## 2 Achievements of PAI Techniques in the Past Five Years
Based on one of these illuminators, [PERSON] and [PERSON] developed a PLD-PAT system with a spatial resolution of 384 \(\upmu\)m. Their pulse diode illuminator possesses a wavelength of 803 nm and a single-element piezoelectric transducer with a center frequency of 2.25 MHz (70% fractional bandwidth) to circularly scan and accept PA signals produced in samples [35; 36]. The system is capable of dynamic in vivo imaging within 5 s with a high signal-to-noise ratio (SNR) of \(\sim\)48, while preserving the skin and skull. This is useful for the non-invasive study of neurofunctional activities as well as the characterization of pharmacokinetic and biodistribution profiles in the brain. Since then, [PERSON] and [PERSON] have modified their PLD-PAT system using an unfocused ultrasonic transducer (UST) with a 5 MHz center frequency to detect venous sinus distension in vivo, which is caused by intracranial hypotension (IH) in small animals. The IH was induced through a 45 \(\upmu\)L cerebrospinal fluid (CSF) extraction, using a needle connected to a draw syringe. Five minutes after CSF extraction, an increase of \(\sim\)30% was observed in the sagittal sinus area with a width of 40% \(\pm\) 5% (from 493 \(\upmu\)m to 677 \(\upmu\)m) [37]. Pulsed light emitting diodes (LEDs) have recently made an appearance in PAI as illuminating sources [38], particularly for low cost, portable/hand-held devices. Differing from solid-state lasers and laser diodes, LEDs are non-coherent and eye-safe devices, making them more applicable in the clinical setting. On the other hand, their lower optical energy and greater divergence relative to PLDs, renders pulsed LEDs more challenging for PAI. Last year, a theoretical simulation of LED-based PAI showed that brain tumour margin vessels can be imaged for the safe resection of glioma [39], but there has not yet been a report for in vivo brain imaging using LED-PAI. However, with the technical progress of LED devices, the authors believe that LED-based PAI can become a potential tool for preclinical and clinical brain imaging applications. Aside from brain imaging, other LED and PLD-based PAI applications can be found in the referenced literature [40; 41; 42]. In the past few years, fiber lasers have also been applied to PAI, OR-PAM in particular, as excitation sources for PA generation [43]. Compared to solid-state lasers, fiber lasers prove to be more compact and offer higher efficiency without an external water-cooling system. In comparison to laser diodes and LEDs, fiber lasers provide considerably better beam orientation and easier focusing. Moreover, fiber lasers have a high pulse repetition frequency (up to MHz), making them suitable for the construction of ultrafast OR-PAMs [44; 45]. Furthermore, based on their good beam quality and high pulse energy, fiber lasers, combined with a stimulation Raman frequency-shifting fiber, can produce wavelength-selectable optical sources [46], that are well-suited for building multi-wavelength OR-PAM systems [14; 47]. As of relatively recently, [PERSON] et al. have developed a high-pulse energy fiber laser, capable of providing an output energy of \(\sim\)10 mJ with a variable pulse duration range of 10 ns-500 ns and a pulse repetition frequency of up to 1 kHz [48]. This compact fiber laser offers a practical excitation source for a portable PAT, which could be used for deep brain imaging. The development of wearable PAI has been ongoing since 2015, when the first wearable PAT device was mounted on a rat's head while the animal was awake and moving around. Compared with rats under anaesthesia, it was observed that its cerebral blood volume (CBV) changed at a quicker rate over time, and was larger in amplitude for rats in a fully awake, moving state. This PAI setup achieved a lateral resolution of ~0.5 mm and an axial resolution of ~0.1 mm at a depth of up to 11 mm in phantom evaluation. It was capable of imaging blood vessels to a depth of 5 mm, maintaining an intact scalp and skull bone [49].