Methods for imaging pulmonary and cardiac vasculature and evaluating blood flow using dissolved polarized 129Xe

• US 6,491,895 B2
• Filed: 12/15/2000
• Issued: 12/10/2002
• Est. Priority Date: 03/18/1998
• Status: Expired due to Fees

• Current Assignee: Polarean, Inc. (Polarean Imaging Plc)
• Original Assignee: Medi-Physics Incorporated (General Electric Company)
• Inventors: Driehuys, Bastiaan, Bogorad, Paul Lev, Hasson, Kenton Christopher
• Primary Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US09/737,880
• Publication Number:
  US 20010000727A1
• Time in Patent Office: 725 Days
• Field of Search: 424/1.11, 424/9.1, 424/9.3, 424/9.32, 424/9.2, 424/9.36, 534/7
• US Class Current: 424/9.36
• CPC Class Codes: A61B 5/0263 using NMR
• CPC Class Codes: A61B 5/02755 Radioactive tracers
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61K 49/1815 compo-inhalant, e.g. breath tests
• CPC Class Codes: G01R 33/5601 involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent
• CPC Class Codes: G01R 33/563 of moving material, e.g. flow contrast angiography

Abstract

MR spectroscopy and imaging methods for imaging pulmonary and cardiac vasculature and the cardiac region and evaluating blood flow or circulatory deficits use dissolved phase polarized ¹²⁹Xe gas and large flip angle excitation pulses. Pulmonary and cardiac vasculature MRI images are obtained by delivering gas to a patient via inhalation such as with a breath-hold delivery -procedure, exciting the dissolved phase gas with a large flip angle pulse, and generating a corresponding image. Preferably, the image is obtained using multi-echo imaging techniques. Blood flow is quantified using low field MR spectroscopy and an RF excitation pulse with a frequency which corresponds to the resonance of the dissolved phase ¹²⁹Xe.

Claims

1. A method for evaluating the effects of a drug therapy on a patient, comprising the steps of:

positioning a subject in a MR spectroscopy system for detecting spectroscopic signals in a subject having a pulmonary vasculature;

delivering a first dose of gaseous polarized ¹²⁹Xe to the subject such that a portion of the gaseous polarized ¹²⁹Xe enters into the pulmonary vasculature and into an associated blood flow path;

exciting the polarized ¹²⁹Xe dissolved in blood in the blood flow path with a first MR spectroscopy RF excitation pulse sequence;

obtaining a first MR spectroscopy response signal based on said exciting step;

administering a drug therapy to the patient;

delivering, after said administering step, a second dose of gaseous polarized ¹²⁹Xe to the subject such that a portion of the gaseous polarized ¹²⁹Xe enters into the pulmonary vasculature and into an associated blood flow path;

exciting the polarized ¹²⁹Xe dissolved in blood in the blood flow path after said second delivering step with a second MR spectroscopy RF excitation pulse sequence;

obtaining a second MR spectroscopy response signal based on said second exciting step; and

comparing the first and second spectroscopic response signals to evaluate the effect of the drug therapy administered to the patient.

2. A method according to claim 1, wherein said exciting steps are carried out using large angle excitation pulses.

3. A method according to claim 1, wherein the MR Spectroscopy System comprises a magnetic field operably associated therewith, and wherein the magnetic field strength is less than about 0.5 T.

4. A method according to claim 1, wherein said evaluating step determines one of the vasodilator effect and the vasocontractory effect of the drug therapy.

5. A method according to claim 1, wherein the drug therapy is a hypertensive agent.

21. A method according to claim 1, wherein the first and second response signals represent the blood-dissolved component of polarized ¹²⁹Xe, and wherein said method further comprises evaluating the first and second response signals to generate quantitative measures of in vivo perfusion in a subject.

22. A method according to claim 1, further comprising evaluating the response signals to determine the slope of the associated dissolved phase polarized ¹²⁹Xe signal intensity in the blood over time.

23. A method according to claim 1, wherein the first and second response signals correspond to polarized ¹²⁹Xe dissolved in blood;

and wherein said method further comprises;

exciting the polarized ¹²⁹Xe in gas lung spaces with a third MR spectroscopy RF excitation pulse sequence;

obtaining a third MR spectroscopy response signal based on said lung space exciting step; and

comparing the data from the third MR response signal of hyperpolarized gas in the gas lung space to data from at least one of the first and second response signals of dissolved phase hyperpolarized ¹²⁹Xe in blood.

24. A method according to claim 1, wherein the RF excitation pulse sequence of the first and second exciting steps is a volume selective pulse.

25. A method according to claim 23, wherein said comparing step accounts for the polarization level and concentration of the polarized ¹²⁹Xe on signal intensity.

26. A method according to claim 22, further comprising evaluating the slope to assess blood flow rate.

27. A method according to claim 26, further comprising employing cardiac gating to time or sequence the data acquisition of the first and second response signals.

28. A method according to claim 1, wherein said first and second exciting steps are carried out by generating an RF excitation pulse having a large flip angle that is configured with a frequency that can selectively excite dissolved phase hyperpolarized ¹²⁹Xe in a subject by centering the pulse frequency on the dissolved phase ¹²⁹Xe resonance frequency below the corresponding gas phase excitation resonance frequency.

29. A method according to claim 1, further comprising analyzing the data associated with the first and second response signals associated with dissolved polarized ¹²⁹Xe in a subject to quantitatively measure blood flow in vivo.

30. A method according to claim 29, wherein the analyzing step is carried out to provide real-time blood flow information.

6. A method for evaluating blood flow and/or vasculature of a patient, comprising the steps of:

positioning a subject in a MR spectroscopy system for detecting spectroscopic signals in a subject having a pulmonary vasculature;

delivering gaseous polarized ¹²⁹Xe to the subject such that a portion of the gaseous polarized ¹²⁹Xe enters into the pulmonary vasculature and into an associated blood flow path;

exciting the polarized ¹²⁹Xe in the blood flow path with at least one MR spectroscopy RF excitation pulse;

obtaining a first MR spectroscopy signal of the polarized ¹²⁹Xe dissolved in blood based on said exciting step;

obtaining a second MR spectroscopy signal of the polarized ¹²⁹Xe dissolved in blood based on said exciting step temporally spaced apart a selected time interval from said first obtaining step; and

evaluating the blood flow of the patient based on the spectroscopic signals of said obtaining steps.

7. A method according to claim 6, wherein said evaluating step evaluates whether there is blockage in the cardiac blood flow path.

8. A method according to claim 6, wherein said evaluating step is carried out to identify the presence of abnormal perfusion along the vasculature.

9. A method according to claim 6, wherein said evaluating step is performed to provide real-time blood flow data.

10. A method according to claim 9, further comprising the step of administering a medication to a subject and evaluating its effect on the blood flow rate of a subject.

11. A method according to claim 10, wherein said evaluating step is carried out by monitoring the intensity of the dissolved polarized ¹²⁹Xe response signal over time to obtain data about the blood flow or vasculature of the subject.

12. A method according to claim 6, wherein said evaluating step comprises assessing cerebral perfusion.

13. A method according to claim 6, wherein the first and second MR spectroscopic signals from said first and second obtaining steps have a signal strength associated therewith, and wherein said evaluating step comprises comparing the signal strength of the first and second spectroscopic ¹²⁹Xe response signals over time to evaluate the blood flow rate of the subject.

14. A method according to claim 13, wherein said first and second MR excitation pulses comprise about 90 degree flip angle excitation pulses.

31. A method according to claim 6, wherein said method further comprises evaluating the first and second spectroscopic signals to generate quantitative measures of in vivo perfusion in a subject.

32. A method according to claim 6, further comprising evaluating the spectroscopic signals to determine the slope of dissolved phase hyperpolarized ¹²⁹Xe signal intensity in blood over time.

33. A method according to claim 6, wherein said delivering step is via ventilation or inhalation into the patient'"'"'s gas lung spaces, and wherein said method further comprises:

exciting the polarized ¹²⁹Xe in the gas lung spaces with a RF excitation pulse sequence;

obtaining a third MR spectroscopic signal based on said lung space exciting step; and

comparing the third MR spectroscopic signal of hyperpolarized gas in the gas lung space to at least one of the first and second spectroscopic signals of dissolved phase hyperpolarized ¹²⁹Xe in blood.

34. A method according to claim 6, wherein the RF excitation pulse sequence of the exciting step is a volume selective pulse.

35. A method according to claim 33, wherein said comparing step accounts for the polarization level and concentration of the polarized ¹²⁹Xe on signal intensity.

36. A method according to claim 32, further comprising evaluating the slope to assess blood flow rate.

37. A method according to claim 6, further comprising employing cardiac gating to time or sequence the data acquisition of the first and second spectroscopic signals.

38. A method according to claim 6, wherein said first and second exciting steps are carried out by generating an RF excitation pulse having a large flip angle that is configured with a frequency that can selectively excite dissolved phase hyperpolarized ¹²⁹Xe in a subject by centering the pulse frequency on the dissolved phase ¹²⁹Xe resonance frequency below a corresponding gas phase excitation resonance frequency.

15. A method for assessing the presence or absence of abnormalities in the vasculature or blood flow path of a subject, comprising the steps of:

administering gaseous polarized ¹²⁹Xe to a subject in vivo such that the gaseous polarized ¹²⁹Xe enters the subject'"'"'s lungs and travels to the subject'"'"'s vasculature, wherein it dissolves;

transmitting at least one large angle MR spectroscopy excitation pulse to the ¹²⁹Xe after it travels, dissolved in blood, into the subject'"'"'s vasculature based on said administering step;

obtaining at least one polarized dissolved ¹²⁹Xe spectroscopic response signal based on said transmitting step, the response signal having an associated intensity line shape, slope, and signal strength associated therewith; and

evaluating data associated with the line shape, signal strength, and/or intensity provided by the spectroscopic response signal associated with the dissolved polarized ¹²⁹Xe in blood to determine anomalies in the vasculature and/or blood flow path of the subject based on said obtaining step.

16. A method according to claim 15, wherein said evaluating step comprises assessing at least one of (a) perfusion deficits in the pulmonary vasculature or the cardiac vasculature, (b) pulmonary vasculature emboli, (c) blood flow related circulatory system deficits, and (d) restrictions and obstructions in the blood flow path of the subject.

17. A method according to claim 15, wherein said evaluating step is carried out by monitoring the intensity of the at least one dissolved polarized ¹²⁹Xe response signal over time to obtain diagnostic information.

18. A method according to claim 15, wherein said evaluating step is carried out to assess cerebral perfusion.

19. A method according to claim 17, wherein said evaluating step comprises assessing blood flow path blockage or restrictions.

20. A method according to claim 15, wherein said evaluating step comprises at least one of:

(a) identifying the presence or absence of cardiac ischemias or infarcts;

(b) identifying thrombi or plaques;

(c) determining therapeutic windows for administering heparin, vasodilators, antihypertensive agents, and calcium antagonists;

(d) evaluating the severity or existence of ischemias;

(e) evaluating therapies in the treatment of cerebral vasospasm;

(f) assessing ischemia in large tissue masses;

(g) assessing the relationship between blood metabolites and cerebral perfusion in cerebral ischemia for the diagnosis or treatment of Alzheimer'"'"'s disease;

(h) evaluating therapies for stroke;

(i) evaluating risk factors for stroke;

(j) evaluating induced brain hypothermia on cerebral perfusion during neurosurgery for stroke;

(k) evaluating the effects of age on cerebral perfusion; and

(l) assessing the effect of narcotics on the ischemic brain.

39. A method according to claim 15, wherein the at least one obtaining step is repeated a plurality of times to provide a plurality of spectroscopic response signals for ¹²⁹Xe dissolved in blood having a signal strength associated therewith, and wherein the evaluating step considers a plurality of the response signals.

40. A method according to claim 39, wherein the evaluating step generates quantitative measures of in vivo perfusion in a subject.

41. A method according to claim 39, further comprising evaluating the response signals to determine the slope of the associated dissolved phase polarized ¹²⁹Xe signal intensity in the blood over time.

42. A method according to claim 39, wherein said method further comprises:

exciting the polarized ¹²⁹Xe in gas lung spaces with an MR spectroscopy RF excitation pulse sequence;

obtaining a ¹²⁹Xe gas-based MR spectroscopy response signal based on said lung space exciting step; and

comparing data from the MR response signal of hyperpolarized gas in the gas lung space to data from at least one of the plurality of response signals of dissolved phase hyperpolarized ¹²⁹Xe in blood.

43. A method according to claim 15, wherein the transmitted excitation pulse is a volume selective pulse.

44. A method according to claim 42, wherein said comparing step accounts for the polarization level and concentration of the polarized ¹²⁹Xe on signal intensity.

45. A method according to claim 41, further comprising evaluating the slope to assess blood flow rate.

46. A method according to claim 45, further comprising employing cardiac gating to time or sequence the data acquisition of the plurality of dissolved polarized ¹²⁹Xe response signals.

47. A method according to claim 39, wherein said transmitting step is carried out by generating an RF excitation pulse having a large flip angle that is configured with a frequency that can selectively excite dissolved phase hyperpolarized ¹²⁹Xe in a subject by centering the pulse frequency on the dissolved phase ¹²⁹Xe resonance frequency below the corresponding gas phase excitation resonance frequency.

48. A method according to claim 39, further comprising analyzing the data associated with the response signals associated with dissolved polarized ¹²⁹Xe in a subject to quantitatively assess blood flow in vivo.

49. A method according to claim 48, wherein the analyzing step is carried out to provide real-time blood flow information.

50. A method according to claim 39, wherein said method further comprises evaluating the spectroscopic signals to generate quantitative measures of in vivo perfusion in a subject.