We studied the performance of three-dimensional fluorescence tomography of diffuse media in the presence of heterogeneities. Experimental measurements were acquired using an imaging system consisting of a parallel plate-imaging chamber and a lens coupled charge coupled device camera, which enables conventional planar imaging as well as fluorescence tomography. To simulate increasing levels of background heterogeneity, we employed phantoms made of a fluorescent tube surrounded by several absorbers in different combinations of absorption distribution. We also investigated the effect of low absorbing thin layers (such as membranes). We show that the normalized Born approach accurately retrieves the position and shape of the fluorochrome even at high background heterogeneity. We also demonstrate that the quantification is relatively insensitive to a varying degree of heterogeneity and background optical properties. Findings are further contrasted to images obtained with the standard Born expansion and with a normalized approach that divides the fluorescent field with excitation measurements through a homogeneous medium.
Fluorescence tomography of diffuse media can yield optimal three-dimensional imaging when multiple projections over 360 degrees geometries are captured, compared with limited projection angle systems such as implementations in the slab geometry. We demonstrate how it is possible to perform noncontact, 360 degrees projection fluorescence tomography of mice using CCD-camera-based detection in free space, i.e., in the absence of matching fluids. This approach achieves high spatial sampling of photons propagating through tissue and yields a superior information content data set compared with fiber-based 360 degrees implementations. Reconstruction feasibility using 36 projections in 10 degrees steps is demonstrated in mice.
Fluorescence imaging of tissues has gained significant attention in recent years due to the emergence of appropriate reporter technologies that enable noninvasive sensing of molecular function in vivo. Two major approaches have been used so far for fluorescence molecular imaging, i.e., epi-illumination (reflectance) imaging and fluorescence molecular tomography. Transillumination is an alternative approach that has been employed for imaging tissues in the past and could be similarly beneficial for fluorescence molecular imaging. We investigate data normalization schemes in reflectance and transillumination mode and experimentally demonstrate that normalized transillumination offers significant advantages over planar reflectance imaging and over nonnormalized methods. Our observations, based on phantoms and on postmortem and in vivo mouse measurements display image quality improvement, superior depth sensitivity, and improved imaging accuracy over the nonnormalized methods examined. Normalized planar imaging retains implementation simplicity and could be used to improve on standard fluorescence reflectance imaging and as a simplified alternative to the more integrated and accurate tomographic methods.
Fluorescence molecular tomography is an emerging imaging technique that resolves the bio-distribution of engineered fluorescent probes developed for in vivo reporting of specific cellular and sub-cellular targets. The method can detect fluorochromes in picomole amounts or less, imaged through entire animals, but the detection sensitivity and imaging performance drop in the presence of background, non-specific fluorescence. In this study, we carried out a theoretical and an experimental investigation on the effect of background fluorescence on the measured signal and on the tomographic reconstruction. We further examined the performance of three subtraction methods based on physical models of photon propagation, using experimental data on phantoms and small animals. We show that the data pre-processing with subtraction schemes can improve image quality and quantification when non-specific background florescence is present.
The small perturbations method has been extensively used for waves scattering by rough surfaces. The standard method developped by Rice is difficult to apply when we consider second and third order of scattered fields as a function of the surface height. Calculations can be greatly simplified with the use of reduced Rayleigh equations, because one of the unknown fields can be eliminated. We derive a new set of four reduced equations for the scattering amplitudes, which are applied to the cases of a rough conducting surface, and to a slab where one of the boundary is a rough surface. As in the one-dimensional case, numerical simulations show the appearance of enhanced backscattering for these structures.
We present the first, to our knowledge, experimental images of complex-shaped phantoms embedded in diffuse media by use of optical tomography. Imaging is based on a complete-angle projection tomographic technique that utilizes transmitted early photons. Results are contrasted with measurements obtained at later gates as well as pseudocontinuous-wave data. The scanning system developed employs noncontact illumination and detection technologies that allow for high spatial sampling of transmitted photons. Combining this system with complete-angle illumination is found to be an important strategy toward improved imaging performance, resulting in a better-posed inversion problem. The appropriateness of reconstruction algorithms similar to those employed in x-ray computed tomography are showcased, and suggestions for model improvements are provided.
The objective of this study was to model the pharmacokinetics (PKs) of robenacoxib in cats using a nonlinear mixed‐effects (NLME) approach, leveraging all available information collected from cats receiving robenacoxib s.c. and/or i.v.: 47 densely sampled laboratory cats and 36 clinical cats sparsely sampled preoperatively. Data from both routes were modeled sequentially using Monolix 4.3.2. Influence of parameter correlations and available covariates (age, gender, bodyweight, and anesthesia) on population parameter estimates were evaluated by using multiple samples from the posterior distribution of the random effects. A bicompartmental disposition model with simultaneous zero and first‐order absorption best described robenacoxib PKs in blood. Clearance was 0.502 L/kg/h and the bioavailability was high (78%). The absorption constant point estimate (Ka = 0.68 h−1) was lower than beta (median, 1.08 h−1), unveiling flip‐flop kinetics. No dosing adjustment based on available covariates information is advocated. This modeling work constitutes the first application of NLME in a large feline population.
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