IP Library Granted Patent US 9,901,285
Granted Patent B2
US 9,901,285 · App. 13/680,612 · Granted Feb 27, 2018

Systems and methods using nuclear magnetic resonance (NMR) spectroscopy to evaluate pain and degenerative properties of tissue

Inventors: Sharmila Majumdar (Alameda, CA); John Kurhanewicz (South San Francisco, CA); Jeffrey C. Lotz (San Mateo, CA); David S. Bradford (Sausalito, CA); Kayvan Keshari (Stockton, CA)
Assignee: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
A61B5/055A61B5/4824G01N24/08G01R33/483A61B5/4514A61B5/4528G01R33/465G01R33/485
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Quick Facts
Patent No.
US 9,901,285
App. No.
13/680,612
Granted
Feb 27, 2018
Kind
B2
Abstract

NMR spectroscopy is performed on intervertebral disc tissue. Extent of degeneration is determined based on the NMR spectroscopy. Correlation between NMR spectral regions and at least one of tissue degeneration and pain are made. Accordingly, NMR spectroscopy is used to determine location and/or extent of at least one of degeneration or pain associated with a region of tissue, such as for example in particular disc degeneration, or discogenic pain. NMR spectral peak ratios, such as between N-Acetyl/cho and cho/carb, are readily acquired and analyzed to predict degree of tissue degeneration and/or pain for: tissue samples using HR-MAS spectroscopy; and larger portions of anatomy such as joint segments such as a spine, using clinical 3T MRI systems with surface head or knee coils; and tissue regions such as discs within spines of living patients using 3T MRI systems with a surface spine coil, thus providing a completely non-invasive diagnostic toolset and method to image and localize degeneration and/or pain.

Claims (34)

1. A medical diagnostic system for providing diagnostic information from a respective nuclear magnetic resonance (NMR) spectrum generated and acquired from each of a first region and a second region of tissue of a pain patient for determining if degenerative nociceptive pain is occurring in the respective regions, comprising:

an NMR spectroscopy system in a configuration that is operable to apply a magnetic pulse sequence to artificially induce NMR signals in each of the first and second regions, and to acquire said NMR signals, to thereby generate NMR spectroscopic data related to a respective NMR spectrum from each of the first region and second region and to provide the NMR spectroscopic data related to each respective NMR spectrum in a form that is processable, wherein the NMR spectroscopy system in the configuration comprises a local detector coil assembly in a configuration that is operable, in response to the applied magnetic pulse sequence, to acquire the NMR spectroscopic data from each of the respective first and second regions positioned in the NMR spectroscopy system;

a computer processor;

a non-transitory computer-readable memory storing instructions in the form of a computer readable software program executable by the computer processor to process the NMR spectroscopic data provided by the NMR spectroscopy system;

wherein said instructions, when executed by the computer processor, perform operations to:

determine first and second ratio values for the first and second regions, respectively, wherein each of the first and second ratio values is based at least in part on a ratio between spectral parameters associated with (a) an n-Acetyl-related resonance region of the respective NMR spectrum associated with chondroitin sulfate or a metabolite or degradation product thereof, and (b) a lactate-related resonance region of the respective NMR spectrum; and

provide diagnostic information at least in part based upon said first and second ratio values, and wherein the diagnostic information corresponds with degenerative nociceptive pain.

2. The system of claim 1 , wherein the computer program is further executable by the computer processor to process the NMR spectroscopic data to determine each respective ratio value based at least in part upon a measured feature of an n-Acetyl-realted resonance region of the respective NMR spectrum.

3. The system of claim 1 , wherein the computer program is further executable by the computer processor to process the NMR spectroscopic data to determine the diagnostic information based at least in part upon a collagen-related factor.

4. The system of claim 1 , wherein the computer program is further executable by the computer processor to process the NMR spectroscopic data to determine the diagnostic information based at least in part upon a measured feature of a choline-related region of the respective NMR spectrum.

5. The system of claim 1 , wherein the computer program is further executable by the computer processor to process the NMR spectroscopic data to determine the diagnostic information based at least in part upon a measured feature of a carbohydrate-related region of the respective NMR spectrum.

6. The system of claim 1 , wherein the computer program is further executable by the computer processor to process the NMR spectroscopic data to determine the diagnostic information based at least in part upon a measured feature of a region of the NMR spectrum associated with a collagen-related factor that comprises a chemical entity indicative of collagen break-down in the respective region.

7. The system of claim 1 , wherein the computer program is further executable by the computer processor to process the NMR spectroscopic data to determine the diagnostic information based at least in part upon a first calculated ratio between a measured feature of the respective NMR spectrum associated with a proteoglycan-related factor and a measured feature of the NMR spectrum associated with a lactate-related factor, and a second ratio between a measured feature of the NMR spectrum associated with the proteoglycan-related factor and a measured feature of the NMR spectrum associated with a collagen-related factor in the respective region.

8. The system of claim 1 , wherein the NMR spectroscopy system comprises a 3 Tesla NMR system.

9. The system of claim 1 , wherein the NMR spectroscopy system in the configuration further comprises:

a first single voxel region prescribed to coincide with the first region of tissue in a first configuration;

wherein the NMR spectroscopy system is operable in the first configuration to apply the magnetic pulse sequence to induce a first NMR signal at the first single voxel region and acquire a first portion of the NMR spectroscopic data from the first single voxel region via the local detector coil assembly;

a second single voxel region prescribed to coincide with the second region of tissue in a second configuration;

wherein the NMR spectroscopy system is operable in the second configuration to apply the magnetic pulse sequence to induce a first NMR signal at the first single voxel region and acquire a second portion the NMR spectroscopic data from the second single voxel region via the local detector coil assembly.

10. The system of claim 1 , wherein the at least one computer program is further executable by the computer processor to display a respective curve related to each respective NMR spectrum, and a portion of the curve comprises each said spectral parameter.

11. The system of claim 1 , wherein:

respective spectral parameters of the lactate-related resonance region and the n-Acetyl-related resonance region correspond to a lactate-related chemical factor and a proteoglycan-related chemical factor, respectively, in each respective region; and

wherein the ratio values comprise ratios between respective amounts of said chemical factors.

12. The system of claim 1 , wherein said instructions, when executed by the computer processor, perform operations to compare the first and second ratio values, wherein the diagnostic information is based at least in part on the comparison of the first and second ratio values.

13. The system of claim 12 , wherein the diagnostic information comprises a determination of where the degenerative nociceptive pain is being experienced between the first and second regions based at least in part on the comparison of the first and second ratio values.

14. A method for diagnosing whether local degenerative nociceptive pain is occurring in a first region of tissue versus a second region of tissue of a pain patient, comprising:

analyzing at least a lactate-related resonance region and a proteoglycan-related resonance region from nuclear magnetic resonance (NMR) spectroscopic data associated with a respective nuclear magnetic resonance (NMR) spectrum generated via acquired NMR signals induced in the first region via a magnetic pulse sequence applied via an NMR spectroscopy system, wherein the NMR spectroscopy system comprises a local detector coil assembly in a configuration that is operable, in response to the applied magnetic pulse sequence, to acquire the NMR signals and generate the spectroscopic data from the respective first region positioned in the NMR spectroscopy system;

producing a first ratio value from the analysis for the respective NMR spectrum from the first region and that indicates a ratio between spectral parameters associated with the lactate-related resonance region and the proteoglycan-related resonance region;

performing the analyzing and producing operations also for the second region of tissue of the patient positioned in the NMR spectroscopy system in order to produce a second ratio value for the second region;

comparing the first and second ratio values to determine where the local degenerative nociceptive pain is being experienced between the first and second regions based at least in part on the comparison of the first and second ratio values; and

wherein the analyzing and the producing are performed by running a computer software program by a computer processor.

15. The method of claim 14 , further comprising:

configuring an NMR spectroscopy system in a configuration that is operable to apply a magnetic pulse sequence to induce NMR signals, acquire the induced NMR signals, and generate and acquire the NMR spectroscopic data for the acquired NMR signals, from the first and second regions; and

acquiring the NMR signals and generating the corresponding NMR spectroscopic data from the first and second regions by operating the NMR spectroscopy system in the configuration.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 10, 2013
From: MAJUMDAR, SHARMILA; KURHANEWICZ, JOHN; LOTZ, JEFFREY C.; BRADFORD, DAVID S.; KESHARI, KAYVAN
To: REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE
Reel/Frame 031448/0534 →
Continuity (5)
Continuation 11829847 · Jul 27, 2007
Continuation In Part PCTUS2006003036 · Jan 30, 2006
Provisional Application 60737110 · Nov 15, 2005
Provisional Application 60648241 · Jan 28, 2005
Related Publication 20130144155A1 · Jun 6, 2013