Patent Publication Number: US-2022226664-A1

Title: Localized Voltage Generation in Volume Conductors

Description:
FIELD OF THE INVENTION 
     The present invention relates to the fields of acoustics, electromagnetics, and medicine. Specifically, the present invention relates to modulation and control of electrical signals within a volume conductor. 
     BACKGROUND OF THE INVENTION 
     The electrical potentials and currents in a volume conductor in response to an external electrical or magnetic stimulus have been extensively studied and modeled, and although it is possible to optimize an external stimulus to produce deeper penetration into the bulk of a volume conductor, it is not in general possible to produce a voltage or current far from the volume conductor&#39;s surface without producing a larger voltage or current close to the surface. This poses challenges in the fields of medicine and biology, where biological tissue acts as a volume conductor. It is often desirable to electrically stimulate electrically sensitive or active biological tissues, but these sensitive or active tissues often lie deep within an organism, requiring a significant stimulus to be applied to the surface of the organism in order to reach the deep tissues. This approach has the disadvantage that the resulting electrical stimulus has very poor spatial localization and may stimulate nearby tissues, the stimulation of which is undesirable. For this reason, it is often necessary to insert electrodes into biological tissue when localized stimulation is n required, an action which is invasive and generally undesirable. 
     For this reason, a method of producing localized electrical stimulation of a region deep within a volume conductor is valuable to the fields of biology and medicine. Such a method may also be useful in other fields such as plasma physics, where a plasma acts as a volume conductor, or microfluidics, where control and steering of colloidal particles using electrical potentials is an active area of research. 
     SUMMARY OF THE DESCRIPTION 
     The effect generated by the present invention is a band-limited electrical signal localized within a volume conductor. This effect is brought about by the application of a non-localized high-frequency electromagnetic stimulus to the bulk of the volume conductor, simultaneous with the application of a high-frequency acoustic stimulus which is synchronized or partially synchronized with the electromagnetic stimulus and which attains a maximum amplitude at a target focal point within the volume conductor. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The present invention is illustrated by way of example and not limitation in the figures of the accompanying drawings in which like references indicate similar elements. 
         FIG. 1  illustrates the essential elements of the present invention and their relation to one another, as well as a representation of the desired effects. 
         FIG. 2  illustrates application of a focused acoustic wave with displacement parallel to the direction of an electric field applied to the bulk material, according to one embodiment of the present invention. 
         FIG. 3  illustrates the effect of the acoustoelectric effect on the volume conductor in the focal region of the acoustic wave for the acoustic/electric oscillation shown in  FIG. 2 . 
         FIG. 4  illustrates the effect of nonuniform acoustic displacement on the volume conductor in the focal region of the acoustic wave for the acoustic/electric oscillation shown in  FIG. 2 . 
         FIG. 5  illustrates application of a focused acoustic wave with displacement perpendicular to a magnetic field applied to the bulk material, according to one embodiment of the present invention. 
         FIG. 6  illustrates the effect of electromagnetic induction on the volume conductor in the focal region of the acoustic wave for the acoustic/magnetic oscillation shown in  FIG. 5 . 
         FIG. 7  illustrates application of both electric and magnetic field components in conjunction with a focused acoustic wave and their synchronization to generate a localized effect, according to one embodiment of the present invention. 
         FIG. 8  illustrates the generation of an intermediate-frequency acoustic effect localized at the intersection of two focused, higher-frequency acoustic waves and its synchronization with applied magnetic or electric fields, according to one embodiment of the present invention. 
     
    
    
     DETAILED DESCRIPTION 
     Various embodiments and aspects of the inventions will be described with reference to details discussed below, and the accompanying drawings will illustrate the various embodiments. The following description and drawings are illustrative of the invention and are not to be construed as limiting the invention. Numerous specific details are described to provide a thorough understanding of various embodiments of the present invention. However, in certain instances, well-known or conventional details are not described in order to provide a concise discussion of embodiments of the present inventions. 
     A first necessary element of the present invention is the application of an electromagnetic stimulus to the bulk of the volume conductor. This stimulus may be primarily electric, such as the application of an electric potential across the volume conductor, as shown in  FIG. 2 , primarily magnetic, such as the application of a magnetic field to the volume conductor, as shown in  FIG. 5 , or a combination of electric and magnetic, as shown in  FIG. 7 . The electromagnetic stimulus may be applied using any of the known application methods, including surface electrodes and field coils. The electromagnetic stimulus may be substantially uniform over the volume conductor, or it may have a generally greater amplitude in the vicinity of the target focal region, but because of the properties of volume conductors, its amplitude will inevitably be greatest near the surface of the volume conductor. 
     A second necessary element of the present invention is an acoustic stimulus. The acoustic stimulus may have any required frequency components, including ultrasound or infrasound. The acoustic stimulus is generated and applied to the volume conductor in such a way that the acoustic displacement, velocity, or pressure, or the component of the displacement, velocity, or pressure that synchronizes with the electromagnetic stimulus, attains a maximum amplitude in a focal region within the volume conductor. The focal region may comprise the entire volume conductor, but in most embodiments, it comprises a volume contained within the bulk of the volume conductor away from the surface of the volume conductor. The acoustic stimulus may be generated, shaped, and applied to the volume conductor using any of a number of known methods, including phased arrays, acoustic lenses, and shaped transducers. The acoustic stimulus may also be constructed such that a high-frequency primary stimulus gives rise to an intermediate-frequency secondary stimulus generated at the focal region by way of radiation pressure modulation, a phenomenon used in the known field of vibro-acoustography and illustrated in  FIG. 8 . Additionally, the acoustic stimulus may form a standing wave, a traveling wave, or a combination of standing and traveling waves. 
     A third necessary element of the present invention is a coordination between the acoustic stimulus and the electromagnetic stimulus. The electromagnetic and acoustic stimuli must be temporally coordinated such that the acoustic activity in the target focal region is synchronized or partially synchronized with the electromagnetic stimulus in such a way that the response of the volume conductor to the electromagnetic stimulus is modulated so as to produce a lower-frequency component. This modulation may arise as a result of various effects, including electromagnetic induction on a moving portion of the volume conductor as illustrated in  FIG. 6 , the acoustoelectric effect on volume conductors as illustrated in  FIG. 3 , and nonuniform acoustic displacement of the volume conductor as illustrated in  FIG. 4 . 
       FIG. 1  illustrates the necessary components of the present invention. The volume conductor  1  contains a target focal region  2  in which a certain electrical response is desired. An electromagnetic stimulus  3  is applied to the bulk of the volume conductor  1 , including the focal region  2 . The acoustic stimulus  4  has a synchronization relation  5  with the electromagnetic stimulus  3  and is applied to the volume conductor  1 , and particularly to the focal region  2 . The electromagnetic stimulus  3  produces a higher-frequency response  6  in the bulk of the volume conductor  1 , while in the focal region  2 , the combination of the acoustic stimulus  4  and the electromagnetic stimulus  3  produces both the higher-frequency response  6  found throughout the volume conductor  1  and a desired lower-frequency response  7 . 
       FIG. 2  illustrates an embodiment of the present invention in which the electromagnetic stimulus  3  is primarily electric and is applied to the volume conductor  1  via surface electrodes  8 . The electromagnetic stimulus  3  in this case comprises a sinusoidal waveform with period T. The acoustic stimulus  4  is applied by a phased array ultrasound transducer  9  in contact with the volume conductor  1 . In this case, the acoustic stimulus  4  comprises a sinusoidal waveform  10 , also with period T, and focused on the target focal region  2 . In this case, the unmodulated voltage  11  produced in the volume conductor  1  far from the focal region  2  is a simple sinusoidal waveform of period T, with a constant lower-frequency component  12  of zero. The focal region&#39;s voltage  13  consists of a sinusoidal waveform of period T with a nonzero lower-frequency component  7  consisting of a constant DC voltage. The lower-frequency component  7  is produced as a result of the combination of the acoustoelectric effect illustrated in  FIG. 3  and the effect of nonuniform acoustic displacements illustrated in  FIG. 4 . Although the lower-frequency response  7  in this example is a DC signal, changing the synchronization relation between the electromagnetic stimulus  3  and the acoustic stimulus  4  can produce a lower-frequency component  7  with a variety of waveforms. 
       FIG. 3  illustrates the mechanism by which the acoustoelectric effect gives rise to a lower-frequency response  7  in the focal region  2  when a primarily electric stimulus  3  is applied in conjunction with a synchronized or partially synchronized acoustic stimulus  4 . During a first phase  14  of the electric and acoustic stimuli, the pressure in the −x side  15  of the focal region  2  is elevated, while the pressure in the +x side  16  is reduced. Due to the acoustoelectric effect, this results in a reduction in the resistivity of the −x side  17  and an increase in the resistivity of the +x side  18 . At the same time, in this embodiment, the electric stimulus  3  is applied with a negative potential on the +x side of the volume conductor  1 . The result is an electric potential gradient  19  which decreases steadily with increasing x, except in the focal region  2 , where the reduced resistivity  17  and increased resistivity  18  results in a central-region potential  20  which is somewhat elevated over the unmodulated electric potential  21 . During a second phase of the electric and acoustic stimuli, the pressure in the −x side  15  of the focal region  2  is reduced, while the pressure in the +x side  16  is elevated, resulting in an increase in the resistivity of the −x side  17  and a decrease in the resistivity of the +x side  18 . At the same time, in this embodiment, the electric stimulus  3  is applied with a positive potential on the +x side of the volume conductor  1 . The result is an electric potential gradient  19  which increases steadily with increasing x, except in the focal region  2 , where the increased resistivity  17  and decreased resistivity  18  results in a central-region potential  20  which is somewhat elevated over the unmodulated electric potential  21 . The resulting average case  23  between the first phase  14  and the second phase  22  (and also, in this embodiment, the average of all phases of the electric and acoustic stimuli) has an average electrical potential  19  which is zero except in the focal region  2 , where the central-region potential  20  is more positive than the zero-valued unmodulated electric potential  21 . 
       FIG. 4  illustrates the mechanism by which nonuniform acoustic displacements give rise to a lower-frequency response  7  in the focal region  2  when a primarily electric stimulus  3  is applied in conjunction with a synchronized or partially synchronized acoustic stimulus  4 . In this embodiment, during a first phase  14  of the electric and acoustic stimuli, the position  24  of the central element of the focal region  2  is displaced in the −x direction relative to the positions  25  of the elements at the edge of the focal region. At the same time, in this embodiment, the electric stimulus  3  is applied with a negative potential on the +x side of the volume conductor  1 . The result is an electric potential gradient  19  which decreases steadily with increasing x (neglecting the effects of the acoustoelectric effect, illustrated in  FIG. 3 ). Because the central element has a position  24  displaced toward the more positive potential, it takes on a potential  26  which is elevated relative to the mean of the potentials  27  at the edge of the focal region. During a second phase  22  of the electric and acoustic stimuli, the position  24  of the central element of the focal region  2  is displaced in the +x direction relative to the positions  25  of the elements at the edge of the focal region. At the same time, in this embodiment, the electric stimulus  3  is applied with a positive potential on the +x side of the volume conductor  1 . The result is an electric potential gradient  19  which increases steadily with increasing x (neglecting the effects of the acoustoelectric effect, illustrated in  FIG. 3 ). Because the central element has a position  24  displaced toward the more positive potential, it takes on a potential  26  which is elevated relative to the mean of the potentials  27  at the edge of the focal region. The resulting average case  23  between the first phase  14  and the second phase  22  (and also, in this embodiment, the average of all phases of the electric and acoustic stimuli) has an average electrical potential  19  which is zero except in the focal region  2 , where the average potential  28  of the elements in this region are more positive than the zero-valued unmodulated electric potential  21 . 
       FIG. 5  illustrates an embodiment of the present invention in which the electromagnetic stimulus  3  is primarily magnetic and is applied to the volume conductor  1  via field coils  29 . The electromagnetic stimulus  3  in this case comprises a sinusoidal waveform with period T. The direction of the magnetic field  30  in this embodiment is perpendicular to the direction of displacement of the (longitudinal) acoustic stimulus  4  and is shown in the +z direction (out of page). The acoustic stimulus  4  is applied by a phased array ultrasound transducer  9  in contact with the volume conductor  1 . In this case, the acoustic stimulus  4  comprises a sinusoidal waveform  10 , also with period T, and focused on the target focal region  2 . In this case, both the unmodulated voltage  11  and the low-pass filtered voltage  12  produced in the volume conductor  1  far from the focal region  2  is equal to a constant voltage of zero. The focal region&#39;s voltage  13  consists of a sinusoidal waveform of period T/2 having minimum voltage of zero. This waveform therefore has a nonzero lower-frequency component  7  consisting of a constant DC voltage. The lower-frequency component  7  is produced as a result of the electromagnetic induction caused by the interaction of the magnetic field  30  and the acoustic movement of the volume conductor  1 , illustrated in  FIG. 6 . Although the lower-frequency response  7  in this example is a DC signal, changing the synchronization relation between the electromagnetic stimulus  3  and the acoustic stimulus  4  can produce a lower-frequency component  7  with a variety of waveforms. 
       FIG. 6  illustrates the mechanism by which electromagnetic induction gives rise to a lower-frequency response  7  in the focal region  2  when a primarily magnetic stimulus  3  is applied in conjunction with a synchronized or partially synchronized acoustic stimulus  4 . In this embodiment, during a first phase  14  of the magnetic and acoustic stimuli, the velocity  31  of the elements of the volume conductor  1  in the x-direction (denoted s x ) is strongly positive in the central area of the focal region  2 . At the same time, in this embodiment, the magnetic field  30  is applied in the −z direction (into the page in this figure) throughout the volume conductor  1 . As a result of the movement  31  of the central elements of the volume conductor  1  in the +x direction and the applied magnetic field  30  in the −z direction, an induced electromotive force produces a potential difference  32  in the +y direction in the central areas of the focal region  2 . During a second phase  22  of the magnetic and acoustic stimuli, the velocity  31  of the elements of the volume conductor  1  in the x-direction is strongly negative in the central area of the focal region  2 . At the same time, in this embodiment, the magnetic field  30  is applied in the +z direction (out of the page in this figure) throughout the volume conductor  1 . As a result of the movement of the central elements of the volume conductor  1  in the −x direction and the applied magnetic field  30  in the +z direction, an induced electromotive force produces a potential difference  32  in the +y direction in the central areas of the focal region  2 . The resulting average case  23  between the first phase  14  and the second phase  22  (and also, in this embodiment, the average of all phases of the electric and acoustic stimuli) has an average electrical potential difference  32  which is approximately zero except in the focal region  2 , where the average potential difference is primarily positive and much larger in magnitude than the potential difference outside the focal area  2 . 
       FIG. 7  illustrates an embodiment of the present invention in which the electromagnetic stimulus  3  comprises a mixture of electric and magnetic stimulus. In this example, the magnetic field  30  is applied to the volume conductor  1  via field coils  29  with a direction perpendicular to the direction of displacement of the (longitudinal) acoustic stimulus. The electric field portion of the electromagnetic stimulus  3  is applied to the volume conductor  1  via surface electrodes  8  in a direction parallel to the direction of the acoustic stimulus  4 . Both the electric and magnetic portions of the electromagnetic stimulus  3  comprise sinusoidal waveforms with period T. In this figure, the electric field and the acoustic stimulus are directed in the x direction, and the magnetic field is directed in the z direction (out of page). The acoustic stimulus  4  is applied by a phased array ultrasound transducer  9  in contact with the volume conductor  1 . In this case, the acoustic stimulus  4  comprises a sinusoidal waveform  10 , also with period T, and focused on the target focal region  2 . In this case, the lower-frequency component  7  of the voltage response in the focal region  2  is directed in a desired direction  33  midway between the +x and +y directions, at 45 degrees relative to the +y direction and 45 degrees relative to the +x direction. Thus, the unmodulated voltage  34  measured perpendicular to this direction (in the direction midway between the −x and +y directions) consists of a sinusoidal waveform, and its lower-frequency component  35  is zero. On the other hand, the unmodulated voltage  36  measured in the desired direction  33  consists of a sinusoidal waveform with a positive DC offset, so the desired lower-frequency component  7  is positive. Although the lower-frequency response  7  in this example is a DC signal in a fixed direction, changing the synchronization relation between the electric component of the electromagnetic stimulus  3 , the magnetic component of the electromagnetic stimulus  3 , and the acoustic stimulus  4  can produce a lower-frequency component  7  which varies arbitrarily in both magnitude and direction. 
       FIG. 8  illustrates an embodiment of the present invention in which the electromagnetic stimulus  3  is primarily electric and is applied to the volume conductor  1  via surface electrodes  8 . The electromagnetic stimulus  3  in this case comprises a sinusoidal waveform with frequency f e . The acoustic stimulus  4  is applied by a pair of phased array ultrasound transducers  9  in contact with the volume conductor  1 . In this case, the acoustic stimulus  4  is composed of two separate acoustic waves, one  37  with a higher acoustic frequency generated by a sinusoidal waveform  38  with frequency f h , and one  39  with a lower acoustic frequency generated by a sinusoidal waveform  40  with frequency f l  such that f h −f l =f e /2. By this means, at the intersection of the acoustic waves  37  and  39  in the focal region  2 , a summed acoustic waveform  41  is produced which has a base frequency (f h +f l )/2 and a modulation frequency of f e . Due to acoustic radiation pressure, the net pressure  42  in the focal region  2  is highest at the peaks of the modulated signal, producing an intermediate-frequency acoustic pressure component  43  with frequency f e . 
     In this case, the focal region&#39;s voltage  13  consists of a sinusoidal waveform of frequency f e  with a nonzero lower-frequency component  7  consisting of a constant DC voltage. The lower-frequency component  7  is produced as a result of the intermediate-frequency acoustic radiation waveform  43  interacting with the electromagnetic stimulus  3  via a combination of the acoustoelectric effect illustrated in  FIG. 3  and the effect of nonuniform acoustic displacements illustrated in  FIG. 4 . Although the lower-frequency response  7  in this example is a DC signal, changing the synchronization relation between the electromagnetic stimulus  3  and the acoustic stimulus  4  can produce a lower-frequency component  7  with a variety of waveforms.