Noninvasive and in-vitro measurement of glucose and cholesterol by nuclear magnetic resonance spectroscopy

• US 5,685,300 A
• Filed: 03/10/1995
• Issued: 11/11/1997
• Est. Priority Date: 04/01/1994
• Status: Expired due to Term

• Current Assignee: Kuenstner J. Todd
• Original Assignee: Kuenstner J. Todd
• Inventors: Kuenstner, J. Todd
• Primary Examiner(s): Smith, Ruth S.
• Application Number:
  US08/401,828
• Time in Patent Office: 977 Days
• Field of Search: 128/632, 128/653.2, 128/653.3, 324/307, 324/308, 324/309, 324/312, 324/71, 324/74, 436/79, 436/95, 436/108, 436/173
• US Class Current: 600/366
• CPC Class Codes: G01R 33/465 applied to biological material, e.g. in vitro testing
• CPC Class Codes: Y10T 436/144444 Glucose
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

A method of noninvasive and in-vitro glucose and cholesterol concentration measurement employing nuclear magnetic resonance (NMR) spectroscopy is described. The measurement comprises a ratio formed by dividing the area of the resonance of the desired analyte, e.g., glucose or cholesterol, by the area of the water resonance in a spectrum of blood or tissue. In the in-vivo setting, the spectrum is obtained either in linkage with the pulsation of blood or by using a slice selection gradient such as that employed in the magnetic resonance imager. This measurement is then correlated to a traditional serum analyte concentration.

Claims

1. A method for determining in-vivo the concentration of an analyte, said method comprising the steps of:

a. obtaining an NMR spectrum of capillary bed tissue in the in-vivo setting at a plurality of resonances, said plurality including at least one analyte resonance and at least one reference resonance;

b. forming a ratio by dividing the area of the analyte resonance by the area of the reference resonance in said NMR spectrum; and

c. correlating said ratio to reference data to determine the concentration of the analyte.

2. The method of claim 1, wherein said step of obtaining an NMR spectrum is determined in linkage with the pulsation of blood.

3. The method of claim 2, wherein said step determined in linkage with the pulsation of blood further comprises the steps of isolating an NMR spectrum due to arterial blood by:

a. obtaining an NMR spectrum at said plurality of resonances, from capillary bed tissue during the peak of blood pulsation through the tissue;

b. obtaining an NMR spectrum at said plurality of resonances from said capillary bed tissue during the trough of a blood pulsation through the tissue;

c. subtracting said NMR spectrum obtained at said trough of blood pulsation from said NMR spectrum obtained at said peak of blood pulsation to determine the NMR spectrum for the arterial blood; and

d. wherein the step of correlating the ratio of said resonances further comprises;

comparing the NMR spectrum due to arterial blood to said reference data.

4. The method of claim 1, wherein the analyte resonance is selected from the group consisting of:

glucose, cholesterol, urea, pH, sodium and magnesium.

5. The method of claim 1, wherein said step of obtaining an NMR spectrum further comprises the step of utilizing a slice selection gradient to localize the tissue to be analyzed.

6. The method of claim 5, wherein said slice selection gradient is generated by a magnetic resonance imager.

7. The method of claim 5, wherein said slice selection gradient analyzes the tissue selected from the group consisting of:

the inferior vena cava, the aorta, the heart chambers, the neck veins, the lungs and capillary bed tissue of a finger.

8. The method of claim 1, wherein the reference resonance is a water resonance.

9. The method of claim 8, wherein the concentration of said analyte is directly measured by utilizing said ratio formed by dividing the area of the analyte resonance by the area of the reference resonance.

10. The method of claim 8, wherein the concentration of said analyte is indirectly measured following the steps of:

a. obtaining an NMR spectrum at an aliphatic proton resonance;

b. comparing the area under the aliphatic proton resonance to the area of the reference resonance; and

c. utilizing the aliphatic proton resonance to define a bridge for comparing the analyte and reference resonances to each other.

11. A method for determining the concentration of an analyte in a blood sample, said method comprising the steps of:

a. obtaining an NMR spectrum at a plurality of resonances from the blood sample, said plurality of resonances including at least on analyte resonance and at least one reference resonance;

b. forming a ratio by dividing the area of the analyte resonance by the area of the reference resonance in said NMR spectrum; and

c. correlating the ratio of these resonances with reference data to determine the concentration of the analyte.

12. The method of claim 11, wherein the blood sample is whole blood.

13. The method of claim 11, wherein a single blood sample is analyzed concurrently for multiple analytes.

14. The method of claim 11, wherein the reference resonance is a water resonance.

15. The method of claim 11, wherein the analyte resonance is selected from the group consisting of:

glucose, cholesterol, urea, pH, sodium and magnesium.