# Photoacoustic Imaging in Oxygen Detection
## 3 Photoacoustic Imaging in pO\({}_{2}\) Measurement
(2014, 2015), who have also conducted further studies with methylene blue (MB) solution to demonstrate this concept and pushed it to in vivo. They have built a multi-modal system integrating ultrasound imaging, regular photoacoustic imaging, as well as PALI (Figure 4b) to map the distribution of oxygen partial pressure in tissue, from which hypoxic areas can be clearly identified (Pump, 2016; Pump, 2016). Based on these studies, they further developed treatment/imaging modality referred to as PDT-PALI (Figure 4c), which enables real-time feedback of three essential parameters during a PDT therapy: tissue oxygen, light penetration in tumor location, and distribution of photosensitizer (Pump, 2016; Pump, 2016). Lifetime-based PAT technique by using G2 molecules for blood oxygenation sensing (Pump, 2016; Pump, 2016) and MB loaded polyacrylamide nanoparticles (MB-PAA NPs) for tumor oxygen sensing (Pump, 2016) have also been demonstrated by other groups. Figure 4: _Cont._  
Although in the early stage, detecting tissue pO\({}_{2}\) by photoacoustic technology shows great potentials in both research and clinical theranostics. In vivo complexity has made production or transportation study of proteins, ions, or oxygen challenging. Technical development for deep tissue functional imaging is in urgent demand for comprehensive understanding of biological processes. Photoacoustic imaging is entering its translational stage, and expansion of its applications will greatly help promote this progress. Due to the intrinsic fine resolution, real-time imaging ability, deep penetration depth, etc., PAI is highly promising for deep tissue pO\({}_{2}\) measurement. Future work should stress the accuracy, finer resolution, deeper penetration, real-time imaging, and combination with sO\({}_{2}\) monitoring to get the overall knowledge of the region of interest. For example, through wavefront engineering [52], it has potential to achieve whole body detection of oxygen distribution in a real-time and non-invasive way, which is a long-sought goal in both biomedical research and clinics. In addition, works discussed above applying lifetime method exploited specific oxygen-sensitive dyes, which detected triplet oxygen molecules while generating singlet oxygen at the same time. This can act as a double-edged sword, which is bad for normal cells if there is too much of such byproduct, but can be good for theragnostic performance in cancerous cells. In this regard, it is highly preferable to develop oxygen sensitive dyes that have peak absorption in the near infrared region (being suitable for in vivo PAI) yet produce few adverse effects to cells. These kinds of studies can potentially greatly facilitate tissue hypoxia detection, early cancer diagnosis, as well as hyperbaric or radiation therapy. Figure 4: (**a**) Photoacoustic lifetime imaging for hypoxia detection (reproduced with permission from [42]); (**b**) Schematic of in vivo multimodal imaging system, which is capable of generating US (ultrasound), PAI, and PALI images using the same hardware (reproduced with permission from [45]. Copyright SPIE, 2013); (**c**) A combined PDT/PALI therapy/imaging system. A common fiber-optic bundle is used to deliver light into the tissue. A 660 nm emitting laser-diode is used for PDT. Open development platform is used for ultrasound multi-channel data acquisition. A 64-element US linear array is used for US, PAI, and PALI imaging operation. A FPGA (field programmable gate array) module is used to synchronized laser firing and signal acquisition. A PC is used as a system controller, data processing, and display (reproduced with permission from [47]. Copyright SPIE, 2014).