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From the scientific viewpoint, the deepest ocean includes the least known regions on Earth. Advanced technologies, complex logistics and very specific expertise, requiring adequate funding, are needed for in situ observation of the deep sea. In this paper we present the results of the inspection of the floor of the deepest site in the Mediterranean Sea, the 5122 m in depth Calypso Deep in the Ionian Sea, with the Human Occupied Vehicle (HOV) Limiting Factor by Caladan Oceanic in 2020. The dive videos show the floor of the Calypso Deep littered by anthropogenic debris, with litter concentrations among the highest ever recorded in a deep sea environment. The dominant litter category by material type is plastics, accounting for 88 % of the identified litter items. No interactions have been found between litter and the rare life forms identified so far in the deep Ionian Sea. This illustrates that the deep sea is often a final sink for pollution and as such deserves more attention on associated processes and impacts. Harmonized monitoring and assessment should include the deep sea areas in order to enable efficient mitigation. Our findings provide a strong argument in favour of the urgent implementation at global scale of policy actions to reduce ocean littering thus easing the conservation of unique marine habitats, including the deepest on Earth. Our results also appeal to the society at large in terms of consumption habits, waste reduction, care of the environment and the pressing need for action to protect our ocean., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 European Union. Published by Elsevier Ltd.. All rights reserved.)

Objective: To conduct an economic evaluation estimating the cost per live birth after controlled ovarian stimulation (COS) using Follitropin Alpha (Gonal-F), in the Greek National Health System setting. A secondary objective was to predict the live birth rateof the In Vitro Fertilization (IVF) procedure., Methods: A single arm, multi-center, prospective, non-interventional study was conducted on which economic, efficacy and safety data were collected by six of the largest IVF centers. The participants were 350 female patients. Three statistical methods were employed for the analysis of the study outcomes, namely (a) Generalized Linear Modeling for the estimation of the costs of IVF treatment, (b) multivariable logistic regression and (c) an Artificial Neural Network (ANN) model for live birth prediction., Results: The mean total cost of IVF therapy per patient was estimated at €3728 (95% CI: €3679-€3780), while the total cost per live birth was €14,872 (95% CI: €12,441-€17,951). The live birth rate after 3 complete IVF cycles was estimated at 22.9%, while the percentage of those suffering from OHSS was limited at 0.57%. In logistic regression, the Ovarian Sensitivity Index (OSI) was a factor found to be positively associated with live birth (OR 7.39, 95% CI: 1.84-29.71). For the ANN, important predictors included number of gestational sacs and the duration of infertility., Conclusion: The present study constitutes the largest single-arm study based on real data in Greece to date. The cost of IVF treatment and the cost per live birth are not insignificant in this NHS setting. The live birth rate, cost per oocyte, and the cost per live birth are in line with literature. OSI was a main contributing factor to the accurate prediction of the live birth rate, while age and BMI were found to be negatively correlated.

The brain operates at millisecond timescales but despite of that, the study of its functional networks is approached with time invariant methods. Equally, for a variety of brain conditions treatment is delivered with fixed temporal protocols unable to monitor and follow the rapid progression and therefore the cycles of a disease. To facilitate the understanding of brain network dynamics we developed Neurocraft, a user friendly software suite. Neurocraft features a highly novel signal processing engine fit for tracking evolving network states with superior time and frequency resolution. A variety of analytics like dynamic connectivity maps, force-directed representations and propagation models, allow for the highly selective investigation of transient pathophysiological dynamics. In addition, machine-learning tools enable the unsupervised investigation and selection of key network features at individual and group-levels. For proof of concept, we compared six seizure-free and non seizure-free focal epilepsy patients after resective surgery using Neurocraft. The network features were calculated using 50 intracranial electrodes on average during at least 120 epileptiform discharges lasting less than one second, per patient. Powerful network differences were detected in the pre-operative data of the two patient groups (effect size = 1.27), suggesting the predictive value of dynamic network features. More than one million patients are treated with cardiac and neuro modulation devices that are unable to track the hourly or daily changes in a subject's disease. Decoding the dynamics of transition from normal to abnormal states may be crucial in the understanding, tracking and treatment of neurological conditions. Neurocraft provides a user-friendly platform for the research of microscale brain dynamics and a stepping stone for the personalised device-based adaptive neuromodulation in real-time., (© 2021. The Author(s).)

We investigated modulation of functional neuronal connectivity by a proprioceptive stimulus in sixteen young people with dystonia and eight controls. A robotic wrist interface delivered controlled passive wrist extension movements, the onset of which was synchronised with scalp EEG recordings. Data were segmented into epochs around the stimulus and up to 160 epochs per subject were averaged to produce a Stretch Evoked Potential (StretchEP). Event-related network dynamics were estimated using a methodology that features Wavelet Transform Coherency (WTC). Global Microscale Nodal Strength (GMNS) was introduced to estimate overall engagement of areas into short-lived networks related to the StretchEP, and Global Connectedness (GC) estimated the spatial extent of the StretchEP networks. Dynamic Connectivity Maps showed a striking difference between dystonia and controls, with particularly strong theta band event-related connectivity in dystonia. GC also showed a trend towards higher values in dystonia than controls. In summary, we demonstrate the feasibility of this method to investigate event-related neuronal connectivity in relation to a proprioceptive stimulus in a paediatric patient population. Young people with dystonia show an exaggerated network response to a proprioceptive stimulus, displaying both excessive theta-band synchronisation across the sensorimotor network and widespread engagement of cortical regions in the activated network.

Background: Exploding head syndrome is a rarely reported benign sensory parasomnia that may nonetheless have significant impact on patients' quality of life and their perceived well-being. To date, the mechanisms underlying attacks, characterised by a painless perception of abrupt, loud noises at transitional sleep-wake or wake-sleep states, are by and large unclear., Methods and Results: In order to address the current gap in the knowledge of potential underlying pathophysiology, a retrospective case-control study of polysomnographic recordings of patients presenting to a tertiary sleep disorders clinic with exploding head syndrome was conducted. Interictal (non-attack associated) electroencephalographic biomarkers were investigated by performing macrostructural and event-related dynamic spectral analyses of the whole-night EEG. In patients with exploding head syndrome, additional oscillatory activity was recorded during wakefulness and at sleep/wake periods. This activity differed in its frequency, topography and source from the alpha rhythm that it accompanied., Conclusion: Based on these preliminary findings, we hypothesise that at times of sleep-wake transition in patients with exploding head syndrome, aberrant attentional processing may lead to amplification and modulation of external sensory stimuli.

Background: The microstructural EEG elements and their functional networks relate to many neurophysiological functions of the brain and can reveal abnormalities. Despite the blooming variety of methods for estimating connectivity in the EEG of a single subject, a common pitfall is seen in relevant studies; grand averaging is used for estimating the characteristic connectivity patterns of a group of subjects. This averaging may distort results and fail to account for the internal variability of connectivity results across the subjects of a group., New Method: In this study, we propose a novel methodology for the cross-subject network investigation of EEG graphoelements. We used dimensionality reduction techniques in order to reveal internal connectivity properties and to examine how consistent these are across a number of subjects. In addition, graph theoretical measures were utilized to prioritize regions according to their network attributes., Results: As proof of concept, we applied this method on fast sleep spindles across 10 healthy subjects. Neurophysiological findings revealed subnetworks of the spindle events across subjects, highlighting a predominance for occipito-parietal areas and their connectivity with frontal regions., Comparison With Existing Methods: This is a new approach for the examination of within-group connectivities in EEG research. The results accounted for more than 85% of the overall data variance and the detected subnetworks were found to be meaningful down-projections of the grand average of the group, suggesting sufficient performance for the proposed methodology., Conclusion: We conclude that the proposed methodology can serve as an observatory tool for the EEG connectivity patterns across subjects, providing a supplementary analysis of the existing topography techniques., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

We studied slow (≤2.5 Hz) nonevolving generalized periodic epileptiform discharges (GPEDs) in the electroencephalogram (EEG) of comatose patients after cardiac arrest (CA) in search of evidence that could assist early diagnosis of possible hypoxic nonconvulsive status epilepticus (NCSE) and its differentiation from terminal brain anoxia (BA), which can present with a similar EEG pattern. We investigated the topography of the GPEDs in the first post-CA EEGs of 13 patients, using voltage-mapping, and compared findings between two patients with NCSE and GPEDs > 2.5 Hz (group 1), and 11 with GPEDs ≤ 2 Hz, of whom six had possible NCSE (group 2) and five had terminal BA (group 3). Voltage mapping showed frontal maximum for the negative phase of the GPEDs in all patients of groups 1 and 2, but not in any of the patients of group 3, who invariably showed maximization of the negative phase posteriorly. Morphology, amplitude, and duration of the GPEDs varied across the groups, without distinctive features for possible NCSE. These findings provide evidence that, in hypoxic coma after CA with slow GPEDs, anterior topography of the maximum GPED negativity on voltage mapping may be a distinctive biomarker for possible NCSE contributing to the coma.

The current trend for Magnetic Resonance Imaging points towards higher magnetic fields. Even though sensitivity and resolution are increased in stronger fields, T1 contrast is often reduced, and this represents a challenge for contrast agent design. Field-dependent measurements of relaxivity are thus important to characterize contrast agents. At present, the field-dependent curves of relaxivity are usually carried out in the field range of 0 T to 2 T, using fast field cycling relaxometers. Here, we employ a high-speed sample shuttling device to switch the magnetic fields experienced by the nuclei between virtually zero field, and the center of any commercial spectrometer. We apply this approach on rare-earth (mixed Gadolinium-Europium) vanadate nanoparticles, and obtain the dispersion curves from very low magnetic field up to 11.7 T. In contrast to the relaxivity profiles of Gd chelates, commonly used for clinical applications, which display a plateau and then a decrease for increasing magnetic fields, these nanoparticles provide maximum contrast enhancement for magnetic fields around 1-1.5 T. These field-dependent curves are fitted using the so-called Magnetic Particle (MP) model and the extracted parameters discussed as a function of particle size and composition. We finally comment on the new possibilities offered by this approach.

Field-dependent NMR studies of bio-molecular systems using a sample shuttling hardware operating on a high-field NMR apparatus have provided valuable structural and dynamic information. We have recently published a design of a compact sample transportation device, called "field-cycler", which was installed in a commercial spectrometer and which provided highly precise positioning and stability during high speed shuttling. In this communication, we demonstrate the first use of a sample shuttling device on a commercial high field standard bore NMR spectrometer, equipped with a commercial triple resonance cryogenically cooled NMR probe. The performance and robustness of the hardware operating in 1D and 2D field cycling experiments, as well as the impact of the sample shuttling time on the signal intensity are discussed.

During Non-Rapid Eye Movement sleep (NREM) the brain is relatively disconnected from the environment, while connectedness between brain areas is also decreased. Evidence indicates, that these dynamic connectivity changes are delivered by microstructural elements of sleep: short periods of environmental stimuli evaluation followed by sleep promoting procedures. The connectivity patterns of the latter, among other aspects of sleep microstructure, are still to be fully elucidated. We suggest here a methodology for the assessment and investigation of the connectivity patterns of EEG microstructural elements, such as sleep spindles. The methodology combines techniques in the preprocessing, estimation, error assessing and visualization of results levels in order to allow the detailed examination of the connectivity aspects (levels and directionality of information flow) over frequency and time with notable resolution, while dealing with the volume conduction and EEG reference assessment. The high temporal and frequency resolution of the methodology will allow the association between the microelements and the dynamically forming networks that characterize them, and consequently possibly reveal aspects of the EEG microstructure. The proposed methodology is initially tested on artificially generated signals for proof of concept and subsequently applied to real EEG recordings via a custom built MATLAB-based tool developed for such studies. Preliminary results from 843 fast sleep spindles recorded in whole night sleep of 5 healthy volunteers indicate a prevailing pattern of interactions between centroparietal and frontal regions. We demonstrate hereby, an opening to our knowledge attempt to estimate the scalp EEG connectivity that characterizes fast sleep spindles via an "EEG-element connectivity" methodology we propose. The application of the latter, via a computational tool we developed suggests it is able to investigate the connectivity patterns related to the occurrence of EEG microstructural elements. Network characterization of specified physiological or pathological EEG microstructural elements can potentially be of great importance in the understanding, identification, and prediction of health and disease.

To explore the EEG boundary of nonconvulsive status epilepticus (NCSE) and the concept of "possible NCSE", we studied 14 consecutive patients with ≤ 2-Hz nonevolving periodic generalized epileptiform discharges (GPDs) in their first EEG after out of hospital cardiac arrest (OHCA). The pattern was associated with myoclonus in 11 patients. EG reactivity to antiseizure drugs (benzodiazepines and propofol), but without clinical improvement, was noted in 8 patients, satisfying the diagnostic criteria of "possible NCSE". Resolution of GPDs and emergence of physiological rhythms in follow-up EEGs and/or subsequent clinical improvement were noted in 6 of them, strongly suggesting that the initial slow nonevolving GPD pattern reflected NCSE significantly contributing to their coma. Background rhythms from 10 to 90% of the periods between GPDs were noted in 9 patients and appeared to correlate with reactivity of the GPD pattern to antiseizure drugs when 20% or more. Ten patients died, and four were discharged to longer care rehabilitation centers. Although based on few observations, preliminary evidence appears to indicate that in this context, nonevolving GPD frequencies as low as 0.8 Hz can reflect clinically significant NCSE and, therefore, warrant appropriate testing for possible reactivity. There is also some preliminary indication that background rhythms may be another important diagnostic and, perhaps, prognostic indicator, but this needs to be tested in large prospective studies. This article is part of a Special Issue entitled "Status Epilepticus"., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Standard Magnetic Resonance magnets produce a single homogeneous field volume, where the analysis is performed. Nonetheless, several modern applications could benefit from the generation of multiple homogeneous field volumes along the axis and inside the bore of the magnet. In this communication, we propose a straightforward method using a combination of ring structures of permanent magnets in order to cancel the gradient of the stray field in a series of distinct volumes. These concepts were demonstrated numerically on an experimentally measured magnetic field profile. We discuss advantages and limitations of our method and present the key steps required for an experimental validation.

Current EEG criteria for the diagnosis of non-convulsive status epilepticus in critically ill patients with repetitive generalised or focal epileptiform discharges primarily rely on a widely accepted low cut-off frequency limit of 2.5-3 Hz for non-evolving patterns, or on discharge evolution of frequency, location or mophology. The secondary criterion is a significant clinical or EEG improvement following acute administration of a rapidly acting antiepileptic drug, such as lorazepam. We describe a comatose patient after out-of-hospital cardiac arrest, in whom very slow (1-Hz), non-evolving generalised periodic epileptiform discharges against an almost completely depressed background would suggest substantial anoxic damage and poor neurological outcome. Yet, reloading with propofol for diagnostic purposes completely dispersed generalised periodic epileptiform discharges and revealed previously absent biological activity, raising the possibility of non-convulsive status epilepticus that was subsequently confirmed. Brain MRI showed no significant anoxic brain damage and EEG improved, but the patient died from severe cardiopulmonary complications. These observations suggest that in rare cases, slow, non-evolving generalised periodic epileptiform discharges may reflect non-convulsive status epilepticus rather than diffuse irreversible cerebral anoxia, while reloading with propofol can be used as an additional secondary diagnostic criterion.

Background: Although atrial fibrillation (AF) is a highly prevalent health problem with high morbidity and mortality, data regarding the clinical characteristics and management of AF in the Greek population are scarce. The "Current Clinical Practice in the MANAGEment of Atrial Fibrillation in Greece" study (MANAGEAF) aimed to assess the epidemiological features as well as the daily clinical practice in the management of Greek patients with AF., Methods: Taking into consideration the distribution of the Greek population, 603 consecutive patients over 18 years of age, with any type of AF, presenting at the emergency departments or outpatient clinics of 27 different centers, were included in our study., Results: The mean age of the patients was 68.5 ± 12.1 years, with male patients representing 52.5% of the study population. The most common AF type in our cohort was non-paroxysmal AF (60%), including the patients with permanent (24.1%), persistent (17.4%), long-standing (4.8%) and first diagnosed AF (13.8%). Hypertension was the most common comorbidity (70.3%). A history of stroke or transient ischemic attack was detected in 9.2% of the patients, while 6.2% had a history of gastrointestinal bleeding. About half of the patients (49.3%) were treated with anticoagulant drugs, mainly vitamin K antagonists (46.9%), while 34.2% were on antiplatelet drugs, aspirin and/or clopidogrel. The mean INR level (1.7 ± 0.8) was sub-therapeutic, although the mean values for CHADS2 and CHA2DS2-VASc scores were 1.6 ± 1.2 and 3.0 ± 1.7, respectively., Conclusion: The MANAGE-AF baseline results indicate unsatisfactory levels of compliance with the current guidelines for the management of AF in Greece. Considering the undisputed effectiveness of anticoagulant treatment for preventing AF-related strokes, MANAGE-AF demonstrates the need for optimization of our therapeutic strategies for the management of cardioembolic stroke risk.

Analysis of model organisms, such as the submillimeter-size Caenorhabditis elegans, plays a central role in understanding biological functions across species and in characterizing phenotypes associated with genetic mutations. In recent years, metabolic phenotyping studies of C. elegans based on (1)H high-resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy have relied on the observation of large populations of nematodes, requiring labor-intensive sample preparation that considerably limits high-throughput characterization of C. elegans. In this work, we open new platforms for metabolic phenotyping of C. elegans mutants. We determine rich metabolic profiles (31 metabolites identified) from samples of 12 individuals using a (1)H NMR microprobe featuring high-resolution magic-angle coil spinning (HR-MACS), a simple conversion of a standard HR-MAS probe to μHR-MAS. In addition, we characterize the metabolic variations between two different strains of C. elegans (wild-type vs slcf-1 mutant). We also acquire a NMR spectrum of a single C. elegans worm at 23.5 T. This study represents the first example of a metabolomic investigation carried out on a small number of submillimeter-size organisms, demonstrating the potential of NMR microtechnologies for metabolomics screening of small model organisms.

Understanding the molecular determinants underlying protein function requires the characterization of both structure and dynamics at atomic resolution. Nuclear relaxation rates allow a precise characterization of protein dynamics at the Larmor frequencies of spins. This usually limits the sampling of motions to a narrow range of frequencies corresponding to high magnetic fields. At lower fields one cannot achieve sufficient sensitivity and resolution in NMR. Here, we use a fast shuttle device where the polarization builds up and the signals are detected at high field, while longitudinal relaxation takes place at low fields 0.5 < B0 < 14.1 T. The sample is propelled over a distance up to 50 cm by a blowgun-like system in about 50 ms. The analysis of nitrogen-15 relaxation in the protein ubiquitin over such a wide range of magnetic fields offers unprecedented insights into molecular dynamics. Some key regions of the protein feature structural fluctuations on nanosecond time scales, which have so far been overlooked in high-field relaxation studies. Nanosecond motions in proteins may have been underestimated by traditional high-field approaches, and slower supra-τ(c) motions that have no effect on relaxation may have been overestimated. High-resolution relaxometry thus opens the way to a quantitative characterization of nanosecond motions in proteins.

The magic-angle coil spinning (MACS) resonator allows a simple approach for nanoliter nuclear magnetic resonance (NMR) detections with enhanced sensitivity and high-resolution under sample magic-angle spinning (MAS). Currently, the spectral resolution acquired with MACS is not efficient for detailed characterization of semisolids like biopsies, where subhertz resolution is necessary. Here, we describe the two sources of line broadening from MACS, sample temperature gradient and anisotropic magnetic susceptibility, and present a refined high-resolution magic-angle coil spinning (HR-MACS) resonator that improves the spectral resolution. We demonstrate with the high quality HR-MACS NMR spectra of micronematodes and tissue biopsy, and illustrate its potential for NMR-based metabolomics of nanoliter tissue samples.

High-resolution magic-angle sample spinning (HR-MAS) (1)H NMR spectroscopy of tissue biopsies combined with chemometric techniques has emerged as a valuable methodology for disease diagnosis and environmental assessments. However, the tissue mass required for such experiments is of the order of 10 mg, and this can compromise the metabolic evaluation because of tissue heterogeneity. Tissue availability is often a limitation for clinical studies due to histopathological requirements, which are currently the gold standard for diagnosis, for example, in the case of tumors. Here, we introduce the use of a rotating micro-NMR detector that optimizes the coil filling factor such that mass-limited samples can be measured. We show the results for measuring nanoliter volume tissue biopsies using a commercial HR-MAS probe for the first time. The method has been tested with bovine muscle and human gastric mucosal tumor tissue samples. The gain in mass sensitivity is approximate up to 17-fold, and the adequate spectral resolution (3 Hz) allows the measurement of the metabolite profiles in nanoliter volume samples, thereby limiting the ambiguity resulting from heterogeneous tissues; thus, the approach presents diagnostic potential for studies by metabonomics of mass-limited biopsies.

This article describes the development and testing of the first automatically microfabricated probes to be used in conjunction with the magic angle coil spinning (MACS) NMR technique. NMR spectroscopy is a versatile technique for a large range of applications, but its intrinsically low sensitivity poses significant difficulties in analyzing mass- and volume-limited samples. The combination of microfabrication technology and MACS addresses several well-known NMR issues in a concerted manner for the first time: (i) reproducible wafer-scale fabrication of the first-in-kind on-chip LC microresonator for inductive coupling of the NMR signal and reliable exploitation of MACS capabilities; (ii) improving the sensitivity and the spectral resolution by simultaneous spinning the detection microcoil together with the sample at the "magic angle" of 54.74° with respect to the direction of the magnetic field (magic angle spinning - MAS), accompanied by the wireless signal transmission between the microcoil and the primary circuit of the NMR spectrometer; (iii) given the high spinning rates (tens of kHz) involved in the MAS methodology, the microfabricated inserts exhibit a clear kinematic advantage over their previously demonstrated counterparts due to the inherent capability to produce small radius cylindrical geometries, thus tremendously reducing the mechanical stress and tearing forces on the sample. In order to demonstrate the versatility of the microfabrication technology, we have designed MACS probes for various Larmor frequencies (194, 500 and 700 MHz) testing several samples such as water, Drosophila pupae, adamantane solid and LiCl at different magic angle spinning speeds.

Mapping (or plotting) the magnetic field has a critical importance for the achievement of the homogeneous magnetic field necessary to standard MR experiments. A powerful tool for this purpose is the Spherical Harmonic Expansion (SHE), which provides a simple way to describe the spatial variations of a field in free space. Well-controlled non-zero spatial variations of the field are critical to MRI. The resolution of the image is directly related to the strength of the gradient used to encode space. As a result, it is desirable to have strong variations of the field. In that case, the SHE cannot be used as is, because the field modulus variations are affected by the variations of all components of the field. In this paper, we propose a method based on the SHE to characterize such variations, theoretically and experimentally, in the limit of an axisymmetric magnetic field. Practical applications of this method are proposed through the examples of single-sided magnet design and characterization, along with Stray-Field Imaging (STRAFI)., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We propose using singly-tuned μ-coils and (1)H-detection to obtain high-sensitivity in lieu of miniaturizing cumbersome multi-resonance circuits, with the existing MAS probe circuitry/coil providing RF at other frequencies. We demonstrate two key building blocks in solid-state NMR: cross-polarization and heteronuclear decoupling. As well, a (1)H-detected 2D HMQC is obtained.

We introduce a cylindrical permanent magnet design that generates a homogeneous and strong magnetic field having an arbitrary inclination with respect to the axis of the cylinder. The analytical theory of 3 D magnetostatics has been applied to this problem, and a hybrid magnet structure has been designed. This structure contains two magnets producing a longitudinal and transverse component for the magnetic field, whose amplitudes and homogeneities can be fully controlled by design. A simple prototype has been constructed using inexpensive small cube magnets, and its magnetic field has been mapped using Hall and NMR probe sensors. This magnet can, in principle, be used for magic angle field spinning NMR and MRI experiments allowing for metabolic chemical shift profiling in small living animals., (Copyright © 2010 John Wiley & Sons, Ltd.)

We report on the use of optical Faraday rotation to monitor the nuclear-spin signal in a set of model (19)F- and (1)H-rich fluids. Our approach integrates optical detection with high-field, pulsed NMR so as to record the time-resolved evolution of nuclear-spins after rf excitation. Comparison of chemical-shift-resolved resonances allows us to set order-of-magnitude constrains on the relative amplitudes of hyperfine coupling constants for different bonding geometries. When evaluated against coil induction, the present detection modality suffers from poorer sensitivity, but improvement could be attained via multipass schemes. Because illumination is off-resonant i.e., the medium is optically transparent, this methodology could find extensions in a broad class of fluids and soft condensed matter systems.

We demonstrate the possibility of multidimensional contrast (T(1)-, T(2)-weighted and triple-quantum filtered) magnetic resonance imaging using a simple and effective solid-state NMR technique, stray-field imaging with sample magic-angle spinning (STRAFI-MAS). This imaging technique can be easily implemented in today's standard solid-state NMR laboratory, making it a potentially valuable imaging application to material science., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: To revisit and illustrate the potential of a simple and effective multidimensional stray-field imaging technique with magic-angle spinning, known as STRAFI-MAS., Materials and Methods: STRAFI-MAS images are acquired with a standard NMR magnet and a traditional magic-angle sample spinning (MAS) probe. The stray-field gradients are achieved by placing the MAS probe, along the z-direction, at a distance from the center of the magnet. No pulsed-field gradients are applied. The multidimensional spatial encoding is carried out by synchronizing the radiofrequency pulses with the sample MAS rotation., Results: Two-dimensional (2D) and 3D multinuclear images of various phantoms, including a tibia bone and silicon carbide, are recorded. Images of inorganic solids containing quadrupolar nuclei, (23)Na and (27)Al, are also explored for the first time by STRAFI-MAS., Conclusion: We have demonstrated that STRAFI-MAS is a simple and user-friendly technique for multidimensional imaging without the need of imaging equipment. With the current advancements in NMR and MRI methodologies, STRAFI-MAS is expected to be further developed and improved. We anticipate that STRAFI-MAS can spark a wide spectrum of interest, from material to bio science, where can benefit from high-resolution images., (2010 Wiley-Liss, Inc.)

Starting from general results of magnetostatics, we give fundamental considerations on the design and characterization of permanent magnets for NMR based on harmonic analysis and symmetry. We then propose a simple geometry that takes advantage of some of these considerations and discuss the practical aspects of the assembly of a real magnet based on this geometry, involving the characterization of its elements, the optimization of the layout and the correction of residual inhomogeneities due to material and geometry imperfections. We report with this low-cost, light-weight magnet (100 euros and 1.8 kg including the aluminum frame) a field of 120 mT (5.1 MHz proton) with a 10 ppm natural homogeneity over a sphere of 1.5 mm in diameter., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

High-resolution magic-angle spinning has become a valuable tool to study biologic samples; however, there are only a few high-resolution magic-angle spinning methodologies that have been explored specifically to deal with small semisolid biomaterials such as tissues. Here, we report a novel high-resolution (1)H NMR spectroscopic approach using magic-angle coil spinning. We demonstrate its potential for intact tissues by combining a resonant microcoil with a large-volume commercial magic-angle spinning rotor, where the microcoil offers incredible sensitivity and the large-volume magic-angle spinning rotor provides stable slow magic-angle spinning. This approach provides high-resolution spectra with high sensitivity and the preservation of living biologic specimens for an accurate chemical analysis.

We present an original method for field stability measurements in a bath of liquid helium. This method is used to validate the power supply of a superconductive magnet operating in driven mode. The experiment consists in the measurement of the NMR signal of a sample of liquid (3)He, placed inside the field of a test magnet driven by a power supply. The homogeneity of the magnet is a strongly limiting factor for measurements but through the use of an inductively coupled microcoil and careful signal processing, a precision of 5.5 ppm was achieved., (Copyright 2009 Elsevier Inc. All rights reserved.)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is one of the major causes of sudden death. Myocardial atrophy with subsequent fibro-fatty replacement predominantly affects right ventricular myocardium and results in global and regional dysfunction as well as areas of slow conduction and dispersion of refractoriness, which are prerequisites for reentrant ventricular tachyarrhythmias. ARVC is commonly presented in patients <65 years old. However, few cases of elderly people suffering from this cardiomyopathy have been reported in the literature. We present a case of an 82-year-old woman with sustained ventricular tachycardia due to first diagnosed ARVC.

The application of nuclear magnetic resonance (NMR) to systems of limited quantity has stimulated the use of micro-coils (diameter <1mm). One method recently proposed for the union of micro-coils with Magic Angle sample Spinning (MAS), involves the integration of a tuned micro-coil circuit within standard MAS rotors inductively coupled to the MAS probe coil, termed "magic-angle coil spinning" (MACS). The spinning of conductive materials results in the creation of circulating Foucault (eddy) currents, which generate heat. We report the first data acquired with a 4mm MACS system and spinning up to 10kHz. The need to spin faster necessitates improved methods to control heating. We propose an approximate solution to calculate the power losses (heat) from the eddy currents for a solenoidal coil, in order to provide insight into the functional dependencies of Foucault currents. Experimental tests of the dependencies reveal conditions which result in reduced sample heating and negligible temperature distributions over the sample volume.

We describe the case of a 58-year-old man who developed acute severe anemia and thrombocytopenia after the administration of tirofiban following coronary artery angioplasty. The intravenous administration of IgG immunoglobulin completely resolved both the anemia and the thrombocytopenia. Although thrombocytopenia has been reported as a sequela to the use of tirofiban, there has been no prior report of a link between tirofiban use and anemia. Our successful resolution of both the anemia and the thrombocytopenia with immunoglobulin supports the theory that these severe sequelae of tirofiban are of autoimmune origin.

The Permanent Scatterers Interferometric SAR technique (PSInSAR) is a method that accurately estimates the near vertical terrain deformation rates, of the order of ∼1 mm year(-1), overcoming the physical and technical restrictions of classic InSAR. In this paper the method is strengthened by creating a robust processing chain, incorporating PSInSAR analysis together with algorithmic adaptations for Permanent Scatterer Candidates (PSCs) and Permanent Scatterers (PSs) selection. The processing chain, called PerSePHONE, was applied and validated in the geophysically active area of the Gulf of Corinth. The analysis indicated a clear subsidence trend in the north-eastern part of the gulf, with the maximum deformation of ∼2.5 mm year(-1) occurring in the region north of the Gulf of Alkyonides. The validity of the results was assessed against geophysical/geological and geodetic studies conducted in the area, which include continuous seismic profiling data and GPS height measurements. All these observations converge to the same deformation pattern as the one derived by the PSInSAR technique.

Background: This study was designed to investigate the association of the 894G>T polymorphism in the eNOS gene with risk of acute myocardial infarction (AMI), extent of coronary artery disease (CAD) on coronary angiography, and in-hospital mortality after AMI., Methods: We studied 1602 consecutive patients who were enrolled in the GEMIG study. The control group was comprised by 727 individuals, who were randomly selected from the general adult population., Results: The prevalence of the Asp298 variant of eNOS was not found to be significantly and independently associated with risk of AMI (RR = 1.08, 95%CI = 0.77-1.51, P = 0.663), extent of CAD on angiography (OR = 1.18, 95%CI = 0.63-2.23, P = 0.605) and in-hospital mortality (RR = 1.08, 95%CI = 0.29-4.04, P = 0.908)., Conclusion: In contrast to previous reports, homozygosity for the Asp298 variant of the 894G>T polymorphism in the eNOS gene was not found to be associated with risk of AMI, extent of CAD and in-hospital mortality after AMI.

The role of heart rate reduction in the management of myocardial ischemia and chronic stable angina is pivotal. However, broad use and appropriate dosing of commonly used rate-slowing drugs is limited by their poor tolerability. Ivabradine is a selective inhibitor of the If currents of the sinoatrial node cells. If currents activity determines the slope of the depolarization curve towards the threshold level controlling heart rate in patients with sinus rhythm. Ivabradine, a compound of the benzocyclobutane (S 16257), exhibits a unique specificity for the If current and has a more favorable profile of adverse reactions compared to other If inhibitors. Accordingly, ivabradine has been used in the treatment of stable angina, where it presented anti-anginal and anti-ischemic effects equivalent to the effects of atenolol and amlodipine. Clinical studies proved the efficacy of ivabradine in patients with stable angina, while clinical data are awaited to verify its probable value in the treatment of atrial tachyarrhythmias and tachycardia due to ventricular dysfunction. Thus, the clinical value of ivabradine, which has completed clinical development for stable angina, is expected to exceed its role in the treatment of myocardial ischemia. In this context, ivabradine, promising efficacious and safe pharmacological management of heart rate, is a huge step in cardiovascular therapeutics.

High-resolution nuclear magnetic resonance spectra from samples located in inhomogeneous static and radio frequency magnetic fields can be obtained by applying a train of z-rotation radio frequency pulses to repeatedly refocus the inhomogeneous broadening during signal detection. z-rotation pulses based on an adiabatic double passage are effective over wide bandwidths using a limited amount of radio frequency power at the expense of being time consuming and, consequently, sensitive to motion of the spin bearing molecules. The signal damping resulting from molecular self-diffusion during the pulse was studied experimentally and using Brownian dynamics simulations. The results show that the analytical expression for diffusion damping during a double spin echo is a reasonable approximation for the signal decay during an adiabatic z-rotation pulse. Methods to alleviate the effects of diffusion are discussed.

High-resolution NMR spectra of materials subject to anisotropic broadening are usually obtained by rotating the sample about the magic angle, which is 54.7 degrees to the static magnetic field. In projected magic angle spinning (p-MAS), the sample is spun about two angles, neither of which is the magic angle. This provides a method of obtaining isotropic spectra while spinning at shallow angles. The p-MAS experiment may be used in situations where spinning the sample at the magic angle is not possible due to geometric or other constraints, allowing the choice of spinning angle to be determined by factors such as the shape of the sample, rather than by the spin physics. The application of this technique to bovine tissue samples is demonstrated as a proof of principle for future biological or medical applications., (2005 Wiley-Liss, Inc)

Resolved NMR spectra from samples in inhomogeneous B0 and B1 fields can be obtained with the so-called "ex situ" methodology, employing a train of composite or adiabatic z-rotation RF pulses to periodically refocus the inhomogeneous broadening during the detection of the time-domain signal. Earlier schemes relied on a linear correlation between the inhomogeneous B0 and B1 fields. Here the pulse length, bandwidth, and amplitude of the adiabatic pulses of the hyperbolic secant type are adjusted to improve the refocusing for a setup with non-linear correlation. The field correlation is measured using a two-dimensional nutation experiment augmented with a third dimension with varying RF carrier frequency accounting for off-resonance effects. The pulse optimization is performed with a computer algorithm using the experimentally determined field correlation and a standard adiabatic z-rotation pulse as a starting point for the iterative optimization procedure. The shape of the z-rotation RF pulse is manipulated to provide refocusing for the conditions given by the sample-, magnet-, and RF-coil geometry.

Magnetic resonance imaging (MRI) encounters fundamental limits in circumstances in which the static magnetic field is not sufficiently strong to truncate unwanted, so-called concomitant components of the gradient field. This limitation affects the attainable optimal image fidelity and resolution most prominently in low-field imaging. In this article, we introduce the use of pulsed magnetic-field averaging toward relaxing these constraints. It is found that the image of an object can be retrieved by pulsed low fields in the presence of the full spatial variation of the imaging encoding gradient field even in the absence of the typical uniform high-field time-independent contribution. In addition, error-compensation schemes can be introduced through the application of symmetrized pulse sequences. Such schemes substantially mitigate artifacts related to evolution in strong magnetic-field gradients, magnetic fields that vary in direction and orientation, and imperfections of the applied field pulses.

Magic-angle sample spinning is one of the cornerstones in high-resolution NMR of solid and semisolid materials. The technique enhances spectral resolution by averaging away rank 2 anisotropic spin interactions, thereby producing isotropic-like spectra with resolved chemical shifts and scalar couplings. In principle, it should be possible to induce similar effects in a static sample if the direction of the magnetic field is varied (e.g., magic-angle rotation of the B0 field). Here we will review some recent experimental results that show progress toward this goal. Also, we will explore some alternative approaches that may enable the recovery of spectral resolution in cases where the field is rotating off the magic angle. Such a possibility could help mitigate the technical problems that render difficult the practical implementation of this method at moderately strong magnetic fields.

A way to use adiabatic radiofrequency pulses and modulated magnetic-field gradient pulses, together constituting a "shim pulse," for NMR spectroscopy and imaging is demonstrated. These pulses capitalize on phase shifts derived from probe gradient coils to compensate for nonlinear intrinsic main magnetic field homogeneity for spectroscopy, as well as for deviations from linear gradients for imaging. This approach opens up the possibility of exploiting cheaper, less-than-perfect magnets and gradient coils for NMR applications.

Mechanical rotation of a sample at 54.7 degrees with respect to the static magnetic field, so-called magic-angle spinning (MAS), is currently a routine procedure in nuclear magnetic resonance (NMR). The technique enhances the spectral resolution by averaging away anisotropic spin interactions thereby producing isotropic-like spectra with resolved chemical shifts and scalar couplings. It should be possible to induce similar effects in a static sample if the direction of the magnetic field is varied, e.g., magic-angle rotation of the B0 field (B0-MAS). Here, this principle is experimentally demonstrated in a static sample of solid hyperpolarized xenon at approximately 3.4 mT. By extension to moderately high fields, it is possible to foresee interesting applications in situations where physical manipulation of the sample is inconvenient or impossible. Such situations are expected to arise in many cases from materials to biomedicine and are particularly relevant to the novel approach of ex situ NMR spectroscopy and imaging.

A pulse sequence consisting of an excitation pulse and two adiabatic full-passage pulses with scaled relative peak amplitudes is combined with phase encoding to recover chemical shift information within 3D images in a 1D inhomogeneous static magnetic field with a matched rf field gradient. The results are discussed in the context of ex situ magnetic resonance and imaging. The future directions of our research in implementing the ex situ technique in a real one-sided system are also discussed.

The use of inhomogeneous but spatially correlated static and radiofrequency (RF) magnetic fields offers a potential methodology for performing magnetic resonance spectroscopy of samples placed outside the bore of the magnet. However, its practical implementation still presents challenging problems, among them the control of nuclear spins over broad frequency offset intervals. The present study introduces an efficient method of encoding the phase of the magnetization when the variation of the static field along the sample is much larger than the RF amplitude. The procedure is based on the use of consecutively applied full-passage adiabatic pulses. The induced phase modulation is broadband and selective because it does not depend on the offset relative to the central frequency and the limits can be sharply defined. Finally, the encoded phase depends almost linearly on the local RF amplitude. All these features enable the recovery of an inhomogeneity-free spectrum with amplitudes close to the theoretically attainable maximum.

In this paper we demonstrate experimentally that the continuously phase-modulated homonuclear decoupling sequence DUMBO-1 is suitable for high-resolution proton NMR spectroscopy of rigid solids. Over a wide range of experimental conditions, we show on the model sample L-alanine as well as on small peptides that proton linewidths of less than 0.5 ppm can be obtained under DUMBO-1 decoupling. In particular the DUMBO-1 sequence yields well resolved proton spectra both at slow and fast MAS. The DUMBO-1 decoupling scheme can in principle be inserted in any multi-nuclear or multi-dimensional solid-state NMR experiment which requires a high-resolution 1H dimension. An example is provided with the 13C-1H MAS-J-HMQC experiment.

The experimental lineshapes of the carboxyl and methyl carbon resonances of fully 13C enriched L-Alanine are studied in detail at different MAS frequencies and decoupling field strengths. Complex lineshapes at intermediate spinning speeds were explained by the joint effect of off rotational resonance and coherent CSA-dipolar cross-correlation. Whereas off rotational-resonance effects lead to complex lineshapes due to a splitting of some energy levels, coherent CSA-dipolar cross-correlation introduces either a differential intensity and/or a differential broadening of the lines of the J-multiplet. The conditions which lead to such effects are explained and experimentally verified. Additional simulations show that these effects can be expected over a wide range of static magnetic fields and are not restricted to L-Alanine.

We show how high-resolution NMR spectra can be obtained for solids for which the spectra are normally broadened due to structural disorder. The method relies on correlations in the chemical shifts between pairs of coupled spins. It is found experimentally that there are strong correlations in the chemical shifts between neighboring spins in both phosphorus-31 and carbon-13 spectra. These correlations can be exploited not only to provide resolution in two-dimensional spectra, but also to yield "chains" of correlated chemical shifts, constituting a valuable new source of structural information for disordered materials.

In a recent publication we presented a method to obtain highly resolved NMR spectra in the presence of an inhomogeneous B(0) field with the help of a matched RF gradient. If RF gradient pulses are combined with "ideal" 90 degrees pulses to form inhomogeneous z rotation pulses, the line broadening caused by the B(0) gradient can be refocused, while the full chemical shift information is maintained. This approach is of potential use for NMR spectroscopy in an inhomogeneous magnetic field produced by an "ex-situ" surface spectrometer. In this contribution, we extend this method toward two-dimensional spectroscopy with high resolution in one or both dimensions. Line narrowing in the indirect dimension can be achieved by two types of nutation echoes, thus leading to depth-sensitive NMR spectra with full chemical shift information. If the nutation echo in the indirect dimension is combined with a stroboscopic acquisition using inhomogeneous z-rotation pulses, highly resolved two-dimensional correlation spectra can be obtained in matched field gradients. Finally, we demonstrate that an INEPT coherence transfer from proton to carbon spins is possible in inhomogeneous B(0) fields. Thus, it is possible to obtain one-dimensional (13)C NMR spectra with increased sensitivity and two-dimensional HETCOR spectra in the presence of B(0) gradients of 0.4 mT/cm. These schemes may be of some value for ex-situ NMR analysis of materials and biological systems.

In this article a method is suggested for restricting a sample (spatial localization) by preparing the magnetization with a phase-modulated radiofrequency pulse which inverts magnetization only over a very narrow range of radiofrequency field strengths. This is the most efficient method, in terms of sensitivity, of restricting the sample to improve rf homogeneity. The method is demonstrated by using it to improve the resolution obtained in a homonuclear dipolar decoupling experiment.