KEYWORDS: Luminescence, Principal component analysis, Tomography, Tumors, Data modeling, Animal model studies, Absorption, 3D modeling, Tissues, Bioluminescence
We present here a new dynamic fluorescence tomographic model that makes use of spatial-temporal constraints in order to reconstruction both fluorescent biomarkers and anatomical structure simultaneously within reasonable accuracy. A discrete cosine transformation (DCT) is used to compress images in the spatial and temporal domains. The appropriate set of dominant DCT components is found from analyzing mouse internal structure and measurements of dynamic time traces of fluorescent signals. These sought characteristic functions are used later as spatial-temporal constraints in the reconstruction, which can aid to bring internal structure of major organs as well as fluorescent biomarkers into the reconstruction image. We use radiative transfer equation (RTE) as a light propagation model that provides more accurate predictions of light distribution in small geometries and high absorbing media. In addition, the reconstructed tomographic images are processed with principal components analysis (PCA) in order to differential between various regions with different functional kinetic behaviors. The performance of this new method is tested using a dynamic data of fluorescent signals resulting from changes in tumor vasculature in response to anti-angiogenesis, and the preliminary results have been presented to show the potential of the proposed dynamic fluorescence tomographic model.
Based on light propagation theory, the measurements of a contact-free imaging system with generalized optical components can be obtained from a linear transformation of the light intensity distribution on the surface of the imaging object. In this work, we derived the linear measurement operator needed to perform this transformation. Numerical experiments were designed and conducted for validation.
Whole body in vivo optical imaging of small animals has widened its applications and increased the capabilities for preclinical researches. However, most commercial and prototype optical imaging systems are camera-based systems using epi- or trans- illumination mode, with limited views of small animals. And for more accurate tomographic image reconstruction, additional data and information of a target animal is necessary. To overcome these issues, researchers have suggested several approaches such as maximizing the detection area or using the information of other highresolution modalities such as CT, MRI or Ultrasound, or using multi-spectral signals. As one of ways to maximizing the detection area of a target animal, we present a new fluorescence and bioluminescence imaging system for small animals, which can image entire surface of a target animal simultaneously. This system uses double mirror reflection scheme and it consists of input unit, imaging unit with two conical mirrors, the source illumination part and the surface scanner, and the detection unit with an intensified CCD camera system. Two conical mirrors are configured that a larger size mirror captures a target animal surface, and a smaller size mirror projects this captured image onto a CCD camera with one acquisition. With this scheme, we could capture entire surface of a target animal simultaneously and improve back reflection issue between a mirror and an animal surface of a single conical mirror scheme. Additionally, we could increase accessibility to an animal for multi-modality integration by providing unobstructed space around a target animal.
It is well acknowledged that treatment efficacy could be increased and unnecessary toxicities reduced if a rapid
assessment strategy were available to allow individual tailoring of cancer therapy. In this work we focus on using optical
tomographic imaging to detect tumor response to anti-angiogenic treatment within the first 5 days of therapy. For this
study we used two models with well-characterized and divergent responses to inhibition of vascular endothelial growth
factor (VEGF). SK-NEP and NGP cells were implanted intrarenally into NCR nude mice and the resulting tumors were
monitored until a threshold of 1-2 g was reached. Optical tomographic imaging with a dual-wavelength (λ = 765nm and
830nm) continuous wave system, was performed prior to the first treatment with the anti-VEGF bevacizumab (BV), as
well as 1, 3, and 5 days later. We found that the SK-NEP tumor model, known to be responsive to BV treatment, shows
a decrease in hemoglobin levels over the 5 days. Mice implanted with the NGP tumor model, known to be less
responsive to treatment, do not show such decreases. These results were further validated with histopathological findings
that showed a decrease in tumor vascularization in treated SK-NEP mice. These results suggest that optical tomography
is a promising tool for monitoring early tumor response to drug therapy.
We present an instrument for simultaneous imaging of the rodent brain with frequency-domain optical tomography and
magnetic resonance imaging. The instrument uses a custom-built fiber optic probe that allows for measurements in backreflectance
geometry. The probe consists of 13 source and 26 detector fibers and is small enough to fit inside of a microMRI RF coil with an inner diameter of 38mm. Illumination by the source fibers is time demultiplexed by an optical fiber switch. A gain-modulated image intensifier CCD camera focuses onto the endpoints of large-core gradedindex detector fibers and collects the frequency-domain data. Imaging can be performed with source-modulation frequencies up to 1 GHz. The instrument is capable of acquiring multi-frequency optical tomography data at 2 wavelengths, and the data can be used to generate 3D maps of hemoglobin concentrations. At the same time magnetic resonance images can be acquired with in-plane resolution smaller than 100 micron. To illustrate the performance of the instrument we show results of small animal studies that involve inhalation of 100% carbogen and chemically induced seizures.
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