Investigation On Time Domain Diffuse Fluorescence Tomography With CT-analogous Scanning Mode

Diffuse fluorescence tomography is emerging as one of the most promising tool for small animal imaging.With the aid of specific fluorescent probes,the modality aims at in-vivo visualizing interior molecular and cellular events from the reconstruction of fluorescent targets distribution.Nowadays,the DFT systems can be classified into three measurement modes: time domain,frequency domain and continuous-wave domain.Among them,time domain technique can provide the most organize information.It enables quantitative recovering the distribution of the fluorescence yield,and extracting the lifetime information through temporally resolving the fluorescence responses to a pulsed excitation.It can recover fluorescent yield and lifetime distributions simultaneously with the incomparable compared to other measurement modes.The time-resolved DFT system,based on the time-correlated single photon counting(TCSPC)technology,is one of the main methods for time domain measurement.TCSPC having super-high sensitivity can record low-level light singles with picoseconds resolution and extremely high precision,which is usually combined with photomultiplier(PMT)in the time domain system.Conventionally,time domain DFT systems based on PMT-TCSPC require using a limited number of detector-source fibers put in contact with the object of investigation,which restricts the improvement of spatial sampling density and the data scale,leading to the intensified ill-posedness of reconstruction process and reduced the image quality.A CT-analogous mode of time domain DFT based on PMT-TCSPC has been proposed to achieve the high spatial sampling density and sensitivity.And we developed an integrated automation system with functions of experimental measurement,curve display,data storage and calibration.We have applied the experiments on the developed time-resolved system.The results show that the spatial resolution and sensitivity of the system can be improved by increasing spatial sampling density.The proposed system can reconstruct the fluorescence yield distribution of Cy5.5 target with a high sensitivity and fidelity,as the concentration is above 1nM/L and the edge-to-edge distance of fluorescence targets is not less than 4mm.In addition,we performed the preliminary study in in-vivo small-animal imaging.Comparison results of DFT and XCT images show that the proposed method can achieve accurate positioning of fluorescence heterogeneity in mice,and verify effectiveness and feasibility for the application in small-animal imaging.In order to overcome the limits of the schemes-based on diffusion light model,a DFT method based on early photon migration model has been presented and preliminary validated by the phantom experiments.The results show that the approach can recover the positions and shapes of the targets with a reasonable accuracy.