Methods for modifying electrical currents in neuronal circuits

• US 20110092800A1
• Filed: 02/17/2010
• Published: 04/21/2011
• Est. Priority Date: 04/30/2002
• Status: Active Grant

• Current Assignee: Brigham and Women's Hospital Incorporated
• Original Assignee: Brigham and Women's Hospital Incorporated
• Inventors: McDannold, Nathan, Jolesz, Ferenc A., Yoo, Seung-Schik, Bystrisky, Alexander
• Granted Patent: US 9,592,409 B2
• Time in Patent Office: Days
• US Class Current: 600/411
• CPC Class Codes: A61B 2090/374 NMR or MRI
• CPC Class Codes: A61B 5/0036 including treatment, e.g., using an implantable medical device, ablating, ventilating
• CPC Class Codes: A61B 5/0042 for the brain
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 5/369 Electroencephalography [EEG] devices for psychotechnics A61B5/16
• CPC Class Codes: A61B 6/037 Emission tomography
• CPC Class Codes: A61N 2007/0021 Neural system treatment
• CPC Class Codes: A61N 2007/0026 Stimulation of nerve tissue
• CPC Class Codes: A61N 2007/0078 with multiple treatment transducers
• CPC Class Codes: A61N 7/00 Ultrasound therapy lithotripsy A61B17/22, A61B17/225; massage using supersonic vibration A61H23/00 ; using ultrasound for introducing media into the body A61M37/0092
• CPC Class Codes: A61N 7/02 Localised ultrasound hyperthermia hyperthermia in general A61F7/00

Abstract

A method for modifying neuronal activity in a subject with focused ultrasound pulses (“FUP”) is provided. Such a methods is applicable for research, treatment, and diagnosis of psychiatric, neurological, and neuroendocrine disorders whose biological mechanisms include neuronal circuits in the brain. The application of focused ultrasound pulses is generally via multiple ultrasound transducers that are housed in a cap worn by the subject. The application of FUP at different tone burst duration, total sonication duration, and pulse repetition frequency settings results in either the inducement of either an increase or decrease in neuronal activity.

Claims

1. A method for modifying neuronal activity in a subject with an ultrasound system, the steps comprising:

a) identifying a location in the subject that is to receive pulses of focused ultrasound;

b) applying, with the ultrasound system and to the identified location, pulses of focused ultrasound, each pulse of focused ultrasound having a tone burst duration (TBD) in a range of 2-100 milliseconds (ms) and being applied during a sonication period having a duration less than around 2 seconds in order to increase neuronal activity, and each pulse of focused ultrasound having a TBD less than around 2 ms and being applied during a sonication period having a duration greater than around 2 seconds in order to decrease neuronal activity.

2. The method as recited in claim 1 in which the pulses of focused ultrasound are applied in step b) at a selected pulse repetition frequency (PRF) in the range of 100-1000 hertz (Hz) in order to further decrease neuronal activity, and at a selected PRF below around 100 Hz in order to further increase neuronal activity.

3. The method as recited in claim 2 in which applying the pulses of focused ultrasound at a selected PRF in the range of 100-1000 Hz when the sonication period has a duration greater than around 2 seconds induces an increase in neuronal activity that is followed by a period of suppressed neuronal activity.

4. The method as recited in claim 1 in which the pulses of focused ultrasound are applied in step b) with an acoustic intensity in the range of 10-350 watts per centimeter squared (W/cm²).

5. The method as recited in claim 1 in which step a) includes:

a)i) acquiring, with a magnetic resonance imaging (MRI) system, image data from the subject;

a)ii) reconstructing an image of the subject from the acquired image data; and

a)iii) identifying the location in the subject using the reconstructed image.

6. The method as recited in claim 1 further comprising:

c) acquiring, with an imaging system, images of the subject while step b) is performed, the acquired images being indicative of the modified neuronal activity induced by the applied pulses of focused ultrasound;

d) administering a pharmaceutical medication to the subject; and

e) repeating steps b) and c) in order to acquire images indicative of neuronal activity that is induced by the applied pulses of focused ultrasound and altered in response to the administered pharmaceutical medication.

7. The method as recited in claim 6 further comprising comparing the images acquired in step e) with the images acquired in step c) in order to assess an efficacy of the pharmaceutical medication.

8. The method as recited in claim 1 in which the identified location in the subject is selected to include at least one of gray matter and white matter.

9. The method as recited in claim 1 further comprising:

c) acquiring, with an imaging system, images of the subject while step b) is performed, the acquired images being indicative of the modified neuronal activity induced by the applied pulses of focused ultrasound;

d) adjusting a parameter of the applied pulses of focused ultrasound using the acquired images of the subject; and

e) repeating step b) using the adjusted parameter of the applied pulses of focused ultrasound.

10. The method as recited in claim 9 in which the adjusted parameter of the pulses of focused ultrasound includes at least one of the TBD, the duration of the sonication period, a pulse repetition frequency at which the pulses of focused ultrasound are applied, an acoustic intensity, an ultrasound frequency, a focal depth and a focal diameter.

11. The method as recited in claim 1 further comprising:

c) acquiring, with an imaging system, images of the subject while step b) is performed, the acquired images being indicative of the modified neuronal activity induced by the applied pulses of focused ultrasound;

d) repeatedly performing steps a)-c) over a period of time of sufficient length so that neuronal circuits are significantly modified by the repeated application of pulses of focused ultrasound; and

wherein the neuronal circuits are modified such that at least one of a psychiatric, neurological, and neuroendocrine disorder is treated, and the modified neuronal circuits are assessed using the images acquired in step c).

12. A method for modifying neuronal activity in a subject with an ultrasound system, the steps comprising:

a) identifying a location in the subject that is to receive pulses of focused ultrasound;

b) applying, with the ultrasound system and to the identified location, pulses of focused ultrasound at a selected pulse repetition frequency (PRF) in the range of 100-1000 hertz (Hz) in order to decrease neuronal activity, and at a selected PRF below around 100 Hz in order to increase neuronal activity.

13. The method as recited in claim 12 in which the duration of each pulse of focused ultrasound applied in step b) has a selected tone burst duration (TBD) in the range of 2-100 milliseconds (ms) in order to further increase neuronal activity, and a selected TBD below 2 ms in order to further decreased neuronal activity.

14. The method as recited in claim 12 in which the duration of the applied pulses of focused ultrasound in step b) has a selected total sonication duration (TSD) below around 2 seconds in order to further increase neuronal activity, and a selected TSD greater than around 2 seconds in order to further decrease neuronal activity.

15. The method as recited in claim 14 in which applying the pulses of focused ultrasound at a selected PRF in the range of 100-1000 Hz for a TSD greater than around 2 seconds induces an increase in neuronal activity that is followed by a period of suppressed neuronal activity.

16. The method as recited in claim 12 in which the pulses of focused ultrasound are applied in step b) with an acoustic intensity in the range of 10-350 watts per centimeter squared (W/cm²).

17. A method for adjusting a magnetic resonance guided focused ultrasound (MRgFUS) treatment plan with a magnetic resonance imaging (MRI) system and an ultrasound system, the steps comprising:

a) positioning a subject in the MRI system;

b) identifying a location in the subject that is to receive treatment;

c) applying pulses of focused ultrasound to the identified location with the ultrasound system in order to modify neuronal activity at the identified location;

d) acquiring, with the MRI system and substantially contemporaneously with step c), functional image data from the subject;

e) reconstructing a series of functional images of the subject using the functional image data, the functional images being indicative of the modified neuronal activity; and

f) adjusting a parameter of the MRgFUS treatment plan using the reconstructed series of functional images.

18. The method as recited in claim 17 in which step b) includes:

b)i) acquiring, with the MRI system, image data from the subject;

b)ii) reconstructing an image of the subject from the acquired image data; and

b)iii) identifying the location in the subject using the reconstructed image.

19. The method as recited in claim 17 in which step b) includes:

b)i) acquiring, with the ultrasound system, an image of the subject; and

b)ii) identifying the location in the subject using the acquired image.

20. The method as recited in claim 17 in which the parameter of the MRgFUS treatment plan includes at least one of an acoustic intensity at which focused ultrasound is applied, a focused ultrasound frequency, a focal depth, and a focal diameter.