## 2 Achievements of PAI Techniques in the Past Five Years
The researchers then modified the setup by using three layers of fully functional acoustic transducer arrays to build a three-dimensional wearable PAI system (3D-wPAT). Moreover, the in-plane spatial resolution was improved to 200 \(\upmu\)m and acquired a 3D brain image within 167 ms. The experiment revealed that 3D-wPAT can detect visually evoked responses in the primary visual cortex and map cerebral oxygen saturation via multi-wavelength irradiation in behaving hyperoxic rats [50]. Further, [PERSON] et al. reported a wearable OR-PAM mounted on a rat head, in which the imaging probe weighed only 8 g, allowing the rat to move around freely. The lateral and axial resolution of the acquired PA images were 2.25 \(\upmu\)m and 105 \(\upmu\)m, respectively, and only 10 s were required to image an area of 1.2 mm \(\times\) 1.2 mm [51]. This wearable OR-PAM successfully monitored both morphological and functional variations in the vasculature of the cerebral cortex during the induction of ischemia and reperfusion. Last year, a fully portable and wearable PAM was reported [52], allowing a mouse to move around freely without the hindrance of any external devices connected via a cable or fiber (WiFi or wireless connection, as shown in Figure 3). Although the report does not contain in vivo data, displaying only phantom study results, wearable devices with a wireless connection are being used more often. Wearable PAI devices for the human head are more complicated to implement than those designed for small animals. Their practical realization typically suffers from the complex assembly, unviability of full-hat rotation around the human head, US coupling and the necessity of hundreds of US data acquisition channels required to cover the whole brain. Last year, a modular PAI hat was developed for neonatal brain imaging, consisting of multiple PAI disc modules, measuring 2 inches in diameter [53]. Conforming to the shape of the head, these modules were assembled onto a hat to cover the entire neonatal brain. Each of the PAI discs integrated source optical fibers and either densely packed US elements (to eliminate the need for rotation) or fewer US elements (usually in a trapezoidal shape) on a rotating disc (to reduce the number of data acquisition channels). Through an innovative modular design, the system minimized challenges posed by backend electronics. Most high-resolution optical imaging of small animal brains has been carried out under anaesthesia to decrease motion artifacts. However, there is direct evidence that brain activity during wakefulness cannot be reliably inferred from the observations of  
Figure 3: Illustration of a wearable PAM for mouse brain imaging (Reprinted with permission from Ref. [52]. 2020, IEEE). anesthetized animals [54]. Moreover, anaesthetic-induced changes in cerebral hemodynamics have been reported in humans and primates [55; 56]. To solve this problem, [PERSON] et al. developed a so-called head-restrained PAM system, in which the head of a fully awake mouse was restrained by a nut-bolt configuration [57]. In this configuration, a small nut was attached to the exposed mouse skull using dental cement. Fixed in a customized head plate with a bolt, the mouse head could be angularly adjusted using a rotation mount to align the region of interest perpendicular to the imaging head. It could be vertically adjusted using a right-angle clamp to allow the mouse's limbs to comfortably rest on the surface of a spherical treadmill. The treadmill consisted of two hollow polystyrene hemispheres, 8 inches in diameter, situated in a homemade cylindrical holder. The slightly compressed air from the bottom of the holder created a thin cushion to float the treadmill, allowing the mouse to move freely with a reduced reaction force. The head-restrained PAM enabled a simultaneous imaging of its cerebrovascular anatomy, total concentration and oxygen saturation of its hemoglobin and blood flow.