Early-photon fluorescence tomography: spatial resolution improvements and noise stability considerations

Abstract

In vivo tissue imaging using near-infrared light suffers from low spatial resolution and poor contrast recovery because of highly scattered photon transport. For diffuse optical tomography (DOT) and fluorescence molecular tomography (FMT), the resolution is limited to about 5–10% of the diameter of the tissue being imaged, which puts it in the range of performance seen in nuclear medicine. This paper introduces the mathematical formalism explaining why the resolution of FMT can be significantly improved when using instruments acquiring fast time-domain optical signals. This is achieved through singular-value analysis of the time-gated inverse problem based on weakly diffused photons. Simulations relevant to mouse imaging are presented showing that, in stark contrast to steady-state imaging, early time-gated intensities (within 200 ps or 400 ps) can in principle be used to resolve small fluorescent targets (radii from 1.5 to 2.5 mm) separated by less than 1.5 mm.

Implicit and explicit prior information in near-infrared spectral imaging: accuracy, quantification and diagnostic value

“…Such approaches can be categorized into several different data types, as outlined in table 1. These [7][8][9] spectral derivative data multiple analyte analysis [10][11][12] fluorescence/excitation ratio fluorescence imaging [13][14][15] multi-distance data estimation of slopes with linear approximations robust tissue spectroscopy systems insensitive to slight shape changes [16][17][18] small-volume sampling scatter spectroscopy fibre probes with size less than effective scatter distance [19][20][21][22] absorption spectroscopy fibre probes sensitive to absorption only [23,24] fluorescence spectroscopy fibre probes sensitive to fluorescence and not tissue [25,26] temporal signals millisecond variations in tissue oxygen saturation and haemodynamic sampling [8,27,28] microsecond sampling flash photolysis analysis of biochemical changes in vivo [29,30] picosecond sampling ultrafast signals to reduce model dependence [31][32][33][34][35] high-frequency phase shift derivative with distance frequency-domain spectroscopy of tissue [36,37] lifetime-based signals fluorophore identification or microenvironment analysis [38] include: (i) ratiometric or derivative data at two or more different wavelengths, (ii) multiple-distance ratio or derivative data, (iii) small spatial volumes that either limit the effect of physical boundaries through scatter and/or absorption, or allow simpler empirical modelling, and (iv) temporal signals that are less sensitive to boundaries and/or more robustly insensitive to shape changes. The use of prior information about the tissue to be sampled is still essential in the design process with these systems, but can be implemented in the very first step o...…”

Locating and classifying fluorescent tags behind turbid layers using time-resolved inversion

“…Time-resolved FLI is useful for fluorescence localization in turbid media using asymptotic decay approximations 11 and early photons [12][13][14] , with hybrid models under study 15 . Though fluorescence decay broadens the pulse duration, early-photon FLI measurements can still localize objects using the relatively fast rise time 16,17 .…”

Instrumentation considerations for measurement of early arriving photons in diffuse optical tomography

“…Altering source-detector offset also reduced the "early photon effect", but as we have noted this was predicted by Monte Carlo simulations. As noted above, these results are significant because narrower instrument PDSFs lead directly to improved tomographic imaging resolution for time-resolved DOT and DFT systems [9]. We have attempted to design our experiments so as to measure the effect of these instrumentation parameters on the measured PDSFs as directly as possible but as we have noted isolating the particular effect (or combination of effects) responsible is not straightforward and is the subject of ongoing work.…”

“…Time-resolved measurement of so-called 'early arriving photons' is a fairly established approach to reduce this scatter and has been studied by a number of groups previously [5][6][7][8][9][10]. Conceptually, photons that arrive first at a detector from a high-speed pulsed laser source have propagated over shorter total pathlengths.…”