Abstract

BackgroundThe bioluminescent enzyme firefly luciferase (Luc) or variants of green fluorescent protein (GFP) in transformed cells can be effectively used to reveal molecular and cellular features of neoplasia in vivo. Tumor cell growth and regression in response to various therapies can be evaluated by using bioluminescent imaging. In bioluminescent imaging, light propagates in highly scattering tissue, and the diffusion approximation is sufficiently accurate to predict the imaging signal around the biological tissue. The numerical solutions to the diffusion equation take large amounts of computational time, and the studies for its analytic solutions have attracted more attention in biomedical engineering applications.MethodsBiological tissue is a turbid medium that both scatters and absorbs photons. An accurate model for the propagation of photons through tissue can be adopted from transport theory, and its diffusion approximation is applied to predict the imaging signal around the biological tissue. The solution to the diffusion equation is formulated by the convolution between its Green's function and source term. The formulation of photon diffusion from spherical bioluminescent sources in an infinite homogeneous medium can be obtained to accelerate the forward simulation of bioluminescent phenomena.ResultsThe closed form solutions have been derived for the time-dependent diffusion equation and the steady-state diffusion equation with solid and hollow spherical sources in a homogeneous medium, respectively. Meanwhile, the relationship between solutions with a solid sphere source and ones with a surface sphere source is obtained.ConclusionWe have formulated solutions for the diffusion equation with solid and hollow spherical sources in an infinite homogeneous medium. These solutions have been verified by Monte Carlo simulation for use in biomedical optical imaging studies. The closed form solution is highly accurate and more computationally efficient in biomedical engineering applications. By using our analytic solutions for spherical sources, we can better predict bioluminescent signals and better understand both the potential for, and the limitations of, bioluminescent tomography in an idealized case. The formulas are particularly valuable for furthering the development of bioluminescent tomography.

Highlights

  • The bioluminescent enzyme firefly luciferase (Luc) or variants of green fluorescent protein (GFP) in transformed cells can be effectively used to reveal molecular and cellular features of neoplasia in vivo

  • The radiative transfer equation can be reduced to the diffusion equation, but this still does not permit exact solutions in most cases

  • These results indicate that the directly computed data using the solution formula for a spherical solid source are in an excellent agreement with their counterparts indirectly computed using the solution for a spherical surface source

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Summary

Introduction

The bioluminescent enzyme firefly luciferase (Luc) or variants of green fluorescent protein (GFP) in transformed cells can be effectively used to reveal molecular and cellular features of neoplasia in vivo. Aydin et al [3] introduced a two-dimensional, finite element spherical harmonics radiation transport method for the simulation of light propagation in tissue They derived a photontransport forward model in turbid media that treats weak inhomogeneities through a Born approximation of the Boltzmann radiative transfer equation. Fishkin et al [7] derived analytical expressions based on the diffusion approximation that describe the photon density in a uniform, infinite, strongly scattering medium that contains a sinusoidally intensity-modulated point source of light. They reported good agreement between their analytical and experimental results. These solutions to the diffusion equation were derived for a point source only

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