NL2032802B1

NL2032802B1 - MRI compatible robotic device for ablation treatment

Info

Publication number: NL2032802B1
Application number: NL2032802A
Authority: NL
Inventors: Abayazid Momen; Wardhana Girindra; Jacobus Futterer Johannes
Original assignee: Univ Twente
Priority date: 2022-08-18
Filing date: 2022-08-18
Publication date: 2024-02-27
Also published as: WO2024039245A1

Abstract

MRI compatible robotic device for Ablation Treatment, wherein said robotic device comprises: - a base member for placement on an outer skin surface of a human body; - a needle holding member for holding at least two needles; - a positioning system for moving the needle holding member with respect to the base member in at least two degrees of freedom for positioning the at least two needles at any orientation and at any location within an area of the outer skin surface of the human body that is covered by the robotic device.

Description

MRI compatible robotic device for ablation treatment

The present invention relates to a MRI compatible robotic device for ablation treatment, in particular Frreversible Electroporation (IRE) treatment.

Ablation treatment is used for ablating, and thereby destroying, tumors in liver, lungs, pancreas, and kidney in human beings. Irreversible Electroporation treatment (IRE) has been evolving as an alternative technique for conventional thermal treatments such as radiofrequency ablation, microwave ablation, cryoablation etc.

Some minimally invasive ablation techniques which are used to treat tumors are Radio Frequency

Ablation (RFA), Micro-Wave Ablation (MWA) and Cryo-Ablation (CA). Though these methods are useful and safe to use, they are accompanied by primary defects, caused by the fact that the ablation is typically performed with the application of heat or cold. By using thermal energy, radio frequency ablation and microwave ablation are found to cause damage to the structure adjacent to the tumor tissue. In cold techniques such as cryoablation, the extremely low temperature used to treat tumors is found to cause extensive exposure times, even to ablate smaller tumor masses.

Irreversible Electroporation (IRE) is one of the minimally invasive ablation techniques which uses neither high nor low temperature extremities, preventing damage to the structures adjacent to the tumor tissues. IRE is a unique and non-thermal technique that is used to treat tumors in the prostate region, liver, pancreas and kidney. The treatment process involves the application of electric pulses of differing strength within a period of few seconds to destroy the cell membranes of the tumor cells. It has been considered as a convenient procedure in treating complex tumors that involve crucial structures in the liver, pancreas and kidney

IRE technique is administered by inserting the needles manually around the tumor area using image guidance process such as Magnetic Resonance Imaging (MRI), ultrasound, etc. The needles must be carefully placed at the appropriate position to enable equal distribution of electric field around the tumor which requires a highly skilled operator. High voltage pulses are passed between the needles to kill the tumor cells. To enable a successful treatment, certain parameters like position, distance between the needles, parallelism and depth of insertion must be carefully determined before the start of the treatment.

To achieve a successful ablation, the treatment is carried out by inserting needles in perfect parallel arrangement, at a pre-defined distance that varies between 1 and 2.5 cm around the tumor mass.

The needles are typically inserted manually by operators with the help of Magnetic Resonance

Imaging. Accurate needle placement around the tumor is essential to destroy it completely, which means that a manual placement operation is typically ineffective. When more than two needles are used, several attempts may be required for surgeons to properly place the needles around the tumor in parallel position, at a pre-defined distance. This leads to a decrease in the success rate of the ablation, which ultimately results in an increase of the total treatment duration.

It is an object of the invention to alleviate at least a part of the above mentioned problems.

Specifically, it is an object of the invention to improve the placement accuracy of the needles used in ablation treatment, more in particular in Irreversible Electroporation treatment (IRE).

Thereto, the invention provides a MRI compatible robotic device for ablation treatment, in particular Irreversible Electroporation (IRE) treatment, wherein said robotic device comprises: - a base member for placement on an outer skin surface of a human body; -aneedle holding member for holding at least two needles; - a positioning system for moving the needle holding member with respect to the base member in at least two degrees of freedom for positioning the at least two needles at any orientation and at any location within an area of the outer skin surface of the human body that is covered by the robotic device. In particular, the positioning system is arranged for simultaneously positioning the at least two needles in parallel at any orientation and at any location within the area

Tumor ablation treatments like prostate biopsies, RFA, microwave ablation and brachytherapy use single and multiple needle insertion techniques to treat tumors. The needle can be inserted into the target lesion through Computed Tomography (CT) or ultrasound image guidance for ablation.

Nonetheless, these procedures face some obstacles while treating residual tumors as they need multiple ablations while treating tumors in the adjacent vessels. This creates additional processing of image guidance by emitting more ionization radiation to the patients for tumor ablation. To overcome these issues, Magnetic Resonance Imaging (MRI) has been found to be a better replacement for other imaging methods. It provides accurate images with real time monitoring of tumor ablation because of its high capability of defining solid tumors like carcinomas and sarcomas in soft tissue contrasts. For this, the robotic device is positioned on an outer skin surface of a (human) body and the imaging step is performed with the robotic device positioned on the body, such that the location of the tumor with respect to the robotic device can be obtained.

As such, it is preferred that the robotic device is MRI compatible, although this is not essential in case other imaging techniques are uses. This disclosure thus also covers the robotic device which is not necessarily MRI compatible.

The robotic device can thereby aid in the process of inserting the needles, which are also commonly referred to as probes, in the correct positions and orientations, such that a successful ablation treatinent can be performed. This is done, as is described above, using the imaging techniques, preferably MRI, for identitying the size and/or location tumor. On the basis of these data, the optimal positions and/or orientations of the needles can be determined. The robotic devices than aids in positioning the needles in the correct position and orientation. The needle holder can then be configured for guiding the needles during the insertion step, by an operator, of the needles into the body. As noted above, a (virtually) perfect parallel placement of the needles improves the quality of the IRE treatment.

In a preferred embodiment, the first degree of freedom of the positioning system is defined by a rotation of the needle holding system around a central axis that is perpendicular to a lower contacting surface of the base member, wherein, when in use, the lower contacting surface of the base member is substantially parallel to a tangential plane of the area of the outer skin surface of the human body that is covered by the robot. This enables a compact robot-arrangement that can reach locations within the area of the outer skin surface of the human body that is covered by the robotic device. lt is preferred that the second degree of freedom of the positioning system is defined by a rotation of the needle holding system around a pitch axis that is substantially perpendicular to the central axis. This enables a compact robot-arrangement that can orient the needle holder with respect to (a tangential surface) of the outer skin surface within the area of the outer skin surface of the human body that is covered by the robotic device.

Preferably, the positioning system is further arranged for moving the needle holding member with respect to the base member in a third degree of freedom, wherein said third degree of freedom is defined by a translation of the needle holding system in a first translational direction having at least a component that is substantially perpendicular to the central axis. This allows a greater freedom of the robotic device to achieve the desired orientation and position of the needles to be inserted.

Ttis preferred that the positioning system is further arranged for moving the needle holding member with respect to the base member in a fourth degree of freedom, wherein said fourth degree of freedom is defined by a translation of the needle holding system in a second translational direction having at least a component that is substantially perpendicular to the central axis and that is substantially perpendicular to the first translational direction. Hereby, any position and orientation (within the predefined area) of the needles to be placed can be achieved in a straightforward manner.

In a preferred embodiment, the positioning system comprises a stacked stage system, wherein the stacked stage system is movable with respect to the base member, wherein the stacked stage system comprises: - a first stage that is arranged to be driven in the first degree of freedom, in particular arranged to be rotationally driven around a central axis that is perpendicular to a lower contacting surface of the base member; - an upper stage that is coupled to the first stage and arranged to be driven by the first stage in the first degree of freedom, wherein the upper stage is movable with respect to the first stage in a second degree of freedom, in particular wherein the upper stage is rotatable with respect to the first stage around a pitch axis that is substantially perpendicular to the central axis, wherein the pitch axis is movable in the first degree of freedom with the first stage; - wherein said needle holding member is connected to the upper stage; - preferably, driving means for driving the respective stages of the stacked stage system;

The stacked setup of the positioning system allows to create a compact positioning system with the desired number of degrees of freedom. Furthermore, simple movements of single stages combine to obtain the desired total freedom of movement and orientation of the needles in the needle holder.

It is then further preferred that the stacked stage system further comprises: - a first intermediate stage that is arranged in between the first stage and upper stage, wherein the first intermediate stage is arranged to be driven by the first stage in the first degree of freedom, wherein the first intermediate stage is movable with respect to the first stage in the third degree of freedom, in particular wherein the first intermediate stage is arranged to be movable with respect to the first stage in a first translational direction having at least a component that is substantially perpendicular to the central axis: and wherein the upper stage is rotatable with respect to the first intermediate stage around a pitch axis that is substantially perpendicular to the central axis, wherein the pitch axis is movable with the first intermediate stage in the third degree of freedom. Hereby, an additional stage having a relatively simple movement, greatly enhances the performance of the total robotic device, while still remaining compact enough to fit, for instance, the bore of an MRI system.

For a similar reason it is then even further preferred that the stacked stage system further comprises: - a second intermediate stage that is arranged in between the first intermediate stage and the upper stage, wherein the second intermediate stage is arranged to be driven by the first stage in the first 5 degree of freedom and arranged to be driven by the first intermediate stage in the third degree of freedom, wherein the second intermediate stage is movable with respect to the first intermediate stage in the fourth degree of freedom, in particular wherein the second intermediate stage is arranged to be movable with respect to the first intermediate stage in a second translational direction having at least a component that is substantially perpendicular to the central axis and that is substantially perpendicular to the first translational direction; and wherein the upper stage is rotatable with respect to the second intermediate stage around a pitch axis that is substantially perpendicular to the central axis, wherein the pitch axis is further movable with the second intermediate stage in the fourth degree of freedom.

Preferably, the pitch axis is arranged to be substantially parallel to the first translation direction, or wherein the pitch axis is substantially parallel to the second translational direction. Hereby, the respective motions are independent, such that the compact positioning system is obtained that is furthermore relatively easy to control using forward kinematics.

Itis preferred that the positioning system, in particular said driving means of the first stage, comprises a first rotational drive for driving the needle holding member in the first degree of freedom; preferably wherein said first rotational drive comprises a first motor, preferably a stepper motor, and pinion, wherein said pinion engages a cylindrically shaped gear track that is arranged on the base member. This allows for a compact arrangement that is furthermore relatively easy to control using forward kinematics. Preferred types of drives for use in the positioning system are, for instance, those comprising hydraulic, pretnatic, plezoelectrie and/or ultrasonic actuators, 4s these are typically MRI compatible.

Preferably, the positioning system, in particular said driving means of the first intermediate stage, comprises a first linear drive for driving the needle holding member in the third degree of freedom.

Alternatively, or additionally, the positioning system, in particular said driving means of the second intermediate stage, comprises a second linear drive for driving the needle holding member in the fourth degree of freedom. This also enables a compact arrangement that is furthermore relatively easy to control using forward kinematics.

In a preferred embodiment, the positioning system, in particular said driving means of the upper stage, comprises a second rotational drive for driving the needle holding member in the second degree of freedom; preferably wherein the needle holding member is arranged to pivot with respect to base member around a pivoting point. The desired orientation of the needle module, and thereby, in use, the plurality of needles in said holder, can be easily set by the robotic device.

Preferably, the second rotational drive comprises a third linear drive that is arranged to have a respective third linear driving direction that is substantially perpendicular to the pitch axis and wherein said third linear drive is spaced apart from the pitch axis in a direction that is perpendicular with respect to the third linear driving direction and that is perpendicular with respect to the pitch axis, such that the needle holding member is arranged to rotate around the pivot axis upon driving the third linear drive. By driving the linear motor back and forth, the pitch angle of the needle holder is varied. The relation between a linear distance traveled and a change in the pitch angle is determined by the, predefined, geometry of the robotic device, in particular the positioning system, such that it can be controlled using relatively simple forward kinematic control.

It 1s further preferred that the second rotational drive comprises a fourth linear drive that is arranged to have a respective fourth linear driving direction that is substantially parallel to the third linear driving direction and wherein said fourth linear drive is spaced apart from the third linear drive in a direction that is perpendicular with respect to the third and fourth linear driving directions and that is perpendicular with respect to the pitch axis, such that the needle holding member is arranged to pivot around the pivot axis upon non-synchronously driving the third and fourth linear drives. Using the fourth linear drive, the linear motion parallel to the third and fourth linear drives and rotation motion around the pitch angle can be controlled independent from one and another, such that a greater freedom of motion of the needle holder is obtained.

It is then even further preferred that one of said third and fourth linear drives is one of said first and second linear drives, such that a more compact positioning system is obtained. Due to the limited space inside the bore of an MRI apparatus, a compact system is preferred.

In a preferred embodiment, the needle holding member is arranged for holding two or more spaced apart needles, wherein said holding member comprises an array of needle holding positions that are adjacent to, and spaced apart from, each other in an at least one-dimensional, preferably linear, array, preferably said holding member comprises an array of needle holding positions that are adjacent to, and spaced apart from, each other in a two-dimensional, preferably linear, grid,

preferably having a plurality of rows and columns. Such a one, or two, dimensional array allows for positioning the respective needles at predefined distances and/or orientations with respect to each other, such that the needle holding member only has to be oriented a single time, at which point the respective needles can be inserted, in the correct locations and orientation, at once by the operator.

Preferably, the needle holding member is removably coupled to the robotic device. This allows to used different needle holding members having, for instance, one-, or two-, dimensional arrays having different configurations in terms of spacing (i.e. distance between the respective needles) and layout (linear array, curved array, etc.), that can be specific to the treatment and/or patient.

It is preferred that the needle holding member comprises a grid holding frame that is arranged for removably holding one or more needle holding grids, wherein a more needle holding grid comprises a plurality of openings forming needle holding positions. Like above, this also allows to modify the needle-arrangement in the needle holding device.

Preferably, the robotic device has a maximum height, as seen in the direction of the central axis, of no more than 350 mm. preferably no more than 250 mm. Hereby, the robotic device fits the majority of MRI devices.

In a preferred embodiment, the area that is covered by the robotic device is between 0.0025 m2 - 0.09 m2, preferably 0.01 m2 — 0.05 m2, more preferably 0.02 m2 - 0.04 m2. This allows to cover a typically sized tumor, while limiting the dimensions, such that the robotic device remains suitable to be positioned on the human body and fits the majority of MRI devices.

The robotic device is preferably made from, preferably only, nonmetallic, non-magnetic and non- conductive materials and/or wherein said robotic device is MR safe according to the ASTM F2503 standard. Hereby, the robotic device can be used inside of an MRI device while having only a limited and acceptable effect on the imaging results of the MRI device. Preferably materials for making the robotic device are plastics and non-magnetic metals such as titanium, aluminum, brass, copper, bronze and/or aluminum bronze alloys.

In a second aspect, the invention relates to a method of ablation treatment, in particular irreversible electroporation (IRE) treatment, comprising the steps of: - determining a treatment area of the body of a patient using an imaging device, such as a magnetic resonance imaging device;

- providing a robotic device according to any of the preceding claims on a treatment area of the body of a patient; - positioning, using the robotic device, a needle at an insertion position in the treatment area; - inserting said needle in the insertion position.

The present invention is further illustrated by the following figures. which show preferred embodiments of the robotic device according to the invention, and are not intended to limit the scope of the invention in any way, wherein: - Figure 1 shows an upper three-dimensional perspective view of a first embodiment of the robotic device according to the invention. - Figure 2 shows a lower three-dimensional perspective view of the first embodiment of the robotic device according to the invention. - Figure 3 shows a cross-sectional view of the first embodiment of the robotic device according to the invention. - Figure 4 schematically shows the functioning of a gear rack stepper motor as applied in the first embodiment of the robotic device. - Figure 5 shows an upper three-dimensional perspective view of a second embodiment of the robotic device according to the invention. - Figure 6 shows an upper three-dimensional perspective view of a third embodiment of the robotic device according to the invention. - Figure 7 shows, in different views, joint motion of the third embodiment of the robotic device, with (al) top view showing (a2) translation motion in x axis by motor ¢1 and (a3) rotation motion in z axis by motor g4: (b1) side view showing two translation motion in y axis for (b2) motor g2 and (b3) motor g3, combined translation for pitch motion in the robotic device according to the invention. - Figure 8 shows a diagram showing the geometry of the robot in the y-z plane. Initial reference configuration of the first embodiment robotic device is shown in the left subimage, where the needle is located at the center of the workspace pointing straight downwards, using actuator configuration g = [q1, q2. q3. q4]T = [0, 0, 0, O]T. The orientation of the needle around the x axis is adjusted by the motion of motor q2 and q3 in the y axis as shown in the right subimage. - Figure 9 shows an overview of eight target positions (blue circle) that was located under the first embodiment of the robotic device based for accuracy test. - Figure 10 shows MR images of the abdominal phantom during tumor targeting test with the first embodiment of the robotic device;

- Figure 11 shows MR images (for the first embodiment of the robotic device) of the phantom plastic bottle in three operating condition with T1 and T2 image sequence. The ROI for signal and noise is represented by blue circle and red squares respectively.

Figures 1 - 3 show a first embodiment of the robotic device 100 according to the invention in different views. The robotic device 100 is seen to comprise a base member 101 for placement on an outer skin of a human body, having a lower contacting surface 116 for abutting the outer skin, and further comprises a positioning system 102 for moving the needle holding member 103. The needle holding member 103 comprises a grid holding frame 104, holding a number of removable (i.e. replaceable) needle holding grids 105 in a number of grid receiving sections 109, that is arranged to pivot, with respect to the base member 101 around the pivot axis II, thereby enabling the second degree of freedom of the robotic device 100. The positioning system 102 is preferably arranged with a second rotational drive (not shown) for driving this pivoting, i.e. rotational, motion. The needle holding grids 105 comprise a plurality of needle holding positions 106 that are arranged in two-dimensional arrays having a number of rows and columns. It is noted here that the grid does not have to be a rectangular shape, but any (irregular) shape is possible. The needle holding positions 106, that are arranged as through-holes for guiding needles (not shown in figure 1) used for the ablation treatment, are arranged in linear grid, such that the respective holes are evenly spaced apart.

At least the orientation of the needles can be changed, by pivoting the holding member 103. For this purpose, the positioning system 102 can be arranged with a second rotational drive 107, such that the second rotational drive 107, in combination with the needle holding member 103, effectively forms the top stage 108 of the positioning system 102. The base member 101 is further seen to comprise mounting brackets 110 for connecting straps and/or other mounting means (not shown) for securing the robotic device 100 to the patient. shows a lower three-dimensional perspective view of the robotic device 100 of figure 1, wherein a cover of the first rotational drive 111 is not shown to enable a view on the active components of the rotational drive 111. A gear rack stepper motor 112 and circular gear rack 113 comprising a plurality of protruding teeth are comprised in the rotational drive 111. The circular gear rack 113 is movably, i.e. rotatably, arranged within the base member 101. The gear rack stepper motor 112 is composed of two actuators 114 surrounded by a housing 115 that pushes against the gear rack 113.

The gear rack 113 is a wedge mechanism comprised of tiny teeth, preferably of 2.5 mm, on both sides. The tooth size of the wedge mechanism is what determines the step resolution. The teeth provide actuator’s grip to progress into different states, which then move the first rotational drive 111 forward or backwards.

The actuators 114 can be any type of linear actuators (i.e. hydraulic, piezo-electric, etc.) that is MR compatible. In the current example, the actuators are pneumatic actuators, in which case they comprise two pistons having four housing chambers. Two chambers are needed for each piston, with one residing on the top and one on the bottom. The housings of the actuators 114 are pressurized in an orderly manner by having each piston move back and forth in the double-acting cylinder. This is done to create the stepping movement that moves the first rotational drive 111 forward and backwards. Only one piston, the one which was pressurized formerly, can be fully engaged to the rack. During movement, the most recently pressurized piston temporarily releases its grip, allowing the other piston to fully engage to the gear rack 113. From this motion, five consecutive gear rack stepper motor can be identified exist in the stepper motor, which are shown in figure 4.

The circular gear rack 113 is connected to a circular shaped first stage member 117, such that, upon driving the first rotational drive 111, the circular shaped first stage member 117 rotates, with respect to the base member 101, around the central axis I, that is substantially perpendicular to the lower contacting surface 116 of the base member 101, thereby enabling the first degree of freedom of the robotic device. The first stage 118 of the positioning system 102 is thereby formed by the circular gear rack 113 that is movably arranged in base member 101, the first rotational drive 111 and the circular shaped first stage member 117 that is coupled to the circular gear rack 113. The robotic device 100 is thereby movable in two degrees of freedom for positioning multiple needles at any orientation and at any location within an area of the outer skin surface of the human body that is covered by the robotic device. Any lack of translational degrees of freedom of the positioning system in the plane parallel to the lower contacting surface 116 is overcome in the specific example by the use of the needle holding grids, allowing to position the needles at any location within the area of the outer skin surface of the human body that is covered by the robotic device, by carefully selecting the correct needle holding (and/or guiding) position 106.

Figure 5 shows an upper three-dimensional perspective view of a second embodiment of the robotic device 200 according to the invention, wherein the base member 101 and the first stage 118 are identical to the respective parts in the robotic device 100 according to the first embodiment.

A first intermediate stage 210 is arranged on top the of the first stage 118, such that the first intermediate stage 210 is arranged to be driven by the first stage 118 in the first degree of freedom,

wherein the first intermediate stage 210 is arranged to be movable with respect to the first stage 118 in a first translational direction IE having at least a component that is substantially perpendicular to the central axis I; in particular, upon rotation of the first stage 118, the first translational direction HI rotates in the plane perpendicular to the central axis I. The first intermediate stage 210 comprises a guiding track 211 on top of which a first intermediate stage carriage 212 runs that is movable along the first translational direction HI. Preferably, the guiding track 211 comprises a linear gear rack and the first intermediate stage carriage 212 comprises a gear rack stepper motor, as is shown in figure 4, for driving the carriage 212 along the first translational direction II, thereby enabling the third degree of freedom. The guiding track 211 is thereto coupled to the circular shaped first stage member 117

A second intermediate stage 220 is arranged on top the of the first intermediate stage 210, such that the second intermediate stage 220 is arranged to be driven by the first stage 118 in the first degree of freedom and the first intermediate stage 210 along the first translational direction HI, wherein the second intermediate stage 220 is arranged to be movable with respect to the first intermediate stage 210 in a second translational direction I'V having at least a component that is substantially perpendicular to the central axis I and that is substantially perpendicular to the first translational direction HI. The second intermediate stage 220 comprises a guiding track 221 on top of which a second intermediate stage carriage 222 runs that is movable along the second translational direction IV, thereby enabling the fourth degree of freedom. The guiding track 221 is thereto coupled to the first intermediate stage carriage 212. Preferably, the guiding track 211 comprises a linear gear rack and the first intermediate stage carriage 212 comprises a gear rack stepper motor, as is shown in figure 4, for driving the carriage 212 along the first translational direction IL

The top stage 230, to which the needle holding member 203 is coupled, is arranged on top of the second intermediate stage 220, in particular it is pivotally coupled to second intermediate stage carriage 222. Like the needle holding member 103 of the first embodiment, this needle holding member 203 comprises a grid holding frame 204, holding a number of removable (i.e. replaceable) needle holding grids 205 in a number of grid receiving sections 209 arranged in a rectangular array of a plurality of (e.g. three) rows and a plurality of (e.g. three) columns, that is arranged to pivot, with respect to the base member 101 around the pivot axis II, thereby enabling the second degree of freedom of the robotic device 200. The top stage 230 is preferably arranged with a second rotational drive (not shown) for driving this pivoting, i.e. rotational, motion. The needle holding grids 205 comprise a plurality of needle holding positions 206 that are arranged in two-dimensional arrays having a number of rows and columns.

Figure 6 shows an upper three-dimensional perspective view of a third embodiment of the robotic device 300 according to the invention. The robotic device 300 comprises the same base member 103 and first stage 118 as the robotic devices of figures 1 — 5. Like the robotic device 200 of figure 5, the robot device 300 comprises a first intermediate stage 310, a second intermediate stage 320 and a top stage 330, these are, however, slightly different in their (driving) arrangement.

A frame member 301 is arranged on top of, and connected to, the circular shaped first stage member 117. The first intermediate stage 310, a second intermediate stage 320 and a top stage 330 are arranged within the frame member 117. The driving system for the first intermediate stage 310 and the top stage 330 are combined by arranging two space apart, parallel arranged, linear drives 313, 314. The first primary linear drives 313, of these drives, comprises a guiding track 311 on top of which a first primary intermediate stage carriage 312 runs. The first secondary linear drive 314, of these drives, comprises a guiding track 315 on top of which a first secondary intermediate stage carriage 316 runs in the direction parallel to the first primary intermediate stage carriage 312, such that both drives are arranged to move the needle holding member 303 along the first translational direction IN. The functioning of these parallel arranged drives 313, 314 is explained in more detail below.

Like in the second embodiment, the second intermediate stage 320 is coupled to a carriage of the first primary and/or secondary linear drive 313, 314 The second intermediate stage 320 is thus arranged on top the of the first intermediate stage 310, such that the second intermediate stage 320 is arranged to be driven by the first stage 118 in the first degree of freedom and the first intermediate stage 210 along the first translational direction IH. The second intermediate stage 320 is arranged to be movable with respect to the first intermediate stage 310 in a second translational direction IV having at least a component that is substantially perpendicular to the central axis I and that is substantially perpendicular to the first translational direction HI.

The top stage 330, arranged for rotating the needle holding member 303 around a pitch axis I, is arranged on top of the second intermediate stage 320 in a functionally similar fashion as in the second embodiment 200. The drive arrangement is different though, as the pitch movement is driven by driving the parallel arranged drives 313, 314 of the first intermediate stage in non-equal manner, such that this difference in movement results in a pitching movement of the needle holding member 303.

Like the robotic device 200 of figure 5, robotic device 300 is able to move the needle holding member 303 with respect to the base member in four degrees of freedom for positioning the at least two needles 308 at any orientation and at any location within an area of the outer skin surface of the human body that is covered by the robotic device 300.

Additionally, the needle holding member 303 now comprises a one-dimensional, linear, array of needle holding positions 306. The needle holding member 303 is further shown to comprise two needles 308. The needle holding member 303 may be removably coupled to the top stage 330.

It is noted that the wording “arranged on top” is used, with respect to the stages, to operatively describe the relationship between the respective stages, and not there exact (geometrical) placement. H a stage A is arranged on top of stage B, then stage B is operatively coupled with stage A in such a way that, upon moving stage A, stage B moves along. Stage B can than be coupled to stage A on a side, a top, a bottom or in any other manner that allows the prescribed functionality. The hereabove described drives, typically comprise motors for driving said drives.

PROTOTYPE TEST

Overview of Robot Structure

Figure 7 shows the robotic device according to the third embodiment, wherein the robot components were 3D printed with Makerpoint Ultimaker Tough PLA material (Makerpoint

Holding, Wageningen, The Netherlands) and were fixed together using nylon screws and bolts.

These materials were chosen because they are lightweight and MRI compatible. After all components were assembled, the robot had a total weight of 240 g and dimensions of 140 mm x 147 mm x 113 mm.

The robot was designed to guide the simultaneous insertion of two electrodes at a fixed distance of 10-25 mm. A multiple needle holder in the robot ensured parallel placement of the electrodes. The distance between the electrodes must be at least 10 mm and not exceed 20-25 mm for optimal treatment. If more than two electrodes are required, they can be inserted in sequence, following a planned path to avoid collision of the electrodes with the robot frame.

The robot had four pneumatic motors, each of which provides actuation to four separate joint states q 92, gz, and g4, as shown in Fig. 7. Motor ¢, provides translation along the x axis (4th DOF).

Motor q2 and g3 are mounted in parallel to provide translation along the y axis when moved together (3rd DOF) and rotation around the x axis when moved differentially (2nd DOF). Finally, motor ga provides rotation around the z axis (1st DOF).

Joint movement in the robot was actuated using pneumatic stepper motors that were produced at the University of Twente. The motor was 3D printed with Stratasys Objet Eden260 (Stratasys Ltd.,

Eden Prairie, MN, USA) using FullCure720 material. The motor was moved using a double acting cylinder that was controlled by four pneumatic tubes made of a polyurethane. In this prototype. two types of motors were used: a linear motor and a rotational stepper motor. The resolution of the motor depends on the size of the stepper teeth / rack. The smallest step size for the linear motor was 0.625 mm, and the minimum angle for the rotational motor was 0.5 degrees. The motor position and joint motion of the robot prototype are shown in Fig. 7.

Forward Kinematics

Two intermediary variables 8 and due, (Fig. 8), were used to derive the forward kinematics of the first intermediate stage 310 and the top stage 330. 8 represents the change in orientation around the x axis (i.e. pitch rotation) due to ¢» and gz, while dwge is the needle translation movement along the v axis at z = 0. Other variables, such as the horizontal distance between the center of the top motor and the needle position (dseedte = 26 mm), the vertical distance of q2 and gs (Zoot: = 40 mm), and the vertical distance between the target at z = 0 and g: (fue = 51.9 mm), were derived from the dimensions of the robot prototype.

The orientation change 9 can be written in terms of q2 and g3 by: 8 = atan2 1 12 . (1)

Ino tor

Furthermore, dure can be calculated by extrapolating the line made by two points (2, q2, lor + large) and (*, @3, larger) to the reference target plane at z = 0. target = are (43 q2) + gz. (2) motor

Finally, the mapping from the actuator space to the end effector space is given by the transformation matrix Te... This transformation matrix can be derived by compounding the transformation for each degree of freedom, including the insertion motion:

Tee = Tga Taarger To Tai Tainseru 3) 0

Te = [fe >] 5 oe] | Rg a] lix3 1 0 O1x3 1

Ozx1 1 di 0 i | 5 | 0 0 Ginsert!

O3x1 1 105, 1 where fis a 3x3 identity matrix, ¢inen is the needle insertion degree of freedom (manually performed), and the rotation matrices are given by: cosq, —sing, 0 [1 0 (UN

Raga = En da COSQ4 0 ,Rg = : cos@ —sin 0 0 1 0 sin8 cos6

Workspace Analysis

The robot workspace is limited during operation by the motion of the pneumatic stepper motor and collision of the needle with the robot frame at the target plane (z = 0). Using forward kinematics, the boundary of the workspace can be calculated by substituting ¢1,¢2 ¢3 and g4, which gives a cone-shaped boundary.

The cone-shaped robot workspace has a top diameter of 119.18 mm for electrode insertion on the skin and becomes larger depending on the depth of the electrode. The robot can also support a large insertion angle normal to the skin surface, with a maximum tilt of 32.3°. With proper placement on the patient’s body, the robot workspace is large enough to cover the maximum tumor size, including the safety margin for IRE treatment (>% 90 sun), and the maximum angulation for the electrode (> 10°) as discussed in Section TI-A.

EXPERIMENTS AND RESULTS

The robot was controlled using Robot Operating System (ROS) Melodic in Ubuntu 18.04 operating system. The needle trajectory was calculated using the ROS MovelT package. By providing the position of the target, MovelT calculated the inverse kinematics of the robot while preventing collision of the joint position. After obtaining the joint position, Arduino Mega 2560 was used to activate the pneumatic valve and actuate the pneumatic motor into the desired position. Open-loop control was used to move the pneumatic motor based on the motor step.

Needle Accuracy Test

Accuracy of the robot in free air was tested by inserting a needle into the target points as depicted in Fig. 9. We opted to use only a single needle in this accuracy test, as the additional needles will move together due to the rigid connection to the needle holder. The positioning error of one needle should not differ compared to multiple needles, since the motion between the needles are relative to each other. Error is mainly introduced by the fabrication accuracy of the multiple needle holder which is 3D printed with submillimeter accuracy.

The robot was set to start at position T4 (the center of the robot coordinate) before moving to the other target points, from T1 to T8. The needle was inserted 15 times for each target and a variety of needle insertion orientations were also evaluated. In the first experiment, the needle was inserted parallel to the z axis. In the next experiment, the needle angle was increased incrementally by 5° until a maximum angle of 25° in the x direction.

Accuracy values of the robot are presented in Table I. In a parallel position, the robot accuracies were 0.21 + 0.14 mm for the x axis and 0.70 + 0.50 mm for the y axis. We also found that the error increased in the direction of needle orientation. For instance, the position error in the y axis increased as the needle angle increased. This can be explained by the number of motors that were used to achieve the target position. On the axis where the orientation is given, two stepper motors were needed to control the needle tip, while on the other axis, only one motor was needed.

The accuracy in the z direction was not reported because the needle was inserted manually. This was intended to mimic the clinical procedure. Robot actuation is used to guide the needle to the desired position, and the clinician should be the one who has full responsibility and control over the insertion process due to regulation and safety concerns.

MRI Accuracy Test

We tested the ability of the robot to target several tumors in a triple modality 3D abdominal phantom (Model 057A; CIRS Inc., Norfolk, VA, USA) under MRI guidance. The robot was placed on top of the phantom, which left enough space inside the MRI bore. Fish oil capsules were used as fiducial markers on the phantom (four capsules) and robot (three capsules). The T2 sequence was used to obtain MRI images. The initial scan was performed with an image dimensions of 768 x 768 x 192 pixels and image spacing of 0.49 mm x 0.49 mm x 1 mm. From this scan, several important objects were segmented from the phantom, including: phantom shell, liver, tumors, and fish oil markers, using 3D Slicer software.

In Slicer, these objects were manually segmented using pixel intensity information as a guidance for object region and boundaries. Segmentation quality was improved using the painting tool to refine the object selection. These segmentations were exported to STL files and used for robot registration. Fiducial registration wizards from the SlicerlGT module were used to register the segmentation files from MRI images to the robot coordinates.

Four tumors were selected as targets from the phantom. The accuracy of needle insertion in the axial and coronal planes was assessed. Robot inverse kinematics was used to calculate the required joint positions, using the center of the tumor as the target point. The needles were manually inserted, and the MRI images of the phantom were taken to evaluate the result.

Insertion results are shown in Fig. 10. The distance between the needle tip and the tumor center was measured using 3D Slicer. In the coronal plane, the insertion error was 2.53 £2.56 mm. In the axial plane, the accuracy was lower with an error of 8.73 + 1.95 mm.

The error we observed during registration of the robot and MRI images may have contributed to the higher error observed in this experiment compared to the accuracy test result. Our finding that deeper tumors have a higher error than tumors located closer to the skin surface indicates that error in needle orientation increases as the target deepens. Needle deviation might also occur because of tissue compression deformation, and may contribute to the error.

Needle 0 degree 5degrees | 10 degrees | 15 degrees | 20 degrees | 25 degrees

Mean 021 070 062 081 072 110 032 118 032 142 037 160 error | | 5

Std 014 050 0.18 053 026 0.66 021 073 0.23 061 029 075 deviation

TABLEIROBOT mmm

POSITIONING ACCURACY (in mm)

Image Quality Testing

The image quality test evaluated the effect of the robot on the quality of the MRI images. In this test, the robot was operated inside a Magnetom Aera 1.5T MRI scanner. A standard Siemens 1900 ml phantom plastic bottle (model# 8624186; 3.75 g NiSO4 x 6H:0 + 5g NaCl) next to the robot was used to check the homogeneity of the MRI images. Three operating conditions were set for the experiment. Scans were performed in three ways: (1) with a phantom only as a control image, (2) with a phantom and robot in the OFF state, and (3) with a phantom and robot in the ON state.

Two image sequences, TI and T2, were used during the test. The images for both sequences had a field of view of 320 x 320 x 20 with a voxel size of 0.625 mm x 0.625 mm and a slice thickness of 3.5 mm. The image quality was evaluated by measuring the signal-to-noise ratio (SNR) of the phantom MR images using the NEMA standard:

Ssignat

SNR = 22e (4) noise where Ssigna is the mean pixel value in the region of interest (ROI) of the signal and noise is the standard deviation of all pixels in the ROI of the noise.

Fig. 11 shows the ROI for both signal and noise, including the normalized SNR results. A maximum of 10% SNR loss is acceptable when demonstrating the MRI compatibility of the robot.

The maximum decrease in SNR due to the robot presence was less than 1.08% for the T1 sequence and 1.03% for the T2 sequence. No significant differences were observed in the SNR when the robot was in the ON and OFF states and no artifacts were observed in the MRI images. This showed that our robot prototype can be used in an MRI scanner bore.

The present invention is not limited to the embodiment shown, but extends also to other embodiments falling within the scope of the appended claims.

Claims

CONCLUSIONS

1. MRI compatible robotic device for ablation treatment, wherein the robotic device comprises: - a base member for placement on an outer skin surface of a human body; - a needle-holding member for holding at least two needles; - a positioning system for moving the needle-holding member in at least two degrees of freedom relative to the base member for positioning the at least two needles in any orientation and at any location within an area of the outer skin surface of the human body that covered by the robot device.

2. MRI-compatible robotic device according to claim 1, wherein the positioning system is adapted to simultaneously position the two needles parallel in an arbitrary orientation and at an arbitrary location within the area.

An MRI compatible robotic device according to claim 1 or 2, wherein the first degree of freedom of the positioning system is defined by a rotation of the needle holding system about a central axis perpendicular to a lower contact surface of the base member, during use with the lower contact surface of the base member is substantially parallel to a tangential plane of the area of the outer skin surface of the human body covered by the robot.

An MRI-compatible robotic device according to any one of the preceding claims, wherein the second degree of freedom of the positioning system is defined by a rotation of the needle-holding system about an inclination axis that is substantially perpendicular to the central axis.

5. MRI-compatible robot device according to any one of the preceding claims, wherein the positioning system is further adapted to move the needle-holding member relative to the base member in a third degree of freedom, wherein the third degree of freedom is defined by a translation of the needle-holding system in a first translational direction with at least one component substantially perpendicular to the central axis.

6. MRI compatible robot device according to any one of the preceding claims, wherein the positioning system is further adapted to move the needle-holding member relative to the base member in a fourth degree of freedom, wherein the fourth degree of freedom is defined by a translation of the needle-holding system in a second translation direction with at least one component that is substantially perpendicular to the central axis and that is substantially perpendicular to the first translation direction.

7. MRI compatible robot device according to any one of the preceding claims, wherein the positioning system comprises a stacked stair system, wherein the stacked stair system is movable relative to the base member, wherein the stacked stair system comprises: - a first stage that is adapted to be driven in the first degree of freedom, and which is particularly adapted to be rotatably driven about a central axis perpendicular to a lower contact surface of the base member; - an upper stage that is coupled to the first stage and designed to be driven by the first stage in the first degree of freedom, whereby the upper stage is movable relative to the first stage in a second degree of freedom, in particular where the upper stage stage is rotatable relative to the first stage about an axis of inclination that is substantially perpendicular to the central axis, wherein the axis of inclination is movable with the first stage in the first degree of freedom, - wherein the needle-holding member is connected to the upper stage; - preferably drive means for driving the respective stairs of the stacked stair system.

An MRI compatible robot device according to claim 7, wherein the stacked stage system further comprises: - a first intermediate stage arranged between the first stage and the upper stage, the first intermediate stage being arranged to be driven by the first stage in the first degree of freedom , wherein the first intermediate stage is movable relative to the first stage in the third degree of freedom, in particular wherein the first intermediate stage is designed to be movable relative to the first stage in a first translational direction with at least one component that is substantially perpendicular is on the central axis; and

- wherein the upper stage is rotatable relative to the first intermediate stage about an inclination axis that is substantially perpendicular to the central axis, wherein the inclination axis is movable with the first intermediate stage in the third degree of freedom.

9. MRI compatible robot device according to claim 8, wherein the stacked stage system further comprises: - a second intermediate stage arranged between the first intermediate stage and the upper stage, wherein the second intermediate stage is arranged to be driven by the first stage in the first degree of freedom and is adapted to be driven by the first intermediate stage in the third degree of freedom, wherein the second intermediate stage is movable relative to the first intermediate stage in the fourth degree of freedom, in particular wherein the second intermediate stage is adapted to be movable relative to the first intermediate stage to be in a second translational direction with at least one component that is substantially perpendicular to the central axis and that is substantially perpendicular to the first translational direction; and - wherein the upper stage is rotatable relative to the second intermediate stage about an inclination axis that is substantially perpendicular to the central axis, wherein the inclination axis is further movable with the second intermediate stage in the fourth degree of freedom.

10. MRI compatible robot device according to claim 8 or 9, wherein the tilt axis is arranged to be substantially parallel to the first translation direction, or wherein the tilt axis is substantially parallel to the second translation direction.

11. MRI-compatible robot device according to any one of the preceding claims, wherein the positioning system, in particular the drive means of the first stage, comprise(s) a first rotation drive for driving the needle-holding member at the first degree of freedom, preferably wherein the first rotational drive comprises a first motor, wherein an engaging member of the first motor engages a cylindrically shaped gear track arranged on the base member.

12. MRI-compatible robot device according to at least claim 5 or 8, wherein the positioning system, in particular the drive means of the first intermediate stage, comprises a first linear drive for driving the needle-holding member in the third degree of freedom.

13. MRI-compatible robot device according to at least claim 6 or 9, wherein the positioning system, in particular the drive means of the second intermediate stage, comprises a second linear drive for driving the needle-holding member in the fourth degree of freedom.

14. MRI compatible robot device according to any one of the preceding claims, wherein the positioning system, in particular the driving means of the upper stage, comprises a second rotational drive for driving the needle-holding member in the second degree of freedom: preferably wherein the needle-holding member is adapted to pivot about a pivot point relative to the basic member.

The MRI compatible robot device of claim 14, wherein the second rotational drive comprises a third linear drive configured to exhibit a respective third linear drive direction substantially perpendicular to the tilt axis and wherein the third linear drive is spaced from the tilt axis in a direction perpendicular to the third linear drive direction and perpendicular to the tilt axis, such that the needle-holding member is adapted to rotate about the pivot axis when driving the third linear drive.

The MRI compatible robotic device of claim 15, wherein the second rotational drive comprises a fourth linear drive configured to exhibit a respective fourth linear drive direction substantially parallel to the third linear drive direction and wherein the fourth linear drive is spaced apart of the third linear drive in a direction that is perpendicular to the third and fourth linear drive directions and that is perpendicular to the axis of inclination, such that the needle-holding member is adapted to pivot around the pivot axis when the third and fourth linear drive are not driven synchronously. drives.

An MRI compatible robot device according to claim 16 in combination with claim 12 or 13, wherein one of the third and fourth linear drives is one of the first and second linear drives.

18. MRI compatible robot device according to any one of the preceding claims, wherein the needle holding member is adapted to hold two or more spaced needles, wherein the holding member comprises a matrix of needle holding positions that are adjacent and spaced apart in an at least one-dimensional linear matrix, wherein the holding member preferably comprises a matrix of needle holding positions that are adjacent and spaced from each other in a two-dimensional, preferably linear grid, which preferably has a number of rows and columns.

19. MRI-compatible robot device according to any one of the preceding claims, wherein the needle-holding member is releasably coupled to the robot device.

20. MRI compatible robot device according to claim 18 or 19, wherein the needle-holding member comprises a grid-holding frame that is adapted to detachably hold one or more needle-holding grids, wherein a multiple needle-holding grid comprises a number of openings that form needle-holding positions.

21. MRI-compatible robot device according to any one of the preceding claims, wherein the robot device has a maximum height, viewed in the direction of the central axis, of not more than 350 mm, preferably not more than 250 mm.

An MRI compatible robotic device according to any one of the preceding claims, wherein an area covered by the robotic device is between 0.0025 m? — 0.09 m?, preferably 0.01 m? - 0.05 m?, more preferably 0.02 m? - 0.04 m? amounts to.

23. MRI compatible robot device according to any one of the preceding claims, wherein the robot device is made of, preferably exclusively, non-metallic, non-magnetic and non-conductive materials and/or wherein the robot device is MR safe according to the ASTM F2503 standard.

24. Method of ablation treatment, in particular irreversible electroporation (IRE) treatment, comprising the steps of: - determining a treatment area of a patient's body using an imaging device, such as a magnetic resonance imaging device, - providing a robotic device according to any one of the preceding claims in a treatment area of a patient's body; - positioning a needle at an insertion position in the treatment area using the robot device;

- inserting the needle into the insertion position.