# Photoacoustic Imaging in Oxygen Detection
## 3 Photoacoustic Imaging in pO\({}_{2}\) Measurement  
So far, clinical pO\({}_{2}\) monitoring mainly rely on the oxygen polarographic needle (Eppendorf(r) electrode), positron emission tomography (PET), or magnetic resonance imaging (MRI) based methods. As an invasive approach, Eppendorf(r) electrode has been used since 1993 [28], which contributes to most of the current knowledge about tissue hypoxia. The clinical used PET [29; 30] concentrates more on oxygen metabolism, i.e., the glycolysis (F-18-fluorodeoxyglucose (FDG) as an in vivo glycolytic marker which reflects the alterations of glucose metabolism in cancer cells). PET has super sensitivity and good temporal resolution, but poor spatial resolution. PET cannot differentiate two isotopes that are injected simultaneously, as they give two \(\gamma\)-rays with the same energy. In addition,  
Figure 2: (**a**) PAM measurement of hemodynamic responses to a hyperthermic challenge (red bars) and the relative changes (reproduced with permission from [22]. Copyright SPIE, 2011). (**b**) Simultaneous PAM of (**i**) vascular anatomy; (**ii**) oxygen saturation of hemoglobin (sO\({}_{2}\)); and (**iii**) blood flow speed in a nude mouse ear in vivo and their dynamics (reproduced with permission from [23]. Copyright The Optical Society, 2015). (**c**) Quantification of mouse brain oxygenation responses to electrical stimulations (reproduced with permission from [24]. Copyright Nature Publishing Group, 2015). (**d**) Longitudinal in vivo imaging of regional tissue sO\({}_{2}\) during development (reproduced with permission from [25]. Copyright The Optical Society, 2017). PET imaging cannot be exploited for too long time or with frequency because of its radiative nature. MRI techniques for oxygen sensing rely on the probes containing the elements of \({}^{19}\)F or \({}^{1}\)H [31], which are not radioactive and less expensive than PET. MRI techniques can give finer spatial resolution, which is very favored to obtain more detailed anatomical images. However, MRI typically has a low imaging speed, which limits its applications in time-resolved imaging scenarios [32]. Moreover, relying on magnetic fields, this method is not suitable for patients who wear magnetic metal devices or cardiac pacemakers; the generated heat and the big noise during the measuring process may make patients feel uncomfortable and harm them [33]. Therefore, none of the aforementioned methods can be used as a routine tool for noninvasive, high temporal and spatial resolution, and low-cost human tissue oxygen sensing. The biggest concern in tissue pO\({}_{2}\) imaging may come from its huge heterogeneity [34]. Till now, neither PET nor MRI can completely provide simultaneous temporal and spatial real-time monitoring of tissue oxygen levels. Optical methods have played more and more important roles in biomedicine, and has the ability to present high temporal and spatial resolution [35]. Methods for biological oxygen partial pressure sensing are mostly through a luminescence quenching way, which images the lifetime of an oxygen-sensitive dye. Luminescence quenching method was proposed in 1935 [36], then first implemented in 1987 [37], and has been the major method used in biological-oxygen-related studies. In luminescence-based methods, phosphorescence and delayed fluorescence quenching are the two major mechanisms. Figure 3a shows that the delayed fluorescence (green and dashed) and phosphorescence (orange) related to triplet state lifetime are most commonly used. Collision between ambient oxygen and triplet-state molecules provides basic principle of this method, in which energy transfer leads to decreased triplet-state population and thus shortens the lifetime of this state. In Figure 3b [38], how the lifetime systems normally works is briefly shown. The general time window for an image is given by the integration time of the camera that turns the camera into a ready-to-accept-light state.