Augmenting CT cardiac roadmaps with segmented streaming ultrasound

Static X-ray computed tomography (CT) volumes are often used as anatomic roadmaps during catheter-based cardiac interventions performed under X-ray fluoroscopy guidance. These CT volumes provide a high-resolution depiction of soft-tissue structures, but at only a single point within the cardiac and respiratory cycles. Augmenting these static CT roadmaps with segmented myocardial borders extracted from live ultrasound (US) provides intra-operative access to real-time dynamic information about the cardiac anatomy. In this work, using a customized segmentation method based on a 3D active mesh, endocardial borders of the left ventricle were extracted from US image streams (4D data sets) at a frame rate of approximately 5 frames per second. The coordinate systems for CT and US modalities were registered using rigid body registration based on manually selected landmarks, and the segmented endocardial surfaces were overlaid onto the CT volume. The root-mean squared fiducial registration error was 3.80 mm. The accuracy of the segmentation was quantitatively evaluated in phantom and human volunteer studies via comparison with manual tracings on 9 randomly selected frames using a finite-element model (the US image resolutions of the phantom and volunteer data were 1.3 x 1.1 x 1.3 mm and 0.70 x 0.82 x 0.77 mm, respectively). This comparison yielded 3.70±2.5 mm (approximately 3 pixels) root-mean squared error (RMSE) in a phantom study and 2.58±1.58 mm (approximately 3 pixels) RMSE in a clinical study. The combination of static anatomical roadmap volumes and dynamic intra-operative anatomic information will enable better guidance and feedback for image-guided minimally invasive cardiac interventions

Metabolic memory underlying minimal residual disease in breast cancer.

Funder: European Molecular Biology LaboratoryFunder: European Molecular Biology Laboratory (EMBL)Tumor relapse from treatment-resistant cells (minimal residual disease, MRD) underlies most breast cancer-related deaths. Yet, the molecular characteristics defining their malignancy have largely remained elusive. Here, we integrated multi-omics data from a tractable organoid system with a metabolic modeling approach to uncover the metabolic and regulatory idiosyncrasies of the MRD. We find that the resistant cells, despite their non-proliferative phenotype and the absence of oncogenic signaling, feature increased glycolysis and activity of certain urea cycle enzyme reminiscent of the tumor. This metabolic distinctiveness was also evident in a mouse model and in transcriptomic data from patients following neo-adjuvant therapy. We further identified a marked similarity in DNA methylation profiles between tumor and residual cells. Taken together, our data reveal a metabolic and epigenetic memory of the treatment-resistant cells. We further demonstrate that the memorized elevated glycolysis in MRD is crucial for their survival and can be targeted using a small-molecule inhibitor without impacting normal cells. The metabolic aberrances of MRD thus offer new therapeutic opportunities for post-treatment care to prevent breast tumor recurrence

Dilepton production in proton-proton collisions at BEVALAC energies

The dilepton production in elementary ${pp\to e^{+}e^{-}X}$ reactions at BEVALAC energies $T_{lab}=1\div 5$ GeV is investigated. The calculations include direct ${e^{+}e^{-}}$ decays of the vector mesons $\rho ^{0}$, $\omega$, and $\phi$, Dalitz decays of the $\pi ^{0}$-, $\eta$-, $$-, $\omega$-, and $\phi$-mesons, and of the baryon resonances $$ $...$ . The subthreshold vector meson production cross sections in $pp$ collisions are treated in a way sufficient to avoid double counting with the inclusive vector meson production. The vector meson dominance model for the transition form factors of the resonance Dalitz decays $R\to e^{+}e^{-}N$ is used in an extended form to ensure correct asymptotics which are in agreement with the quark counting rules. Such a modification gives an unified and consistent description of both $R\to N\gamma$ radiative decays and $R\to N\rho (\omega)$ meson decays. The effect of multiple pion production on the experimental efficiency for the detection of the dilepton pairs is studied. We find the dilepton yield in reasonable agreement with the experimental data for the set of intermediate energies whereas at the highest energy $T_{lab}=4.88$ GeV the number of dilepton pairs is likely to be overestimated experimentally in the mass range $M=300\div 700$ MeV.Comment: 25 pages (IOP style), 5 figures, revised manuscript accepted for publication in JP

A statistical method for retrospective cardiac and respiratory motion gating of interventional cardiac x-ray images

Purpose: Image-guided cardiac interventions involve the use of fluoroscopic images to guide the insertion and movement of interventional devices. Cardiorespiratory gating can be useful for 3D reconstruction from multiple x-ray views and for reducing misalignments between 3D anatomical models overlaid onto fluoroscopy. Methods: The authors propose a novel and potentially clinically useful retrospective cardiorespiratory gating technique. The principal component analysis (PCA) statistical method is used in combination with other image processing operations to make our proposed masked-PCA technique suitable for cardiorespiratory gating. Unlike many previously proposed techniques, our technique is robust to varying image-content, thus it does not require specific catheters or any other optically opaque structures to be visible. Therefore, it works without any knowledge of catheter geometry. The authors demonstrate the application of our technique for the purposes of retrospective cardiorespiratory gating of normal and very low dose x-ray fluoroscopy images. Results: For normal dose x-ray images, the algorithm was validated using 28 clinical electrophysiology x-ray fluoroscopy sequences (2168 frames), from patients who underwent radiofrequency ablation (RFA) procedures for the treatment of atrial fibrillation and cardiac resynchronization therapy procedures for heart failure. The authors established end-systole, end-expiration, and end-inspiration success rates of 97.0%, 97.9%, and 97.0%, respectively. For very low dose applications, the technique was tested on ten x-ray sequences from the RFA procedures with added noise at signal to noise ratio (SNR) values of √50, √10, √8, √6, √5, √2 and √1 to simulate the image quality of increasingly lower dose x-ray images. Even at the low SNR value of √2, representing a dose reduction of more than 25 times, gating success rates of 89.1%, 88.8%, and 86.8% were established. Conclusions: The proposed technique can therefore extract useful information from interventional x-ray images while minimizing exposure to ionizing radiation. © 2014 American Association of Physicists in Medicine

Developmentally Regulated Post-translational Modification of Nucleoplasmin Controls Histone Sequestration and Deposition

SummaryNucleoplasmin (Npm) is an abundant histone chaperone in vertebrate oocytes and embryos. During embryogenesis, regulation of Npm histone binding is critical for its function in storing and releasing maternal histones to establish and maintain the zygotic epigenome. Here, we demonstrate that Xenopus laevis Npm post-translational modifications (PTMs) specific to the oocyte and egg promote either histone deposition or sequestration, respectively. Mass spectrometry and Npm phosphomimetic mutations used in chromatin assembly assays identified hyperphosphorylation on the N-terminal tail as a critical regulator for sequestration. C-terminal tail phosphorylation and PRMT5-catalyzed arginine methylation enhance nucleosome assembly by promoting histone interaction with the second acidic tract of Npm. Electron microscopy reconstructions of Npm and TTLL4 activity toward the C-terminal tail demonstrate that oocyte- and egg-specific PTMs cause Npm conformational changes. Our results reveal that PTMs regulate Npm chaperoning activity by modulating Npm conformation and Npm-histone interaction, leading to histone sequestration in the egg

Orientational ordering of commensurate Fe(CO)5 monolayers on graphite

URL:http://link.aps.org/doi/10.1103/PhysRevB.27.5864 DOI:10.1103/PhysRevB.27.5864Elastic neutron diffraction and Mössbauer spectroscopy have been used to study the structure, orientational-disordering (OD) transition, and melting of an Fe(CO)5 submonolayer adsorbed on Grafoil. The OD transition occurs between 150 and 167 K from a two-sublattice (√7×√21) structure to a nearly (√7×√7) phase in which the molecules are believed to rotate about the surface normal. Mössbauer spectra exhibit a more abrupt variation with temperature near melting at 170 K than through the OD transition.This work was supported by NSF under Grants No. DMR-7905958 and No. INT-8012228, Israel-U.S. Binational Science Foundation Grant No. 2687, and the Danish Research Counci

Developmentally Regulated Post-translational Modification of Nucleoplasmin Controls Histone Sequestration and Deposition

SummaryNucleoplasmin (Npm) is an abundant histone chaperone in vertebrate oocytes and embryos. During embryogenesis, regulation of Npm histone binding is critical for its function in storing and releasing maternal histones to establish and maintain the zygotic epigenome. Here, we demonstrate that Xenopus laevis Npm post-translational modifications (PTMs) specific to the oocyte and egg promote either histone deposition or sequestration, respectively. Mass spectrometry and Npm phosphomimetic mutations used in chromatin assembly assays identified hyperphosphorylation on the N-terminal tail as a critical regulator for sequestration. C-terminal tail phosphorylation and PRMT5-catalyzed arginine methylation enhance nucleosome assembly by promoting histone interaction with the second acidic tract of Npm. Electron microscopy reconstructions of Npm and TTLL4 activity toward the C-terminal tail demonstrate that oocyte- and egg-specific PTMs cause Npm conformational changes. Our results reveal that PTMs regulate Npm chaperoning activity by modulating Npm conformation and Npm-histone interaction, leading to histone sequestration in the egg