Burst ultrasound reconstruction with signal templates and related methods and systems
The application of a step function increase in acoustic pressure during ultrasound imaging using gas vesicle contrast, along with capturing successive frames of ultrasound imaging and extracting time-series vectors for pixels of the frames, allows for improved imaging down to even the cell level. Template vectors can be used to implement signal separation of the time-series vectors to improve detection.
1. A method of ultrasound imaging to be used on a target site contrasted with gas vesicles (GVs) having an acoustic collapse pressure threshold, the method comprising:
applying ultrasound to the target site at a peak positive pressure less than the acoustic collapse pressure threshold;
increasing peak positive pressure (PPP) to above the selective acoustic collapse pressure value threshold as a step function;
imaging the target site in successive frames during the increasing;
extracting a time-series vector for each of at least one pixel of the successive frames; and
detecting from the time-series vectors a transient signal from, due to the increasing PPP, fluid displacement from collapsing of the GVs or cavitating bubbles released from the GVs, the detecting being in a time domain of the successive frames, the transient signal providing an increase in contrast signal in the ultrasound imaging.
2. The method of claim 1 , further comprising performing a signal separation algorithm separating a signal due to the GVs from other signals on the time-series vectors using at least one template vector estimated by averaging pixel time series from regions of interest containing known samples.
3. The method of claim 2 , wherein the signal separation algorithm includes template projection.
4. The method of claim 2 , wherein the signal separation algorithm includes template unmixing.
5. The method of claim 4 , wherein the at least one template vector is based on data from linear scatterers, noise, gas vesicles, or a combination thereof.
6. The method of claim 1 , wherein the successive frames comprise a frame prior to GVs collapse, a frame during GVs collapse, and a frame after GVs collapse.
7. The method of claim 1 , further comprising delivering the GVs to the target site.
8. The method of claim 7 , wherein the delivering the GVs to the target site comprises using an acoustic reporter gene to express the GVs.
9. The method of claim 8 , wherein the target site comprises a mammalian cell with the acoustic reporter gene.
10. The method of claim 1 , wherein the increasing includes increasing the PPP to a hiBURST regime.
11. The method of claim 10 , wherein the PPP in hiBURST regime is 4.3 MPa or higher.
12. The method of claim 1 , wherein the increasing includes increasing the PPP to a loBURST regime.
13. The method of claim 12 , wherein the PPP in loBURST regime is no higher than 3.7 MPa.
14. A system for imaging a target site contrasted with gas vesicles (GVs) having an acoustic collapse pressure threshold, the system comprising:
an ultrasound source capable of producing peak positive pressure both below and above the acoustic collapse pressure threshold;
an ultrasound imager configured to capture successive frames from the target site; and
a processor configured to:
calculate a time-series vector for each of at least one pixel of the successive frames and
detect from the time-series vectors a transient signal from, due to the increasing PPP, fluid displacement from collapsing of the GVs or cavitating bubbles released from the GVs, the detecting being in a time domain of the successive frames, and the transient signal providing an increase in contrast signal in the imaging.
15. The system of claim 14 , wherein the processor is further configured to perform a signal separation algorithm separating a signal due to the GVs from other signals on the time-series vectors using at least one template vector estimated by averaging pixel time series from regions of interest containing known samples.
16. The system of claim 15 , wherein the signal separation algorithm includes template projection.
17. The system of claim 15 , wherein the signal separation algorithm includes template unmixing.
18. The system of claim 17 , wherein the at least one template vector is based on data from linear scatterers, noise, gas vesicles, or a combination thereof.
19. The system of claim 14 , wherein the successive frames comprise a frame prior to GVs collapse, a frame during GVs collapse, and a frame after GVs collapse.
20. The system of claim 14 , further comprising a means for introducing the gas vesicles at the target site.
21. The system of claim 20 , wherein the delivering the GVs to the target site comprises using an acoustic reporter gene to express the GVs.
22. The system of claim 21 , wherein the acoustic reporter gene is in a mammalian cell.