## 2 Achievements of PAI Techniques in the Past Five Years  
A typical OR-PAM has an optical-acoustic confocal system (as shown in Figure 1a), in which the optical beam focus point overlaps the transducer focus range to achieve optimum lateral resolution and detection sensitivity. This confocal system has two glass prisms [29; 30; 31], maintaining coaxial aligning of the exciting light beam and accepted PA waves. As the two glass prisms must be immersed in coupling water for acoustic detection and scanning, an acoustic impedance mismatch can be observed at the glass/water boundary, resulting in a lower transmission speed when a PA wave moves across the boundary before detection. To avoid this, a novel OR-PAM setup has been developed, with the two prisms removed, as shown in Figure 2[32]. In the reported setup, the exciting laser pulse was passed through a polyvinylidene dil fluoride (PVDF) transducer with a hollow core and was reflected to a mouse brain using a home-made MEMS scanner, which also reflected PA signals from the brain to the PVDF transducer. Although the PVDF transducer had a lower sensitivity than the more commonly used lead zirconate titanate (PZT) ceramic transducers, avoiding the mismatch at the prism-water boundary resulted in a \(\sim\)50% increase in overall PAM detection sensitivity. It must be mentioned that PVDF transducers often offer a broader bandwidth than PZT transducers, improving the axial resolution of PAM. The new functional PAM has achieved high-sensitivity volumetric imaging using a 1 MHz one-dimensional imaging rate with a 2.7 \(\upmu\)m lateral and a 30 \(\upmu\)m axial resolution, revealing capillary-level vascular dynamics. Its detection sensitivity can probably be further improved by using a PZT ceramic transducer with a hollow core to replace the PVDF transducer. This is because a PZT has a much higher piezoelectric effect than a PVDF, although PVDF offers an improved acoustic coupling and transmission efficiency in water. In PAI, solid-state lasers are commonly used as illumination sources in tomographic or macroscopic imaging, due to their high pulse energy output (\(\sim\)10-100 mJ). With a pulse  
Figure 2: Schematic of a functional OR-PAM system without acoustic impedance mismatch: KGW, KGd (WO4) 2 crystal; \(\lambda/2\), half-wave plate; BPF, band-pass filter; DAQ, data acquisition unit; and UT, US transducer (Reprinted from Ref. [32]). duration in the nanosecond range, these properties are essential for highly efficient PA generation. However, their bulky size (sub-meter), heavy weight (a few tens of kg), high cost (>20 k\(\epsilon\)), and the relatively low pulse repetition frequency (\(\sim\)100 Hz) mean solid-state lasers are unsuitable for clinical and portable applications. Over the last fifteen years, researchers have started to use high-power pulse laser diodes (PLDs) as an illumination source, largely because laser diodes are smaller in size (centimeters), lighter in weight (-grams), less expensive (\(\sim\)100 s \(\epsilon\)) and have a high pulse repetition frequency (-10 kHz). However, a key limitation of pulsed laser diodes in PAI is their low peak output power (\(\sim\)20 u\(\beta\)100 ns), especially in the nanosecond pulse duration range (\(\sim\)ul)@10 ns). Fortunately, by combining more than ten laser diodes at the 905 nm wavelength, it is possible to obtain PAI with similar SNR at the depth of 1 cm as with a 10 mJ Q-switched Nd: YAG laser, provided that the stress confinement condition is fulfilled [33]. However, this requires sacrificing the lateral resolution to some extent [34]. As a result, PLDs have been used exclusively for PAI of superficial vascular structures. Recently, the Quantel-Laser company has introduced high-power laser diode illuminators with greatly improved output pulse energy (on the order of mJ @ 30 ns) at a pulse repetition frequency of several kHz, enabling PAT imaging of deep brain areas in mice or rats.