Adaptive Extended-Kalman-Filtering Based Image Reconstructions In Pharmacokinetic Diffuse Fluorescence Tomography

An evidently higher permeability of fluorophore is observed in the cancerous tissue due to the proliferation of the 'leaky' angiogenetic microvessels compared to normal tissue with“tight”vessels.Therefore,imaging of the pharmacokinetic-rates can provide physiologically and pathologically relevant information for tumor differentiation.As a noninvasive and in vivo measurement method,pharmacokinetic diffuse fluorescence tomography(DFT)has attracted more and more attention.In pharmacokinetic DFT,the extended Kalman filtering(EKF)based on the compartmental kinetic model is a recursive estimation method with numerous advantages including:simultaneous estimation of pharmacokinetic parameters and ICG concentrations in each compartment explicitly,which are not accessible in vivo by means of static DFT;potential real-time monitoring of ICG pharmacokinetic parameters and ICG concentrations in different compartments,which is not accessible by curve-fitting method;effective modeling of multiple compartments,and multiple measurement systems governed by coupled ordinary differential equations,in the presence of measurement noise and uncertainties in the compartmental model dynamics,which provides better fit than the exponential models.In conclusion,the EKF-based pharmacokinetic DFT is a promising method for real-time monitoring of the in vivo fluorescent metabolic process.Firstly,we propose an adaptive extended Kalman filtering(EKF)for pharmacokinetic DFT,where the forgetting-factor is updated at each recursive stage to compensate the inaccuracy of the initial states and to emphasize the effect of the current data.This algorithm called as indirect method firstly reconstructs the time-course of ICG concentration by the conventional DFT and then synchronously estimates the pharmacokinetic-rates and compartmental concentration using the adaptive-EKF approach for the two-compartment model.Numerical simulations suggest that the proposed adaptive-EKF can obtain preferable pharmacokinetic-rate images to both the conventional and enhanced-EKF.Then,we propose a direct strategy for the pharmacokinetic DFT,by combine the DFT imaging into the adaptive-EKF scheme for the generalized multi-compartment model with the instantaneous sampling within the generalized framework of a discrete-detector-based CT-scanning mode.This strategy eliminates the interim errors of the DFT reconstruction and relaxes the restrictions on the equipment with high temporal resolution.The proposed method is validated by simulated data for the two-compartment model.Numerical simulations suggest that the proposed method can achieve simultaneous reconstructions of the compartmental concentrations and the pharmacokinetic-rates with higher accuracy than the indirect strategy.In addition,on the basis of the imaging methods mentioned above,this paper employs the pharmacokinetic DFT measurement with a priori anatomical structure of the liver for the elimination experiment of the ICG in mice,so as to provide a new measuring method and imaging theory for clinical diagnosis of liver function.Numerical simulations validate that a priori information can improve the imaging quality of the ICG concentration curve and pharmacokinetic-rates.Using a specifically-developed 4-channel photomultiplier tube(PMT)-based photon-counting DFT system with CT-scanning mode,the phantom experiments verify the feasibility and the accuracy of the system and the algorithm.On this basis,this article has carried on the ICG metabolic experiment of the healthy mice obtaining the ICG metabolic curve and the pharmacokinetic-rates with a priori knowledge from the CT results.