Magnetic resonance with stimulation

• US 20060039856A1
• Filed: 10/21/2005
• Published: 02/23/2006
• Est. Priority Date: 11/02/2001
• Status: Abandoned Application

• Current Assignee: Mclean Hospital (Mass General Brigham, Inc.)
• Original Assignee: Mclean Hospital (Mass General Brigham, Inc.)
• Inventors: Renshaw, Perry, Lukas, Scott, Frederick, Blaise deB., Cowan, Ronald
• Application Number:
  US11/255,806
• Publication Number:
  US 20060039856A1
• Time in Patent Office: Days
• US Class Current: 424/1.110
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 5/4064 Evaluating the brain A61B5/031, A61B5/369, A61B5/14553 take precedence
• CPC Class Codes: A61B 5/4082 Diagnosing or monitoring movement diseases, e.g. Parkinson, Huntington or Tourette
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 49/06 Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
• CPC Class Codes: G01R 33/4806 Functional imaging of brain activation

Abstract

This invention involves blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) using external stimuli. Different colors of light can be used as the stimulus to assess differential BOLD response to diagnose neurological disorders (e.g., Parkinson'"'"'s disease, attention deficit disorder, schizophrenia, and substance abuse). In addition, very low dose administration of a drug that affects intracerebral vasculature can enhance BOLD response, facilitating detection and improving diagnostic capabilities. Using a very low dose of d-amphetamine, BOLD response to blue light is increased.

Claims

1. A method of diagnosing altered dopaminergic function based at least in part on a subject'"'"'s blood oxygen level dependent responses comprising:

(a) applying a functional magnetic resonance imaging sequence to the subject;

(b) exposing the subject to photic stimulation using light having at least two wavelengths during the functional magnetic resonance imaging sequence; and

(c) processing data obtained during the functional magnetic resonance sequence to evaluate blood oxygen level dependent responses of the subject to the at least two wavelengths of light.

2. The method of claim 1 wherein the subject is a human.

3. The method of claim 1 wherein the subject is a human brain.

4. The method of claim 1 further comprising

(d) using the evaluation of blood oxygen level responses to diagnose whether the subject has Parkinson'"'"'s disease, schizophrenia, or attention deficient disorder.

5. The method of claim 1 wherein the photic stimulation is alternated with periods without photic stimulation during the functional magnetic resonance sequence.

6. The method of claim 1 wherein the light having at least two wavelengths comprises red light and blue light.

7. The method of claim 1 wherein the at least two wavelengths are approximately 470 nm and 660 nm.

8. The method of claim 1 further comprising

(d) administering a drug to the subject.

9. The method of claim 8 wherein the drug is methylphenidate, epinephrine, norepinephrine, ephedrine, levoephedrine, phenlyephrine, cocaine, albuterol, metaproterenol, terbutaline, dobutamine, caffeine, theophylline, theobromine, pentoxifylline, a nitric oxide antagonists, an endothelin antagonists, a bradykinin antagonists, a substance P antagonists, a vasoactive intestinal polypeptide antagonist, an angiotensin agonist, an atrial natriuretic hormone antagonist, a neuropeptide Y agonist, or a combination of one or more of these agents.

10. A method of enhancing contrast in functional magnetic resonance imaging by increasing blood oxygen level dependent response to a stimulus, the method comprising:

(a) administering a drug that enhances contrast by affecting intracerebral vasculature to a subject, in a dosage selected to minimize its effect on a central nervous system;

(b) applying a functional magnetic resonance imaging sequence to the subject while the drug is affecting intracerebral vasculature;

(c) stimulating the subject while the drug is affecting intracerebral vasculature; and

(d) processing data obtained during the functional magnetic resonance sequence to evaluate blood oxygen level dependent responses to the stimulus while the drug is affecting intracerebral vasculature.

11. The method of claim 10 wherein the subject is a human brain.

12. The method of claim 10 further comprising

(d) diagnosing whether the subject has Parkinson'"'"'s disease, schizophrenia, or attention deficient disorder.

13. The method of claim 10 wherein the stimulus is photic stimulation.

14. The method of claim 13 wherein the photic stimulation is alternated with periods without photic stimulation.

15. The method of claim 13 wherein the photic stimulation comprises light having at least two wavelengths.

16. The method of claim 15 wherein the light having at least two wavelengths comprises red light and blue light.

17. The method of claim 10 wherein the at least two wavelengths are approximately 470 nm and 660 nm.

18. The method of claim 10 wherein the drug is methylphenidate, epinephrine, norepinephrine, ephedrine, levoephedrine, phenlyephrine, cocaine, albuterol, metaproterenol, terbutaline, dobutamine, caffeine, theophylline, theobromine, pentoxifylline, a nitric oxide antagonists, an endothelin antagonists, a bradykinin antagonists, a substance P antagonists, a vasoactive intestinal polypeptide antagonist, an angiotensin agonist, an atrial natriuretic hormone antagonist, a neuropeptide Y agonist, or a combination of one or more of these agents.

19. The method of claim 10 wherein the drug is d-amphetamine and the dosage is less than about 3 mg.

20. The method of claim 19 wherein the dosage is about 2.5 mg.

21. A method of magnetic resonance imaging to measure blood oxygen level dependent responses of a subject to light having at least two wavelengths:

(a) administering about 2.5 mg of d-amphetamine to the subject;

(b) applying a functional magnetic resonance imaging sequence to the subject;

(a) exposing the subject to photic stimulation using red and blue light during the functional magnetic resonance imaging sequence; and

(d) processing data obtained during the functional magnetic resonance sequence to evaluate blood oxygen level dependent responses of the subject to the red and blue light.