Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms

Abstract

We present a multichannel tomographic technique to detect f luorescent objects embedded in thick (6.4 cm) tissue-like turbid media using early-arriving photons. The experiments use picosecond laser pulses and a streak camera with single photon counting capability to provide short time resolution and high signal-to-noise ratio. The tomographic algorithm is based on the Laplace transform of an analytical diffusion approximation of the photon migration process and provides excellent agreement between the actual positions of the f luorescent objects and the experimental estimates. Submillimeter localization accuracy and 4-to 5-mm resolution are demonstrated. Moreover, objects can be accurately localized when f luorescence background is present. The results show the feasibility of using early-arriving photons to image f luorescent objects embedded in a turbid medium and its potential in clinical applications such as breast tumor detection.

Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo

“…It should be noted that, somewhat counterintuitively, the temporal kinetics of the early portion of the fluorescence emission curve are dominated by the photon propagation through the media as opposed to the fluorescence decay lifetime of the fluorochrome (13). Therefore, the early arriving excitation and emission photons arrive at the detector at approximately the same time gate.…”

“…To describe the propagation of the early arriving photons, a cumulant approximation to the Boltzmann transport equation was used (18,19) and by using normalization of the photon density to the intrinsic photon propagation between the source-detector pair. This approximation is more accurate than time-resolved diffusion theory at early times (13,14), because it correctly models the propagation of ballistic photons and early-diffuse photons at early-time gates. We have experimentally validated this early-photon propagation model by using experimental measurements of the 3-point Green's function through the medium.…”

“…To develop a next-generation optical tomographic method that can selectively reduce the effects of tissue scattering to improve imaging accuracy, we developed a system to use early arriving photons, that is, photons emitted from an ultrafast laser source (i.e., pulse width Ͻ1 ps) that propagate through tissue and are the first to arrive at a time-gated detector a distance away from the source (9)(10)(11)(12)(13)(14)(15)(16). The scattering of these early photons is strongly biased in the forward direction and correspondingly they experience a lower number of total scattering events.…”

“…Early photons have been used previously in planar transillumination studies of breast tissue samples (9,10). The use of early photons in combination with theoretical models of early-photon propagation have also been considered in the past and yielded systems with the ability to localize relatively simple objects such as 1 or 2 absorbing or fluorescent spheres embedded in a homogenous scattering fluid (13,14) or, as in our previous work, complex shaped absorbing optical phantoms (15,16). These methods, however, were never extended to in vivo imaging and consequently they have not been shown to be biologically useful.…”

Time-resolved optical fluorescence spectroscopy of heterogeneous turbid media with special emphasis on brain tissue structures including diseased regions: A sensitivity analysis

“…Therefore, the diffusive optical imaging requires an interpretation on measurements performed from sources and detectors spaced over the boundaries of the interrogated tissue. In this way, relevant parameters linked to the localization of fluorescent inclusions in homogeneous media have been reported by different groups [10][11][12][13][14][15][16][17][18][19]. Optimizing analysis of these types of data is an area of very active research in order to improve depth sensitivity [20][21][22][23][24] and quantify fluorescence rate [25,26] in the human brain.…”