Effect of tissue optics on wavelength optimization for quantum dot-based surface and subsurface fluorescence imaging

Abstract

Abstract. Optimization is an important but relatively unexplored aspect of contrast-enhanced fluorescence imaging, since minimizing contrast agent usage reduces the associated cost and potential toxicity. In a previous study, the authors developed a quantitative experimental approach to optimize quantum dot (QD)-based imaging using homogenized liver as a model tissue. In this follow-up study, the authors further extend and validate the approach using eight different tissues and five QDs emission wavelengths, and introduce quantitative imaging performance metrics, namely the threshold QD concentration and wavelength optimization gain. These metrics allow quantification of the improvements through spectral optimization in terms of reduced QD dose and identify the conditions that make the optimization process worthwhile. The authors show that, for most tissues, the most important parameter to optimize is the emission wavelength, yielding improvements of up to four orders of magnitude, followed by the excitation wavelength (up to 20-fold improvement) and the excitation filter bandwidth (up to 50% improvement). The authors also observe, by means of the optimization gain metric, that tissues exhibiting both high autofluorescence and strong pigmentation are generally better candidates for excitation wavelength optimization. This work contributes to the development of robust and quantitative dosimetry for QD-based fluorescence imaging near to the tissue surface.

Quantum dot imaging in the second near-infrared optical window: studies on reflectance fluorescence imaging depths by effective fluence rate and multiple image acquisition

“…1,2 The degrees of absorption, scattering, and autofluorescence vary dramatically depending on the wavelength of light. Conventional reflectance fluorescence imaging typically shows the tissue penetration depth in the order of a few to tens of milimeters.…”

Widefield quantitative multiplex surface enhanced Raman scattering imagingin vivo

“…Since light attenuation in tissue varies with wavelength, increasing depth in tissue causes ambiguity: e.g., the signal from S481 measured at 864 nm could be 5% lower than that from S421 measured at 896 nm as a result of a 5% difference in NP concentration or to a 5% change in light attenuation. Hence, it becomes necessary to apply an appropriate tissue optical model: this is certainly possible and has been used in fluorescence applications, 28,29 but adds complexity to the instrumentation required and to the image analysis.…”

Mitigating fluorescence spectral overlap in wide-field endoscopic imaging

“…63,64 Due to the uncertain toxicity and unknown side-effects, QDs are currently not FDA approved and are less likely to be used in human trials than organic dyes. QDs have a symmetric and Gaussian-like emission spectral profile, and therefore have less cross-talk than organic dyes.…”