Chenghu Qin

Spectrally resolved bioluminescence tomography with adaptive finite element analysis: methodology and simulation

As a molecular imaging technique, bioluminescence tomography (BLT) with its highly sensitive detection and facile operation can significantly reveal molecular and cellular information in vivo at the whole-body small animal level. However, because of complex photon transportation in biological tissue and boundary detection data with high noise, bioluminescent sources in deeper positions generally cannot be localized. In our previous work, we used achromatic or monochromatic measurements and an a priori permissible source region strategy to develop a multilevel adaptive finite-element algorithm. In this paper, we propose a spectrally solved tomographic algorithm with a posteriori permissible source region selection. Multispectral measurements, and anatomical and optical information first deal with the nonuniqueness of BLT and constrain the possible solution of source reconstruction. The use of adaptive mesh refinement and permissible source region based on a posteriori measures not only avoids the dimension disaster arising from the multispectral measured data but also reduces the ill-posedness of BLT and therefore improves the reconstruction quality. Reconsideration of the optimization method and related modifications further enhance reconstruction robustness and efficiency. We also incorporate into the method some improvements for reducing computational burdens. Finally, using a whole-body virtual mouse phantom, we demonstrate the capability of the proposed BLT algorithm to reconstruct accurately bioluminescent sources in deeper positions. In terms of optical property errors and two sources of discernment in deeper positions, this BLT algorithm represents the unique predominance for BLT reconstruction.

A fast reconstruction algorithm for fluorescence molecular tomography with sparsity regularization

Through the reconstruction of the fluorescent probe distributions, fluorescence molecular tomography (FMT) can three-dimensionally resolve the molecular processes in small animals in vivo. In this paper, we propose an FMT reconstruction algorithm based on the iterated shrinkage method. By incorporating a surrogate function, the original optimization problem can be decoupled, which enables us to use the general sparsity regularization. Due to the sparsity characteristic of the fluorescent sources, the performance of this method can be greatly enhanced, which leads to a fast reconstruction algorithm. Numerical simulations and physical experiments were conducted. Compared to Newton method with Tikhonov regularization, the iterated shrinkage based algorithm can obtain more accurate results, even with very limited measurement data.

An optimal permissible source region strategy for multispectral bioluminescence tomography

Multispectral bioluminescence tomography (BLT) attracts increasing more attention in the area of small animal studies because multispectral data acquisition could help in the 3D location of bioluminescent sources. Generally, BLT problem is ill-posed and a priori information is indispensable to reconstruction bioluminescent source uniquely and quantitatively. In this paper, we propose a spectrally solved bioluminescence tomography algorithm with an optimal permissible source region strategy. Being the most different from earlier studies, an optimal permissible source region strategy which is automatically selected without human intervention is developed to reduce the ill-posedness of BLT and therefore improves the reconstruction quality. Furthermore, both numerical stability and computational efficiency benefit from the strategy. In the numerical experiments, a heterogeneous phantom is used to evaluate the proposed algorithm and the synthetic data is produced by Monte Carlo method for avoiding the inverse crime. The results demonstrate the feasibility and potential of our methodology for reconstructing the distribution of bioluminescent sources.

Evaluation of the simplified spherical harmonics approximation in bioluminescence tomography through heterogeneous mouse models

In vivo bioluminescence imaging (BLI) has played a more and more important role in biomedical research of small animals. Bioluminescence tomography (BLT) further translates the BLI optical information into three-dimensional bioluminescent source distribution, which could greatly facilitate applications in related studies. Although the diffusion approximation (DA) is one of the most widely-used forward models, higher-order approximations are still needed for in vivo small animal imaging. In this work, as a relatively accurate and higher-order approximation theory, the performance of the simplified spherical harmonics approximation (SPN) in BLT is evaluated detailedly in heterogeneous small animals. In the numerical validations, the SPN based results demonstrate better imaging quality compared with diffusion approximation heterogeneously under various source locations over wide optical domain. Although the evaluation for the effects of the optical property mismatch indicates the sensitivity of SPN is similar with DA model in the source localization, it may offer improved performance with much less artifacts. In what follows, heterogeneous experimental BLT reconstructions using in vivo mouse further evaluate the capability of the higher-order method for practical biomedical applications.

Cone beam micro-CT system for small animal imaging and performance evaluation

A prototype cone-beam micro-CT system for small animal imaging has been developed by our group recently, which consists of a microfocus X-ray source, a three-dimensional programmable stage with object holder, and a flat-panel X-ray detector. It has a large field of view (FOV), which can acquire the whole body imaging of a normal-size mouse in a single scan which usually takes about several minutes or tens of minutes. FDK method is adopted for 3D reconstruction with Graphics Processing Unit (GPU) acceleration. In order to reconstruct images with high spatial resolution and low artifacts, raw data preprocessing and geometry calibration are implemented before reconstruction. A method which utilizes a wire phantom to estimate the residual horizontal offset of the detector is proposed, and 1D point spread function is used to assess the performance of geometric calibration quantitatively. System spatial resolution, image uniformity and noise, and low contrast resolution have been studied. Mouse images with and without contrast agent are illuminated in this paper. Experimental results show that the system is suitable for small animal imaging and is adequate to provide high-resolution anatomic information for bioluminescence tomography to build a dual modality system.

Whole-Body Cerenkov Luminescence Tomography with the Finite Element SP 3 Method

Generation of an accurate Cerenkov luminescence imaging model is a current issue of nuclear tomography with optical techniques. The article takes a pro-active approach toward whole-body Cerenkov luminescence tomography. The finite element framework employs the equation of radiative transfer via the third-order simplified spherical harmonics approximation to model Cerenkov photon propagation in a small animal. After this forward model is performed on a digital mouse with optical property heterogeneity and compared with the Monte Carlo method, we investigated the whole body reconstruction algorithm along a regularization path via coordinate descent. The endpoint of the follow-up study is the in vivo application, which provides three-dimensional biodistribution of the radiotracer uptake in the mouse from measured partial boundary currents. The combination of the forward and inverse model with elastic-net penalties is not only validated by numerical simulation, but it also effectively demonstrates in vivo imaging in small animals. Our exact reconstruction method enables optical molecular imaging to best utilize Cerenkov radiation emission from the decay of medical isotopes in tissues.

New Optical Molecular Imaging Systems

Molecular imaging has become a research focus in recent years, which provides an effective information acquisition, analysis and processing methodology at cellular and molecular levels for biomedical study. As an important molecular imaging technique, optical molecular imaging, especially fluorescence and bioluminescence imaging, has attracted remarkable attention in tumor study and drug development for its excellent performance, non-radiativity and high cost-effectiveness in comparison with conventional imaging modalities. Generally speaking, optical molecular imaging is regarded as the combination of traditional medical imaging technology and modern molecular biology, in which the advanced optics, biology, information, medicine, and other techniques are being married to non-invasively obtain in vivo physiological and pathological information sensitively, quantitatively, and specifically. Further, with the research of imaging theories, algorithms and molecular probes, optical imaging systems have been rapidly developed for biomedical study in molecular imaging discipline, including planar imaging systems, tomographic imaging systems, and multimodality fusion systems, and so on. This review focuses on some typical optical molecular imaging systems, especially for in vivo small animal use. It also provides a brief discussion on the future development and application of the optical molecular imaging systems.

Cerenkov luminescence tomography for in vivo radiopharmaceutical imaging

Cerenkov luminescence imaging (CLI) is a cost-effective molecular imaging tool for biomedical applications of radiotracers. The introduction of Cerenkov luminescence tomography (CLT) relative to planar CLI can be compared to the development of X-ray CT based on radiography. With CLT, quantitative and localized analysis of a radiopharmaceutical distribution becomes feasible. In this contribution, a feasibility study of in vivo radiopharmaceutical imaging in heterogeneous medium is presented. Coupled with a multimodal in vivo imaging system, this CLT reconstruction method allows precise anatomical registration of the positron probe in heterogeneous tissues and facilitates the more widespread application of radiotracers. Source distribution inside the small animal is obtained from CLT reconstruction. The experimental results demonstrated that CLT can be employed as an available in vivo tomographic imaging of charged particle emitters in a heterogeneous medium.

Three-dimensional Bioluminescence Tomography based on Bayesian Approach

Bioluminescence tomography (BLT) poses a typical ill-posed inverse problem with a large number of unknowns and a relatively limited number of boundary measurements. It is indispensable to incorporate a priori information into the inverse problem formulation in order to obtain viable solutions. In the paper, Bayesian approach has been firstly suggested to incorporate multiple types of a priori information for BLT reconstruction. Meanwhile, a generalized adaptive Gaussian Markov random field (GAGMRF) prior model for unknown source density estimation is developed to further reduce the ill-posedness of BLT on the basis of finite element analysis. Then the distribution of bioluminescent source can be acquired by maximizing the log posterior probability with respect to a noise parameter and the unknown source density. Furthermore, the use of finite element method makes the algorithm appropriate for complex heterogeneous phantom. The algorithm was validated by numerical simulation of a 3-D micro-CT mouse atlas and physical phantom experiment. The reconstructed results suggest that we are able to achieve high computational efficiency and accurate localization of bioluminescent source.

A fast bioluminescent source localization method based on generalized graph cuts with mouse model validations

Bioluminescence imaging (BLI) makes it possible to elucidate molecular and cellular signatures to better understand the effects of human disease in small animal models in vivo. The unambiguous three-dimensional bioluminescent source information obtained by bioluminescence tomography (BLT) could further facilitate its applications in biomedicine. However, to the best of our knowledge, the existing gradient-type reconstruction methods in BLT are inefficient, and often require a relatively small volume of interest (VOI) for feasible results. In this paper, a fast generalized graph cuts based reconstruction method for BLT is presented, which is to localize the bioluminescent source in heterogeneous mouse tissues via max-flow/min-cut algorithm. Since the original graph cuts theory can only handle graph-representable problem, the quadratic pseudo-boolean optimization is incorporated to make the graph representable and tractable, which is called generalized graph cuts (GGC). The internal light source can be reconstructed from the whole domain, so a priori knowledge of VOI can be avoided in this method. In the simulation validations, the proposed method was validated in a heterogeneous mouse atlas, and the source can be localized reliably and efficiently by GGC; and compared with gradient-type method, the proposed method is about 25-50 times faster. Moreover, the experiments for sensitivity to the measurement errors of tissue optical properties demonstrate that, the reconstruction quality is not much affected by mismatch of parameters. In what follows, in vivo mouse BLT reconstructions further demonstrated the potential and effectiveness of the generalized graph cut based reconstruction method.