Patent Description:
Transcranial magnetic stimulation (TMS) is a noninvasive technique used to apply brief magnetic pulses to the brain, or to other human organs, and to thereby activate neuronal structures. The pulses are administered by passing high currents by a stimulator through an electromagnetic coil externally placed upon the patient (for example, placed on the scalp for brain treatment), inducing electrical currents in the underlying tissue, thereby producing a localized axonal depolarization. This technique has become a major tool in central nervous system research, as well as a potentially promising treatment option for various neurobehavioral and neurological disorders.

Most known TMS coils stimulate superficial brain regions in the brain cortex, but the rate of decay of the induced magnetic and electric field as a function of distance from the coil is high. Hence the efficacy of affecting deeper neuronal structures is low. Stimulating deeper neuronal structures may be feasible if the intensity of the induced field is greatly increased. Yet operation at such increased intensity may increase the risk for seizures and for physiological damage to the tissue.

A method for deep brain TMS with minimal stimulation of superficial regions is disclosed in <CIT>, wherein deep brain stimulation is made possible while minimizing side effects. The device described therein includes a base and an extension portion, the base having individual windings for individual paths of current flow, and the extension portion designed so as to minimize unwanted stimulation of other regions of the brain.

However, there is a need for more specifically designed coils, which can target particular areas of the brain including deep neuronal structures with minimal effect on other brain regions. Examples of specific brain regions that may be desired to be stimulated are frontal lobe regions, occipital lobe regions, parietal lobe regions, right temporal regions and left temporal regions. Other examples may include activation of brain regions including deeper brain regions in a certain circumference of the brain, such as around a particular axial slice.

Thus, there is a need for specifically designed coils for deep TMS which are location-specific for frontal lobe, occipital lobe, parietal lobe or temporal lobe brain regions. The coils must induce the desired distribution of the electric field in the brain, and simultaneously induce electric field intensity in the relevant brain tissue which will be feasible for neuronal stimulation with available TMS stimulators for most of the population. The stimulation intensity is routinely calibrated individually for each subject based on his or her motor threshold. Hence the coil efficiency must guarantee that the motor threshold and stimulation intensity for most of the relevant population is within an acceptable range with respect to available stimulators power outputs.

The coils design must be efficient with respect to energy consumption, coil heating rate, compact size and ease of operation.

<CIT> discloses a system including a helmet, a positioning portion, a stimulator and a cooling system. The helmet includes a coil for deep brain magnetic stimulation. The coil has a base portion, and return portions, which may include a protruding return portion and a contacting return portion.

<CIT> discloses a magnetic stimulator comprising a frame and an electrically conductive coil having a partially toroidal or ovate base and an outwardly projecting extension portion. The electrically conductive coil may comprise one or more windings of electrically conductive material (such as a wire) coupled to the frame. The coil is electrically connected to a power supply. Further background art is disclosed in <CIT>.

The invention provides a coil for transcranial magnetic stimulation as claimed in claim <NUM>.

The definition of the base relates to the functional elements of the coil carrying electric currents. However, there is no limitation regarding other elements of the device, such as mechanical components, cases and covers. Thus, certain elements of the base may be encased in a case containing additional coil elements such as return elements and other elements.

The coil must induce the desired distribution of the electric field in the brain, and simultaneously induce an electric field intensity in the relevant brain tissue which is high enough to induce neuronal stimulation.

Several features of the coil are important in order to achieve the above goals. These include:.

Although materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable materials are described below. In addition, the materials and examples are illustrative only and not intended to be limiting.

The above and further advantages of the present invention may be better understood by referring to the following description in conjunction with the accompanying drawings in which:.

It will be appreciated that for simplicity and clarity of illustration, elements shown in the drawings have not necessarily been drawn accurately or to scale. For example, the dimensions of some of the elements may be exaggerated relative to other elements for clarity or several physical components may be included in one functional block or element. Further, where considered appropriate, reference numerals may be repeated among the drawings to indicate corresponding or analogous elements. Moreover, some of the blocks depicted in the drawings may be combined into a single function.

In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. It will be understood by those of ordinary skill in the art that the present invention may be practiced without these specific details. In other instances, well-known methods, procedures, components and structures may not have been described in detail so as not to obscure the present invention.

The present invention is directed to circular coils for deep TMS. The principles and operation of systems according to the present invention may be better understood with reference to the drawings and accompanying descriptions.

Before explaining at least one embodiment of the present invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings. Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of description and should not be regarded as limiting.

Reference is now made to <FIG>, which is a schematic illustration showing principles of stimulation for circular coils, in accordance with embodiments of the present invention. In the embodiment shown in <FIG>, a schematic illustration of a circular coil depicts the elements of a circular coil in accordance with embodiments of the present invention, but does not depict the actual appearance of these elements. As shown in <FIG>, circular coil <NUM> includes a base portion <NUM> and a return portion <NUM>. A "circular coil" is defined as a coil wherein base portion <NUM> encircles at least a portion of the body part and return portion <NUM> encircles at least a portion of the body part. Base portion <NUM> and return portion <NUM> are depicted schematically in <FIG> as being semi-circular in shape. However, it should be readily apparent that other shapes are possible and may also be configured to encircle a body part in accordance with embodiments of the present invention, as will be described further hereinbelow - for example with reference to <FIG>. Base portion <NUM> includes multiple stimulating elements <NUM>, depicted in <FIG> with arrows to illustrate the direction of electrical flow. Multiple stimulating elements <NUM> are shown as individual stimulating elements labeled first stimulating element <NUM>, second stimulating element <NUM>, third stimulating element <NUM>, fourth stimulating element <NUM> and fifth stimulating element <NUM>. It should be readily apparent that although five individual stimulating elements are shown in <FIG> schematically, circular coil <NUM> may include any suitable number of stimulating elements and are not limited to the amounts shown herein. Multiple stimulating elements <NUM> are substantially parallel to one another and are spaced apart from one another by distances, wherein first and second stimulating elements <NUM> and <NUM> are separated by a first stimulating distance D1, second and third stimulating elements <NUM> and <NUM> are separated by a second stimulating distance D2, third and fourth stimulating elements <NUM> and <NUM> are separated by a third stimulating distance D3, fourth and fifth stimulating elements <NUM> and <NUM> are separated by a fourth stimulating distance D4, and so on. Stimulating distances D1, D2, D3, etc. may be equal to one another or may vary in a random or periodic manner. The direction of electrical stimulation of each of stimulating elements <NUM> is substantially the same and is at least partially circular. That is, current flows through each of multiple stimulating elements in a curved or circular path, and multiple stimulating elements <NUM> are nested within one another, such that current flows in the same curved or circular path for each of stimulating elements <NUM>-<NUM> but separated by distances D1-D4.

Return portion <NUM> includes multiple return elements <NUM>. Return elements <NUM> are depicted in <FIG> with arrows to illustrate the direction of electrical flow. Multiple return elements <NUM> are shown as individual return elements labeled first return element <NUM>, corresponding to first stimulating element <NUM>, second return element <NUM> corresponding to second stimulating element <NUM>, third return element <NUM> corresponding to third stimulating element <NUM>, fourth return element <NUM> corresponding to fourth stimulating element <NUM> and fifth return element <NUM> corresponding to fifth stimulating element <NUM>. It should be readily apparent that although five individual return elements are shown in <FIG> schematically, circular coil <NUM> may include any suitable number of return elements and are not limited to the amounts shown herein. Generally, the number of return elements <NUM> corresponds to the number of stimulating elements <NUM>. Multiple return elements <NUM> are substantially parallel to one another and are spaced apart from one another by distances, wherein first and second return elements <NUM> and <NUM> are separated by a first return distance D10, second and third return elements <NUM> and <NUM> are separated by a second return distance D11, third and fourth stimulating elements <NUM> and <NUM> are separated by a third return distance D12, fourth and fifth return elements <NUM> and <NUM> are separated by a fourth return distance D13, and so on. Stimulating distances D10, D11, D12, etc. may be equal to one another or may vary in a random or periodic manner. It should be readily apparent from <FIG> that the direction of electrical flow for return elements <NUM> is a continuation of the circular path of electrical flow for stimulating elements <NUM>. Thus, if electrical flow for stimulating elements <NUM> is in a clockwise direction, electrical flow for return elements <NUM> is also in a clockwise direction. If electrical flow for stimulating elements <NUM> is in a counter-clockwise direction, electrical flow for return elements <NUM> is also in a counter-clockwise direction. In some embodiments, stimulating elements <NUM> are electrically connected to return elements <NUM> via connecting elements <NUM>. As shown in <FIG>, connecting elements <NUM> carry electrical flow in the same clockwise or counterclockwise direction as stimulating elements <NUM> and return elements <NUM>.

Reference is now made to <FIG>, which are schematic illustrations of base portion <NUM> in accordance with embodiments of the present invention. In one embodiment, as shown schematically in <FIG>, base portion <NUM> includes a first base portion group <NUM> and a second base portion group <NUM>. First base portion group <NUM> may be separated from second base portion group <NUM> by a first base portion group distance D20. In some embodiments, additional base portion groups may be included as well, and separated from one another by additional base portion group distances. Each base portion group is defined as a group by one of several criteria, including location, spacing, and connection to return elements. For example, first base portion group <NUM> may include multiple stimulating elements each separated by equal distances D1 and D2, while second base portion group <NUM> may include multiple stimulating elements separated from one another by equal distances D3 and D4, wherein D1 and D2 are different than D3 and D4. In another embodiment, first base portion group <NUM> may be configured to be positioned on one portion of the head while second base portion group <NUM> may be configured to be positioned on another portion of the head. In yet another embodiment, first base portion group <NUM> may be connected to return elements which are in contact with the head and second base portion group <NUM> may be connected to return elements which are protruding from the head. It should be readily apparent that a direction of current flow in first base portion group <NUM> is substantially the same as a direction of current flow in second base portion group <NUM>.

Reference is now made to <FIG> and <FIG>, which are illustrations of base portion <NUM> in accordance with additional embodiments of the present invention. In the embodiments shown herein, base portion <NUM> includes multiple stimulating elements <NUM> which follow a modified curved path. For example, as shown in <FIG>, each of multiple stimulating elements <NUM> is configured in a step formation on two ends of a substantially semi-circular path. As another example, as shown in <FIG>, each of multiple stimulating elements <NUM> is configure in a partially outwardly curved and partially straight formation. Many other configurations are possible. In all of the embodiments, multiple stimulating elements are configured to conform to the shape of the body part, such as the head, and to encircle at least a portion of the body part.

Return portion <NUM> may follow a similar pattern as base portion <NUM> or may have a different configuration. For example, as shown in <FIG>, base portion <NUM> may include a step configuration while return portion <NUM> may be semi-circular. As another example, as shown in <FIG>, base portion <NUM> may include a first base portion group <NUM> having a first configuration and a second base portion group <NUM> having a second configuration, while return portion <NUM> has a single configuration for all of return elements <NUM>. Alternatively, return portion <NUM> may include multiple return portion groups.

Reference is now made to <FIG>, which is an illustration of a return portion <NUM>, in accordance with embodiments of the present invention. Depicted in <FIG> is a return portion <NUM> configured to be positioned on a side of the head, although it should be readily apparent that similar configurations of return portion <NUM> may be used for other areas, such as a rear portion of the head, for example. Return elements <NUM> are shown at two different heights, wherein some of return elements <NUM> are configured to be in contact with a body part and are on a same plane as base portion <NUM> (not shown). These return elements <NUM> are referred to as contacting return elements <NUM>. Some of return elements <NUM> are configured to be protruding from the plane of base portion <NUM>, and are referred to as protruding return elements <NUM>. Protruding return elements <NUM> may be at a vertical distance or a horizontal distance from base portion <NUM>, as long as protruding return elements <NUM> are configured to protrude from circular coil <NUM> such that they are configured not to contact the body part which base portion <NUM> is configured to contact. Thus, connecting elements <NUM> may be horizontal connecting elements <NUM> or may be vertical connecting elements <NUM> or may have additional configurations as needed to connect return portion <NUM> to base portion <NUM>.

In some embodiments, some of multiple return elements <NUM> are contacting return elements <NUM> and some of multiple return elements <NUM> are protruding return elements <NUM>. In examples not according to the claimed invention, all of multiple return elements <NUM> are contacting return elements <NUM>. In some examples not according to the claimed invention, all of multiple return elements <NUM> are protruding return elements <NUM>. Any combination of protruding and/or contacting return elements is possible.

Reference is now made to <FIG>, which is an illustration of anatomical sections of a head <NUM>. For the purposes of illustrating the present invention, head <NUM> has four sections: a frontal section <NUM> at a front portion of head <NUM>, a parietal section <NUM> to the rear of frontal section <NUM> and at a top portion of head <NUM>, a temporal section <NUM> on the side of head <NUM> and an occipital section <NUM> at a rear portion of head <NUM>. Circular coil <NUM> is configured such that base portion <NUM> with stimulating elements <NUM> are positionable on and at least partially encircle a first section of head <NUM>, and return portion <NUM> with return elements <NUM> are positionable on and at least partially encircle a second section of head <NUM> which is different than the first section. Thus, for example, base portion <NUM> may be positioned on frontal section <NUM> and return portion <NUM> on parietal section <NUM>. Alternatively, base portion <NUM> may be positioned on parietal section <NUM> and return portion positioned on occipital section <NUM>. In other examples base portion <NUM> may be positioned on frontal section <NUM> and return portion <NUM> on occipital section <NUM>. In this way, base portion <NUM> stimulates a section of the brain, while return portion brings returning current back at a section which is remote from the stimulated section of the brain. In some embodiments, both base portion <NUM> and return portion <NUM> are adjacent to the head, and in some embodiments, base portion <NUM> is adjacent to the head while return portion <NUM> is remote from the head. In some embodiments, connecting elements <NUM> are adjacent to the head and in other embodiments, connecting elements <NUM> are remote from the head.

Reference is now made to <FIG>, which is a perspective illustration of a coil <NUM> which is an example of a circular coil <NUM> in accordance with embodiments of the present invention. Coil <NUM> includes a base portion <NUM> having a first base portion group <NUM> of multiple stimulating elements <NUM>, a second base portion group <NUM> of multiple stimulating elements <NUM> and a third base portion group <NUM> of multiple stimulating elements <NUM>. Coil <NUM> further includes a return portion <NUM> including return elements <NUM> corresponding to multiple stimulating elements <NUM>. Thus, return portion <NUM> also includes a first return portion group <NUM> corresponding to first base portion group <NUM>, a second return portion group <NUM> corresponding to second base portion group <NUM>, and a third return portion group <NUM> corresponding to third base portion group <NUM>. In the embodiment shown herein, base portion <NUM> is configured to be positioned on a frontal section <NUM> of head <NUM> and return portion <NUM> is configured to be positioned on an occipital section <NUM> of head <NUM>. First base portion group <NUM> is positioned at a top portion of base portion <NUM>, and first return portion group <NUM>, corresponding to first base portion group <NUM>, is comprised of protruding return elements <NUM>. Second base portion group <NUM> is positioned below first base portion group <NUM>, and distances between multiple stimulating elements <NUM> of second base portion group <NUM> are greater than distances between multiple stimulating elements <NUM> of first group <NUM>. Second return portion group <NUM> corresponding to first base portion group <NUM> is comprised of contacting return elements <NUM>, which are configured to contact and at least partially encircle an occipital section <NUM> of head <NUM>. Third base portion group <NUM> is positioned below first and second base portion groups <NUM> and <NUM>, and includes multiple stimulating elements <NUM> which have a different shape than multiple stimulating elements <NUM> of first and second base portion groups <NUM> and <NUM>. Third return portion group <NUM> corresponding to third base portion group <NUM> is comprised of contacting return elements <NUM> and is positioned above second return portion group <NUM>. Third return portion group <NUM> is also configured to be positioned on occipital section <NUM> of head <NUM>. Connecting elements <NUM> include vertical connecting elements <NUM> and horizontal connecting elements <NUM> wherein horizontal connecting elements <NUM> protrude from base portion <NUM>.

Coil <NUM> is used to stimulate lateral and medial prefrontal and orbitofrontal brain regions with a bilateral symmetry, and may be useful for treating, for example, Alzheimer's disease.

Reference is now made to <FIG>, which is a perspective illustration of a coil <NUM>, which is an example of a circular coil <NUM> in accordance with embodiments of the present invention. Coil <NUM> is similar in construction to coil <NUM>. However, third base portion group <NUM> of coil <NUM> has a different configuration than third base portion group <NUM> of coil <NUM>. Third base portion <NUM> of coil <NUM> has a step configuration such as that shown in <FIG>.

Reference is now made to <FIG>, which is a perspective illustration of a coil <NUM>, which is an example of a circular coil <NUM> not in accordance with the claimed invention.

Coil <NUM> includes a base portion <NUM> having a first base portion group <NUM> of multiple stimulating elements <NUM> and a second base portion group <NUM> of multiple stimulating elements <NUM>. Coil <NUM> further includes a return portion <NUM> including return elements <NUM> corresponding to multiple stimulating elements <NUM>. In the embodiment shown herein, base portion <NUM> is configured to be positioned on an occipital section <NUM> of head <NUM> and return portion <NUM> is configured to be positioned on a top of parietal section <NUM> of head <NUM>. Alternatively, base portion <NUM> may be positioned on a parietal section <NUM> and return portion may be positioned on an occipital portion <NUM> of head <NUM>. First base portion group <NUM> is positioned at a lower portion of base portion <NUM> and second base portion group <NUM> is positioned higher than first base portion group <NUM> and is separated from first base portion group <NUM> by a distance D20. Return elements <NUM> of return portion <NUM> are contacting return elements <NUM>, which are configured to contact and at least partially encircle portion of head <NUM>. Connecting elements <NUM> are configured to contact the head as well.

Coil <NUM> is used to stimulate occipital brain regions and regions in the cerebellum and may be useful for treating, for example, Parkinson's disease or migraine.

The field distribution produced by coil <NUM> of <FIG> was measured in a human head phantom model. A probe was moved in three directions inside the phantom model using a displacement system with <NUM> resolution, and the field distribution of coil <NUM> was measured in the whole head model volume with <NUM> resolution. Axial and coronal field maps were produced. The field maps were superimposed on anatomical T1-weighted MRI coronal slices, to show the induced field in each anatomical brain region.

Reference is now made to <FIG>, which is an illustration of electric field distribution maps of coil <NUM> as measured in the human head phantom model. The field maps are shown for stimulator output set at <NUM>% of threshold. The dark pixels indicate field magnitude above the threshold for neuronal activation. The threshold was set to <NUM> V/m, which is within the accepted range of thresholds required for hand motor activation. The intensity of stimulator power output used for drawing the maps representing the distribution of the electric field for coil <NUM> was set to the level required to obtain <NUM>% of the neural motor threshold, at a depth of <NUM>, according to the approximate depth of hand motor cortex sites. It can be seen that when placing the base portion of coil <NUM> over the prefrontal cortex, supra-threshold field is induced bilaterally in lateral prefrontal, medial prefrontal and orbitofrontal regions and in parietal regions. Coil <NUM> is being used in a clinical trial studying the safety and efficacy of treating subjects suffering from Alzheimer's disease. Subjects receive <NUM> treatments per week for <NUM> weeks and <NUM> treatment /week for an additional <NUM> weeks. Assessments are performed at <NUM>- <NUM> weeks and also after <NUM> weeks, i.e. <NUM> weeks after treatment completion. Analysis after <NUM> patients revealed that in the group treated with this coil at <NUM> frequency there was improvement of <NUM> points at the end of the <NUM> week treatment period and additional improvement of <NUM> points at the <NUM> week follow up (total improvement of <NUM> points). The sham group showed no change at <NUM> weeks and a <NUM> point worsening at the <NUM> week follow up (total worsening of <NUM> points). The percentage of patients improving more than <NUM> points (responders) in the stimulation group was <NUM>%, as opposed to <NUM>% in the sham group. From the analysis of individual patient data, it appears that those subjects with more severe cognitive dysfunction at baseline may have experienced more improvement from the active treatment than those with less severe cognitive dysfunction at baseline. In the computerized MindstreamsTr4 global cognitive score, a significant (p<<NUM>) difference was observed in the improvement of the group receiving the treatment, relative to the changes measured in the sham control group in the <NUM> and <NUM> weeks time points.

Reference is now made to <FIG>, which is an illustration of electric field distribution maps of coil <NUM> of <FIG>. The field distribution produced by coil <NUM> was measured using the same method as for <FIG>. The field maps are shown for stimulator output set at <NUM>% of motor threshold. It can be seen that when placing the base portion of the coil over the prefrontal cortex, supra-threshold field is induced bilaterally in lateral prefrontal, medial prefrontal and orbitofrontal regions and in parietal regions.

Reference is now made to <FIG>, which is an illustration of electric field distribution maps of coil <NUM> of <FIG>. The field distribution produced by coil <NUM> was measured using the same method as for <FIG>. The field maps are shown for stimulator output set at <NUM>% of motor threshold. It can be seen that when placing the base portion of the coil over the occipital cortex, supra-threshold field is induced bilaterally in occipital and cerebellar regions and in parietal regions.

Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination.

Claim 1:
A coil for magnetic stimulation of a head, the coil (<NUM>) comprising:
a base portion (<NUM>) including multiple adjacent stimulating elements (<NUM>), said base portion (<NUM>) configured to encircle at least a portion of a first section of the head and to provide electrical flow in a substantially clockwise or counter-clockwise path;
a protruding return portion (<NUM>) including multiple adjacent protruding return elements (<NUM>), said protruding return portion (<NUM>) configured to encircle and protrude from the head,
and to provide electrical flow in a continuation of the clockwise or counter-clockwise circular path of said base portion (<NUM>), wherein all of said multiple stimulating elements of said base portion are configured to contact the head and wherein all of said multiple protruding return elements are configured to protrude from the head; and
a contacting return portion (<NUM>) including multiple contacting return elements (<NUM>), said contacting return portion is configured to encircle and contact at least a portion of a second section of the head and to provide electrical flow in a continuation of the clockwise or counter-clockwise path of said base portion, characterised in that said first section is a frontal section of the head, and said second section is an occipital section of the head.