Magnetic resonance imaging Locus Coeruleus abnormality in amnestic Mild Cognitive Impairment is associated with future progression to dementia.

BACKGROUND AND PURPOSE: Human neuropathological studies indicate that the pontine nucleus Locus Coeruleus (LC) undergoes significant and early degeneration in Alzheimer's disease. This line of evidence alongside experimental data suggests that the LC functional/structural decay may represent a critical factor for Alzheimer's disease pathophysiological and clinical progression. In the present prospective study, we used Magnetic Resonance Imaging (MRI) with LC-sensitive sequence (LC-MRI) to investigate in vivo the LC involvement in Alzheimer's disease progression, and whether specific LC-MRI features at baseline are associated with prognosis and cognitive performance in amnestic Mild Cognitive Impairment. METHODS: LC-MRI parameters were measured at baseline by a template-based method on 3.0-T magnetic resonance images in 34 patients with Alzheimer's disease dementia, 73 patients with amnestic Mild Cognitive Impairment, and 53 cognitively intact individuals. A thorough neurological and neuropsychological assessment was performed at baseline and 2.5-year follow-up. RESULTS: In subjects with Mild Cognitive Impairment who converted to dementia (n = 32), the LC intensity and number of LC-related voxels were significantly lower than in cognitively intact individuals, resembling those observed in demented patients. Such a reduction was not detected in Mild Cognitive Impairment individuals, who remained stable at follow-up. In Mild Cognitive Impairment subjects converting to dementia, LC-MRI parameter reduction was maximal in the rostral part of the left nucleus. Structural equation modeling analysis showed that LC-MRI parameters positively correlate with cognitive performance. CONCLUSIONS: Our findings highlight a potential role of LC-MRI for predicting clinical progression in Mild Cognitive Impairment and support the key role of LC degeneration in the Alzheimer clinical continuum.

Analysis, comparison and representation of occupational exposure to a static magnetic field in a 3-T MRI site.

The purpose of this study is to analyze exposure to the time-varying magnetic field caused by worker movements in a 3-T clinical magnetic resonance imaging (MRI) scanner. Measurements of the static magnetic field (B) in the proximity of the MRI scanner were performed to create a detailed map of the spatial gradient of B, in order to indicate the areas at high risk of exposure. Moreover, a personal exposure recording system was used in order to analyze and compare exposure to the static magnetic field during different routine procedures in MRI. We found that for all of the performed work activities, exposure was compliant with International Commission on Non-Ionizing Radiation Protection levels. However, our findings confirm that there is great variability of exposure between different workers and suggest the importance of performing personal exposure measurements and of detailed knowledge of the magnetic field spatial distribution.

Locus Coeruleus magnetic resonance imaging in cognitively intact elderly subjects.

The locus coeruleus is the main noradrenergic nucleus of the brain and is often affected in neurodegenerative diseases. Recently, magnetic resonance imaging with specific T1-weighted sequences for neuromelanin has been used to evaluate locus coeruleus integrity in patients with these conditions. In some of these studies, abnormalities in locus coeruleus signal have also been found in healthy controls and related to ageing. However, this would be at variance with recent post-mortem studies showing that the nucleus is not affected during normal ageing. The present study aimed at evaluating locus coeruleus features in a well-defined cohort of cognitively healthy subjects who remained cognitively intact on a one-year follow-up. An ad-hoc semiautomatic analysis of locus coeruleus magnetic resonance was applied. Sixty-two cognitively intact subjects aged 60-80 years, without significant comorbidities, underwent 3 T magnetic resonance with specific sequences for locus coeruleus. A semi-automatic tool was used to estimate the number of voxels belonging to locus coeruleus and its intensity was obtained for each subject. Each subject underwent extensive neuropsychological testing at baseline and 12 months after magnetic resonance scan. Based on neuropsychological testing 53 subjects were cognitively normal at baseline and follow up. No significant age-related differences in locus coeruleus parameters were found in this cohort. In line with recent post-mortem studies, our in vivo study confirms that locus coeruleus magnetic resonance features are not statistically significantly affected by age between 60 and 80 years, the age range usually evaluated in studies on neurodegenerative diseases. A significant alteration of locus coeruleus features in a cognitively intact elderly subject might be an early sign of pathology.

Absence of T1 Hyperintensity in the Brain of High-risk Patients After Multiple Administrations of High-dose Gadobutrol for Cardiac Magnetic Resonance.

PURPOSE: A prospective study was conducted to evaluate signal changes in the dentate nucleus, globus pallidus, pons, and thalamus (normalized to the deep cerebellum white matter) in T1-weighted magnetic resonance (MR) images after serial injections of gadobutrol in patients with thalassemia without neurological lesions. METHODS: In this study three groups were scanned at both 1.5 T and 3 T: 15 thalassemia patients transfused and chelated with ≥4 gadobutrol administrations at a high dose (0.2 mmol/kg per scan) for late gadolinium enhancement (LGE) cardiovascular MR, 8 thalassemia patients and 13 healthy subjects who had never received gadolinium-based contrast agents (GBCA). RESULTS: Signal intensity (SI) ratios at 1.5 T in all regions were comparable among the three groups and were not correlated with the number of gadobutrol administrations. In healthy subjects SI ratios were significantly different among the 4 regions, being higher in the pallidus. The SI ratios at 1.5 T were significantly higher and not correlated with SI ratios at 3 T or with iron overload in the same regions assessed by the T2* technique. CONCLUSION: This article describes the lack of increased SI in T1-weighted MR images after repeated administration of gadobutrol for cardiovascular MR studies in a high-risk population (high dose per scan, iron overload that can facilitate the transmetalation of gadolinium) scanned at 3 T and 1.5 T.

Lung magnetic resonance imaging in systemic sclerosis: a new promising approach to evaluate pulmonary involvement and progression.

INTRODUCTION/OBJECTIVES: Interstitial lung disease (ILD) is frequent and highly disabling in systemic sclerosis (SSc). Magnetic resonance imaging (MRI) is not routinely used to evaluate the lung, due to poorer spatial resolution compared to high-resolution computed tomography (HRCT). We aimed to compare lung MRI signal with HRCT and evaluate the role of MRI in predicting ILD progression. METHODS: Thirty SSc patients underwent lung MRI and HRCT. STIR and T1 mapping sequences were acquired before and after gadolinium injection. Patients were classified as normal (group 1 with normal HRCT and MRI), discordant (group 2 without ILD signs on HRCT but areas of hyperintensity on MRI), and abnormal (group 3 with ILD signs on HRCT and areas of hyperintensity on MRI). Patients were followed up for ILD progression. RESULTS: Mean STIR and T1 values were different between the three groups (p < 0.0001). STIR values correlated with HRCT score (R = 0.79, p < 0.0001), lung ultrasound B-lines (R = 0.73, p < 0.0001), and %DLco (R = - 0.63, p = 0.0001). Nine events were recorded during a follow-up of 25 ± 20 months. Continuous STIR values were independently associated with events (HR 1.018; CI 1.005-1.031, p = 0.005). A STIR value >90 ms discriminated patients at a higher risk of worsening pulmonary involvement (HR 8.80; CI 1.81-42.74; p < 0.007). CONCLUSIONS: Lung MRI can detect SSc-related ILD, with good correlations with other ILD markers. STIR values, independently of HRCT appearance, may predict worsening lung involvement. Lung MRI, although very preliminary, is a promising tool that in a near future could help selecting patients for an early treatment of SSc-related ILD and a more appropriate use of HRCT. Key points • Lung MRI has the potential to differentiate inflammation-predominant versus fibrosis-predominant lesions, but it is not currently used in routine clinical practice to assess SSc-related ILD. • Lung MRI STIR and T1 values are significantly different between patients with and without SSc-related ILD. STIR values, independently of HRCT appearance, are also able to predict worsening lung involvement over time. • These preliminary data suggest that, in a near future, MRI could support the choice for an early treatment of SSc-related ILD, as well as a more appropriate use of HRCT.

CMR for myocardial iron overload quantification: calibration curve from the MIOT Network.

OBJECTIVES: R2* cardiac magnetic resonance (CMR) allows the non-invasive measurement of myocardial iron. We calibrated cardiac R2* values against myocardial tissue-measured iron concentration by using a segmental approach and we assessed the iron distribution. METHODS: Five hearts of thalassemia patients were donated after death/transplantation to the CoreLab of the Myocardial Iron Overload in Thalassemia Network. A multislice multiecho R2* approach was adopted. After CMR, used as guidance, the heart was cut in three short-axis slices and each slice was cut into different equiangular segments according to AHA segmentation and differentiated into endocardial and epicardial layers. Tissue iron concentration was measured by atomic absorption spectrometer technique. RESULTS: Fifty-five samples were used since only for two hearts all the 16 samples were analyzed. Mean iron concentration was 4.71 ± 4.67 mg/g dw. Segmental iron levels ranged from 0.24 to 13.78 mg/g dw. The coefficient of variability of iron for myocardial segments ranged from 8.08 to 24.54% (mean 13.49 ± 6.93%). Iron concentration was significantly higher in the epicardial than in the endocardial layer (5.99 ± 6.01 vs 4.84 ± 4.87 mg/g dw; p = 0.042). Four different circumferential regions (anterior, septal, inferior, and lateral) were defined. A circumferential heterogeneity was noted, with more iron in the anterior region, followed by the inferior region. The direct nonlinear fitting of R2* and [Fe] data led to the calibration curve: [Fe] = 0.0022 ∙ (R2*-ROI)1.462 (R-square = 0.956). CONCLUSIONS: Our data further validate R2* CMR using a segmental approach as a sensitive and early technique for quantifying iron distribution in the current clinical practice. KEY POINTS: • Calibration in humans for cardiovascular magnetic resonance R2* against myocardial iron concentration was provided. • A circumferential heterogeneity in cardiac iron distribution was detected: more iron was observed in the anterior region, followed by the inferior region. This finding corroborates the use of a segmental T2* CMR approach in the clinical practice to detect a heterogeneous iron distribution. • The comparison between the cardiac T2* values obtained with the region-based and the pixel-wise approaches showed a significant correlation and no significant difference but, in presence of significant iron load, the region-based approach resulted in significantly higher T2* values.

Cardiac magnetic resonance predicts ventricular arrhythmias in scleroderma: the Scleroderma Arrhythmia Clinical Utility Study (SAnCtUS).

OBJECTIVES: Cardiac rhythm disturbances constitute the most frequent cardiovascular cause of death in SSc. However, electrocardiographic findings are not a part of risk stratification in SSc. We aimed to translate 24 h Holter findings into a tangible risk prediction score using cardiovascular magnetic resonance. METHODS: The Scleroderma Arrhythmia Clinical Utility Study (SAnCtUS) was a prospective multicentre study including 150 consecutive SSc patients from eight European centres, assessed with 24 h Holter and cardiovascular magnetic resonance, including ventricular function, oedema (T2 ratio) and late gadolinium enhancement (%LGE). Laboratory/clinical parameters were included in multivariable corrections. A combined endpoint of sustained ventricular tachycardia requiring hospitalization and sudden cardiac death at a median (interquartile range) follow-up of 1 (1.0-1.4) year was generated. RESULTS: Only T2 ratio and %LGE were significant predictors of ventricular rhythm disturbances, but not of supraventricular rhythm disturbances, after multivariable correction and adjustment for multiple comparisons. Using decision-tree analysis, we created the SAnCtUS score, a four-category scoring system based on T2 ratio and %LGE, for identifying SSc patients at high risk of experiencing ventricular rhythm disturbance at baseline. Increasing SAnCtUS scores were associated with a greater disease and arrhythmic burden. All cases of non-sustained ventricular tachycardia (n = 7) occurred in patients with the highest SAnCtUS score (=4). Having a score of 4 conveyed a higher risk of reaching the combined endpoint in multivariable Cox regression compared with scores 1/2/3 [hazard ratio (95% CI): 3.86 (1.14, 13.04), P = 0.029] independently of left ventricular ejection fraction and baseline ventricular tachycardia occurrence. CONCLUSION: T2 ratio and %LGE had the greatest utility as independent predictors of rhythm disturbances in SSc patients.

Cardiac Magnetic Resonance Evaluation of Pulmonary Transit Time and Blood Volume in Adult Congenital Heart disease.

BACKGROUND: Management of adults with repaired congenital heart disease (CHD) is still challenging. Heart failure secondary to residual anatomical sequels or arrhythmic events is not rare in this population. MRI has emerged as an accurate tool to quantify pulmonary transit time (PTT) of intravenous contrast agents and pulmonary blood volume (PBV). PURPOSE: To determine the relationship between PTT, and conventional indexes of ventricular dysfunction and heart failure in a cohort of adults with CHD and to assess its association with adverse outcomes. STUDY TYPE: Retrospective. SUBJECTS: 89 adult CHD patients (56 males, age 34 ± 11 years) and 14 age- and sex-matched healthy subjects. FIELD STRENGTH/SEQUENCE: First-pass perfusion and standard sequences for ventricular volumes and function and flow analysis at 1.5T. ASSESSMENT: PTT was calculated as the time required for a bolus of contrast agent to pass from the right ventricle to the left atrium, expressed both in seconds (PTTS) and number of heartbeats (PTTB). The pulmonary blood volume index (PBVI) was measured by the product of PTTB and the pulmonary artery stroke volumes. STATISTICAL TESTS: Student's independent t-test analysis of variance (ANOVA) and Mann-Whitney nonparametric; Pearson's or Spearman's correlation; Kaplan-Meier method. RESULTS: PTTS and PTTB were significantly higher in patients than in controls (7.6 ± 3 vs. 5.6 ± 1.2 sec, P = 0.01 and 8 ± 3 vs. 6 ± 1 bpm, P = 0.01, respectively). PTTS showed negative correlation with left ventricle ejection fraction (LVEF) and cardiac index (CI) (r = -0.3, P = 0.004, and r = -0.4, P < 0.001, respectively) as well as with left ventricle and atrial volumes. By Kaplan-Meier survival analysis, PTTB >8 bpm was associated with significant increased risk of adverse outcome at mid-term follow-up. Moreover, patients with both increased PTTB and PBV have higher amino-terminal portion of the prohormone brain natriuretic peptide (NT-proBNP) and lower LVEF. DATA CONCLUSION: PTT is prolonged in adult CHD in comparison with healthy subjects, likely reflecting reduced CI and ventricular dysfunction. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:779-786.

The Procedure for Quantitative Characterization and Analysis of Magnetic Fields in Magnetic Resonance Sites for Protection of Workers: A Pilot Study.

Concerning the occupational exposure in magnetic resonance imaging (MRI) facilities, the worker behavior in the magnetic resonance (MR) room is of such particular importance that there is the need for a simple but reliable method to alert the worker of the highest magnetic field exposure. Here, we describe a quantitative analysis of occupational exposure in different MRI working environments: in particular, we present a field measurement method integrated with a software tool for an accurate mapping of the fringe field in the proximity of the magnetic resonance bore. Three illustrative assessment studies are finally presented, compared and discussed, considering an example of a realistic path followed by an MRI worker during the daily procedure. The results show that the basic restrictions set by ICNIRP can be exceeded during standard procedure even in 1.5 T scanners. Using the described simplified metrics, it is possible to introduce behavioral rules on how to move around an MRI room that could be more useful than a numerical limit to aid magnetic field risk mitigation strategies.

Artifacts by Misalignment of Cardiac Magnetic Resonance Phased-array Coil Elements: From Simulation to In vivo Test.

BACKGROUND: Cardiac magnetic resonance evaluations generally require a radiofrequency coil setup comprising a transmit whole-body coil and a receive coil. In particular, radiofrequency phased-array coils are employed to pick up the signals emitted by the nuclei with high signal-tonoise ratio and a large region of sensitivity. METHODS: Literature discussed different technical issues on how to minimize interactions between array elements and how to combine data from such elements to yield optimum Signal-to-Noise Ratio images. However, image quality strongly depends upon the correct coil position over the heart and of one array coil portion with respect to the other. RESULTS: In particular, simple errors in coil positioning could cause artifacts carrying to an inaccurate interpretation of cardiac magnetic resonance images. CONCLUSION: This paper describes the effect of array elements misalignment, starting from coil simulation to cardiac magnetic resonance acquisitions with a 1.5 T scanner. Phased-array coil simulation was performed using the magnetostatic approach; moreover, phantom and in vivo experiments with a commercial 8-elements cardiac phased-array receiver coil permitted to estimate signal-to-noise ratio and B1 mapping for aligned and shifted coil.

Multicenter validation of the magnetic resonance T2* technique for quantification of pancreatic iron.

OBJECTIVES: To assess the transferability of the magnetic resonance imaging (MRI) multislice multiecho T2* technique for pancreatic iron overload assessment. METHODS: Multiecho T2* sequences were installed on ten 1.5-T MRI scanners of the three main vendors. Five healthy subjects (n = 50) were scanned at each site. Five patients with thalassemia (n = 45) were scanned locally at each site and were rescanned at the reference site within 1 month. T2* images were analyzed using a previously validated software and the global pancreatic T2* value was calculated as the mean of T2* values over the head, body, and tail. RESULTS: T2* values of healthy subjects were above 26 ms and showed inter-site homogeneity. The T2* values measured in the MRI sites were comparable to the correspondent values observed in the reference site (12.02 ± 10.20 ms vs 11.98 ± 10.47 ms; p = 0.808), and the correlation coefficient was 0.978 (p < 0.0001). Coefficients of variation (CoVs) ranged from 4.22 to 9.77%, and the CoV for all the T2* values independently from the sites was 8.55%. The intraclass correlation coefficient (ICC) for each MRI site was always excellent and the global ICC was 0.995, independently from the sites. The mean absolute difference in patients with pancreatic iron (n = 39) was -0.15 ± 1.38 ms. CONCLUSION: The gradient-echo T2* MRI technique is an accurate and reproducible means for the quantification of pancreatic iron and may be transferred among MRI scanners by different vendors in several centers. KEY POINTS: • The gradient-echo T2* MRI technique is an accurate and reproducible means for the quantification of pancreatic iron. • The gradient-echo T2* MRI technique for the quantification of pancreatic iron may be transferred among MRI scanners by different vendors in several centers. • Pancreatic iron might serve as an early predictor of cardiac siderosis and is the strongest overall predictor of glucose dysregulation.

Estimation of pancreatic R2* for iron overload assessment in the presence of fat: a comparison of different approaches.

OBJECTIVES: To propose a method for estimating pancreatic relaxation rate, R2*, from conventional multi-echo MRI, based on the nonlinear fitting of the acquired magnitude signal decay to MR signal models that take into account both the signal oscillations induced by fat and the different R2* values of pancreatic parenchyma and fat. MATERIALS AND METHODS: Single-peak fat (SPF) and multi-peak fat (MPF) models were introduced. Single-R2* and dual-R2* assumptions were considered as well. Analyses were conducted on simulated data and 20 thalassemia major patients. RESULTS: Simulations revealed the ability of the MPF model to correctly estimate the R2* value in a large range of fat fractions and R2* values. From the comparison between the results obtained with a single R2* value for water and fat and the dual-R2* approach, the latter is more accurate in both water R2* and fat fraction estimation. In patient's data analysis, a strong concordance was found between SPF and MPF estimated data with measurements done with manual signal correction and from fat-saturated images. The MPF method showed better reproducibility. CONCLUSION: The MPF dual-R2* approach improves reproducibility and reduces image analysis time in the assessment of pancreatic R2* value in patients with iron overload.

TOWARDS A PERSONALISED AND INTERACTIVE ASSESSMENT OF OCCUPATIONAL EXPOSURE TO MAGNETIC FIELD DURING DAILY ROUTINE IN MAGNETIC RESONANCE.

Magnetic resonance imaging (MRI) is one of the most common sources of electromagnetic (EM) fields as a diagnostic technique widely used in medicine. MRI staff during the working day is constantly exposed to static and spatially heterogeneous magnetic field. Also, moving around the MRI room to perform their functions, workers are exposed to slowly time-varying magnetic fields that induce electrical currents and fields in the body. The development of new exposure assessment methodologies to collect exposure data at a personal level using simple everyday equipment is hence necessary, also in view of future epidemiological studies. This paper describes the design and testing of a novel device for assessing personal exposure to static and time-varying magnetic fields during daily clinical practice. The dosemeter will be also used to ensure effective training of technicians who will be instructed to avoid, where possible, risk behaviour in terms of high exposure.

Biomolecular imaging of 13C-butyrate with dissolution-DNP: Polarization enhancement and formulation for in vivo studies.

Magnetic Resonance Spectroscopy of hyperpolarized isotopically enriched molecules facilitates the non-invasive real-time investigation of in vivo tissue metabolism in the time-frame of a few minutes; this opens up a new avenue in the development of biomolecular probes. Dissolution Dynamic Nuclear Polarization is a hyperpolarization technique yielding a more than four orders of magnitude increase in the 13C polarization for in vivo Magnetic Resonance Spectroscopy studies. As reported in several studies, the dissolution Dynamic Nuclear Polarization polarization performance relies on the chemico-physical properties of the sample. In this study, we describe and quantify the effects of the different sample components on the dissolution Dynamic Nuclear Polarization performance of [1-13C]butyrate. In particular, we focus on the polarization enhancement provided by the incremental addition of the glassy agent dimethyl sulfoxide and gadolinium chelate to the formulation. Finally, preliminary results obtained after injection in healthy rats are also reported, showing the feasibility of an in vivo Magnetic Resonance Spectroscopy study with hyperpolarized [1-13C]butyrate using a 3T clinical set-up.

Prediction of cardiac complications for thalassemia major in the widespread cardiac magnetic resonance era: a prospective multicentre study by a multi-parametric approach.

Aims: Cardiovascular magnetic resonance (CMR) has dramatically changed the clinical practice in thalassemia major (TM), lowering cardiac complications. We prospectively reassessed the predictive value of CMR parameters for heart failure (HF) and arrhythmias in TM. Methods and results: We considered 481 white TM patients (29.48 ± 8.93 years, 263 females) enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network. Myocardial and liver iron overload were measured by T2* multiecho technique. Atrial dimensions and biventricular function were quantified by cine images. Late gadolinium enhancement images were acquired to detect myocardial fibrosis. Mean follow-up was 57.91 ± 18.23 months. After the first CMR scan 69.6% of the patients changed chelation regimen. We recorded 18 episodes of HF. In the multivariate analysis the independent predictive factors were myocardial fibrosis (HR = 10.94, 95% CI = 3.28-36.43, P < 0.0001), homogeneous MIO (compared with no MIO) (HR = 5.56, 95% CI = 1.37-22.51, P = 0.016), ventricular dysfunction (HR = 4.33, 95% CI = 1.39-13.43, P = 0.011). Arrhythmias occurred in 16 patients. Among the CMR parameters only the atrial dilation was identified as univariate prognosticator (HR = 4.26 95% CI=1.54-11.75, P = 0.005). Conclusions: CMR guided the change of chelation therapy in nearly 70% of patients, leading to a lower risk of iron-mediated HF and of arrhythmias than previously reported. Homogeneous MIO remained a risk factor for HF but also myocardial fibrosis and ventricular dysfunction identified patients at high risk. Arrhythmias were independent of MIO but increased with atrial dilatation. CMR by a multi-parametric approach dramatically improves cardiac outcomes and provides prognostic information beyond cardiac iron estimation.

Autonomic, functional, skeletal muscle, and cardiac abnormalities are associated with increased ergoreflex sensitivity in mitochondrial disease.

AIMS: Mitochondrial disease (MD) is a genetic disorder affecting skeletal muscles, with possible myocardial disease. The ergoreflex, sensitive to skeletal muscle work, regulates ventilatory and autonomic responses to exercise. We hypothesized the presence of an increased ergoreflex sensitivity in MD patients, its association with abnormal ventilatory and autonomic responses, and possibly with subclinical cardiac involvement. METHODS AND RESULTS: Twenty-five MD patients (aged 46 ± 3 years, 32% male) with skeletal myopathy but without known cardiac disease, underwent a thorough evaluation including BNPs, galectin-3, soluble suppression of tumorigenesis 2 (sST2), high sensitivity troponin T/I, catecholamines, ECG, 24-h ECG recording, cardiopulmonary exercise testing, echocardiography, cardiac/muscle magnetic resonance (C/MMR), and ergoreflex assessment. Thirteen age- and sex-matched healthy controls were chosen. Among these myopathic patients, subclinical cardiac damage was detected in up to 80%, with 44% showing fibrosis at CMR. Ergoreflex sensitivity was markedly higher in patients than in controls (64% vs. 37%, P < 0.001), and correlated with muscle fat to water ratio and extracellular volume at MMR (both P < 0.05). Among patients, ergoreflex sensitivity was higher in those with cardiac involvement (P = 0.034). Patients showed a lower peak oxygen consumption (VO2 /kg) than controls (P < 0.001), as well as ventilatory inefficiency (P = 0.024). Ergoreflex sensitivity correlated with reduced workload and peak VO2 /kg (both P < 0.001), and several indicators of autonomic imbalance (P < 0.05). Plasma norepinephrine was the unique predictor of myocardial fibrosis at univariate analysis (P < 0.05). CONCLUSIONS: Skeletal myopathy in MD is characterized by enhanced ergoreflex sensitivity, which is associated with a higher incidence of cardiac involvement, exercise intolerance, and sympathetic activation.

From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study.

Angelman syndrome (AS) is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A) gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show normal magnetic resonance imaging (MRI) findings, although mild dysmyelination may be observed. In this study, we adopted a quantitative MRI analysis with voxel-based morphometry (FSL-VBM) method to investigate disease-related changes in the cortical/subcortical grey matter (GM) structures. Since 2006 to 2013 twenty-six AS patients were assessed by our multidisciplinary team. From those, sixteen AS children with confirmed maternal 15q11-q13 deletions (mean age 7.7 ± 3.6 years) and twenty-one age-matched controls were recruited. The developmental delay and motor dysfunction were assessed using Bayley III and Gross Motor Function Measure (GMFM). Principal component analysis (PCA) was applied to the clinical and neuropsychological datasets. High-resolution T1-weighted images were acquired and FSL-VBM approach was applied to investigate differences in the local GM volume and to correlate clinical and neuropsychological changes in the regional distribution of GM. We found bilateral GM volume loss in AS compared to control children in the striatum, limbic structures, insular and orbitofrontal cortices. Voxel-wise correlation analysis with the principal components of the PCA output revealed a strong relationship with GM volume in the superior parietal lobule and precuneus on the left hemisphere. The anatomical distribution of cortical/subcortical GM changes plausibly related to several clinical features of the disease and may provide an important morphological underpinning for clinical and neurobehavioral symptoms in children with AS.

A radiofrequency system for in vivo hyperpolarized 13 C MRS experiments in mice with a 3T MRI clinical scanner.

Hyperpolarized carbon-13 magnetic resonance spectroscopy (MRS) is a powerful tool to explore tissue metabolic state, by permitting the study of intermediary metabolism of biomolecules in vivo. However, a number of technological problems still limit this technology and need innovative solutions. In particular, the low molar concentration of derivate metabolites give rise to low signal-to-noise ratio (SNR), which makes the design and development of dedicated radiofrequency (RF) coils a fundamental task. In this article, the authors describe the simulation and the design of a RF coils configuration for MR experiments in mice, constituted by a 1 H whole body volume RF coil for imaging and a 13 C single circular loop surface RF coil for performing 13 C acquisitions. After the building, the RF system was employed in an in vivo experiment in a mouse injected with hyperpolarized [1-13 C]pyruvate by using a 3 T clinical MR scanner. SCANNING 38:710-719, 2016. © 2016 Wiley Periodicals, Inc.