Sodium magnetic reasonance imaging used in diagnosing tumors and assessing response to treatment

• US 6,681,132 B1
• Filed: 05/13/1999
• Issued: 01/20/2004
• Est. Priority Date: 05/13/1999
• Status: Expired due to Term

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Wu, Edward X., Kline, Richard Paul, Katz, Jose
• Primary Examiner(s): Smith, Ruth S.
• Application Number:
  US09/317,068
• Time in Patent Office: 1,713 Days
• Field of Search: 600/410, 436/63, 436/64, 436/173, 324/307, 324/309, 424/9.2
• US Class Current: 600/410
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: G01R 33/4838 using spatially selective suppression or saturation of MR signals
• CPC Class Codes: G01R 33/5602 by filtering or weighting based on different relaxation times within the sample, e.g. T1 weighting using an inversion pulse
• CPC Class Codes: G01R 33/5607 by reducing the NMR signal of a particular spin species, e.g. of a chemical species for fat suppression, or of a moving spin species for black-blood imaging
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

The present invention provides a method for measuring the magnetic resonance signal of an intracellular population of predetermined nuclei in a cell-containing sample by: a) applying to the sample a first radio frequency pulse, in a magnetic field, b) after a set time interval (T_I), applying to the sample a second radio frequency pulse sufficient to cause a measurable signal, and c) measuring the measurable signal for the sample so produced, which method is utilized in methods of (i) determining the effectiveness of chemotherapy, (ii) detecting and characterizing tumors, and (iii) determining cell death in a cell-containing sample.

Claims

1. A method for measuring the magnetic resonance signal of an intracellular population of predetermined nuclei in a cell-containing sample comprising:

(a) applying to the sample a first radio frequency pulse, in a magnetic field, sufficient to cause alignment of the predetermined nuclei within the sample;

(b) after a set time interval (T_I), applying to the sample a second radio frequency pulse, in a magnetic field, sufficient to cause a measurable signal in the plane transverse to the direction of nuclear alignment in step (a);

(c) suppressing the measurable signal in the transverse plane attributable to the extracellular population of predetermined nuclei in the sample; and

(d) applying image encoding techniques for acquisition of the measurable signal attributable to the intracellular population of predetermined nuclei in the sample,

(e) detecting and analyzing the measurable signal to obtain a weighted image;

(f) obtaining an unweighted image of the measurable signal; and

(g) comparing the weighted image to the unweighted image of the measurable signal,

so as to thereby measure the magnetic resonance signal of the intracellular population of predetermined nuclei in the sample.

2. The method of claim 1, wherein the magnetic field strength is 1 to 15 tesla.

3. The method of claim 1, wherein the magnetic field strength is 1 to 5 tesla.

4. The method of claim 1, wherein the magnetic field is generated by a magnetic coil having a field strength of 4.23 tesla.

5. The method of claim 4, wherein the magnetic coil is tuned for sodium.

6. The method of claim 5, wherein the magnetic coil is multiple-tuned.

7. The method of claim 4, wherein T_I is 25 msec.

8. The method of claim 1, wherein the set time interval (T_I) alone permits suppression of the measurable signal attributable to the extracellular nuclei.

9. The method of claim 8, wherein suppressing the measurable signal comprises minimizing such signal.

10. The method of claim 8, wherein suppressing the measurable signal attributable to the extracellular nuclei comprises the use of phantoms.

11. The method of claim 8, wherein the first pulse is 180°

, and the second pulse is 90°

, and (T_I) is (ln2)T₁.

12. The method of claim 1, wherein the predetermined nuclei are sodium nuclei.

13. The method of claim 1, whereby the intracellular and extracellular populations of predetermined nuclei have different longitudinal relaxation times.

14. The method of claim 1, wherein the weighted image and the unweighted image are compared pixel to pixel.

15. The method of claim 1, wherein the weighted image and the unweighted image are compared region to region.

16. The method of claim 1, wherein the weighted image and the unweighted image are compared algebraically.

17. The method of claim 1, wherein the sample is in a subject.

18. The method of claim 17, wherein the subject is a mammal.

19. In The method of claim 18, wherein the subject is a human.

20. The method of claim 1, wherein step (c) is achieved by selecting a suitable (T_I).

21. The method of claim 1, wherein step (c) is achieved by applying a multiple quantum filter.

22. A method for determining the effectiveness of chemotherapy using a chemotherapeutic agent in a subject afflicted with a cancerous tumor comprising:

(a) measuring, according to the method of claim 1, the magnetic resonance signal of an intracellular predetermined nuclei population in a subject to whom the chemotherapeutic agent has been administered; and

(b) comparing the signal so measured with a standard, so as to thereby determine the effectiveness of the chemotherapy in the subject.

23. The method of claim 22, wherein the subject is a mammal.

24. The method of claim 23, wherein the mammal is a human.

25. The method of claim 22, wherein the chemotherapeutic agent is administered via intravenous injection, infusion, liposome-mediated delivery, topical, nasal, oral, anal, ocular or otic delivery.

26. The method of claim 22, wherein the cancerous tumor is a prostate or breast tumor.

27. A method for detecting and characterizing a tumor in a sample comprising:

(a) measuring, according to the method of claim 1, the magnetic resonance signal of an intracellular predetermined nuclei population in the sample; and

(b) comparing the signal so measured with a standard, so as to thereby detect and characterize a tumor in the sample.

28. The method of claim 27, wherein the tumor is cancerous.

29. The method of claim 27, wherein the sample is in a subject.

30. The method of claim 29, wherein the subject is a mammal.

31. The method of claim 30, wherein the subject is a human.

32. A method for detecting cell death in a cell-containing sample comprising:

(a) measuring, according to the method of claim 1, the magnetic resonance signal of an intracellular predetermined nuclei population in the sample; and

(b) comparing the signal so measured with a standard, so as to thereby detect cell death in the sample.

33. The method of claim 32, wherein the sample is in a subject.

34. The method of claim 33, wherein the subject is a mammal.

35. The method of claim 34, wherein the subject is a human.

36. The method of claim 1, wherein the first radio frequency pulse is 180°

and the second radio frequency pulse is 90°

.

37. The method of claim 1, wherein the image acquired is a two-dimensional image or three dimensional image.