Abstract
Diffuse fluorescence tomography requires high contrast-to-background ratios to accurately reconstruct inclusions of interest. This is a problem when imaging the uptake of fluorescently labeled molecularly targeted tracers in tissue, which can result in high levels of heterogeneously distributed background uptake. We present a dual-tracer background subtraction approach, wherein signal from the uptake of an untargeted tracer is subtracted from targeted tracer signal prior to image reconstruction, resulting in maps of targeted tracer binding. The approach is demonstrated in simulations, a phantom study, and in a mouse glioma imaging study, demonstrating substantial improvement over conventional and homogenous background subtraction image reconstruction approaches.
Highlights
Fluorescence tomography (FT) is a promising molecular imaging modality that is capable of mapping biomolecule distributions in tissue without requiring the use of ionizing radiation, such as is required in competing nuclear medicine modalities
Data were created from forward model simulations on a 25-mm diameter two-dimensional (2-D) circular mesh with 1521 nodes corresponding to 2496 triangular elements, carried out using the open-source software, NIRFAST.[26]
It is clear that the quality of the fluorescence reconstruction was exceedingly sensitive to the level of background fluorescence, with substantial artifacts appearing after the third image, corresponding to a 4∶1 contrast-to-background ratio (CBR)
Summary
Fluorescence tomography (FT) is a promising molecular imaging modality that is capable of mapping biomolecule distributions in tissue without requiring the use of ionizing radiation, such as is required in competing nuclear medicine modalities. After injection, the tracer is dispersed throughout the body and over time it is cleared from the plasma and tissues that are devoid of the biomolecule of interest. It is retained in areas where it has bound to the targeted biomolecule, providing fluorescent contrast only in tissues where the receptor is ‘over-expressed.’. The strength of this approach is that the targeted molecule can be synthesized to bind most biomolecules of interest, and as long as the chosen biomolecule is in a region that can be accessed by the tracer, the approach should be practicable.
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