Skeletal muscle optoacoustics reveals patterns of circulatory function and oxygen metabolism during exercise.

Imaging skeletal muscle function and metabolism, as reported by local hemodynamics and oxygen kinetics, can elucidate muscle performance, severity of an underlying disease or outcome of a treatment. Herein, we used multispectral optoacoustic tomography (MSOT) to image hemodynamics and oxygen kinetics within muscle during exercise. Four healthy volunteers underwent three different hand-grip exercise challenges (60s isometric, 120s intermittent isometric and 60s isotonic).

Non-invasive multispectral optoacoustic tomography resolves intrahepatic lipids in patients with hepatic steatosis.

Hepatic steatosis is characterized by intrahepatic lipid accumulation and may lead to irreversible liver damage if untreated. Here, we investigate whether multispectral optoacoustic tomography (MSOT) can offer label-free detection of liver lipid content to enable non-invasive characterization of hepatic steatosis by analyzing the spectral region around 930 nm, where lipids characteristically absorb. In a pilot study, we apply MSOT to measure liver and surrounding tissues in five patients with liver steatosis and five healthy volunteers, revealing significantly higher absorptions at 930 nm in the patients, while no significant difference was observed in the subcutaneous adipose tissue of the two groups.

Mass spectrometry imaging discriminates glioblastoma tumor cell subpopulations and different microvascular formations based on their lipid profiles.

Glioblastoma is a prevalent malignant brain tumor and despite clinical intervention, tumor recurrence is frequent and usually fatal. Genomic investigations have provided a greater understanding of molecular heterogeneity in glioblastoma, yet there are still no curative treatments, and the prognosis has remained unchanged. The aggressive nature of glioblastoma is attributed to the heterogeneity in tumor cell subpopulations and aberrant microvascular proliferation.

Weighted model-based optoacoustic reconstruction for partial-view geometries.

Acoustic heterogeneities in biological samples are known to cause artifacts in tomographic optoacoustic (photoacoustic) image reconstruction. A statistical weighted model-based reconstruction approach was previously introduced to mitigate such artifacts. However, this approach does not reliably provide high-quality reconstructions for partial-view imaging systems, which are common in preclinical and clinical optoacoustics.

Multi-Aspect Optoacoustic Imaging of Breast Tumors under Chemotherapy with Exogenous and Endogenous Contrasts: Focus on Apoptosis and Hypoxia.

Breast cancer is a complex tumor type involving many biological processes. Most chemotherapeutic agents exert their antitumoral effects by rapid induction of apoptosis. Another main feature of breast cancer is hypoxia, which may drive malignant progression and confer resistance to various forms of therapy.

Multispectral optoacoustic tomography of lipid and hemoglobin contrast in human carotid atherosclerosis.

Several imaging techniques aim at identifying features of carotid plaque instability but come with limitations, such as the use of contrast agents, long examination times and poor portability. Multispectral optoacoustic tomography (MSOT) employs light and sound to resolve lipid and hemoglobin content, both features associated with plaque instability, in a label-free, fast and highly portable way. Herein, 5 patients with carotid atherosclerosis, 5 healthy volunteers and 2 excised plaques, were scanned with handheld MSOT.

Resolution of Spatial and Temporal Heterogeneity in Bevacizumab-Treated Breast Tumors by Eigenspectra Multispectral Optoacoustic Tomography.

Understanding temporal and spatial hemodynamic heterogeneity as a function of tumor growth or therapy affects the development of novel therapeutic strategies. In this study, we employed eigenspectra multispectral optoacoustic tomography (eMSOT) as a next-generation optoacoustic method to impart high accuracy in resolving tumor hemodynamics during bevacizumab therapy in two types of breast cancer xenografts (KPL-4 and MDA-MB-468). Patterns of tumor total hemoglobin concentration (THb) and oxygen saturation (sO) were imaged in control and bevacizumab-treated tumors over the course of 58 days (KPL-4) and 16 days (MDA-MB-468), and the evolution of functional vasculature "normalization" was resolved macroscopically.

Multispectral optoacoustic tomography of muscle perfusion and oxygenation under arterial and venous occlusion: A human pilot study.

Perfusion and oxygenation are critical parameters of muscle metabolism in health and disease. They have been both the target of many studies, in particular using near-infrared spectroscopy (NIRS). However, difficulties with quantifying NIRS signals have limited a wide dissemination of the method to the clinics.

Fluorescence imaging reversion using spatially variant deconvolution.

Fluorescence imaging opens new possibilities for intraoperative guidance and early cancer detection, in particular when using agents that target specific disease features. Nevertheless, photon scattering in tissue degrades image quality and leads to ambiguity in fluorescence image interpretation and challenges clinical translation. We introduce the concept of capturing the spatially-dependent impulse response of an image and investigate Spatially Adaptive Impulse Response Correction (SAIRC), a method that is proposed for improving the accuracy and sensitivity achieved.

Could the postoperative residual of urine predict the outcome of TVTOmidurethral sling procedure in female patients?

Objective: To assess if the amount of postoperative postvoid residual of urine that is within the normal range (less than 100 mls) could predict the outcome of TVTO (Tension -free vaginal tape obturator) procedure.

Study Design: Second Department of Obstetrics and Gynecology, Aretaieio Hospital, University of Athens, Greece. Patients that had been submitted to TVTO procedure between 2013 and 2017 were reviewed and outcome was assessed.

Identification of Diverse Integron and Plasmid Structures Carrying a Novel Carbapenemase Among Species.

A novel carbapenem-hydrolyzing beta-lactamase, called IMP-63, was identified in three clonally distinct strains of and two strains of isolated within a 4 year timeframe in three French hospitals. The gene that encodes this carbapenemase turned out to be located in the variable region of four integrons (In, In, In, and In) and to coexist with novel or rare gene cassettes (, , ) and insertion elements (IS, IS). All these integrons except one (In) were flanked by a copy of insertion sequence IS next to the putative gene, and were carried by non-conjugative plasmids (pNECK1, pROUSS1, pROUSS2, pROUE1).

Rapid identification of Candida sp. by MALDI-TOF mass spectrometry subsequent to short-term incubation on a solid medium.

Rapid identification of Candida species is important for appropriate antifungal therapy of fungemia. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) system is a useful tool to identify bacteria and yeasts. In this study, we evaluated the feasibility of identifying yeasts after a short-term incubation on a solid medium.

High resolution volumetric imaging of primary and secondary tumor spheroids using multi-angle Light Sheet Fluorescence Microscopy (LSFM).

Breast cancer and Glioblastoma brain cancer are severe malignancies with poor prognosis. In this study, primary Glioblastoma and secondary breast cancer spheroids are formed and treated with the well-known Temozolomide and Doxorubicin chemotherapeutics, respectively. High resolution imaging of both primary and secondary cancer cell spheroids is possible using a custom multi-angle Light Sheet Fluorescence Microscope.

Integrating in vitro experiments with in silico approaches for Glioblastoma invasion: the role of cell-to-cell adhesion heterogeneity.

Glioblastoma cells adopt migration strategies to invade into the brain parenchyma ranging from individual to collective mechanisms, whose role and dynamics are not yet fully understood. In this work, we explore Glioblastoma heterogeneity and recapitulate its invasive patterns both in vitro, by utilizing primary cells along with the U87MG cell line, and in silico, by adopting discrete, individual cell-based mathematics. Glioblastoma cells are cultured three-dimensionally in an ECM-like substrate.

Multispectral Optoacoustic Tomography of Brown Adipose Tissue.

MSOT has revolutionized biomedical imaging because it allows anatomical, functional, and molecular imaging of deep tissues in vivo in an entirely noninvasive, label-free, and real-time manner. This imaging modality works by pulsing light onto tissue, triggering the production of acoustic waves, which can be collected and reconstructed to provide high-resolution images of features as deep as several centimeters below the body surface. Advances in hardware and software continue to bring MSOT closer to clinical translation.

Demonstrating Improved Multiple Transport-Mean-Free-Path Imaging Capabilities of Light Sheet Microscopy in the Quantification of Fluorescence Dynamics.

Optical microscopy constitutes, one of the most fundamental paradigms for the understanding of complex biological mechanisms in the whole-organism and live-tissue context. Novel imaging techniques such as light sheet fluorescence microscopy (LSFM) and optical projection tomography (OPT) combined with phase-retrieval algorithms (PRT) can produce highly resolved 3D images in multiple transport-mean-free-path scales. Our study aims to exemplify the microscopic capabilities of LSFM when imaging protein dynamics in Caenorhabditis elegans and the distribution of necrotic cells in cancer cell spheroids.

Optical projection tomography via phase retrieval algorithms.

We describe a computational method for accurate, quantitative tomographic reconstructions in Optical Projection Tomography, based on phase retrieval algorithms. Our method overcomes limitations imposed by light scattering in opaque tissue samples under the memory effect regime, as well as reduces artifacts due to mechanical movements, misalignments or vibrations. We make use of Gerchberg-Saxton algorithms, calculating first the autocorrelation of the object and then retrieving the associated phase under four numerically simulated measurement conditions.

Phase-Retrieved Tomography enables Mesoscopic imaging of Opaque Tumor Spheroids.

We present a new Phase-Retrieved Tomography (PRT) method to radically improve mesoscopic imaging at regimes beyond one transport mean-free-path and achieve high resolution, uniformly throughout the volume of opaque samples. The method exploits multi-view acquisition in a hybrid Selective Plane Illumination Microscope (SPIM) and Optical Projection Tomography (OPT) setup and a three-dimensional Gerchberg-Saxton phase-retrieval algorithm applied in 3D through the autocorrelation sinogram. We have successfully applied this innovative protocol to image optically dense 3D cell cultures in the form of tumor spheroids, highly versatile models to study cancer behavior and response to chemotherapy.

Multispectral Optoacoustic Tomography (MSOT) of Human Breast Cancer.

In a pilot study, we introduce fast handheld multispectral optoacoustic tomography (MSOT) of the breast at 28 wavelengths, aiming to identify high-resolution optoacoustic (photoacoustic) patterns of breast cancer and noncancerous breast tissue. We imaged 10 female patients ages 48-81 years with malignant nonspecific breast cancer or invasive lobular carcinoma. Three healthy volunteers ages 31-36 years were also imaged.

A hybrid discrete-continuous model of in vitro spheroid tumor growth and drug response.

Anti-cancer therapy efficacy in solid tumors mainly depends on drug transportation through the vasculature system and the extracellular matrix, on diffusion gradients and clonal heterogeneity within the tumor mass, as well as on the responses of the individual tumor cells to drugs and their interactions with each other and their local microenvironment. In this work, we develop a mathematical predictive model for tumor growth and drug response based on 3D spheroids experiments that possess several in vivo features of tumors and are considered better for drug screening. The model takes into account the diffusion gradients of both oxygen and drug through the tumor volume, describes the tumor population at cell level and assumes a simple underlying cellular dose-response curve that is translated to a cell death probability.

Immunohistochemical expression of hormonal receptors, collagen, elastin, and proteoglycans in genuine urinary incontinence.

Purpose: To study the expression of hormonal receptors, collagen, elastin, proteoglycans, and VIP in the vaginal wall of women with stress urinary incontinence (SUI).

Materials And Methods: Fifty-eight specimens of the anterior vaginal wall (28 women with SUI) were processed by Ventana immunostaining method.

Results: Both groups were compatible for age, BMI, and obstetric history.

Molecular epidemiology of OXA-48-producing Klebsiella pneumoniae in France.

We characterized 53 OXA-48-producing Klebsiella pneumoniae (OXA-48-Kp) isolated between 2011 and 2013 in 21 French hospitals. All the isolates were genotyped using MLST and PFGE and the population structure of the species was determined by a nucleotide-based analysis of the entire K. pneumoniae MLST database.

Subcellular localization of regulator of G protein signaling RGS7 complex in neurons and transfected cells.

The R7 family of regulators of G protein signaling (RGS) is involved in many functions of the nervous system. This family includes RGS6, RGS7, RGS9, and RGS11 gene products and is defined by the presence of the characteristic first found in Disheveled, Egl-10, Pleckstrin (DEP), DEP helical extension (DHEX), Gγ-like, and RGS domains. Herein, we examined the subcellular localization of RGS7, the most broadly expressed R7 member.

Mutagenicity of tamoxifen DNA adducts in human endometrial cells and in silico prediction of p53 mutation hotspots.

Tamoxifen elevates the risk of endometrial tumours in women and alpha-(N(2)-deoxyguanosinyl)-tamoxifen adducts are reportedly present in endometrial tissue of patients undergoing therapy. Given the widespread use of tamoxifen there is considerable interest in elucidating the mechanisms underlying treatment-associated cancer. Using a combined experimental and multivariate statistical approach we have examined the mutagenicity and potential consequences of adduct formation by reactive intermediates in target uterine cells.