IP Library Granted Patent US 12,496,447
Granted Patent B2
US 12,496,447 · App. 17/424,995 · Granted Dec 16, 2025

Systems and methods for combined ultrasound and electrical stimulation for treating a subject

Inventors: Hubert Lim (Minneapolis, MN); Daniel Zachs (Minneapolis, MN); Claire Kaiser (Minneapolis, MN)
Assignee: REGENTS OF THE UNIVERSITY OF MINNESOTA
A61N1/36034A61N1/0492A61N1/36021A61N1/36031A61N7/00A61N2007/0026
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Quick Facts
Patent No.
US 12,496,447
App. No.
17/424,995
Granted
Dec 16, 2025
Kind
B2
Abstract

Systems and methods are provided for combined ultrasound and electrical stimulation for treating inflammation, autoimmune disorders, rheumatoid arthritis, and the like. Noninvasive ultrasound stimulation may be applied to the spleen, joints, limbs, or a region experiencing pain that has local swelling, and electrical stimulation may be applied to the face, neck, or other body region to access a peripheral nerve, vagus nerve, trigeminal nerve, or other nerves in appropriately-timed patterns to drive therapeutic effects. Stimulation timings or delay timings may be optimized based upon a desired clinical effect or treatment. Multiple targets may be stimulated in a coordinated fashion to better mimic natural physiology. A wearable ultrasound phased array device may be used to beam form energy to target the spleen while also having imaging capabilities to track the motion of the spleen to maintain localized stimulation of target regions.

Claims (68)

1 . A method for coordinated ultrasound and electrical stimulation of a subject, comprising:

applying ultrasound stimulation to a first target of the subject,

the first target comprising an intraabdominal organ comprising the spleen;

applying electrical stimulation to a second target of the subject using a surface electrode,

the second target comprising a body surface of the subject comprising at least one of a face, a neck, an ear, or a location on the subject proximal to a vagus nerve or trigeminal nerve;

determining stimulation parameters and a timing delay between the first target and the second target based upon at least one of a physical size of the subject, a transit time of a signal between the first target and the second target, a speed of a signal between the first target and the second target, a heartrate of the subject, physiological requirements of a specific disease being treated, blood samples to assess changes in relevant molecular and biomarkers relevant to stimulation, EEG brain activity of localized regions related to at least one of the first or second targets, or a severity of inflammation in the subject; and

applying the coordinated ultrasound stimulation and electrical stimulation to the subject using the determined timing delay and stimulation parameters.

2 . The method of claim 1 , wherein the timing delay is in the range of 0 to 1000 ms.

3 . The method of claim 2 , wherein the timing delay is less than 300 ms.

4 . The method of claim 1 , wherein the coordinated ultrasound stimulation and electrical stimulation includes using at least one wearable device located on the subject.

5 . The method of claim 1 , further comprising compensating for motion of the first target using ultrasound beam steering.

6 . The method of claim 1 , wherein determining stimulation parameters includes determining ultrasound stimulation parameters including at least one of:

a duty cycle,

a frequency,

a pressure,

a duration,

a beam focus, or

a pulse pattern.

7 . The method of claim 6 , wherein the pulse pattern includes at least one of:

unmodulated burst of pulses,

sinusoid modulated pulse trains,

chirp pulses, or

spike pulses.

8 . The method of claim 1 , wherein determining stimulation parameters includes determining electrical stimulation parameters including at least one of:

a current,

a voltage,

a frequency,

a duration,

a phase,

a phase pattern, or

a pulse pattern.

9 . A system for coordinated ultrasound and electrical stimulation of a subject, comprising:

an ultrasound transducer to stimulate a first target of the subject,

the first target comprising an intraabdominal organ comprising the spleen;

an electrical stimulator to stimulate a second target of the subject using a surface electrode,

the second target comprising a body surface of the subject comprising at least one of a face, a neck, an ear, or a location on the subject proximal to a vagus nerve or trigeminal nerve; and

a computer system configured to:

determine stimulation parameters and a timing delay between the first target and the second target based upon at least one of a physical size of the subject, a transit time of a signal between the first target and the second target, a speed of a signal between the first target and the second target, a heartrate of the subject, physiological requirements of a specific disease being treated, blood samples to assess changes in relevant molecular and biomarkers relevant to stimulation, EEG brain activity of localized regions related to at least one of the first or second targets, or a severity of inflammation in the subject; and

apply the coordinated ultrasound stimulation and electrical stimulation to the subject using the determined timing delay and stimulation parameters.

10 . The system of claim 9 , wherein the timing delay is in the range of 0 to 1000 ms.

11 . The system of claim 10 , wherein the timing delay is less than 300 ms.

12 . The system of claim 9 , wherein the first target is the spleen.

13 . The system of claim 9 , wherein the coordinated ultrasound stimulation and electrical stimulation includes using at least one wearable device located on the subject.

14 . The system of claim 9 , further comprising wherein the computer system is configured to compensate for motion of the first target using ultrasound beam steering.

15 . The system of claim 9 , wherein determining stimulation parameters includes determining ultrasound stimulation parameters including at least one of:

a duty cycle,

a frequency,

a pressure,

a duration,

a beam focus, or

a pulse pattern.

16 . The system of claim 15 , wherein the pulse pattern includes at least one of:

unmodulated burst of pulses,

sinusoid modulated pulse trains,

chirp pulses, or

spike pulses.

17 . The system of claim 9 , wherein determining stimulation parameters includes determining electrical stimulation parameters including at least one of:

a current,

a voltage,

a frequency,

a duration,

a phase,

a phase pattern, or

a pulse pattern.

18 . The system of claim 9 , wherein the computer system, when applying the coordinated ultrasound stimulation and electrical stimulation to the subject, is further configured to:

apply the coordinated ultrasound stimulation and electrical stimulation to the subject to treat a condition of the subject, wherein the condition comprises rheumatoid arthritis.

19 . The method of claim 1 , wherein applying the coordinated ultrasound stimulation and electrical stimulation to the subject further comprises:

applying the coordinated ultrasound stimulation and electrical stimulation to the subject to treat a condition of the subject, wherein the condition comprises rheumatoid arthritis.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 25, 2021
From: LIM, HUBERT; ZACHS, DANIEL; KAISER, CLAIRE
To: REGENTS OF THE UNIVERSITY OF MINNESOTA
Reel/Frame 057286/0153 →
Continuity (2)
Provisional Application 62816857 · Mar 11, 2019
Related Publication 20220080197A1 · Mar 17, 2022
References Cited (35)
US 3236240A · Bradley · 1966 [cited by applicant]
US 20060167500A1 · Towe · 2006 [cited by examiner]
US 20070219470A1 · Talish · 2007 [cited by examiner]
US 20110150924A1 · Della Rocca et al. · 2011 [cited by applicant]
US 20130012840A1 · Feferberg · 2013 [cited by examiner]
US 20130274832A1 · Manion · 2013 [cited by examiner]
US 20140058292A1 · Alford et al. · 2014 [cited by applicant]
US 20150148878A1 · Yoo et al. · 2015 [cited by applicant]
US 20190001129A1 · Rosenbluth et al. · 2019 [cited by applicant]
US 20190083817A1 · Okusa · 2019 [cited by examiner]
US 20200046992A1 · Tracey · 2020 [cited by examiner]
US 20230241387A1 · Levine · 2023 [cited by examiner]
CN 101888876A · 2010 [cited by applicant]
CN 108882885A · 2018 [cited by applicant]
JP 2001286484A · 2001 [cited by applicant]
JP 2017535364A · 2017 [cited by applicant]
WO 0145550A2 · 2001 [cited by applicant]
WO 2017011298A1 · 2017 [cited by applicant]
Lim et al. “Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis” Nature Communications vol. 10, Article No. 951 (2019) (Year: 2019). [cited by examiner]
Puleo et al. “Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation” Nature Communications vol. 10, Article No. 952 (2019) (Year: 2019). [cited by examiner]
Abe et al., C1 Neurons Mediate a Stress-Induced Anti-Inflammatory Reflex in Mice, Nature Neuroscience, 2017, 20(5):700-707. [cited by applicant]
Arthritis Today Magazine, What Happens if your Anti-TNF Drug Doesn't Work?, http://blog.arthritis.org/living-with-arthritis/anti-tnf-drug-failure/, Dec. 1, 2015, 5 pages. [cited by applicant]
Binstadt et al., The Same Systematic Autoimmune Disease Provokes Arthritis and Endocarditis via Distinct Mechanisms, Proceedings of the National Academy of Sciences, 2009, 106(39):16758-16763. [cited by applicant]
Chao et al., Ultrasound Phantoms Made of Gelatin Covered with Hydrocolloid Skin Dressing, The Journal of Emergency Medicine, 2013, 45(2):240-243. [cited by applicant]
Downs et al., Non-Invasive Peripheral Nerve Stimulation via Focused Ultrasound in Vivo, Physics in Medicine & Biology, 2018, 63(3):035011, pp. 1-11. [cited by applicant]
Gibofsky, Overview of Epidemiology, Pathophysiology, and Diagnosis of Rheumatoid Arthritis, The American Journal of Managed Care, 2012, 18(13):S295-S302. [cited by applicant]
Gigliotti et al., Ultrasound Modulates the Splenic Neuroimmune Axis in Attenuating AKI, Journal of the American Society of Nephrology, 2015, 26(10):2470-2481. [cited by applicant]
Inoue et al., Vagus Nervus Stimulation Mediates Protection from Kidney Ischemia-Reperfusion Injury Through α7nAChR+ Spelnocytes, The Journal of Clinical Investigation, 2016, 126(5):1939-1952. [cited by applicant]
Juan et al., Vagus Nerve Modulation Using Focused Pulsed Ultrasound: Potential Applications and Preliminary Observations in a Rat, International Journal of Imaging Systems and Technology, 2014, 24(1):67-71. [cited by applicant]
Morrow et al., Versatile, Reusable, and Inexpensive Ultrasound Phantom Procedural Trainers, Journal of Ultrasound in Medicine, 2016, 35(4):831-841. [cited by applicant]
Straub, Complexity of the Bi-Directional Neuroimmune Junction in the Spleen, Trends in Pharmacological Sciences, 2004, 25(12):640-646. [cited by applicant]
Tracey, The Inflammatory Reflex, Nature, 2002, 420(6917):853-859. [cited by applicant]
Zachs et al., Noninvasive Ultrasound Stimulation of the Spleen to Treat Inflammatory Arthritis, Nature Communications, 2019, 10(1):951, pp. 1-10. [cited by applicant]
European Patent Office, Extended Search Report, Application No. 20770765.4, Nov. 18, 2022, 8 pages. [cited by applicant]
PCT International Search Report and Written Opinion, PCT/US2020/021811, Jun. 12, 2020, 11 pages. [cited by applicant]