Fluorescence imaging beyond the ballistic regime by ultrasound pulse guided digital phase conjugation

Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, Virginia, 20147, USA.
Nature Photonics (Impact Factor: 32.39). 10/2012; 6(10):657-661. DOI: 10.1038/nphoton.2012.205
Source: PubMed


Fluorescence imaging 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 imaging beyond the ballistic regime by combining single cycle pulsed ultrasound modulation and digital optical phase conjugation. We demonstrate a near isotropic 3D localized sound-light interaction zone. 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 imaging 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.

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Available from: Reto Fiolka, Apr 07, 2015
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    • "The single-shot DOPC of a full-field image requires extremely high precision in aligning optical paths, which was recently achieved through using an interferometer with a Sagnac-like ring design [40]. Recently, DOPC with ultrasound modulation has demonstrated potential for optical focusing inside turbid media [12] and high-resolution deep-tissue imaging [13] [14] "
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    • "In summary, the multi-modal imaging systems and technology can compensate the limit of detection depth in fluorescence imaging by imaging processing method and set the standard for many important applications in biological research and clinical trials 72. "
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    • "Wavefront shaping allows compensation for and exploitation of scattering due to spatial inhomogenieties in the refractive index of a material [7]. In this way it is possible to image through [8] [9] and inside [10] [11] [12] [13] [14] opaque materials, which is of great importance in biomedical imaging. Light propagating through an opaque material can be controlled in time by spatially shaping the incident wavefront [15] [16] [17] with applications such as pulse compression. "
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