Fundamental considerations for multiwavelength photoacoustic molecular imaging

Photoacoustic technology offers great promise for molecular imaging in vivo since it offers significant penetration, and optical contrast with ultrasonic spatial resolution. In this article we examine fundamental technical issues impacting capabilities of photoacoustic tomography for molecular imaging. First we examine how reconstructed photoacoustic tomography images are related to true absorber distributions by studying the modulation transfer function of a circular scanning tomographic system employing a modified filtered backprojection algorithm. We then study factors influencing quantitative estimation by developing a forward model of photoacoustic signal generation, and show conditions for which the system of equations can be inverted. Errors in the estimated optical fluence are shown to be a source of bias in estimates of molecular agent concentration. Finally we discuss noise propagation through the matrix inversion procedure and discuss implications for molecular imaging sensitivity and system design.