WO2018136429A1

WO2018136429A1 - Method of deep stimulation transcranial magnetic stimulation

Info

Publication number: WO2018136429A1
Application number: PCT/US2018/013900
Authority: WO
Inventors: Gary H. Glover; Amit Etkin
Original assignee: The Board Of Trustees Of The Leland Stanford Junior University
Priority date: 2017-01-19
Filing date: 2018-01-16
Publication date: 2018-07-26

Abstract

A method and device are disclosed for targeting deep brain structures. The method can include placing a transcranial magnetic stimulation device adjacent to a patient's scalp, wherein the transcranial magnetic stimulation device comprises a plurality of annular coils. The method can also include providing each of the plurality of annular coils with an amplitude and direction such that the magnetic field adjacent to the coil array is reduce and the magnetic field at greater depths survives. A device for targeting deep brain structures can include a plurality of transcranial magnetic stimulation coils, wherein each of the plurality of transcranial magnetic stimulation coils are configured to be annular to each of the other plurality of transcranial magnetic stimulation coils. The device can also include a plurality of power supplies configured to independently control each of the plurality of transcranial magnetic stimulation coils.

Description

METHOD OF DEEP STIMULATION TRANSCRANIAL MAGNETIC

STIMULATION

INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

[0001] Any and all applications for which a foreign or domestic priority claim is identified in the Application Data Sheet as filed with the present application are hereby incorporated by reference under 37 CFR 1.57.

BACKGROUND

[0002] Deep brain stimulation is hampered by square law reduction in field intensity with depth using conventional coils. Simply increasing the coil current fails because scalp stimulation limits the amplitude that can be applied to deep structures within the brain. For example, two elements of the default mode network, the PCC and ACC, are 50-60 and 30-40 mm deep, respectively, and impossible to target with current technology. Furthermore, positioning the Transcranial Magnetic Stimulation ("TMS") coil on the brain is currently done by trial and error, typically using muscle twitching, e.g. digits.

BRIEF DESCRIPTION OF THE DRAWINGS

[0003] Various embodiments are depicted in the accompanying drawings for illustrative purposes, and should in no way be interpreted as limiting the scope of the embodiments. Furthermore, various features of different disclosed embodiments can be combined to form additional embodiments, which are part of this disclosure.

[0004] Figure 1 illustrates an array TMS concept having a simulated magnetic field for a compound coil having 2 elements that suppress stimulation near the scalp surface in order to access deeper targets without over-stimulating regions near the brains surface.

[0005] Figure 2A illustrates a compound array having three elements positioned on a 17 cm spherical phantom used to simulate a brain.

[0006] Figure 2B-2C illustrates the measured magnetic field for a standard single element coil (2 A) and a 3 -coil array (2C). [0007] Figure 2D illustrates a graph of the magnetic field, and the single coil field and compound coil field of Figures 2B and 2C.

[0008] Figure 3A illustrates the depth of the magnetic field reached within brain tissue for various embodiments of the TMS Array.

[0009] Figure 3B illustrates an embodiment of the TMS array.

[0010] Figures 3C-3E illustrate measurements of the magnetic field made using an embodiment of the MRI mapping method.

[0011] Figures 4A-4D illustrate example color overlay maps.

DETAILED DESCRIPTION

Background

[0012] Present Transcranial Magnetic Stimulation ("TMS") systems are based on one or more single-loop coils, which generate a rapidly changing magnetic field as combinations of dipoles depending on the configuration, (often a two-coil figure-eight). With the coil placed as closely as possible adjacent to the human scalp, the intent is for the time-varying magnetic field to penetrate the brain, and induce electric field changes that transiently alter firing rates of neurons under the coil. In some embodiments, this can modulate local brain activity. Such technology can be used clinically for various therapeutic applications such as diminishing depression, as well as for neuroscience applications by virtue of temporary alteration of brain states in circuits under investigation.

[0013] While this technology works well for stimulating relatively shallow brain regions such as sensorimotor cortex or dorsolateral prefrontal cortex, it cannot reach deep brain structures such a posterior cingulate or amygdala, because the magnetic field falls off rapidly (as a dipole). This falling off of the magnetic field is illustrated in Figure 1 as shown by the blue curve. In some examples, this lack of penetration depth cannot be overcome by increasing the drive current. Increasing the drive current can cause muscles near the scalp to be over-stimulated, causing painful discomfort and/or harm to the shallow brain tissue.

[0014] While a number of studies have investigated methods for targeting deep brain structures with TMS, none have investigated using arrays of coils to allow steering to depths of 60 mm while allowing compatibility with fMRI. For example, the H-coil can achieve the aforementioned depth but will not fit in the RF coil. Overview of Multi-Coil TMS Array

[0015] To mitigate depth limitations of conventional technology, disclosed is a MRI-compatible array of TMS coils that can be configured to, for example, facilitate important studies of deep brain structures (e.g. up to 6 cm from the scalp).

[0016] As discussed above, Figure 1 shows an array TMS concept illustrating a simulated magnetic field for a compound coil having 2 elements (green and yellow) that suppress stimulation near the scalp surface in order to access deeper targets without over- stimulating regions near the brain surface. This design generates 85% of the field at the scalp (shown as Line j) compared with that from a conventional coil (shown as Linei) for the same field at depth of 35 mm.

[0017] In some embodiments, the amplitude and direction of each element's current is adjusted such that fields from the various elements buck each other along the plane close to the coil array. In some examples, the bucking of the various elements reduces the total field near the scalp, while at greater depths, the field survives. An example of the aforementioned is shown in Figures 2A-2D.

[0018] Turning to Figure 2A, illustrated is a compound array having three elements positioned on a 17 cm spherical phantom. The compound array can be configured to simulate a brain. Figure 2B illustrates a depiction of a measured magnetic field for a standard single element coil. Figure 2C illustrates a depiction of a measured magnetic for a 3-coil array. A comparison between Figure 2B and 2C shows a suppression of the field near the surface. Figure 2D depicts the magnetic field in phantom (shown as Lines), a single coil filed (shown as Lines), and a compound coil field (shown as Line₄). As discussed above, Figure 2D illustrates how the interference from the compound elements effectively eliminates the field near the surface while allowing deep penetration of the magnetic field.

[0019] In some embodiments, the test coils can have 2, 3, 4, 5, or 6 annular elements. In some examples, each coil element in the array can be configured to include separate power supplies and software. This can allow each coil element to be controlled for the desired depth of penetration. It may be possible to find fixed combinations that will allow fewer power supplies to energize the combined elements.

[0020] In some embodiments, each coil element in the array can include separate power supplies and/or software. This can allow each of the coil elements to be controlled for the desired depth of penetration. In some examples, the array of TMS coils can have any number of configurations to allow for fewer or more power supplies to energize the each of the coil elements.

[0021] In some examples, the device can include a combination of compound arrays into super arrays. In some embodiments, these super arrays will allow steering of the magnetic field by treating each compound array as a separate element. In some examples, by adjusting the currents in each compound element, the magnetic field can be steered laterally. In some embodiments, this can be accomplished by through destructive and/or constructive linear interference from the compound elements.

Methods of Mapping Multi-Coil TMS Arrays

[0022] As discussed above, disclosed below is a novel array based on guidance from electromagnetic (EM) modeling, utilizing an innovative rapid 3D field mapping method. With such arrays, time- sequential TMS pulse trains can be used to further examine causal relationships. In some embodiments, the methods can include software that will allow electronic steering of the targets. The software can be programed to disclose mapping techniques that will also be used to rapidly verify the target position at low stimulation amplitude before full stimulation is applied. In some embodiments, the verification of the target position can occur as quickly as less than 8 seconds.

[0023] In some embodiments, disclosed is a novel 3D field mapping method that can be configured to be used with the TMS array. The mapping method can provide information that can be used to, for example, develop the coil technology and to verify correct targeting location in the brain during use.

Example 1

[1)024 ] A 3T fMRI-TMS can be implemented concurrent with a Figure- 8 coil. This system can be used to provide mapping capabilities. In some embodiments, this system includes a compact compressed-air-cooled coil to enable rTMS. In some embodiments, the system includes at least one penetration-panel filter. In some embodiments, the system includes circuitry triggered by the scanner to protect the RF coil from the large TMS dB/dt pulses. Such circuitry can be necessary to prevent the destruction of RF preamps and T/R switch PIN-diodes. In some embodiments, the system can include a precise timing software to trigger the scanner and TMS stimulator. Example 2

[1)025 ] In some examples, the above-referenced device includes modeling software to enable optimal designs of array coils. Using Maxwell's equations, coil arrays can be simulated and modeled in low power single- or few-turn #24 magnet wire coils as shown in Figure 3B. In some embodiments, the model can include a 17 cm sphere phantom. In some examples, a preliminary design uses 4 coils nearly co-planar on the scalp surface and a larger coil ~ 30 mm deeper. As shown in Figure 3A, the 5 coil array shows near extinction of field until a depth of 45 mm, then subsequently a slow roll off. In some examples, the power deposited in a 5 coil array can be nearly 7.9 times that of single coil. As illustrated in Figure 3A, maximum field is illustrated at 6 cm deep with a magnetic field of only 9% at the surface.

[0026] Figures 3C-3E illustrate measurements made using our MRI mapping method. Figure 3C illustrates the magnetic field of a conventional coil at 5 mm slice increments; Figure 3D illustrates the magnetic field of a 3-coil array at 5 mm slice increments; and Figure 3E illustrates the magnetic field of a 5 -coil array at 5 mm slice increments. These designs were developed by iterative hand optimization, calculating fields only on the axis. In some examples, the MRI mapping method can be built on SemCad X (commercial electromagnetic (EM) finite element package) that calculates the B and E fields in 2 dimensions (depth and radial distance from array axis) using its built- in models of human brain dielectric properties.

[0027] The aforementioned program will solve a regularized iterative problem, for example:

[0028] where E is the electric field and P_t is the power deposited in the z^'th coil element. The B fields will also be calculated, for comparison with low power

measurements.

[0029] In some embodiments, the total power will be considerably higher for an array than for a single loop (e.g. this can be nearly 8 times as shown in Figures 3A-3D) or even a conventional Figure-8 coil. In some examples, this can be mitigated by making the elements out of hollow Cu tubing and using chilled (deionized) water cooling.

Because the specific heat of water is many times that of air, this can be used to eliminate cooling concerns. [0030] In some examples, because the coil elements are distributed in space, this can provide heat dissipation. In some embodiments, because large amounts of Cu in the RF field can distort the magnetic fields, this can requires an increase of about 1.5 dB in transmitter gain resulting in a concomitant SNR loss. In some embodiments, the 4 coils of our preliminary design will lead to a similar or smaller loss (the SNR loss is much smaller than might be expected for the same reason demonstrated with EEG caps). To test the effect of the larger element, we replaced the single turn magnet wire with the proposed 2 turn 6.3 mm ID Cu coil, and observed only a 0.2 dB loss when placed coaxial with the magnet bore (roughly the orientation used to target cortical areas in this proposal, and a loss of 1.4 dB in the worst orientation.

Example 3 -

[0031] Also disclosed is a technique for three-dimensional magnetic field mapping. This method can involve scanning the TMS array in the 3T magnet. The method can use a 6 channel programmable power supply to excite the array elements as desired with o(100 ma/element) and acquire a volume of phase images, then the pulse sequence turns off the current and acquires a second volume and subtracts the phases. In some embodiments, a spiral sequence with 5ms TE is used to make color overlay maps of 32 slices on the scanner in about 6s for scanning and about 2s of postprocessing and display. This is illustrated in Figures 4A-4D. Figure 4A illustrates the measured magnetic field for a conventional figure-eight coil. While only measurements along the z- axis of the magnetic field can be measured with MRI, these maps are very useful in verifying target regions during setup of the TMS-fMRI scan (see e.g., Figures 4B-4D). Another example was provided above in Figure 3A illustrating maps for the 5 coil array on phantom where slices are space 5 mm apart. In some embodiments, the technique for three-dimensional magnetic field mapping includes an interface for the actual TMS coils. The coils can have high power connectors that plug into the conventional single coil stimulators. Example 4

[1)032 ] In some embodiments, the TMS array includes 6 array elements. Such an arrangement can be configured to reach 60 mm with adequate amplitude (to target PCC). In some examples, this mechanical design can be able to adjust the element currents to target shallower structures, such as the ACC (30-40 mm) or cortical regions that are closer to the scalp surface.

[0033] For example, Figure 4B shows that the field at depth is not highly localized; experimental results (not shown) demonstrate that the single coil element can be replaced with two concentric coils that reduce the amplitude near the scalp.

[0034] In some embodiments the TMS array will be a low power model. In some examples, the resulting design can be constructed using water cooled Cu coils, with housing fabricated as a 3D-printed structure.

[0035] Any structure, feature, or step in any embodiment can be used in place of, or in addition to, any structure, feature, or step in any other embodiment, or omitted. This disclosure contemplates all combinations of features from the various disclosed embodiments. No feature, structure, or step is essential or indispensable.

Claims

WHAT IS CLAIMED IS:

1. A method for targeting deep brain structures, the method comprising: placing a transcranial magnetic stimulation device adjacent to a patient's scalp, wherein the transcranial magnetic stimulation device comprises a plurality of annular coils; and

providing each of the plurality of annular coils with an amplitude and direction such that the magnetic field adjacent to the coil array is reduce and the magnetic field at greater depths survives.

2. The method of Claim 1, wherein the transcranial magnetic stimulation device comprises up to 6 annular coils.

3. The method of Claim 1, wherein the magnetic field is provided at a depth of 6 cm from the patient' s scalp.

4. A device for targeting deep brain structures, the device comprising:

a plurality of transcranial magnetic stimulation coils, wherein each of the plurality of transcranial magnetic stimulation coils are configured to be annular to each of the other plurality of transcranial magnetic stimulation coils; and

a plurality of power supplies configured to independently control each of the plurality of transcranial magnetic stimulation coils.

5. The device of Claim 4, wherein the device comprises 6 annular transcranial magnetic stimulation coils.

6. The device of Claim 4, wherein the device is configured to provide a magnetic field 6 cm below a patient' s scalp.