Real-time spectroscopic photoacoustic/ultrasound (PAUS) scanning with simultaneous fluence compensation and motion correction for quantitative molecular imaging

For over two decades photoacoustic (PA) imaging has been tested clinically, but successful human trials have been minimal. To enable quantitative clinical spectroscopy, the fundamental issues of wavelength-dependent fluence variations and inter-wavelength motion must be overcome. Here we propose a new real-time, spectroscopic photoacoustic/ultrasound (PAUS) imaging approach using a compact, 1-kHz rate wavelength-tunable laser. Instead of illuminating tissue over a large area, the fiber-optic delivery system surrounding an US array sequentially scans a narrow laser beam, with partial PA image reconstruction for each laser pulse. The final image is then formed by coherently summing partial images at a 50-Hz video rate. This scheme enables (i) automatic laser-fluence compensation in spectroscopic PA imaging and (ii) inter-wavelength motion correction using US speckle tracking, which have never been shown before in real-time systems. The 50-Hz video rate PAUS system is demonstrated in vivo using a murine model of drug delivery monitoring.