Imaging performance of a hybrid x-ray computed tomography-fluorescence molecular tomography system using priors.

PURPOSE: The performance is studied of two newly introduced and previously suggested methods that incorporate priors into inversion schemes associated with data from a recently developed hybrid x-ray computed tomography and fluorescence molecular tomography system, the latter based on CCD camera photon detection. The unique data set studied attains accurately registered data of high spatially sampled photon fields propagating through tissue along 360 degrees projections. METHODS: Approaches that incorporate structural prior information were included in the inverse problem by adding a penalty term to the minimization function utilized for image reconstructions. Results were compared as to their performance with simulated and experimental data from a lung inflammation animal model and against the inversions achieved when not using priors. RESULTS: The importance of using priors over stand-alone inversions is also showcased with high spatial sampling simulated and experimental data. The approach of optimal performance in resolving fluorescent biodistribution in small animals is also discussed. CONCLUSIONS: Inclusion of prior information from x-ray CT data in the reconstruction of the fluorescence biodistribution leads to improved agreement between the reconstruction and validation images for both simulated and experimental data.

Fundamentals of optical imaging.

Optical imaging techniques offer simplistic while highly sensitive modalities for molecular imaging research. In this chapter, the major instrumental necessities for microscopic and whole-animal imaging techniques are introduced. Subsequently, the resulting imaging modalities using visible or near-infrared light are presented and discussed. The aim is to show the current capabilities and application fields of optics.

Effects of Pax8 and TTF-1 thyroid transcription factor gene transfer in hepatoma cells: imaging of functional protein-protein interaction and iodide uptake.

UNLABELLED: The thyroid transcription factors TTF-1 and Pax8 cooperate in the transcriptional activation of thyroid-specific genes such as thyroglobulin (Tg), thyroperoxidase (TPO), and sodium/iodide symporter (NIS). METHODS: Dog TTF-1 (dTTF-1) and the human Pax8 (hPax8) gene were transfected in Morris hepatoma (MH3924A) cells to investigate (a) the possible visualization of functional protein-protein interaction and (b) the induction of thyroid-specific gene expression. In MH3924A cell lines expressing dTTF-1, hPax8, or both, the activation of human Tg (hTg), human TPO (hTPO), or rat NIS (rNIS) promoter/enhancer was measured using firefly luciferase reporter constructs. Furthermore, the possible induction of thyroid-specific genes was investigated in iodide uptake and reverse transcription polymerase chain reaction (RT-PCR) experiments. RESULTS: Low transcriptional activation of these constructs was observed in cells expressing either hPax8 or dTTF-1 alone. In contrast, the hTg and hTPO and, to a lesser extent, the rNIS regulatory region were significantly activated in cell lines expressing both transcription factors. Imaging the transcriptional activation of the thyroid-specific regulatory regions by Pax8 and TTF-1 was possible in nude mice implanted with MHhPax8dTTF-1 cells using a cooled charge-coupled device camera. Na(125)I uptake experiments and RT-PCR showed no effect of hPax8 and dTTF-1 on endogenous thyroid-specific gene expression in genetically modified cells. CONCLUSION: The activation of thyroid-specific promoter/enhancer elements in Morris hepatoma cells depends on the functional interaction of hPax8 and dTTF-1. The cooperation of these 2 transcription factors can be visualized in vitro as well as in vivo. With regard to a possible application for radioiodine therapy, further modifications are required.

[Principles of optical and fluorescence mediated tomography in turbid media]. / Grundlagen optischer und fluoreszenzgestützter Tomographie in diffusen Medien.

Three-dimensional, tomographic imaging of biological tissues by means of visible light is becoming increasingly important. Current progress in the mathematical-physical modelling of photon propagation in scattering media allows spatially-resolved reconstructions of optical parameters with common computing hardware. Especially in the field of molecular imaging, optical tomography promises a transfer of knowledge from successful in vitro assays (as evaluated by fluorescence microscopy) to in vivo imaging of living animals. In the latter case, spatial resolution is not as critical as the ability to quantify the concentration of fluorescence-labelled probes, a task not solvable by the use of common planar imaging techniques. In this article, the theoretical foundations of optical tomography are introduced along with some examples of applications.

Experimental fluorescence tomography of tissues with noncontact measurements.

Noncontact optical measurements from diffuse media could facilitate the use of large detector arrays at multiple angles that are well suited for diffuse optical tomography applications. Such imaging strategy could eliminate the need for individual fibers in contact with tissue, restricted geometries, and matching fluids. Thus, it could significantly improve experimental procedures and enhance our ability to visualize functional and molecular processes in vivo. In this paper, we describe the experimental implementation of this novel concept and demonstrate capacity to perform small animal imaging.

Hybrid system for simultaneous fluorescence and x-ray computed tomography.

A hybrid imaging system for simultaneous fluorescence tomography and X-ray computed tomography (XCT) of small animals has been developed and presented. The system capitalizes on the imaging power of a 360 ( degrees )-projection free-space fluorescence tomography system, implemented within a microcomputed tomography scanner. Image acquisition is based on techniques that automatically adjust a series of imaging parameters to offer a high dynamic range dataset. Image segmentation further allows the incorporation of structural priors in the optical reconstruction problem to improve the imaging performance. The functional system characteristics are showcased, and images from a brain imaging study are shown, which are reconstructed using XCT-derived priors into the optical forward problem.

Fast automatic segmentation of anatomical structures in x-ray computed tomography images to improve fluorescence molecular tomography reconstruction.

The recent development of hybrid imaging scanners that integrate fluorescence molecular tomography (FMT) and x-ray computed tomography (XCT) allows the utilization of x-ray information as image priors for improving optical tomography reconstruction. To fully capitalize on this capacity, we consider a framework for the automatic and fast detection of different anatomic structures in murine XCT images. To accurately differentiate between different structures such as bone, lung, and heart, a combination of image processing steps including thresholding, seed growing, and signal detection are found to offer optimal segmentation performance. The algorithm and its utilization in an inverse FMT scheme that uses priors is demonstrated on mouse images.

Adjoint time domain method for fluorescent imaging in turbid media.

Application of adjoint time domain methods to the inverse problem in 3D fluorescence imaging is a novel approach. We demonstrate the feasibility of this approach experimentally on the basis of a time gating technique completely in the time domain by using a small number of time windows. The evolution of the fluorescence energy density function inside a highly scattering cylinder was reconstructed together with optical parameters. Reconstructed energy density was used in localizing two fluorescent tubes. Relatively accurate reconstruction demonstrates the effectiveness and the potential of the proposed technique.

Comparison of noncontact and fiber-based fluorescence-mediated tomography.

We present a comparative experimental phantom study of fiber-based and noncontact fluorescence tomography with respect to quantitation and localization of reconstructed fluorescent inclusions in turbid media such as tissue. Noncontact acquisition is usually considered potentially superior to fiber-based techniques because of the availability of a large number of detector readouts through a CCD. Our results indicate, however, that noncontact acquisition itself might improve the quality of reconstructions significantly, even without increasing the number of detectors and thus keeping the inverse problem moderately complex.

Noncontact optical tomography of turbid media.

Optical tomography of turbid media has so far been limited by systems that require fixed geometries or measurements employing fibers. We present a system that records noncontact optical measurements from diffuse media of arbitrary shapes and retrieves the three-dimensional surface information of the diffuse medium. We further present a novel method of combining this composite data set and obtain accurate fluorescence reconstructions. This approach offers significant experimental simplicity and yields high-information-content datasets. The performance of this novel tomographic approach is demonstrated with experimental reconstructions of phantoms.

Free-space propagation of diffuse light: theory and experiments.

In this Letter we present a simple and novel theoretical approach for modeling the intensity distribution from an arbitrarily shaped turbid volume in a noncontact geometry by considering diffuse light propagation in free space. This theory is validated with experiments for a diffusive volume of known geometry in a noncontact situation, both with and without the presence of an embedded absorber. The implications of this new formulation in the context of optical tomography in turbid media are discussed.