Abstract
An advantage of fluorescence methods over other imaging modalities is the ability to concurrently resolve multiple moieties using fluorochromes emitting at different spectral regions. Simultaneous imaging of spectrally separated agents is helpful in interrogating multiple functions or establishing internal controls for accurate measurements. Herein, we investigated multimoiety imaging in the context of a limited-projection-angle hybrid fluorescence molecular tomography (FMT), and x-ray computed tomography implementation and the further registration with positron emission tomography (PET) data. Multichannel FMT systems may image fluorescent probes of varying distribution patterns. Therefore, it is possible that different channels may require different use of priors and regularization parameters. We examined the performance of automatically estimating regularization factors implementing priors, using data-driven regularization specific for limited-projection-angle schemes. We were particularly interested in identifying the implementation variations between hybrid-FMT channels due to probe distribution variation. For this reason, initial validation of the data-driven algorithm on a phantom was followed by imaging different agent distributions in animals, assuming superficial and deep seated activity. We further demonstrate the benefits of combining hybrid FMT with PET to gain multiple readings on the molecular composition of disease.
Highlights
Fluorescence molecular tomography (FMT) reconstructs the biodistribution of fluorescent agents and reporters that enable noninvasive in vivo imaging of cells and cellular moieties in small animals or other tissues.[1,2,3,4] This basic ability can study disease progression or monitor therapy noninvasively in vivo using nonionizing energy.[4,5] An important feature of fluorescence tomography is the ability to visualize different functional or molecular parameters in the same animal, using fluorochromes emitting at different spectral bands
The top two phantom slices show the same reconstruction with regularization factors computed with λ3, but with different scaling to bring out the maximum signal in the right tube
We aimed at enabling simultaneous investigation of multiple molecules using limited-projection-angle, hybrid FMT-x-ray computed tomography (XCT), a capacity not documented before in the literature
Summary
Fluorescence molecular tomography (FMT) reconstructs the biodistribution of fluorescent agents and reporters that enable noninvasive in vivo imaging of cells and cellular moieties in small animals or other tissues.[1,2,3,4] This basic ability can study disease progression or monitor therapy noninvasively in vivo using nonionizing energy.[4,5] An important feature of fluorescence tomography is the ability to visualize different functional or molecular parameters in the same animal, using fluorochromes emitting at different spectral bands. One advantage of approaches like this is the creation of internal controls using, e.g., an active and an inactive form of an agent, each labeled with a different fluorochrome.[6,7] In this example, biodistribution and delivery of the agent can be separated by active targeting on the same animal by comparing the images at the two fluorescence channels. Different contrast mechanisms can be concurrently studied, e.g., the relative expression of different receptors or the relative concentrations of different types of cells
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