Non-invasive pH-dependent imaging using quantitative chemical exchange saturation transfer (qCEST)

Patent metadata

Field	Value
Publication number	US-11547348-B2
Application number	US-201716305221-A
Country	US
Kind code	B2
Filing date	Jun 8, 2017
Priority date	Jun 8, 2016
Publication date	Jan 10, 2023
Grant date	Jan 10, 2023

Abstract

In various embodiments, the invention teaches systems and methods for magnetic resonance imaging. In some embodiments, the invention teaches systems and methods for determining the source of pain in intervertebral discs by measuring one or more physiological biomarkers associated with disc pain and/or disc degeneration.

First claim

What is claimed is:

1. A method for detecting a condition in a subject, comprising:
performing a scan of a region of the subject's body using a magnetic resonance imaging (MRI) scanner;
generating an image of the region of the subject's body from the performed scan using a quantitative chemical exchange saturation transfer (qCEST) sequence;
processing the image to detect one or more physiological biomarkers within the image of the region,
wherein the physiological biomarkers comprise a labile proton exchange rate (k sw ) between a solute pool and a water pool; and
determining that the subject has the condition if the labile proton exchange rate is increased relative to a reference value,
wherein the increased labile proton exchange rate is greater than 200 exchanges/second.

2. The method of claim 1 , wherein the increased labile proton exchange rate is correlated to a low pH value.

3. . The method of claim 2 , wherein the low pH value is from 5.6 to 6.99.

4. The method of claim 2 , wherein the low pH value is indicative of the subject having the condition.

5. The method of claim 1 , wherein the increased labile proton exchange rate is from 201 to 1000 exchanges/second.

6. The method of claim 1 , wherein the reference value is a reference labile proton exchange rate, wherein the reference labile proton exchange rate is from 100 to 200 exchanges/second.

7. The method of claim 6 , wherein the reference labile proton exchange rate is correlated to a reference pH value.

8. The method of claim 7 , wherein the reference pH value is from 7.0 to 7. 2.

9. The method of claim 1 , wherein the condition is intervertebral disc degeneration, discogenic pain, discogenic low back pain, chronic low back pain, low back pain, back pain, chronic back pain, progressive intervertebral disc degeneration, osteoarthritis, rheumatoid arthritis, an articular cartilage injury, or temporomandibular disc degeneration, or combinations thereof.

10. The method of claim 1 , wherein the region of the subject's body comprises a joint or an intervertebral disc.

11. The method of claim 1 , wherein the condition is a painful condition.

12. The method of claim 1 , wherein the increased labile proton exchange rate is correlated with an upregulation of one or more pain-related factors in the subject.

13. The method of claim 12 , wherein the one or more pain-related factors are bradykinin receptor B1 (BDKRB1), calcitonin gene-related peptide (CGRP), or catechol-O-methyltransferase (COMT).

14. The method of claim 1 , wherein the increased labile proton exchange rate is correlated with an upregulation of one or more inflammation-related factors in the subject.

15. The method of claim 14 , wherein the inflammation-related factor is interleukin-6 (IL-6).

16. The method of claim 1 , wherein the increased labile proton exchange rate is correlated with an upregulation of one or more neurogenic factors in the subject.

17. The method of claim 16 , wherein the neurogenic factor is brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF).

18. The method of claim 1 , wherein the quantitative chemical exchange saturation transfer (qCEST) sequence is a two dimension (2D) quantitative chemical exchange saturation transfer (qCEST) sequence, or a three dimension (3D) quantitative chemical exchange saturation transfer (qCEST) sequence.

19. The method of claim 1 , wherein the MRI scanner is a 1.5 T MRI scanner, a 3.0 T MRI scanner, or a 7.0 T MRI scanner.

20. The method of claim 1 , further comprising determining that an origin of the subject's condition is within the region of the subject's body where the physiological biomarker was measured.

21. The method of claim 1 , further comprising selecting one or more treatments for the subject if the condition is determined.

22. A method for prognosing a condition associated with tissue degeneration and/or pain in a subject, comprising:
performing a scan of a region of the subject's body using a magnetic resonance imaging (MRI) scanner;
generating an image of the region of the subject's body from the performed scan using a quantitative chemical exchange saturation transfer (qCEST) sequence;
processing the image to detect one or more physiological biomarkers within the image of the region,
wherein the physiological biomarkers comprise a labile proton exchange rate (k sw ) between a solute pool and a water pool; and
prognosing the condition by comparing a measurement of one or more physiological biomarkers to a previous measurement of the same one or more physiological biomarkers, wherein an increase in the labile proton exchange rate over time is a poor prognosis of the condition, wherein the increased labile proton exchange rate is greater than 200 exchanges/second.

23. A method for determining the risk of developing a condition in a subject, comprising:
performing a scan of a region of the subject's body using a magnetic resonance imaging (MRI) scanner;
generating an image of the region of the subject's body from the performed scan using a quantitative chemical exchange saturation transfer (qCEST) sequence;
processing the image to detect one or more physiological biomarkers within the image of the region,
wherein the physiological biomarkers comprise a labile proton exchange rate (k sw ) between a solute pool and a water pool; and
comparing the labile proton exchange rate from the subject to a reference value, wherein an increase in the labile proton exchange rate from the subject compared to the reference value is indicative of an increased risk of the subject developing the condition, wherein the increased labile proton exchange rate is greater than 200 exchanges/second.

24. The method of claim 23 , wherein the condition is intervertebral disc degeneration, discogenic pain, discogenic low back pain, chronic low back pain, low back pain, back pain, chronic back pain, progressive intervertebral disc degeneration, osteoarthritis, rheumatoid arthritis, an articular cartilage injury, or temporomandibular disc degeneration, or combinations thereof.

Assignees

• Cedars Sinai Medical Center

Inventors

• Gazit Dan
• Li Debiao
• Pelled Gadi
• Gazit Zulma
• Zhou Zhengwei

Classifications

• G01R33/5605

  by transferring coherence or polarization from a spin species to another, e.g. creating magnetization transfer contrast [MTC], polarization transfer using nuclear Overhauser enhancement [NOE] · CPC title

• G01R33/4838

  using spatially selective suppression or saturation of MR signals · CPC title

• A61B5/055 Primary

  involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging · CPC title

• A61B5/4566 Primary

  Evaluating the spine (A61B5/4561 takes precedence) · CPC title

• A61B5/4824

  Touch or pain perception evaluation (A61B5/4821 takes precedence) · CPC title