Genetic influences of the effect of circulating inflammatory cytokines on osteoarthritis in humans.

OBJECTIVE: The causal relationship between inflammatory cytokines and Osteoarthritis (OA) has not been well investigated. This study investigated the causal role of inflammatory cytokines in the risk of OA and total joint arthroplasty using the Mendelian randomization (MR) method. METHOD: Single nucleotide polymorphisms (SNPs) robustly associated with inflammatory cytokines were used as instrumental variables. The inverse-variance weighted (IVW) method with false discovery rate (FDR) adjusted P-value (q-value) for multiple comparisons were used as the main MR method to estimate causal effects based on the summary-level data for OA (knee and hip OA, respectively) and total joint arthroplasty (TJA). Sensitivity analyses validated the robustness of the results and ensured the absence of heterogeneity and horizontal pleiotropy. RESULTS: After FDR adjustment, macrophage colony-stimulating factor (MCSF) and vascular endothelial growth factor (VEGF) were identified as causally associated with knee OA (MCSF, odds ratio [OR]: 1.16, 95% confidence interval [CI]: 1.09-1.23, q = 5.05 × 10-5; VEGF, OR: 1.09, 95% CI: 1.04-1.15, q = 0.011). We also observed that genetically predicted MCSF and VEGF were positively associated with the risk of TJA, and MCP3 was negatively associated with for the risk of TJA, although the effects seem fairly modest. Sensitivity analysis further excluded the influence of heterogeneity and horizontal pleiotropy. CONCLUSIONS: Inflammatory cytokines, namely MCSF and VEGF, were causally associated with knee OA, which could enhance our understanding of inflammation in OA pathology.

[Study on revision of standard limits for nitrogen dioxide in "Standards for indoor air quality（GB/T 18883-2022）" in China].

Nitrogen dioxide (NO2) is an important indoor air pollutant, with both outdoor and indoor sources contributing to indoor NO2 exposure levels. Considering the association of high NO2 exposure with adverse health effects, the Standards for indoor air quality (GB/T 18883-2022) have been revised to further restrict indoor NO2 limit values. The 1-h average concentration limit value for NO2 has been reduced from 0.24 mg/m3 to 200 µg/m3.This study analyzed the technical contents related to the determination of the limits of indoor NO2 in Standards for Indoor Air Quality (GB/T 18883-2022), including source, exposure level, health effects, and the process and evidence basis for determining the limit value. It also proposed prospects for the direction for the implementation of the indoor NO2 standard.

[A panel study on the acute respiratory effects of ambient particles of different sizes on children in Shanghai].

Objective: To explore the association between size-fractionated particle number concentrations (PNC) and respiratory health in children. Methods: From November 2018 to June 2019, there were 65 children aged 6-9 years from an elementary school in shanghai recruited in this panel study with three rounds of follow-up. The forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and exhaled nitric oxide (FeNO) levels were measured and buccal mucosa samples of children were collected at each follow-up visit. The level of PNC, temperature and humidity of the elementary school was monitored from 3 days before each physical examination to the end of the physical examination. The linear mixed effects model was used to analyze the association between PNC and indicators of respiratory health in children. Results: Linear mixed effects model analysis revealed that, at lag 2 day, an interquartile range increase in PNC for particles measuring 0.25-0.40 µm was associated with the absolute changes in FVC, FEV1 and abundance-based coverage estimator (ACE) about -60.15 ml (95%CI:-88.97 ml, -31.32 ml), -34.26 ml (95%CI:-63.22 ml, -5.31 ml), -6.00 (95%CI:-9.15, -2.84) and percentage change in FeNO about 12.10% (95%CI: 3.05%, 21.95%), respectively. These adverse health effects increased with the decrease of particle size. Conclusion: The short-term exposure to particulate matter is associated with reduced lung function, buccal microbe diversity and higher airway inflammation level among children. These adverse health effects may increase with the decrease of particle size.

Nephrotoxicity of continuous amphotericin B in critically ill patients with abdominal sepsis: a retrospective analysis with propensity score matching.

BACKGROUND: Continuous infusion of conventional amphotericin B (CCAB) is used in ICUs for pre-emptive treatment of invasive fungal infections. Amphotericin B has previously been associated with nephrotoxicity. OBJECTIVES: To investigate if CCAB with therapeutic drug monitoring (TDM) results in renal impairment over time in critically ill patients with abdominal sepsis. PATIENTS AND METHODS: The study was conducted at mixed medical-surgical ICUs of two large teaching hospitals in the Netherlands. Consecutive patients who were treated on the ICUs between 2006 and 2019 for abdominal sepsis, with or without CCAB, were included. CCAB dosing was guided by TDM. Serum creatinine concentrations and renal failure scores of patients with CCAB treatment were compared with those without CCAB treatment. Excluded were: (i) patients treated with CCAB for less than 72 h; and (ii) patients with renal replacement therapy. RESULTS: A total of 319 patients were included (185 treated with CCAB and 134 controls). A multiple linear regression model showed that the serum creatinine concentration was independent of CCAB treatment (ß = -0.023; 95% CI = -12.2 to 7.2; P = 0.615). Propensity score matching resulted in 134 pairs of CCAB-treated and non-treated patients. Again, the analysis of these pairs showed that the cumulative CCAB dose was not associated with serum creatinine concentration during intensive care treatment (ß = 0.299; 95% CI = -0.38 to 0.98; P = 0.388). CONCLUSIONS: CCAB with TDM did not result in renal impairment over time in critically ill patients with abdominal sepsis.

Protective effects of dietary fish-oil supplementation on skin inflammatory and oxidative stress biomarkers induced by fine particulate air pollution: a pilot randomized, double-blind, placebo-controlled trial.

BACKGROUND: Exposure to fine particulate matter (with an aerodynamic diameter ≤ 2·5 µm, PM2·5 ) air pollution has been associated with skin-related diseases or disorders. OBJECTIVES: To evaluate the potential skin-protective effects of fish-oil supplementation against PM2·5 exposure. MATERIALS AND METHODS: This is an exploratory analysis based on a pilot randomized, double-blind, placebo-controlled trial among 65 healthy young adults between September 2017 and January 2018 in Shanghai, China. We randomly assigned participants to take either fish oil or placebo 2·5 g daily for four consecutive months. Four rounds of skin D-Squame® tape samples were collected in the last 2 months, and five secondary biomarkers of skin inflammation and oxidative stress were measured. Fixed-site PM2·5 concentrations on campus were measured in real time. We used linear mixed-effect models to analyse the associations between short-term PM2·5 exposure and biomarkers in each group. RESULTS: The 24-h average PM2·5 concentration was 34·68 ± 15·83 µg m-3 . There were generally weaker associations between PM2·5 and biomarkers in the fish-oil group than in the placebo group, but the associations and the between-group differences varied by biomarkers and lag periods. Compared with the placebo group, for a 10-µg m-3 increase in PM2·5 concentration, the increments of interleukin-1α and carbonyl protein in the fish-oil group were 41·55% smaller [95% confidence interval (CI) 4·61-78·48%] at lag 0-48 h and 22·01% smaller (95% CI 11·25-32·77%) at lag 0-24 h, respectively. No significant between-group differences were observed for other biomarkers. CONCLUSIONS: This study suggested that dietary fish-oil supplementation may improve biomarkers of skin inflammation and oxidative-stress response to short-term PM2·5 exposure.

Non-surgical treatment of knee osteoarthritis.

Knee osteoarthritis is one of the most common degenerative diseases causing disability in elderly patients. Osteoarthritis is an increasing problem for ageing populations, such as that in Hong Kong. It is important for guidelines to be kept up to date with the best evidence-based osteoarthritis management practices available. The aim of this study was to review the current literature and international guidelines on non-surgical treatments for knee osteoarthritis and compared these with the current guidelines in Hong Kong, which were proposed in 2005. Internationally, exercise programmes for non-surgical management of osteoarthritis have been proven effective, and a pilot programme in Hong Kong for comprehensive non-surgical knee osteoarthritis management has been successful. Long-term studies on the effectiveness of such exercise programmes are required, to inform future changes to guidelines on osteoarthritis management.

[Research progress of ambient air pollution and human health in China].

As one of the major environmental and health problems in China, ambient air pollution has attracted substantial public concerns. This paper reviews the current evidence on air pollution and population health in China, including acute health effect studies, chronic health effect studies, disease burden, and interventions studies. Future research directions are also discussed.

[Impact of fine particulate matters on the daily number of emergency visits and outpatient visits of 5 hospitals in Beijing, Shanghai, and Guangzhou, 2013-2015].

Objective: To explore the effect of fine particulate matters (PM(2.5)) exposure on emergency visits and outpatient visits of 5 hospitals in Beijing, Shanghai and Guangzhou from 2013 to 2015. Methods: Using convenient sampling method, 5 general hospitals in Beijing, Shanghai and Guangzhou were selected which included Beijing hospital, China-Japan friendship hospital, Xinhua hospital affiliated to Shanghai jiaotong University School of Medicine, the liwan hospital of the third affiliated hospital and the first affiliated hospital of Guangzhou Medical University. The emergency and outpatient data, air pollution monitoring data and meteorological data were collected from January 1, 2013 to December 31, 2015. A generalized additive model was used to analyze the effect of PM(2.5) exposure on daily hospital emergency and outpatient visits, and Meta analysis was used to obtain the combined effect value. Results: The number of emergency and outpatient visits of 5 hospitals was 1 378 501 and 18 139 779 in total, respectively. The mean±SD of PM(2.5) exposures in Beijing hospital, China-Japan friendship hospital, Xinhua hospital affiliated to Shanghai jiaotong University School of Medicine, the liwan hospital of the third affiliated hospital and the first affiliated hospital of Guangzhou Medical University were (81.8±68.7), (83.2±69.7), (54.4±34.1), (43.5±24.8) µg/m(3), respectively. Results of single pollutant model analysis showed that 0-1 day lag concentrations of PM(2.5) had the largest effect on emergency visits and outpatient visits. For a 10 µg/m(3) increase of PM(2).5 concentration, excess risk (ER) (95%CI) of emergency and outpatient visits was 0.56% (0.14%, 0.99%) and0.63% (0.07%, 1.19%), respectively. After adjusting for O(3), NO(2), SO(2), and CO, for a 10 µg/m(3) increase of PM(2.5) concentrations, the ER (95%CI) of emergency visits was 0.50% (0.10%, 0.90%), 0.34% (-0.02%, 0.69%), 0.36% (0.02%, 0.69%) and 0.56% (0.10%, 1.03%), respectively and the ER (95% CI) of outpatient visits was 0.65% (0.08%, 1.21%), 0.29% (-0.17%, 0.75%), 0.48% (-0.06%, 1.03%) and 0.48%(-0.02%, 0.99%), respectively. Conclusion: Our results suggested that PM(2.5) exposure can increase emergency and outpatient visits of 5 hospitals in Beijing, Shanghai and Guangzhou.

Sensory nerve degeneration in a mouse model mimicking early manifestations of familial amyloid polyneuropathy due to transthyretin Ala97Ser.

AIMS: Sensory nerve degeneration and consequent abnormal sensations are the earliest and most prevalent manifestations of familial amyloid polyneuropathy (FAP) due to amyloidogenic transthyretin (TTR). FAP is a relentlessly progressive degenerative disease of the peripheral nervous system. However, there is a lack of mouse models to replicate the early neuropathic manifestations of FAP. METHODS: We established human TTR knock-in mice by replacing one allele of the mouse Ttr locus with human wild-type TTR (hTTRwt ) or human TTR with the A97S mutation (hTTRA97S ). Given the late onset of neuropathic manifestations in A97S-FAP, we investigated nerve pathology, physiology, and behavioural tests in these mice at two age points: the adult group (8 - 56 weeks) and the ageing group (> 104 weeks). RESULTS: In the adult group, nerve profiles, neurophysiology and behaviour were similar between hTTRwt and hTTRA97S mice. By contrast, ageing hTTRA97S mice showed small fibre neuropathy with decreased intraepidermal nerve fibre density and behavioural signs of mechanical allodynia. Furthermore, significant reductions in sural nerve myelinated nerve fibre density and sensory nerve action potential amplitudes in these mice indicated degeneration of large sensory fibres. The unaffected motor nerve physiology replicated the early symptoms of FAP patients, that is, sensory nerves were more vulnerable to mutant TTR than motor nerves. CONCLUSIONS: These results demonstrate that the hTTRA97S mouse model develops sensory nerve pathology and corresponding physiology mimicking A97S-FAP and provides a platform to develop new therapies for the early stage of A97S-FAP.

Engineered nanoparticle exposure and cardiovascular effects: the role of a neuronal-regulated pathway.

Human and animal studies have confirmed that inhalation of particles from ambient air or occupational settings not only causes pathophysiological changes in the respiratory system, but causes cardiovascular effects as well. At an equal mass lung burden, nanoparticles are more potent in causing systemic microvascular dysfunction than fine particles of similar composition. Thus, accumulated evidence from animal studies has led to heightened concerns about the potential short- and long-term deleterious effects of inhalation of engineered nanoparticles on the cardiovascular system. This review highlights the new observations from animal studies, which document the adverse effects of pulmonary exposure to engineered nanoparticles on the cardiovascular system and elucidate the potential mechanisms involved in regulation of cardiovascular function, in particular, how the neuronal system plays a role and reacts to pulmonary nanoparticle exposure based on both in vivo and in vitro studies. In addition, this review also discusses the possible influence of altered autonomic nervous activity on preexisting cardiovascular conditions. Whether engineered nanoparticle exposure serves as a risk factor in the development of cardiovascular diseases warrants further investigation.

[Review on methods in the disease burden assessment attributable to household air pollution].

In the past decades, people's work and life styles have dramatically changed during the rapid economic development and urbanization in China. A national survey reported that Chinese adults spend an average of 81% of daily time in indoor environment. Exposure to indoor air pollution plays key roles for human health but is likely to be neglected due on the relatively lower concentration levels and lower awareness among common people. Till now, published studies focus more on the pollution levels or the toxicological effects of indoor air pollutants but there is a lack of disease burden assessment attributable to indoor air pollution. In this review, several international studies were introduced on the disease burden estimation attributable to indoor air pollution, as well as the estimation methods. The current situation of national study was also reviewed. The strengths and limitations of the representative international studies were discussed. This review is helpful in providing data to guide the research on disease burden assessment attributable to indoor air pollution in China, and further helps to prioritize the indoor air pollution control based on disease burden ranking among pollutants and motivate public policies to protect the public health.

Elevated phosphodiester and T2 levels can be measured in the absence of fat infiltration in Duchenne muscular dystrophy patients.

Quantitative MRI and MRS are increasingly important as non-invasive outcome measures in therapy development for Duchenne muscular dystrophy (DMD). Many studies have focussed on individual measures such as fat fraction and metabolite levels in relation to age and functionality, but much less attention has been given to how these indices relate to each other. Here, we assessed spatially resolved metabolic changes in leg muscles of DMD patients, and classified muscles according to the degree of fat replacement compared with healthy controls. Quantitative MRI (three-point Dixon and multi-spin echo without fat suppression and a tri-exponential fit) and 2D-CSI 31 P MRS scans were obtained from 18 DMD patients and 12 healthy controls using a 3 T and a 7 T MR scanner. Metabolite levels, T2 values and fat fraction were individually assessed for five lower leg muscles. In muscles with extensive fat replacement, phosphodiester over adenosine triphosphate (PDE/ATP), inorganic phosphate over phosphocreatine, intracellular tissue pH and T2 were significantly increased compared with healthy controls. In contrast, in muscles without extensive fat replacement, only PDE/ATP and T2 values were significantly elevated. Overall, our results show that PDE levels and T2 values increase prior to the occurrence of fat replacement and remain elevated in later stages of the disease. This suggests that these individual measures could not only function as early markers for muscle damage but also reflect potentially reversible pathology in the more advanced stages.

Incidental extra-cardiac findings on 13N-ammonia myocardial perfusion PET/CT.

BACKGROUND: The objective of this study was to describe the prevalence of incidental extra-cardiac findings (IECFs) on myocardial perfusion PET/CTs and the prevalence of potentially clinically relevant and clinically irrelevant IECFs, as well as detection rate of previously unknown malignancies. METHODS AND RESULTS: From September 2013 until February 2016, a total of 1397 consecutive patients referred for the evaluation of possible ischemia by 13NH3 PET/CT were prospectively included in a database. IECFs were categorized into three groups: potentially clinically relevant IECFs, IECFs that could potentially cause chest pain, and clinically irrelevant IECFs. Additionally, the prevalence of previously unknown malignancies was determined. In 717 (51%) of these patients, 775 IECFs were reported and 115 IECFs were categorized as potentially clinically relevant in 109 (8%) patients. A total of 145 IECFs that could potentially cause chest pain were detected in 139 (10%) patients and 515 clinically irrelevant IECFs were detected in 469 (34%) of the patients. An unknown primary malignancy was histologically proven in 19 patients (1.4%). CONCLUSIONS: IECFs are detected on myocardial perfusion PET/CT in approximately half of the patients. In the present study, IECFs were potentially clinically relevant in 8% of the patients and in 1.4% an unknown malignancy was found, most of which were lung cancers.

Time-efficient measurement of multi-phase arterial spin labeling MR signal in white matter.

White matter (WM) perfusion has great potential as a physiological biomarker in many neurological diseases. Although it has been demonstrated previously that arterial spin labeling magnetic resonance imaging (ASL-MRI) enables the detection of the perfusion-weighted signal in most voxels in WM, studies of cerebral blood flow (CBF) in WM by ASL-MRI are relatively scarce because of its particular challenges, such as significantly lower perfusion and longer arterial transit times relative to gray matter (GM). Recently, ASL with a spectroscopic readout has been proposed to enhance the sensitivity for the measurement of WM perfusion. However, this approach suffers from long acquisition times, especially when acquiring multi-phase ASL datasets to improve CBF quantification. Furthermore, the potential increase in the signal-to-noise ratio (SNR) by spectroscopic readout compared with echo planar imaging (EPI) readout has not been proven experimentally. In this study, we propose the use of time-encoded pseudo-continuous ASL (te-pCASL) with single-voxel point-resolved spectroscopy (PRESS) readout to quantify WM cerebral perfusion in a more time-efficient manner. Results are compared with te-pCASL with a conventional EPI readout for both WM and GM perfusion measurements. Perfusion measurements by te-pCASL PRESS and conventional EPI showed no significant difference for quantitative WM CBF values (Student's t-test, p = 0.19) or temporal SNR (p = 0.33 and p = 0.81 for GM and WM, respectively), whereas GM CBF values (p = 0.016) were higher using PRESS than EPI readout. WM CBF values were found to be 18.2 ± 7.6 mL/100 g/min (PRESS) and 12.5 ± 5.5 mL/100 g/min (EPI), whereas GM CBF values were found to be 77.1 ± 11.2 mL/100 g/min (PRESS) and 53.6 ± 9.6 mL/100 g/min (EPI). This study demonstrates the feasibility of te-pCASL PRESS for the quantification of WM perfusion changes in a highly time-efficient manner, but it does not result in improved temporal SNR, as does traditional te-pCASL EPI, which remains the preferred option because of its flexibility in use.

Fast Heating of Imploded Core with Counterbeam Configuration.

A tailored-pulse-imploded core with a diameter of 70 µm is flashed by counterirradiating 110 fs, 7 TW laser pulses. Photon emission (>40 eV) from the core exceeds the emission from the imploded core by 6 times, even though the heating pulse energies are only one seventh of the implosion energy. The coupling efficiency from the heating laser to the core using counterirradiation is 14% from the enhancement of photon emission. Neutrons are also produced by counterpropagating fast deuterons accelerated by the photon pressure of the heating pulses. A collisional two-dimensional particle-in-cell simulation reveals that the collisionless two counterpropagating fast-electron currents induce mega-Gauss magnetic filaments in the center of the core due to the Weibel instability. The counterpropagating fast-electron currents are absolutely unstable and independent of the core density and resistivity. Fast electrons with energy below a few MeV are trapped by these filaments in the core region, inducing an additional coupling. This might lead to the observed bright photon emissions.

The influence of inhaled multi-walled carbon nanotubes on the autonomic nervous system.

BACKGROUND: Heart rate and cardiovascular function are regulated by the autonomic nervous system. Heart rate variability (HRV) as a marker reflects the activity of autonomic nervous system. The prognostic significance of HRV in cardiovascular disease has been reported in clinical and epidemiological studies. The present study focused on the influence of inhaled multi-walled carbon nanotubes (MWCNTs) on autonomic nervous system by HRV analysis. METHODS: Male Sprague-Dawley rats were pre-implanted with a telemetry device and kept in the individual cages for recovery. At week four after device implantation, rats were exposed to MWCNTs for 5 h at a concentration of 5 mg/m(3). The real-time EKGs were recorded by a telemetry system at pre-exposure, during exposure, 1 day and 7 days post-exposure. HRV was measured by root mean square of successive differences (RMSSD); the standard deviation of inter-beat (RR) interval (SDNN); the percentage of successive RR interval differences greater than 5 ms (pNN5) and 10 ms (pNN10); low frequency (LF) and high frequency (HF). RESULTS: Exposure to MWCNTs increased the percentage of differences between adjacent R-R intervals over 10 ms (pNN10) (p < 0.01), RMSSD (p < 0.01), LF (p < 0.05) and HF (p < 0.01). CONCLUSIONS: Inhalation of MWCNTs significantly alters the balance between sympathetic and parasympathetic nervous system. Whether such transient alterations in autonomic nervous performance would alter cardiovascular function and raise the risk of cardiovascular events in people with pre-existing cardiovascular conditions warrants further study.

[The impact of ambient fine particulate matter on the blood pressure of an urban population in Shanghai, China: a panel study].

OBJECTIVE: To investigate the impact of particulate matter 2.5 (PM2.5) on the blood pressure of urban residents in Shanghai, China. METHODS: A panel study was conducted from May 27(th) to June 5(th) 2014 in a cohort of 30 adults in an urban community. Participants were 50-80 years old, had lived in the community for at least 5 years, and had a good health status. Key exclusion criteria were current smoking, smoking during the last 3 years, passive smoking, alcohol consumption, and severe cardiopulmonary disease. A total of 28 participants were eligible. Information on demographic characteristics, including of age, sex, height, weight, education, income and chronic comorbidities were collected. Participants were requested to have six weekly blood pressure measurements. Real-time concentrations of PM2.5 and gaseous pollutants were obtained from a nearby air quality monitor during 40 d. Pearson correlation was applied to analyze the correlation between PM2.5 and SO2, NO2, CO and O3. Linear mixed models were applied to analyze the association between PM2.5 and blood pressure, after controlling for time-related trends, day of the week, mean temperature, relative humidity and individual characteristics. RESULTS: The mean systolic and diastolic blood pressure was (124.0±15.0) mmHg (1 mmHg=0.133 kPa) and (74.0±7.7) mmHg, respectively. At 24 h before blood pressure measurement, the mean PM2.5, SO2, NO2, O3 and CO concentration were (8.3±4.9), (46.6±12.9) , (79.2±27.4) µg/m(3) and (0.8±0.2) mg/m(3). The Pearson correlation coefficient R, between PM2.5 and O3, SO2, NO2 and CO was 0.79, 0.59, 0.34 and 0.45, respectively, with corresponding P-values of <0.001, 0.006, 0.012 and 0.009, respectively. The significant correlation between PM2.5 and systolic blood pressure occurred at lag 1 day, was strongest at lag 3 day, but attenuated thereafter. A 10 µg/m(3) increase in 3-day average concentrations of PM2.5 was associated with changes of 1.86 (95%CI: 0.62-3.09) mmHg in systolic blood pressure and -0.05 (95%CI: 0.59-0.50) mmHg in diastolic blood pressure. CONCLUSION: Short-term exposure to PM2.5 may significantly elevate the systolic blood pressure of urban residents in Shanghai.

Evaluation of skeletal muscle DTI in patients with duchenne muscular dystrophy.

Diffusion tensor imaging (DTI) is a popular method to assess differences in fiber organization in diseased and healthy muscle tissue. Previous work has shown that muscle DTI measurements depend on signal-to-noise ratio (SNR), %fat, and tissue T2. The goal of this study was to evaluate the potential biasing effects of these factors on skeletal muscle DTI data in patients with Duchenne Muscular Dystrophy (DMD). MR images were obtained of the right lower leg of 21 DMD patients and 12 healthy controls on a Philips 3T system. DTI measurements were combined with quantitative in-vivo measures of mean water T2, %fat and SNR to evaluate their effect on DTI parameter estimation. All outcome measures were determined within ROIs drawn for six lower leg muscles. Between group analysis, using all ROIs, revealed a significantly elevated FA in the GCL, SOL and PER muscles (p<0.05) and an increased mean diffusivity (p<0.05) and λ3 (p<0.05) in the TA muscle of DMD patients. In-vivo evaluation of the individual confounders showed behaviour in line with predictions from previous simulation work. To account for these confounders, subsequent analysis used only ROIs with SNR greater than 20. With this criterion we found significantly greater MD in the TA muscle of DMD patient (p<0.009) and λ3 in the TA and GCL muscles (p<0.001) of DMD patients, but no differences in FA. As both increased %fat and lower SNR are expected to reduce the apparent MD and λ3, these between-group differences are likely due to pathophysiology. However, the increased FA, observed when using all ROIs, likely reflects the effect of low SNR and %fat on the DTI parameter estimation. These findings suggest that measuring mean water T2, %fat and SNR is essential to ascribe changes in DTI measures to intrinsic diffusion changes or to confounding influences.

Multi-center reproducibility of neurochemical profiles in the human brain at 7 T.

The purpose of this work was to harmonize data acquisition and post-processing of single voxel proton MRS ((1) H-MRS) at 7 T, and to determine metabolite concentrations and the accuracy and reproducibility of metabolite levels in the adult human brain. This study was performed in compliance with local institutional human ethics committees. The same seven subjects were each examined twice using four different 7 T MR systems from two different vendors using an identical semi-localization by adiabatic selective refocusing spectroscopy sequence. Neurochemical profiles were obtained from the posterior cingulate cortex (gray matter, GM) and the corona radiata (white matter, WM). Spectra were analyzed with LCModel, and sources of variation in concentrations ('subject', 'institute' and 'random') were identified with a variance component analysis. Concentrations of 10-11 metabolites, which were corrected for T1 , T2 , magnetization transfer effects and partial volume effects, were obtained with mean Cramér-Rao lower bounds below 20%. Data variances and mean concentrations in GM and WM were comparable for all institutions. The primary source of variance for glutamate, myo-inositol, scyllo-inositol, total creatine and total choline was between subjects. Variance sources for all other metabolites were associated with within-subject and system noise, except for total N-acetylaspartate, glutamine and glutathione, which were related to differences in signal-to-noise ratio and in shimming performance between vendors. After multi-center harmonization of acquisition and post-processing protocols, metabolite concentrations and the sizes and sources of their variations were established for neurochemical profiles in the healthy brain at 7 T, which can be used as guidance in future studies quantifying metabolite and neurotransmitter concentrations with (1) H-MRS at ultra-high magnetic field.