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: 29.96). 10/2012; 6(10):657-661. DOI: 10.1038/nphoton.2012.205
Source: PubMed

ABSTRACT 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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    ABSTRACT: Due to the highly inhomogeneous distributions of refractive indexes, light propagation in complex media such as biological tissue experiences multiple light scattering events. The suppression and control of multiple light scattering events are investigated because they offer the possibility of optical focusing and imaging through biological tissues, and they may open new avenues for diagnosis and treatment of several human diseases. In order to provide insight into how new optical techniques can address the issues of multiple light scattering in biomedical applications, the recent progress in optical wavefront-shaping techniques is summarized.
    Current Applied Physics 02/2015; 15(5). DOI:10.1016/j.cap.2015.02.015 · 2.03 Impact Factor
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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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    ABSTRACT: We present a superpixel method for full spatial phase and amplitude control of a light beam using a digital micromirror device (DMD) combined with a spatial filter. By spatial filtering we combine square regions of nearby micromirrors into superpixels. At each superpixel we are able to independently modulate the phase and the amplitude of light, while retaining a high resolution and all advantages of a DMD such as its very high speed. The method achieves a measured fidelity $F=0.98$ for a high resolution target field with fully independent phase and amplitude and a calculated fidelity $F=0.99993$ for the LG$_{10}$ orbital angular momentum mode, offering one to three orders of magnitude reduction of error with respect to the state of the art Lee holography method.
    Optics Express 05/2014; 22(15). DOI:10.1364/OE.22.017999 · 3.53 Impact Factor
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    • "Although the requirement for a direct optical access to the target was considered as the main limitation for applying wavefront shaping in practical scenarios, several approaches to overcome this apparent limitation have been investigated. These methods include using implanted guide-stars [5] [6], ultrasonic tagging of light [7] [8] [9], and the photoacoustic effect [10]. "
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    ABSTRACT: We implement the photoacoustic transmission-matrix approach on a two-dimensional photoacoustic imaging system, using a 15 MHz linear ultrasound array. Using a black leaf skeleton as a complex absorbing structure, we demonstrate that the photoacoustic transmission-matrix approach allows to reveal structural features that are invisible in conventional photoacoustic images, as well as to selectively control light focusing on absorbing targets, leading to a local enhancement of the photoacoustic signal.
    Optics Letters 05/2014; 39(9):2664-2667. DOI:10.1364/OL.39.002664 · 3.18 Impact Factor
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