Systems and methods of grueneisen-relaxation photoacoustic microscopy and photoacoustic wavefront shaping

1. A method of focusing a light pulse within a focus area using nonlinear photoacoustic wavefront shaping, the method comprising:

obtaining an initial Grueneisen-memory photoacoustic microscopy (GM-PAM) feedback signal using an initial wavefront from within the focus area;

obtaining at least one subsequent GM-PAM feedback signal, each subsequent GM-PAM feedback signal obtained using a subsequent wavefront determined by altering a preceding wavefront according to a wavefront optimization rule using an immediately preceding GM-PAM feedback signal obtained using the preceding wavefront;

selecting an optimized wavefront according to an optimization criterion;

focusing the light pulse comprising the optimized wavefront within the focus area at a single-speckle resolution,

wherein a GM-PAM signal is obtained by:

delivering a first laser pulse comprising one wavefront to the focus area;

detecting a first photoacoustic signal induced by illumination of the focus area by the first laser pulse;

delivering a second laser pulse comprising the one wavefront to the focus area at a lag interval time after the delivery of the first laser pulse;

detecting a second photoacoustic signal induced by illumination of the focus area by the second laser pulse; and

subtracting a first peak-to-peak amplitude of the first photoacoustic signal from a second peak-to-peak amplitude of the second photoacoustic signal to obtain the GM-PAM signal; and

wherein each subsequent wavefront produces a subsequent GM-PAM signal higher than any preceding GM-PAM signal.

2. The method of claim 1 , wherein the wavefront optimization rule comprises a genetic algorithm.

3. The method of claim 1 , wherein the optimization criterion is chosen from:

the optimized wavefront is the wavefront determined after a maximum number of GM-PAM signals have been obtained;

the optimized wavefront is the wavefront for which a difference in a GM-PAM signal associated with the optimized wavefront and the immediately preceding GM-PAM signal is less than a minimum GM-PAM signal difference; and

the optimized wavefront produces a GM-PAM signal greater than a minimum threshold GM-PAM signal.

4. The method of claim 3 , wherein the maximum number of GM-PAM signals ranges from about 100 to about 2000.

5. The method of claim 1 , wherein the lag interval time is less than about 50 μs.

6. The method of claim 1 , wherein each wavefront comprises a spatial phase pattern generated by delivering a laser pulse through a configurable spatial light modulator.

7. The method of claim 6 , wherein the initial wavefront is chosen from a random spatial phase pattern and an optimal spatial phase pattern obtained by a linear photoacoustic wavefront shaping method.

8. The method of claim 1 , wherein the focus area of the GM-PAM signal comprises a lateral resolution of less than about 10 μm.

9. The method of claim 1 , further comprising centering the focus area within an acoustic focus region by:

obtaining a plurality of scanned photoacoustic signals using the optimized wavefront scanned across the acoustic focus region at a plurality of scan locations, wherein the optimized wavefront is scanned across the acoustic focus region by applying a linear phase ramp to an optimized spatial phase pattern associated with the optimized wavefront; and

using the scan location associated with the highest photoacoustic signal of the plurality of scanned photoacoustic signals to center the focus area within the acoustic focus region.

10. The method of claim 1 , wherein a high-fluence laser pulse comprising the optimized wavefront is delivered to the focus area to perform a laser microsurgery, the laser microsurgery comprising a photocoagulation of small blood vessels, a photoablation of tissue, and any combination thereof.

11. A method of Grueneisen-memory photoacoustic microscopy (GM-PAM) of a subject, the method comprising:

delivering a first laser pulse to a focus region;

detecting a first photoacoustic signal induced by illumination of the focus region by the first laser pulse;

after a lag interval time after the delivery of the first laser pulse, delivering a second laser pulse to the focus region, wherein the lag interval time is less than a thermal relaxation time of the subject;

detecting a second photoacoustic signal induced by illumination of the focus region by the second laser pulse; and

subtracting a first peak-to-peak magnitude of the first photoacoustic signal from a second peak-to-peak magnitude of the second photoacoustic signal to obtain a GM-PAM signal corresponding to the focus region,

wherein the first laser pulse and the second laser pulse each comprise a pulse width of less than or equal to about 10 ns.

12. The method of claim 11 , wherein the lag interval time is less than or equal to about 20 μs.

13. The method of claim 11 , wherein a lateral resolution of the GM-PAM is less than about 0.5 μm.

14. The method of claim 11 , wherein the GM-PAM comprises performing optical sectioning at an axial resolution of less than about 5 μm.

15. A method of focusing a light pulse within a focus area using nonlinear photoacoustic wavefront shaping, the method comprising:

obtaining an initial Grueneisen-memory photoacoustic microscopy (GM-PAM) feedback signal using an initial wavefront from within the focus area;

obtaining at least one subsequent GM-PAM feedback signal, each subsequent GM-PAM feedback signal obtained using a subsequent wavefront determined by altering a preceding wavefront according to a wavefront optimization rule using an immediately preceding GM-PAM feedback signal obtained using the preceding wavefront;

selecting an optimized wavefront according to an optimization criterion; and

focusing the light pulse comprising the optimized wavefront within the focus area at a single-speckle resolution,

wherein each wavefront comprises a spatial phase pattern generated by delivering a laser pulse through a configurable spatial light modulator, and

wherein the initial wavefront is chosen from a random spatial phase pattern and an optimal spatial phase pattern obtained by a linear photoacoustic wavefront shaping method.