Xiaochao Qu

GPU-based Monte Carlo simulation for light propagation in complex heterogeneous tissues

As the most accurate model for simulating light propagation in heterogeneous tissues, Monte Carlo (MC) method has been widely used in the field of optical molecular imaging. However, MC method is time-consuming due to the calculations of a large number of photons propagation in tissues. The structural complexity of the heterogeneous tissues further increases the computational time. In this paper we present a parallel implementation for MC simulation of light propagation in heterogeneous tissues whose surfaces are constructed by different number of triangle meshes. On the basis of graphics processing units (GPU), the code is implemented with compute unified device architecture (CUDA) platform and optimized to reduce the access latency as much as possible by making full use of the constant memory and texture memory on GPU. We test the implementation in the homogeneous and heterogeneous mouse models with a NVIDIA GTX 260 card and a 2.40GHz Intel Xeon CPU. The experimental results demonstrate the feasibility and efficiency of the parallel MC simulation on GPU.

Experimental Cerenkov luminescence tomography of the mouse model with SPECT imaging validation

Optical molecular imaging resulting from Cerenkov radiation has become a motivating topic recently and will potentially open new avenues for the study of small animal imaging. Cerenkov-based optical imaging taken from living animals in vivo has been studied with two-dimensional (2D) planar geometry and three-dimensional (3D) homogeneous mouse model. In this study, we performed 3D Cerenkov-based luminescence tomography (CLT) using a heterogeneous mouse model with an implanted Na(131)I radioactive source, which provided the accurate location for the reconstructed source. Furthermore, single photon emission computed tomography (SPECT) was utilized to verify the results of 3D CLT. We reconstructed the localization and intensity of an embedded radioactive source with various concentrations, and established a quantitative relationship between the radiotracer activity and the reconstructed intensity. The results showed the ability of in vivo CLT to recover the radioactive probe distribution in the heterogeneous mouse model and the potential of a SPECT imaging validation strategy to verify the results of optical molecular tomography.

Sparse reconstruction for quantitative bioluminescence tomography based on the incomplete variables truncated conjugate gradient method

In this paper, we present an incomplete variables truncated conjugate gradient (IVTCG) method for bioluminescence tomography (BLT). Considering the sparse characteristic of the light source and insufficient surface measurement in the BLT scenarios, we combine a sparseness-inducing (ℓ1 norm) regularization term with a quadratic error term in the IVTCG-based framework for solving the inverse problem. By limiting the number of variables updated at each iterative and combining a variable splitting strategy to find the search direction more efficiently, it obtains fast and stable source reconstruction, even without a priori information of the permissible source region and multispectral measurements. Numerical experiments on a mouse atlas validate the effectiveness of the method. In vivo mouse experimental results further indicate its potential for a practical BLT system.

In vivo quantitative bioluminescence tomography using heterogeneous and homogeneous mouse models

Bioluminescence tomography (BLT) is a new optical molecular imaging modality, which can monitor both physiological and pathological processes by using bioluminescent light-emitting probes in small living animal. Especially, this technology possesses great potential in drug development, early detection, and therapy monitoring in preclinical settings. In the present study, we developed a dual modality BLT prototype system with Micro-computed tomography (MicroCT) registration approach, and improved the quantitative reconstruction algorithm based on adaptive hp finite element method (hp-FEM). Detailed comparisons of source reconstruction between the heterogeneous and homogeneous mouse models were performed. The models include mice with implanted luminescence source and tumor-bearing mice with firefly luciferase report gene. Our data suggest that the reconstruction based on heterogeneous mouse model is more accurate in localization and quantification than the homogeneous mouse model with appropriate optical parameters and that BLT allows super-early tumor detection in vivo based on tomographic reconstruction of heterogeneous mouse model signal.

3D reconstruction of light flux distribution on arbitrary surfaces from 2D multi-photographic images.

Optical tomography can demonstrate accurate three-dimensional (3D) imaging that recovers the 3D spatial distribution and concentration of the luminescent probes in biological tissues, compared with planar imaging. However, the tomographic approach is extremely difficult to implement due to the complexity in the reconstruction of 3D surface flux distribution from multi-view two dimensional (2D) measurements on the subject surface. To handle this problem, a novel and effective method is proposed in this paper to determine the surface flux distribution from multi-view 2D photographic images acquired by a set of non-contact detectors. The method is validated with comparison experiments involving both regular and irregular surfaces. Reconstruction of the inside probes based on the reconstructed surface flux distribution further demonstrates the potential of the proposed method in its application in optical tomography.

Influence of laser parameters on nanoparticle-induced membrane permeabilization

Light-absorbing nanoparticles that are heated by short laser pulses can transiently increase membrane permeability. We evaluate the membrane permeability by flow cytometry assaying of propidium iodide and fluorescein isothiocyanate dextran (FITC-D) using different laser sources. The dependence of the transfection efficiency on laser parameters such as pulse duration, irradiant exposure, and irradiation mode is investigated. For nano- and also picosecond irradiation, we show a parameter range where a reliable membrane permeabilization is achieved for 10-kDa FITC-D. Fluorescent labeled antibodies are able to penetrate living cells that are permeabilized using these parameters. More than 50% of the cells are stained positive for a 150-kDa IgG antibody. These results suggest that the laser-induced permeabilization approach constitutes a promising tool for targeted delivery of larger exogenous molecules into living cells.

Three-dimensional Noninvasive Monitoring Iodine-131 Uptake in the Thyroid Using a Modified Cerenkov Luminescence Tomography Approach

Background Cerenkov luminescence tomography (CLT) provides the three-dimensional (3D) radiopharmaceutical biodistribution in small living animals, which is vital to biomedical imaging. However, existing single-spectral and multispectral methods are not very efficient and effective at reconstructing the distribution of the radionuclide tracer. In this paper, we present a semi-quantitative Cerenkov radiation spectral characteristic-based source reconstruction method named the hybrid spectral CLT, to efficiently reconstruct the radionuclide tracer with both encouraging reconstruction results and less acquisition and image reconstruction time. Methodology/Principal Findings We constructed the implantation mouse model implanted with a 400 µCi Na131I radioactive source and the physiological mouse model received an intravenous tail injection of 400 µCi radiopharmaceutical Iodine-131 (I-131) to validate the performance of the hybrid spectral CLT and compared the reconstruction results, acquisition, and image reconstruction time with that of single-spectral and multispectral CLT. Furthermore, we performed 3D noninvasive monitoring of I-131 uptake in the thyroid and quantified I-131 uptake in vivo using hybrid spectral CLT. Results showed that the reconstruction based on the hybrid spectral CLT was more accurate in localization and quantification than using single-spectral CLT, and was more efficient in the in vivo experiment compared with multispectral CLT. Additionally, 3D visualization of longitudinal observations suggested that the reconstructed energy of I-131 uptake in the thyroid increased with acquisition time and there was a robust correlation between the reconstructed energy versus the gamma ray counts of I-131 (). The ex vivo biodistribution experiment further confirmed the I-131 uptake in the thyroid for hybrid spectral CLT. Conclusions/Significance Results indicated that hybrid spectral CLT could be potentially used for thyroid imaging to evaluate its function and monitor its treatment for thyroid cancer.

A source reconstruction algorithm based on adaptive hp-FEM for bioluminescence tomography

As a novel modality of molecular imaging, bioluminescence tomography (BLT) is used to in vivo observe and measure the biological process at cellular and molecular level in small animals. The core issue of BLT is to determine the distribution of internal bioluminescent sources from optical measurements on external surface. In this paper, a new algorithm is presented for BLT source reconstruction based on adaptive hp-finite element method. Using adaptive mesh refinement strategy and intelligent permissible source region, we can obtain more accurate information about the location and density of sources, with the robustness, stability and efficiency improved. Numerical simulations and physical experiment were both conducted to verify the performance of the proposed algorithm, where the optical data on phantom surface were obtained via Monte Carlo simulation and CCD camera detection, respectively. The results represent the merits and potential of our algorithm for BLT source reconstruction.

Multilevel, hybrid regularization method for reconstruction of fluorescent molecular tomography

In this paper, a multilevel, hybrid regularization method is presented for fluorescent molecular tomography (FMT) based on the hp-finite element method (hp-FEM) with a continuous wave. The hybrid regularization method combines sparsity regularization and Landweber iterative regularization to improve the stability of the solution of the ill-posed inverse problem. In the first coarse mesh level, considering the fact that the fluorescent probes are sparsely distributed in the entire reconstruction region in most FMT applications, the sparse regularization method is employed to take full advantage of this sparsity. In the subsequent refined mesh levels, since the reconstruction region is reduced and the initial value of the unknown parameters is provided from the previous mesh, these mesh levels seem to be different from the first level. As a result, the Landweber iterative regularization method is applied for reconstruction. Simulation experiments on a 3D digital mouse atlas and physical experiments on a phantom are conducted to evaluate the performance of our method. The reconstructed results show the potential and feasibility of the proposed approach.

A multi-phase level set framework for source reconstruction in bioluminescence tomography

We propose a novel multi-phase level set algorithm for solving the inverse problem of bioluminescence tomography. The distribution of unknown interior source is considered as piecewise constant and represented by using multiple level set functions. The localization of interior bioluminescence source is implemented by tracing the evolution of level set function. An alternate search scheme is incorporated to ensure the global optimal of reconstruction. Both numerical and physical experiments are performed to evaluate the developed level set reconstruction method. Reconstruction results show that the proposed method can stably resolve the interior source of bioluminescence tomography.