Accelerating vasculature imaging in tumor using mesoscopic fluorescence molecular tomography via a hybrid reconstruction strategy.

Mesoscopic fluorescent molecular tomography (MFMT) enables to image fluorescent molecular probes beyond the typical depth limits of microscopic imaging and with enhanced resolution compared to macroscopic imaging. However, MFMT is a scattering-based inverse problem that is an ill-posed inverse problem and hence, requires relative complex iterative solvers coupled with regularization strategies. Inspired by the potential of deep learning in performing image formation tasks from raw measurements, this work proposes a hybrid approach to solve the MFMT inverse problem.

Accelerating Monte Carlo modeling of structured-light-based diffuse optical imaging via "photon sharing".

The increasing use of spatially modulated imaging and single-pixel detection techniques demands computationally efficient methods for light transport modeling. Herein, we report an easy-to-implement yet significantly more efficient Monte Carlo (MC) method for simultaneously simulating spatially modulated illumination and detection patterns accurately in 3D complex domains. We have implemented this accelerated algorithm, named "photon sharing," in our open-source MC simulators, reporting 13.

System configuration optimization for mesoscopic fluorescence molecular tomography.

Tissue engineering applications demand 3D, non-invasive, and longitudinal assessment of bioprinted constructs. Current emphasis is on developing tissue constructs mimicking conditions; however, these are increasingly challenging to image as they are typically a few millimeters thick and turbid, limiting the usefulness of classical fluorescence microscopic techniques. For such applications, we developed a Mesoscopic Fluorescence Molecular Tomography methodology that collects high information content data to enable high-resolution tomographic reconstruction of fluorescence biomarkers at millimeters depths.

Fast fit-free analysis of fluorescence lifetime imaging via deep learning.

Fluorescence lifetime imaging (FLI) provides unique quantitative information in biomedical and molecular biology studies but relies on complex data-fitting techniques to derive the quantities of interest. Herein, we propose a fit-free approach in FLI image formation that is based on deep learning (DL) to quantify fluorescence decays simultaneously over a whole image and at fast speeds. We report on a deep neural network (DNN) architecture, named fluorescence lifetime imaging network (FLI-Net) that is designed and trained for different classes of experiments, including visible FLI and near-infrared (NIR) FLI microscopy (FLIM) and NIR gated macroscopy FLI (MFLI).

Hyperspectral wide-field time domain single-pixel diffuse optical tomography platform.

We present the design and comprehensive instrumental characterization of a time domain diffuse optical tomography (TD-DOT) platform based on wide-field illumination and wide-field hyperspectral time-resolved single-pixel detection for functional and molecular imaging in turbid media. The proposed platform combines two digital micro-mirror devices (DMDs) to generate structured light and a spectrally resolved multi-anode photomultiplier tube (PMT) detector in time domain for hyperspectral data acquisition over 16 wavelength channels based on the time-correlated single-photon counting (TCSPC) technique. The design of the proposed platform is described in detail and its characteristics in spatial, temporal and spectral dimensions are calibrated and presented.

Net-FLICS: fast quantitative wide-field fluorescence lifetime imaging with compressed sensing - a deep learning approach.

Macroscopic fluorescence lifetime imaging (MFLI) via compressed sensed (CS) measurements enables efficient and accurate quantification of molecular interactions in vivo over a large field of view (FOV). However, the current data-processing workflow is slow, complex and performs poorly under photon-starved conditions. In this paper, we propose Net-FLICS, a novel image reconstruction method based on a convolutional neural network (CNN), to directly reconstruct the intensity and lifetime images from raw time-resolved CS data.

Direct approach to compute Jacobians for diffuse optical tomography using perturbation Monte Carlo-based photon "replay".

Perturbation Monte Carlo (pMC) has been previously proposed to rapidly recompute optical measurements when small perturbations of optical properties are considered, but it was largely restricted to changes associated with prior tissue segments or regions-of-interest. In this work, we expand pMC to compute spatially and temporally resolved sensitivity profiles, i.e.

Improving mesoscopic fluorescence molecular tomography via preconditioning and regularization.

Mesoscopic fluorescence molecular tomography (MFMT) is a novel imaging technique capable of obtaining 3-D distribution of molecular probes inside biological tissues at depths of a few millimeters with a resolution up to ~100 μm. However, the ill-conditioned nature of the MFMT inverse problem severely deteriorates its reconstruction performances. Furthermore, dense spatial sampling and fine discretization of the imaging volume required for high resolution reconstructions make the sensitivity matrix (Jacobian) highly correlated, which prevents even advanced algorithms from achieving optimal solutions.

Compressive hyperspectral time-resolved wide-field fluorescence lifetime imaging.

Spectrally resolved fluorescence lifetime imaging and spatial multiplexing have offered information content and collection-efficiency boosts in microscopy, but efficient implementations for macroscopic applications are still lacking. An imaging platform based on time-resolved structured light and hyperspectral single-pixel detection has been developed to perform quantitative macroscopic fluorescence lifetime imaging (MFLI) over a large field of view (FOV) and multiple spectral bands simultaneously. The system makes use of three digital micromirror device (DMD)-based spatial light modulators (SLMs) to generate spatial optical bases and reconstruct by images over 16 spectral channels with a time-resolved capability (~40 ps temporal resolution) using fewer than optical measurements.

Improving mesoscopic fluorescence molecular tomography through data reduction.

Mesoscopic fluorescence molecular tomography (MFMT) is a novel imaging technique that aims at obtaining the 3-D distribution of molecular probes inside biological tissues at depths of a few millimeters. To achieve high resolution, around 100-150μm scale in turbid samples, dense spatial sampling strategies are required. However, a large number of optodes leads to sizable forward and inverse problems that can be challenging to compute efficiently.

Generalized mesh-based Monte Carlo for wide-field illumination and detection via mesh retessellation.

Monte Carlo methods are commonly used as the gold standard in modeling photon transport through turbid media. With the rapid development of structured light applications, an accurate and efficient method capable of simulating arbitrary illumination patterns and complex detection schemes over large surface area is in great need. Here we report a generalized mesh-based Monte Carlo algorithm to support a variety of wide-field illumination methods, including spatial-frequency-domain imaging (SFDI) patterns and arbitrary 2-D patterns.

Wide-field fluorescence molecular tomography with compressive sensing based preconditioning.

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.

Hyperspectral time-resolved wide-field fluorescence molecular tomography based on structured light and single-pixel detection.

We present a time-resolved fluorescence diffuse optical tomography platform that is based on wide-field structured illumination, single-pixel detection, and hyperspectral acquisition. Two spatial light modulators (digital micro-mirror devices) are employed to generate independently wide-field illumination and detection patterns, coupled with a 16-channel spectrophotometer detection module to capture hyperspectral time-resolved tomographic data sets. The main system characteristics are reported, and we demonstrate the feasibility of acquiring dense 4D tomographic data sets (space, time, spectra) for time domain 3D quantitative multiplexed fluorophore concentration mapping in turbid media.