Abstract:
A quadrupolar-solenoidal electro-magnet creates more nearly parallel field lines and a coaxial magnetic bias resulting in allowing deeper magnetic field penetration with reduced depth attenuation and greater focality than available with the commonly used Figure-8 dual toroidal magnets, thereby overcoming the trade-offs inherent in currently standard practice for transcranial magnetic stimulation magnetic field generation and the proposed transcranial magnetic stimulation coil designs. When quadrupole electro-magnets are used with solenoids, the axis of the electro-magnets can be focused at the target within the desired tissue and at greater depth.

Description:
BACKGROUND 
     Transcranial magnetic stimulation (TMS) is a non-invasive technique that is used clinically and as an investigatory method in many research and therapeutic applications. Use of TMS on both normal and pathological brain functions has been studied, and TMS has been used in the treatment of neurological and psychiatric disorders including major depression, schizophrenia, dystonia, autism, pain relief, and chronic migraine. Magnetic fields can penetrate and induce electric fields in tissue of other types, as well, tissues such as muscle, liver, and kidney. 
     Traditionally, TMS uses brief, intense pulses of electric current delivered to a coil placed adjacent to the subject&#39;s head. During the pulses, changes in the magnetic field internal to the target brain tissue create resultant electric fields within the brain via electro-magnetic induction. The induced electric field modulates the neural transmembrane potentials and, hence, neural activity. The focus of activation in the brain is approximated by the volume where the induced electric field is nearly maximal. This location depends on stimulating coil field strength, coil geometry, and coil placement. 
     A dual toroid Figure-8 magnet configuration is commonly used for generating the magnetic field for brain stimulation, but a variety of innovative coil designs are now being proposed and studied. 
     To map direct neural activity stimulated using TMS, the induced electric field distributions generated by different coil designs have been characterized by theoretical calculations, numerical simulation models, and measurements of the electric currents induced in phantoms or in vivo. Analytical studies have used idealized circular and Figure-8 coil geometries. Only a few commercial coils have been modeled in computational analyses. Thus, field distribution data for many commercial, experimental, or proposed TMS coil designs remain unavailable. Knowledge of electric field spatial distributions generated with specific coil designs and how these fields compare with those generated by alternative coil designs is valuable in the design and interpretation of basic research and clinical studies. Indubitably, the development of novel coil design has been inhibited by the lack of theoretical comparison of the efficacy of presently available or proposed designs. 
     The two most salient electric field spatial considerations with respect to TMS are depth of penetration (especially field attenuation with depth and with respect to orientation of the coil&#39;s major axis) and focality—the ability of a chosen coil to focus (concentrate) a magnetic field deep within the subject tissue. Actual proposed or implemented coil designs have been developed with the objective of improving one or both of these field characteristics. All designs require a tradeoff between attenuation with depth and focality. Focality is important in attempting to target small volumes while simultaneously avoiding similar effects in adjacent non-targeted volumes. 
     There has also been substantial interest in direct, non-invasive stimulation of brain volumes deeper than the superficial cortex, but electric fields in such deep brain targeting capability is limited by the rapid attenuation with penetration depth. Fields from larger coils penetrate deeper but have reduced focality. Reduced focality is a serious limitation to both clinical and basic neuroscience applications because stimulation of non-target brain regions may affect clinical outcomes, and certainly affect the degree to which any observed changes in behavior can be attributed to stimulation alone. A constant background fear by researchers or clinicians has been associated with understanding and controlling electric field depth and focality. This fear concerns an increased risk of accidental seizure and other adverse side effects. 
     The variety of types of magnetic fields which might be of interest in the study of magnetic brain stimulation has been described by Deng et al. In these studies a spherical saline-filled phantom was used to model the human head. 
     Additional relevant information may be found in “Three-dimensional distribution of the electric field induced in the brain by transcranial magnetic stimulation using Figure-8 and deep H-Coils,” by Roth, Amir, Levkovitz, and Zangen in the Journal of Clinical Neurophysiology (2007 February; 24(1):31-8); “Coil Design Considerations for Deep-Brain Transcranial Magnetic Stimulation (dTMS),” by Deng, Peterchev, and Lisanby, 30th Annual International IEEE EMBS Conference, Vancouver, British Columbia, Canada, Aug. 20-24, 2008; and “Electric field depth-focality tradeoff in transcranial magnetic stimulation: Simulation comparison of 50 coil designs,” in Brain Stimulation 6 (2013) 1-13 Brainsway, 19 Hartum Street, Bynet Building, 3rd floor, Har Hotzvim, Jerusalem 9777518, Israel. 
     The Brainsway reference provides a wide-ranging description of a whole family of coils called Hesed (H) coils that have been proposed to achieve effective stimulation of deep brain structures. The Hesed coils have complex winding patterns and larger dimensions compared to conventional TMS coils and consequently can be expected to have reduced electro-magnetic field depth attenuation and reduced focality. It has been proposed to use high-permeability ferromagnetic cores to improve the electric efficiency, field penetration, and focality of Hesed coils. 
     In short, there has long been interest in transcranial magnetic stimulation but as yet no effective way to produce controlled, predictable and safe stimulation deep inside the brain. A device that would achieve these goals would be advantageous in research and in medical treatment. 
     SUMMARY 
     This disclosure describes a method of creating more nearly parallel magnetic force field lines at a significant distance from the electro-magnetic apparatus that generates the magnetic field. The electro-magnetic apparatus has a quadrupole electro-magnet that may include a solenoid with or without a ferromagnetic core coaxial with the quadrupole. The quadrupole functions like a magnetic lens, and thus permits focusing of the magnetic force field lines. Such a construction, placed adjacent to the subject tissue creates field lines capable of deeper penetration. 
     The electro-magnetic apparatus comprises a quadrupole having two elongated C-shaped electro-magnets oriented so that the poles comprise a North-South-North-South sequence about a common axis perpendicular to the plane of the ends of the elongated C-shaped magnets. This arrangement will provide for increased depth of field penetration and improve focality in various brain stimulation models including TMS. One or more solenoidal electro-magnets may be mounted coaxially to the quadrupole electro-magnets&#39; axis thereby providing a driving force for charged particles (for example, drug ions) and permitting deep penetration, not only of the magnetic field for TMS but also for introducing charged particles directly into the cerebrospinal fluid (CSF) surrounding the brain. 
     By using an electro-magnetic apparatus that includes at least one electro-magnetic quadrupole lens and at least one coaxially mounted solenoid, a unidirectional, focused, magnetic field can be established that may be used in two ways. First, it produces an electric stimulation in the brain believed to have therapeutic effect and useful for TMS experimental evaluations and clinical treatments. Second, it will both accelerate and focus a beam of charged particles by generating a force field parallel to the quadrupole axis. That focused beam drives the charged particles deep into biological tissue, including into tissue other than the brain, with minimal field divergence. The quadrupole design focuses a flow of charged particles while the solenoidal field accelerates the flow. The charged particles may include pharmaceuticals. 
     Solenoidal coils lead to more nearly parallel field lines that remain bunched together at greater distances from the plane perpendicular to the electro-magnetically coil axis. The combination of a solenoid and quadrupole electro-magnets biases the quadrupolar field by the solenoidal field in such a manner that charged particles may be transported along the common solenoidal-quadrupolar axis and concentrated in small, nearly spherical regions deep within biological tissues including, for example, the brain, kidneys, liver, and muscles. 
     The described electro-magnetic apparatus is mounted to an articulating arm that allows it to be rotated in both the sagittal and coronal planes and in planes parallel to the sagittal and coronal planes. The focused beam from the electro-magnetic apparatus may be used to for treatment of neurological and psychiatric disorders and delivery of pharmaceuticals to the target area. 
     A feature of the invention is an elongated, C-shaped, electro-magnet having non-parallel pole piece faces coupled with a similar, opposing, inverted, and elongated C-shaped electro-magnet so that the north and south poles of the two electro-magnets alternate at regularly spaced intervals, thereby creating a symmetrical quadrupolar magnetic field. Pole pieces in the preferred quadrupole arrangement are oriented at 45° with respect to the proposed elongated C-shaped electro-magnets. 
     To drive this electro-magnetic apparatus for tissue penetration, pulses of direct current must be generated. A power supply for generating the pulses may require energy storage and one or more phase-adjusting capacitors. Pulses less than 10 microseconds are suitable for brain stimulation and can produce magnetic fields of several Teslas. 
     Another feature of the disclosure is extending of the pole pieces parallel to the electro-magnetically quadrupole axis, so that this elongated electro-magnetic assembly may be as much as approximately ten times the length of the internal portion of the axis of the electro-magnet, resulting in an aspect ratio several times (2-10×) that of a standard C-shaped electro-magnet. 
     Another feature of the disclosure is that the solenoid may have a ferromagnetic core, mounted coaxially with the quadrupole&#39;s focal axis. 
     Yet another feature of the disclosure is a solenoidal coil that has an axis coaxial with the quadrupole&#39;s focal axis and is inserted within the C-shaped quadrupole electro-magnets, and is either wholly contained within the quadrupole or extends from one or both of the quadrupole&#39;s ends beyond the planes defined by the ends of the quadrupole. 
     A feature of the disclosure is the mounting of the electro-magnetic apparatus to an articulating arm so that it can be rotated in either the sagittal and coronal planes about a point located on the intersection of those planes or any two planes parallel to the sagittal and coronal planes. The sagittal plane is the vertical plane passing through the top of the head and dividing the nose. The coronal plane passes vertically through the top of the head and the ears. The sagittal plane and the coronal plane are perpendicular to each other with the intersection being the line passing vertically through the center of the top of the head. 
     Another feature of the disclosure is the use of a stacked array of multiple quadrupoles having poles oriented at 90° with respect to the adjacent quadrupole in order to achieve improved focality, and use of this stacked array combined with solenoids to achieve a focused beam capable of deeper penetration while creating a driving field for charged particles. The number of quadrupoles in the array is preferably an even number greater than four. 
     Those skilled in the art of transcranial magnetic stimulation will appreciate many other features and their advantages from a careful reading of the detailed description, accompanied by the drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In the drawings, 
         FIG. 1  is a left rear perspective view of the present electro-magnetic beam generator, according to an aspect of the disclosure; 
         FIG. 2  is a left front perspective view of the present electro-magnetic beam generator, according to an aspect of the disclosure; 
         FIG. 3  is a right side view of the present electro-magnetic beam generator, according to an aspect of the disclosure; 
         FIG. 4  is a left side view of the present electro-magnetic beam generator, according to an aspect of the disclosure; 
         FIG. 5  is a front view of the present electro-magnetic beam generator, according to an aspect of the disclosure; 
         FIG. 6  is a bottom view of the present electro-magnetic beam generator, according to an aspect of the disclosure; 
         FIG. 7  is a top view of the present electro-magnetic beam generator, according to an aspect of the disclosure; 
         FIG. 8  is a rear view of the present electro-magnetic beam generator, according to an aspect of the disclosure; 
         FIG. 9  is a perspective view of the present electro-magnetic beam generator suspended from a positioning arm, according to an aspect of the disclosure—Sagittal and Coronal Planes for Human Head. 
     
    
    
     DETAILED DESCRIPTION 
     Referring now to  FIGS. 1-8 , there is shown an electro-magnetic apparatus  10  suitable for transcranial stimulation and other purposes. Apparatus  10  includes a quadrupole  14  having a common axis  18  with a solenoid  22 . 
     Quadrupole  14  is constructed of two elongated C-shaped electro-magnets  26 ,  28 , each having a coil  30 ,  32 . Electro-magnet  26  has non-parallel pole pieces  34 ,  36 , and electro-magnet  30  has non-parallel pole pieces  40 ,  42 . Pole pieces  34 ,  36 ,  40 ,  42 , represent magnetic North, South, North, South, respectively. 
     Electro-magnet  26  is inverted with respect to electro-magnet  28  so that North-South poles alternate at regularly spaced intervals, thereby creating a symmetrical quadrupole field. Additionally, pole pieces  34 ,  36 ,  40 ,  42 , in the preferred quadrupole arrangement are at 45° to their respective elongated C-shaped electro-magnets  26 ,  28 , as best seen in  FIG. 5 . 
     A driving power supply  50  for quadrupole  14  and a power supply  52  for solenoid  22  may require energy storage plus one or more additional phase-adjusting capacitors in order to apply pulsed direct current. Current is carried from power supply  50  to and from coils  30 ,  32 , via conductors  54 ,  56 , and  58 , and to power supply  52  via conductors  62 ,  64 . 
     Pole pieces  34 ,  36 ,  40 ,  42 , may extend in a direction parallel to common axis  18  by as much as approximately 10 times the length of coils  30 ,  32 . The elongation of electro-magnetic apparatus  10  may create an aspect ratio several times (2-10×) that of a standard C-shaped electro-magnet. 
     For example, pole pieces  34 ,  36 ,  40 ,  42  may be made of a ferromagnetic material 1-3 mm thick. Pole pieces  34 ,  36 ,  40 ,  43  may be made by bending, or otherwise shaping, and then annealing steel plate to obtain the 45 degree angle, being careful to obtain uniformity at the Neel boundaries in the immediate vicinity of the bend. Alternatively, a 3-dimensional printer may be used to form a model of a pole piece and the core as a single unit. A sand mold may be made from the model, filled with ferromagnetic material, and sintered. Other manufacturing methods known to those skilled in the art may alternatively be used. 
     Solenoid  22  may also extend beyond one or both of the planes defined by the ends of the pole pieces  34 ,  36 ,  40 ,  42 . Solenoid  22  may have a core  70 , as shown, which may be hollow and may be made of a ferromagnetic material or may be made of a non-ferromagnetic material. Core  70  provides support for the coils of solenoid  22 . 
     Common axis  18  is the focal axis of quadrupole  14  and the axis of solenoid  22  and is therefore the axis of electro-magnetic device  10 . Having common axis  18  for both quadrupole  14  and solenoid  22  creates a magnetic field bias which can be used to drive charged particles along common axis  18  into the subject tissue. 
     Referring now to  FIG. 9 , there is illustrated the present electro-magnetic apparatus in a housing  74  suspended from an articulated arm  78  so as to be placed in position to stimulate the brain  82  of a patient  86 . Articulating arm  78  has a swivel base  90 , a pivotable first section  94 , and a pivotable second section  98  and a rotatable end effector  102 , all of which provide for positioning and orienting of housing  74  so that the common axis  22  of electro-magnetic apparatus  10 , as illustrated in  FIGS. 1-8 , can be pointed at and brought close to any part of brain  82  of patient  86 . In particular, articulating arm  78  must be capable of positioning housing  74  so that electro-magnetic apparatus  10  can be rotated in both the sagittal and coronal planes about a point located on the intersection of those planes as well as any and all planes parallel to these two planes so that a region of interest anywhere in brain  82  of patient  86  may be exposed to the magnetic field generated. The sagittal plane is the vertical plane passing through the top of the head and the nose. The coronal plane is the vertical plane that passes through the top of the head and the ears. The sagittal plane and the coronal plane are perpendicular to each other with the intersection being the line passing vertically through the top of the head. 
     In addition to brain stimulation, quadrupole  14  comprises two extended C-shaped electro-magnets  26 ,  30 , with or without solenoid  22 , which is able to drive a focused charged particle beam into the subject tissue (brain, muscle, bone, liver, kidney, etc.). When used to deliver charged particles to tissues other than brain tissues, the same articulating arm  78  may be used to position housing  74  with respect to the tissue of patient  86  to which the charged particles are to be delivered. 
     For delivering charged particles, a stacked array of quadrupoles  14  aligned along a common axis  18  with a longer solenoid  22  may be used to further improve focality at greater depth. Also, in addition to using several quadrupoles, the number of poles may be increased beyond the four poles in quadrupole  14  to six, eight or a higher (even) number of poles. 
     The length of the longer solenoid could be co-terminus with the length of the stacked quadrupoles or might extend beyond the ends of the stacked quadrupole ends, or be limited within the plane of the quadrupole ends. Adjacent electro-magnetic apparatuses  10 , as illustrated in  FIGS. 1-8 , can be placed coaxially, their ends separated by a short distance—between 0.1-1.0 times the apparatus length—from one another and each quadrupole oriented so that its poles are at 90° with respect to the next quadrupole assembly. 
     Those skilled in the art of transcranial magnetic stimulation apparatus design will appreciate that many modifications and substitutions may be made to the aspects of the disclosure presented above without departing from the spirit and scope of the appended claims.