Jiulou Zhang

Fluorescence molecular tomography reconstruction via discrete cosine transform-based regularization

Abstract. Fluorescence molecular tomography (FMT) as a noninvasive imaging modality has been widely used for biomedical preclinical applications. However, FMT reconstruction suffers from severe ill-posedness, especially when a limited number of projections are used. In order to improve the quality of FMT reconstruction results, a discrete cosine transform (DCT) based reweighted L1-norm regularization algorithm is proposed. In each iteration of the reconstruction process, different reweighted regularization parameters are adaptively assigned according to the values of DCT coefficients to suppress the reconstruction noise. In addition, the permission region of the reconstructed fluorophores is adaptively constructed to increase the convergence speed. In order to evaluate the performance of the proposed algorithm, physical phantom and in vivo mouse experiments with a limited number of projections are carried out. For comparison, different L1-norm regularization strategies are employed. By quantifying the signal-to-noise ratio (SNR) of the reconstruction results in the phantom and in vivo mouse experiments with four projections, the proposed DCT-based reweighted L1-norm regularization shows higher SNR than other L1-norm regularizations employed in this work.

Iterative Correction Scheme Based on Discrete Cosine Transform and L1 Regularization for Fluorescence Molecular Tomography With Background Fluorescence

Goal: High-intensity background fluorescence is generally encountered in fluorescence molecular tomography (FMT), because of the accumulation of fluorescent probes in nontarget tissues or the existence of autofluorescence in biological tissues. The reconstruction results are affected or even distorted by the background fluorescence, especially when the distribution of fluorescent targets is relatively sparse. The purpose of this paper is to reduce the negative effect of background fluorescence on FMT reconstruction. Methods: After each iteration of the Tikhonov regularization algorithm, 3-D discrete cosine transform is adopted to filter the intermediate results. And then, a sparsity constraint step based on L1 regularization is applied to restrain the energy of the objective function. Results: Phantom experiments with different fluorescence intensities of homogeneous and heterogeneous background are carried out to validate the performance of the proposed scheme. The results show that the reconstruction quality can be improved with the proposed iterative correction scheme. Conclusion and Significance: The influence of background fluorescence in FMT can be reduced effectively because of the filtering of the intermediate results, the detail preservation, and noise suppression of L1 regularization.

Measurements of magnetic fields by a ring laser

The principle of measuring magnetic fields with a ring laser system is discussed. The main source of error, the Zeeman effect, is studied, and a corresponding technique to reduce it is described. An experimental setup is developed with a Faraday cell of a large product of the Verdet constant and the length. The experimental device obtains a sensitivity of 0.5 nT and a stability of 2 nT.

Multiparametric evaluation of hindlimb ischemia using time-series indocyanine green fluorescence imaging

Peripheral arterial disease (PAD) can further cause lower limb ischemia. Quantitative evaluation of the vascular perfusion in the ischemic limb contributes to diagnosis of PAD and preclinical development of new drug. In vivo time-series indocyanine green (ICG) fluorescence imaging can noninvasively monitor blood flow and has a deep tissue penetration. The perfusion rate estimated from the time-series ICG images is not enough for the evaluation of hindlimb ischemia. The information relevant to the vascular density is also important, because angiogenesis is an essential mechanism for post-ischemic recovery. In this paper, a multiparametric evaluation method is proposed for simultaneous estimation of multiple vascular perfusion parameters, including not only the perfusion rate but also the vascular perfusion density and the time-varying ICG concentration in veins. The target method is based on a mathematical model of ICG pharmacokinetics in the mouse hindlimb. The regression analysis performed on the time-series ICG images obtained from a dynamic reflectance fluorescence imaging system. The results demonstrate that the estimated multiple parameters are effective to quantitatively evaluate the vascular perfusion and distinguish hypo-perfused tissues from well-perfused tissues in the mouse hindlimb. The proposed multiparametric evaluation method could be useful for PAD diagnosis. The estimated perfusion rate and vascular perfusion density maps (left) and the time-varying ICG concentration in veins of the ankle region (right) of the normal and ischemic hindlimbs.

Unmixing multiple adjacent fluorescent targets with multispectral excited fluorescence molecular tomography.

Fluorescence molecular tomography (FMT) can visualize biological activities at cellular and molecular levels in vivo, and has been extensively used in drug delivery and tumor detection research of small animals. The ill-posedness of the FMT inverse problem makes it difficult to reconstruct and unmix multiple adjacent fluorescent targets that have different functional features but are labeled with the same fluorochrome. A method based on independent component analysis for multispectral excited FMT was proposed in our previous study. It showed that double fluorescent targets with certain edge-to-edge distance (EED) could be unmixed by the method. In this study, the situation is promoted to unmix multiple adjacent fluorescent targets (i.e., more than two fluorescent targets and EED=0). Phantom experiments on the resolving ability of the proposed algorithm demonstrate that the algorithm performs well in unmixing multiple adjacent fluorescent targets in both lateral and axial directions. And also, we recovered the locational information of each independent fluorescent target and described the variable trends of the corresponding fluorescent targets under the excitation spectrum. This method is capable of unmixing multiple fluorescent targets with small EED but labeled with the same fluorochrome, and may be used in imaging of nonspecific probe targeting and metabolism of drugs.

Fast reconstruction of fluorophore concentration variation based on the derivation of the diffusion equation.

The information of fluorophore concentration variation (FCV) has the potential for drug development and tumor studies, but the reconstruction of FCV is time-consuming in dynamic fluorescence molecular tomography (DFMT). In this paper, a time-efficient reconstruction method for FCV is presented. The system equation of this method is derived from the derivation of the diffusion equation, and its size does not change with the number of frames. The computational time can be significantly reduced by using this method because the images of different frames are reconstructed separately. Simulations and phantom experiments are performed to validate the performance of the proposed method. The results show that compared with the previous method, the proposed method can obtain better results and consumes less computational time with the same number of iterations. In addition, the time consumption in a single iteration of the proposed method increases much slower with the number of frames.

In vivo simultaneous multispectral fluorescence imaging with spectral multiplexed volume holographic imaging system.

A simultaneous multispectral fluorescence imaging system incorporating multiplexed volume holographic grating (VHG) is developed to acquire multispectral images of an object in one shot. With the multiplexed VHG, the imaging system can provide the distribution and spectral characteristics of multiple fluorophores in the scene. The implementation and performance of the simultaneous multispectral imaging system are presented. Further, the system’s capability in simultaneously obtaining multispectral fluorescence measurements is demonstrated with in vivo experiments on a mouse. The demonstrated imaging system has the potential to obtain multispectral images fluorescence simultaneously.

Direct reconstruction method for time-domain fluorescence molecular lifetime tomography.

For the reconstruction of time-domain fluorescence molecular lifetime tomography, conventional methods based on the Laplace or Fourier transform utilize only part of the information from the measurement data, and rely on the selection of transformation factors. To make the best of all the measurement data, a direct reconstruction algorithm is proposed. The fluorescence yield map is first reconstructed with a full-time gate, and then an objective function for the inverse lifetime tomography (instead of the lifetime) is developed so as to avoid dealing with the singularity of the zero points in the lifetime image. Through simulations and physical phantom experiments, the proposed algorithm is demonstrated to have high localization accuracy for fluorescent targets, high quantification accuracy for fluorescence lifetime, and good contrast between different fluorescence targets.

Fast reconstruction of fluorescence molecular tomography via a permissible region extraction strategy.

In order to obtain precise reconstruction results in fluorescence molecular tomography (FMT), large-scale matrix equations would be solved in the inverse problem generally. Thus, much time and memory needs to be consumed. In this paper, a permissible region extraction strategy is proposed to solve this problem. First, a preliminary result is rapidly reconstructed using the weight matrix compressed by principal component analysis or uniform sampling. And then the reconstructed target area in this preliminary result is considered as the a priori permissible region to guide the final reconstruction. Phantom experiments with double fluorescent targets are performed to test the performance of the strategy. The results illustrate that the proposed strategy can significantly accelerate the image reconstruction in FMT almost without quality degradation.

Tunable narrowband volume holographic imaging spectrometer for macroscopic fluorescence molecular tomography

Abstract. A simple, compact, and inexpensive tunable volume holographic imaging spectrometer is presented to acquire narrowband multispectral fluorescence measurements. It is constructed with three simple achromatic lenses, a transmission volume hologram, and a detector array. Experiments are carried out to evaluate the performance of this spectrometer. The experimental results indicate that the tunable spectrometer can operate at a wavelength range from 400 to 700 nm. Additionally, this spectrometer can provide a lateral field-of-view greater than 33 mm and a spatial resolution of 1.0 mm under narrow band illumination (full-width-half-maximum bandwidth 20 nm). Multispectral fluorescence molecular tomography experiments are conducted with this spectrometer to test the applicability of narrowband multispectral macroscopy.