Quantitative tomographic imaging of intermolecular FRET in small animals

Venugopal, Vivek; Chen, Jin; Barroso, Margarida; Intes, Xavier

doi:10.1364/boe.3.003161

Cited by 75 publications

(65 citation statements)

References 45 publications

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“…These gates were selected on the rising part of the TPSF as it correlates to resolution improvement in the reconstruction, whereas late gates are critical in lifetime multiplexed studies, which we do not consider herein. 16,27 Figure 13(a) and 13(b) shows the 50% iso-volumes of the effective quantum yield obtained by solving the inverse problem by least-squares minimization. The lower number of source-detector pairs available when using the uniform pattern set (more than 36% reduction) leads to reduced tomographic information in the measurements as discussed previously.…”

Section: Reconstruction Resultsmentioning

confidence: 99%

Adaptive wide-field optical tomography

Venugopal

Intes

2013

J. Biomed. Opt.

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Abstract. We describe a wide-field optical tomography technique, which allows the measurement-guided optimization of illumination patterns for enhanced reconstruction performances. The iterative optimization of the excitation pattern aims at reducing the dynamic range in photons transmitted through biological tissue. It increases the number of measurements collected with high photon counts resulting in a dataset with improved tomographic information. Herein, this imaging technique is applied to time-resolved fluorescence molecular tomography for preclinical studies. First, the merit of this approach is tested by in silico studies in a synthetic small animal model for typical illumination patterns. Second, the applicability of this approach in tomographic imaging is validated in vitro using a small animal phantom with two fluorescent capillaries occluded by a highly absorbing inclusion. The simulation study demonstrates an improvement of signal transmitted (∼2 orders of magnitude) through the central portion of the small animal model for all patterns considered. A corresponding improvement in the signal at the emission wavelength by 1.6 orders of magnitude demonstrates the applicability of this technique for fluorescence molecular tomography. The successful discrimination and localization (∼1 mm error) of the two objects with higher resolution using the optimized patterns compared with nonoptimized illumination establishes the improvement in reconstruction performance when using this technique.

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Section: Reconstruction Resultsmentioning

confidence: 99%

Adaptive wide-field optical tomography

Venugopal

Intes

2013

J. Biomed. Opt.

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“…Similar compressive imaging work in FMT was reported later on by Ducros et al who used a wavelet base [5]. Beside validations in well-controlled settings, the method has been applied in vivo to quantify FRET signals [6], with applications in drug delivery monitoring [7].…”

Section: Introductionmentioning

confidence: 73%

“…A 20mm thick phantom with optical properties of μ a = 0.1cm −1 and μ s ' = 9.6cm −1 was created using the recipe described in ref 6 and validated via time-resolved spectroscopy. Two tubes (3.0mm diameter and 15.5mm center-center distance) with different fluorescence dyes, Alexa Fluor 750 and 3.3′-diethylthiatricarbocyanine iodide, were placed at 10mm depth in the phantom.…”

Section: Experimental Validationmentioning

confidence: 99%

Wide-field fluorescence molecular tomography with compressive sensing based preconditioning

Yao¹,

Pian²,

Intes³

2015

Biomed. Opt. Express

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Wide-field optical tomography based on structured light illumination and detection strategies enables efficient tomographic imaging of large tissues at very fast acquisition speeds. However, the optical inverse problem based on such instrumental approach is still ill-conditioned. Herein, we investigate the benefit of employing compressive sensing-based preconditioning to wide-field structured illumination and detection approaches. We assess the performances of Fluorescence Molecular Tomography (FMT) when using such preconditioning methods both in silico and with experimental data. Additionally, we demonstrate that such methodology could be used to select the subset of patterns that provides optimal reconstruction performances. Lastly, we compare preconditioning data collected using a normal base that offers good experimental SNR against that directly acquired with optimal designed base. An experimental phantom study is provided to validate the proposed technique.

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“…This is because FD% is positively dependent on A:D ratios and independent of acceptor levels in clustered interactions [9,18,19]. Specifically, the fluorescence intensity of donor is reduced when FRET occurs.…”

Section: Evaluation Of the Awfi Performance For Ex Vivo Biodistributionmentioning

confidence: 99%

“…FLIM can overcome the limitations caused by fluorescence intensity based FRET, such as spectral bleed-through and crosstalk. The combination of FLIM and FRET is a promising modality for monitoring the dynamics of therapeutic drug release in the treatment of diseases with high spatial and temporal resolution from in vitro [8] to in vivo [9].…”

Section: Introductionmentioning

confidence: 99%

Spatial light modulator based active wide-field illumination for ex vivo and in vivo quantitative NIR FRET imaging

Zhao¹,

Abe²,

Rajoria³

et al. 2014

Biomed. Opt. Express

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Fluorescence lifetime imaging is playing an increasing role in drug development by providing a sensitive method to monitor drug delivery and receptor-ligand interactions. However, the wide dynamic range of fluorescence intensity emitted by ex vivo and in vivo samples presents challenges in retrieving information over the whole subject accurately and quantitatively. To overcome this challenge, we developed an active widefield illumination (AWFI) strategy based on a spatial light modulator that acquires optimal fluorescence signals by enhancing the dynamic range, signal to noise ratio, and estimation of lifetime-based parameters. We demonstrate the ability of AWFI to estimate Förster resonance energy transfer (FRET) donor fraction from dissected organs with high accuracy (standard deviation <6%) over the whole field of view, in contrast with the homogenous wide-field illumination. We further report its successful application to quantitative FRET imaging in a live mouse. AWFI allows improved detection of weak signals and enhanced quantitative accuracy in ex vivo and in vivo molecular fluorescence quantitative imaging. The technique allows for robust quantitative estimation of the bio-distribution of molecular probes and lifetime-based parameters over an extended imaging field exhibiting a large range of fluorescence intensities and at a high acquisition speed (less than 1 min).

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Quantitative tomographic imaging of intermolecular FRET in small animals

Cited by 75 publications

References 45 publications

Adaptive wide-field optical tomography

Adaptive wide-field optical tomography

Wide-field fluorescence molecular tomography with compressive sensing based preconditioning

Spatial light modulator based active wide-field illumination for ex vivo and in vivo quantitative NIR FRET imaging

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