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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    • "Currently, wavefront shaping techniques have become widely investigated in two methods in the field of biomedical optics. The first method optimizes the wavefront of an incident beam into a turbid medium via an SLM in order to generate an optical focus behind or inside the turbid medium [7] [8] [9] [10] [11] [12] [13]. The second method delivers optical information through a highly scattered layer via characterizing and exploiting multiple light scattering [14- 16]. "
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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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