IP Library Granted Patent US 11,129,543
Granted Patent B2
US 11,129,543 · App. 17/259,134 · Granted Sep 28, 2021

Soft tissue matrix characterization using stretched exponential relaxation modeling

Inventors: Corey P. Neu (Boulder, CO); Robert L. Wilson (Boulder, CO); David Reiter (Decatur, GA)
Assignee: The Regents of the University of Colorado
A61B5/055A61B5/0515A61B5/4566A61B5/742A61B2560/02
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Quick Facts
Patent No.
US 11,129,543
App. No.
17/259,134
Granted
Sep 28, 2021
Kind
B2
Abstract

A process for more sensitive characterization of tissue composition for generating a quantitative MRI (qMRI) map and corresponding delta analysis. Intervertebral disc degeneration (IVDD), resulting in the depletion of hydrophilic glycosaminoglycans (GAGs) located in the nucleus pulposus (NP), can lead to debilitating neck and back pain. Magnetic Resonance Imaging (MRI) is a promising means of IVD assessment due to the correlation between GAG content and MRI relaxation values. T1 and T2 relaxation data were obtained from healthy cervical IVDs, and relaxation data was modeled using both conventional and stretched exponential (SE) decays. Normalized histograms of the resultant quantitative MRI (qMRI) maps were fit with stable distributions. SE models fit relaxation behavior with lower error compared to monoexponential models, indicating anomalous relaxation behavior in healthy IVDs. SE model parameters T1 and T1 increased with IVD segment, while conventional monoexponential measures did not vary. The improved model fit and correlation between both SE T1 and T1 with IVD level suggests these parameters are more sensitive biomarkers for detection of GAG content variation.

Claims (47)

1. A method for detecting intervertebral disc degeneration (IVDD) in a subject comprising the steps of:

measuring a T1 ρSE relaxation time of glycosaminoglycan (GAG) in a disc of the subject using magnetic resonance imaging;

comparing the measured T1 ρSE relaxation time to a baseline T1 ρSE relaxation time indicative of healthy tissue;

measuring a α T1 ρ relaxation time of GAG in the disc of the subject using magnetic resonance imaging;

comparing the determined α T1 ρ relaxation time to a baseline α T1 ρ relaxation time indicative of healthy tissue; and

determining a decrease in the GAG content in the disc of the subject based on results of the comparing step for both the T1 ρSE relaxation time to a baseline T1 ρSE relaxation time and the α T1 ρ relaxation time to a baseline α T1 relaxation time, wherein a decrease in the GAG content in the disc of a subject is indicative of IVDD in the subject.

2. The method according to claim 1 wherein T1 ρSE relaxation time of GAG is measured in the nucleus pulposus (NP) of the subject using magnetic resonance imaging and wherein a decrease in the GAG content in the NP of a subject is indicative of IVDD in the subject.

3. The method according to claim 1 wherein the magnetic resonance imaging is processed using a pixel-by-pixel method.

4. A method of monitoring progress of intervertebral disc degeneration (IVDD) in a subject comprising the steps of:

measuring a baseline T1 ρSE relaxation time of glycosaminoglycan (GAG) in a nucleus pulposus (NP) of a subject using magnetic resonance imaging;

measuring one or more additional T1 ρSE relaxation times;

comparing at least one of the one or more additional T1 ρSE relaxation times measured to the baseline value of the T1 ρSE relaxation time;

measuring a baseline α T1 ρ relaxation time of GAG in the NP of the subject using magnetic resonance imaging;

measuring one or more additional α T1 ρ relaxation times;

comparing at least one of the one or more additional α T1 ρ relaxation times measured to the baseline value of the α T1 ρ relaxation time; and

determining a decrease in the GAG content in the NP of the subject based on results of the comparing step for both the T1 ρSE relaxation time to a baseline T1 ρSE relaxation time and the α T1 ρ relaxation time to a baseline α T1 relaxation time, wherein a decrease in the GAG content in the NP of a subject is indicative of continued IVDD in the subject.

5. A method of evaluating the effectiveness of an intervertebral disc degeneration (IVDD) treatment comprising the steps of:

measuring a baseline T1 ρSE relaxation time of glycosaminoglycan (GAG) in a nucleus pulposus (NP) of a subject prior to or upon initiation of the treatment using magnetic resonance imaging;

measuring a baseline α T1 ρ relaxation time of the GAG in the NP of a subject prior to or upon initiation of the treatment using magnetic resonance imaging;

initiating the treatment of the IVDD in the subject;

measuring one or more additional T1 ρSE relaxation times after initiation of the treatment;

comparing at least one of the one or more additional T1 ρSE relaxation times measured after initiation of the treatment to the baseline value of the T1 ρSE relaxation time;

measuring one or more additional α T1 ρ relaxation times after initiation of the treatment;

comparing at least one of the one or more additional α T1 ρ relaxation times measured after initiation of the treatment to the baseline value of the α T1 ρ relaxation time; and

determining a change in the GAG content in the NP of the subject based on results of the comparing step for both the T1 ρSE relaxation time to a baseline T1 ρSE relaxation time and the α T1 ρ relaxation time to a baseline α T1 relaxation time, wherein an increase in GAG content is indicative of treatment effectiveness.

6. The method according to claim 5 wherein the magnetic resonance imaging is processed using a pixel-by-pixel method.

7. A method for detecting intervertebral disc degeneration (IVDD) in a subject comprising the steps of:

measuring a α T1 ρ relaxation time of glycosaminoglycan (GAG) in a disc of the subject using magnetic resonance imaging;

comparing the measured α T1 ρ relaxation time to a baseline T1 ρSE relaxation time indicative of healthy tissue; and

determining a decrease in the GAG content in the disc of the subject based on results of the comparing step, wherein a decrease in the GAG content in the disc of a subject is indicative of IVDD in the subject.

8. A method for detecting intervertebral disc degeneration (IVDD) in a subject comprising the steps of:

measuring a α T1 ρ relaxation time of glycosaminoglycan (GAG) in a nucleus pulposus (NP) of the subject using magnetic resonance imaging;

comparing the determined α T1 ρ relaxation time to a baseline α T1 ρ relaxation time indicative of healthy tissue; and

determining a decrease in the GAG content in the NP of the subject based on results of the comparing step, wherein a decrease in the GAG content in the NP of a subject is indicative of IVDD in the subject.

9. The method according to claim 8 wherein the magnetic resonance imaging is processed using a pixel-by-pixel method.

10. A method of monitoring progress of intervertebral disc degeneration (IVDD) in a subject comprising the steps of:

measuring a baseline α T1 ρ relaxation time of glycosaminoglycan (GAG) in a nucleus pulposus (NP) of a subject using magnetic resonance imaging;

measuring one or more additional α T1 ρ relaxation times;

comparing at least one of the one or more additional α T1 ρ relaxation times measured to the baseline value of the α T1 ρ relaxation time; and

determining progress of intervertebral disc degeneration based on results of said comparing step.

11. A method of evaluating the effectiveness of an intervertebral disc degeneration (IVDD) treatment comprising the steps of:

measuring a baseline α T1 ρ relaxation time of glycosaminoglycan (GAG) in a nucleus pulposus (NP) of a subject prior to or upon initiation of the treatment using magnetic resonance imaging;

initiating the treatment of the IVDD in the subject;

measuring one or more additional α T1 ρ relaxation times after initiation of the treatment;

comparing at least one of the one or more additional α T1 ρ relaxation times measured after initiation of the treatment to the baseline value of the α T1 ρ relaxation time; and

determining an effectiveness of the treatment based on results of the comparing step.

12. The method according to claim 11 wherein the magnetic resonance imaging is processed using a pixel-by-pixel method.

Assignments (4)
CONFIRMATORY LICENSE Recorded Nov 14, 2023
From: UNIVERSITY OF COLORADO
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065566/0374 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 17, 2021
From: WILSON, ROBERT L.
To: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE
Reel/Frame 055624/0103 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 17, 2021
From: NEU, COREY P.
To: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE
Reel/Frame 055626/0301 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 3, 2021
From: REITER, DAVID
To: EMORY UNIVERSITY
Reel/Frame 055481/0772 →
Continuity (3)
Provisional Application 62695603 · Jul 9, 2018
Provisional Application 62695152 · Jul 8, 2018
Related Publication 20210244307A1 · Aug 12, 2021