Gas-filled structures and related compositions, methods and systems for magnetic resonance imaging

Patent metadata

Field	Value
Publication number	US-10955496-B2
Application number	US-201715663600-A
Country	US
Kind code	B2
Filing date	Jul 28, 2017
Priority date	Jul 28, 2016
Publication date	Mar 23, 2021
Grant date	Mar 23, 2021

Abstract

Gas vesicle protein structures and related compositions, methods, and systems for singleplexed and/or multiplexed magnetic resonance imaging of a target site alone or in combination with ultrasound are described, in which the gas vesicle protein structures provide contrast for the imaging.

First claim

The invention claimed is:

1. A contrast-enhanced magnetic resonance imaging method comprising:
imaging a target site comprising a gas vesicle protein structure (GVPS), the GVPS containing gas having a gas susceptibility value different from a bulk material susceptibility at the target site to obtain a MRI image, the imaging comprising detecting volume susceptibilities of the target site and/or relaxation rates of nuclear spins of atoms in the bulk material; wherein the MRI image is QSM, T2, T2*, T2- or T2*-weighted map.

2. The magnetic resonance imaging method of claim 1 , wherein the GVPS is a GVPS selected from a species of Anabaena bacteria, Halobacterium archaea, or Bacillus megaterium.

3. The magnetic resonance imaging method of claim 1 , wherein the GVPS is provided in a contrast agent having a concentration equal to or lower than 100 nM.

4. The magnetic resonance imaging method of claim 1 ,
wherein the imaging the target site obtains a series of MRI images of the target site, and the method further comprises:
detecting an increase or decrease in MRI contrast.

5. The magnetic resonance imaging method of claim 4 , wherein the increase or decrease in MRI contrast is an increase or decrease in R 2 or R 2 * relaxation rates.

6. The magnetic resonance imaging method of claim 1 , wherein the GVPS is provided in a contrast agent having a concentration equal to or lower than 10 nM.

7. The magnetic resonance imaging method of claim 1 , wherein the GVPS is provided in a contrast agent having a concentration equal to or lower than 1 nM.

8. The magnetic resonance imaging method of claim 1 , wherein the GVPS is provided in a contrast agent and the MRI image is a first MRI image, the method further comprising
collapsing the GVPS by applying collapsing ultrasound to the target site, the collapsing ultrasound applied at a collapsing ultrasound pressure greater than a selectable acoustic collapse pressure value derived from an acoustic collapse pressure profile of the GVPS, and
after collapsing, imaging the target site to obtain a second MRI image of the target site.

9. The magnetic resonance imaging method of claim 1 , wherein
the GVPS is part of a first GVPS type exhibiting a first acoustic collapse pressure profile and a first selectable acoustic collapse pressure value,
the target site further comprises a second GVPS type exhibiting a second acoustic collapse pressure profile and a second selectable acoustic collapse pressure value, and
the MRI image is a first MRI image,

the method comprising:
selectively collapsing the first GVPS type by applying collapsing ultrasound to the target site, the collapsing ultrasound applied at a first acoustic collapse pressure value equal to or higher than the first selectable acoustic collapse pressure value and lower than the second selectable acoustic collapse pressure value; and
imaging the target site containing at least the second, uncollapsed GVPS type to obtain a second MRI image of the target site.

10. The magnetic resonance imaging method of claim 8 , wherein the collapsing ultrasound pressure is higher than a midpoint collapse pressure of the GVPS.

11. The magnetic resonance imaging method of claim 8 , wherein the collapsing ultrasound pressure is higher than a complete collapse pressure of the GVPS.

12. The magnetic resonance imaging method of claim 8 , wherein the GVPS comprise a GvpC protein selected from the group consisting of ΔGvpC, ΔN&C, and GvpCWT, and the selectable acoustic collapse pressure value is 571 kPa for ΔGvpC, 657 kPa for ΔN&C, and 869 kPa for GvpCWT.

13. The magnetic resonance imaging method of claim 8 , further comprising subtracting the second MRI image from the first MRI image to provide a background-free magnetic resonance imaging of the target site.

14. The magnetic resonance imaging method of claim 9 , further comprising, after imaging the target site containing at least the second, uncollapsed GVPS type,
selectively collapsing the second gas vesicle structure type by applying collapsing ultrasounds to the target site, the collapsing ultrasounds applied at a second acoustic collapse pressure value equal to or higher than the second selectable acoustic collapse pressure value of the second GVPS type.

15. The magnetic resonance imaging method of claim 9 , further comprising:
after selectively collapsing the second GVPS type, imaging the target site by applying an external magnetic field to the target site.

16. The magnetic resonance imaging method of claim 9 , wherein the first GVPS type and the second GVPS type are selected from GVPS types species of Anabaena bacteria and Halobacterium bacteria.

17. The magnetic resonance imaging method of claim 9 , wherein the first GVPS type comprises ΔGvpC and the second GVPS type comprises ΔN&C, and the selectable acoustic collapse pressure value is 630 kPa.

18. The magnetic resonance imaging method of claim 9 , wherein the acoustic collapse pressure value of the first gas vesicle protein structure type is selected from the acoustic collapse pressure profile at a value between 0.05% and 95% collapse.

19. The magnetic resonance imaging method of claim 9 , wherein the acoustic collapse pressure value of the first GVPS type is selected from the acoustic collapse pressure profile at a value of 50% collapse.

20. The magnetic resonance imaging method of claim 9 , wherein the acoustic collapse pressure value of the first GVPS type is selected from the acoustic collapse pressure profile at a value that optimally maximizes collapse of the first GVPS type while minimizing collapse of the second GVPS type.

21. The magnetic resonance imaging method of claim 20 , wherein the optimally maximizing collapse of the first GVPS type while minimizing collapse of the second GVPS type is determined by maximizing f1(p)−f2(p), wherein f1(p)=(1+e (p-p c )/Δp ) −1 and f2(p)=(1+e (p-p c )/Δp ) −1 and f1(p) and f2(p) correspond to an acoustic collapse profile of the first GVPS and the second GVPS, respectively.

22. A contrast-enhanced magnetic resonance imaging method comprising:
imaging a target site comprising a gas vesicle protein structure (GVPS), the GVPS containing gas having a gas susceptibility value different from a bulk material susceptibility at the target site to obtain a MRI image, the imaging comprising detecting volume susceptibilities of the target site and/or relaxation rates of nuclear spins of atoms in the bulk material, wherein the gas susceptibility is different from the bulk material susceptibility by at least 3 ppm.

23. The magnetic resonance imaging method of claim 21 , wherein the MRI image is QSM, T2, T2*, T2- or T2*-weighted map.

24. The magnetic resonance imaging method of claim 22 , wherein the GVPS is provided in a contrast agent having a concentration equal to or lower than 100 nM.

25. The magnetic resonance imaging method of claim 22 , wherein the GVPS is provided in a contrast agent and the MRI image is a first MRI image, the method further comprising
collapsing the GVPS by applying collapsing ultrasound to the target site, the collapsing ultrasound applied at a collapsing ultrasound pressure greater than a selectable acoustic collapse pressure value derived from an acoustic collapse pressure profile of the GVPS, and
after collapsing, imaging the target site to obtain a second MRI image of the target site.

26. A contrast-enhanced magnetic re

Assignees

• California Inst Of Techn

Inventors

• Lu George J
• Shapiro Mikhail G
• FARHADI Arash
• Szablowski Jerzy O

Classifications

• A61B5/055 Primary

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

• Y02A90/10

  Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation · CPC title

• G01R33/5601

  involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent · CPC title

• G01R33/5602

  by filtering or weighting based on different relaxation times within the sample, e.g. T1 weighting using an inversion pulse · CPC title

• A61B8/4416

  related to combined acquisition of different diagnostic modalities, e.g. combination of ultrasound and X-ray acquisitions · CPC title