3D shape based reconstruction of experimental data in Diffuse Optical Tomography

Diffuse optical tomography (DOT) aims at recovering three-dimensional images of absorption and scattering parameters inside diffusive body based on small number of transmission measurements at the boundary of the body. This image reconstruction problem is known to be an ill-posed inverse problem, which requires use of prior information for successful reconstruction. We present a shape based method for DOT, where we assume a priori that the unknown body consist of disjoint subdomains with different optical properties. We utilize spherical harmonics expansion to parameterize the reconstruction problem with respect to the subdomain boundaries, and introduce a finite element (FEM) based algorithm that uses a novel 3D mesh subdivision technique to describe the mapping from spherical harmonics coefficients to the 3D absorption and scattering distributions inside a unstructured volumetric FEM mesh. We evaluate the shape based method by reconstructing experimental DOT data, from a cylindrical phantom with one inclusion with high absorption and one with high scattering. The reconstruction was monitored, and we found a 87% reduction in the Hausdorff measure between targets and reconstructed inclusions, 96% success in recovering the location of the centers of the inclusions and 87% success in average in the recovery for the volumes

Image-Guided Diffuse Optical Fluorescence Tomography Implemented with Laplacian-Type Regularization

A promising method to incorporate tissue structural information into the reconstruction of diffusion-based fluorescence imaging is introduced. The method regularizes the inversion problem with a Laplacian-type matrix, which inherently smoothes pre-defined tissue, but allows discontinuities between adjacent regions. The technique is most appropriately used when fluorescence tomography is combined with structural imaging systems. Phantom and simulation studies were used to illustrate significant improvements in quantitative imaging and linearity of response with the new algorithm. Images of an inclusion containing the fluorophore Lutetium Texaphyrin (Lutex) embedded in a cylindrical phantom are more accurate than in situations where no structural information is available, and edge artifacts which are normally prevalent were almost entirely suppressed. Most importantly, spatial priors provided a higher degree of sensitivity and accuracy to fluorophore concentration, though both techniques suffer from image bias caused by excitation signal leakage. The use of spatial priors becomes essential for accurate recovery of fluorophore distributions in complex tissue volumes. Simulation studies revealed an inability of the “no-priors” imaging algorithm to recover Lutex fluorescence yield in domains derived from T1 weighted images of a human breast. The same domains were reconstructed accurately to within 75% of the true values using prior knowledge of the internal tissue structure. This algorithmic approach will be implemented in an MR-coupled fluorescence spectroscopic tomography system, using the MR images for the structural template and the fluorescence data for region quantification

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

Noncontact Speckle Contrast Diffuse Correlation Tomography of Blood Flow Distributions in Tissues with Arbitrary Geometries

A noncontact electron multiplying charge-coupled-device (EMCCD)-based speckle contrast diffuse correlation tomography (scDCT) technology has been recently developed in our laboratory, allowing for noninvasive three-dimensional measurement of tissue blood flow distributions. One major remaining constraint in the scDCT is the assumption of a semi-infinite tissue volume with a flat surface, which affects the image reconstruction accuracy for tissues with irregular geometries. An advanced photometric stereo technique (PST) was integrated into the scDCT system to obtain the surface geometry in real time for image reconstruction. Computer simulations demonstrated that a priori knowledge of tissue surface geometry is crucial for precisely reconstructing the anomaly with blood flow contrast. Importantly, the innovative integration design with one single-EMCCD camera for both PST and scDCT data collection obviates the need for offline alignment of sources and detectors on the tissue boundary. The in vivo imaging capability of the updated scDCT is demonstrated by imaging dynamic changes in forearm blood flow distribution during a cuff-occlusion procedure. The feasibility and safety in clinical use are evidenced by intraoperative imaging of mastectomy skin flaps and comparison with fluorescence angiography