IP Library › Granted Patent US 12,405,333
Granted Patent B2
US 12,405,333 · App. 18/037,726 · Granted Sep 2, 2025

Magnetic resonance imaging of glycogen and other polysaccharides by magnetic coupling with water

Inventors: Peter van Zijl (Baltimore, MD); Yang Zhou (Baltimore, MD); Nirbhay N. Yadav (Baltimore, MD)
Assignees: The Johns Hopkins University; Kennedy Krieger Institute, Inc.
G01R33/4828
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Quick Facts
Patent No.
US 12,405,333
App. No.
18/037,726
Granted
Sep 2, 2025
Kind
B2
Abstract

Some embodiments provide a method for magnetic resonance imaging of polysaccharide molecules, that includes providing a magnetic field that is sufficiently homogeneous over an imaging volume, generating a spatial encoding in the magnetic field, and acquiring one or more water proton signal intensity measurements at each of multiple voxels within the imaging volume. The signal intensity measurements are acquired at one or more irradiation frequencies at lower parts-per-million (ppm) than a baseline frequency associated with free water protons. The method includes generating, based on the water proton signal intensity measurements in each voxel, a water proton signal intensity map of the relayed Nuclear Overhauser Effect (rNOE) exchange process of aliphatic protons in the polysaccharide molecules to free water protons in the imaging volume, and generating, using a calibration of the water proton signal intensity measurements for the rNOE exchange process, a concentration map of the polysaccharide molecules in the imaging volume.

Claims (55)

1. A system for magnetic resonance imaging of polysaccharide molecules, comprising:

a primary magnet configured to provide a magnetic field that is sufficiently homogeneous over an imaging volume;

a magnetic gradient coil configured to generate a spatial encoding in the magnetic field;

a radiofrequency coil configured to acquire one or more water proton signal intensity measurements at each of a plurality of voxels within the imaging volume, wherein said signal intensity measurements are acquired in each voxel at a one or more irradiation frequencies, said irradiation frequencies at lower parts-per-million (ppm) than a baseline frequency associated with free water protons; and

a data processor configured to:

generate, based on the water proton signal intensity measurements in each voxel, a water proton signal intensity map of the relayed Nuclear Overhauser Effect (rNOE) exchange process of aliphatic protons in the polysaccharide molecules to free water protons in the imaging volume; and

generate, using a calibration of the water proton signal intensity measurements for said rNOE exchange process, a concentration map of the polysaccharide molecules in the imaging volume.

2. A method for magnetic resonance imaging of polysaccharide molecules, comprising:

providing a magnetic field that is sufficiently homogeneous over an imaging volume;

generating a spatial encoding in the magnetic field;

acquiring one or more water proton signal intensity measurements at each of a plurality of voxels within the imaging volume, wherein said signal intensity measurements are acquired in each voxel at a one or more irradiation frequencies, said irradiation frequencies at lower parts-per-million (ppm) than a baseline frequency associated with free water protons;

generating, based on the water proton signal intensity measurements in each voxel, a water proton signal intensity map of the relayed Nuclear Overhauser Effect (rNOE) exchange process of aliphatic protons in the polysaccharide molecules to free water protons in the imaging volume; and

generating, using a calibration of the water proton signal intensity measurements for said rNOE exchange process, a concentration map of the polysaccharide molecules in the imaging volume.

3. The system of claim 1 , wherein the water proton signal intensity measurements are acquired after irradiation of the imaging volume using a magnetic labelling pulse sequence.

4. The system of claim 1 , wherein the data processor is further configured to generate the water proton signal intensity map based on a plurality of resonances associated with magnetization transfer of aliphatic protons to free water via the rNOE process.

5. The system of claim 1 , wherein the polysaccharide molecules comprise one of glycogen molecules, chemically modified polysaccharide molecules, labelled polysaccharide molecules, polysaccharides connected to binding substrates, endogenous polysaccharides, and exogenous polysaccharides.

6. The system of claim 1 , wherein the imaging volume comprises at least one of a tumor, a brain, a heart, a liver, and a skeletal muscle.

7. The system of claim 1 ,

wherein the one or more water proton signal intensity measurements are a plurality of signal intensity measurements comprising one or more water proton signal intensity measurements acquired in each voxel at a one or more additional irradiation frequencies, said additional irradiation frequencies at lower ppm than the baseline frequency associated with free water protons,

wherein the data processor is further configured to correct the plurality of water proton signal intensity measurements based on a mixed direct water saturation and magnetization transfer contrast (MTC) background.

8. The system of claim 1 , wherein the concentration map of the polysaccharide molecules is sensitive to the size of polysaccharide molecules within each voxel.

9. The system of claim 1 , wherein the concentration map of the polysaccharide molecules is sensitive to the concentration of polysaccharide molecules within each voxel.

10. The system of claim 1 , wherein the concentration map of the polysaccharide molecules is statistically independent of temperature.

11. The system of claim 1 , wherein the concentration map of the polysaccharide molecules is statistically independent of pH.

12. The system of claim 1 ,

wherein the water proton signal intensity measurements are acquired prior to an administration of exogenous polysaccharides to the imaging volume,

wherein the radiofrequency coil is further configured to acquire one or more water proton signal intensity measurements at each of the plurality of voxels within the imaging volume, subsequent to the administration of exogenous polysaccharides, and

wherein the data processor is further configured to generate a series of concentration maps of the polysaccharide molecules in the imaging volume, said series of concentration maps characterizing a temporal variation of the concentration of polysaccharides in the imaging volume due to the administration of exogenous polysaccharides.

13. The system of claim 1 ,

wherein the water proton signal intensity measurements are acquired prior to an intervention that modifies endogenous polysaccharides in the imaging volume,

wherein the radiofrequency coil is further configured to acquire one or more water proton signal intensity measurements at each of the plurality of voxels within the imaging volume, subsequent to the intervention, and

wherein the data processor is further configured to generate a series of concentration maps of the polysaccharide molecules in the imaging volume, said series of concentration maps characterizing a temporal variation of the concentration of polysaccharides in the imaging volume due to the intervention.

14. The method of claim 2 , wherein the water proton signal intensity measurements are acquired after irradiation of the imaging volume using a magnetic labelling pulse sequence.

15. The method of claim 2 , wherein generating the water proton signal intensity map is based on a plurality of resonances associated with magnetization transfer of aliphatic protons to free water via the rNOE process.

16. The method of claim 2 , wherein the polysaccharide molecules comprise one of glycogen molecules, chemically modified polysaccharide molecules, labelled polysaccharide molecules, polysaccharides connected to binding substrates, endogenous polysaccharides, and exogenous polysaccharides.

17. The method of claim 2 , wherein the imaging volume comprises at least one of a tumor, a brain, a heart, a liver, and a skeletal muscle.

18. The method of claim 2 ,

wherein the one or more water proton signal intensity measurements are a plurality of signal intensity measurements comprising one or more water proton signal intensity measurements acquired in each voxel at a one or more additional irradiation frequencies, said additional irradiation frequencies at lower ppm than the baseline frequency associated with free water protons,

the method further comprising correcting the plurality of water proton signal intensity measurements based on a mixed direct water saturation and magnetization transfer contrast (MTC) background.

19. The method of claim 2 , wherein the concentration map of the polysaccharide molecules is sensitive to the size of polysaccharide molecules within each voxel.

20. The method of claim 2 , wherein the concentration map of the polysaccharide molecules is sensitive to the concentration of polysaccharide molecules within each voxel.

21. The method of claim 2 , wherein the concentration map of the polysaccharide molecules is statistically independent of temperature.

22. The method of claim 2 , wherein the concentration map of the polysaccharide molecules is statistically independent of pH.

23. The method of claim 2 , wherein the water proton signal intensity measurements are acquired prior to an administration of exogenous polysaccharides to the imaging volume, the method further comprising:

acquiring one or more water proton signal intensity measurements at each of the plurality of voxels within the imaging volume, subsequent to the administration of exogenous polysaccharides; and

generating a series of concentration maps of the polysaccharide molecules in the imaging volume, said series of concentration maps characterizing a temporal variation of the concentration of polysaccharides in the imaging volume due to the administration of exogenous polysaccharides.

24. The method of claim 2 , wherein the water proton signal intensity measurements are acquired prior to an intervention that modifies endogenous polysaccharides in the imaging volume, the method further comprising:

acquiring one or more water proton signal intensity measurements at each of the plurality of voxels within the imaging volume, subsequent to the intervention, and

generating a series of concentration maps of the polysaccharide molecules in the imaging volume, said series of concentration maps characterizing a temporal variation of the concentration of polysaccharides in the imaging volume due to the intervention.

25. The system of claim 3 , wherein the magnetic labeling pulse sequence is one of a saturation transfer pulse sequence, an inversion pulse sequence, and an excitation pulse sequence.

26. The system of claim 12 , wherein the administration of exogenous polysaccharides comprises an injection of a contrast agent which comprises polysaccharide molecules.

27. The system of claim 13 , wherein the intervention comprises one of an administered drug or chemical compound, an exercise regimen, an intake of food, and a fasting regimen.

28. The method of claim 14 , wherein the magnetic labeling pulse sequence is one of a saturation transfer pulse sequence, an inversion pulse sequence, and an excitation pulse sequence.

29. The method of claim 23 , wherein the administration of exogenous polysaccharides comprises an injection of a contrast agent which comprises polysaccharide molecules.

30. The method of claim 24 , wherein the intervention comprises one of an administered drug or chemical compound, an exercise regimen, an intake of food, and a fasting regimen.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 25, 2023
From: VAN ZIJL, PETER; ZHOU, YANG
To: THE JOHNS HOPKINS UNIVERSITY
Reel/Frame 065341/0939 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 25, 2023
From: YADAV, NIRBHAY N.
To: KENNEDY KRIEGER INSTITUTE, INC.
Reel/Frame 065341/0985 →
Continuity (2)
Provisional Application 63117774 · Nov 24, 2020
Related Publication 20230408611A1 · Dec 21, 2023
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