Dictionary Learning Method Based on K-Sparse Approximation and Orthogonal Procrustes Analysis for Reconstruction in Bioluminescence Tomography.

Bioluminescence tomography (BLT) is one kind of noninvasive optical molecular imaging technology, widely used to study molecular activities and disease progression inside live animals. By combining the optical propagation model and inversion algorithm, BLT enables three-dimensional imaging and quantitative analysis of light sources within organisms. However, challenges like light scattering and absorption in tissues, and the complexity of biological structures, significantly impact the accuracy of BLT reconstructions. Here, we propose a dictionary learning method based on K-sparse approximation and Orthogonal Procrustes analysis (KSAOPA). KSAOPA uses an iterative alternating optimization strategy, enhancing solution sparsity with k-coefficients Lipschitzian mappings for sparsity(K-LIMAPS) in the sparse coding stage, and reducing errors with Orthogonal Procrustes analysis in the dictionary update stage, leading to stable and precise reconstructions. We assessed the method performance through simulations and in vivo experiments, which showed that KSAOPA excels in localization accuracy, morphological recovery, and in vivo applicability compared to other methods.

Characterization of a commercial bioluminescence tomography-guided system for pre-clinical radiation research.

BACKGROUND: Widely used Cone-beam computed tomography (CBCT)-guided irradiators have limitations in localizing soft tissue targets growing in a low-contrast environment. This hinders small animal irradiators achieving precise focal irradiation. PURPOSE: To advance image-guidance for soft tissue targeting, we developed a commercial-grade bioluminescence tomography-guided system (BLT, MuriGlo) for pre-clinical radiation research. We characterized the system performance and demonstrated its capability in target localization. We expect this study can provide a comprehensive guideline for the community in utilizing the BLT system for radiation studies. METHODS: MuriGlo consists of four mirrors, filters, lens, and charge-coupled device (CCD) camera, enabling a compact imaging platform and multi-projection and multi-spectral BLT. A newly developed mouse bed allows animals imaged in MuriGlo and transferred to a small animal radiation research platform (SARRP) for CBCT imaging and BLT-guided irradiation. Methods and tools were developed to evaluate the CCD response linearity, minimal detectable signal, focusing, spatial resolution, distortion, and uniformity. A transparent polycarbonate plate covering the middle of the mouse bed was used to support and image animals from underneath the bed. We investigated its effect on 2D Bioluminescence images and 3D BLT reconstruction accuracy, and studied its dosimetric impact along with the rest of mouse bed. A method based on pinhole camera model was developed to map multi-projection bioluminescence images to the object surface generated from CBCT image. The mapped bioluminescence images were used as the input data for the optical reconstruction. To account for free space light propagation from object surface to optical detector, a spectral derivative (SD) method was implemented for BLT reconstruction. We assessed the use of the SD data (ratio imaging of adjacent wavelength) in mitigating out of focusing and non-uniformity seen in the images. A mouse phantom was used to validate the data mapping. The phantom and an in vivo glioblastoma model were utilized to demonstrate the accuracy of the BLT target localization. RESULTS: The CCD response shows good linearity with < 0.6% residual from a linear fit. The minimal detectable level is 972 counts for 10 × 10 binning. The focal plane position is within the range of 13-18 mm above the mouse bed. The spatial resolution of 2D optical imaging is < 0.3 mm at Rayleigh criterion. Within the region of interest, the image uniformity is within 5% variation, and image shift due to distortion is within 0.3 mm. The transparent plate caused < 6% light attenuation. The use of the SD imaging data can effectively mitigate out of focusing, image non-uniformity, and the plate attenuation, to support accurate multi-spectral BLT reconstruction. There is < 0.5% attenuation on dose delivery caused by the bed. The accuracy of data mapping from the 2D bioluminescence images to CBCT image is within 0.7 mm. Our phantom test shows the BLT system can localize a bioluminescent target within 1 mm with an optimal threshold and only 0.2 mm deviation was observed for the case with and without a transparent plate. The same localization accuracy can be maintained for the in vivo GBM model. CONCLUSIONS: This work is the first systematic study in characterizing the commercial BLT-guided system. The information and methods developed will be useful for the community to utilize the imaging system for image-guided radiation research.

Multi-target reconstruction based on subspace decision optimization for bioluminescence tomography.

BACKGROUND AND OBJECTIVE: Bioluminescence tomography (BLT) is a noninvasive optical imaging technique that provides qualitative and quantitative information on the spatial distribution of tumors in living animals. Researchers have proposed a list of algorithms and strategies for BLT reconstruction to improve its reconstruction quality. However, multi-target BLT reconstruction remains challenging in practical clinical applications due to the mutual interference of optical signals and difficulty in source separation. METHODS: To solve this problem, this study proposes the subspace decision optimization (SDO) approach based on the traditional iterative permissible region strategy. The SDO approach transforms a single permissible region into multiple subspaces by clustering analysis. These subspaces are shrunk based on subspace shrinking optimization to achieve spatial continuity of the permissible regions. In addition, these subspaces are merged to construct a new permissible region and then the next iteration of reconstruction is carried out to ensure the stability of the results. Finally, all the iterative results are optimized based on the normal distribution model and the distribution properties of the targets to ensure the sparsity of each target and the non-biasing of the overall results. RESULTS: Experimental results show that the SDO approach can automatically identify and separate different targets, ensuring the accuracy and quality of multi-target BLT reconstruction results. Meanwhile, SDO can combine various types of reconstruction algorithms and provide stable and high-quality reconstruction results independent of the algorithm parameters. CONCLUSIONS: The SDO approach provides an integrated solution to the multi-target BLT reconstruction problem, realizing the whole process including target recognition, separation, reconstruction, and result enhancement, which can extend the application domain of BLT.

A deep-learning assisted bioluminescence tomography method to enable radiation targeting in rat glioblastoma.

Objective. A novel solution is required for accurate 3D bioluminescence tomography (BLT) based glioblastoma (GBM) targeting. The provided solution should be computationally efficient to support real-time treatment planning, thus reducing the x-ray imaging dose imposed by high-resolution micro cone-beam CT.Approach. A novel deep-learning approach is developed to enable BLT-based tumor targeting and treatment planning for orthotopic rat GBM models. The proposed framework is trained and validated on a set of realistic Monte Carlo simulations. Finally, the trained deep learning model is tested on a limited set of BLI measurements of real rat GBM models.Significance. Bioluminescence imaging (BLI) is a 2D non-invasive optical imaging modality geared toward preclinical cancer research. It can be used to monitor tumor growth in small animal tumor models effectively and without radiation burden. However, the current state-of-the-art does not allow accurate radiation treatment planning using BLI, hence limiting BLI's value in preclinical radiobiology research.Results. The proposed solution can achieve sub-millimeter targeting accuracy on the simulated dataset, with a median dice similarity coefficient (DSC) of 61%. The provided BLT-based planning volume achieves a median encapsulation of more than 97% of the tumor while keeping the median geometrical brain coverage below 4.2%. For the real BLI measurements, the proposed solution provided median geometrical tumor coverage of 95% and a median DSC of 42%. Dose planning using a dedicated small animal treatment planning system indicated good BLT-based treatment planning accuracy compared to ground-truth CT-based planning, where dose-volume metrics for the tumor fall within the limit of agreement for more than 95% of cases.Conclusion. The combination of flexibility, accuracy, and speed of the deep learning solutions make them a viable option for the BLT reconstruction problem and can provide BLT-based tumor targeting for the rat GBM models.

A Graph-guided Hybrid Regularization Method For Bioluminescence Tomography.

BACKGROUND AND OBJECTIVE: Bioluminescence tomography (BLT) is a powerful and sensitive imaging technique having great potential in preclinical application, such as tumor imaging, monitoring and therapy, etc. Regularization plays an important role in BLT reconstruction for considering the priori information to overcome the inherent ill-posedness of the inverse problem. Therefore, well-designed regularization term and sophisticated algorithm for solving the consequent optimization problem are key to improve the BLT quality. METHODS: To balance the sparsity, smoothness and morphological characteristics of the bioluminescence targets, we constructed a novel Graph-Guided Hybrid Regularization (GGHR) method by combining graph-guided penalty term with L1 and L2 norm regularizer. To solve the corresponding minimization problem with hybrid penalties, the dual decomposition and Nesterov's smoothing technique were adopted to decouple and transform the non-separable and non-smooth graph-guided penalty term into a differential smooth approximation form, which was solved by the fast iterative shrinkage thresholding algorithm. RESULTS: The performance of the proposed GGHR method was verified and evaluated through a series of simulation, phantom and in vivo experiments. The comparison results demonstrated that the GGHR method outperformed current mainstream reconstruction algorithms in spatial localization, morphology recovery and in vivo practicality. CONCLUSIONS: The proposed GGHR method is a robust and practicality reconstruction algorithm for further highlighting the positive effect of hybrid regularization on BLT applications.

ABPO-TVSCAD: alternating Bregman proximity operators approach based on TVSCAD regularization for bioluminescence tomography.

Objective.Bioluminescence tomography (BLT) is a promising non-invasive optical medical imaging technique, which can visualize and quantitatively analyze the distribution of tumor cells in living tissues. However, due to the influence of photon scattering effect and ill-conditioned inverse problem, the reconstruction result is unsatisfactory. The purpose of this study is to improve the reconstruction performance of BLT.Approach.An alternating Bregman proximity operators (ABPO) method based on TVSCAD regularization is proposed for BLT reconstruction. TVSCAD combines the anisotropic total variation (TV) regularization constraints and the non-convex smoothly clipped absolute deviation (SCAD) penalty constraints, to make a trade-off between the sparsity and edge preservation of the source. ABPO approach is used to solve the TVSCAD model (ABPO-TVSCAD for short). In addition, to accelerate the convergence speed of the ABPO, we adapt the strategy of shrinking the permission source region, which further improves the performance of ABPO-TVSCAD.Main results.The results of numerical simulations andin vivoxenograft mouse experiment show that our proposed method achieved superior accuracy in spatial localization and morphological reconstruction of bioluminescent source.Significance.ABPO-TVSCAD is an effective and robust reconstruction method for BLT, and we hope that this method can promote the development of optical molecular tomography.

A deep learning and Monte Carlo based framework for bioluminescence imaging center of mass-guided glioblastoma targeting.

Objective.Bioluminescence imaging (BLI) is a valuable tool for non-invasive monitoring of glioblastoma multiforme (GBM) tumor-bearing small animals without incurring x-ray radiation burden. However, the use of this imaging modality is limited due to photon scattering and lack of spatial information. Attempts at reconstructing bioluminescence tomography (BLT) using mathematical models of light propagation show limited progress.Approach.This paper employed a different approach by using a deep convolutional neural network (CNN) to predict the tumor's center of mass (CoM). Transfer-learning with a sizeable artificial database is employed to facilitate the training process for, the much smaller, target database including Monte Carlo (MC) simulations of real orthotopic glioblastoma models. Predicted CoM was then used to estimate a BLI-based planning target volume (bPTV), by using the CoM as the center of a sphere, encompassing the tumor. The volume of the encompassing target sphere was estimated based on the total number of photons reaching the skin surface.Main results.Results show sub-millimeter accuracy for CoM prediction with a median error of 0.59 mm. The proposed method also provides promising performance for BLI-based tumor targeting with on average 94% of the tumor inside the bPTV while keeping the average healthy tissue coverage below 10%.Significance.This work introduced a framework for developing and using a CNN for targeted radiation studies for GBM based on BLI. The framework will enable biologists to use BLI as their main image-guidance tool to target GBM tumors in rat models, avoiding delivery of high x-ray imaging dose to the animals.

Quantitative molecular bioluminescence tomography.

SIGNIFICANCE: Bioluminescence imaging and tomography (BLT) are used to study biologically relevant activity, typically within a mouse model. A major limitation is that the underlying optical properties of the volume are unknown, leading to the use of a "best" estimate approach often compromising quantitative accuracy. AIM: An optimization algorithm is presented that localizes the spatial distribution of bioluminescence by simultaneously recovering the optical properties and location of bioluminescence source from the same set of surface measurements. APPROACH: Measured data, using implanted self-illuminating sources as well as an orthotopic glioblastoma mouse model, are employed to recover three-dimensional spatial distribution of the bioluminescence source using a multi-parameter optimization algorithm. RESULTS: The proposed algorithm is able to recover the size and location of the bioluminescence source while accounting for tissue attenuation. Localization accuracies of <1 mm are obtained in all cases, which is similar if not better than current "gold standard" methods that predict optical properties using a different imaging modality. CONCLUSIONS: Application of this approach, using in-vivo experimental data has shown that quantitative BLT is possible without the need for any prior knowledge about optical parameters, paving the way toward quantitative molecular imaging of exogenous and indigenous biological tumor functionality.

Multispectral Differential Reconstruction Strategy for Bioluminescence Tomography.

Bioluminescence tomography (BLT) is a promising in vivo molecular imaging tool that allows non-invasive monitoring of physiological and pathological processes at the cellular and molecular levels. However, the accuracy of the BLT reconstruction is significantly affected by the forward modeling errors in the simplified photon propagation model, the measurement noise in data acquisition, and the inherent ill-posedness of the inverse problem. In this paper, we present a new multispectral differential strategy (MDS) on the basis of analyzing the errors generated from the simplification from radiative transfer equation (RTE) to diffusion approximation and data acquisition of the imaging system. Through rigorous theoretical analysis, we learn that spectral differential not only can eliminate the errors caused by the approximation of RTE and imaging system measurement noise but also can further increase the constraint condition and decrease the condition number of system matrix for reconstruction compared with traditional multispectral (TM) reconstruction strategy. In forward simulations, energy differences and cosine similarity of the measured surface light energy calculated by Monte Carlo (MC) and diffusion equation (DE) showed that MDS can reduce the systematic errors in the process of light transmission. In addition, in inverse simulations and in vivo experiments, the results demonstrated that MDS was able to alleviate the ill-posedness of the inverse problem of BLT. Thus, the MDS method had superior location accuracy, morphology recovery capability, and image contrast capability in the source reconstruction as compared with the TM method and spectral derivative (SD) method. In vivo experiments verified the practicability and effectiveness of the proposed method.

Quantitative Bioluminescence Tomography for In Vivo Volumetric-Guided Radiotherapy.

Several groups, including ours, have initiated efforts to develop small-animal irradiators that mimic radiation therapy (RT) for human treatment. The major image modality used to guide irradiation is cone-beam computed tomography (CBCT). While CBCT provides excellent guidance capability, it is less adept at localizing soft tissue targets growing in a low image contrast environment. In contrast, bioluminescence imaging (BLI) provides strong image contrast and thus is an attractive solution for soft tissue targeting. However, commonly used 2D BLI on an animal surface is inadequate to guide irradiation, because optical transport from an internal bioluminescent tumor is highly susceptible to the effects of optical path length and tissue absorption and scattering. Recognition of these limitations led us to integrate 3D bioluminescence tomography (BLT) with the small animal radiation research platform (SARRP). In this chapter, we introduce quantitative BLT (QBLT) with the advanced capabilities of quantifying tumor volume for irradiation guidance. The detail of system components, calibration protocol, and step-by-step procedure to conduct the QBLT-guided irradiation are described.

In vivo bioluminescence tomography-guided radiation research platform for pancreatic cancer: an initial study using subcutaneous and orthotopic pancreatic tumor models.

Genetically engineered mouse model(GEMM) that develops pancreatic ductal adenocarcinoma(PDAC) offers an experimental system to advance our understanding of radiotherapy(RT) for pancreatic cancer. Cone beam CT(CBCT)-guided small animal radiation research platform(SARRP) has been developed to mimic the RT used for human. However, we recognized that CBCT is inadequate to localize the PDAC growing in low image contrast environment. We innovated bioluminescence tomography(BLT) to guide SARRP irradiation for in vivo PDAC. Before working on the complex PDAC-GEMM, we first validated our BLT target localization using subcutaneous and orthotopic pancreatic tumor models. Our BLT process involves the animal transport between the BLT system and SARRP. We inserted a titanium wire into the orthotopic tumor as the fiducial marker to track the tumor location and to validate the BLT reconstruction accuracy. Our data shows that with careful animal handling, minimum disturbance for target position was introduced during our BLT imaging procedure(<0.5mm). However, from longitudinal 2D bioluminescence image(BLI) study, the day-to-day location variation for an abdominal tumor can be significant. We also showed that the 2D BLI in single projection setting cannot accurately capture the abdominal tumor location. It renders that 3D BLT with multiple-projection is needed to quantify the tumor volume and location for precise radiation research. Our initial results show the BLT can retrieve the location at 2mm accuracy for both tumor models, and the tumor volume can be delineated within 25% accuracy. The study for the subcutaneous and orthotopic models will provide us valuable knowledge for BLT-guided PDAC-GEMM radiation research.

Sparse-graph manifold learning method for bioluminescence tomography.

In preclinical researches, bioluminescence tomography (BLT) has widely been used for tumor imaging and monitoring, imaged-guided tumor therapy, and so forth. For these biological applications, both tumor spatial location and morphology analysis are the leading problems needed to be taken into account. However, most existing BLT reconstruction methods were proposed for some specific applications with a focus on sparse representation or morphology recovery, respectively. How to design a versatile algorithm that can simultaneously deal with both aspects remains an impending problem. In this study, a Sparse-Graph Manifold Learning (SGML) method was proposed to balance the source sparseness and morphology, by integrating non-convex sparsity constraint and dynamic Laplacian graph model. Furthermore, based on the nonconvex optimization theory and some iterative approximation, we proposed a novel iteratively reweighted soft thresholding algorithm (IRSTA) to solve the SGML model. Numerical simulations and in vivo experiments result demonstrated that the proposed SGML method performed much superior to the comparative methods in spatial localization and tumor morphology recovery for various source settings. It is believed that the SGML method can be applied to the related optical tomography and facilitate the development of optical molecular tomography.

Filtered maximum likelihood expectation maximization based global reconstruction for bioluminescence tomography.

The reconstruction of bioluminescence tomography (BLT) is severely ill-posed due to the insufficient measurements and diffuses nature of the light propagation. Predefined permissible source region (PSR) combined with regularization terms is one common strategy to reduce such ill-posedness. However, the region of PSR is usually hard to determine and can be easily affected by subjective consciousness. Hence, we theoretically developed a filtered maximum likelihood expectation maximization (fMLEM) method for BLT. Our method can avoid predefining the PSR and provide a robust and accurate result for global reconstruction. In the method, the simplified spherical harmonics approximation (SPN) was applied to characterize diffuse light propagation in medium, and the statistical estimation-based MLEM algorithm combined with a filter function was used to solve the inverse problem. We systematically demonstrated the performance of our method by the regular geometry- and digital mouse-based simulations and a liver cancer-based in vivo experiment. Graphical abstract The filtered MLEM-based global reconstruction method for BLT.

Bayesian sparse-based reconstruction in bioluminescence tomography improves localization accuracy and reduces computational time.

Bioluminescence tomography (BLT) provides fundamental insight into biological processes in vivo. To fully realize its potential, it is important to develop image reconstruction algorithms that accurately visualize and quantify the bioluminescence signals taking advantage of limited boundary measurements. In this study, a new 2-step reconstruction method for BLT is developed by taking advantage of the sparse a priori information of the light emission using multispectral measurements. The first step infers a wavelength-dependent prior by using all multi-wavelength measurements. The second step reconstructs the source distribution based on this developed prior. Simulation, phantom and in vivo results were performed to assess and compare the accuracy and the computational efficiency of this algorithm with conventional sparsity-promoting BLT reconstruction algorithms, and results indicate that the position errors are reduced from a few millimeters down to submillimeter, and reconstruction time is reduced by 3 orders of magnitude in most cases, to just under a few seconds. The recovery of single objects and multiple (2 and 3) small objects is simulated, and the recovery of images of a mouse phantom and an experimental animal with an existing luminescent source in the abdomen is demonstrated. Matlab code is available at https://github.com/jinchaofeng/code/tree/master.

A hybrid clustering algorithm for multiple-source resolving in bioluminescence tomography.

Bioluminescence tomography is a preclinical imaging modality to locate and quantify internal bioluminescent sources from surface measurements, which experienced rapid growth in the last 10 years. However, multiple-source resolving remains a challenging issue in BLT. In this study, it is treated as an unsupervised pattern recognition problem based on the reconstruction result, and a novel hybrid clustering algorithm combining the advantages of affinity propagation (AP) and K-means is developed to identify multiple sources automatically. Moreover, we incorporate the clustering analysis into a general multiple-source reconstruction framework, which can provide stable reconstruction and accurate resolving result without providing the number of targets. Numerical simulations and in vivo experiments on 4T1-luc2 mouse model were conducted to assess the performance of the proposed method in multiple-source resolving. The encouraging results demonstrate significant effectiveness and potential of our method in preclinical BLT applications.

Optical molecular imaging-guided radiation therapy part 1: Integrated x-ray and bioluminescence tomography.

PURPOSE: X-ray CT faces challenges in differentiating tumors from surrounding healthy tissues. A bioluminescence tomography (BLT) system which can directly reconstruct the internal luminescent tumors, was developed and integrated with CT system to accurately guide radiation dose delivery. METHODS: The BLT system, employing a lens-coupled CCD camera, was physically registered with an onboard cone beam CT system in an image-guided small animal arc radiation treatment system (iSMAART). The onboard CT provides animal anatomy and accurate surface contour used to construct the three-dimensional mesh for the BLT reconstruction. Bioluminescence projections were captured from multiple angles, once every 90° rotation. The BLT reconstruction was performed on an orthotopic prostate tumor model to evaluate its robustness and accuracy in locating and delineating bioluminescent tumors. The location and volume of the tumor identified from iodinated contrast CT was used to validate the BLT performance. Phantom experiment was also conducted to confirm the precision of BLT-guided radiation. RESULTS: The BLT was able to accurately locate the bioluminescent tumors with < 0.5 mm error. The tumor volume in BLT was significantly correlated with that in the iodinated contrast CT (R2 = 0.81, P < 0.001). Phantom experiments further validated that BLT can be used to guide radiation with submillimeter accuracy. CONCLUSION: Together with CT, BLT can provide precision radiation guidance and robust tumor volume assessment in small animal cancer research.

Reconstruction Method for In Vivo Bioluminescence Tomography Based on the Split Bregman Iterative and Surrogate Functions.

PURPOSE: Bioluminescence tomography (BLT) can provide in vivo three-dimensional (3D) images for quantitative analysis of biological processes in preclinical small animal studies, which is superior than the conventional planar bioluminescence imaging. However, to reconstruct light sources under the skin in 3D with desirable accuracy and efficiency, BLT has to face the ill-posed and ill-conditioned inverse problem. In this paper, we developed a new method for BLT reconstruction, which utilized the mathematical strategies of the split Bregman iterative and surrogate functions (SBISF) method. PROCEDURES: The proposed method considered the sparsity characteristic of the reconstructed sources. Thus, the sparsity itself was regarded as a kind of a priori information, and the sparse regularization is incorporated, which can accurately locate the position of the sources. Numerical simulation experiments of multisource cases with comparative analyses were performed to evaluate the performance of the proposed method. Then, a bead-implanted mouse and a breast cancer xenograft mouse model were employed to validate the feasibility of this method in in vivo experiments. RESULTS: The results of both simulation and in vivo experiments indicated that comparing with the L1-norm iteration shrinkage method and non-monotone spectral projected gradient pursuit method, the proposed SBISF method provided the smallest position error with the least amount of time consumption. CONCLUSIONS: The SBISF method is able to achieve high accuracy and high efficiency in BLT reconstruction and hold great potential for making BLT more practical in small animal studies.

L p Regularization for Bioluminescence Tomography Based on the Split Bregman Method.

PURPOSE: Bioluminescence tomography (BLT) is a promising in vivo optical imaging technique in preclinical research at cellular and molecular levels. The problem of BLT reconstruction is quite ill-posed and ill-conditioned. In order to achieve high accuracy and efficiency for its inverse reconstruction, we proposed a novel approach based on L p regularization with the Split Bregman method. PROCEDURES: The diffusion equation was used as the forward model. Then, we defined the objective function of L p regularization and developed a Split Bregman iteration algorithm to optimize this function. After that, we conducted numerical simulations and in vivo experiments to evaluate the accuracy and efficiency of the proposed method. RESULTS: The results of the simulations indicated that compared with the conjugate gradient and iterative shrinkage methods, the proposed method is more accurate and faster for multisource reconstructions. Furthermore, in vivo imaging suggested that it could clearly distinguish the viable and apoptotic tumor regions. CONCLUSIONS: The Split Bregman iteration method is able to minimize the L p regularization problem and achieve fast and accurate reconstruction in BLT.

Enhanced immunotherapy of SM5-1 in hepatocellular carcinoma by conjugating with gold nanoparticles and its in vivo bioluminescence tomographic evaluation.

SM5-1 is a humanized mouse monoclonal antibody, targeting an over-expressed membrane protein of approximately 230 kDa in hepatocellular carcinoma (HCC). SM5-1 can be used for target therapy in hepatocellular carinoma due to its ability of inhibiting cell growth and inducing apoptosis. However, the tumor inhibition efficacy of SM5-1 in HCC cancer treatment remains low. In this study, we synthesized SM5-1-conjugated gold nanoparticles (Au-SM5-1 NPs) and investigated their anticancer efficacy in HCC both in vitro and in vivo. The tumor inhibition rates of Au-SM5-1 NPs for subcutaneous tumor mice were 40.10% ± 4.34%, 31.37% ± 5.12%, and 30.63% ± 4.87% on day 12, 18, and 24 post-treatment as determined by bioluminescent intensity. In addition, we investigated the antitumor efficacy of Au-SM5-1 NPs in orthotopic HCC tumor models. The results showed that the inhibition rates of Au-SM5-1 NPs can reach up to 39.64% ± 4.87% on day 31 post-treatment determined by the bioluminescent intensity of the abdomen in tumor-bearing mice. Furthermore, three-dimensional reconstruction results of the orthotopic tumor revealed that Au-SM5-1 NPs significantly inhibited tumor growth compared with SM5-1 alone. Our results suggested that the developed Au-SM5-1 NPs has great potential as an antibody-based nano-drug for HCC therapy.

Multi-modal molecular diffuse optical tomography system for small animal imaging.

A multi-modal optical imaging system for quantitative 3D bioluminescence and functional diffuse imaging is presented, which has no moving parts and uses mirrors to provide multi-view tomographic data for image reconstruction. It is demonstrated that through the use of trans-illuminated spectral near infrared measurements and spectrally constrained tomographic reconstruction, recovered concentrations of absorbing agents can be used as prior knowledge for bioluminescence imaging within the visible spectrum. Additionally, the first use of a recently developed multi-view optical surface capture technique is shown and its application to model-based image reconstruction and free-space light modelling is demonstrated. The benefits of model-based tomographic image recovery as compared to 2D planar imaging are highlighted in a number of scenarios where the internal luminescence source is not visible or is confounding in 2D images. The results presented show that the luminescence tomographic imaging method produces 3D reconstructions of individual light sources within a mouse-sized solid phantom that are accurately localised to within 1.5mm for a range of target locations and depths indicating sensitivity and accurate imaging throughout the phantom volume. Additionally the total reconstructed luminescence source intensity is consistent to within 15% which is a dramatic improvement upon standard bioluminescence imaging. Finally, results from a heterogeneous phantom with an absorbing anomaly are presented demonstrating the use and benefits of a multi-view, spectrally constrained coupled imaging system that provides accurate 3D luminescence images.