A Finite Element Mesh Aggregating Approach to Multiple-Source Reconstruction in Bioluminescence Tomography

A finite element mesh aggregating approach is presented to reconstruct images of multiple internal bioluminescence sources. Rather than assuming independence between mesh nodes, the proposed reconstruction strategy exploits spatial structure of nodes and aggregation feature of density distribution on the finite element mesh to adaptively determine the number of sources and to improve the quality of reconstructed images. With the proposed strategy integrated in the regularization-based reconstruction process, reconstruction algorithms need no a priori knowledge of source number; even more importantly, they can automatically reconstruct multiple sources that differ greatly in density or power

Bioluminescence tomography using eigenvectors expansion and iterative solution for the optimized permissible source region

A reconstruction algorithm for bioluminescence tomography (BLT) has been developed. The algorithm numerically calculates the Green’s function at different wavelengths using the diffusion equation and finite element method. The optical properties used in calculating the Green’s function are reconstructed using diffuse optical tomography (DOT) and assuming anatomical information is provided by x-ray computed tomography or other methods. A symmetric system of equations is formed using the Green’s function and the measured light fluence rate and the resulting eigenvalue problem is solved to get the eigenvectors of this symmetric system of equations. A space can be formed from the eigenvectors obtained and the reconstructed source is written as an expansion of the eigenvectors corresponding to non-zero eigenvalues. The coefficients of the expansion are found to obtain the reconstructed BL source distribution. The problem is solved iteratively by using a permissible source region that is shrunk by removing nodes with low probability to contribute to the source. Throughout this process the permissible region shrinks from the entire object to just a few nodes. The best estimate of the reconstructed source is chosen that which minimizes the difference between the calculated and measured light fluence rates. 3D simulations presented here show that the reconstructed source is in good agreement with the actual source in terms of locations, magnitudes, sizes, and total powers for both localized multiple sources and large inhomogeneous source distributions

Mathematical Methods in Tomography

This is the seventh Oberwolfach conference on the mathematics of tomography, the first one taking place in 1980. Tomography is the most popular of a series of medical and scientific imaging techniques that have been developed since the mid seventies of the last century

Fluorescence molecular tomography: Principles and potential for pharmaceutical research

Fluorescence microscopic imaging is widely used in biomedical research to study molecular and cellular processes in cell culture or tissue samples. This is motivated by the high inherent sensitivity of fluorescence techniques, the spatial resolution that compares favorably with cellular dimensions, the stability of the fluorescent labels used and the sophisticated labeling strategies that have been developed for selectively labeling target molecules. More recently, two and three-dimensional optical imaging methods have also been applied to monitor biological processes in intact biological organisms such as animals or even humans. These whole body optical imaging approaches have to cope with the fact that biological tissue is a highly scattering and absorbing medium. As a consequence, light propagation in tissue is well described by a diffusion approximation and accurate reconstruction of spatial information is demanding. While in vivo optical imaging is a highly sensitive method, the signal is strongly surface weighted, i.e., the signal detected from the same light source will become weaker the deeper it is embedded in tissue, and strongly depends on the optical properties of the surrounding tissue. Derivation of quantitative information, therefore, requires tomographic techniques such as fluorescence molecular tomography (FMT), which maps the three-dimensional distribution of a fluorescent probe or protein concentration. The combination of FMT with a structural imaging method such as X-ray computed tomography (CT) or Magnetic Resonance Imaging (MRI) will allow mapping molecular information on a high definition anatomical reference and enable the use of prior information on tissue’s optical properties to enhance both resolution and sensitivity. Today many of the fluorescent assays originally developed for studies in cellular systems have been successfully translated for experimental studies in animals. The opportunity of monitoring molecular processes non-invasively in the intact organism is highly attractive from a diagnostic point of view but even more so for the drug developer, who can use the techniques for proof-of-mechanism and proof-of-efficacy studies. This review shall elucidate the current status and potential of fluorescence tomography including recent advances in multimodality imaging approaches for preclinical and clinical drug development

Improved bioluminescence and fluorescence reconstruction algorithms using diffuse optical tomography, normalized data, and optimized selection of the permissible source region

Reconstruction algorithms are presented for two-step solutions of the bioluminescence tomography (BLT) and the fluorescence tomography (FT) problems. In the first step, a continuous wave (cw) diffuse optical tomography (DOT) algorithm is used to reconstruct the tissue optical properties assuming known anatomical information provided by x-ray computed tomography or other methods. Minimization problems are formed based on L1 norm objective functions, where normalized values for the light fluence rates and the corresponding Green’s functions are used. Then an iterative minimization solution shrinks the permissible regions where the sources are allowed by selecting points with higher probability to contribute to the source distribution. Throughout this process the permissible region shrinks from the entire object to just a few points. The optimum reconstructed bioluminescence and fluorescence distributions are chosen to be the results of the iteration corresponding to the permissible region where the objective function has its global minimum This provides efficient BLT and FT reconstruction algorithms without the need for a priori information about the bioluminescence sources or the fluorophore concentration. Multiple small sources and large distributed sources can be reconstructed with good accuracy for the location and the total source power for BLT and the total number of fluorophore molecules for the FT. For non-uniform distributed sources, the size and magnitude become degenerate due to the degrees of freedom available for possible solutions. However, increasing the number of data points by increasing the number of excitation sources can improve the accuracy of reconstruction for non-uniform fluorophore distributions

Use of prior information and probabilistic image reconstruction for optical tomographic imaging

Preclinical bioluminescence tomographic reconstruction is underdetermined. This work addresses the use of prior information in bioluminescence tomography to improve image acquisition, reconstruction, and analysis. A structured light surface metrology method was developed to measure surface geometry and enable robust and automatic integration of mirrors into the measurement process. A mouse phantom was imaged and accuracy was measured at 0.2mm with excellent surface coverage. A sparsity-regularised reconstruction algorithm was developed to use instrument noise statistics to automatically determine the stopping point of reconstruction. It was applied to in silico and in simulacra data and successfully reconstructed and resolved two separate luminescent sources within a plastic mouse phantom. A Bayesian framework was constructed that incorporated bioluminescence properties and instrument properties. Distribution expectations and standard deviations were estimated, providing reconstructions and measures of reconstruction uncertainty. The reconstructions showed superior performance when applied to in simulacra data compared to the sparsity-based algorithm. The information content of measurements using different sets of wavelengths was quantified using the Bayesian framework via mutual information and applied to an in silico problem. Significant differences in information content were observed and comparison against a condition number-based approach indicated subtly different results

Development of an optical imaging platform for functional imaging of small animals using wide-field excitation

The design and characterization of a time-resolved functional imager using a wide-field excitation scheme for small animal imaging is described. The optimal operation parameters are established based on phantom studies. The performance of the platform for functional imaging and the simultaneous 3D reconstruction of absorption and scattering coefficients is investigated in vitro