Photoacoustic neuroimaging
The photoacoustic effect, first discovered by Alexander Bell in 1880 (Bell 1880), refers to the formation of sound waves following light absorption in an object. The conversion of optical energy to acoustic energy allows visualization of deep tissue optical absorption with acoustically defined spatial resolution. Starting in the 1990s, with the advent of short-pulsed lasers and highsensitivity ultrasound transducers, the photoacoustic effect began to be utilized for biomedical imaging (Kruger 1994, Karabutov et al. 1996, Oraevsky et al. 1997, Wang et al. 2002). In 2003, Wang et al. (2003a, b) reported the first functional photoacoustic tomography (PAT), which imaged hemodynamic response noninvasively in the rat brain. Since then, the field has been growing rapidly, and PAT is now becoming an important neuroimaging modality (Wang 2009, Hu and Wang 2010, Wang and Hu 2012, Xia and Wang 2013). Similar to other commonly used neuroimaging modalities, such as functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy, PAT images brain functions through the neurovascular coupling effect, which refers to the close correlation between local neural activity and changes in cerebral hemodynamics (Attwell and Iadecola 2002). Because photoacoustic signals originate from optical absorption, PAT readily benefits from endogenous oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR) contrasts. The two forms of hemoglobin possess different optical absorption coefficients (Horecker 1943), and their concentrations can be quantified through spectral inversion. Thus, PAT provides label-free functional brain imaging of oxygen saturation (sO2) and total hemoglobin concentration (CHb). In comparison, the blood-oxygen-level dependent signal in fMRI mainly originates from HbR (Steinbrink et al. 2006), and thus fMRI cannot distinguish between increased blood oxygenation and decreased blood volume (Stein et al. 2009). Compared with purely optical imaging modalities, PAT breaks through the optical diffusion limit, allowing high-resolution imaging of cortical vasculature through an intact scalp. Moreover, the imaging depth and spatial resolution of PAT are fully scalable across both optical and ultrasonic dimensions, providing an unprecedented opportunity to bridge the gap between microscopic and macroscopic neuroimaging. PAT also benefits from advances in exogenous contrast agents, such as organic dyes, nanoparticles, and reporter genes, allowing exploration of molecular pathways underlying neurological disorders (Hammoud et al. 2007, Kim et al. 2010). In this chapter, we review the advances in photoacoustic neuroimaging. The second section introduces the principle of PAT and describes various photoacoustic neuroimaging systems. The third section highlights representative photoacoustic neuroimaging studies, and the last section discusses further improvements in photoacoustic neuroimaging. It should be noted that PAT also has applications in many other biomedical areas, including oncology (Mallidi et al. 2011), dermatology (Favazza et al. 2011a, b), and cardiology (Taruttis et al. 2012, Wang et al. 2012). Interested readers can refer to Kim et al. (2010), Beard (2011), Mallidi et al. (2011), Wang and Hu (2012), and Xia and Wang (2014) for recent reviews of PAT.
