Optical Molecular Imaging Techniques Research Articles

Fluorescence molecular tomography based on an online maximum a posteriori estimation algorithm

Fluorescence molecular tomography (FMT) is a non-invasive, radiation-free, and highly sensitive optical molecular imaging technique for early tumor detection. However, inadequate measurement information along with significant scattering of near-infrared light within the tissue leads to high ill-posedness in the inverse problem of FMT. To improve the quality and efficiency of FMT reconstruction, we build a reconstruction model based on log-sum regularization and introduce an online maximum a posteriori estimation (OPE) algorithm to solve the non-convex optimization problem. The OPE algorithm approximates a stationary point by evaluating the gradient of the objective function at each iteration, and its notable strength lies in the remarkable speed of convergence. The results of simulations and experiments demonstrate that the OPE algorithm ensures good reconstruction quality and exhibits outstanding performance in terms of reconstruction efficiency.

Logarithmic total variation regularization via preconditioned conjugate gradient method for sparse reconstruction of bioluminescence tomography

Background and objectiveBioluminescence Tomography (BLT) is a powerful optical molecular imaging technique that enables the noninvasive investigation of dynamic biological phenomena. It aims to reconstruct the three-dimensional spatial distribution of bioluminescent sources from optical measurements collected on the surface of the imaged object. However, BLT reconstruction is a challenging ill-posed problem due to the scattering effect of light and the limitations in detecting surface photons, which makes it difficult for existing methods to achieve satisfactory reconstruction results. In this study, we propose a novel method for sparse reconstruction of BLT based on a preconditioned conjugate gradient with logarithmic total variation regularization (PCG-logTV). MethodThis PCG-logTV method incorporates the sparsity of overlapping groups and enhances the sparse structure of these groups using logarithmic functions, which can preserve edge features and achieve more stable reconstruction results in BLT. To accelerate the convergence of the algorithm solution, we use the preconditioned conjugate gradient iteration method on the objective function and obtain the reconstruction results. We demonstrate the performance of our proposed method through numerical simulations and in vivo experiment. Results and conclusionsThe results show that the PCG-logTV method obtains the most accurate reconstruction results, and the minimum position error (LE) is 0.254mm, which is 26%, 31% and 34% of the FISTA (0.961), IVTCG (0.81) and L1-TV (0.739) methods, and the root mean square error (RMSE) and relative intensity error (RIE) are the smallest, indicating that it is closest to the real light source. In addition, compared with the other three methods, the PCG-logTV method also has the highest DICE similarity coefficient, which is 0.928, which means that this method can effectively reconstruct the three-dimensional spatial distribution of bioluminescent light sources, has higher resolution and robustness, and is beneficial to the preclinical and clinical studies of BLT.

In Vivo Bioluminescence for the Detection of the Fate of Pancreatic Islet Organoids Post-transplantation.

Pancreatic islet transplantation is a promising cell replacement treatment for patients afflicted with type 1 diabetes (T1D), which is an autoimmune disease resulting in the destruction of insulin-producing islet β-cells. However, the shortage of donor pancreatic islets significantly hampers the widespread application of this strategy as routine therapy. Pluripotent stem cell-derived insulin-producing islet organoids constitute a promising alternative β-cell source for T1D patients. Early after transplantation, it is critical to know the fate of transplanted islet organoids, but determining their survival remains a significant technical challenge. Bioluminescence imaging (BLI) is an optical molecular imaging technique that detects the survival of living cells using light emitted from luciferase-expressing bioreporter cells. Through BLI, the post-transplantation fate of islet organoids can be evaluated over time in a noninvasive fashion with minimal intervention, thus making BLI an ideal tool to determine the success of the transplant and improving cell replacement therapy approaches for T1D.

Elastic net-based non-negative iterative three-operator splitting strategy for Cerenkov luminescence tomography.

Cerenkov luminescence tomography (CLT) provides a powerful optical molecular imaging technique for non-invasive detection and visualization of radiopharmaceuticals in living objects. However, the severe photon scattering effect causes ill-posedness of the inverse problem, and the location accuracy and shape recovery of CLT reconstruction results are unsatisfactory for clinical application. Here, to improve the reconstruction spatial location accuracy and shape recovery ability, a non-negative iterative three operator splitting (NNITOS) strategy based on elastic net (EN) regularization was proposed. NNITOS formalizes the CLT reconstruction as a non-convex optimization problem and splits it into three operators, the least square, L1/2-norm regularization, and adaptive grouping manifold learning, then iteratively solved them. After stepwise iterations, the result of NNITOS converged progressively. Meanwhile, to speed up the convergence and ensure the sparsity of the solution, shrinking the region of interest was utilized in this strategy. To verify the effectiveness of the method, numerical simulations and in vivo experiments were performed. The result of these experiments demonstrated that, compared to several methods, NNITOS can achieve superior performance in terms of location accuracy, shape recovery capability, and robustness. We hope this work can accelerate the clinical application of CLT in the future.

PEGylated β-NaGdF4/Tb@CaF2 Core/Shell Nanophosphors for Enhanced Radioluminescence and Folate Receptor Targeting

Lanthanide-doped nanocrystals have been examined extensively as contrast agents for various optical molecular imaging techniques. One of the greatest strengths of these nanomaterials is their ability to enable novel imaging modalities, such as X-ray excited radioluminescence imaging, which leverages the exceptional tissue depth penetration of X-rays and reduced tissue autofluorescence. Here, we report a uniquely engineered NaGdF4/Tb@CaF2 nanoscintillator with substantial lattice mismatch through integration of coprecipitation and thermal decomposition synthetic routes. We observed greatly enhanced radioluminescence by the NaGdF4/15%Tb@CaF2 core/shell nanocrystals, which results from the minimized surface quenching and localized structure transformation. Polyethylene glycol coated NaGdF4/15%Tb@CaF2 nanocrystals demonstrated robust aqueous colloidal stability and were well tolerated by a panel of cell lines. The core/shell NaGdF4/15%Tb@CaF2 nanophosphors were subsequently decorated with targeting folate ligands and investigated as an X-ray luminescence imaging probe in vitro. Overall, the results suggest that these optimized radioluminescent nanophosphors have the potential to enable X-ray excited optical emission for biological imaging and serve as energy mediators in theranostic applications.

Penalty method for source reconstruction of multispectral bioluminescence tomography

Bioluminescence tomography (BLT) is a promising optical molecular imaging technique in preclinical research. One key problem for BLT is how to deal with the severe ill-posedness and obtain accurate and stable reconstruction. We propose a penalty method for recovering bioluminescence sources, in which we transform reconstruction of BLT into an L1/2-norm penalty problem and solve it via a nonmonotone proximal gradient method with a suitable penalty parameter update scheme. Simulations and phantom experiments based on multispectral measurements were designed to evaluate the proposed reconstruction method. The encouraging results show that the proposed method has better reconstruction accuracy and image quality than the comparative methods.

Illuminate hepatobiliary and pancreatic surgery using optical molecular imaging methods

Since the concept of molecular imaging was put forward in 1999, optical molecular imaging techniques have been widely applied in the field of biomedical and clinical research. Its unique application value is especially shown in hepatobiliary surgery, such as in liver tumor imaging, anatomical liver resection, liver transplant angiography, cholangiography, and bile or pancreatic leakage prevention. Optical molecular imaging techniquelights uptargeted areas in surgical operations and provides convenience in carrying out precision operation. This paper reviewed the advantages of optical molecular imaging technology in clinical research and discussed its limitations in translational surgery, and put forward possible directions in improvement for the future. Key words: Optical molecular imaging; Liver surgery; Intraoperative fluorescence image-guided surgery; Indocyanine green

Fast in vivo bioluminescence tomography using a novel pure optical imaging technique

Bioluminescence tomography (BLT) is a novel optical molecular imaging technique that advanced the conventional planar bioluminescence imaging (BLI) into a quantifiable three-dimensional (3D) approach in preclinical living animal studies in oncology. In order to solve the inverse problem and reconstruct tumor lesions inside animal body accurately, the prior structural information is commonly obtained from X-ray computed tomography (CT). This strategy requires a complicated hybrid imaging system, extensive post imaging analysis and involvement of ionizing radiation. Moreover, the overall robustness highly depends on the fusion accuracy between the optical and structural information. Here, we present a pure optical bioluminescence tomographic (POBT) system and a novel BLT workflow based on multi-view projection acquisition and 3D surface reconstruction. This method can reconstruct the 3D surface of an imaging subject based on a sparse set of planar white-light and bioluminescent images, so that the prior structural information can be offered for 3D tumor lesion reconstruction without the involvement of CT. The performance of this novel technique was evaluated through the comparison with a conventional dual-modality tomographic (DMT) system and a commercialized optical imaging system (IVIS Spectrum) using three breast cancer xenografts. The results revealed that the new technique offered comparable in vivo tomographic accuracy with the DMT system ([Formula: see text]) in much shorter data analysis time. It also offered significantly better accuracy comparing with the IVIS system ([Formula: see text]) without sacrificing too much time.

Multi-atlas registration and adaptive hexahedral voxel discretization for fast bioluminescence tomography.

Bioluminescence tomography (BLT) has been a valuable optical molecular imaging technique to non-invasively depict the cellular and molecular processes in living animals with high sensitivity and specificity. Due to the inherent ill-posedness of BLT, a priori information of anatomical structure is usually incorporated into the reconstruction. The structural information is usually provided by computed tomography (CT) or magnetic resonance imaging (MRI). In order to obtain better quantitative results, BLT reconstruction with heterogeneous tissues needs to segment the internal organs and discretize them into meshes with the finite element method (FEM). It is time-consuming and difficult to handle the segmentation and discretization problems. In this paper, we present a fast reconstruction method for BLT based on multi-atlas registration and adaptive voxel discretization to relieve the complicated data processing procedure involved in the hybrid BLT/CT system. A multi-atlas registration method is first adopted to estimate the internal organ distribution of the imaged animal. Then, the animal volume is adaptively discretized into hexahedral voxels, which are fed into FEM for the following BLT reconstruction. The proposed method is validated in both numerical simulation and an in vivo study. The results demonstrate that the proposed method can reconstruct the bioluminescence source efficiently with satisfactory accuracy.

Research on the interaction mechanism between quantum dots and radionuclides for the improvement of Cerenkov luminescence imaging

Cerenkov luminescence imaging (CLI) is a relatively new optical molecular imaging technique. The nature of Stokes shift in quantum dots (QD) can be used to improve the quality of CLI. However, the interaction mechanism of QD with Cerenkov light remains unclear. In this work, the interaction mechanism between QD and radionuclides emitting β rays, γ rays, and Cerenkov light was investigated. The 96-well plates were used to test the different levels of radioactivity of radionuclides with different QD concentrations. Transparent vials were used to determine the relationship between QD fluorescence intensity and the distance from QD to the radionuclide. In addition, black paper was used to block the transmission of Cerenkov light through the QD vials. A linear relationship was found between the number of photons and the radioactivity of radionuclides when the QD concentration was kept constant. Similarly, the number of photons was linearly related to the QD concentration when the radioactivity of radionuclides was kept constant. Furthermore, with the increases in the distance between radionuclides and quantum dots, the number of photons was exponentially decreased. Meanwhile, the number of photons emitted from QD excited by Cerenkov light accounted for 20% the total number of photons excited by 131I radionuclide. The result proved that QD was not only excited by Cerenkov light but also by other rays.

TH-AB-204-01: Cherenkov- Excited Luminescence Scanned Imaging (CELSI) for High-Resolution, Deep-Tissue, in Vivo Optical Molecular Imaging with Limited Radiation Dose

Purpose: A new imaging modality Cherenkov-excited luminescence scanned imaging (CELSI) is demonstrated illustrating that LINAC beams induce Cherenkov emission within tissue, and that in-turn can excite luminescence of optical probes. This is achieved in a highly spatially confined fashion thereby allowing scanned imaging of distributions of luminescent sources. Methods: A 5 mm thick line-excitation megavoltage X-ray beam (6 MV) was collimated and moved by the multi-leaf collimator (MLC) of a linear accelerator (LINAC), to scan in 3 orthogonal directions. The scan in this demonstration was through a rat abdomen for lymph node imaging. The node was injected with oxygen-sensitive phosphor (Oxyphor PtG4), having strong luminescence lifetime, which is sensitive to the local oxygen concentration. During the scanning, Cherenkov-excited luminescence was continuously integrated by an intensified charge-coupled device (ICCD) synchronized to radiation pulses, and the position of the total signal was back-projected to the position of the scanning beam. Results: The lymph node was accurately located in the axillary region by CELSI imaging. Through lifetime measurement of the luminescence signal from within the lymph node, the pO2 was found to be reporting the true oxygenation level. Phantom studies validated that an inclusion with size below 1 mm could be reconstructed through a layer of 20 mm thick tissue equivalent phantom material. Concentrations of PtG4 down to 100 nM were detectable and capillary tubes containing the probe with diameters down to 200 µm could be resolved by CELSI, at 5 mm depth in tissue equivalent phantoms. Conclusion: CELSI is reported here for the first time, as an innovative optical molecular imaging technique by utilizing the LINAC as an optical scanning and excitation device. Potential applications of CELSI include reconstructions of interested optical probes and recoveries of local physiological information with relatively high spatial resolution.

New Researches and Application Progress of Commonly Used Optical Molecular Imaging Technology

Optical molecular imaging, a new medical imaging technique, is developed based on genomics, proteomics and modern optical imaging technique, characterized by non-invasiveness, non-radiativity, high cost-effectiveness, high resolution, high sensitivity and simple operation in comparison with conventional imaging modalities. Currently, it has become one of the most widely used molecular imaging techniques and has been applied in gene expression regulation and activity detection, biological development and cytological detection, drug research and development, pathogenesis research, pharmaceutical effect evaluation and therapeutic effect evaluation, and so forth, This paper will review the latest researches and application progresses of commonly used optical molecular imaging techniques such as bioluminescence imaging and fluorescence molecular imaging.

Abstract CN08-01: Expediting clinical translation of optical molecular imaging techniques in oncology and its role in preventive medicine

Abstract In recent years, significant progress has been made in both optical imaging systems and fluorescent contrast agents for clinical applications. NIRF imaging with a free-floating imaging device mounted on the ceiling of the operating theatre or on a microscope articulating arm during surgery for cancer will enable visualization of tumor delineation, locoregional metastases, remnant disease as well as e.g. tumor-containing lymph nodes. Hereby, the surgeon can both detect (diagnostic) and excise (therapeutic) malignant tissue and possible residual disease at the same time. The use of NIRF optical imaging has a range of advantages. Most prominent among these is the fact that it is very safe technology, simple to operate, fast, high resolution (as low as 1 mm), relatively inexpensive and makes use of non-ionizing radiation. Based on the above, it is clear that intra-operative imaging is on the verge of entering standard clinical practice for surgery. Not only the imaging system but also the availability of clinical grade tumor-targeted probes is of the utmost importance for a successful introduction into clinical practice. This talk will give an overview of the current concepts and future perspectives of intraoperative fluorescence image-guided surgery using non-targeted and targeted optical contrast agents for the first-time ever used in patients with ovarian cancer and the anticipated developments within the next 5 years. It will become clear that agencies like the FDA and EMA will play a major role in bringing this technology into the clinic and the necessity of standardization of methodology when applied in multinational multicenter studies. Moreover, the role of optical molecular imaging as a screening instrument in preventive medicine will be outlined. Citation Format: Gooitzen M. van Dam. Expediting clinical translation of optical molecular imaging techniques in oncology and its role in preventive medicine. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr CN08-01.

A generalized hybrid algorithm for bioluminescence tomography

Bioluminescence tomography (BLT) is a promising optical molecular imaging technique on the frontier of biomedical optics. In this paper, a generalized hybrid algorithm has been proposed based on the graph cuts algorithm and gradient-based algorithms. The graph cuts algorithm is adopted to estimate a reliable source support without prior knowledge, and different gradient-based algorithms are sequentially used to acquire an accurate and fine source distribution according to the reconstruction status. Furthermore, multilevel meshes for the internal sources are used to speed up the computation and improve the accuracy of reconstruction. Numerical simulations have been performed to validate this proposed algorithm and demonstrate its high performance in the multi-source situation even if the detection noises, optical property errors and phantom structure errors are involved in the forward imaging.

Antibody-labeled fluorescence imaging of dendritic cell populations in vivo

We report an optical molecular imaging technique that exploits local administration of fluorophore-conjugated antibodies and confocal fluorescence microscopy to achieve high-contrast imaging of host cell populations in normal and tumor tissue in living mice. The method achieves micron-scale spatial resolution to depths greater than 100 mum. We illustrate the capabilities of this approach by imaging two dendritic cell populations in the skin and normal and tumor vasculature in vivo.

Molecular imaging with optics: primer and case for near-infrared fluorescence techniques in personalized medicine

We compare and contrast the development of optical molecular imaging techniques with nuclear medicine with a didactic emphasis for initiating readers into the field of molecular imaging. The nuclear imaging techniques of gamma scintigraphy, single-photon emission computed tomography, and positron emission tomography are first briefly reviewed. The molecular optical imaging techniques of bioluminescence and fluorescence using gene reporter/probes and gene reporters are described prior to introducing the governing factors of autofluorescence and excitation light leakage. The use of dual-labeled, near-infrared excitable and radio-labeled agents are described with comparative measurements between planar fluorescence and nuclear molecular imaging. The concept of time-independent and -dependent measurements is described with emphasis on integrating time-dependent measurements made in the frequency domain for 3-D tomography. Finally, we comment on the challenges and progress for translating near-infrared (NIR) molecular imaging agents for personalized medicine.