Combination of acamprosate and baclofen (PXT864) as a potential new therapy for amyotrophic lateral sclerosis.

There is currently no therapy impacting the course of amyotrophic lateral sclerosis (ALS). The only approved treatments are riluzole and edaravone, but their efficacy is modest and short-lasting, highlighting the need for innovative therapies. We previously demonstrated the ability of PXT864, a combination of low doses of acamprosate and baclofen, to synergistically restore cellular and behavioral activity in Alzheimer's and Parkinson's disease models. The overlapping genetic, molecular, and cellular characteristics of these neurodegenerative diseases supported investigating the effectiveness of PXT864 in ALS. As neuromuscular junction (NMJ) alterations is a key feature of ALS, the effects of PXT864 in primary neuron-muscle cocultures injured by glutamate were studied. PXT864 significantly and synergistically preserved NMJ and motoneuron integrity following glutamate excitotoxicity. PXT864 added to riluzole significantly improved such protection. PXT864 activity was then assessed in primary cultures of motoneurons derived from SOD1G93A rat embryos. These motoneurons presented severe maturation defects that were significantly improved by PXT864. In this model, glutamate application induced an accumulation of TDP-43 protein in the cytoplasm, a hallmark that was completely prevented by PXT864. The anti-TDP-43 aggregation effect was also confirmed in a cell line expressing TDP-43 fused to GFP. These results demonstrate the value of PXT864 as a promising therapeutic strategy for the treatment of ALS.

How Computational Experiments Can Improve Our Understanding of the Genetic Architecture of Common Human Diseases.

Susceptibility to common human diseases such as cancer is influenced by many genetic and environmental factors that work together in a complex manner. The state of the art is to perform a genome-wide association study (GWAS) that measures millions of single-nucleotide polymorphisms (SNPs) throughout the genome followed by a one-SNP-at-a-time statistical analysis to detect univariate associations. This approach has identified thousands of genetic risk factors for hundreds of diseases. However, the genetic risk factors detected have very small effect sizes and collectively explain very little of the overall heritability of the disease. Nonetheless, it is assumed that the genetic component of risk is due to many independent risk factors that contribute additively. The fact that many genetic risk factors with small effects can be detected is taken as evidence to support this notion. It is our working hypothesis that the genetic architecture of common diseases is partly driven by non-additive interactions. To test this hypothesis, we developed a heuristic simulation-based method for conducting experiments about the complexity of genetic architecture. We show that a genetic architecture driven by complex interactions is highly consistent with the magnitude and distribution of univariate effects seen in real data. We compare our results with measures of univariate and interaction effects from two large-scale GWASs of sporadic breast cancer and find evidence to support our hypothesis that is consistent with the results of our computational experiment.

Benchmarking relief-based feature selection methods for bioinformatics data mining.

Modern biomedical data mining requires feature selection methods that can (1) be applied to large scale feature spaces (e.g. 'omics' data), (2) function in noisy problems, (3) detect complex patterns of association (e.g. gene-gene interactions), (4) be flexibly adapted to various problem domains and data types (e.g. genetic variants, gene expression, and clinical data) and (5) are computationally tractable. To that end, this work examines a set of filter-style feature selection algorithms inspired by the 'Relief' algorithm, i.e. Relief-Based algorithms (RBAs). We implement and expand these RBAs in an open source framework called ReBATE (Relief-Based Algorithm Training Environment). We apply a comprehensive genetic simulation study comparing existing RBAs, a proposed RBA called MultiSURF, and other established feature selection methods, over a variety of problems. The results of this study (1) support the assertion that RBAs are particularly flexible, efficient, and powerful feature selection methods that differentiate relevant features having univariate, multivariate, epistatic, or heterogeneous associations, (2) confirm the efficacy of expansions for classification vs. regression, discrete vs. continuous features, missing data, multiple classes, or class imbalance, (3) identify previously unknown limitations of specific RBAs, and (4) suggest that while MultiSURF∗ performs best for explicitly identifying pure 2-way interactions, MultiSURF yields the most reliable feature selection performance across a wide range of problem types.

Uniaxial 2D Superlattice of Fe4 Molecular Magnets on Graphene.

We demonstrate that electrospray deposition enables the fabrication of highly periodic self-assembled arrays of Fe4H single molecule magnets on graphene/Ir(111). The energetic positions of molecular states are probed by means of scanning tunneling spectroscopy, showing pronounced long- and short-ranged spatial modulations, indicating the presence of both locally varying intermolecular as well as adsorption-site dependent molecule-substrate interactions. From the magnetic field dependence of the X-ray magnetic circular dichroism signal, we infer that the magnetic easy axis of each Fe4H molecule is oriented perpendicular to the sample surface and that after the deposition the value of the uniaxial anisotropy is identical to the one in bulk. Our findings therefore suggest that the observed interaction of the molecules with their surrounding does not modify the molecular magnetism, resulting in a two-dimensional array of molecular magnets that retain their bulk magnetic properties.

Non-contrast-enhanced MR angiography in critical limb ischemia: performance of quiescent-interval single-shot (QISS) and TSE-based subtraction techniques.

PURPOSE: The aim of this study was to evaluate diagnostic performance of non-contrast-enhanced 2D quiescent-interval single-shot (QISS) and 3D turbo spin-echo (TSE)-based subtraction magnetic resonance angiography (MRA) in the assessment of peripheral arteries in patients with critical limb ischemia (CLI). MATERIALS AND METHODS: Nineteen consecutive patients (74 % male, 72.8 ± 9.9 years) with CLI underwent 2D QISS and 3D TSE-based subtraction MRA at 1.5 T. Axial-overlapping QISS MRA (3 mm/2 mm; 1 × 1 mm2) covered from the toes to the aortic bifurcation while coronal 3D TSE-based subtraction MRA (1.3 × 1.2 × 1.3 mm3) was restricted to the calf only. MRA data sets (two readers) were evaluated for stenosis (≥50 %) and image quality. Results were compared with digital subtraction angiography (DSA). RESULTS: Two hundred and sixty-seven (267) segments were available for MRA-DSA comparison, with a prevalence of stenosis ≥50 % of 41.9 %. QISS MRA was rated as good to excellent in 79.5-96.0 % of segments without any nondiagnostic segments; 89.8-96.1 % of segments in 3D TSE-based subtraction MRA were rated as nondiagnostic or poor. QISS MRA sensitivities and specificities (segmental) were 92 % and 95 %, respectively, for reader one and 81-97 % for reader two. Due to poor image quality of 3D TSE-based subtraction MRA, diagnostic performance measures were not calculated. CONCLUSION: QISS MRA demonstrates excellent diagnostic performance and higher robustness than 3D TSE-based subtraction MRA in the challenging patient population with CLI. KEY POINTS: • QISS MRA allows reliable diagnosis of peripheral artery stenosis in critical limb ischemia. • Robustness of TSE-based subtraction MRA is limited in critical limb ischemia. • QISS MRA allows robust therapy planning in PAD patients with resting leg pain.

Optimization of 4D vessel-selective arterial spin labeling angiography using balanced steady-state free precession and vessel-encoding.

Vessel-selective dynamic angiograms provide a wealth of useful information about the anatomical and functional status of arteries, including information about collateral flow and blood supply to lesions. Conventional x-ray techniques are invasive and carry some risks to the patient, so non-invasive alternatives are desirable. Previously, non-contrast dynamic MRI angiograms based on arterial spin labeling (ASL) have been demonstrated using both spoiled gradient echo (SPGR) and balanced steady-state free precession (bSSFP) readout modules, but no direct comparison has been made, and bSSFP optimization over a long readout period has not been fully explored. In this study bSSFP and SPGR are theoretically and experimentally compared for dynamic ASL angiography. Unlike SPGR, bSSFP was found to have a very low ASL signal attenuation rate, even when a relatively large flip angle and short repetition time were used, leading to a threefold improvement in the measured signal-to-noise ratio (SNR) efficiency compared with SPGR. For vessel-selective applications, SNR efficiency can be further improved over single-artery labeling methods by using a vessel-encoded pseudo-continuous ASL (VEPCASL) approach. The combination of a VEPCASL preparation with a time-resolved bSSFP readout allowed the generation of four-dimensional (4D; time-resolved three-dimensional, 3D) vessel-selective cerebral angiograms in healthy volunteers with 59 ms temporal resolution. Good quality 4D angiograms were obtained in all subjects, providing comparable structural information to 3D time-of-flight images, as well as dynamic information and vessel selectivity, which was shown to be high. A rapid 1.5 min dynamic two-dimensional version of the sequence yielded similar image features and would be suitable for a busy clinical protocol. Preliminary experiments with bSSFP that included the extracranial vessels showed signal loss in regions of poor magnetic field homogeneity. However, for intracranial vessel-selective angiography, the proposed bSSFP VEPCASL sequence is highly SNR efficient and could provide useful information in a range of cerebrovascular diseases. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

Highly Ordered Surface Self-Assembly of Fe4 Single Molecule Magnets.

Single molecule magnets (SMMs) have attracted considerable attention due to low-temperature magnetic hysteresis and fascinating quantum effects. The investigation of these properties requires the possibility to deposit well-defined monolayers or spatially isolated molecules within a well-controlled adsorption geometry. Here we present a successful fabrication of self-organized arrays of Fe4 SMMs on hexagonal boron nitride (h-BN) on Rh(111) as template. Using a rational design of the ligand shell optimized for surface assembly and electrospray as a gentle deposition method, we demonstrate how to obtain ordered arrays of molecules forming perfect hexagonal superlattices of tunable size, from small islands to an almost perfect monolayer. High-resolution low temperature scanning tunneling microscopy (STM) reveals that the Fe4 molecule adsorbs on the substrate in a flat geometry, meaning that its magnetic easy axis is perpendicular to the surface. By scanning tunneling spectroscopy (STS) and density functional theory (DFT) calculations, we infer that the majority- and minority-spin components of the spin-split lowest unoccupied molecular orbital (LUMO) can be addressed separately on a submolecular level.

Highly undersampled contrast-enhanced MRA with iterative reconstruction: Integration in a clinical setting.

PURPOSE: To integrate, optimize, and evaluate a three-dimensional (3D) contrast-enhanced sparse MRA technique with iterative reconstruction on a standard clinical MR system. METHODS: Data were acquired using a highly undersampled Cartesian spiral phyllotaxis sampling pattern and reconstructed directly on the MR system with an iterative SENSE technique. Undersampling, regularization, and number of iterations of the reconstruction were optimized and validated based on phantom experiments and patient data. Sparse MRA of the whole head (field of view: 265 × 232 × 179 mm(3) ) was investigated in 10 patient examinations. RESULTS: High-quality images with 30-fold undersampling, resulting in 0.7 mm isotropic resolution within 10 s acquisition, were obtained. After optimization of the regularization factor and of the number of iterations of the reconstruction, it was possible to reconstruct images with excellent quality within six minutes per 3D volume. Initial results of sparse contrast-enhanced MRA (CEMRA) in 10 patients demonstrated high-quality whole-head first-pass MRA for both the arterial and venous contrast phases. CONCLUSION: While sparse MRI techniques have not yet reached clinical routine, this study demonstrates the technical feasibility of high-quality sparse CEMRA of the whole head in a clinical setting. Sparse CEMRA has the potential to become a viable alternative where conventional CEMRA is too slow or does not provide sufficient spatial resolution.

Highly undersampled peripheral Time-of-Flight magnetic resonance angiography: optimized data acquisition and iterative image reconstruction.

OBJECT: The aim of this study was to investigate the acceleration of peripheral Time-of-Flight magnetic resonance angiography using Compressed Sensing and parallel magnetic resonance imaging (MRI) while preserving image quality and vascular contrast. MATERIALS AND METHODS: An analytical sampling pattern is proposed that combines aspects of parallel MRI and Compressed Sensing. It is used in combination with a dedicated Split Bregman algorithm. This approach is compared with current state-of-the-art patterns and reconstruction algorithms. RESULTS: The acquisition time was reduced from 30 to 2.5 min in a study using ten volunteer data sets, while showing improved sharpness, better contrast and higher accuracy compared to state-of-the-art techniques. CONCLUSION: This study showed the benefits of the proposed dedicated analytical sampling pattern and Split Bregman algorithm for optimizing the Compressed Sensing reconstruction of highly accelerated peripheral Time-of-Flight data.

Hemodynamic quantification in brain arteriovenous malformations with time-resolved spin-labeled magnetic resonance angiography.

BACKGROUND AND PURPOSE: Unenhanced time-resolved spin-labeled magnetic resonance angiography enables hemodynamic quantification in arteriovenous malformations (AVMs). Our purpose was to identify quantitative parameters that discriminate among different AVM components and to relate hemodynamic patterns with rupture risk. METHODS: Sixteen patients presenting with AVMs (7 women, 9 men; mean age 37.1±15.9 years) were assigned to the high rupture risk or low rupture risk group according to anatomic AVM characteristics and rupture history. High temporal resolution (<70 ms) unenhanced time-resolved spin-labeled magnetic resonance angiography was performed on a 3-T MR system. After dedicated image processing, hemodynamic quantitative parameters were computed. T tests were used to compare quantitative parameters among AVM components, between the high rupture risk and low rupture risk groups, and between the hemorrhagic and nonhemorrhagic groups. RESULTS: Among the quantitative parameters, time-to-peak (P<0.001) and maximum outflow gradient (P=0.01) allowed discriminating various intranidal flow patterns with significantly different values between feeding arteries and draining veins. With 9 AVMs classified into the high rupture risk group (whose 6 were hemorrhagic) and 7 into the low rupture risk group, the observed venous-to-arterial time-to-peak ratio was significantly lower in the high rupture risk (P=0.003) and hemorrhagic (P=0.001) groups. CONCLUSIONS: Unenhanced time-resolved spin-labeled magnetic resonance angiography allows AVM-specific combined anatomic and quantitative analysis of AVM hemodynamics.

Time-resolved spin-labeled MR angiography for the depiction of cerebral arteriovenous malformations: a comparison of techniques.

PURPOSE: To assess time-resolved spin-labeled (SL) magnetic resonance (MR) angiographic imaging with a large acquisition time window over two cardiac cycles for characterization of cerebral arteriovenous malformations (AVMs). MATERIALS AND METHODS: This study was institutional review board-approved. Sixteen patients presented with an AVM, provided informed consent, and were prospectively included. Time-resolved SL MR angiographic images with acquisition window that covered two cardiac cycles (acquisition time, 10-12 min; temporal resolution, 60 msec) or one cardiac cycle and time-of-flight (TOF) MR angiographic images were acquired with a 3-T MR imager. A diagnostic confidence index was used for image quality evaluation; scores were 0, no diagnosis, to 3, high image quality. AVM characterization consisted of arterial feeder, nidus size, and venous drainage type identification compared with those at digital subtraction angiography (DSA). κ coefficients were computed to determine interobserver and intermodality agreement. RESULTS: Time-resolved SL MR angiographic imaging over two cardiac cycles provided a median diagnostic confidence index of 2.5 for arterial feeders, 3.0 for nidus, and 3.0 for venous drainage. Venous drainage depiction quality was higher with time-resolved SL MR angiography over two cardiac cycles than with time-resolved SL MR angiography over one cardiac cycle (P < .001) and TOF MR angiography (P < .001). For AVM characterization, interobserver agreement was very good to excellent, and agreement with DSA showed κ of 0.85 for arterial feeders, κ of 1.00 for nidus size, and κ of 0.82 for venous drainage. CONCLUSION: Time-resolved SL MR angiographic imaging over two cardiac cycles is a reliable clinical tool for cerebral AVM characterization, which showed very good to excellent agreement with DSA.

The liberal illusion of uniqueness.

In two studies, we demonstrated that liberals underestimate their similarity to other liberals (i.e., display truly false uniqueness), whereas moderates and conservatives overestimate their similarity to other moderates and conservatives (i.e., display truly false consensus; Studies 1 and 2). We further demonstrated that a fundamental difference between liberals and conservatives in the motivation to feel unique explains this ideological distinction in the accuracy of estimating similarity (Study 2). Implications of the accuracy of consensus estimates for mobilizing liberal and conservative political movements are discussed.

Non-contrast-enhanced 4D MR angiography with STAR spin labeling and variable flip angle sampling: a feasibility study for the assessment of Dural Arteriovenous Fistula.

INTRODUCTION: This study aimed to evaluate the feasibility of non-contrast-enhanced 4D magnetic resonance angiography (NCE 4D MRA) with signal targeting with alternative radiofrequency (STAR) spin labeling and variable flip angle (VFA) sampling in the assessment of dural arteriovenous fistula (DAVF) in the transverse sinus. METHODS: Nine patients underwent NCE 4D MRA for the evaluation of DAVF in the transverse sinus at 3 T. One patient was examined twice, once before and once after the interventional treatment. All patients also underwent digital subtraction angiography (DSA) and/or contrast-enhanced magnetic resonance angiography (CEMRA). For the acquisition of NCE 4D MRA, a STAR spin tagging method was used, and a VFA sampling was applied in the data readout module instead of a constant flip angle. Two readers evaluated the NCE 4D MRA data for the diagnosis of DAVF and its type with consensus. The results were compared with those from DSA and/or CEMRA. RESULTS: All patients underwent NCE 4D MRA without any difficulty. Among seven patients with patent DAVFs, all cases showed an early visualization of the transverse sinus on NCE 4D MRA. Except for one case, the type of DAVF of NCE 4D MRA was agreed with that of reference standard study. Cortical venous reflux (CVR) was demonstrated in two cases out of three patients with CVR. CONCLUSION: NCE 4D MRA with STAR tagging and VFA sampling is technically and clinically feasible and represents a promising technique for assessment of DAVF in the transverse sinus. Further technical developments should aim at improvements of spatial and temporal coverage.

Radiotherapy-activated NBTXR3 nanoparticles promote ferroptosis through induction of lysosomal membrane permeabilization.

PURPOSE: Radiotherapy-activated NBTXR3 (NBTXR3 + RT) has demonstrated superior efficacy in cancer cell destruction and tumor growth control, compared to radiotherapy (RT), in preclinical and clinical settings. Previous studies highlighted the immunomodulatory properties of NBTXR3 + RT, such as modification of tumor cell immunogenicity/adjuvanticity, producing an effective local tumor control and abscopal effect, related to an enhanced antitumor immune response. Furthermore, NBTXR3 + RT has shown potential in restoring anti-PD1 efficacy in a refractory tumor model. However, the early events leading to these results, such as NBTXR3 endocytosis, intracellular trafficking and primary biological responses induced by NBTXR3 + RT remain poorly understood. METHODS: We analyzed by transmission electron microscopy endocytosis and intracellular localization of NBTXR3 nanoparticles after endocytosis in various cell lines, in vitro and in vivo. A kinetic of NBTXR3 endocytosis and its impact on lysosomes was conducted using LysoTracker staining, and a RNAseq analysis was performed. We investigated the ability of NBTXR3 + RT to induce lysosomal membrane permeabilization (LMP) and ferroptosis by analyzing lipid peroxidation. Additionally, we evaluated the recapture by cancer cells of NBTXR3 released from dead cells. RESULTS: NBTXR3 nanoparticles were rapidly internalized by cells mainly through macropinocytosis and in a less extend by clathrin-dependent endocytosis. NBTXR3-containing endosomes were then fused with lysosomes. The day following NBTXR3 addition, we measured a significant increase in LysoTracker lysosome labeling intensity, in vitro as in vivo. Following RT, a significant lysosomal membrane permeabilization (LMP) was measured exclusively in cells treated with NBTXR3 + RT, while RT had no effect. The day post-irradiation, a significant increase in lipid peroxidation, a biomarker of ferroptosis, was measured with NBTXR3 + RT compared to RT. Moreover, we demonstrated that NBTXR3 nanoparticles released from dead cells can be recaptured by cancer cells. CONCLUSIONS: Our findings provide novel insights into the early and specific biological effects induced by NBTXR3 + RT, especially LMP, not induced by RT in our models. The subsequent significant increase in lipid peroxidation partially explains the enhanced cancer cell killing capacity of NBTXR3 + RT compared to RT, potentially by promoting ferroptosis. This study improves our understanding of the cellular mechanisms underlying NBTXR3 + RT and highlights its potential as an agnostic therapeutic strategy for solid cancers treatment.

Technical considerations in MR angiography: an image-based guide.

As the complexity of the magnetic resonance angiography (MRA) techniques grows, it becomes more difficult for the practicing radiologist to appreciate the physical principles underlying these studies. Nevertheless, such an understanding is requisite for improving clinical image quality. As radiologists are most accustomed to dealing with medical images in everyday practice, it seems natural that an image-based approach to teaching MRA physics, rather than complex mathematical equations or pulse sequence diagrams, would be preferable. This article adopts such an approach. Simple ways to improve MRA image quality are emphasized along with new technologies and their physical basis. The ultimate goal of the article is to facilitate the practicing radiologist becoming more aware of the variety of MR techniques available, being more confident in modifying sequence parameters to improve image quality and reduce contrast dose, and understanding the basis behind newer MRA techniques.

A Comparison of Devices for Race Day Characterization of North American Turfgrass Thoroughbred Racing Surfaces.

Both pre-race meet and daily turf surface condition measurements are required by regulations adopted as part of the Horseracing Integrity and Safety Act (HISA). The Orono Biomechanical Surface Tester (OBST) is the primary device used for characterizing a racing surface and is used for the pre-meet inspections. Tools that are better suited for the daily testing of turf surfaces are also needed to meet the new federal regulations. The purpose of this study was to compare five simple tools commonly used in turf applications to the OBST. Data were collected with each of the six devices at plots chosen to approximate the current and potential compositions of North American turf racetracks. Correlations and linear regression models were then established between the simple tool measurements and the parameters measured by the OBST. The moisture probe was found to be the primary device for race day characterization due to its strong correlation to OBST measurements. The Longchamp Penetrometer is also prioritized for daily measurements due to its established correlation to horse performance and injuries. The Clegg Impact Hammer provides further improvement of the linear regression model. The Turf Shear Tester and GoingStick® were not found to correlate well to the biomechanically based device.

T-one insensitive steady state imaging: a framework for purely T2-weighted TrueFISP.

A new conceptual framework called T-one insensitive steady state imaging is proposed for fast generation of MR images with pure T(2) contrast. This is accomplished by imaging between nonequally spaced inversion pulses, with the magnetization vector alternatively residing in states parallel and antiparallel to B(0) for durations TP(i) and TA(i), respectively. With TP(i) and TA(i) adequately chosen, identical signal time evolution can be obtained for different T(1) values, i.e., T(1) contrast can efficiently be removed from resultant images. As a specific realization of this principle, T-one insensitive steady state imaging sequences are presented which use True free induction steady precession readout blocks between the inversion pulses. While the conventional True free induction steady precession signal time course would be determined by both T(2) and T(1), a pure T(2) dependence is realized with successfully suppressed influence of longitudinal relaxation, and images with essentially T(2) contrast alone are obtained. Analytical expressions are provided for the description of the ideal signal behavior, which help in creating pathways for sequence parameter optimization. The performance of the technique is analyzed with Bloch equation simulations. In vivo results obtained in healthy volunteers and brain tumor patients are presented.

Time-resolved MR angiography of renal artery stenosis in a swine model at 3 Tesla using gadobutrol with digital subtraction angiography correlation.

PURPOSE: To establish the minimum dose required for detection of renal artery stenosis using high temporal resolution, contrast enhanced MR angiography (MRA) in a porcine model. MATERIALS AND METHODS: Surgically created renal artery stenoses were imaged with 3 Tesla MR and digital subtraction angiography (DSA) in 12 swine in this IACUC approved protocol. Gadobutrol was injected intravenously at doses of 0.5, 1, 2, and 4 mL for time-resolved MRA (1.5 × 1.5 mm(2) spatial resolution). Region of interest analysis was performed together with stenosis assessment and qualitative evaluation by two blinded readers. RESULTS: Mean signal to noise ratio (SNR) and contrast to noise ratio (CNR) values were statistically significantly less with the 0.5-mL protocol (P < 0.001). There were no statistically significant differences among the other evaluated doses. Both readers found 10/12 cases with the 0.5-mL protocol to be of inadequate diagnostic quality (κ = 1.0). All other scans were found to be adequate for diagnosis. Accuracies in distinguishing between mild/insignificant (<50%) and higher grade stenoses (>50%) were comparable among the higher-dose protocols (sensitivities 73-93%, specificities 62-100%). CONCLUSION: Renal artery stenosis can be assessed with very low doses (~0.025 mmol/kg bodyweight) of a high concentration, high relaxivity gadolinium chelate formulation in a swine model, results which are promising with respect to limiting exposure to gadolinium based contrast agents.

Non-enhanced ECG-gated respiratory-triggered 3-D steady-state free-precession MR angiography with slab-selective inversion: initial experience in visualisation of renal arteries in free-breathing children without renal artery abnormality.

BACKGROUND: ECG-gated non-enhanced balanced steady-state free precession (bSSFP) MR angiography requires neither breath-holding nor administration of contrast material. OBJECTIVE: To investigate the image quality of free-breathing ECG-gated non-enhanced bSSFP MR angiography of renal arteries in children. MATERIALS AND METHODS: Fourteen boys and seven girls (mean age, 9.7 years; range, 7 weeks-17 years) with no history of renovascular disease were included. MRI was performed at 1.5 T. Subjective image quality of axial and coronal maximum-intensity-projection reconstructions of four segments (I, aorta and renal artery ostium; II, main renal artery; III, segmental branches; IV, intrarenal vessels) was evaluated using a 4-point scale (4 = excellent, 3 = good, 2 = acceptable, 1 = non-diagnostic). RESULTS: Image quality was excellent for segments I (mean ± SD, 3.9 ± 0.3) and II (4.0 ± 0.1), good for segment III (3.4 ± 0.9) and acceptable for segment IV (2.3 ± 1.1 ). Mean image quality did not differ between sedated and non-sedated children. CONCLUSION: bSSFP MR angiography enables visualisation of renal arteries in children.

Breath biomarkers of total body irradiation in non-human primates.

Background.Radiation exposure causes oxidative stress, eliciting production of metabolites that are exhaled in the breath as volatile organic compounds (VOCs). We evaluated breath VOCs as potential biomarkers for use in radiation biodosimetry.Methods.Five anesthetized non-human primates receive total body irradiation (TBI) of three daily fractions of 120 cGy per day for three days, resulting in a cumulative dose of 10.8 Gy. Breath samples were collected prior to irradiation and after each radiation fraction, and analyzed with gas chromatography mass spectrometry.Results.TBI elicited a prompt and statistically significant increase in the abundance of several hundred VOCs in the breath, including some that were increased more than five-fold, with100% sensitivity and 100% specificity for radiation exposure. The most significant breath VOC biomarkers of radiation mainly comprised straight-chain n-alkanes (e.g. hexane), as well as methylated alkanes (e.g. 3-methyl-pentane) and alkane derivatives (e.g. 2-butyl-1-octanol), consistent with metabolic products of oxidative stress. An unidentified breath VOC biomarker increased more than ten-fold following TBI, and rose linearly with the total cumulative dose of radiation (R2= 0.92).Conclusions.TBI of non-human primates elicited increased production of breath VOCs consistent with increased oxidative stress. These findings provide a rational basis for further evaluation of breath VOC biomarkers in human radiation biodosimetry.