  Fluorescence microscopy has revolutionized biomedical research over the past
three decades. Its high molecular specificity and unrivaled single molecule
level sensitivity have enabled breakthroughs in a variety of research fields.
For in vivo applications, its major limitation is the superficial imaging depth
as random scattering in biological tissues causes exponential attenuation of
the ballistic component of a light wave. Here we present fluorescence
microscopy beyond the ballistic regime by combining single cycle pulsed
ultrasound modulation and digital optical phase conjugation. We demonstrate
near isotropic 3D localized sound-light interaction with an imaging depth as
high as thirteen scattering path lengths. With the exceptionally high optical
gain provided by the digital optical phase conjugation system, we can deliver
sufficient optical power to a focus inside highly scattering media for not only
fluorescence microscopy but also a variety of linear and nonlinear spectroscopy
measurements. This technology paves the way for many important applications in
both fundamental biology research and clinical studies.
