Factors affecting performance of fetal blood T2 measurements for noninvasive estimation of oxygen saturation.

PURPOSE: To ultimately make accurate and precise fetal noninvasive oxygen saturation (sO2 ) measurements by T2 -prepared bSSFP more widely available by systematically assessing error sources in order to potentially reduce perinatal mortality in cardiovascular malformations and fetal growth restriction. METHODS: T2 -prepared bSSFP data were acquired in phantoms; in flowing blood in adults in the superior sagittal sinus, ascending and descending aorta, and main pulmonary artery; and in the fetal descending aorta and umbilical vein. T2 was assessed in relation to T2 two- or three-parameter curve-fitting techniques, SSFP readout, refocusing time delay (τ), constant and pulsatile blood flow, and impact of T1 recovery. Further, fetal T2 and sO2 variability were quantified in the descending aorta and umbilical vein in healthy fetuses and fetuses with cardiovascular malformation (gestational weeks 32-38). RESULTS: In phantoms, three-parameter fitting was accurate irrespective of phase FOV (<4 ms; i.e., <2%), and T2 was overestimated (up to 23 ms/10%; p = 0.001) beyond ±30 Hz off-resonance. In the adult aorta, T2 was underestimated during higher blood flow velocities and pulsatility for τ = 16 ms (-41 ms/-17%; p = 0.008). In fetuses, two-parameter fitting overestimated T2 compared with three-parameter fitting (+33 ms/+18%; p = 0.03). T2 variability was 18 ms/15% in the fetal descending aorta and 28 ms/14% in the umbilical vein. The resulting estimated sO2 variability was ∼10% (15% of sO2 value) in the fetal descending aorta. CONCLUSIONS: Errors due to T2 -fitting techniques, off-resonance, flow velocity, and insufficient T1 recovery between image acquisitions could be mitigated by using three-parameter fitting with included saturation-prepared images approximating infinite T2 -preparation time, adequate shimming covering the fetus and placenta, and by modifying acquisition parameters. Variability in fetal blood T2 and sO2 , however, indicate that it is currently not feasible to use these methods for prediction of disease.

Exploration of physical and chemical cues on retinal cell fate.

Identification of the key components in the physical and chemical milieu directing donor cells into a desired phenotype is a requirement in the investigation of bioscaffolds for the advancement of cell-based therapies for retinal neurodegeneration. We explore the effect of electrospun poly-ε-caprolactone (PCL) fiber scaffold topography and functionalization and culture medium, on the behavior of mouse retinal cells. Dissociated mouse retinal post-natal cells were seeded on random or aligned oriented fibers, with or without laminin coating and cultured with either basic or neurotrophins enriched medium for 7days. Addition of laminin in combination with neurotrophins clearly promoted cell- morphology, fate, and neurite extension. Nanotopography per se significantly affected cell morphology, with mainly bipolar profiles on aligned fibers and more multipolar profiles on random fibers. Laminin induced a remarkable 90° switch of neurite orientation. Herewith, we demonstrate that the chemical cue is stronger than the physical cue for the orientation of retinal neurites and describe the requirement of both neurotrophins and extracellular matrix proteins for extended neurite outgrowth and formation of complex retinal neuronal networks. Therefore, tailor-made PCL fiber mats, which can be physically and chemically modified, indeed influence cell behavior and hence motivate further retinal restorative studies using this system.

Unravelling the mechanisms of CE-SSFP in imaging myocardium at risk: The effect of relaxation times on myocardial contrast.

PURPOSE: The aim of this study was to investigate the contrast mechanisms of Contrast-enhanced steady-state free-precession (CE-SSFP) through the utilization of Bloch simulations in an experimental porcine model and in patients with acute myocardial infarction. METHODS: Six pigs and ten patients with myocardial infarction underwent CMR and tissue characterization at 1.5 T whereas a Bloch simulation framework was utilized to simulate the CE-SSFP signal formation and compare it against the actual CE-SSFP signal acquired from the experimental porcine model and the patient population. The relaxation times of remote, salvaged, and infarcted myocardium were calculated after the injection of gadolinium, at the time of CE-SSFP acquisition. Simulations were performed using the same CE-SSFP pulse sequence as used on the scanner on a set of spins with the calculated relaxation times from the CMR scans. RESULTS: The normalized signal intensities of salvaged and infarcted myocardium obtained with simulations were lower than the corresponding normalized signal intensities obtained in vivo in pigs (p < 0.05, 134% vs 153%) and in patients (p < 0.05, 126% vs 145%). The results from simulations showed a linear relationship to the results obtained in the experimental porcine model (r2 = 0.61) and in patients (r2 = 0.69). CONCLUSION: The T1 and T2 values of remote, salvaged, and infarcted myocardium only partly explain the signal intensities in CE-SSFP images. Bloch simulations suggest that there may be more elements that contribute to the CE-SSFP contrast. Integration of other aspects of the MR experiment into the simulation model could further help to fully unravel the mechanisms of CE-SSFP.

Li10SnP2S12: an affordable lithium superionic conductor.

The reaction of Li2S and P2S5 with Li4[SnS4], a recently discovered, good Li(+) ion conductor, yields Li10SnP2S12, the thiostannate analogue of the record holder Li10GeP2S12 and the second compound of this class of superionic conductors with very high values of 7 mS/cm for the grain conductivity and 4 mS/cm for the total conductivity at 27 °C. The replacement of Ge by Sn should reduce the raw material cost by a factor of ~3.

Validation and quantification of left ventricular function during exercise and free breathing from real-time cardiac magnetic resonance images.

Exercise cardiovascular magnetic resonance (CMR) can unmask cardiac pathology not evident at rest. Real-time CMR in free breathing can be used, but respiratory motion may compromise quantification of left ventricular (LV) function. We aimed to develop and validate a post-processing algorithm that semi-automatically sorts real-time CMR images according to breathing to facilitate quantification of LV function in free breathing exercise. A semi-automatic algorithm utilizing manifold learning (Laplacian Eigenmaps) was developed for respiratory sorting. Feasibility was tested in eight healthy volunteers and eight patients who underwent ECG-gated and real-time CMR at rest. Additionally, volunteers performed exercise CMR at 60% of maximum heart rate. The algorithm was validated for exercise by comparing LV mass during exercise to rest. Respiratory sorting to end expiration and end inspiration (processing time 20 to 40 min) succeeded in all research participants. Bias ± SD for LV mass was 0 ± 5 g when comparing real-time CMR at rest, and 0 ± 7 g when comparing real-time CMR during exercise to ECG-gated at rest. This study presents a semi-automatic algorithm to retrospectively perform respiratory sorting in free breathing real-time CMR. This can facilitate implementation of exercise CMR with non-ECG-gated free breathing real-time imaging, without any additional physiological input.

Author Correction: Electrospun nerve guide conduits have the potential to bridge peripheral nerve injuries in vivo.

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Electrospun nerve guide conduits have the potential to bridge peripheral nerve injuries in vivo.

Electrospinning can be used to mimic the architecture of an acellular nerve graft, combining microfibers for guidance, and pores for cellular infiltration. We made electrospun nerve guides, from polycaprolactone (PCL) or poly-L-lactic acid (PLLA), with aligned fibers along the insides of the channels and random fibers around them. We bridged a 10 mm rat sciatic nerve defect with the guides, and, in selected groups, added a cell transplant derived from autologous stromal vascular fraction (SVF). For control, we compared to hollow silicone tubes; or autologous nerve grafts. PCL nerve guides had a high degree of autotomy (8/43 rats), a negative indicator with respect to future usefulness, while PLLA supported axonal regeneration, but did not outperform autologous nerve grafts. Transplanted cells survived in the PLLA nerve guides, but axonal regeneration was not enhanced as compared to nerve guides alone. The inflammatory response was partially enhanced by the transplanted cells in PLLA nerve grafts; Schwann cells were poorly distributed compared to nerve guide without cells. Tailor-made electrospun nerve guides support axonal regeneration in vivo, and can act as vehicles for co-transplanted cells. Our results motivate further studies exploring novel nerve guides and the effect of stromal cell-derived factors on nerve generation.

Decomposition of P4O10 in DMSO.

Intermediate states of degradation of phosphorus pentoxide in dimethyl sulfoxide (DMSO), also known as Onodera reagent, are studied. We found that DMSO is not dissolving P4O10, but rather reacting with it. A rather complex mixture of phosphate species is formed, many with ester functions. Several not yet described phosphate species could be identified by NMR and MS. Finally, we present a possible decomposition scheme of P4O10 in DMSO.

Stationary and portable sequencing-based approaches for tracing wastewater contamination in urban stormwater systems.

Urban sewer systems consist of wastewater and stormwater sewers, of which only wastewater is processed before being discharged. Occasionally, misconnections or damages in the network occur, resulting in untreated wastewater entering natural water bodies via the stormwater system. Cultivation of faecal indicator bacteria (e.g. Escherichia coli; E. coli) is the current standard for tracing wastewater contamination. This method is cheap but has limited specificity and mobility. Here, we compared the E. coli culturing approach with two sequencing-based methodologies (Illumina MiSeq 16S rRNA gene amplicon sequencing and Oxford Nanopore MinION shotgun metagenomic sequencing), analysing 73 stormwater samples collected in Stockholm. High correlations were obtained between E. coli culturing counts and frequencies of human gut microbiome amplicon sequences, indicating E. coli is indeed a good indicator of faecal contamination. However, the amplicon data further holds information on contamination source or alternatively how much time has elapsed since the faecal matter has entered the system. Shotgun metagenomic sequencing on a subset of the samples using a portable real-time sequencer, MinION, correlated well with the amplicon sequencing data. This study demonstrates the use of DNA sequencing to detect human faecal contamination in stormwater systems and the potential of tracing faecal contamination directly in the field.

Immunocytochemical Profiling of Cultured Mouse Primary Retinal Cells.

Primary retinal cell cultures and immunocytochemistry are important experimental platforms in ophthalmic research. Translation of retinal cells from their native environment to the in vitro milieu leads to cellular stress, jeopardizing their in vivo phenotype features. Moreover, the specificity and stability of many retinal immunochemical markers are poorly evaluated in retinal cell cultures. Hence, we here evaluated the expression profile of 17 retinal markers, that is, recoverin, rhodopsin, arrestin, Chx10, PKC, DCX, CRALBP, GS, vimentin, TPRV4, RBPMS, Brn3a, ß-tubulin III, NeuN, MAP2, GFAP, and synaptophysin. At 7 and 18 days of culture, the marker expression profiles of mouse postnatal retinal cells were compared with their age-matched in vivo retinas. We demonstrate stable in vitro expression of all markers, except for arrestin and CRALBP. Differences in cellular expression and location of some markers were observed, both over time in culture and compared with the age-matched retina. We hypothesize that these differences are likely culture condition dependent. Taken together, we suggest a thorough evaluation of the antibodies in specific culture settings, before extrapolating the in vitro results to an in vivo setting. Moreover, the identification of specific cell types may require a combination of different genes expressed or markers with structural information.

Low temperature synthesis of ionic phosphates in dimethyl sulfoxide.

A new synthesis route for phosphates in an organic solvent at low temperatures is presented. The synthesis was done by dispersing a nitrate salt and phosphorus pentoxide in dimethyl sulfoxide. The synthesis can be performed under water-free conditions and yielded several organic and inorganic phosphates. Crystal structure solution of bistetramethylammonium hydrogencyclotriphosphate, [N(CH3)4]2HP3O9, was achieved by combining information gained from powder X-ray diffraction, liquid NMR and solid state (2D) NMR. The molecular structure of rubidium cyclotetraphosphate, Rb4P4O12, was determined using liquid state NMR and solid state (2D) NMR spectroscopy.