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

• US 6,346,229 B1
• Filed: 03/17/1999
• Issued: 02/12/2002
• Est. Priority Date: 03/18/1998
• Status: Expired due to Term

• Current Assignee: Polarean, Inc. (Polarean Imaging Plc)
• Original Assignee: Medi-Physics Incorporated (General Electric Company)
• Inventors: Bogorad, Paul Lev, Hasson, Kenton Christopher, Driehuys, Bastiaan
• Primary Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US09/271,476
• Time in Patent Office: 1,063 Days
• Field of Search: 424/9.1, 424/9.3, 424/9.32, 424/9.36
• 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 method 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 MRI imaging the pulmonary and/or cardiac vasculature using dissolved-phase polarized ¹²⁹Xe, comprising the steps of:

delivering polarized ¹²⁹Xe gas to a predetermined region of the patient'"'"'s body, the polarized gas having a dissolved imaging phase associated therewith;

exciting a predetermined region of the patient'"'"'s body having a portion of the dissolved phase polarized gas therein with at least one large flip angle RF excitation pulse;

acquiring at least one MR image associated with the dissolved phase polarized gas after said exciting step,

wherein said delivering step includes having the patient inhale the polarized ¹²⁹Xe gas into the lungs, the polarized ¹²⁹Xe having a gas phase resonance which is higher than the dissolved-phase resonance, and wherein at least a portion of the polarized ¹²⁹Xe gas enters into the pulmonary vasculature in a dissolved-phase, and wherein at least a portion of the dissolved-phase polarized ¹²⁹Xe then enters the blood stream with an associated perfusion rate wherein a differential MRI image is obtained which comprising data associated with the physiology of the lungs of the patient, the physiology of the vasculature of the patient, blood flow in the patient, and perfusion in the patient, the data corresponding to both the ¹²⁹Xe gas and dissolved-gas phase, and wherein said differential image is obtained by exciting the ¹²⁹Xe gas phase with an RF pulse having an excitation pulse frequency which corresponds to the resonance of the gas phase and exciting the dissolved phase with an RF pulse having an excitation frequency which corresponds to the resonance of the dissolved phase, and wherein the gas phase RF excitation pulse is a small flip angle pulse and the dissolved phase RF excitation pulse is a large flip angle pulse.

5. A method according to claim 1, wherein the at least one image is a multi-echo image.

6. A method according to claim 5, wherein the multi-echo image is one of a slice selective and volume selective image pattern.

2. A method for MRI imaging the pulmonary and/or cardiac vasculature using dissolved-phase polarized ¹²⁹Xe, comprising the steps of:

delivering polarized ¹²⁹Xe gas to a predetermined region of the patient'"'"'s body, the polarized gas having a dissolved imaging phase associated therewith;

exciting a predetermined region of the patient'"'"'s body having a portion of the dissolved phase polarized gas therein with at least one large flip angle RF excitation pulse;

acquiring at least one MR image associated with the dissolved phase polarized gas after said exciting step,

wherein said delivering step comprises having the patient inhale the polarized ¹²⁹Xe gas into the lungs, the polarized ¹²⁹Xe having a gas phase resonance which is higher than the dissolved-phase resonance, and wherein at least a portion of the polarized ¹²⁹Xe gas enters into the pulmonary vasculature in a dissolved-phase, and wherein at least a portion of the dissolved-phase polarized ¹²⁹Xe then enters the blood stream with an associated perfusion rate; and

delivering via inhalation a quantity of polarized ³He gas, and wherein a MRI differential image is obtained comprising data corresponding to the polarized gas ³He in the lungs in addition to the dissolved phase polarized ¹²⁹Xe.

3. A method for MRI imaging the pulmonary and/or cardiac vasculature using dissolved-phase polarized ¹²⁹Xe, comprising the steps of:

delivering polarized ¹²⁹Xe gas to a predetermined region of the patient'"'"'s body, the polarized gas having a dissolved imaging phase associated therewith;

exciting a predetermined region of the patient'"'"'s body having a portion of the dissolved phase polarized gas therein with at least one large flip angle RF excitation pulse; and

acquiring at least one MR image associated with the dissolved phase polarized gas after said exciting step,

wherein said exciting step is repeated within a predetermined repetition time, the predetermined repetition time being less than the time it takes for a given volume of blood to move from the lungs to the heart, wherein said delivering step comprises inhalation of the polarized ¹²⁹Xe gas into the lungs, the ¹²⁹Xe having a gas phase resonance which is higher than the dissolved-phase resonance, wherein at least a portion of the polarized ¹²⁹Xe gas enters into the pulmonary vasculature in a dissolved-phase, wherein at least a portion of the dissolved-phase polarized ¹²⁹Xe then enters the blood stream with an associated perfusion rate and

wherein said inhalation delivering step comprises a breath-hold delivery period.

4. A method according to claim 3, wherein the breath-hold period is at least 10 seconds.

7. A method for MRI imaging the pulmonary and/or cardiac vasculature using dissolved-phase polarized ¹²⁹Xe, comprising the steps of:

delivering polarized ¹²⁹Xe gas to a predetermined region of the patient'"'"'s body, the polarized gas having a dissolved imaging phase associated therewith;

exciting a predetermined region of the patient'"'"'s body having a portion of the dissolved phase polarized gas therein with at least one large flip angle RF excitation pulse; and

acquiring at least one MR image associated with the dissolved phase polarized gas after said exciting step,

wherein said exciting step is repeated within a predetermined repetition time, the predetermined repetition time being less than the time it takes for a given volume of blood to move from the lungs to the heart,

wherein said delivering step comprises inhalation of the polarized ¹²⁹Xe gas into the lungs, the ¹²⁹Xe having a gas phase resonance which is higher than the dissolved-phase resonance, wherein at least a portion of the polarized ¹²⁹Xe gas enters into the pulmonary vasculature in a dissolved-phase, wherein at least a portion of the dissolved-phase polarized ¹²⁹Xe then enters the blood stream with an associated perfusion rate, and wherein the repetition time is decreased to emphasize a signal associated with capillaries in the pulmonary region.

8. A method for MRI imaging the pulmonary and/or cardiac vasculature using dissolved-phase polarized ¹²⁹Xe, comprising the steps of:

delivering polarized ¹²⁹Xe gas to a predetermined region of the patient'"'"'s body, the polarized gas having a dissolved imaging phase associated therewith;

exciting a predetermined region of the patient'"'"'s body having a portion of the dissolved phase polarized gas therein with at least one large flip angle RF excitation pulse; and

acquiring at least one MR image associated with the dissolved phase polarized gas after said exciting step,

wherein said exciting step is repeated within a predetermined repetition time, the predetermined repetition time being less than the time it takes for a given volume of blood to move from the lungs to the heart,

wherein said delivering step comprises inhalation of the polarized ¹²⁹Xe gas into the lungs, the ¹²⁹Xe having a gas phase resonance which is higher than the dissolved-phase resonance, wherein at least a portion of the polarized ¹²⁹Xe gas enters into the pulmonary vasculature in a dissolved-phase, wherein at least a portion of the dissolved-phase polarized ¹²⁹Xe then enters the blood stream with an associated perfusion rate, and wherein the repetition time is increased to include distal vasculature relative to the pulmonary capillaries.

10. A method according to claim 8, wherein said acquiring step acquires at least 32 echoes per each excitation pulse.

9. A method for MRI imaging the pulmonary and/or cardiac vasculature using dissolved-phase polarized 129Xe, comprising the steps of:

delivering polarized ¹²⁹Xe gas to a predetermined region of the patient'"'"'s body, the polarized gas having a dissolved imaging phase associated therewith;

exciting a predetermined region of the patient'"'"'s body having a portion of the dissolved phase polarized gas therein with at least one large flip angle RF excitation pulse; and

acquiring at least one MR image associated with the dissolved phase polarized gas after said exciting step,

wherein said exciting step is repeated within a predetermined repetition time, the predetermined repetition time being less than the time it takes for a given volume of blood to move from the lungs to the heart, wherein dissolved-phase ¹²⁹Xe has an associated decay time constant (T1) corresponding to its polarization life and a transverse relaxation time in blood (T₂*), and wherein for T₂* greater than about 100 ms, said acquiring step employs one of EPI and RARE multi-echo imaging methods.

11. A method for MRI imaging the pulmonary and/or cardiac vasculature using dissolved-phase polarized ¹²⁹Xe, comprising the steps of:

delivering polarized ²⁹Xe gas to a predetermined region of the patient'"'"'s body, the polarized gas having a dissolved imaging phase associated therewith;

exciting a predetermined region of the patient'"'"'s body having a portion of the dissolved phase polarized gas therein with at least one large flip angle RF excitation pulse; and

acquiring at least one MR image associated with the dissolved phase polarized gas after said exciting step,

wherein said exciting step is repeated within a predetermined repetition time, the predetermined repetition time being less than the time it takes for a given volume of blood to move from the lungs to the heart, and

wherein cardiac gating is used so that said acquiring step is timed such that it is performed during slow blood flow periods.

12. A method for MRI imaging the pulmonary and/or cardiac vasculature using dissolved-phase polarized ¹²⁹Xe, comprising the steps of:

delivering polarized ¹²⁹Xe gas to a predetermined region of the patient'"'"'s body, the polarized gas having a dissolved imaging phase associated therewith;

exciting a predetermined region of the patient'"'"'s body having a portion of the dissolved phase polarized gas therein with at least one large flip angle RF excitation pulse; and

acquiring at least one MR image associated with the dissolved phase polarized gas after said exciting step,

wherein said exciting step is repeated within a predetermined repetition time, the predetermined repetition time being less than the time it takes for a given volume of blood to move from the lungs to the heart,

wherein said delivering step comprises inhalation of the polarized ¹²⁹Xe gas into the lungs, the ¹²⁹Xe having a gas phase resonance which is higher than the dissolved-phase resonance, wherein at least a portion of the polarized ¹²⁹Xe gas enters into the pulmonary vasculature in a dissolved-phase, wherein at least a portion of the dissolved-phase polarized ¹²⁹Xe then enters the blood stream with an associated perfusion rate, wherein the at least one image is a multi-echo image, and wherein the multi-echo imaging uses one of gradient recalled and RF recalled echoes.

13. A method for evaluating the blood flow of a patient, comprising the steps of:

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

delivering gaseous polarized ¹²⁹Xe to the subject;

dissolving a portion of the gaseous polarized ¹²⁹Xe into the pulmonary vasculature having an associated blood flow path;

exciting the dissolved portion of the ¹²⁹Xe with an MR spectroscopy RF excitation pulse; and

evaluating blood flow of the patient based on a spectroscopic signal corresponding to

the dissolved polarized ¹²⁹Xe, wherein said evaluating step includes the step of

exciting the dissolved ¹²⁹Xe with a large angle RF excitation pulse,

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.

14. A method according to claim 13, wherein said evaluating step is performed to provide real-time blood flow information.

15. A method for quantitatively evaluating the blood flow rate of a subject, comprising the steps of:

administering gaseous polarized ¹²⁹Xe to a subject such that the gaseous polarized ¹²⁹Xe enters the subject'"'"'s lungs;

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

obtaining a first polarized dissolved ¹²⁹Xe spectroscopic response signal based on said large flip angle pulse transmitting step, the first response signal having a signal strength associated therewith;

obtaining a second polarized dissolved ¹²⁹Xe spectroscopic response signal based on said at least one large flip angle pulse transmitting step, the second response signal having a signal strength associated therewith, wherein said second polarized dissolved ¹²⁹Xe response signal obtaining step is temporally spaced apart a time interval from said first dissolved response signal obtaining step;

monitoring the increase in signal strength of the dissolved polarized ¹²⁹Xe response signal over time based on said first and second dissolved response signal obtaining steps;

transmitting a predetermined flip angle RF excitation pulse to the gaseous ¹²⁹Xe residing in the lung void space based on said administering step;

obtaining a first polarized ¹²⁹Xe gas spectroscopic response signal based on said predetermined flip angle gaseous excitation transmitting step;

comparing the polarized ¹²⁹Xe gas response signal with the first and second dissolved polarized ¹²⁹Xe response signals; and

evaluating the blood flow rate of the subject based on said comparing step.

16. A method according to claim 15, further comprising the step of quantitatively determining the blood flow rate of the subject based on said comparing step.

17. A method according to claim 15, further comprising obtaining a third polarized dissolved ¹²⁹Xe spectroscopic response signal based on said at least one large flip angle pulse transmitting step, the third response signal having a signal strength associated therewith, wherein said third dissolved response signal obtaining step is temporally spaced apart a time interval from said first and second dissolved response signal obtaining steps.

18. A method according to claim 16, wherein said at least one large flip angle transmitting step comprises transmitting two temporally separate large flip angle pulses.

19. A method according to claim 16, further comprising the step of calculating the slope of a line corresponding to the dissolved ¹²⁹Xe response signal intensity over pulse repetition time.

20. A method according to claim 19, further comprising the step of mathematically dividing the slope with the value of the ¹²⁹Xe gas response signal generated in said gas response signal obtaining step.

21. A method according to claim 16, further comprising the step of numerically fitting a line to the signal strength of the first and second dissolved ¹²⁹Xe response signals to calculate the slope of the line corresponding to the dissolved ¹²⁹Xe response signals.

22. A method according to claim 15, further comprising the step of generating a Magnetic Resonance image of the polarized ¹²⁹Xe in the lungs of the subject subsequent to said administering step.

23. A method according to claim 15, further comprising the step of administering a physiologically active medication to a subject and evaluating its affect on the blood flow rate of a subject.

24. A method according to claim 16, further comprising the step of determining a lung volume representative of the subject'"'"'s lungs and using the determined lung volume in said quantitative determination step.

25. A method according to claim 16, further comprising the step of normalizing the blood flow rate obtained in said determining step by considering the subject'"'"'s heart rate.

26. A method according to claim 15, further comprising the step of evaluating the existence of perfusion deficiencies or abnormalities.

27. A method according to claim 26, wherein said evaluating step is carried out by monitoring the intensity of the dissolved polarized ¹²⁹Xe response signal over time to obtain diagnostic information.

28. A method according to claim 27, wherein said evaluating step includes assessing cerebral perfusion.

29. A method for quantitatively evaluating the blood flow rate of a subject, comprising the steps of:

administering gaseous polarized ¹²⁹Xe to a subject such that the gaseous polarized ¹²⁹Xe enters the subject'"'"'s lungs;

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

obtaining a first polarized dissolved ¹²⁹Xe spectroscopic response signal based on said large flip angle pulse transmitting step, the first response signal having a signal strength associated therewith;

obtaining a second polarized dissolved ¹²⁹Xe spectroscopic response signal based on said at least one large flip angle pulse transmitting step, the second response signal having a signal strength associated therewith, wherein said second dissolved polarized ¹²⁹Xe response signal obtaining step is temporally spaced apart a time interval from said first dissolved polarized ¹²⁹Xe response signal obtaining step;

monitoring the increase in signal strength of the dissolved polarized ¹²⁹Xe response signal over time based on said first and second dissolved response signal obtaining steps; and

evaluating the blood flow rate of the subject based on said monitoring step.

30. A method according to claim 29, further comprising the steps of administering a medication to the subject and monitoring the efficacy of the medication based on said evaluating blood flow rate step.

31. A method according to claim 29, wherein said evaluating step comprises the steps of:

transmitting a predetermined flip angle RF excitation pulse to the gaseous ¹²⁹Xe residing in the lung void space based on said administering step;

obtaining a first polarized ¹²⁹Xe gas spectroscopic response signal having an associated signal strength based on said predetermined flip angle gaseous excitation transmitting step;

comparing the polarized ¹²⁹Xe gas phase response signal with the first and second dissolved ¹²⁹Xe response signals; and

quantitatively determining the blood flow rate of the subject based on said comparing step.

32. A method according to claim 29, further comprising the step of calculating the slope of a line corresponding to the dissolved polarized ¹²⁹Xe signal intensity over pulse repetition time.

33. A method according to claim 31, further comprising the step of mathematically dividing the slope with the value of the polarized ¹²⁹Xe gas response signal strength generated in said gas phase obtaining step.

34. A method according to claim 29, further comprising the step of generating a Magnetic Resonance image of the polarized ¹²⁹Xe in the lungs of the subject subsequent to said administering step.

35. A method according to claim 31, further comprising the step of identifying a lung volume representative of the subject'"'"'s lungs and using the identified lung volume in said blood flow rate determination step.

36. A method according to claim 31, further comprising the step of normalizing the blood flow rate obtained in said determining step by taking into account the subject'"'"'s heart rate.

37. A method according to claim 29, further comprising the step of evaluating the existence of perfusion deficiencies or abnormalities.

38. A method for quantitatively evaluating perfusion abnormalities and/or the blood flow rate of a subject, comprising the steps of:

administering gaseous polarized ¹²⁹Xe to a subject such that the gaseous polarized ¹²⁹Xe enters the subject'"'"'s lungs;

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

obtaining a first polarized dissolved ¹²⁹Xe spectroscopic response signal based on said large flip angle pulse transmitting step, the first response signal having a signal strength associated therewith;

obtaining a second polarized dissolved ¹²⁹Xe spectroscopic response signal based on said at least one large flip angle pulse transmitting step, the second response signal having a signal strength associated therewith, wherein said second dissolved polarized ¹²⁹Xe response signal obtaining step is temporally spaced apart a time interval from said first dissolved polarized ¹²⁹Xe obtaining step;

monitoring the signal strength of the dissolved polarized ¹²⁹Xe response signal over time based on said first and second dissolved polarized ¹²⁹Xe response signal obtaining steps; and

evaluating at least one of perfusion function or blood flow in the blood flow path of the subject based on said monitoring step.

39. A method according to claim 38, 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.

40. A method according to claim 38, wherein said evaluating step is carried out by monitoring the intensity of the dissolved polarized ¹²⁹Xe response signal over time to obtain diagnostic information.

41. A method according to claim 40, wherein said evaluating step comprises assessing cerebral perfusion.

42. A method according to claim 40, wherein said evaluating step comprises assessing blood flow path blockage or restrictions.

43. A method according to claim 38, wherein said evaluating step comprises one or more 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.

44. A method for MRI imaging the pulmonary and/or cardiac vasculature using polarized ¹²⁹Xe dissolved in the blood stream, comprising the steps of:

administering gaseous polarized ¹²⁹Xe to a subject such that the gaseous polarized ¹²⁹Xe enters the subject'"'"'s lungs;

transmitting at least one large flip angle RF excitation pulse from an MR apparatus to a first quantity of the ¹²⁹Xe after it travels, dissolved, into the subject'"'"'s vasculature based on said administering step;

substantially destroying the polarization of the ¹²⁹Xe dissolved in the subject'"'"'s vasculature based on said first transmitting step;

delaying a predetermined period of time and then transmitting a second large flip angle RF excitation pulse from the MR apparatus to a second quantity of the ¹²⁹Xe after it travels, dissolved, into the subject'"'"'s vasculature, wherein the predetermined time is sufficient to allow the uptake of the second quantity of polarized ¹²⁹Xe into the vasculature based on said administering step;

obtaining first and second response signals for the polarized dissolved ¹²⁹Xe based on the corresponding first and second transmitting steps, the first and second response signals each having a signal strength associated therewith;

transmitting a third RF excitation pulse from the MR apparatus to excite the ¹²⁹Xe gas in the lung of the subject;

obtaining a third response signal corresponding to the third transmitting step; and

acquiring at least one MR image comprising data provided by said first and second obtaining steps associated with the dissolved polarized ¹²⁹Xe in the vasculature and at least one MR image comprising data provided by said third obtaining step associated with the ¹²⁹Xe in the lung, wherein the predetermined time between said first and second transmitting steps is defined as a pulse repetition time,

wherein said pulse repetition time is less than about 3 seconds, and wherein the first, second, and third obtaining steps are carried out during a single imaging session.

45. A method according to claim 44, wherein said at least one image is a differential MRI image comprising data corresponding to both the polarized ¹²⁹Xe gas in the lungs and the polarized dissolved ¹²⁹Xe in the vasculature.

46. A method according to claim 44, wherein the at least one image is a multi-echo image, and wherein the multi-echo imaging uses one of gradient recalled and RF recalled echoes.

47. A method according to claim 44, wherein the pulse repetition time is decreased to emphasize a signal associated with capillaries in the pulmonary region.

48. A method according to claim 44, wherein the pulse repetition time is increased to include distal vasculature relative to the pulmonary capillaries.

49. A method according to claim 44, wherein dissolved-phase ¹²⁹Xe has an associated decay time constant (T1) corresponding to its polarization life and a transverse relaxation time in blood (T₂*) greater than about 100 ms and said acquiring step employs one of EPI and RARE multi-echo imaging methods.

50. A method according to claim 44, wherein cardiac gating is used so that said acquiring step is timed such that it is performed during slow blood flow periods.

51. A method according to claim 44, wherein said method further comprising the step of providing a cardiac coil which is positioned proximate to the cardiac region of the subject, the cardiac coil being configured to spatially limit the excitation pulses transmitted to the subject.

52. A method according to claim 44, wherein the MR image of the dissolved polarized ¹²⁹Xe MR image and the MR image of the polarized ¹²⁹Xe gas in the lung are obtained during a single breath-hold inhalation cycle.