Techniques for neuromodulation

Patent metadata

Field	Value
Publication number	US-11040199-B2
Application number	US-201716091486-A
Country	US
Kind code	B2
Filing date	Apr 4, 2017
Priority date	Apr 4, 2016
Publication date	Jun 22, 2021
Grant date	Jun 22, 2021

Abstract

The subject matter of the present disclosure generally relates to techniques for neuromodulation of lymphatic tissue that include applying one or more energy pulses to a neuron of a subject, e.g., via an electrode positioned to deliver sufficient energy to the neuron, to modulate immune function. For example, an adaptive immune reflex of a subject may be modulated via neuromodulation.

First claim

The invention claimed is:

1. A system for neuromodulation of lymphatic tissue, comprising:
an electrode assembly configured to apply one or more energy pulses to a neuron of a subject to deliver sufficient energy to the neuron to neurally modulate a lymphatic tissue in response to applying the one or more energy pulses; and
a pulse generator configured to generate the one or more energy pulses;
a controller configured to cause the pulse generator to generate the one or more energy pulses according to stimulation parameters to cause the lymphatic tissue to be neurally modulated; and
a noninvasive assessment device configured to acquire image data of the lymphatic tissue and identify a change in a characteristic of the lymphatic tissue based on the image data and as a result of the energy applied to the neuron, wherein the controller is configured to modify the stimulation parameters based on the identified change in the characteristic, wherein the noninvasive assessment device is a noninvasive ultrasound device configured to acquire the image data.

2. The system of claim 1 , wherein the stimulation parameters of the one or more energy pulses are selected such that an immune function of the subject is neurally modulated to result in an increase in a number of cells in a cell population in the lymphatic tissue, a decrease in a number of cells in a cell population in a contralateral lymphatic tissue, or both.

3. The system of claim 1 , wherein the lymphatic tissue is a lymph node.

4. The system of claim 1 , wherein the electrode assembly is adapted to be located in direct contact with the neuron.

5. The system of claim 1 , wherein the stimulation parameters cause the electrode assembly to apply the one or more energy pulses with an energy in a range of 0.5V to less than 10V, and wherein the noninvasive assessment device is configured to identify an increase in size of the lymphatic tissue based on the image data.

6. The system of claim 1 , wherein the subject is a subject with a diagnosis of an autoimmune disorder.

7. The system of claim 1 , wherein the subject has one or more symptoms of tissue swelling, need to alter liquid content of the tissue, need for containment of an antigen, infection, foreign or host cell locally, need for local immune cell recruitment, need for removal of specific immune cells locally, need to alter the phenotype, activity or immune response of immune cells within the lymphatic and surrounding tissue, or need to alter a phenotype, activity or immune response of cells within the lymphatic and surrounding tissue.

8. The system of claim 1 , wherein a change in the immune function as a result of the neuromodulation is detectable in the subject within 30 minutes of applying the one or more energy pulses.

9. The system of claim 1 , wherein the stimulation parameters cause the electrode assembly to apply the one or more energy pulses with an energy at about 20 Hz.

10. A system of neuromodulation, comprising:
an electrode assembly configured to apply one or more energy pulses to a neuron of a subject to deliver sufficient energy to the neuron to modulate immune function of a lymphatic tissue such that a concentration of norepinephrine or epinephrine in the lymphatic tissue or a lymphatic fluid is increased at least 100% relative to a pre-stimulation baseline in response to the one or more energy pulses, wherein the one or more energy pulses are applied with an energy in a range of 0.5V to 10V;
a controller configured to cause the one or more energy pulses to be generated; and
a noninvasive imager configured to acquire image data of the lymphatic tissue during or after delivering the energy to the neuron, wherein the controller is configured to modify one or more parameters of the energy pulses based on the image data.

11. The system of claim 10 , wherein the subject has one or more symptoms of tissue swelling, need to alter liquid content of the tissue, need for containment of an antigen, infection, foreign or host cell locally, need for local immune cell recruitment, need for removal of specific immune cells locally, need to alter the phenotype, activity or immune response of immune cells within the lymphatic and surrounding tissue, or need to alter a phenotype, activity or immune response of cells within the lymphatic and surrounding tissue.

12. The system of claim 10 , wherein the one or more energy pulses are applied according to stimulation parameters that are associated with neurotransmitter or neuropeptide release.

13. The system of claim 10 , wherein the increase in concentration is as measured in one or both of a lymphatic tissue sample or a lymphatic fluid sample.

14. The system of claim 10 , wherein the noninvasive imager is an ultrasound imaging device comprising a noninvasive probe configured to acquire the image data, wherein the controller is configured to modify the one or more parameters of the energy pulses based on a determination of a change in size of a structure of the lymphatic tissue based on the image data.

15. The system of claim 14 , wherein the determination of the change in size is an increase in estimated volume of the structure relative to a baseline unstimulated state, wherein upon determining that the change in size is greater than a threshold, the controller is configured to decrease the applied energy to a lower level.

16. A system of closed-loop neuromodulation, comprising:
a pulse generator configured to apply one or more energy pulses to a neuron innervating a lymphatic tissue and according to one or more stimulation parameters of at least one of the one or more energy pulses to modulate a lymphatic function of the lymphatic tissue;
a noninvasive assessment device configured to receive information related to a size of the lymphatic tissue, wherein the noninvasive assessment device is a noninvasive ultrasound device comprising an acoustic probe configured to acquire image data, and wherein the information related to the size is based on the image data; and
a controller configured to control the pulse generator to apply the one or more energy pulses according to the one or more stimulation parameters and to change the one or more stimulation parameters based on the information.

17. The system of claim 16 , wherein the controller is configured change a frequency of the one or more energy pulses based on the information.

18. The system of claim 16 , wherein the controller is configured change a voltage of the one or more energy pulses based on the information.

19. The system of claim 16 , wherein the image data is image data of a directly stimulated lymph node, and wherein the information related to the size is an increase of at least 25% in an estimated volume of the directly stimulated lymph node relative to a baseline unstimulated state determined based on the image data.

Assignees

• General Electric Comany
• Gen Electric

Inventors

• Puleo Christopher Michael
• Ashe Jeffrey Michael
• Cotero Victoria Eugenia
• Marino Michael Ernest

Classifications

• A61N1/3606 Primary

  adapted for a particular treatment · CPC title

• A61N1/36071 Primary

  Pain · CPC title

• A61N1/36153

  Voltage (A61N1/3616 takes precedence) · CPC title

• A61N1/36171

  Frequency · CPC title

• A61N2/006

  for magnetic stimulation of nerve tissue · CPC title