Simple time-domain optical method for estimating the depth and concentration of a fluorescent inclusion in a turbid medium

Advanced Research Technologies, Inc., St. Laurent, Quebec, Canada.
Optics Letters (Impact Factor: 3.29). 11/2004; 29(19):2258-60. DOI: 10.1364/OL.29.002258
Source: PubMed


A simple time-domain optical method for estimating the depth and concentration of fluorescent inclusions in turbid media is described. We demonstrate direct depth estimation of a localized fluorescent object from the temporal position of the temporal point-spread function maximum. The depth estimation permits recovery of the fluorophore concentration, both of which are essential quantities for optical molecular imaging studies. Since the maximum is independent of the fluorophore concentration, excitation laser power, detector gain, and other system-dependent factors, this method ensures a robust and efficient approach.

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    • "Using time-resolved photo-sensing methods, the spread of the temporally focused (i.e., narrow pulse) light input is characterized to reveal the underlying biological tissue: the pulse intensity signifies tissue attenuation, the pulse width is tightly related to tissue scattering, and the pulse delay is related to both tissue thickness and scattering. More in-depth discussions of the quantitative relation of these parameters can be found in [62, 65, 66, 67, 68, 69, 70]. A special case of the temporal modulation methods is the so-called early photon (also known as ballistic photon) imaging method, which uses ultrafast laser and detector time-gating to reduce the TPSF of the imaging system, thereby improving the spatial resolution [71, 72, 73]. "
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    ABSTRACT: Diffuse optical imaging is highly versatile and has a very broad range of applications in biology and medicine. It covers diffuse optical tomography, fluorescence diffuse optical tomography, bioluminescence, and a number of other new imaging methods. These methods of diffuse optical imaging have diversified instrument configurations but share the same core physical principle - light propagation in highly diffusive media, i.e., the biological tissue. In this review, the author summarizes the latest development in instrumentation and methodology available to diffuse optical imaging in terms of system architecture, light source, photo-detection, spectral separation, signal modulation, and lastly imaging contrast.
    Full-text · Article · Mar 2014 · Photonics
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    • "Perhaps the most important approximation made in deriving the analytic expression for the fluorescence ratio is the so-called point-like approximation. The point-like approximation has also been used in the past for localization of fluorescent inclusions using time-domain signals (Hall et al 2004, Han and Hall 2008, Laidevant et al 2007). The analysis presented in section 3 supports the validity of this approximation by showing a strong correlation between the theoretical model and experimental fluorescence ratio data. "
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    ABSTRACT: Here we derived analytical solutions to diffuse light transport in biological tissue based on spectral deformation of diffused near-infrared measurements. These solutions provide a closed-form mathematical expression which predicts that the depth of a fluorescent molecule distribution is linearly related to the logarithm of the ratio of fluorescence at two different wavelengths. The slope and intercept values of the equation depend on the intrinsic values of absorption and reduced scattering of tissue. This linear behavior occurs if the following two conditions are satisfied: the depth is beyond a few millimeters and the tissue is relatively homogeneous. We present experimental measurements acquired with a broad-beam non-contact multi-spectral fluorescence imaging system using a hemoglobin-containing diffusive phantom. Preliminary results confirm that a significant correlation exists between the predicted depth of a distribution of protoporphyrin IX molecules and the measured ratio of fluorescence at two different wavelengths. These results suggest that depth assessment of fluorescence contrast can be achieved in fluorescence-guided surgery to allow improved intra-operative delineation of tumor margins.
    Full-text · Article · Nov 2011 · Physics in Medicine and Biology
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    • "In a continuous wave fDOT setup (CW-fDOT), one illuminates the sample with one or several continuous excitation sources and the emitted fluorescent light is detected on an array of detectors that is usually a CCD sensor [1, 4–6]. In a time domain fDOT system (TD-fDOT), the sample is illuminated with short light pulses and a time-resolved detection is performed using photon-counting methods with a single detector [7, 8] or with optimized arrangements of detectors [9, 11, 12, 14, 43] to get simultaneously temporal and spatial informations. "
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    ABSTRACT: Using a Cramer-Rao analysis, we study the theoretical performances of a time and spatially resolved fDOT imaging system for jointly estimating the position and the concentration of a point-wide fluorescent volume in a diffusive sample. We show that the fluorescence lifetime is a critical parameter for the precision of the technique. A time resolved fDOT system that does not use spatial information is also considered. In certain cases, a simple steady-state configuration may be as efficient as this time resolved fDOT system.
    Full-text · Article · Jun 2011 · Biomedical Optics Express
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