Search

EP-3762089-B1 - NEUROMODULATION TECHNIQUES

EP3762089B1EP 3762089 B1EP3762089 B1EP 3762089B1EP-3762089-B1

Inventors

  • PULEO, CHRISTOPHER MICHAEL
  • COTERO, VICTORIA EUGENIA

Dates

Publication Date
20260513
Application Date
20190306

Claims (12)

  1. A modulation system (10) comprising: at least one energy application device (12); and a controller (16) configured to: focus the at least one energy application device (12) on a first region of interest of a first tissue, the first tissue comprising a first plurality of axon terminals of respective neurons, one or more of the plurality of axon terminals forming synapses between individual axon terminals and respective non-neuronal cells, wherein the first region of interest comprises a first subset of the first plurality of axon terminals; adjustably control the at least one energy application device to apply a first energy to the first region of interest to selectively modulate a first molecule of interest; focus the at least one energy application device on a second region of interest, wherein the second region of interest comprises a second subset of axon terminals; and adjustably control the at least one energy application device to apply a second energy to the second region of interest to selectively modulate the first molecule of interest or a second molecule of interest; wherein the at least one energy application device is an ultrasound probe; wherein the controller is configured to cause the ultrasound probe to operate in an imaging mode configured to acquire reference image data of the first tissue and/or the second tissue before the application of the first energy or the second energy and post-treatment image data of the first tissue and/or the second tissue after the application of the first energy or the second energy; characterised in that the controller is configured to: determine a displacement measurement of the first tissue and/or the second tissue based on a comparison of the reference image data and the post-treatment image data; and modify a modulation parameter of the first energy or the second energy based on the displacement measurement.
  2. The system (10) of claim 1, wherein the controller (16) is configured to receive, from an assessment device (20), an input indicative of a first molecule concentration, a second molecule concentration, or both, and preferably wherein the assessment device is a blood glucose monitor.
  3. The system (10) of claim 1 wherein the first region of interest is in a first organ and the second region of interest is in a second organ different than the first organ.
  4. The system (10) of claim 3, wherein the first organ is a pancreas and the second organ is a liver.
  5. The system (10) of claim 3, wherein the first organ is a pancreas and the second organ is a gastrointestinal tissue.
  6. The system (10) of claim 1, wherein in selective modulation of the first molecule via the first energy or the second energy the controller (16) is configured to cause a change in a characteristic of the first molecule or a change in a first molecule concentration relative to a baseline concentration before the energy is applied to the first region of interest, the second region of interest, or both.
  7. The system (10) of claim 6, wherein in selective modulation of the second molecule via the second energy the controller (16) is configured to cause a change in a characteristic of the second molecule or a change in a second molecule concentration relative to a baseline concentration before the energy is applied to the second region of interest.
  8. The system (10) of claim 7, wherein the first molecule concentration is a glucose concentration and the second molecule concentration is an insulin concentration, and preferably wherein the glucose concentration is a blood glucose concentration and the insulin concentration is a pancreatic tissue insulin concentration.
  9. The system (10) of claim 7, wherein the first molecule concentration is a glucose concentration and the second molecule concentration is a GLP-1 concentration, and preferably wherein the glucose concentration is a blood glucose concentration and the GLP-1 concentration is a hypothalamic GLP-1 concentration.
  10. The system (10) of claim 7, wherein the selective modulation of the first molecule comprises a change in a glucose concentration and the selective modulation of the second molecule comprises a change in a GLUT2 concentration, phosphorylation, translocation, or a combination thereof, and preferably wherein the glucose concentration is a blood glucose concentration and the GLUT2 concentration is a pancreatic tissue GLUT2 concentration.
  11. The system (10) of claim 1, wherein the controller (16) is configured to modify the modulation parameter of the first energy or the second energy based on the displacement measurement being below a threshold displacement associated with a first molecule concentration change.
  12. The system of claim 11, wherein the controller (16) is configured to modify the modulation parameter of the second energy based on the displacement measurement being below a threshold displacement associated with a second molecule concentration change.

Description

BACKGROUND The subject matter disclosed herein relates to neuromodulation and more specifically, to techniques for modulating a physiological response using energy applied from an energy source. Neuromodulation has been used to treat a variety of clinical conditions. For example, electrical stimulation at various locations along the spinal cord has been used to treat chronic back pain. Such treatment may be performed by an implantable device that periodically generates electrical energy that is applied to a tissue to activate certain nerve fibers, which in turn may result in a decreased sensation of pain. In the case of spinal cord stimulation, the stimulating electrodes are generally positioned in the epidural space, although the pulse generator may be positioned somewhat remotely from the electrodes, e.g., in the abdominal or gluteal region, but connected to the electrodes via conducting wires. In other implementations, deep brain stimulation may be used to stimulate particular areas of the brain to treat movement disorders, and the stimulation locations may be guided by neuroimaging. Such central nervous system stimulation is generally targeted to the local nerve or brain cell function and is mediated by electrodes that deliver electrical pulses and that are positioned at or near the target nerves. However, positioning electrodes at or near the target nerves is challenging. For example, such techniques may involve surgical placement of the electrodes that deliver the energy. In addition, specific tissue targeting via neuromodulation is challenging. Electrodes that are positioned at or near certain target nerves mediate neuromodulation by triggering an action potential in the nerve fibers, which in turn results in neurotransmitter release at a nerve synapse and synaptic communication with the next nerve. Such propagation may result in a relatively larger or more diffuse physiological effect than desired, as current implementation of implanted electrodes stimulate many nerves or axons at once. Because the neural pathways are complex and interconnected, a more targeted modulated effect may be more clinically useful EP 2 821 103 A1 relates to methods and devices for modulating the activity of living cells. BRIEF DESCRIPTION OF THE INVENTION The invention is defined in claim 1. Particular embodiments of the invention are defined in the dependent claims. Any methods of treatment described hereinafter are presented for illustrative purposes only, but are not claimed as such. BRIEF DESCRIPTION OF THE DISCLOSURE In one embodiment, a modulation system is provided. The system includes at least one energy application device; and a controller configured to focus the at least one energy application device on a first region of interest of a first tissue, the first tissue comprising a first plurality of axon terminals of respective neurons, one or more of the plurality of axon terminals forming synapses between individual axon terminals and respective non-neuronal cells, wherein the first region of interest comprises a first subset of the first plurality of axon terminals; adjustably control the at least one energy application device to apply a first energy to the first region of interest to selectively modulate a first molecule of interest; focus the at least one energy application device on a second region of interest, wherein the second region of interest comprises a second subset of axon terminals; and adjustably control the at least one energy application device to apply a second energy to the second region of interest to selectively modulate the first molecule of interest or a second molecule of interest. In another embodiment, a modulation system is provided that includes at least one energy application device configured to apply energy to a first region of interest of a first tissue in a subject, the first tissue comprising a plurality of axon terminals of respective neurons, the axon terminals forming synapses between individual axon terminals and respective non-neuronal cells and to a second region of interest of a second tissue in the subject. The system also includes a controller configured to spatially select the first region of interest of the first tissue and the second region of interest in the second tissue; focus the energy on the first region of interest and the second region of interest; and adjustably control application of the energy via the at least one energy application device to the first region of interest to induce preferential activation of a subset of the synapses, the subset being located in the first region of interest, to cause a first molecule concentration of a first molecule to change and control application of the energy via the at least one energy application device to the second region of interest to cause a second molecule concentration of a second molecule to change. In another embodiment, a modulation system is provided that includes an energy application device configured to ap