Our customized imaging system incorporates a computer-controlled scanning, triggering, and data-acquisition system and a combined light delivery and ultrasound probe based on confocal dark-field laser illumination optics. Readers are referred to our previous work16,17 for specific details about the instrumentations and explanations on light delivery probe and imaging procedures. In brief, a digital-input-output (DIO) card (NI PCI-6542, National Instruments, Inc., USA) is used to generate a pulse sequence that is sent to the ultrasound pulser/receiver (5073PR, Panametrics; Waltham, Massachusetts) and/or laser to enable different imaging modes. Currently our system can provide ultrasound (US) B-mode, photoacoustic (PA) mode, and Doppler US mode. In PA mode, a tuneable optical parametric oscillator (Surelite OPO Plus, Continuum; Santa Clara, California) is pumped by a Q-switch Nd:YAG laser (Surelite III, Continuum; Santa Clara, California) with a repetition rate of 10 Hz. The tuning range is from 410 to 710 nm. PA and Doppler US modes are combined by using the DIO card to interleave laser and US triggers so that images can be co-registered. A 25-MHz single element transducer (V324-SM, 12.7-mm focal length, Panametrics; Waltham, Massachusetts) is positioned inside the light delivery probe and can be adjusted vertically to match its focus point with the laser focus. Radio frequency (RF) data received by the US pulser/receiver is digitized by an eight-channel PCI data-acquisition card (CS8289, Gage Cobra, Gage Applied Systems, Inc., USA) with 12-bit dynamic range and sampling rates as high as 125 M Samples/s.