Apparatus and method for combined photoacoustic and ultrasound diagnosis

1. A combined photoacoustic and ultrasound diagnosis method, comprising operations of:

(a) transmitting a first ultrasound signal to a subject to which a contrast agent having microbubbles has been administered, detecting an echo signal generated due to reflection of the first ultrasound signal by the microbubbles, and displaying an ultrasound image produced based on the echo signal, wherein the first ultrasound signal has a mechanical index at which the microbubbles do not burst;

(b) transmitting a second ultrasound signal to the subject to burst the microbubbles to form microbubble flakes, wherein the second ultrasound signal has a mechanical index at which the microbubbles burst; and

(c) irradiating the subject with a laser signal, detecting a photoacoustic signal generated due to the microbubble flakes stimulated by the laser signal, and then, displaying a photoacoustic image produced based on the photoacoustic signal,

wherein the microbubbles each comprise:

a lipid shell colored with dye; and

a filling gas encapsulated by the lipid shell,

wherein a concentration of the dye in a dye solution used to hydrate the lipid shell is in a range of 0.5 mM to 20 mM, and

wherein the dye is azure blue, evans blue, indocyanine green, brilliant blue, nile blue, methylene blue, or a combination thereof.

2. The combined photoacoustic and ultrasound diagnosis method of claim 1 , wherein the first ultrasound signal has the mechanical index of less than 0.5.

3. The combined photoacoustic and ultrasound diagnosis method of claim 1 , wherein the microbubbles contain a drug that is to be delivered to an organ in the subject.

4. The combined photoacoustic and ultrasound diagnosis method of claim 1 , wherein the second ultrasound signal has the mechanical index of 0.5 to 1.9.

5. The combined photoacoustic and ultrasound diagnosis method of claim 1 , wherein the microbubbles contain a drug that is to be delivered to an organ in the subject, and the operation (b) begins when arriving of the microbubbles at the organ is confirmed.

6. The combined photoacoustic and ultrasound diagnosis method of claim 1 , wherein the dye absorbs incident light having a wavelength of 500 nm to 1,300 nm.

7. The combined photoacoustic and ultrasound diagnosis method of claim 1 , wherein the concentration of the dye in the dye solution used to hydrate the lipid shell is in a range of 15 mM to 20 mM.

8. The combined photoacoustic and ultrasound diagnosis method of claim 1 , wherein the lipid shell comprises a phospholipid.

9. The combined photoacoustic and ultrasound diagnosis method of claim 8 , wherein the phospholipid comprises 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid (DPPA); 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC); 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC); 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC); 1,2-dibehenoyl-sn-glycero-3-phosphocholine (DBPC); 1,2-diarachidoyl-sn-glycero-3-phosphatidylcholine (DAPC); 1,2-dilignoceroyl-sn-glycero-3-phosphatidylcholine (DLgPC); 1,2-dipalmitoyl-sn-glycero-3-[phosphor-rac-(1-glycerol)] (DPPG); or a mixture thereof.

10. The combined photoacoustic and ultrasound diagnosis method of claim 1 , wherein a particle diameter of the lipid shell is in a range of 0.5 μm to 10 μm.

11. The combined photoacoustic and ultrasound diagnosis method of claim 1 , wherein a wall thickness of the lipid shell is in a range of 1 nm to 200 nm.

12. The combined photoacoustic and ultrasound diagnosis method of claim 1 , wherein the filling gas is a biologically inactive gas.

13. The combined photoacoustic and ultrasound diagnosis method of claim 1 , wherein the filling gas comprises perfluorocarbon, sulphur hexafluoride, perfluoromethane, perfluoroethane, perfluoropropane, perfluorobutane, perfluoropentane, perfluorohexane, perfluoroheptane, perfluorooctane, perfluorononane, perfluorodecane, perfluorobenzene, perfluorotriethylamine, perfluorooctylbromide, or a mixture thereof.

14. The combined photoacoustic and ultrasound diagnosis method of claim 1 , wherein a drug is located inside the lipid shell.

15. The combined photoacoustic and ultrasound diagnosis method of claim 1 , wherein the operation (c) begins when or after the operation (b) begins.

16. A combined photoacoustic and ultrasound diagnosis apparatus, comprising

a laser irradiation unit which irradiates a subject with a laser signal;

an ultrasound signal transducer which transmits a first ultrasound signal to the subject, detects an echo signal generated due to reflection of the first ultrasound signal by microbubbles in the subject, transmits a second ultrasound signal to the subject to burst the microbubbles to form microbubble flakes, and detects a photoacoustic signal generated due to stimulation of the microbubble flakes by the laser signal, wherein the first ultrasound signal has a mechanical index at which the microbubbles do not burst, and the second ultrasound signal has a mechanical index at which the microbubbles burst;

an image processor which produces a photoacoustic image based on the photoacoustic signal and an ultrasound image based on the echo signal; and

a display unit which displays the photoacoustic image and ultrasound image,

wherein the microbubbles each comprise:

a lipid shell colored with dye; and

a filling gas encapsulated by the lipid shell,

wherein the dye is azure blue, evans blue, indocyanine green, brilliant blue, nile blue, methylene blue, or a combination thereof,

wherein the ultrasound signal transducer detects the photoacoustic signal when bursting the microbubbles, and

wherein a concentration of the dye in a dye solution used to hydrate the lipid shell is in a range of 0.5 mM to 20 mM.

17. A combined photoacoustic and ultrasound diagnosis method, comprising operations of:

(a) transmitting a first ultrasound signal to a subject to which a contrast agent having microbubbles has been administered, detecting an echo signal generated due to reflection of the first ultrasound signal by the microbubbles, and displaying an ultrasound image produced based on the echo signal, wherein the first ultrasound signal has a mechanical index at which the microbubbles do not burst;

(b) transmitting a second ultrasound signal to the subject to burst the microbubbles to form microbubble flakes, wherein the second ultrasound signal has a mechanical index at which the microbubbles burst; and

(c) irradiating the subject with a laser signal, detecting a photoacoustic signal generated due to the microbubble flakes stimulated by the laser signal, and then, displaying a photoacoustic image produced based on the photoacoustic signal,

wherein the microbubbles each comprise:

a lipid shell colored with dye; and

a filling gas encapsulated by the lipid shell, wherein the dye is azure blue, evans blue, indocyanine green, brilliant blue, nile blue, methylene blue, or a combination thereof,

wherein the operation (c) begins after the operation (b) begins, and

wherein a concentration of the dye in a dye solution used to hydrate the lipid shell is in a range of 0.5 mM to 20 mM.

18. A combined photoacoustic and ultrasound diagnosis apparatus, comprising a laser irradiation unit which irradiates a subject with a laser signal;

an ultrasound signal transducer which transmits a first ultrasound signal to the subject, detects an echo signal generated due to reflection of the first ultrasound signal by microbubbles in the subject, transmits a second ultrasound signal to the subject to burst the microbubbles to form microbubble flakes, and detects a photoacoustic signal generated due to stimulation of the microbubble flakes by the laser signal, wherein the first ultrasound signal has a mechanical index at which the microbubbles do not burst, and the second ultrasound signal has a mechanical index at which the microbubbles burst;

an image processor which produces a photoacoustic image based on the photoacoustic signal and an ultrasound image based on the echo signal; and

a display unit which displays the photoacoustic image and ultrasound image,

wherein the microbubbles each comprise:

a lipid shell colored with dye; and

a filling gas encapsulated by the lipid shell,

wherein the dye is azure blue, evans blue, indocyanine green, brilliant blue, nile blue, methylene blue, or a combination thereof,

wherein the ultrasound signal transducer detects the photoacoustic signal after bursting the microbubbles, and

wherein a concentration of the dye in a dye solution used to hydrate the lipid shell is in a range of 0.5 mM to 20 mM.