computer tomographic radiological image, of at least part of a brain, wherein a device in accordance with aspects of the invention was attached to the corresponding head when the representation was acquired, so that said fiducial markers are included in said representation; ii) using image processing means, for example using an appropriately programmed data processor, detecting the positions of said fiducial markers in said representation; the data processor may for example detect the contours of the spherical fiducial markers based on a threshold grey value, as the fiducial markers made of titanium lead to dark spots in the image; iii) using computing means, determining a position of said imaged brain area with respect to the predetermined positions of said fiducial markers. This preferably comprises computing a transform that maps the coordinates of the reference space as define by the detected fiducial markers, to a coordinate system of the stereotactic space.

The device in accordance with aspects of the invention is first attached to a subject's head; then the acquisition of a three-dimensional radiological representation of said head including said attached device if performed.

In accordance with a preferred embodiment of the method in accordance with the invention, the second step of the method comprises determining the position of the center of gravity of each fiducial marker.

Grunert et al. (“ Accuracy of stereotactic coordinate transformation using a localisation frame and computed tomographic imaging”, Neurosurg. Rev., 22 (4) (1999), pp. 173-187) suggested to use the intensity weighted center-of-gravity for the detection of fiducial rod center lines in CT imaging. They noted that for cylinder shaped rods, with rotational symmetric intersections, the accuracy of these methods is below the voxel size. Furthermore, they reported the accuracy of the method to be only weakly dependent on the slice thickness, as a larger slice thickness leads to a symmetric partial voluming effect in rotational symmetric fiducials that is effectively cancelled by the center- of-gravity based method.

In their study, using CT imaging with comparable in-plane resolution to nowadays scanners (matrix size up to 512x512, field-of-view set to cover a stereotactic localizer frame), they found an accuracy of approximately 125 pm, one tenth of their slice thickness of 1.25 mm. They measured accuracy by predicting a shift of the z coordinates in stereotactic CT, i.e. CT scans with the localizer frame aligned with the scanner gantry. The precision of 125 pm is in the range of the accuracy of the CT movement, thus the algorithmic precision might be even better but not detectable due to measurement errors of this method.

While cylindrical fiducials have the advantage of independence to slice thickness (within realistic thickness bounds), they have the strong disadvantage of only yielding two coordinates, in expression the x and y coordinate in stereotactic CT.

Interestingly, for a reasonable slice thickness, in particular, smaller than the ball radius, the inventors have found it to be possible to introduce a 3D variant of the center-of-gravity based algorithm allowing to infer x, y and z coordinate from ball fiducials with very high accuracy.

Note that for the center-of-gravity method the input image is without loss of generality assumed to contain only positive values. If an image intensity range contains negative values, all intensities could be shifted into the positive half-space by adding an appropriate bias term to all intensity values, e.g. a value of 1024 for typical CT scans.

In order to present results relating to the proposed method, it is important to note that three different error terms are often not clearly differentiated in the literature; however, they measure distinct phenomena and feature different properties.

First, Fiducial Localization Error, FLE, states the distance between the true position of a fiducial marker and the detected position. Often fiducial markers have to be detected in two spaces involved in the registration. For example, consider fiducial screws attached to the skull used to drive a registration of a CT image of a head to instruments tracked in the physical space. In this case FLE appears at the detection of the fiducials in the CT image as well as at the detection procedure in the physical space (e.g. by touching the fiducial screw heads with a tracked pointer device). However, for modeling purposes it is standard to assume one space as noise free and shift the error to the other space. This trick greatly eases analytic treatment. It is common to report the expected FLEs over all fiducials, summarizing fiducial detection accuracy in one scalar. The expected (absolute) FLE is often denoted by (FLE) and the expected squared (FLE?) is commonly reported.

For in depth analysis it might be useful to analyse not only a scalar FLE quantity over all fiducials, but the displacement vector of each individual fiducial from its true position. For a set of N fiducials with indexes i = /, ..., N the vectorial FLE for each fiducial is typically reported as FLE; : N — R¥. While FLE distributions may be easily modeled in simulations, the particular instance of FLE that is realized in a particular task is unobservable.

Second, the Fiducial Registration Error, FRE, states the goodness of fit between two homologous point sets x, y after rigid registration. It is therefore defined as the mean squared difference between

14 ; LU101433 the point pairs after x was transformed to match y resulting in x. For the homologous point pairs ( Xi yD it then holds FRE? = 32%; - vl Note that the term FRE is often used synonymous for FRE2 as reporting of squared quantities was typical for the original papers by Fitzpatrick et al. However, in certain situations the root mean squared difference is indeed considered in the sense of FRE = JFRE?. Thus, the definition used should be checked carefully when comparing different literature. In an analogous way as for the FLE, the FRE could be reported as a vectoral quantity of individual displacement vectors between registered points. For a set of N fiducial pairs (Xp Y;) with indexes i = 1, ..., Nthe vectorial FRE for each fiducial is could be defined as FRE; = Xi — y, However, in certain situations one might be interested in the magnitude of displacement, i.e. the length of the displacement vectors FRE, = |; - villa- Again, the precise definition used has to be carefully checked.

Third, the target registration error, TRE, might be considered as the most important quantity. TRE is the quantity relevant for the user of a registration system, as it measures the registration error at a point in space. TRE is spatially varying, thus the calculation of a single "average" TRE value for a registration task bears the danger of losing important information. À notation making this dependence to a "target" point under consideration explicit is TRE(p), where p € R° for the typical 3D registration problem in image guided surgery. The presentation of a first-order approximation for the expected value of TRE by Fitzpatrick, West and Maurer in IEEE Trans Med Imaging. 1998 Oct;17(5):694-702, "Predicting error in rigid-body point-based registration”, thus was a cornerstone for image guided procedures.

The expected accuracy was evaluated using a target registration error simulation environment developed for this work. Results for an r.m.s. fiducial localization error of 1 mm indicate that for a setup of two opposing pairs of regions having spherical fiducial markers, a TRE lower than 0.3 mm is achieved over the entire stereotactic space. For a single pair of mutually opposing regions, a minimum of 0.39 mm is observed at the center, while the TRE increases to the sides that do not bear fiducial markers to about 1 mm. Even if only one plate is used, a local minimum of 0,75 mm is observed in the vicinity of the fiducial markers. As ball-shaped fiducial significantly larger than the slice-thickness of a CT image could be detected automatically with very high precision, the expected FLE for the 6 mm titanium balls is much lower. The values in the figure can be linearly scaled by multiplying with the expected FLE. FLE is an unobservable quantity. However, the expected FLE for a specific setup could be estimated from repeated FRE measurements. Given the measured FRE data from a phantom, which uses the same type of ball fiducials, the r.m.s.s. FLE could be estimated to approximately 0.1 mm when using the center-of-gravity algorithm on CT with 0.5 mm slice-thickness. Furthermore, for balls of 6 mm diameter each point within the enclosing sphere is less than 3 mm distant to the ball center. Thus, the maximum possible FLE is bounded by 3 mm for any method that is accurate enough to detect the center somewhere within the true ball.

The suggested device and method in accordance with embodiments of the invention, are not only applicable for stereotactic planning, but further enable 2D/3D registrations, e.g. to align 2D-Xray images with stereotactic planning data. By registering post-operative data to the stereotactic planning the 2D/3D registration is also usable to align 2D data with post-operative 3D datasets. Thus, the proposed system is well suited to combine additional 2D information with 3D electrode reconstructions produced by the PaCER method (https://adhusch.github.io/PaCER/stable/). It is interesting to note that this usage of the proposed system is possible without requiring that the stereotactic planning was done with the system itself. Instead stereotactic planning could be done using standard localizer plates (for example N-shaped localizers), which is a necessity because newly proposed alternatives are now not yet available as a registration option in the approved planning software. However, immediate post-operative X-Ray with the stereotactic base frame still mounted (as it is recommended and approved by the vendors of directional leads) could be carried out with the proposed device mounted to the frame. A registration of the X-ray to the 3D space is possible as the (virtual) position of the proposed device's fiducials in the frame-space are known, even without them present in the CT image. The only drawback of this method is that the accuracy of the positions is affected by the standard plates used to define the frame-space to CT image space relation.

The methods outlined here above are preferably implemented using processing means such as a data processor, for example a central processing unit, CPU, of a computing device which is appropriately programmed, or by specific electronic circuitry, as it is known in the art. The skilled person is capable of providing such programming code means or circuitry providing the required functionality based on the description that has been given, based on the drawings and without undue further burden. It should be understood that the detailed description of specific preferred embodiments is given by way of illustration only, since various changes and modifications within the scope of the invention will be apparent to the skilled person. The scope of protection is defined by the following set of claims.

The work leading to this invention has received support from the Fonds National de la Recherche, FNR, in Luxembourg under grant No.

AFR 5748689.

Claims

1. A head-mountable device (100, 200) for introducing fiducial markers (10, 11, 12, 13) during radiological imaging of the head, comprising head fixing means and a circumferential frame (110, 210), characterized in that the frame comprises at least one pair (120; 220, 250) of circumferentially spaced and mutually facing regions (130,140; 230,240; 260, 270) , wherein each region comprises receiving means (132,142; 232,242,262, 272) for receiving a set of fiducial markers in predetermined positions, and wherein the arrangement of the predetermined positions is different within each region.

2. The device (200) according to claim 1, wherein the frame (210) comprises two pairs of opposing regions (230,240; 260,270).

3. The device (100, 200) according to any of claims 1 or 2, wherein the arrangement of the predetermined positions in a first region (130; 230,260) of a pair (120; 220,250) is such that they do not orthogonally project onto the predetermined positions of the second region (140; 240,270) of said pair.

4. The device according to any of claims 1 to 3, wherein each region (230,240,260,270) is defined by a fiducial marker holder that is removably coupled to said frame.

5. A set comprising at least one pair of fiducial marker holders adapted for being mounted to a head-mountable device, each fiducial marker holder (330, 340, 360, 370) defining a region having receiving means (332,342,362, 372) for receiving a set of fiducial markers in predetermined positions, wherein the arrangement of the predetermined positions is different for each fiducial marker holder.

6. The device or set according to any of claims 1 to 5, wherein the receiving means (132,142; 232,242,262,272) comprise a cavity in each of said predetermined positions.

7. The device or set according to any of claims 1 to 6, comprising a set of fiducial markers (10, 11, 12, 13) for the receiving means of each region, wherein the fiducial markers of a set of fiducial markers are held in the predetermined positions of the respective receiving means.

8. The device or set according to claim 7, wherein each set of fiducial markers comprises a plurality of fiducial markers.

9. The device or set according to any of claims 7 or 8, wherein the fiducial markers comprise spherical fiducial markers.

10. The device or set according to claim 9, wherein all spherical fiducial markers have the same dimensions, and a diameter comprised between 4 and 8 mm.

11. The device or set according to any of claims 7 to 10, wherein the fiducial markers comprise titanium.

12. The device or set according to any of claims 7 to 11, wherein the fiducial markers are solid fiducial markers.

13. The device according to any of claims 1 to 4 or 6 to 12 wherein the head fixing means comprise a plurality of mounting screws.

14. A stereotactic frame comprising a localizer device (100, 200), characterized in that the localizer device conforms to any of claims 1 to 13.

15. A method for determining the spatial position of an imaged brain area with respect to a stereotactic localizer device, the method comprising the following steps: i) providing a three-dimensional representation of at least part of a brain, wherein a device in accordance with any of claims 7 to 13 was attached to the corresponding head when the representation was acquired, so that said fiducial markers are included in said representation; ii) using image processing means, detecting the positions of said fiducial markers in said representation; iii) using computing means, determining a position of said imaged brain area with respect to the pre-determined positions of said fiducial markers.

16. The method according to claim 14, wherein the first step comprises - attaching a device in accordance with any of claims 7 to 13 to a subject's head; - acquiring a three-dimensional radiological representation of said head including said device. |

17. The method according to any of claims 15 or 16, wherein the second step comprises determining the position of the center of gravity of each fiducial marker.

18. The method according to any of claims 15 to 17, wherein said representation is a three- dimensional computer-tomography image.

19. A computer program comprising computer readable code means, which, when run on a computer, causes the computer to carry out the method according to any of claims 15 to 17.

20. A computer program product comprising a computer readable medium on which the computer program according to claim 19 is stored.

21. A computing device comprising a memory element and a data processor, wherein the data processor is configured for carrying out the method according to any of claims 15 to 18.