Multi-site transcranial magnetic stimulation transducer

Abstract

A multi-site TMS (Transcranial Magnetic Stimulation) transducer is disclosed comprising one or more transducer modules adapted to be positioned on a subject's scalp for TMS, each of the one or more transducer modules comprising five or more coils for TMS of a cortical target of the subject.

Description

[Technical Field]

[0001] Field The present invention relates to transcranial magnetic stimulation (TMS). In particular, the present disclosure relates to multi-locus TMS. [Background technology]

[0002] background Transcranial magnetic stimulation induces focused electric fields (E-fields) in the brain by applying a strong, rapidly changing magnetic field. TMS is routinely performed in thousands of hospitals worldwide for diagnosis (e.g., to measure corticospinal excitability), preoperative planning (to locate eloquent areas of the brain), and treatment (e.g., to treat depression or chronic pain). Current state-of-the-art equipment uses optically guided navigation to move a handheld TMS coil so that cortical sites selected from individual magnetic resonance images (MRIs) are stimulated. Multisite stimulation with commercially available technologies is cumbersome and, at best, limited to stimulating two or three distant cortical targets using several bulky stimulators. Summary of the Invention [Problem to be solved by the invention]

[0003] the purpose The object is to alleviate the above-mentioned inconveniences.

[0004] In particular, it is an object to provide an improved multi-site TMS transducer. [Means for solving the problem]

[0005] overview To overcome this limitation, multisite TMS (mTMS) instrumentation and methods have been developed that allow flexible stimulation of cortical regions. This can be done sequentially on adjacent cortical regions on a time scale of 0.1 to 10,000 milliseconds, significantly improving the suitability of TMS for studying interactions between cortical regions. The implementation of mTMS is made possible by advanced coil design methods. In the context of the present invention, so-called minimum-energy (which can also refer to the minimum amount of energy required) coils and coil sets (or transducers) can be fabricated to induce the desired E-field pattern in the cortex. These methods can be used to design optimal coils and transducers that are located on flat or curved surfaces. As a result, TMS efficiency can be improved, for example, by a factor of two. While planar coils can provide an optimal setup, if the coil is capable of spanning a large portion of the scalp (which can be said to have a wide scalp footprint), such a wide coil may not be practical for mTMS. A key criterion for the efficiency of a TMS coil or transducer is its fit to the scalp. Any gap between the coil and the scalp can significantly increase the required energy delivered by the stimulation electronics, and if the gap is too large, it will be impossible to achieve the desired E-field strength within the cortex.

[0006] According to a first aspect, a multi-site TMS transducer includes one or more transducer modules adapted to be positioned on a subject's scalp for TMS. This allows the transducer modules to follow the contours of the scalp, thereby minimizing the gap between the transducer modules and the scalp. The presence of multiple transducer modules enables efficient multi-site TMS through a modular configuration, where the stimulating E-field can be electronically controlled by adjusting the current in the coils of the transducer modules without moving the coils. Importantly, each of the one or more transducer modules includes five or more coils for TMS of a subject's cortical targets. This allows any maximum of the induced E-field to be moved in two dimensions across the scalp and the E-field maximum to be rotated around an axis that may be substantially perpendicular to the inner surface of the skull. Notably, this allows for fine-tuning and control of the location and orientation of the global maximum of the E-field. This also allows for control of the location of the center of gravity and / or the associated orientation of the E-field within any region of the E-field, e.g., within regions where the E-field amplitude exceeds a threshold (such as 90 or 95% of the global maximum of the E-field). The threshold may be relative (as in the example above) or absolute. This type of averaging over regions of high E-field amplitude can be useful to avoid problems with the global maximum. Because cortical regions below the scalp have complex conductive geometries, the global E-field maximum may exhibit jumps from gyrus to gyrus, even when the overall E-field profile varies more smoothly.

[0007] It should be noted that in practice, six coils would likely be required to achieve this behavior. If the electric field has two components, the first component can be referred to as the "x-component," and the second component can be referred to as the "y-component." To control the x-component of the E-field, three degrees of freedom (i.e., intensity and two-dimensional (2D) position) might be expected, requiring three coils. Similarly, to control the y-component of the E-field, three degrees of freedom (i.e., its maximum value and 2D position) might be expected, requiring three coils. However, the physics of the problem have been found to ensure that only five degrees of freedom are required for rotation and micromotion. This is also applicable to TMS. With only five coils, the maximum value may be controllable only within a limited region. By utilizing more coils (e.g., dozens of coils, depending on the desired level of focality of the E-field maximum), the E-field maximum can be controlled over substantially the entire cortical surface. The location of the maximum value is not a linear measure.

[0008] Thus, the transducer and one or more transducer modules can be configured such that the magnitude and two positions of the E-field maxima for both E-field components are controlled by five or more coils. This can be done within a limited area for any or each of the transducer modules. With multiple transducer modules, this can be done over an extended area beyond the reach of a single transducer module.

[0009] It should be noted that the transducer and transducer module can be configured so that the cortical target is varied. This can be done by changing the way current is driven through the five or more coils. The transducer can be configured so that two separate targets are stimulated consecutively using the same five or more coils, i.e., utilizing the same transducer module. This can be done without pause, for example, at intervals of 0.5 to 100 ms.

[0010] In one embodiment, the windings of any or all of the five or more coils span a three-dimensional volume. In this manner, the coils can be positioned to protrude from the scalp rather than be packed against it, thereby providing expanded space for coil design. This can improve the coil winding efficiency and, in turn, improve the overall energy efficiency of the transducer. In a further embodiment, the windings of any or all of the one or more transducer modules at the bottom of the corresponding transducer module (i.e., at the end of the transducer module configured to be positioned against the scalp) are laterally confined within the bottom region and extend laterally beyond the bottom region when moving longitudinally away from the bottom. This can provide expanded space for coil design in one or both of the depth dimension (i.e., the longitudinal dimension) as well as the lateral dimension (i.e., the dimension parallel to the surface of the scalp). Thus, the lateral extent of the coils can be greater than the scalp footprint of the corresponding transducer module, allowing flexibility in coil design.

[0011] In one embodiment, the bottom of any or all of the one or more transducer modules is curved to conform to the scalp, which can reduce the gap between the transducer module or its coils and the scalp, thereby improving the efficiency of the transducer module for TMS by reducing the energy required to be supplied by the stimulation electronics.

[0012] In one embodiment, the bottom of any or all of the one or more transducer modules is hexagonal and / or pentagonal in shape, which allows multiple transducer modules to be positioned close together to minimize gaps between the transducer modules, thereby improving the presence of E-fields even at the boundaries of the transducer modules.

[0013] In one embodiment, the one or more transducer modules include multiple transducer modules adapted to be positioned adjacent to one another on the subject's scalp for TMS. The modular configuration of the transducers enables efficient multi-site TMS, where cortical targets can be stimulated even beyond the effective stimulation area of any individual transducer module.

[0014] In one embodiment, the bottoms of the plurality of transducer modules form one or more patterns of one or more hexagons and / or one or more pentagons surrounded by pentagons, particularly five such hexagons that may surround the pentagon, thereby allowing for a tightly fitted configuration of the transducer modules.

[0015] In one embodiment, the bases of the transducer modules form one or more patterns of a hexagon surrounded by three hexagons and three pentagons. The surrounding hexagons and pentagons can alternately surround a (central) hexagon. This allows for different tight-fit configurations of transducer modules.

[0016] In one embodiment, the bottoms of the multiple transducer modules form one or more patterns in which a central transducer module is surrounded by multiple surrounding transducer modules, and the bottoms of any or all of the surrounding transducer modules have irregular shapes that expand the scalp footprint of the corresponding transducer module as they move away from the central transducer module. This allows the scalp footprint of the corresponding surrounding transducer module to be much larger than the scalp footprint of the central module. This, in turn, allows the coil windings of the corresponding surrounding module to be placed in a larger space, thereby improving stimulation efficiency.

[0017] In one embodiment, the transducer is configured to simultaneously activate any or all of five or more coils of two or more adjacent transducer modules of the plurality of transducer modules to stimulate a single cortical target, thereby stimulating a cortical target beyond the reach of the individual transducer modules, for example, in a boundary region between two or more transducer modules.

[0018] In one embodiment, five or more coils are adapted to generate a signal space of five or more dimensions, each of the five or more coils corresponding to an orthogonal basis vector of the signal space. This allows for an improved coil design in which the currents in the five or more coils do not couple with each other. To this end, the five or more coils may have negligible mutual inductance.

[0019] In one embodiment, the five or more coils in any or all of the multiple transducer modules have a mutual inductance coupling coefficient less than 0.1. In a further embodiment, the coupling coefficient is less than 0.05. It is noted that the mutual inductance M of two coils can be calculated as M=k*sqrt(L1*L2), where L1 and L2 are the self-inductances of the two coils, respectively, and k is the mutual inductance coupling coefficient. Here, "sqrt" denotes the square root of the product in the following parentheses. As shown in the embodiment, low mutual inductance between coils in a transducer is beneficial because it reduces the voltage the coils induce on each other during a TMS pulse. In one embodiment, the five or more coils include one or more circular coils.

[0020] In one embodiment, the five or more coils include one or more figure-eight coils. In certain embodiments, this includes two figure-eight coils that may be perpendicular to one another. Here, a "figure-eight coil" may refer to a coil that forms two loops or two sets of loops with windings intersecting between them, thereby forming a shape reminiscent of the number "eight." The two figure-eight coils may be rotated relative to one another about their longitudinal axes, which may be defined by the common point where the two coils intersect. If perpendicular, the rotation may be substantially 90 degrees.

[0021] Generally, any coil disclosed herein can form a loop or set of loops. Coils, including circular coils and figure-eight coils, can have tightly wound loops (adjacent turns touching or nearly touching throughout the entire winding path), which can form a set of loops for the coil, where the loops within a set can be stacked to follow each other. To improve efficiency, the coil windings can be crossed so that the windings of one loop of a coil, such as a figure-eight coil, touch the windings of another loop near a common point, as shown in FIG. 1 . Gaps can occur between the loops away from the common point.

[0022] In one embodiment, the five or more coils include one or more four-leaf clover coils. In a specific embodiment, this includes two four-leaf clover coils that can be rotated about a common longitudinal axis. The rotation can be about 45 degrees, e.g., 40 to 50 degrees, so that the two coils can form a substantially eight-leaf pattern. Here, a "four-leaf clover coil" can refer to a coil that forms four loops or four sets of loops, with the windings intersecting at a single region or point between them, thereby forming a shape reminiscent of a four-leaf clover.

[0023] In one embodiment, the five or more coils include one circular coil, two figure-eight coils that may be perpendicular to each other, and two four-leaf clover coils that may be rotated about a common longitudinal axis relative to each other, for example as described above.

[0024] In one embodiment, the five or more coils have the same axis of symmetry, which may be the longitudinal axis, i.e., the axis substantially perpendicular to the scalp when the transducer is positioned on the scalp for TMS.

[0025] The present solution allows mTMS to be delivered in a controllable manner, in particular it allows for virtually continuous mTMS over the scalp, or any targeted area thereof.

[0026] It should be understood that the above-described aspects and embodiments can be used in any combination with each other. Some of the aspects and embodiments can be combined to form further embodiments of the present invention.

[0027] BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are included to provide a further understanding of and form a part of this specification, illustrate examples and, together with the description, serve to explain the principles of the present disclosure. [Brief explanation of the drawings]

[0028] [Figure 1] 1 illustrates TMS using a transducer according to an example. [Figure 2] Two example transducers are shown in coronal and top views. [Figure 3a] 1 illustrates the shape of a transducer module according to an example. [Figure 3b] 1 illustrates a pattern of a transducer module according to an example. [Figure 4a] 1 shows an example of a transducer module. [Figure 4b] 1 shows an example of a transducer module. [Figure 5] 10 shows a further example of a transducer module. [Figure 6] 10 illustrates further configurations of transducer modules according to examples. DETAILED DESCRIPTION OF THE INVENTION

[0029] In the accompanying drawings, like reference signs are used to designate equivalent or at least functionally equivalent parts.

[0030] Detailed Description The detailed description provided below in connection with the accompanying drawings is intended as an illustration of examples and is not intended to represent the only manner in which the examples can be constructed or utilized, however, different examples may achieve the same or equivalent functions and structures.

[0031] FIG. 1 illustrates an example 100 of TMS on a subject. The subject has a scalp 110 against which a transducer 120 is positioned for TMS. In this example, the transducer is a planar transducer that can control the location, direction, and intensity of stimulation in an approximately 30 mm x 30 mm cortical region to provide electronically movable focal targeting in that region. The transducer can have five coils for TMS. Subfigures a-e show example coil windings for each of the five coils.

[0032] A multi-site TMS (mTMS) transducer (also referred to as a "transducer") may be provided that has greater coverage of the subject's cortex. The transducer may include one or more transducer modules, particularly multiple transducer modules, each of which may be adapted to cover a different portion of the subject's scalp. Because the transducer is modular, it may include or be composed of separate units, each of which may be adapted to be placed directly on the scalp, either separately or together with any or all of the other transducer modules. The transducer modules may be adapted to be positioned adjacent to one another on the subject's scalp for TMS. This may be done with or without gaps between the transducer modules. The transducer may include a frame that supports and / or couples any or all of the transducer modules. Any or all of the transducer modules may be enclosed in a casing that may be part of the transducer. The casing may be common to the transducer modules. The frame may be part of the casing. The casing and / or frame may be flexible, allowing it to deform to conform to the shape of the scalp.

[0033] Each of the one or more transducer modules can include five or more coils for TMS of a cortical target of a subject. The coils can be configured to provide an E field to the cortex for TMS. Having five coils for a module allows for control of the E field in both a translational direction across the cortex and a rotational direction about a rotational dimension that can be perpendicular or substantially perpendicular to the inner surface of the skull at the location of the cortical region and / or E field maximum / cortical target for TMS. The transducers can be configured to provide current to the coils to move the electric field maximum corresponding to the cortical target (e.g., in two dimensions across the cortex). The transducers can also be configured to provide current to the coils to rotate the electric field maximum corresponding to the cortical target. The five or more coils may have negligible mutual inductance with each other. Generally, the five or more coils generate a signal space of five or more dimensions, and each of the five or more coils can be adapted to correspond to an orthogonal basis vector of the signal space.

[0034] As a contrasting example, one can imagine a module with only three coils, for example, using simple circular coils aligned along three orthogonal axes. Two of these coils can contact the scalp at one of their edges, thus resembling a figure-of-eight coil (they generate an electric field maximum below the edge that contacts the scalp, with the E field maximum directed primarily along the winding direction. If you start with a figure-of-eight coil and bend its winding upward, you get this kind of circular coil). These two coils can therefore rotate the E field maximum. And the third circular coil can function in principle similarly to any circular coil included in this invention. In such a three-coil module, there is no four-leaf clover coil. In such a three-coil module, the coils are relatively small and therefore inefficient (the magnetic field and corresponding electric field they generate decay rapidly as a function of distance). A figure-of-eight coil (along the scalp) is more efficient at inducing an electric field than a circular coil contacting the scalp at its edge.

[0035] The effect of four or more coils can also be explained by first realizing that a vector-valued electric field can be essentially composed of two perpendicular components, both of which are approximately tangential to the inner surface of the skull (for non-spherical geometries such as the head, there can be three components, but one of them is small compared to the others). As shown above, the present solution allows control of the magnitude and location (in two dimensions across the scalp) of the maximum of both of these components of the E field (six parameters in total). As shown above, the physics of the problem combines the two components in a way that reduces the number of required degrees of freedom to five.

[0036] The transducer is flexible and can adapt to various head shapes and sizes to minimize the coil-to-cortex distance. To this end, the individual transducer modules can be flexible, e.g., five or more coils. However, the five or more coils can be rigid, in which case the modular design of the transducer allows all of the separate transducer modules to be placed directly on the scalp.

[0037] FIG. 2 shows two examples of transducers 200. On the left, one or more transducer modules 120 are two-dimensional, meaning that the coils of the transducer modules are arranged to form a two-dimensional surface for positioning against the scalp. This surface can be flat or curved, the latter option allowing for improved conformance to the scalp. Within a transducer module, the coils can be stacked on top of each other. The two-dimensional form results from the individual coils being arranged to form a two-dimensional surface for TMS.

[0038] On the right, one or more transducer modules 210 are three-dimensional, meaning that the coils, particularly the windings, of the transducer module are arranged across three dimensions. Within the transducer module, the coils can be arranged in an intertwined fashion. The three-dimensional configuration results from the individual coils being arranged such that their windings extend in all three dimensions for TMS. This can be true for any or all of the five or more coils. In particular, there can be at least five coils with windings for TMS extending in all three dimensions. The five or more coils can be nested relative to one another.

[0039] The three-dimensional configuration can improve the efficiency of stimulating areas below the module boundaries. This is shown in FIG. 2 (top: coronal section, bottom: top view), where the coil windings of the transducer modules 120, 210 can extend to the boundaries of the transducer modules. In two dimensions (2D), the illustrated transducer module 120 is composed of planar coils stacked on top of each other, while in three dimensions (3D), the coils of the transducer module 210 span a volume. In 2D, the coils of a single transducer module can be used to move the stimulation location within an area 220 that is small compared to the scalp footprint of the module. In 3D, the coils of a single transducer module can be used to move the stimulation location within an area 222 that is comparable to the scalp footprint of the module, i.e., more than half the scalp footprint, or even substantially equal to the scalp footprint. Alternatively, transducers can be configured so that movement of the stimulation location is limited to an area smaller than the scalp footprint, e.g., 10-50 percent of the scalp footprint or less. Even if a transducer or transducer module configured in this manner does not have a large, continuous area over which the stimulation location can be moved, it can still control stimulation within a relatively large area around the center of multiple modules. This is a further improvement over conventional transducers with planar transducer modules. The transducer can be configured to simultaneously activate the coils of any or all adjacent transducer modules. This can be done to further expand the cortical area available for stimulation. This allows the cortical area for stimulation to extend beyond the cortical area corresponding to any single transducer module and into the boundary region 224 between two or more transducer modules. For clarity, the example shown in Figure 2 shows only two transducer modules (coronal section view) and three transducer modules (top view).In the simplest configuration, the one or more transducer modules consist of a single transducer module. At a minimum, the multiple transducer modules consist of two transducer modules, but it should be understood that the number of these transducer modules may typically be more than two or three, for example, ten or more.

[0040] A transducer module or its coils with a three-dimensional winding geometry allows for a three-dimensional return path for the current injected therein for TMS. In two dimensions, the current loop at the boundary must be constricted to form a complete loop (which can result in inefficient TMS). In three dimensions, the current loop for a transducer module or its coils does not need to be constricted because it can be completed by a return wire above another wire. This can improve design efficiency.

[0041] By having the coil windings span a three-dimensional volume, the efficiency of the coil can be improved compared to a planar design with a corresponding scalp footprint. A three-dimensional transducer module maximizes the area over which the stimulation site can be moved in the cortex if the transducer's scalp footprint is fixed. The three-dimensional transducer module allows the transducer to stimulate a sufficiently large area of the cortex. This overcomes the fundamental limitation of existing technology, where 2D transducers can only adjust the stimulation target within a small cortical area. For example, even an optimized planar five-coil mTMS transducer, such as that shown in Figure 1, has a surface area of approximately 10 cm. 2 Although the three-dimensional winding geometry allows for stimulation only in cortical regions within a relatively large area, the (three-dimensional) transducers disclosed herein can be provided in significantly smaller sizes.

[0042] FIG. 3a illustrates several possible shapes of transducer modules. One or more of the transducer modules can include or consist of transducer modules having a polygonal shape. This can include a hexagonal 310 and / or pentagonal 320 shape (as in the example shown in FIG. 2). This shape can correspond to the boundary of the transducer module, particularly the boundary at the module's end that defines its scalp footprint. Thus, the boundary can be considered to correspond to the shape of the transducer module's bottom. This can directly correspond to the shape of any or all of the five or more coils at the module's bottom. The bottom can be flat or curved, which allows the module, particularly its coils, to conform to the shape of the scalp, thereby reducing or minimizing the distance between the coils and the cortex. On the left side of FIG. 3a, the module has a flat bottom. On the right side of FIG. 3a, the module has a curved bottom. The number, positioning, and shape of the modules can be such that the modules efficiently cover any relevant cortical area. Although the illustration is provided in terms of a sphere 300, in practice, the transducer may have modules arranged in an open pattern, such as an open spherical pattern. The transducer may include at least a hemispherical pattern of transducers, although smaller arrangements are also possible. The spherical or hemispherical pattern need not correspond to an exact (hemi)sphere, but may conform to the shape of the scalp. The transducer may include pentagonal transducer modules surrounded by hexagons, e.g., transducer modules with five hexagons each connected to a different side of a pentagon. Alternatively or additionally, the transducer may include hexagonal transducer modules surrounded by hexagons and pentagons, e.g., transducer modules with three pentagons and three hexagons each connected to a different side of a central hexagon. Each surrounding / enclosing hexagon may be connected to two surrounding / enclosing pentagons, or vice versa.

[0043] FIG. 3b shows an example of a pattern for a plurality of transducer modules, i.e., when one or more transducer modules include two or more transducer modules. The plurality of transducer modules can be arranged to form one or more patterns 330 in which a central module 340 (of the plurality of transducer modules) is surrounded by a plurality of modules 350 (of the plurality of transducer modules), e.g., five or six modules 350 (of the plurality of transducer modules). The central module can have any suitable shape, such as a pentagon or hexagon. The central module can have a flat or curved bottom. In general, the central module can follow any of the examples described herein for a plurality of transducer modules. The surrounding modules 350 can then form a ring of modules around the central module. The surrounding modules can have a shape, e.g., a polygonal shape, that fits relative to each other and / or the central module, such that there are no gaps between any pair of adjacent surrounding modules and / or between the central module and the surrounding module. The outer edges 352 of any or all of the surrounding modules can have any shape, such as a straight or curved shape, so that the overall shape of the pattern is not limited to a regular polygon. In particular, the outer edges of any or all of the surrounding transducer modules can have a shape such that the surrounding module has an overall irregular shape, such as a straight edge toward the central module but a curved edge away from the central module. Alternatively, the outer edges away from the central module can be straight or partially straight, but the bottom can be overall irregular. As a result, the pattern 330 can have any shape, such as a partially or entirely rounded shape, or particularly a circular or elliptical shape. Having any or all of the surrounding modules with an irregular outer boundary can extend the scalp footprint of the corresponding transducer module.This also allows the coil windings of the corresponding surrounding modules to span a larger space, thereby improving stimulation efficiency. Thus, in this configuration, the surrounding modules can be larger, even much larger, than the central modules.

[0044] Alternatively, a multiple transducer module may consist of only two such modules. This can be very useful in some cases due to its simplicity. The two modules in such a case can be positioned on the scalp so that they are connected to each other along their long edges. The two modules can be positioned so that one is positioned on the left side of the subject's scalp and the other is positioned on the right side of the subject's scalp. Generally, the number of transducer modules in a multiple transducer module can range from two, three, or four to several dozens of modules. In certain embodiments, the multiple transducer modules include at least five or six transducer modules. FIGS. 4a and 4b show examples of a transducer module 210. The transducer module is three-dimensional because it includes a coil 410 that spans three dimensions and protrudes away from the module's base 420, which defines the module's scalp footprint. In both examples, the transducer module includes five coils, corresponding to five (or more) coils for TMS. For clarity, each individual coil is shown separately below the module. In a first example, none of the windings of any of the coils cross the windings of another coil. This is shown in FIG. 4a. In a second example, some or all of the windings of the coils pass through the winding loops of another coil. This is shown in FIG. 4b, where the windings of the third coil 412 and the fourth coil 414 in particular pass through the winding loop of the fifth coil 416. In either case, the bottom of the coils can have the same shape for each of the five coils, as in the illustrated example, where the bottom is circular. The bottom of any or all of the coils can have the same shape and / or size as the bottom of the module, as is also the case in the illustrated example. In the illustrated example, the windings of the coils are confined within the bottom of the transducer module, i.e., they do not extend beyond the bottom (laterally), even if they protrude away from the bottom (in the longitudinal dimension).

[0045] FIG. 5 illustrates an example of a transducer module 210 that may otherwise follow any of the examples presented above, but in which the windings of any or all of the five or more coils 410 extend laterally beyond the bottom 420 (longitudinal) away from the bottom. Thus, the windings at the top of the module cover a larger space than the windings at the bottom of the module. Alternatively, the windings of any or all of the five or more coils extend laterally beyond the bottom region of the transducer module. The bottom region can correspond to the scalp footprint of the transducer module. Or, in other words, the bottom region can correspond to the physical lateral extent of the transducer module at its bottom. The windings may thus extend along only a portion of the circumference of the scalp footprint, or along the entire circumference. The windings of any or all of the coils may extend symmetrically, for example, in a conical pattern. Transducer modules with splayed coil windings also follow the example of Figure 2 (right side), where the windings of adjacent modules may splay so that adjacent transducer modules similarly abut each other in a direction away from the bottom of said transducer module, for example, up to the top of the transducer module.

[0046] FIG. 6 shows examples of different shapes for three-dimensional transducer modules. These include transducer modules having a pentagonal shape 610, a hexagonal shape 620, a tapered shape 630, and a circular shape 640, although various other alternatives are possible as well. In each case, the shape can correspond to the shape of the bottom and / or top of the transducer module. In particular, the shape can correspond to the shape of the windings of any or all of the five or more coils at the bottom of the transducer module. Using pentagonal and / or hexagonal shapes for the bottom coils can minimize the gap between adjacent transducer modules. As shown, the size of the transducer module at the top can be equal to or larger than the size of the transducer module at the bottom. The shapes of the multiple transducer modules can be the same or different for any or all of the transducer modules.

[0047] Energy-optimized 3D TMS coils and 3D mTMS transducers can be designed, for example, by expressing the current density corresponding to the coil in a divergence-free basis. This can be done with meshes such as polygonal and / or polyhedral meshes. An example is a tetrahedral mesh or a triangular 3D mesh surface. One example of such a basis is provided by efficient divergence-free 3D Rao-Wilton-Glisson (RWG) basis functions. Dual (3D) stream functions, for example, can be applied to extract the discrete coil winding paths. These have previously been used to model and visualize flow in 3D.

[0048] An example of a coil design algorithm is as follows: First, the volume V in which the coil windings will reside is determined. transducercan be specified. This can correspond to the volume of the transducer, as defined by the outer boundary of the transducer. The volume may or may not be simply connected and may consist of one or more regions. For computational purposes, the coil volume can be discretized, for example, into tetrahedral or hexahedral elements. Next, a head model (or at least its shape and electrical conductivity) and a set of locations within the head model at which the electric field should be calculated can be specified. The model can be a realistic head model, which can be based, for example, on magnetic resonance imaging and / or computed tomography data of one or more individuals, or a simplified head model, such as a spherical head model. For example, the electric field can be calculated for a set of points on the cortex. Alternatively or additionally, the electric field can be calculated for a set of points on the scalp and / or on the face or other region of interest.

[0049] The set of intended electric field patterns in the head model (i.e., the set of electric field patterns that the coil set should be able to generate) can then be specified. The number of electric fields in this set is N E-field The specifications may be referred to as "intended locations, strengths, and directions of the maximum values of each electric field." Additional specifications may be provided to more precisely constrain the shape of some or all of the electric fields, for example, by requiring that the electric field strength at a certain location be below a threshold. Alternatively, a complete description (orientation, strength) of each electric field may be provided for each location.

[0050] The discretized volume V corresponds to the coil windings. transducer The set of current density distributions in i (r)|i=1,…,N coil For this purpose, various techniques can be used. In the first technique, the current density J i (r)(i=1,…,N E-field ) can be optimized within the coil volume inducing the ith intended electric field. This means that N E-fieldThis can be repeated for all intended electric fields. Then, J i (r)(i=1,…,N E-field ) and process the set of J' i (r), i=1,…,N coil A set of N can be generated, the (linear) combination of which can be used for mTMS. coil The current densities are, for example, the set J i (r)(i=1,…,N E-field )N coil In the second method, E i Set (r) (i=1,…,N E-field ) and E' i Set (r) (i=1,…,N coil ), the (linear) combination of which is N E-field Reproduce the original set of electric fields up to a threshold. coil The electric field is, for example, N E-field N of the set coil Then, E' can be calculated by i Current density J' corresponding to (r) i (r), i=1,…,N coil Optimization can be performed on

[0051] J' i (r), i=1,…,N coil The set of π can be discretized to obtain the winding paths of the coil windings. In particular, the discretization can be performed such that the set of coil windings closely approximates the set of current densities.

[0052] To find the current density corresponding to a given electric field, we use the discretized V transducerA set of divergence-free basis functions for the current density in can be defined. As mentioned above, one example of such a basis is provided by efficient divergence-free 3D RWG basis functions. The weights of the basis functions can be found, for example, by solving a convex optimization problem that minimizes the total magnetic field energy associated with the current density, with constraints in the optimization problem specifying the desired properties of the electric field. Such a convex optimization problem can be solved efficiently, for example, using an interior-point method.

[0053] The electric field calculations can be performed, for example, by utilizing any or all of the following: boundary element method, finite element method, analytical formulas.

[0054] Optimization can be performed in a variety of ways. Using a single head model and a single coil volume, optimization can be repeated with different relative placements of the head and coil volume to obtain an "average" coil winding that allows efficient stimulation across multiple cortical regions, rather than being optimal for only a single cortical region. Furthermore, optimization can be repeated with a single coil volume with different head models to obtain coil windings that generalize well across different heads. Symmetries can be exploited in the optimization to limit the number of independent basis functions, ultimately resulting in a coil module containing coils with some symmetry characteristics. If the coil volume consists of multiple identical but distinct regions, the final coil sets within similar subregions may need to be similar to each other to reduce the number of different coil modules that need to be manufactured.

[0055] As an example, "Coil optimization for transcranial magnetic stimulation in realistic head geometry" (http: / / hdl.handle.net / 10138 / 297793, open access, ISSN 1935-861X) describes a method for optimizing a single TMS coil on a 2D surface (triangular mesh). Also, "Multi-locus transcranial magnetic stimulation—theory and implementation" (https: / / doi.org / 10.101 6 / j.brs . 2018.03.014, open access) describes a method for optimizing a transducer (coil set) on a 2D surface (triangular mesh). The techniques presented in both papers can be adapted to the need for 3D coil optimization, for example, providing five or more coils for a transducer according to the present disclosure, by replacing the 2D basis functions with 3D basis functions.

[0056] Various functions discussed herein may be performed in different orders and / or concurrently with one another.

[0057] Any range or device value given herein can be expanded or modified without losing the effect sought, unless otherwise indicated, and any example can be combined with another example, unless expressly prohibited.

[0058] Although the subject matter has been described in language specific to structural features and / or acts, it should be understood that the subject matter defined in the appended claims is not necessarily limited to the specific features or acts described above. Rather, the specific features and acts described above are disclosed as example forms of implementing the claims, and other equivalent features and acts are intended to be within the scope of the claims.

[0059] It will be understood that the benefits and advantages described above may relate to one embodiment or to several embodiments. The embodiments are not limited to those that solve any or all of the stated problems or have any or all of the stated benefits and advantages. It will be further understood that references to "an" item may refer to one or more of those items.

[0060] The term "comprising" is used herein to mean including specified methods, blocks, or elements, but such blocks or elements do not comprise an exclusive list and a method or apparatus may include additional blocks or elements.

[0061] Numerical descriptors such as "first," "second," etc. are used herein merely as a method of distinguishing between otherwise similarly named components. Numerical descriptors should not be construed as indicating any particular order, such as priority, order of manufacture, or order of occurrence, in any particular structure.

[0062] In this text, the word "plurality" indicates that the entity referred to is plural, i.e., there are two or more entities in number.

[0063] While the present invention has been described in connection with certain types of devices and / or methods, it should be understood that the present invention is not limited to any particular types of devices and / or methods. While the present invention has been described in connection with numerous examples, embodiments, and implementations, the present invention is not so limited, but rather encompasses various modifications and equivalent arrangements falling within the scope of the claims. While various examples have been described above with a certain degree of particularity or with reference to one or more individual embodiments, those skilled in the art may make numerous modifications to the disclosed examples without departing from the scope of this specification.

Claims

1. 1. A multi-site TMS (Transcranial Magnetic Stimulation) transducer comprising one or more transducer modules adapted to be positioned on a subject's scalp for TMS, each of the one or more transducer modules comprising five or more coils for TMS of cortical targets of the subject.

2. 10. The transducer of claim 1, wherein the windings of any or all of the five or more coils span a three-dimensional volume.

3. 3. The transducer of claim 2, wherein the windings at the bottom of the corresponding transducer module of any or all of the one or more transducer modules are laterally confined within a bottom region and extend laterally beyond the bottom region upon longitudinal movement away from the bottom.

4. The transducer of any one of claims 1 to 3, wherein the bottom of the one or more transducer modules is curved to conform to the scalp.

5. A transducer according to any one of claims 1 to 3, wherein the base of any or all of the one or more transducer modules is hexagonal and / or pentagonal in shape.

6. 4. The transducer of claim 1, wherein the one or more transducer modules comprise a plurality of transducer modules adapted to be positioned adjacent to one another on the scalp of the subject for TMS.

7. 7. The transducer of claim 6, wherein the bottoms of the plurality of transducer modules form one or more patterns of one or more hexagons and / or pentagons surrounded by one or more hexagons.

8. The transducer of claim 6 , wherein the bases of the plurality of transducer modules form one or more patterns of a hexagon surrounded by three hexagons and three pentagons.

9. 7. The transducer of claim 6, wherein the bottoms of the plurality of transducer modules form one or more patterns in which a central transducer module is surrounded by a plurality of surrounding transducer modules, and the bottoms of any or all of the surrounding transducer modules have irregular shapes that expand the scalp footprint of the corresponding transducer module as they move away from the central transducer module.

10. 7. The transducer of claim 6, configured to simultaneously activate any or all of the five or more coils of two or more adjacent transducer modules of the plurality of transducer modules to stimulate a single cortical target.

11. 4. A transducer according to claim 1, wherein the five or more coils are adapted to generate a signal space of five or more dimensions, each of the five or more coils corresponding to an orthogonal basis vector of the signal space.

12. A transducer according to any one of claims 1 to 3, wherein the five or more coils of any or all of the one or more transducer modules have a mutual inductance coupling coefficient of less than 0.

1.

13. The transducer of any one of claims 1 to 3, wherein the five or more coils include circular coils.

14. A transducer according to any one of claims 1 to 3, wherein the five or more coils comprise two figure-eight coils perpendicular to each other.

15. 4. A transducer according to claim 1, wherein the five or more coils comprise two four-leaf clover coils rotated about a common longitudinal axis.

16. A transducer according to any one of claims 1 to 3, wherein the five or more coils have the same axis of symmetry.

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