A prospective patient registry to monitor safety, effectiveness, and utilisation of bedaquiline in patients with multidrug-resistant tuberculosis in South Korea.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) represents a major public health concern, with an ongoing need for new effective treatments. Bedaquiline is an oral diarylquinoline that has shown encouraging treatment success and culture conversion rates in MDR-TB. METHODS: A South Korean patient registry was set up across 19 centres between 2016 and 2018 for the prospective collection of data from patients with MDR-TB who received either a bedaquiline-containing or a non-bedaquiline-containing regimen. Treatment was at the physician's discretion (bedaquiline use requiring approval by special committee) and was based on patient characteristics, disease status, and local treatment guidelines. RESULTS: The safety population included 172 patients (88 bedaquiline and 84 non-bedaquiline). The mean (standard deviation, SD) duration of follow-up was 24.3 (9.5) months. Mean (SD) durations of treatment were 5.4 (1.8) months in bedaquiline-treated patients and 15.7 (6.7) months in the non-bedaquiline group. Treatment success (cured and treatment completed according to WHO 2013 treatment outcome definitions) was achieved by 56.3% of bedaquiline-treated and 45.2% of non-bedaquiline-treated patients. Sputum culture conversion rates were 90.4% and 83.7% with and without bedaquiline, respectively. Diarrhoea and nausea were the most frequently reported treatment-emergent adverse events (TEAEs) in the bedaquiline group (27.3% [24/88] and 22.7% [20/88], respectively). The most frequent bedaquiline-related TEAEs were prolonged QT interval (10.2%; 9/88), and diarrhoea and nausea (9.1% each; 8/88). QT interval prolongation was reported in 19.3% (17/88) of bedaquiline-treated and 2.4% (2/84) of non-bedaquiline-treated patients, but bedaquiline was not discontinued for any patient for this reason. There were 13 (14.7%) and three (3.6%) deaths in the bedaquiline-treated and non-bedaquiline groups, respectively. Review of fatal cases revealed no unexpected safety findings, and no deaths were bedaquiline-related. The most common cause of death was worsening cancer (three patients). Patients in the bedaquiline group tended to have poorer baseline risk profiles than non-bedaquiline patients and were more likely to have relapsed or already failed second-line treatment. Interpretation of mortality data was complicated by high rates of loss to follow-up in both groups. CONCLUSIONS: The South Korean registry findings support previous risk/benefit observations and the continued use of bedaquiline as part of combination therapy in patients with MDR-TB.

Immediate activation of chemosensory neuron gene expression by bacterial metabolites is selectively induced by distinct cyclic GMP-dependent pathways in Caenorhabditis elegans.

Dynamic gene expression in neurons shapes fundamental processes in the nervous systems of animals. However, how neuronal activation by different stimuli can lead to distinct transcriptional responses is not well understood. We have been studying how microbial metabolites modulate gene expression in chemosensory neurons of Caenorhabditis elegans. Considering the diverse environmental stimuli that can activate chemosensory neurons of C. elegans, we sought to understand how specific transcriptional responses can be generated in these neurons in response to distinct cues. We have focused on the mechanism of rapid (<6 min) and selective transcriptional induction of daf-7, a gene encoding a TGF-ß ligand, in the ASJ chemosensory neurons in response to the pathogenic bacterium Pseudomonas aeruginosa. DAF-7 is required for the protective behavioral avoidance of P. aeruginosa by C. elegans. Here, we define the involvement of two distinct cyclic GMP (cGMP)-dependent pathways that are required for daf-7 expression in the ASJ neuron pair in response to P. aeruginosa. We show that a calcium-independent pathway dependent on the cGMP-dependent protein kinase G (PKG) EGL-4, and a canonical calcium-dependent signaling pathway dependent on the activity of a cyclic nucleotide-gated channel subunit CNG-2, function in parallel to activate rapid, selective transcription of daf-7 in response to P. aeruginosa metabolites. Our data suggest that fast, selective early transcription of neuronal genes require PKG in shaping responses to distinct microbial stimuli in a pair of C. elegans chemosensory neurons.

Automated Detection of Surgical Implants on Plain Knee Radiographs Using a Deep Learning Algorithm.

Background and Objectives: The number of patients who undergo multiple operations on a knee is increasing. The objective of this study was to develop a deep learning algorithm that could detect 17 different surgical implants on plain knee radiographs. Materials and Methods: An internal dataset consisted of 5206 plain knee antero-posterior X-rays from a single, tertiary institute for model development. An external set contained 238 X-rays from another tertiary institute. A total of 17 different types of implants including total knee arthroplasty, unicompartmental knee arthroplasty, plate, and screw were labeled. The internal dataset was approximately split into a train set, a validation set, and an internal test set at a ratio of 7:1:2. You Only look Once (YOLO) was selected as the detection network. Model performances with the validation set, internal test set, and external test set were compared. Results: Total accuracy, total sensitivity, total specificity value of the validation set, internal test set, and external test set were (0.978, 0.768, 0.999), (0.953, 0.810, 0.990), and (0.956, 0.493, 0.975), respectively. Means ± standard deviations (SDs) of diagonal components of confusion matrix for these three subsets were 0.858 ± 0.242, 0.852 ± 0.182, and 0.576 ± 0.312, respectively. True positive rate of total knee arthroplasty, the most dominant class of the dataset, was higher than 0.99 with internal subsets and 0.96 with an external test set. Conclusion: Implant identification on plain knee radiographs could be automated using a deep learning technique. The detection algorithm dealt with overlapping cases while maintaining high accuracy on total knee arthroplasty. This could be applied in future research that analyzes X-ray images with deep learning, which would help prompt decision-making in clinics.

Single-shot pseudo-centric EPI for magnetization-prepared imaging.

PURPOSE: To implement a single-shot centric-reordered EPI (1sh-CenEPI), which reduces TE significantly, thus enabling to improve SNR for magnetization-prepared imaging. METHODS: We proposed a 1sh-CenEPI in which grouped oscillating readout gradients, phase-encoding blips within each group, and big phase-encoding jumps between two consecutive groups are incorporated to encode whole k-space from the center to the edges in a single shot. The concept was tested on phantoms and human brains at 3 T. In addition, the proposed reordering scheme was applied to pseudo-continuous arterial spin labeling for evaluating the efficiency of the centric reordering in magnetization-prepared imaging. RESULTS: The proposed 1sh-CenEPI reduced TE from 50 ms to 1.4 ms for gradient-echo EPI, and from 100 ms to 7 ms for spin-echo EPI, while the elongation of readout duration was below 10% of the whole readout duration in most cases. The 1sh-CenEPI images exhibited no distinct geometric distortion both in phantom and human brain, comparable to the conventional two-shot center-out EPI. In pseudo-continuous arterial spin labeling results, 3-fold temporal SNR increase and 2-fold spatial SNR increase in the perfusion-weighted images were achieved with 1sh-CenEPI compared with the conventional linear ordering, whereas the cerebral blood flow values were consistent with previous studies. CONCLUSION: The proposed 1sh-CenEPI significantly reduced TE while maintaining similar readout window and providing images comparable to the conventional linear and multishot center-out EPI images. It can be a qualified candidate as a new readout for various magnetization-prepared imaging techniques.

Rapid three-dimensional steady-state chemical exchange saturation transfer magnetic resonance imaging.

PURPOSE: To make clinically feasible whole-brain chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) by enhancing imaging efficiency. METHODS: A novel, whole-brain three-dimensional (3D) steady-state CEST MRI method was introduced by utilizing a time-efficient, fat-suppressed excitation followed by rapid, segmented 3D echo-planar-imaging with incoherent undersampling in k-ω space. Missing signals and CEST-specific spectral images were then jointly estimated directly from incomplete measurements using model-based reconstruction and robust spectral analysis. In vivo studies were performed at 3T both retrospectively (using a fully sampled reference) and prospectively to validate the effectiveness of the proposed method in patients with brain cancer. RESULTS: In retrospective studies, the proposed method exhibits superior accuracies to existing methods in estimating images, z-spectra, and APTw relative to the reference. In prospective patient studies, compared with existing methods, the proposed method is statistically significantly different in contrast-to-noise ratio of the APTw contrast between tumor and normal appearing white matter (NAWM) and amide proton transfer weighted contrast (p < 0.05) while not being significantly different in signal-to-noise ratio in an NAWM region. CONCLUSIONS: We successfully demonstrated that it is feasible to perform whole-brain CEST MRI roughly within 4 minutes for patients with brain cancer. It is expected that the proposed method widens clinical utilities of CEST MRI.

Association of scar distribution with epicardial electrograms and surface ventricular tachycardia QRS duration in nonischemic cardiomyopathy.

INTRODUCTION: The association of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) with epicardial and surface ventricular tachycardia (VT) electrogram features, in nonischemic cardiomyopathy (NICM), is unknown. We sought to define the association of LGE and viable wall thickness with epicardial electrogram features and exit site paced QRS duration in patients with NICM. METHODS: A total of 19 patients (age 53.5 ± 11.5 years) with NICM (ejection fraction 40.2 ± 13.2%) underwent CMR before VT ablation. LGE transmurality was quantified on CMR and coregistered with 2294 endocardial and 2724 epicardial map points. RESULTS: Both bipolar and unipolar voltage were associated with transmural signal intensity on CMR. Longer electrogram duration and fractionated potentials were associated with increased LGE transmurality, but late potentials or local abnormal ventricular activity were more prevalent in nontransmural versus transmural LGE regions (p < .05). Of all critical VT sites, 19% were located adjacent to regions with LGE but normal bipolar and unipolar voltage. Exit site QRS duration was affected by LGE transmurality and intramural scar location, but not by wall thickness, at the impulse origin. CONCLUSIONS: In patients with NICM and VT, LGE is associated with epicardial electrogram features and may predict critical VT sites. Additionally, exit site QRS duration is affected by LGE transmurality and intramural location at the impulse origin or exit.

The PEX1 ATPase Stabilizes PEX6 and Plays Essential Roles in Peroxisome Biology.

A variety of metabolic pathways are sequestered in peroxisomes, conserved organelles that are essential for human and plant survival. Peroxin (PEX) proteins generate and maintain peroxisomes. The PEX1 ATPase facilitates recycling of the peroxisome matrix protein receptor PEX5 and is the most commonly affected peroxin in human peroxisome biogenesis disorders. Here, we describe the isolation and characterization of, to our knowledge, the first Arabidopsis (Arabidopsis thaliana) pex1 missense alleles: pex1-2 and pex1-3pex1-2 displayed peroxisome-related defects accompanied by reduced PEX1 and PEX6 levels. These pex1-2 defects were exacerbated by growth at high temperature and ameliorated by growth at low temperature or by PEX6 overexpression, suggesting that PEX1 enhances PEX6 stability and vice versa. pex1-3 conferred embryo lethality when homozygous, confirming that PEX1, like several other Arabidopsis peroxins, is essential for embryogenesis. pex1-3 displayed symptoms of peroxisome dysfunction when heterozygous; this semidominance is consistent with PEX1 forming a heterooligomer with PEX6 that is poisoned by pex1-3 subunits. Blocking autophagy partially rescued PEX1/pex1-3 defects, including the restoration of normal peroxisome size, suggesting that increasing peroxisome abundance can compensate for the deficiencies caused by pex1-3 and that the enlarged peroxisomes visible in PEX1/pex1-3 may represent autophagy intermediates. Overexpressing PEX1 in wild-type plants impaired growth, suggesting that excessive PEX1 can be detrimental. Our genetic, molecular, and physiological data support the heterohexamer model of PEX1-PEX6 function in plants.

Lead I R-wave amplitude to differentiate idiopathic ventricular arrhythmias with left bundle branch block right inferior axis originating from the left versus right ventricular outflow tract.

INTRODUCTION: Differentiation of right versus left ventricular outflow tract (RVOT vs. LVOT) arrhythmia origin with left bundle branch block right inferior axis (LBRI) morphology is relevant to ablation planning and risk discussion. Our aim was to determine if lead I R-wave amplitude is useful for differentiation of RVOT from LVOT arrhythmias with LBRI morphology. METHODS: The R-wave amplitude in lead I was measured in a retrospective cohort of 75 consecutive patients with LBRI pattern ventricular arrhythmias (VAs) successfully ablated from the RVOT (n = 54), LVOT (n = 16), or the anterior interventricular vein (AIV; n = 5). The optimal R-wave threshold was identified and diagnostic indices were compared with the previously reported transitional zone (TZ) index and V2S/V3R index. RESULTS: An R-wave amplitude greater than or equal to 0.1 mV predicted LVOT origin with 75% sensitivity and 98.2% specificity. In comparison, the TZ and V2S/V3R indices had 50% and 68.8% sensitivity, and 75.9% and 88.9% specificity, respectively, for predicting LVOT origin. The area under the curve (AUC) was 0.85 for lead I R-wave amplitude, 0.87 for V2S/V3R, and 0.72 for the TZ index. Of 36 cases with QS in lead I, 30 (83.3%) were from the anterior RVOT, three (8.3%) from the LVOT, and three (8.3%) from the AIV. CONCLUSION: The presence of R-wave amplitude in lead I (≥0.1 mV) is a simple and useful criterion to identify LVOT cusp or endocardium focus in LBRI arrhythmias. A QS pattern in lead I suggests an origin in the anterior RVOT, or less commonly the adjacent LV summit.

Quality of Anticoagulation and Treatment Satisfaction in Patients with Non-Valvular Atrial Fibrillation Treated with Vitamin K Antagonist: Result from the KORean Atrial Fibrillation Investigation II.

BACKGROUND: Vitamin K antagonist (VKA) to prevent thromboembolism in non-valvular atrial fibrillation (NVAF) patients has limitations such as drug interaction. This study investigated the clinical characteristics of Korean patients treated with VKA for stroke prevention and assessed quality of VKA therapy and treatment satisfaction. METHODS: We conducted a multicenter, prospective, non-interventional study. Patients with CHADS2 ≥ 1 and treated with VKA (started within the last 3 months) were enrolled from April 2013 to March 2014. Demographic and clinical features including risk factors of stroke and VKA treatment information was collected at baseline. Treatment patterns and international normalized ratio (INR) level were evaluated during follow-up. Time in therapeutic range (TTR) > 60% indicated well-controlled INR. Treatment satisfaction on the VKA use was measured by Treatment Satisfaction Questionnaire for Medication (TSQM) after 3 months of follow-up. RESULTS: A total of 877 patients (age, 67; male, 60%) were enrolled and followed up for one year. More than half of patients (56%) had CHADS2 ≥ 2 and 83.6% had CHA2DS2-VASc ≥ 2. A total of 852 patients had one or more INR measurement during their follow-up period. Among those patients, 25.5% discontinued VKA treatment during follow-up. Of all patients, 626 patients (73%) had poor-controlled INR (TTR < 60%) measure. Patients' treatment satisfaction measured with TSQM was 55.6 in global satisfaction domain. CONCLUSION: INR was poorly controlled in Korean NVAF patients treated with VKA. VKA users also showed low treatment satisfaction.

SMS-HSL: Simultaneous multislice aliasing separation exploiting hankel subspace learning.

PURPOSE: To develop a novel, simultaneous multislice reconstruction method that exploits Hankel subspace learning (SMS-HSL) for aliasing separation in the slice direction. METHODS: An SMS signal model with the Hankel-structured matrix was proposed. To efficiently suppress interslice leakage artifacts from a signal subspace perspective, a null space was learned from the reference data combined over all slices other than a slice of interest using singular value decomposition. Given the fact that the Hankel-structured matrix is rank-deficient while the magnitude between the reference and its estimate is similar in k-space, the SMS-HSL was reformulated as a constrained optimization problem with both low-rank and magnitude priors. SMS signals were projected onto a slice-specific subspace while undesired signals were eliminated using the null space operator. The simulations and experiments were performed with increasing multiband factors up to 6 using the SMS-HSL and the split slice-GRAPPA. RESULTS: Compared with the split slice-GRAPPA, the SMS-HSL shows superior performance in suppressing aliasing artifacts and noises at high multiband factors even with: insufficient reference signals, a small number of coils, and a short distance between aliasing voxels. CONCLUSION: We successfully demonstrated the effectiveness of the SMS-HSL over the split slice-GRAPPA for aliasing separation in the slice direction. Magn Reson Med 78:1392-1404, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Current-induced alternating reversed dual-echo-steady-state for joint estimation of tissue relaxation and electrical properties.

PURPOSE: To develop a current-induced, alternating reversed dual-echo-steady-state-based magnetic resonance electrical impedance tomography for joint estimation of tissue relaxation and electrical properties. METHODS: The proposed method reverses the readout gradient configuration of conventional, in which steady-state-free-precession (SSFP)-ECHO is produced earlier than SSFP-free-induction-decay (FID) while alternating current pulses are applied in between the two SSFPs to secure high sensitivity of SSFP-FID to injection current. Additionally, alternating reversed dual-echo-steady-state signals are modulated by employing variable flip angles over two orthogonal injections of current pulses. Ratiometric signal models are analytically constructed, from which T1 , T2 , and current-induced Bz are jointly estimated by solving a nonlinear inverse problem for conductivity reconstruction. Numerical simulations and experimental studies are performed to investigate the feasibility of the proposed method in estimating relaxation parameters and conductivity. RESULTS: The proposed method, if compared with conventional magnetic resonance electrical impedance tomography, enables rapid data acquisition and simultaneous estimation of T1 , T2 , and current-induced Bz , yielding a comparable level of signal-to-noise ratio in the parameter estimates while retaining a relative conductivity contrast. CONCLUSION: We successfully demonstrated the feasibility of the proposed method in jointly estimating tissue relaxation parameters as well as conductivity distributions. It can be a promising, rapid imaging strategy for quantitative conductivity estimation. Magn Reson Med 78:107-120, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Rapid whole-brain gray matter imaging using single-slab three-dimensional dual-echo fast spin echo: A feasibility study.

PURPOSE: To achieve rapid, high resolution whole-brain gray matter (GM) imaging by developing a novel, single-slab three-dimensional dual-echo fast-spin-echo pulse sequence and GM-selective reconstruction. METHODS: Unlike conventional GM imaging that uses time-consuming double-inversion-recovery preparation, the proposed pulse sequence was designed to have two split portions along the echo train, in which the first half was dedicated to yield short inversion recovery (IR)-induced white matter suppression and variable-flip-angle-induced two-step GM signal evolution while the second half cerebrospinal fluid-only signals. Multi-step variable-flip-angle schedules and sampling reordering were optimized to yield high GM signals while balancing cerebrospinal fluid signals between ECHOes. GM-selective images were then reconstructed directly from the weighted subtraction between ECHOes by solving a sparse signal recovery problem. In vivo studies were performed to validate the effectiveness of the proposed method over conventional double-inversion-recovery. RESULTS: The proposed method, while achieving one millimeter isotropic, whole-brain GM imaging within 5.5 min, showed superior performance than conventional double-inversion-recovery in producing GM-only images without apparent artifacts and noise. CONCLUSION: We successfully demonstrated the feasibility of the proposed method in achieving whole-brain GM imaging in a clinically acceptable imaging time. The proposed method is expected to be a promising alternative to conventional double-inversion-recovery in clinical applications. Magn Reson Med 78:1691-1699, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Rapid chemical shift encoding with single-acquisition single-slab 3D GRASE.

PURPOSE: To investigate the feasibility of chemical shift encoded, single-slab 3D GRASE for rapid fat-water separation within a single acquisition. METHODS: The proposed method incorporates signal-to-noise-ratio-optimal chemical shift encoding into single-slab 3D GRASE with variable flip angles. Chemical shift induced phase information was encoded in succession to different positions in k-space by inserting phase encoding blips between adjacent lobes of the oscillating readout gradients. To enhance imaging efficiency, signal prescription-based variable flip angles were used in the long refocusing pulse train. After echo-independent phase correction, missing signals in k-echo space were interpolated using convolution kernels that span over all echoes. Fat-water separation in a single acquisition was performed using both multi-echo fast spin echo and GRASE as compared to conventional multiacquisition fast spin echo with echo shifts. RESULTS: The proposed single-slab 3D GRASE shows superior performance in accurately delineating cartilage structures compared to its counterpart, multi-echo 3D fast spin echo. Compared with multiacquisition fast spin echo with three echo shifts (63 min), the proposed method substantially speeds up imaging time (7 min), and achieves 0.6 mm isotropic resolution in knee imaging with reduced artifacts and noise. CONCLUSION: We successfully demonstrated the feasibility of rapid chemical shift encoding and separation using the proposed, single-acquisition single-slab 3D GRASE for high resolution isotropic imaging within clinically acceptable time. Magn Reson Med 78:1852-1861, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Alternating steady state free precession for estimation of current-induced magnetic flux density: A feasibility study.

PURPOSE: To develop a novel, current-controlled alternating steady-state free precession (SSFP)-based conductivity imaging method and corresponding MR signal models to estimate current-induced magnetic flux density (Bz ) and conductivity distribution. METHODS: In the proposed method, an SSFP pulse sequence, which is in sync with alternating current pulses, produces dual oscillating steady states while yielding nonlinear relation between signal phase and Bz . A ratiometric signal model between the states was analytically derived using the Bloch equation, wherein Bz was estimated by solving a nonlinear inverse problem for conductivity estimation. A theoretical analysis on the signal-to-noise ratio of Bz was given. Numerical and experimental studies were performed using SSFP-FID and SSFP-ECHO with current pulses positioned either before or after signal encoding to investigate the feasibility of the proposed method in conductivity estimation. RESULTS: Given all SSFP variants herein, SSFP-FID with alternating current pulses applied before signal encoding exhibits the highest Bz signal-to-noise ratio and conductivity contrast. Additionally, compared with conventional conductivity imaging, the proposed method benefits from rapid SSFP acquisition without apparent loss of conductivity contrast. CONCLUSION: We successfully demonstrated the feasibility of the proposed method in estimating current-induced Bz and conductivity distribution. It can be a promising, rapid imaging strategy for quantitative conductivity imaging.

Variable-flip-angle single-slab 3D GRASE imaging with phase-independent image reconstruction.

PURPOSE: To develop a single-slab three-dimensional variable-flip-angle gradient- and spin-echo pulse sequence with phase-independent reconstruction that is highly energy- or encoding-efficient for high resolution isotropic imaging at high magnetic field. METHODS: Amplitude modulation in the proposed pulse sequence was alleviated using a variable-flip-angle induced smooth signal evolution along the long echo train. To avoid phase modulation, instead of directly interleaving phase encoding signals with different off-resonance induced phase accumulation over multiple echoes, phase-independent image reconstruction was performed, wherein each echo image was separately reconstructed using convolution-interpolation with echo-interleaving self-calibration and then combined. Numerical and experimental studies were performed at 3.0 T for generation of clinical T2 -weighted contrast to investigate the effectiveness of the proposed method over existing methods. RESULTS: Compared with conventional techniques, the proposed method produces smooth amplitude variation, no ghosting artifacts (no phase modulation), and competitive signal-to-noise ratio. An energy-efficient variable-flip-angle gradient- and spin-echo reduces specific absorption rate by 71% without significant loss of signal-to-noise ratio, while an encoding-efficient one decreases imaging time by 54% with a slight loss of signal-to-noise ratio. CONCLUSION: We successfully demonstrated that the proposed variable-flip-angle gradient- and spin-echo can be a highly promising energy- or encoding-efficient alternative for high resolution isotropic imaging.

Variable-density velocity-selective magnetization preparation for non-contrast-enhanced peripheral MR angiography.

Velocity-selective (VS) magnetization preparation has shown great promise for non-contrast-enhanced (NCE) magnetic resonance angiography (MRA) with the ability to generate positive angiographic contrast directly using a single 3D acquisition. However, existing VS-MRA methods have an issue of aliased saturation around a certain velocity, known as velocity field-of-view (vFOV), which can cause undesired signal loss in arteries. This study aimed to develop a new version of the VS preparation pulse sequence that overcomes the aliased saturation problem in conventional VS preparation. Utilizing the fact that an excitation profile is the Fourier transform of excitation k-space sampling, we sampled the k-space in a non-uniform fashion by scaling gradient pulses accordingly to have aliased excitation diffused over velocity. The variable density sampling function was numerically optimized to maximize the average of the velocity passband signal while minimizing its variance. The optimized variable density VS magnetization was validated through Bloch simulations and applied to peripheral NCE MRA in healthy subjects. The in-vivo experiments showed that the proposed variable density VS-MRA significantly lowered arterial signal loss observed in conventional VS-MRA, as evidenced by a higher arterial signal-to-noise ratio (58.50 ± 14.29 vs. 55.54 ± 12.32; p < 0.05) and improved artery-to-background contrast-to-noise ratio (22.75 ± 7.57 vs. 20.60 ± 6.51; p < 0.05).

Genetic variants that modify neuroendocrine gene expression and foraging behavior of C. elegans.

The molecular mechanisms underlying diversity in animal behavior are not well understood. A major experimental challenge is determining the contribution of genetic variants that affect neuronal gene expression to differences in behavioral traits. In Caenorhabditis elegans, the neuroendocrine transforming growth factor-ß ligand, DAF-7, regulates diverse behavioral responses to bacterial food and pathogens. The dynamic neuron-specific expression of daf-7 is modulated by environmental and endogenous bacteria-derived cues. Here, we investigated natural variation in the expression of daf-7 from the ASJ pair of chemosensory neurons. We identified common genetic variants in gap-2, encoding a Ras guanosine triphosphatase (GTPase)-activating protein homologous to mammalian synaptic Ras GTPase-activating protein, which modify daf-7 expression cell nonautonomously and promote exploratory foraging behavior in a partially DAF-7-dependent manner. Our data connect natural variation in neuron-specific gene expression to differences in behavior and suggest that genetic variation in neuroendocrine signaling pathways mediating host-microbe interactions may give rise to diversity in animal behavior.

SNR-optimized phase-sensitive dual-acquisition turbo spin echo imaging: a fast alternative to FLAIR.

Phase-sensitive dual-acquisition single-slab three-dimensional turbo spin echo imaging was recently introduced, producing high-resolution isotropic cerebrospinal fluid attenuated brain images without long inversion recovery preparation. Despite the advantages, the weighted-averaging-based technique suffers from noise amplification resulting from different levels of cerebrospinal fluid signal modulations over the two acquisitions. The purpose of this work is to develop a signal-to-noise ratio-optimized version of the phase-sensitive dual-acquisition single-slab three-dimensional turbo spin echo. Variable refocusing flip angles in the first acquisition are calculated using a three-step prescribed signal evolution while those in the second acquisition are calculated using a two-step pseudo-steady state signal transition with a high flip-angle pseudo-steady state at a later portion of the echo train, balancing the levels of cerebrospinal fluid signals in both the acquisitions. Low spatial frequency signals are sampled during the high flip-angle pseudo-steady state to further suppress noise. Numerical simulations of the Bloch equations were performed to evaluate signal evolutions of brain tissues along the echo train and optimize imaging parameters. In vivo studies demonstrate that compared with conventional phase-sensitive dual-acquisition single-slab three-dimensional turbo spin echo, the proposed optimization yields 74% increase in apparent signal-to-noise ratio for gray matter and 32% decrease in imaging time. The proposed method can be a potential alternative to conventional fluid-attenuated imaging.

The effect of pulmonary blood flow changes on oxygen-enhanced lung magnetic resonance imaging.

In this study, we investigated the effects of changes in pulmonary blood flow on oxygen-enhanced lung magnetic resonance imaging. Increased pulmonary blood flow was produced by intravenous infusion of sildenafil (0.2 mg/kg) in 10 New Zealand white rabbits. Decreased pulmonary blood flow was produced by single subcutaneous injection of monocrotaline (60 mg/kg). A velocity-encoded cine magnetic resonance imaging for pulmonary blood flow and an oxygen-enhanced lung magnetic resonance imaging were performed at baseline, during sildenafil infusion, and after monocrotaline injection. We compared the baseline data to those obtained during sildenafil infusion and after monocrotaline injection for pulmonary blood flow changes and signal intensity enhancement ratios of oxygen-enhanced lung magnetic resonance imaging. Wilcoxon's signed rank test was used for statistical analysis. There was a significant difference between pulmonary blood flow at baseline (418.6±108.9 mL/min) and after sildenafil (491.9±118.0 mL/min; P=0.005) or between pulmonary blood flow at baseline and after monocrotaline administration (356.3±85.8 mL/min; P=0.017). However, there was no significant difference between the signal intensity enhancement ratios at baseline (23.8±11.4%) and after sildenafil (24.0±7.9%; P=0.953) or the signal intensity enhancement ratios at baseline and after monocrotaline administration (22.7±10.3%; P=0.374). Changes in pulmonary blood flow had little effect on the signal intensity enhancement ratio of oxygen-enhanced lung magnetic resonance imaging.