Fluorescence diffuse optical tomography using upconverting nanoparticles

Abstract

Fluorescence diffuse optical tomography (FDOT) can provide important information in biomedical studies. In this ill-posed problem, suppression of background tissue autofluorescence is of utmost importance. We report a method for autofluorescence-insensitive FDOT using nonlinear upconverting nanoparticles (NaYF4:Yb3+/Tm3+) in a tissue phantom under excitation intensities well below tissue-damage thresholds. Even with the intrinsic autofluorescence from the phantom only, the reconstruction of the nanoparticles is of much better quality than the reconstruction of a Stokes-shifting dye. In addition, the nonlinear power dependence leads to more confined reconstructions and may increase the resolution in FDOT.

Use of nonlinear upconverting nanoparticles provides increased spatial resolution in fluorescence diffuse imaging

“…Upconverting nanoparticles, however, have through-energy transfer upconversion, a 10 orders of magnitude higher fluorescence efficiency than two-photon absorption [11], thus allowing imaging through several millimeters of tissue. With upconverting nanoparticles, it is also possible to perform autofluorescence insensitive measurements-something that has been demonstrated both for planar imaging [12] as well as tomography [13].…”

Multibeam fluorescence diffuse optical tomography using upconverting nanoparticles

“…This leads to a significant reduction of artifacts in the reconstructions. In addition, owing to the quadratic power dependence of the nanoparticles, the reconstructions are more sharply defined compared with the reconstructions of a linear fluorophore [13].…”

“…(2) can be generalized to include more simultaneous excitation beams. The significance of the measurements with dualbeam excitation in the reconstructions was confirmed by the singular-value analysis of the weight matrix, W, whose elements are given by [13] …”

“…Upconverting nanoparticles have been proposed as fluorophores in biomedical imaging [11,12] as well as in FDOT [13]. These nanoparticles can emit antiStokes shifted light when excited at 980 nm [14], which enables the signal to be detected in an autofluorescence-free environment [15].…”

“…The excitation and emission fields can be modeled by two coupled diffusion equations [13]. For quadratic fluorophores, the fluorescence signal detected at a fixed detector position under excitation of the kth beam, ⌫ k , can be described by the forward model…”