Quantitative Photo-acoustic Tomography with Partial Data

Photo-acoustic tomography is a newly developed hybrid imaging modality that combines a high-resolution modality with a high-contrast modality. We analyze the reconstruction of diffusion and absorption parameters in an elliptic equation and improve an earlier result of Bal and Uhlmann to the partial date case. We show that the reconstruction can be uniquely determined by the knowledge of 4 internal data based on well-chosen partial boundary conditions. Stability of this reconstruction is ensured if a convexity condition is satisfied. Similar stability result is obtained without this geometric constraint if 4n well-chosen partial boundary conditions are available, where $n$ is the spatial dimension. The set of well-chosen boundary measurements is characterized by some complex geometric optics (CGO) solutions vanishing on a part of the boundary.Comment: arXiv admin note: text overlap with arXiv:0910.250

Neural networks-based regularization for large-scale medical image reconstruction

In this paper we present a generalized Deep Learning-based approach for solving ill-posed large-scale inverse problems occuring in medical image reconstruction. Recently, Deep Learning methods using iterative neural networks (NNs) and cascaded NNs have been reported to achieve state-of-the-art results with respect to various quantitative quality measures as PSNR, NRMSE and SSIM across different imaging modalities. However, the fact that these approaches employ the application of the forward and adjoint operators repeatedly in the network architecture requires the network to process the whole images or volumes at once, which for some applications is computationally infeasible. In this work, we follow a different reconstruction strategy by strictly separating the application of the NN, the regularization of the solution and the consistency with the measured data. The regularization is given in the form of an image prior obtained by the output of a previously trained NN which is used in a Tikhonov regularization framework. By doing so, more complex and sophisticated network architectures can be used for the removal of the artefacts or noise than it is usually the case in iterative NNs. Due to the large scale of the considered problems and the resulting computational complexity of the employed networks, the priors are obtained by processing the images or volumes as patches or slices. We evaluated the method for the cases of 3D cone-beam low dose CT and undersampled 2D radial cine MRI and compared it to a total variation-minimization-based reconstruction algorithm as well as to a method with regularization based on learned overcomplete dictionaries. The proposed method outperformed all the reported methods with respect to all chosen quantitative measures and further accelerates the regularization step in the reconstruction by several orders of magnitude

A series solution and a fast algorithm for the inversion of the spherical mean Radon transform

An explicit series solution is proposed for the inversion of the spherical mean Radon transform. Such an inversion is required in problems of thermo- and photo- acoustic tomography. Closed-form inversion formulae are currently known only for the case when the centers of the integration spheres lie on a sphere surrounding the support of the unknown function, or on certain unbounded surfaces. Our approach results in an explicit series solution for any closed measuring surface surrounding a region for which the eigenfunctions of the Dirichlet Laplacian are explicitly known - such as, for example, cube, finite cylinder, half-sphere etc. In addition, we present a fast reconstruction algorithm applicable in the case when the detectors (the centers of the integration spheres) lie on a surface of a cube. This algorithm reconsrtucts 3-D images thousands times faster than backprojection-type methods

Inverse Diffusion Theory of Photoacoustics

This paper analyzes the reconstruction of diffusion and absorption parameters in an elliptic equation from knowledge of internal data. In the application of photo-acoustics, the internal data are the amount of thermal energy deposited by high frequency radiation propagating inside a domain of interest. These data are obtained by solving an inverse wave equation, which is well-studied in the literature. We show that knowledge of two internal data based on well-chosen boundary conditions uniquely determines two constitutive parameters in diffusion and Schroedinger equations. Stability of the reconstruction is guaranteed under additional geometric constraints of strict convexity. No geometric constraints are necessary when $2n$ internal data for well-chosen boundary conditions are available, where $n$ is spatial dimension. The set of well-chosen boundary conditions is characterized in terms of appropriate complex geometrical optics (CGO) solutions.Comment: 24 page

Uniqueness of reconstruction and an inversion procedure for thermoacoustic and photoacoustic tomography

The paper contains a simple approach to reconstruction in Thermoacoustic and Photoacoustic Tomography. The technique works for any geometry of point detectors placement and for variable sound speed satisfying a non-trapping condition. A uniqueness of reconstruction result is also obtained

Sparse Regularization with lql^q Penalty Term

We consider the stable approximation of sparse solutions to non-linear operator equations by means of Tikhonov regularization with a subquadratic penalty term. Imposing certain assumptions, which for a linear operator are equivalent to the standard range condition, we derive the usual convergence rate $O(\sqrt{\delta})$ of the regularized solutions in dependence of the noise level $\delta$. Particular emphasis lies on the case, where the true solution is known to have a sparse representation in a given basis. In this case, if the differential of the operator satisfies a certain injectivity condition, we can show that the actual convergence rate improves up to $O(\delta)$.Comment: 15 page

Murine Gammaretrovirus Group G3 Was Not Found in Swedish Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia

BACKGROUND: The recent report of gammaretroviruses of probable murine origin in humans, called xenotropic murine retrovirus related virus (XMRV) and human murine leukemia virus related virus (HMRV), necessitated a bioinformatic search for this virus in genomes of the mouse and other vertebrates, and by PCR in humans. RESULTS: Three major groups of murine endogenous gammaretroviruses were identified. The third group encompassed both exogenous and endogenous Murine Leukemia Viruses (MLVs), and most XMRV/HMRV sequences reported from patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Two sensitive real-time PCRs for this group were developed. The predicted and observed amplification range for these and three published XMRV/HMRV PCRs demonstrated conspicuous differences between some of them, partly explainable by a recombinatorial origin of XMRV. Three reverse transcription real-time PCRs (RTQPCRs), directed against conserved and not overlapping stretches of env, gag and integrase (INT) sequences of XMRV/HMRV were used on human samples. White blood cells from 78 patients suffering from ME/CFS, of which 30 patients also fulfilled the diagnostic criteria for fibromyalgia (ME/CFS/FM) and in 7 patients with fibromyalgia (FM) only, all from the Gothenburg area of Sweden. As controls we analyzed 168 sera from Uppsala blood donors. We controlled for presence and amplifiability of nucleic acid and for mouse DNA contamination. To score as positive, a sample had to react with several of the XMRV/HMRV PCRs. None of the samples gave PCR reactions which fulfilled the positivity criteria. CONCLUSIONS: XMRV/HMRV like proviruses occur in the third murine gammaretrovirus group, characterized here. PCRs developed by us, and others, approximately cover this group, except for the INT RTQPCR, which is rather strictly XMRV specific. Using such PCRs, XMRV/HMRV could not be detected in PBMC and plasma samples from Swedish patients suffering from ME/CFS/FM, and in sera from Swedish blood donors

Molecular Insights into Reprogramming-Initiation Events Mediated by the OSKM Gene Regulatory Network

Somatic cells can be reprogrammed to induced pluripotent stem cells by over-expression of OCT4, SOX2, KLF4 and c-MYC (OSKM). With the aim of unveiling the early mechanisms underlying the induction of pluripotency, we have analyzed transcriptional profiles at 24, 48 and 72 hours post-transduction of OSKM into human foreskin fibroblasts. Experiments confirmed that upon viral transduction, the immediate response is innate immunity, which induces free radical generation, oxidative DNA damage, p53 activation, senescence, and apoptosis, ultimately leading to a reduction in the reprogramming efficiency. Conversely, nucleofection of OSKM plasmids does not elicit the same cellular stress, suggesting viral response as an early reprogramming roadblock. Additional initiation events include the activation of surface markers associated with pluripotency and the suppression of epithelial-to-mesenchymal transition. Furthermore, reconstruction of an OSKM interaction network highlights intermediate path nodes as candidates for improvement intervention. Overall, the results suggest three strategies to improve reprogramming efficiency employing: 1) anti-inflammatory modulation of innate immune response, 2) pre-selection of cells expressing pluripotency-associated surface antigens, 3) activation of specific interaction paths that amplify the pluripotency signal

Inhibition of Src kinase activity attenuates amyloid associated microgliosis in a murine model of Alzheimer’s disease

<p>Abstract</p> <p>Background</p> <p>Microglial activation is an important histologic characteristic of the pathology of Alzheimer’s disease (AD). One hypothesis is that amyloid beta (Aβ) peptide serves as a specific stimulus for tyrosine kinase-based microglial activation leading to pro-inflammatory changes that contribute to disease. Therefore, inhibiting Aβ stimulation of microglia may prove to be an important therapeutic strategy for AD.</p> <p>Methods</p> <p>Primary murine microglia cultures and the murine microglia cell line, BV2, were used for stimulation with fibrillar Aβ1-42. The non-receptor tyrosine kinase inhibitor, dasatinib, was used to treat the cells to determine whether Src family kinase activity was required for the Aβ stimulated signaling response and subsequent increase in TNFα secretion using Western blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. A histologic longitudinal analysis was performed using an AD transgenic mouse model, APP/PS1, to determine an age at which microglial protein tyrosine kinase levels increased in order to administer dasatinib via mini osmotic pump diffusion. Effects of dasatinib administration on microglial and astroglial activation, protein phosphotyrosine levels, active Src kinase levels, Aβ plaque deposition, and spatial working memory were assessed via immunohistochemistry, Western blot, and T maze analysis.</p> <p>Results</p> <p>Aβ fibrils stimulated primary murine microglia via a tyrosine kinase pathway involving Src kinase that was attenuated by dasatinib. Dasatinib administration to APP/PS1 mice decreased protein phosphotyrosine, active Src, reactive microglia, and TNFα levels in the hippocampus and temporal cortex. The drug had no effect on GFAP levels, Aβ plaque load, or the related tyrosine kinase, Lyn. These anti-inflammatory changes correlated with improved performance on the T maze test in dasatinib infused animals compared to control animals.</p> <p>Conclusions</p> <p>These data suggest that amyloid dependent microgliosis may be Src kinase dependent <it>in vitro</it> and <it>in vivo.</it> This study defines a role for Src kinase in the microgliosis characteristic of diseased brains and suggests that particular tyrosine kinase inhibition may be a valid anti-inflammatory approach to disease. Dasatinib is an FDA-approved drug for treating chronic myeloid leukemia cancer with a reported ability to cross the blood-brain barrier. Therefore, this suggests a novel use for this drug as well as similar acting molecules.</p