A Coupled Finite Element-Boundary Element Method for Modeling Diffusion Equation in 3d Multi-Modality Optical Imaging

Three dimensional image reconstruction for multi-modality optical spectroscopy systems needs computationally efficient forward solvers with minimum meshing complexity, while allowing the flexibility to apply spatial constraints. Existing models based on the finite element method (FEM) require full 3D volume meshing to incorporate constraints related to anatomical structure via techniques such as regularization. Alternate approaches such as the boundary element method (BEM) require only surface discretization but assume homogeneous or piece-wise constant domains that can be limiting. Here, a coupled finite element-boundary element method (coupled FE-BEM) approach is demonstrated for modeling light diffusion in 3D, which uses surfaces to model exterior tissues with BEM and a small number of volume nodes to model interior tissues with FEM. Such a coupled FE-BEM technique combines strengths of FEM and BEM by assuming homogeneous outer tissue regions and heterogeneous inner tissue regions. Results with FE-BEM show agreement with existing numerical models, having RMS differences of less than 0.5 for the logarithm of intensity and 2.5 degrees for phase of frequency domain boundary data. The coupled FE-BEM approach can model heterogeneity using a fraction of the volume nodes (4-22%) required by conventional FEM techniques. Comparisons of computational times showed that the coupled FE-BEM was faster than stand-alone FEM when the ratio of the number of surface to volume nodes in the mesh (Ns/Nv) was less than 20% and was comparable to stand-alone BEM ( ± 10%)

Video-Rate Fluorescence Molecular Tomography for Hand-held and Multimodal Molecular Imaging

In the United States, cancer is the second leading cause of death following heart disease. Although, a variety of treatment regimens are available, cancer management is complicated by the complexity of the disease and the variability, between people, of disease progression and response to therapy. Therefore, advancements in the methods and technologies for cancer diagnosis, prognosis and therapeutic monitoring are critical to improving the treatment of cancer patients. The development of improved imaging methods for early diagnosis of cancer and of near real-time monitoring of tumor response to therapy may improve outcomes as well as the quality of life of cancer patients. In the last decade, imaging methods including ultrasound, computed tomography: CT), magnetic resonance imaging: MRI), single photon emission computed tomography: SPECT), and positron emission tomography: PET), have revolutionized oncology. More recently optical techniques, that have access to unique molecular reporting strategies and functional contrasts, show promise for oncologic imaging This dissertation focuses on the development and optimization of a fiber-based, video-rate fluorescence molecular tomography: FMT) instrument. Concurrent acquisition of fluorescence and reference signals allowed the efficient generation of ratio-metric data for 3D image reconstruction. Accurate depth localization and high sensitivity to fluorescent targets were established to depths of \u3e10 mm. In vivo accumulation of indocyanine green dye was imaged in the region of the sentinel lymph node: SLN) following intradermal injection into the forepaw of rats. These results suggest that video-rate FMT has potential as a clinical tool for noninvasive mapping of SLN. Spatial and temporal co-registration of nuclear and optical images can enable the fusion of the information from these complementary molecular imaging modalities. A critical challenge is in integrating the optical and nuclear imaging hardware. Flexible fiber-based FMT systems provide a viable solution. The various imaging bore sizes of small animal nuclear imaging systems can potentially accommodate the FMT fiber imaging arrays. In addition FMT imaging facilitates co-registering the nuclear and optical contrasts in time. In this dissertation, the feasibility of integrating the fiber-based, video-rate FMT system with a commercial preclinical NanoSPECT/CT platform was established. Feasibility of in vivo imaging is demonstrated by tracking a monomolecular multimodal-imaging agent: MOMIA) during transport from the forepaw to the axillary lymph nodes region of a rat. These co-registered FMT/SPECT/CT imaging results with MOMIAs may facilitate the development of the next generation preclinical and clinical multimodal optical-nuclear platforms for a broad array of imaging applications, and help elucidate the underlying biological processes relevant to cancer diagnosis and therapy monitoring. Finally, I demonstrated that video-rate FMT is sufficiently fast to enable imaging of cardiac, respiratory and pharmacokinetic induced dynamic fluorescent signals. From these measurements, the image-derived input function and the real-time uptake of injected agents can be deduced for pharmacokinetic analysis of fluorescing agents. In a study comparing normal mice against mice liver disease, we developed anatomically guided dynamic FMT in conjunction with tracer kinetic modeling to quantify uptake rates of fluorescing agents. This work establishes fiber-based, video-rate FMT system as a practical and powerful tool that is well suited to a broad array of potential imaging applications, ranging from early disease detection, quantifying physiology and monitoring progression of disease and therapies

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

Multi-Modality Diffuse Fluorescence Imaging Applied to Preclinical Imaging in Mice

RÉSUMÉ Cette thèse vise à explorer l'information anatomique et fonctionnelle en développant de nouveaux systèmes d'imagerie de fluorescence macroscopiques à base de multi-modalité. L‘ajout de l‘imagerie anatomique à des modalités fonctionnelles telles que la fluorescence permet une meilleure visualisation et la récupération quantitative des images de fluorescence, ce qui en retour permet d'améliorer le suivi et l'évaluation des paramètres biologiques dans les tissus. Sur la base de cette motivation, la fluorescence a été combinée avec l‘imagerie ultrasonore (US) d'abord et ensuite l'imagerie par résonance magnétique (IRM). Dans les deux cas, les performances du système ont été caractérisées et la reconstruction a été évaluée par des simulations et des expérimentations sur des fantômes. Finalement, ils ont été utilisés pour des expériences d'imagerie moléculaire in vivo dans des modèles de cancer et d‘athérosclérose chez la souris. Les résultats ont été présentés dans trois articles, qui sont inclus dans cette thèse et décrits brièvement ci-dessous. Un premier article présente un système d'imagerie bimodalité combinant fluorescence à onde continue avec l‘imagerie à trois dimensions (3D) US. A l‘aide de stages X-Y motorisés, le système d'imagerie a été en mesure de recueillir l‘émission fluorescente et les échos acoustiques délimitant la surface 3D et la position des inclusions fluorescentes dans l'échantillon. Une validation sur fantômes, a montré que l'utilisation des priors anatomiques provenant des US améliorait la qualité de la reconstruction fluorescente. En outre, un étude pilote in-vivo en utilisant une souris Apo-E a évalué la faisabilité de cette approche d'imagerie double modalité pour de futures études pré-cliniques. Dans un deuxième effort, et sur la base du premier travail, nous avons amélioré le système d'imagerie par fluorescence-US au niveau des algorithmes, de la précision----------ABSTRACT This thesis aims to explore the anatomical and functional information by developing new macroscopic multi-modality fluorescence imaging schemes. Adding anatomical imaging to functional modalities such as fluorescence enables better visualization and recovery of fluorescence images, in turn, improving the monitoring and assessment of biological parameters in tissue. Based on this motivation, fluorescence was combined with ultrasound (US) imaging first and then magnetic resonance imaging (MRI). In both cases, the systems characterization and reconstruction performance were evaluated by simulations and phantom experiments. Eventually, they were applied to in vivo molecular imaging in models of cancer and atherosclerosis in mice. Results were presented in three peer-reviewed journals, which are included in this thesis and shortly described below. A first article presented a dual-modality imaging system combining continuous-wave transmission fluorescence imaging with three dimensional (3D) US imaging. Using motorized X-Y stages, the fluorescence-US imaging system was able to collect boundary fluorescent emission, and acoustic pulse-echoes delineating the 3D surface and position of fluorescent inclusions within the sample. A validation in phantoms showed that using the US anatomical priors, the fluorescent reconstruction quality was significantly improved. Furthermore, a pilot in-vivo study using an Apo-E mouse evaluated the feasibility of this dual-modality imaging approach for future animal studies. In a second endeavor, and based on the first work, we improved the fluorescence-US imaging system in terms of sampling precision and reconstruction algorithms. Specifically, now combining US imaging and profilometry, both the fluorescent target and 3D surface of sample could be obtained in order to achieve improved fluorescence reconstruction. Furthermore,

Direct Regularization from Co-Registered Anatomical Images for MRI-Guided Near-Infrared Spectral Tomographic Image Reconstruction

Combining anatomical information from high resolution imaging modalities to guide near-infrared spectral tomography (NIRST) is an efficient strategy for improving the quality of the reconstructed spectral images. A new approach for incorporating image information directly into the inversion matrix regularization was examined using Direct Regularization from Images (DRI), which encodes the gray-scale data into the NIRST image reconstruction problem. This process has the benefit of eliminating user intervention such as image segmentation of distinct regions. Specifically, the Dynamic Contrast Enhanced Magnetic Resonance (DCE-MR) image intensity value differences within the anatomical image were used to implement an exponentially-weighted regularization function between the image pixels. The algorithm was validated using simulated reconstructions with noise, and the results showed that spatial resolution and robustness of the reconstructed images were significantly improved by appropriate choice of the regularization weight parameters. The proposed approach was also tested on in vivo breast data acquired in a recent clinical trial combining NIRST / MRI for cancer tumor characterization. Relative to the standard “no priors” diffuse recovery, the contrast of the tumor to the normal surrounding tissue increased from 2.4 to 3.6, and the difference between the tumor size segmented from DCE-MR images and reconstructed optical images decreased from 18% to 6%, while there was an overall decrease in surface artifacts

Molecular Imaging

The present book gives an exceptional overview of molecular imaging. Practical approach represents the red thread through the whole book, covering at the same time detailed background information that goes very deep into molecular as well as cellular level. Ideas how molecular imaging will develop in the near future present a special delicacy. This should be of special interest as the contributors are members of leading research groups from all over the world