## 3 Combining PAI and LUI in Biomedicine
### Combined PA and LUI Pulse-Echo Imaging  
PA imaging can be combined with pulse-echo ultrasound imaging. PA imaging has high contrast and can provide spectroscopic information, while ultrasound can provide morphological and anatomical information about the surrounding tissues and structures. Thus, numerous systems combining PA imaging with conventional B-mode ultrasound (US) imaging were proposed (e.g., [105, 106, 107, 108, 109, 110, 111, 112, 113]) and some integrated PAUS systems are commercially available (e.g., Fujifilm VisualSonics Vevo LAZR or Seno Medical Instruments Imagio). LUI may be advantageous, since it may use the same laser pulse to generate the probe pulse and the bandwidth of the probe pulse may be wider (from 1 to 10 MHz). The ultrasound transducers can also be optimized for wideband reception and better acoustic coupling, since they are not used for ultrasound generation. Figure 4: Combined schematic of the passive element (PE)-enriched “PA + speed-of-sound (SoS) + LU” imaging. [PERSON] et al. [41] were, to the best to our knowledge, the first to manufacture a combined \"PA + LU\" system. The system contained a planar array of sixteen 1 mm-wide broadband (1.6-9 MHz) polyvinylidene fluoride (PVDF) piezoelectric transducers glued to the plane-parallel black polymer film (100 \(\upmu\)m thick) as a PA generator and poly (methyl methacrylate) (PMMA) cylindrical focusing acoustic lens (Figure 5) for 2D \"PA + LU\" imaging. The piezoelectric elements were damped, and detected the full PA generation bandwidth. Later [45], the system was equipped with a real-time field-programmable gate array (FPGA)-based data acquisition system, and used for medical needle guidance studies. PA imaging was used to locate the polymeric blood vessel model filled with a diluted Indian ink solution, and LU imaging was used to track the position of the needle tip inside the vessel. The setup was proposed to prevent piercing blood vessels through. In this scenario, both the blood vessel and the needle acted as PA sources, so LUI helped to determine the needle tip position inside the vessel more accurately. The achieved frame rate was 10 Hz. The acceptance angle of the needle was not studied in [45], but it was noted that wideband LU probe pulse reverberates inside the needle, which could be used to identify the needle. It is worth noting that combined \"PA + US\" systems, proposed for needle guidance earlier [114; 115], used PAI differently. There, the needle acted as a cylindrical PA source, and the PA image showed the position of the needle relative to the US array and the injected absorptive agent, while the US image provided anatomical landmarks. In this imaging scenario, the PA imaging helped to enhance the contrast of US images of the needle and effectively double the acceptance angle \(\uptheta\) between the needle and the linear US array. In the purely US needle guidance scenarios, the needle acts as an ultrasonic reflector, since it has an order of magnitude higher acoustic impedance than the surrounding tissue. However, the acoustic wave reflected from the needle travels at the 2\(\uptheta\) angle to the linear array. In PAI of the needle, the wave generated by the needle travels along the normal of the needle, so the angle of incidence on the array is equal to \(\upvartheta\). If the angle of incidence exceeds the angular size of the main lobe of the piezoelectric sensor, the needle becomes \"invisible\". It could also be said that the effective doubling of the acceptance angle occurs because the angular aperture necessary to detect the reflected LU pulse should be twice as large as the angular aperture necessary to detect the PA response. While, in [115], the achieved frame rate (10 Hz) was limited by the repetition rate of the high-power laser and, in [41], the authors used a high repetition rate (\(\sim\)1 kHz) laser with relatively low pulse energy (\(\sim\)2 mJ), and integrated it with a real-time clinical ultrasound scanner.