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

• US 20030152516A1
• Filed: 12/09/2002
• Published: 08/14/2003
• Est. Priority Date: 03/18/1998
• Status: Active Grant

• Current Assignee: Polarean, Inc. (Polarean Imaging Plc)
• Original Assignee: Bastiaan Driehuys, Kenton Christopher Hasson, Paul Lev Bogorad
• Inventors: Bogorad, Paul Lev, Hasson, Kenton Christopher, Driehuys, Bastiaan
• Granted Patent: US 6,808,699 B2
• Time in Patent Office: Days
• US Class Current: 424/9.3
• 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:

sequentially delivering via inhalation a plurality of successive doses of gaseous polarized ¹²⁹Xe to the subject such that a portion of each dose of the gaseous polarized ¹²⁹Xe enters into pulmonary vasculature and an associated blood flow path of a biological subject;

serially obtaining NMR spectroscopic response signals of the plurality of successive doses of the polarized ¹²⁹Xe as the polarized ¹²⁹Xe is taken up into the blood flow path;

administering a drug therapy to the biological subject; and

comparing the serially obtained NMR spectroscopic response signals to evaluate the effect of the drug therapy administered to the patient.

2. A method according to claim 1, wherein the 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.

3. 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.

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.

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

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 of the patient;

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

obtaining a first NMR spectroscopy response signal of the polarized ¹²⁹Xe taken up in the vasculature and/or blood flow path based on said exciting step;

obtaining a second NMR response signal of the polarized ¹²⁹Xe take up in the vasculature and/or blood flow path based on said exciting step temporally spaced apart a selected time interval from said first obtaining step; and

evaluating the patient using data from the first and second NMR response spectroscopic signals of said obtaining steps to assess the blood flow, blood flow path, and/or vasculature of the patient.

7. A method according to claim 6, further comprising the step of administering a medication to a subject and evaluating its effect on the blood flow rate, blood flow path, and/or vasculature of a subject.

8. A method according to claim 6, 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, blood flow path, or vasculature of the subject.

9. A method for assessing the presence or absence of abnormalities in the vasculature, blood flow, 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 is taken up into the subject'"'"'s vasculature and then into the blood stream;

obtaining a plurality of NMR spectroscopic polarized dissolved ¹²⁹Xe spectroscopic response signals, each response signal having an associated intensity curve, slope, and signal strength associated therewith; and

evaluating data associated with the NMR response signal uptake curve, 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, blood flow, and/or blood flow path of the subject based on said obtaining step.

10. A method according to claim 9, 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.

11. A method according to claim 9, further comprising evaluating the slope of the uptake curve of the NMR response signal to assess blood flow rate.

12. A method according to claim 9, further comprising employing cardiac gating to time or sequence the data acquisition of the plurality of dissolved polarized ¹²⁹Xe response signals.

13. A method according to claim 9, further comprising transmitting 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.

14. A method according to claim 9, 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.

15. A method according to claim 14, wherein the analyzing step is carried out to provide real-time blood flow data.

16. A method according to claim 9, wherein said method further comprises evaluating the obtained NMR spectroscopic polarized ¹²⁹Xe signals to generate quantitative measures of in vivo perfusion in a subject.

17. A method according to claim 9, further comprising the step of administering a physiologically active medication to a subject and evaluating its effect on the blood flow rate, vasculature and/or blood flow path of a subject.

18. A method according to claim 10, wherein said evaluating step is carried out by monitoring the intensity of the dissolved polarized ¹²⁹Xe response signals over time to obtain diagnostic data about the physiology of the subject.

19. A method according to claim 9, wherein the NMR spectroscopic signals have a signal strength associated therewith, and wherein said evaluating step comprises comparing the signal strength of the plurality of NMR ¹²⁹Xe response signals over time to evaluate the blood flow rate, blood flow path, and/or vasculature of the subject.

20. A method according to claim 13, wherein said excitation pulses comprise about a pulse with about a 90 degree flip angle.

21. A method according to claim 9, 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.

22. A method according to claim 9, wherein said evaluating step comprises assessing blood flow path blockage or restrictions.

23. A method according to claim 9, 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.