Magnetic Resonance-Based Viscometers and Methods

• US 20110124744A1
• Filed: 08/15/2008
• Published: 05/26/2011
• Est. Priority Date: 08/17/2007
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology, The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Hong, Rui, Cima, Michael J., Weissleder, Ralph, Josephson, Lee
• Granted Patent: US 9,097,644 B2
• Time in Patent Office: Days
• US Class Current: 514/789
• CPC Class Codes: G01N 24/08 by using nuclear magnetic resonance G01N24/12 takes precedence
• CPC Class Codes: G01N 27/745 for detecting magnetic beads used in biochemical assays concerning the assays G01N33/54326; sensors therefor G01R33/1269; automatic analysers therefor G01N35/0098
• CPC Class Codes: G01R 33/465 applied to biological material, e.g. in vitro testing
• CPC Class Codes: G01R 33/50 based on the determination of relaxation times , e.g. T1 measurement by IR sequences; T2 measurement by multiple-echo sequences
• 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

Abstract

This invention relates generally to magnetic resonance (MR)-based methods and kits for measuring the viscosity of liquid samples.

Claims

1. A method for determining viscosity of a liquid, wherein the liquid comprises a solvent, the method comprising:

(i) exposing a sample comprising the liquid and two or more non-settling particles, each of the particles having a positive magnetic susceptibility, to an applied magnetic field, wherein the applied magnetic field is of a strength sufficient to induce the particles to aggregate; and

(ii) measuring a change in a nuclear relaxation property of the solvent caused by aggregation of the particles in the applied magnetic field;

wherein a change in the nuclear relaxation property indicates a change in the viscosity of the liquid.

2. The method of claim 1, wherein the nuclear relaxation property of the solvent is a relaxation time of the solvent.

3. The method of claim 2, wherein step (ii) comprises performing two or more measurements to determine the relaxation time of the solvent, wherein at least two of the measurements are performed over a time interval when the sample is exposed to the applied magnetic field.

4. The method of claim 3, wherein the method further comprises determining a rate of relaxation time change by:

(a) calculating a difference between a relaxation time measured at a start of the time interval and a relaxation time measured at an end of the time interval; and

(b) dividing the difference calculated in step (a) by a duration of the time interval.

5. The method of claim 4, wherein the method further comprises determining the viscosity of the liquid by locating the rate of relaxation time change for the sample on a plot of rates of relaxation time change versus 1/viscosity for two or more liquid standards, wherein viscosity for each standard is known.

6. The method of claim 2, wherein the relaxation time is T₂.

7. The method of claim 1, wherein the solvent is water.

8. The method of claim 1, wherein the solvent is an organic solvent.

10. The method of claim 1, wherein the particle is a microparticle.

11. The method of claim 10, wherein the microparticle is a superparamagnetic microparticle.

12. The method of claim 11, wherein the microparticle comprises a superparamagnetic metal oxide.

16. The method of claim 1, wherein the particle has a magnetic moment of at least about 6×

10<sup>−

12</sup> emu per particle.

17. The method of claim 1, wherein a hydrophilic or hydrophobic moiety is covalently linked to the particle.

18. The method of claim 1, wherein a carboxylic acid group is covalently linked directly or indirectly to the particle.

9. (canceled)

13-15. -15. (canceled)

19-29. -29. (canceled)

30. A kit for determining viscosity of a liquid, comprising

two or more non-settling particles, each of the particles having a positive magnetic susceptibility;

and any one or more of the following;

(i) two or more liquid standards of known viscosity;

(ii) a standard curve or algorithm for determining viscosity;

(iii) a device for measuring changes in a nuclear relaxation property of a solvent; and

(iv) one or more disposable containers for holding the particles and liquid.

31. The kit of claim 30, wherein the standard curve or algorithm for determining viscosity is based on a plot of rates of change in a nuclear relaxation property for two or more liquid standards of known viscosity against (1/known viscosity) for each of the standards.

32. The kit of claim 30, comprising two or more liquid standards of known viscosity and one or more disposable containers for holding the particles and liquid.

33. A method for diagnosing or monitoring a progress of hyperviscosity syndrome in a patient in need of such diagnosing or monitoring, the method comprising:

(i) obtaining a patient sample mixture comprising blood, serum, or plasma from the patient, and two or more non-settling particles, each of the particles having a positive magnetic susceptibility;

(ii) exposing the patient sample mixture to an applied magnetic field, wherein the applied magnetic field is of a strength sufficient to induce the particles to aggregate;

(iii) measuring a change in a nuclear relaxation property of water in the patient sample mixture caused by aggregation of the particles in the applied magnetic field; and

(iv) determining viscosity of the blood, serum, or plasma on the basis of the change in the nuclear relaxation property of the water in the blood, serum, or plasma caused by aggregation of the particles in the applied magnetic field.

34. The method of claim 33, wherein the hyperviscosity syndrome is associated with polycythemia, Waldenströ

m macroglobulinemia, multiple myeloma, or leukemia.

35. The method of claim 33, further comprising treating the a disease or disorder associated with hyperviscosity syndrome by administering one or more therapeutic agents to the patient in an amount effective to treat the disease or disorder.