Singular-value analysis and optimization of experimental parameters in fluorescence molecular tomography.

The advent of specific molecular markers and probes employing optical reporters has encouraged the application of in vivo diffuse tomographic imaging at greater spatial resolutions and hence data-set volumes. This study applied singular-value analysis (SVA) of the fluorescence tomographic problem to determine optimal source and detector distributions that result in data sets that are balanced between information content and size. Weight matrices describing the tomographic forward problem were constructed for a range of source and detector distributions and fields of view and were decomposed into their associated singular values.

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.

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.

In vivo tomographic imaging of near-infrared fluorescent probes.

Fluorescence imaging is increasingly used to probe protein function and gene expression in live animals. This technology could enhance the study of pathogenesis, drug development, and therapeutic intervention. In this article, we focus on three-dimensional fluorescence observations using fluorescence-mediated molecular tomography (FMT), a novel imaging technique that can resolve molecular function in deep tissues by reconstructing fluorescent probe distributions in vivo.

Optical imaging of apoptosis as a biomarker of tumor response to chemotherapy.

A rapid and accurate assessment of the antitumor efficacy of new therapeutic drugs could speed up drug discovery and improve clinical decision making. Based on the hypothesis that most effective antitumor agents induce apoptosis, we developed a near-infrared fluorescent (NIRF) annexin V to be used for optical sensing of tumor environments. To demonstrate probe specificity, we developed both an active (i.

Iterative boundary method for diffuse optical tomography.

The recent application of tomographic methods to three-dimensional imaging through tissue by use of light often requires modeling of geometrically complex diffuse-nondiffuse boundaries at the tissue-air interface. We have recently investigated analytical methods to model complex boundaries by means of the Kirchhoff approximation. We generalize this approach using an analytical approximation, the N-order diffuse-reflection boundary method, which considers higher orders of interaction between surface elements in an iterative manner.

A submillimeter resolution fluorescence molecular imaging system for small animal imaging.

Most current imaging systems developed for tomographic investigations of intact tissues using diffuse photons suffer from a limited number of sources and detectors. In this paper we describe the construction and evaluation of a large dataset, low noise tomographic system for fluorescence imaging in small animals. The system consists of a parallel plate-imaging chamber and a lens coupled CCD camera, which enables conventional planar imaging as well as fluorescence tomography.

Optical-based molecular imaging: contrast agents and potential medical applications.

Laser- and sensitive charge-coupled device technology together with advanced mathematical modelling of photon propagation in tissue has prompted the development of novel optical imaging technologies. Fast surface-weighted imaging modalities, such as fluorescence reflectance imaging (FRI) and 3D quantitative fluorescence-mediated tomography have now become available [1, 2]. These technical advances are paralleled by a rapid development of a whole range of new optical contrasting strategies, which are designed to generate molecular contrast within a living organism.

Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging.

A recent development in biomedical imaging is the non-invasive mapping of molecular events in intact tissues using fluorescence. Underpinning to this development is the discovery of bio-compatible, specific fluorescent probes and proteins and the development of highly sensitive imaging technologies for in vivo fluorescent detection. Of particular interest are fluorochromes that emit in the near infrared (NIR), a spectral window, whereas hemoglobin and water absorb minimally so as to allow photons to penetrate for several centimetres in tissue.

Steady-state blood volume measurements in experimental tumors with different angiogenic burdens a study in mice.

Purpose: To experimentally validate the effectiveness of magnetic resonance (MR) imaging enhanced with long-circulating iron oxide for measurement of vascular volume fractions (VVFs) as indicators of angiogenesis in different experimental tumor models.

Materials And Methods: Tumors with differing degrees of angiogenesis-9L rodent gliosarcoma, DU4475 human mammary adenocarcinoma, HT1080 human fibrosarcoma, and EOMA hemangioendothelioma--were implanted in nude mice. Tumoral VVFs were measured at submillimeter voxel resolutions by using 1.

Fluorescence molecular tomography resolves protease activity in vivo.

Systematic efforts are under way to develop novel technologies that would allow molecular sensing in intact organisms in vivo. Using near-infrared fluorescent molecular beacons and inversion techniques that take into account the diffuse nature of photon propagation in tissue, we were able to obtain three-dimensional in vivo images of a protease in orthopic gliomas. We demonstrate that enzyme-activatable fluorochromes can be detected with high positional accuracy in deep tissues, that molecular specificities of different beacons towards enzymes can be resolved and that tomography of beacon activation is linearly related to enzyme concentration.

MRI-guided diffuse optical spectroscopy of malignant and benign breast lesions.

We present the clinical implementation of a novel hybrid system that combines magnetic resonance imaging (MRI) and near-infrared (NIR) optical measurements for the noninvasive study of breast cancer in vivo. Fourteen patients were studied with a MR-NIR prototype imager and spectrometer. A diffuse optical tomographic scheme employed the MR images as a priori information to implement an image-guided NIR localized spectroscopic scheme.

In vivo imaging of proteolytic activity in atherosclerosis.

Background: Atherosclerotic plaque rupture, the most important cause of acute cardiovascular incidents, has been strongly associated with vascular inflammation. On the basis of the hypothesis that the inflammatory response and proteolysis lead to plaque rupture, we have examined the role of cathepsin B as a model proteolytic enzyme.

Methods And Results: Using western-type diet-fed apoE and apoE/endothelial NO synthase double knockout mice as models of atherosclerosis, we show (1) that cathepsin B is upregulated in atherosclerotic lesions characterized by high degrees of inflammation compared with normal aorta or silent lesions, (2) that intravenously injectable novel cathepsin B imaging beacons are highly activated within active atherosclerotic lesions and colocalize with cathepsin B immunoreactivity, and (3) that cathepsin B activity in atherosclerotic lesions can be imaged in whole animals by using a novel near-infrared tomographic imaging system.

Charge-coupled-device based scanner for tomography of fluorescent near-infrared probes in turbid media.

We present a novel tomographer for three-dimensional reconstructions of fluorochromes in diffuse media. Photon detection is based on charge-coupled device technology that allows the implementation of a large parallel array of detection channels with high sensitivity. Using this instrument we studied the response and detection limits of near-infrared fluorochromes in diffuse media as a function of light intensity and for a wide range of biologically relevant concentrations.

Projection access order in algebraic reconstruction technique for diffuse optical tomography.

Algebraic reconstruction technique (ART) is one of the popular image reconstruction techniques used in diffuse optical tomography (DOT). We investigate in this note the influence of the order in which data are accessed in ART. Simulations mimicking breast tissues in transmission geometry with contrast agent tumour enhancement were used to evaluate the image quality of the diverse projection access investigated.

High throughput magnetic resonance imaging for evaluating targeted nanoparticle probes.

The ability to image specific molecular targets in vivo would have significant impact in allowing earlier disease detection and in tailoring molecular therapies. One of the rate-limiting steps in the development of novel compounds as reporter probes has been the lack of cell-based, biologically relevant, high throughput screening methods. Here we describe the development and validation of magnetic resonance imaging (MRI) as a technique to rapidly screen compounds that are potential MR reporter agents for their interaction with specific cellular targets.

Analytical model for dual-interfering sources diffuse optical tomography.

An analytical model to perform tomographic reconstructions for absorptive inclusions in highly scattering media using dual interfering sources was derived. A perturbation approach within the first order Rytov expansion was used to solve the heterogeneous diffusion equation. Analytical weight functions necessary to solve the inverse problem were obtained.