Gas-filled structures and related compositions, methods and systems to image a target site

Patent metadata

Field	Value
Publication number	US-10493172-B2
Application number	US-201715613104-A
Country	US
Kind code	B2
Filing date	Jun 2, 2017
Priority date	Jun 2, 2016
Publication date	Dec 3, 2019
Grant date	Dec 3, 2019

Abstract

Gas vesicles, protein variants and related compositions methods and systems for singleplexed and/or multiplexed ultrasound imaging of a target site in which a gas vesicle provides contrast for the imaging which is modifiable by application of a selectable acoustic collapse pressure value of the gas vesicle.

First claim

The invention claimed is:

1. An ultrasound imaging method to be used on a target site contrasted with a gas vesicle protein structure (GVPS) type having a selectable acoustic collapse pressure value derived from an acoustic collapse pressure profile of the GVPS type and a hydrostatic collapse pressure profile, a midpoint of the acoustic collapse pressure profile higher than a midpoint of the hydrostatic collapse pressure profile, the method comprising
collapsing the GVPS type by applying collapsing ultrasound to the target site, the collapsing ultrasound applied at a collapsing ultrasound pressure greater than the selectable acoustic collapse pressure value; and
imaging the target site by applying imaging ultrasound to the target site, the imaging ultrasound applied at a first imaging ultrasound pressure selected to provide an uncontrasted image of the target site.

2. The ultrasound imaging method of claim 1 , wherein the collapsing ultrasound pressure is higher than the midpoint of the hydrostatic collapse pressure profile.

3. The ultrasound imaging method of claim 1 , wherein the collapsing ultrasound pressure is higher than the midpoint of the acoustic collapse pressure profile.

4. The ultrasound imaging method of claim 1 , further comprising
further imaging the target site prior to the collapsing by applying imaging ultrasound to the target site, the imaging ultrasound applied at a second imaging ultrasound pressure lower than the selectable acoustic collapse pressure and selected to provide a visible image; and
comparing the visible image of the target site with the uncontrasted image.

5. The ultrasound imaging method of claim 4 , wherein the first imaging ultrasound pressure is equal to the second imaging ultrasound pressure.

6. The ultrasound imaging method of claim 1 , wherein the GVPS is a GVPS from a species of Anabaena bacteria or Halobacterium archaea.

7. The ultrasound imaging method of claim 6 , wherein the GVPS is a GVPS from Anabaena flos - aquae, Halobacterium salinarum or Bacillus megaterium.

8. The ultrasound imaging method of claim 1 , wherein the GVPS comprise a GvpC protein selected from the group consisting of ΔGvpC, ΔN&C, and GvpC WT , and the selectable acoustic collapse pressure value is 571 kPa for ΔGvpC, 657 kPa for ΔN&C, and 869 kPa for GvpC WT .

9. The ultrasound imaging method of claim 1 , further comprising an initial preparation step of
administering to the target site a contrast agent comprising the gas vesicle protein structure.

10. The ultrasound imaging method of claim 1 , wherein the GVPS type comprises
a first gas vesicle protein structure (GVPS) type exhibiting a first acoustic collapse pressure profile and a first selectable acoustic collapse pressure value and
a second GVPS type exhibiting a second acoustic collapse pressure profile and-a second selectable acoustic collapse pressure value,

each GVPS type exhibiting a different acoustic collapse pressure profile defined as a collapse function from which a collapse amount can be determined and a different selectable acoustic collapse pressure value from their corresponding acoustic collapse pressure profile, wherein
the collapsing is performed by 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
the imaging is performed by imaging the target site containing second, uncollapsed, GVPS type by applying imaging ultrasound to the target site, the imaging ultrasound applied at a pressure value lower than the acoustic collapse pressure value of the second gas vesicle structure type.

11. The ultrasound imaging method of claim 10 , further comprising, after the imaging
selectively collapsing the second gas vesicle structure type by applying collapsing ultrasounds to the target site, the collapsing ultrasounds applied at a pressure value equal to or higher than the selectable acoustic collapse pressure value of the second gas vesicle structure type.

12. The ultrasound imaging method of claim 11 , further comprising,
after collapsing the second GVPS type imaging the target site by applying imaging ultrasounds to the target site,
whereby the sequence of visible images of the target site further includes an image indicative of all uncollapsed GVPS types other than the first GVPS type and the second GVPS type.

13. The ultrasound imaging method of claim 10 , further comprising, before collapsing the first gas vesicle protein structure type
imaging the target site by applying ultrasounds to the target site, the ultrasounds applied at a pressure value lower than the selectable acoustic collapse pressure value for the first gas vesicle structure type, thus obtaining an image indicative of uncollapsed first and second gas vesicle protein structure types.

14. The ultrasound imaging method of claim 10 , wherein the first GVPS type and the second GVPS type are selected from GVPS types species of Anabaena bacteria and Halobacterium bacteria.

15. The ultrasound imaging method of claim 14 , wherein the first GVPS type and the second GVPS type are selected from GVPS types of Anabaena flos - aquae, Halobacterium salinarum , and Bacillus megaterium.

16. The ultrasound imaging method of claim 10 , 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.

17. The ultrasound imaging method of claim 10 , wherein the acoustic collapse pressure value of the first gas vesicle protein structure type is selected from the first acoustic collapse pressure profile at a value between 0.05% and 95% collapse.

18. The ultrasound imaging method of claim 17 , wherein the acoustic collapse pressure value of the first gas vesicle protein structure type is selected from the first acoustic collapse pressure profile at a value of 50% collapse.

19. The ultrasound imaging method of claim 10 , wherein the acoustic collapse pressure value of a first gas vesicle protein structure type is selected from the acoustic collapse pressure profile at a value that optimally maximizes collapse of the first gas vesicle protein structure type while minimizing collapse of the second gas vesicle protein structure type.

20. The ultrasound imaging method of claim 19 , 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 and ƒ1(p)=(1+e (p-p c )/Δp ) −1 and ƒ1(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.

21. The ultrasound imaging method of claim 1 , wherein the GVPS type comprises a plurality of gas vesicle protein structure (GVPS) types, each type exhibiting
i) an acoustic collapse pressure profile defined as a collapse function from which a collapse amount can be determined, and
ii) a selectable acoustic collapse pressure value, selectable acoustic collapse pressure values going from a lowest acoustic collapse pressure value to a highest acoustic collapse pressure value, wherein
the collapsing is performed by selectively collapsing GVPS type to a collapse amount higher than a collapse amount of each remaining GVPS type by applying collapsing ultrasound to

Assignees

• California Inst Of Techn

Inventors

• Lakshmanan Anupama
• FARHADI Arash
• Nety Suchita P
• Bourdeau Raymond W
• Shapiro Mikhail

Classifications

• A61K49/0045

  the fluorescent agent being a peptide or protein used for imaging or diagnosis in vivo · CPC title

• A61K49/0093

  Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle · CPC title

• A61K49/0002

  General or multifunctional contrast agents, e.g. chelated agents · CPC title

• A61K49/221

  characterised by the targeting agent or modifying agent linked to the acoustically-active agent · CPC title

• C07K14/195

  from bacteria · CPC title