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Dynamic fluorescence diffuse optical tomography (FDOT) is important for the research of drug delivery, medical diagnosis and treatment. Conventionally, dynamic tomographic images are reconstructed frame by frame, independently. This approach fails to account for the temporal correlations in measurement data. Ideally, the entire image sequence should be considered as a whole and a four-dimensional (4-D) reconstruction should be performed. However, the fully 4-D reconstruction is computationally intensive. In this paper, we propose a new 4-D reconstruction approach for dynamic FDOT, which is achieved by applying a temporal Karhunen-Loève (KL) transformation to the imaging equation. By taking advantage of the decorrelation and compression properties of the KL transformation, the complex 4-D optical reconstruction problem is greatly simplified. To evaluate the performance of the method, simulation, phantom, and in vivo experiments (N=7) are performed on a hybrid FDOT/x-ray computed tomography imaging system. The experimental results indicate that the reconstruction images obtained by the KL method provide good reconstruction quality. Additionally, by discarding high-order KL components, the computation time involved with fully 4-D reconstruction can be greatly reduced in contrast to the conventional frame-by-frame reconstruction.

Dynamic fluorescence diffuse optical tomography (D-FDOT) is important for drug delivery research. However, the low spatial resolution of FDOT and the complex kinetics of drug limit the ability of D-FDOT in resolving metabolic processes of drug throughout whole body of small animals. In this paper, we propose an independent component analysis (ICA)-based method to perform D-FDOT studies. When applied to D-FDOT images, ICA not only generates a set of independent components (ICs) which can illustrate functional structures with different kinetic behaviors, but also provides a set of associated time courses (TCs) which can represent normalized time courses of drug in corresponding functional structures. Further, the drug concentration in specific functional structure at different time points can be recovered by an inverse ICA transformation. To evaluate the performance of the proposed algorithm in the study of drug kinetics at whole-body level, simulation study and phantom experiment are both performed on a full-angle FDOT imaging system with line-shaped excitation pattern. In simulation study, the nanoparticle delivery of indocynaine green (ICG) throughout whole body of a digital mouse is simulated and imaged. In phantom experiment, four tubes containing different ICG concentrations are imaged and used to imitate the uptake and excretion of ICG in organs. The results suggest that we can not only illustrate ICG distributions in different functional structures, but also recover ICG concentrations in specific functional structure at different time points, when ICA is applied to D-FDOT images.

Most current efforts in near-infrared optical tomography are effectively limited to two-dimensional reconstructions due to the computationally intensive nature of full three-dimensional (3-D) data inversion. Previously, we described a new computationally efficient and statistically powerful inversion method APPRIZE (automatic progressive parameter-reducing inverse zonation and estimation). The APPRIZE method computes minimum-variance estimates of parameter values (here, spatially variant absorption due to a fluorescent contrast agent) and covariance, while simultaneously estimating the number of parameters needed as well as the size, shape, and location of the spatial regions that correspond to those parameters. Estimates of measurement and model error are explicitly incorporated into the procedure and implicitly regularize the inversion in a physically based manner. The optimal estimation of parameters is bounds-constrained, precluding infeasible values. In this paper, the APPRIZE method for optical imaging is extended for application to arbitrarily large 3-D domains through the use of domain decomposition. The effect of subdomain size on the performance of the method is examined by assessing the sensitivity for identifying 112 randomly located single-voxel heterogeneities in 58 3-D domains. Also investigated are the effects of unmodeled heterogeneity in background optical properties. The method is tested on simulated frequency-domain photon migration measurements at 100 MHz in order to recover absorption maps owing to fluorescent contrast agent. This study provides a new approach for computationally tractable 3-D optical tomography.

In this paper, we present a new method to form pharmacokinetic-rate images of optical fluorophores directly from near infra-red (NIR) boundary measurements. We first derive a mapping from spatially resolved pharmacokinetic rates to NIR boundary measurements by combining compartmental modeling with a diffusion based NIR photon propagation model. We express this mapping as a state-space equation. Next, we introduce a spatio-temporal prior model for the pharmacokinetic-rate images and combine it with the state-space equation. We address the image formation problem using the extended Kalman filtering framework. We analyze the computational complexity of the resulting algorithms and evaluate their performance in numerical simulations. An important feature of our approach is that the reconstruction of fluorescence concentrations and compartmental modeling are combined into a single step 1) to take advantage of the inherent temporal correlations in dynamic NIR measurements, and 2) to incorporate spatio-temporal a priori information on pharmacokinetic-rate images. Simulation results show that the resulting algorithms are more robust and lead to higher signal-to-noise ratio as compared to existing approaches where the reconstruction of concentrations and compartmental modeling are treated separately. Additionally, we reconstructed pharmacokinetic-rate images using in vivo data obtained from three patients with breast tumors. The reconstruction results show that the pharmacokinetic rates of indocyanine green are higher inside the tumor region as compared to the surrounding tissue.