Acousto-optical imaging is an emerging biodiagnostic technique which provides an optical spectroscopic signature and a spatial localization of an optically absorbing target embedded in a strongly scattering medium. The transverse resolution of the technique is determined by the lateral extent of ultrasound beam focal zone while the axial resolution is obtained by using short ultrasound pulses. Although very promising for medical diagnostic, the practical application of this technique is presently limited by its poor sensitivity. Moreover, any method to enhance the signal-to-noise ratio must obviously satisfy the in vivo safety limits regarding the acceptable power level of both the ultrasonic pressure wave and the laser beam. In this paper, we propose to improve the sensitivity by using a pulsed single-frequency laser source to raise the optical peak power applied to the scattering medium and to collect more ultrasonically tagged photons. Such a laser source also allows illuminating the tissues mainly during the transit time of the ultrasonic wave to maintain the average optical power below the maximum permissible exposure. In our experiment, a single-frequency Nd:YAG laser emitting 500-μs pulses with a peak power superior to 100 W was used. Photons were tagged in few-cm thick optical phantoms with tone bursts generated by an ultrasonic transducer. Tagged photons were detected with a GaAs photorefractive interferometer characterized by a large optical etendue to process simultaneously a large number of speckle grains. When pumped by high intensity laser pulses, such an interferometer also provides the fast response time essential to obtain an apparatus insensitive to the speckle decorrelation due to mechanical vibrations or tissues movements. The use of a powerful long pulse laser appears promising to enhance the signal level in ultrasound modulated optical imaging. When combined with a photorefractive interferometer of large optical etendue, such a source could allow obtaining both the sensitivity and the fast response time necessary for biodiagnostic applications.© (2008) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.