Cationic Poly(Amino Acid) Vaccine Adjuvant for Promoting Both Cell-Mediated and Humoral Immunity Against Influenza Virus.

Powerful adjuvants to augment vaccine efficacy with a less immunogenic vaccine system are in great demand. In this study, a novel squalene-based cationic poly(amino acid) adjuvant (CASq) that elicits both cellular (Th1) and humoral (Th2) immune responses is developed. CASq is demonstrated to promote cellular uptake of viral antigen and stimulate macrophages, leading to active production of interleukin-12. Furthermore, co-administration of inactivated pdm H1N1 vaccine with CASq significantly increases the generation of antigen-specific antibodies and T cell immune responses in mice, as well as resulting in complete prevention of disease symptoms and protection against lethal infection.

Multigrid tomographic inversion with variable resolution data and image spaces.

A multigrid inversion approach that uses variable resolutions of both the data space and the image space is proposed. Since the computational complexity of inverse problems typically increases with a larger number of unknown image pixels and a larger number of measurements, the proposed algorithm further reduces the computation relative to conventional multigrid approaches, which change only the image space resolution at coarse scales. The advantage is particularly important for data-rich applications, where data resolutions may differ for different scales. Applications of the approach to Bayesian reconstruction algorithms in transmission and emission tomography with a generalized Gaussian Markov random field image prior are presented, both with a Poisson noise model and with a quadratic data term. Simulation results indicate that the proposed multigrid approach results in significant improvement in convergence speed compared to the fixed-grid iterative coordinate descent method and a multigrid method with fixed-data resolution.

A general framework for nonlinear multigrid inversion.

A variety of new imaging modalities, such as optical diffusion tomography, require the inversion of a forward problem that is modeled by the solution to a three-dimensional partial differential equation. For these applications, image reconstruction is particularly difficult because the forward problem is both nonlinear and computationally expensive to evaluate. In this paper, we propose a general framework for nonlinear multigrid inversion that is applicable to a wide variety of inverse problems. The multigrid inversion algorithm results from the application of recursive multigrid techniques to the solution of optimization problems arising from inverse problems. The method works by dynamically adjusting the cost functionals at different scales so that they are consistent with, and ultimately reduce, the finest scale cost functional. In this way, the multigrid inversion algorithm efficiently computes the solution to the desired fine-scale inversion problem. Importantly, the new algorithm can greatly reduce computation because both the forward and inverse problems are more coarsely discretized at lower resolutions. An application of our method to Bayesian optical diffusion tomography with a generalized Gaussian Markov random-field image prior model shows the potential for very large computational savings. Numerical data also indicates robust convergence with a range of initialization conditions for this nonconvex optimization problem.

Source-detector calibration in three-dimensional Bayesian optical diffusion tomography.

Optical diffusion tomography is a method for reconstructing three-dimensional optical properties from light that passes through a highly scattering medium. Computing reconstructions from such data requires the solution of a nonlinear inverse problem. The situation is further complicated by the fact that while reconstruction algorithms typically assume exact knowledge of the optical source and detector coupling coefficients, these coupling coefficients are generally not available in practical measurement systems. A new method for estimating these unknown coupling coefficients in the three-dimensional reconstruction process is described. The joint problem of coefficient estimation and three-dimensional reconstruction is formulated in a Bayesian framework, and the resulting estimates are computed by using a variation of iterative coordinate descent optimization that is adapted for this problem. Simulations show that this approach is an accurate and efficient method for simultaneous reconstruction of absorption and diffusion coefficients as well as the coupling coefficients. A simple experimental result validates the approach.

Three-dimensional Bayesian optical diffusion tomography with experimental data.

Reconstructions of a three-dimensional absorber embedded in a scattering medium by use of frequency domain measurements of the transmitted light in a single source-detector plane are presented. The reconstruction algorithm uses Bayesian regularization and iterative coordinate descent optimization, and it incorporates estimation of the detector noise level, the source-detector coupling coefficient, and the background diffusion coefficient in addition to the absorption image. The use of multiple modulation frequencies is also investigated. The results demonstrate the utility of this algorithm, the importance of a three-dimensional model, and that out-of-plane scattering permits recovery of three-dimensional features from measurements in a single plane.

Fluorescence optical diffusion tomography.

A nonlinear, Bayesian optimization scheme is presented for reconstructing fluorescent yield and lifetime, the absorption coefficient, and the diffusion coefficient in turbid media, such as biological tissue. The method utilizes measurements at both the excitation and the emission wavelengths to reconstruct all unknown parameters. The effectiveness of the reconstruction algorithm is demonstrated by simulation and by application to experimental data from a tissue phantom containing the fluorescent agent Indocyanine Green.

Fluorescence optical diffusion tomography using multiple-frequency data.

A method is presented for fluorescence optical diffusion tomography in turbid media using multiple-frequency data. The method uses a frequency-domain diffusion equation model to reconstruct the fluorescent yield and lifetime by means of a Bayesian framework and an efficient, nonlinear optimizer. The method is demonstrated by using simulations and laboratory experiments to show that reconstruction quality can be improved in certain problems through the use of more than one frequency. A broadly applicable mutual information performance metric is also presented and used to investigate the advantages of using multiple modulation frequencies compared with using only one.