Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of Systemic Sclerosis-associated pulmonary fibrosis and pulmonary arterial hypertension. Myth or reality?

Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and multiple internal organs and severe functional and structural microvascular alterations. SSc is considered to be the prototypic systemic fibrotic disorder. Despite currently available therapeutic approaches SSc has a high mortality rate owing to the development of SSc-associated interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), complications that have emerged as the most frequent causes of disability and mortality in SSc. The pathogenesis of the fibrotic process in SSc is complex and despite extensive investigation the exact mechanisms have remained elusive. Myofibroblasts are the cells ultimately responsible for tissue fibrosis and fibroproliferative vasculopathy in SSc. Tissue myofibroblasts in SSc originate from several sources including expansion of quiescent tissue fibroblasts and tissue accumulation of CD34+ fibrocytes. Besides these sources, myofibroblasts in SSc may result from the phenotypic conversion of endothelial cells into activated myofibroblasts, a process known as endothelial to mesenchymal transition (EndoMT). Recently, it has been postulated that EndoMT may play a role in the development of SSc-associated ILD and PAH. However, although several studies have described the occurrence of EndoMT in experimentally induced cardiac, renal, and pulmonary fibrosis and in several human disorders, the contribution of EndoMT to SSc-associated ILD and PAH has not been generally accepted. Here, the experimental evidence supporting the concept that EndoMT plays a role in the pathogenesis of SSc-associated ILD and PAH will be reviewed

Fluorescence lifetime spectroscopy of tissue autofluorescence in normal and diseased colon measured ex vivo using a fiber-optic probe

We present an ex vivo study of temporally and spectrally resolved autofluorescence in a total of 47 endoscopic excision biopsy/resection specimens from colon, using pulsed excitation laser sources operating at wavelengths of 375 nm and 435 nm. A paired analysis of normal and neoplastic (adenomatous polyp) tissue specimens obtained from the same patient yielded a significant difference in the mean spectrally averaged autofluorescence lifetime −570 ± 740 ps (p = 0.021, n = 12). We also investigated the fluorescence signature of non-neoplastic polyps (n = 6) and inflammatory bowel disease (n = 4) compared to normal tissue in a small number of specimens

Attenuation correction for TOF-PET with a limited number of stationary coincidence line-sources

INTRODUCTION Accurate attenuation correction remains a major issue in combined PET/MRI. We have previously presented a method to derive the attenuation map by performing a transmission scan using an annulus-shaped source placed close to the edge of the FOV of the scanner. With this method, simultaneous transmission and emission data acquisition is possible as transmission data can be extracted using Time-of-Flight (TOF) information. As this method is strongly influenced by photon scatter and dead time effects, its performance depends on the accuracy of the correction techniques for these effects. In this work we present a new approach in which the annulus source is replaced with a limited number of line-sources positioned at 35 cm from the center of the FOV. By including the location of the line sources into the algorithm, the extraction of true transmission data can be improved. The setup was validated with simulations studies and evaluated with a phantom study acquired on the LaBr3-based TOF-PET scanner installed at UPENN. MATERIALS AND METHODS First we performed GATE simulations using the digital NCAT phantom. The phantom was segmented into bone, lung and soft-tissue and injected with 6.5 Mbq/kg 18F-FDG. Simultaneous transmission/emission scans of 3 minutes were simulated using 6, 12 and 24 18F-FDG line sources with a total activity of 0.5 mCi. To obtain the attenuation map, the transmission data is first extracted using TOF information. To reduce misclassification of prompt emission data as transmission data, only events on LORs, which pass within a radial distance of 1 cm from at least one line source, are accepted. The attenuation map is then reconstructed using an iterative gradient descent approach. As a proof of concept, the method was evaluated on the LaBr3-based TOF PET scanner using an anthropomorphic torso phantom injected with 2mCi of 18F-FDG. 24 line-sources of 20μCi each were fixed to a wooden template at the back of the scanner. Simultaneous transmission/emission scans were acquired using 24 line sources. RESULTS Simulation results demonstrate that the fraction of scattered emission events classified as transmission data was reduced from 4.32% with the annulus source to 2.29%, 1.25% and 0.63% for the 24, 12 and 6 line sources respectively. The fraction of misclassified true emission events was reduced from 1.10% to 0.42%, 0.24% and 0.13% respectively. Only in case of 6 line sources, the attenuation maps showed severe artifacts. Compared to the classification solely based on TOF-information, preliminary experimental results indicate an improvement in the accuracy of the attenuation coefficients of 10.44%, 0.12% and 5.09% for soft-tissue, lung and bone tissue respectively. CONCLUSION The proposed method can be used for attenuation correction in sequential or simultaneous TOF-PET/MRI systems. The PET transmission and emission data are acquired simultaneously so no acquisition time for attenuation correction is lost in PET or MRI. Attenuation maps with higher accuracy can be obtained by including information about the location of the line-sources. However, at least 12 line sources are needed to avoid severe artifacts

Magnetic susceptibility anisotropy of myocardium imaged by cardiovascular magnetic resonance reflects the anisotropy of myocardial filament α-helix polypeptide bonds.

BackgroundA key component of evaluating myocardial tissue function is the assessment of myofiber organization and structure. Studies suggest that striated muscle fibers are magnetically anisotropic, which, if measurable in the heart, may provide a tool to assess myocardial microstructure and function.MethodsTo determine whether this weak anisotropy is observable and spatially quantifiable with cardiovascular magnetic resonance (CMR), both gradient-echo and diffusion-weighted data were collected from intact mouse heart specimens at 9.4 Tesla. Susceptibility anisotropy was experimentally calculated using a voxelwise analysis of myocardial tissue susceptibility as a function of myofiber angle. A myocardial tissue simulation was developed to evaluate the role of the known diamagnetic anisotropy of the peptide bond in the observed susceptibility contrast.ResultsThe CMR data revealed that myocardial tissue fibers that were parallel and perpendicular to the magnetic field direction appeared relatively paramagnetic and diamagnetic, respectively. A linear relationship was found between the magnetic susceptibility of the myocardial tissue and the squared sine of the myofiber angle with respect to the field direction. The multi-filament model simulation yielded susceptibility anisotropy values that reflected those found in the experimental data, and were consistent that this anisotropy decreased as the echo time increased.ConclusionsThough other sources of susceptibility anisotropy in myocardium may exist, the arrangement of peptide bonds in the myofilaments is a significant, and likely the most dominant source of susceptibility anisotropy. This anisotropy can be further exploited to probe the integrity and organization of myofibers in both healthy and diseased heart tissue

Polycyclic aromatic hydrocarbons and esophageal squamous cell carcinoma

Esophageal cancer (EC) is the 8th most common cancer and the 6th most frequent cause of cancer mortality worldwide. Esophageal squamous cell carcinoma (ESCC) is the most common type of EC. Exposure to polycyclic aromatic hydrocarbons (PAHs) has been suggested as a risk factor for developing ESCC. In this paper we will review different aspects of the relationship between PAH exposure and ESCC. PAHs are a group of compounds that are formed by incomplete combustion of organic matter. Studies in humans have shown an association between PAH exposure and development of ESCC in many populations. The results of a recent case-control study in a high risk population in northeastern Iran showed a dramatic dose-response relationship between PAH content in non-tumor esophageal tissue (the target tissue for esophageal carcinogenesis) and ESCC case status, consistent with a causal role for PAH exposure in the pathogenesis of ESCC. Identifying the main sources of exposure to PAHs may be the first and most important step in designing appropriate PAH-reduction interventions for controlling ESCC, especially in high risk areas. Coal smoke and drinking mate have been suggested as important modifiable sources of PAH exposure in China and Brazil, respectively. But the primary source of exposure to PAHs in other high risk areas for ESCC, such as northeastern Iran, has not yet been identified. Thus, environmental studies to determining important sources of PAH exposure should be considered as a high priority in future research projects in these areas

Cell sources for articular cartilage repair strategies: shifting from mono-cultures to co-cultures

The repair of articular cartilage is challenging due to the sparse native cell population combined with the avascular and aneural nature of the tissue. In recent years cartilage tissue engineering has shown great promise. As with all tissue engineering strategies, the possible therapeutic outcome is intimately linked with the used combination of cells, growth factors and biomaterials. However, the optimal combination has remained a controversial topic and no consensus has been reached. In consequence, much effort has been dedicated to further design, investigate and optimize cartilage repair strategies. Specifically, various research groups have performed intensive investigations attempting to identify the single most optimal cell source for articular cartilage repair strategies. However, recent findings indicate that not the heavily investigated mono cell source, but the less studied combinations of cell sources in co-culture might be more attractive for cartilage repair strategies. This review will give a comprehensive overview on the cell sources that have been investigated for articular cartilage repair strategies. In particular, the advantages and disadvantages of investigated cell sources are comprehensively discussed with emphasis on the potential of co-cultures in which benefits are combined while the disadvantages of single cell sources for cartilage repair are mitigated

Analysis of Passive Charge Balancing for Safe Current-Mode Neural Stimulation

Charge balancing has been often considered as one of the most critical requirement for neural stimulation circuits. Over the years several solutions have been proposed to precisely balance the charge transferred to the tissue during anodic and cathodic phases. Elaborate dynamic current sources/sinks with improved matching, and feedback loops have been proposed with a penalty on circuit complexity, area or power consumption. Here we review the dominant assumptions in safe stimulation protocols, and derive mathematical models to determine the effectiveness of passive charge balancing in a typical application scenario

Potential biomedical applications of ion beam technology

Electron bombardment ion thrusters used as ion sources have demonstrated a unique capability to vary the surface morphology of surgical implant materials. The microscopically rough surface texture produced by ion beam sputtering of these materials may result in improvements in the biological response and/or performance of implanted devices. Control of surface roughness may result in improved attachment of the implant to soft tissue, hard tissue, bone cement, or components deposited from blood. Potential biomedical applications of ion beam texturing discussed include: vascular prostheses, artificial heart pump diaphragms, pacemaker fixation, percutaneous connectors, orthopedic pros-thesis fixtion, and dental implants