Cathodoluminescence from interlayer excitons in a 2D semiconductor heterobilayer.

Photoluminescence has widely been used to study excitons in semiconducting transition metal dichalcogenide (MX2) monolayers, demonstrating strong light-matter interactions and locked spin and valley degrees of freedom. In heterobilayers composed of overlapping monolayers of two different MX2, an interlayer exciton can form, with the hole localised in one layer and the electron in the other. These interlayer excitons are long-lived, field-tunable, and can be trapped by moiré patterns formed at small twist angles between the layers. Here we demonstrate that emission from radiative recombination of interlayer excitons can be observed by cathodoluminescence from a WSe2/MoSe2heterobilayer encapsulated in hexagonal boron nitride. The higher spatial resolution of cathodoluminescence, compared to photoluminescence, allows detailed analysis of sample heterogeneity at the 100 s of nm lengthscales over which twist angles tend to vary in dry-transfer fabricated heterostructures.

Insulin sensitivity and insulin secretion in adults with Friedreich's Ataxia: the role of skeletal muscle.

INTRODUCTION: Friedreich's Ataxia (FRDA) is a multi-system disorder caused by frataxin deficiency. FRDA-related diabetes mellitus (DM) is common. Frataxin supports skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, a mediator of insulin sensitivity. Our objective was to test the association between skeletal muscle health and insulin sensitivity and secretion in adults with FRDA without DM. METHODS: Case-control study (NCT02920671). Glucose and insulin metabolism (stable-isotope oral glucose tolerance tests), body composition (dual-energy x-ray absorptiometry), physical activity (self-report), and skeletal muscle OXPHOS capacity (creatine chemical exchange saturation transfer MRI) were assessed. RESULTS: Participants included 11 individuals with FRDA (4 female), median age 27y (IQR 23, 39), BMI 26.9kg/m2 (24.1, 29.4), and 24 controls (11 female), 29y (26, 39), 24.4kg/m2 (21.8, 27.0). Fasting glucose was higher in FRDA (91 vs. 83mg/dL (5.0 vs. 4.6mmol/L), p<0.05). Individuals with FRDA had lower insulin sensitivity (WBISI 2.8 vs. 5.3, p<0.01), higher post-prandial insulin secretion (insulin secretory rate iAUC 30-180 minutes, 24,652 vs. 17,858, p<0.05), and more suppressed post-prandial endogenous glucose production (-0.9% vs. 26.9% of fasting EGP, p<0.05). In regression analyses, lower OXPHOS and inactivity explained some of the difference in insulin sensitivity. More visceral fat contributed to lower insulin sensitivity independent of FRDA. Insulin secretion accounting for sensitivity (disposition index) was not different. CONCLUSIONS: Lower mitochondrial OXPHOS capacity, inactivity, and visceral adiposity contribute to lower insulin sensitivity in FRDA. Higher insulin secretion appears compensatory, and when inadequate, could herald DM. Further studies are needed to determine if muscle- or adipose-focused interventions could delay FRDA-related DM.

Reliability of In Vivo Creatine-Weighted Chemical Exchange Saturation Transfer (CrCEST) MRI in Calf Skeletal Muscle of Healthy Volunteers at 3 T.

BACKGROUND: Skeletal muscle mitochondrial oxidative phosphorylation (mtOXPHOS) is important for ATP generation and its dysfunction leads to exercise intolerance. Phosphorus magnetic resonance spectroscopy (31P-MRS) is a useful, noninvasive technique for mtOXPHOS assessment but has limitations. Creatine-weighted chemical exchange saturation transfer (CrCEST) MRI is a potential alternative to assess muscle bioenergetics. PURPOSE: To evaluate the interscan repeatability, intra- and interobserver reproducibility of CrCEST during mild plantar flexion exercise. STUDY TYPE: Retrospective. SUBJECTS: Twenty healthy volunteers (age 37.6 ± 12.4 years, 11 females). FIELD STRENGTH/SEQUENCE: 3 T/CEST imaging using gradient echo readout. ASSESSMENT: τCrCEST (postexercise Cr recovery time) was assessed in two scans for each participant, following mild plantar flexion exercises targeting the medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (Sol) muscles. Three observers measured τCrCEST for interobserver reproducibility. Three readings by one observer were used to measure intraobserver reproducibility. Two scans were used for within-participant interscan repeatability. STATISTICAL TESTS: Paired t tests, intraclass correlation coefficient (ICC), and Pearson correlation were conducted. Bland-Altman plots were used to analyze the interobserver variability. A P-value of 0.05 was considered statistically significant. RESULTS: There was excellent intra- (ICC ∈ 0.94 - 0.98 $$ \in \left[0.94-0.98\right] $$ ) and interobserver (ICC ∈ 0.9 - 0.98 $$ \in \left[0.9-0.98\right] $$ ) reproducibility, with moderate interscan repeatability for τCrCEST in LG and MG (ICC ∈ 0.54 - 0.74 $$ \in \left[0.54-0.74\right] $$ ) and poor-to-moderate interscan repeatability in Sol (ICC ∈ 0.24 - 0.53 $$ \in \left[0.24-0.53\right] $$ ). Excellent interobserver reproducibility was confirmed by Bland-Altman plots (fixed bias P-value ∈ 0.08 - 0.87 $$ \in \left[0.08-0.87\right] $$ ). DATA CONCLUSION: CrCEST MRI shows promise in assessing muscle bioenergetics by evaluating τCrCEST during mild plantar flexion exercise with reasonable reliability, particularly in LG and MG. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 1.

Acute nicotinamide riboside supplementation increases human cerebral NAD+ levels in vivo.

PURPOSE: The purpose of this study was to determine the effect of acute nicotinamide riboside (NR) supplementation on cerebral nicotinamide adenine dinucleotide (NAD+) levels in the human brain in vivo by means of downfield proton MRS (DF 1H MRS). METHODS: DF 1H MRS was performed on 10 healthy volunteers in a 7.0 T MRI scanner with spectrally selective excitation and spatially selective localization to determine cerebral NAD+ levels on two back-to-back days: once after an overnight fast (baseline) and once 4 h after oral ingestion of nicotinamide riboside (900 mg). Additionally, two more baseline scans were performed following the same paradigm to assess test-retest reliability of the NAD+ levels in the absence of NR. RESULTS: NR supplementation increased mean NAD+ concentration compared to the baseline (0.458 ± 0.053 vs. 0.392 ± 0.058 mM; p < 0.001). The additional two baseline scans demonstrated no differences in mean NAD+ concentrations (0.425 ± 0.118 vs. 0.405 ± 0.082 mM; p = 0.45), and no difference from the first baseline scan (F(2, 16) = 0.907; p = 0.424). CONCLUSION: These preliminary results confirm that acute NR supplementation increases cerebral NAD+ levels in healthy human volunteers and shows the promise of DF 1H MRS utility for robust detection of NAD+ in humans in vivo.

Personalized and muscle-specific OXPHOS measurement with integrated CrCEST MRI and proton MR spectroscopy.

Creatine chemical exchange saturation transfer (CrCEST) MRI is an emerging high resolution and noninvasive method for measuring muscle specific oxidative phosphorylation (OXPHOS). However, CrCEST measurements are sensitive to changes in muscle pH, which might confound the measurement and interpretation of creatine recovery time (τCr). Even with the same prescribed exercise stimulus, the extent of acidification and hence its impact on τCr is expected to vary between individuals. To address this issue, a method to measure pH pre- and post-exercise and its impact on CrCEST MRI with high temporal resolution is needed. In this work, we integrate carnosine 1H- magnetic resonance spectroscopy (MRS) and 3D CrCEST to establish "mild" and "moderate/intense" exercise stimuli. We then test the dependence of CrCEST recovery time on pH using different exercise stimuli. This comprehensive metabolic imaging protocol will enable personalized, muscle specific OXPHOS measurements in both healthy aging and myriad other disease states impacting muscle mitochondria.

NeuroRehabilitation OnLine: Description of a regional multidisciplinary group telerehabilitation innovation for stroke and neurological conditions using the Template for Intervention Description and Replication checklist.

Background: Providing recommended amounts of rehabilitation for stroke and neurological patients is challenging. Telerehabilitation is viable for delivering rehabilitation and an acceptable adjunct to in-person therapy. NeuroRehabilitation OnLine (NROL) was developed as a pilot and subsequently operationalised as a regional innovation embedded across four National Health Service (NHS) Trusts. Objective: To describe the NROL innovation to assist future implementation and replication efforts. Methods: The Template for Intervention Description and Replication (TIDieR) checklist, with guidance from the TIDieR-Telehealth extension, was used to describe NROL. The description was developed collaboratively by clinical academics, therapists, managers and researchers. Updated Consolidated Framework for Implementation Research domains were used to describe the context in which the innovation was delivered. Results: NROL delivers online group-based real-time neurorehabilitation with technology assistance. It incorporates multidisciplinary targeted therapy and peer support to complement existing therapy. Procedures, materials and structure are detailed to demonstrate how NROL is embedded within a healthcare system. NROL uses existing NHS therapy workforce alongside dedicated NROL roles, including an essential technology support role. Selection of NROL groups is dependent on patient needs. The NROL innovation is tailored over time in response to feedback. NROL described here is successfully integrated within a regional stroke and neurorehabilitation network, aligns with local and national strategies and capitalises on an existing clinical-academic partnership. Conclusion: This comprehensive description of a regional NROL innovation, and clarification of core components, should facilitate other healthcare settings to adapt and implement NROL for their context. Continuous evaluation alongside implementation will ensure maximal impact for neurorehabilitation.

Tunnel junctions based on interfacial two dimensional ferroelectrics.

Van der Waals heterostructures have opened new opportunities to develop atomically thin (opto)electronic devices with a wide range of functionalities. The recent focus on manipulating the interlayer twist angle has led to the observation of out-of-plane room temperature ferroelectricity in twisted rhombohedral bilayers of transition metal dichalcogenides. Here we explore the switching behaviour of sliding ferroelectricity using scanning probe microscopy domain mapping and tunnelling transport measurements. We observe well-pronounced ambipolar switching behaviour in ferroelectric tunnelling junctions with composite ferroelectric/non-polar insulator barriers and support our experimental results with complementary theoretical modelling. Furthermore, we show that the switching behaviour is strongly influenced by the underlying domain structure, allowing the fabrication of diverse ferroelectric tunnelling junction devices with various functionalities. We show that to observe the polarisation reversal, at least one partial dislocation must be present in the device area. This behaviour is drastically different from that of conventional ferroelectric materials, and its understanding is an important milestone for the future development of optoelectronic devices based on sliding ferroelectricity.

Conduction Band Replicas in a 2D Moiré Semiconductor Heterobilayer.

Stacking monolayer semiconductors creates moiré patterns, leading to correlated and topological electronic phenomena, but measurements of the electronic structure underpinning these phenomena are scarce. Here, we investigate the properties of the conduction band in moiré heterobilayers of WS2/WSe2 using submicrometer angle-resolved photoemission spectroscopy with electrostatic gating. We find that at all twist angles the conduction band edge is the K-point valley of the WS2, with a band gap of 1.58 ± 0.03 eV. From the resolved conduction band dispersion, we deduce an effective mass of 0.15 ± 0.02 me. Additionally, we observe replicas of the conduction band displaced by reciprocal lattice vectors of the moiré superlattice. We argue that the replicas result from the moiré potential modifying the conduction band states rather than final-state diffraction. Interestingly, the replicas display an intensity pattern with reduced 3-fold symmetry, which we show implicates the pseudo vector potential associated with in-plane strain in moiré band formation.

Optimization of 1H MR spectroscopy methods for large volume acquisition of low concentration downfield resonances at 3T and 7T.

Purpose: This goal of this study was to optimize spectrally selective 1H MRS methods for large volume acquisition of low concentration metabolites with downfield resonances at 7T and 3T, with particular attention paid to detection of nicotinamide adenine dinucleotide (NAD+) and tryptophan. Methods: Spectrally selective excitation was used to avoid magnetization transfer effects with water, and various sinc pulses were compared to a pure-phase E-BURP pulse. Localization using a single slice selective pulse was compared to voxel-based localization that used three orthogonal refocusing pulses, and low bandwidth refocusing pulses were used to take advantage of the chemical shift displacement of water. A technique for water sideband removal was added, and a method of coil channel combination for large volumes was introduced. Results: Proposed methods were compared qualitatively to previously-reported techniques at 7T. Sinc pulses resulted in reduced water signal excitation and improved spectral quality, with a symmetric, low bandwidth-time product pulse performing best. Single slice localization allowed shorter TEs with large volumes, enhancing signal, while low bandwidth slice selective localization greatly reduced the observed water signal. Gradient cycling helped remove water sidebands, and frequency aligning and pruning individual channels narrowed spectral linewidths. High quality brain spectra of NAD+ and tryptophan are shown in four subjects at 3T. Conclusion: Improved spectral quality with higher downfield signal, shorter TE, lower nuisance signal, reduced artifacts, and narrower peaks was realized at 7T. These methodological improvements allowed for previously unachievable detection of NAD+ and tryptophan in human brain at 3T in under five minutes.

Repeatability of Lac+ measurements in healthy human brain at 3 T.

PURPOSE: In vivo quantification of lactate has numerous applications in studying the pathology of both cerebral and musculoskeletal systems. Due to its low concentration (~0.5-1 mM), and overlap with lipid signals, traditional 1H MR spectra acquired in vivo using a small voxel and short echo time often result in an inadequate signal to detect and resolve the lactate peak, especially in healthy human volunteers. METHODS: In this study, using a semi-LASER acquisition with long echo time (TE = 288 ms) and large voxel size (80 × 70 × 20 mm3), we clearly visualize the combined signal of lactate and threonine. Therefore, we call the signal at 1.33 ppm Lac+ and quantify Lac+ concentration from water suppressed spectra in healthy human brains in vivo. Four participants (22-37 years old; mean age = 28 ± 5.4; three male, one female) were scanned on four separate days, and on each day four measurements were taken. Intra-day values are calculated for each participant by comparing the four measurements on a single day. Inter-day values were calculated using the mean intra-day measurements. RESULTS: The mean intra-participant Lac+ concentration, standard deviation (SD), and coefficient of variation (CV) ranged from 0.49 to 0.61 mM, 0.02 to 0.07 mM, and 4% to 13%, respectively, across four volunteers. The inter-participant Lac+ concentration, SD, and CV was 0.53 mM, ±0.06 mM, and 11%. CONCLUSION: Repeatability is shown in Lac+ measurement in healthy human brain using a long echo time semi-LASER sequence with a large voxel in about 3.5 min at 3 T.

Quantification of NAD + T 1 and T 2 relaxation times using downfield 1 H MRS at 7 T in human brain in vivo.

Introduction: The purpose of this study was to use a single-slice spectrally-selective sequence to measure T 1 and T 2 relaxation times of NAD + proton resonances in the downfield 1 H MRS spectrum in human brain at 7 T in vivo and assess the propagation of relaxation time uncertainty in NAD + quantification. Methods: Downfield spectra from 7 healthy volunteers were acquired at multiple echo times in all subjects to measure T 2 relaxation, and saturation recovery data were to measure T 1 relaxation. The downfield acquisition used a spectrally-selective 90° sinc pulse for excitation centered at 9.1 ppm with a bandwidth of 2 ppm, followed by a 180° spatially-selective Shinnar-Le Roux refocusing pulse for localization. For the multiple echo experiment, spectra were collected with echo times ranging from 13 to 33 ms. For the saturation recovery experiment, saturation was performed prior to excitation using the same spectrally-selective sinc pulse as was used for excitation. Saturation delay times (TS) ranged from 100 to 600 ms. Uncertainty propagation analysis was performed analytically and with Monte Carlo simulation. Results: The mean ± standard deviation of T 1 relaxation times of the H2, H6, and H4 protons were 152.7 ± 16.6, 163.6 ± 22.3, and 169.9 ± 11.2 ms, respectively. The mean ± standard deviation of T 2 relaxation times of the H2, H6, and H4 protons were 32.5 ± 7.0, 27.4 ± 5.2, and 38.1 ± 11.7 ms, respectively. The mean R 2 of the H2 and H6 T 1 fits were 0.98. The mean R 2 of the H4 proton T 1 fit was 0.96. The mean R 2 of the T 2 fits of the H2 and H4 proton resonances were 0.98, while the mean R 2 of the T 2 fits of the H4 proton was 0.93. The relative uncertainty in NAD + concentration due to relaxation time uncertainty was 8.5%-11%. Conclusion: Using downfield spectrally-selective spectroscopy with single-slice localization, we found NAD + T 1 and T 2 relaxation times to be approximately 162 ms and 32 ms respectively in the human brain in vivo at 7 T.

In vivo B 1 + enhancement of calf MRI at 7 T via optimized flexible metasurfaces.

PURPOSE: Ultrahigh field (≥7 T) MRI is at the cutting edge of medical imaging, enabling enhanced spatial and spectral resolution as well as enhanced susceptibility contrast. However, transmit ( B 1 + $$ {\mathrm{B}}_1^{+} $$ ) field inhomogeneity due to standing wave effects caused by the shortened RF wavelengths at 7 T is still a challenge to overcome. Novel hardware methods such as dielectric pads have been shown to improve the B 1 + $$ {\mathrm{B}}_1^{+} $$ field inhomogeneity but are currently limited in their corrective effect by the range of high-permittivity materials available and have a fixed shelf life. In this work, an optimized metasurface design is presented that demonstrates in vivo enhancement of the B 1 + $$ {\mathrm{B}}_1^{+} $$ field. METHODS: A prototype metasurface was optimized by an empirical capacitor sweep and by varying the period size. Phantom temperature experiments were performed to evaluate potential metasurface heating effects during scanning. Lastly, in vivo gradient echo images and B 1 + $$ {\mathrm{B}}_1^{+} $$ maps were acquired on five healthy subjects on a 7 T system. Dielectric pads were also used as a comparison throughout the work as a standard comparison. RESULTS: The metasurfaces presented here enhanced the average relative SNR of the gradient echo images by a factor of 2.26 compared to the dielectric pads factor of 1.61. Average B 1 + $$ {\mathrm{B}}_1^{+} $$ values reflected a similar enhancement of 27.6% with the metasurfaces present versus 8.9% with the dielectric pads. CONCLUSION: The results demonstrate that metasurfaces provide superior performance to dielectric padding as shown by B 1 + $$ {\mathrm{B}}_1^{+} $$ maps reflecting their direct effects and resulting enhancements in image SNR at 7 T.

Frailty and nutrition.

As the ageing population grows and forms a significant category of over 65s in many societies, along with it comes the risk of developing physical and psychological degenerative changes. This presents many challenges for health and social care services in not only identifying those at risk but also managing that risk to try to preserve health and independence for as long as possible. Screening for frailty has supported services to identify those that may be at risk of hospitalisation, requiring long term care or support services at home in older age. Frailty can be exacerbated by the risk of nutritional deficiencies and more severe malnutrition. Therefore, screening for frailty should also include a nutritional assessment, which can be supported by a recognition of the need for nutritional support along with other holistic frailty management.

Application of glutamate weighted CEST in brain imaging of nicotine dependent participants in vivo at 7T.

INTRODUCTION: With nicotine dependence being a significant healthcare issue worldwide there is a growing interest in developing novel therapies and diagnostic aids to assist in treating nicotine addiction. Glutamate (Glu) plays an important role in cognitive function regulation in a wide range of conditions including traumatic brain injury, aging, and addiction. Chemical exchange saturation transfer (CEST) imaging via ultra-high field MRI can image the exchange of certain saturated labile protons with the surrounding bulk water pool, making the technique a novel tool to investigate glutamate in the context of addiction. The aim of this work was to apply glutamate weighted CEST (GluCEST) imaging to study the dorsal anterior cingulate cortex (dACC) in a small population of smokers and non-smokers to determine its effectiveness as a biomarker of nicotine use. METHODS: 2D GluCEST images were acquired on 20 healthy participants: 10 smokers (ages 29-50) and 10 non-smokers (ages 25-69), using a 7T MRI system. T1-weighted images were used to segment the GluCEST images into white and gray matter tissue and further into seven gray matter regions. Wilcoxon rank-sum tests were performed, comparing mean GluCEST contrast between smokers and non-smokers across brain regions. RESULTS: GluCEST levels were similar between smokers and non-smokers; however, there was a moderate negative age dependence (R2 = 0.531) in smokers within the cingulate gyrus. CONCLUSION: Feasibility of GluCEST imaging was demonstrated for in vivo investigation of smokers and non-smokers to assess glutamate contrast differences as a potential biomarker with a moderate negative age correlation in the cingulate gyrus suggesting reward network involvement.

Targeting malnutrition in patients with COPD in the community.

The number of individuals living with chronic obstructive pulmonary disease (COPD) is increasing, but nutritional care can be inconsistent, especially in those with stable COPD. Historically, poor appetite and weight loss have been considered the norm during the progression of COPD into the later stage. However, it is imperative that nutritional assessment, support and management is undertaken from diagnosis, because malnutrition can lead to exacerbations of COPD and increased hospitalisation. Poor nutrition in individuals with COPD has been shown to predict an increase in mortality and with the care of patients taking place principally in the community, the nutritional aspects of care should be assessed, monitored and managed, in accordance with the latest guidance. The lack of a nutritional Quality Outcome Framework indicator for COPD can leave nutrition overlooked, but evidence shows that screening, assessment and planning can have an overall positive impact.

Early-stage mapping of macromolecular content in APPNL-F mouse model of Alzheimer's disease using nuclear Overhauser effect MRI.

Non-invasive methods of detecting early-stage Alzheimer's disease (AD) can provide valuable insight into disease pathology, improving the diagnosis and treatment of AD. Nuclear Overhauser enhancement (NOE) MRI is a technique that provides image contrast sensitive to lipid and protein content in the brain. These macromolecules have been shown to be altered in Alzheimer's pathology, with early disruptions in cell membrane integrity and signaling pathways leading to the buildup of amyloid-beta plaques and neurofibrillary tangles. We used template-based analyzes of NOE MRI data and the characteristic Z-spectrum, with parameters optimized for increase specificity to NOE, to detect changes in lipids and proteins in an AD mouse model that recapitulates features of human AD. We find changes in NOE contrast in the hippocampus, hypothalamus, entorhinal cortex, and fimbria, with these changes likely attributed to disruptions in the phospholipid bilayer of cell membranes in both gray and white matter regions. This study suggests that NOE MRI may be a useful tool for monitoring early-stage changes in lipid-mediated metabolism in AD and other disorders with high spatial resolution.

Implementation of neurological group-based telerehabilitation within existing healthcare during the COVID-19 pandemic: a mixed methods evaluation.

BACKGROUND: There is a need to evaluate if and how telerehabilitation approaches might co-exist within healthcare in the long-term. Our aim was to implement and evaluate a multidisciplinary group-based telerehabilitation approach for people engaging in neurological rehabilitation. METHODS: NeuroRehabilitation OnLine (NROL) was adapted and implemented within an existing healthcare system as a programme of repeating six-week blocks. A robust evaluation was undertaken simultaneously using a convergent parallel design underpinned by implementation frameworks. This included service data, and patient and staff interviews. Implementation success was conceptualised using the outcomes of appropriateness, acceptability and sustainability. RESULTS: Eight NROL blocks delivered 265 sessions with 1347 patient contacts, and NROL continues as part of standard practice. The approach was appropriate for varied demographics and had positive patient opinions and outcomes for many. Staff perceived NROL provided a compatible means to increase therapy and help meet targets, despite needing to mitigate some challenges when fitting the approach within the existing system. NROL was considered acceptable due to good attendance (68%), low drop-out (12%), and a good safety record (one non-injury fall). It was accepted as a new way of working across rehabilitation disciplines as an 'extra layer of therapy'. NROL had perceived advantages in terms of patient and staff resource (e.g. saving time, energy and travel). NROL provided staffing efficiencies (ratio 0.6) compared to one-to-one delivery. Technology difficulties and reluctance were surmountable with dedicated technology assistance. Leadership commitment was considered key to enable the efforts needed for implementation and sustained use. CONCLUSION: Pragmatic implementation of group-based telerehabilitation was possible as an adjunct to neurological rehabilitation within an existing healthcare system. The compelling advantages reported of having NROL as part of rehabilitation supports the continued use of this telerehabilitation approach. This project provides an exemplar of how evaluation can be run concurrently with implementation, applying a data driven rather than anecdotal approach to implementation.

B 1 + $$ {\mathrm{B}}_1

PURPOSE: Nuclear Overhauser effect magnetization transfer ratio (NOEMTR ) is a technique used to investigate brain lipids and macromolecules in greater detail than other techniques and benefits from increased contrast at 7 T. However, this contrast can become degraded because of B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities present at ultra-high field strengths. High-permittivity dielectric pads (DP) have been used to correct for these inhomogeneities via displacement currents generating secondary magnetic fields. The purpose of this work is to demonstrate that dielectric pads can be used to mitigate B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities and improve NOEMTR contrast in the temporal lobes at 7 T. METHODS: Partial 3D NOEMTR contrast images and whole brain B 1 + $$ {\mathrm{B}}_1^{+} $$ field maps were acquired on a 7 T MRI across six healthy subjects. Calcium titanate DP, having a relative permittivity of 110, was placed next to the subject's head near the temporal lobes. Pad corrected NOEMTR images had a separate postprocessing linear correction applied. RESULTS: DP provided supplemental B 1 + $$ {\mathrm{B}}_1^{+} $$ to the temporal lobes while also reducing the B 1 + $$ {\mathrm{B}}_1^{+} $$ magnitude across the posterior and superior regions of the brain. This resulted in a statistically significant increase in NOEMTR contrast in substructures of the temporal lobes both with and without linear correction. The padding also produced a convergence in NOEMTR contrast toward approximately equal mean values. CONCLUSION: NOEMTR images showed significant improvement in temporal lobe contrast when DP were used, which resulted from an increase in B 1 + $$ {\mathrm{B}}_1^{+} $$ homogeneity across the entire brain slab. DP-derived improvements in NOEMTR are expected to increase the robustness of the brain substructural measures both in healthy and pathological conditions.

Identification of new resonances in downfield 1 H MRS of human calf muscle in vivo: Potentially metabolite precursors for skeletal muscle NAD.

PURPOSE: The purpose of this study was to identify and characterize newly discovered resonances appearing in the downfield proton MR spectrum (DF 1 H MRS) of the human calf muscle in vivo at 7T. METHODS: Downfield 1 H MRS was performed on the calf muscle of five healthy volunteers at 7T. A spectrally selective 90° E-BURP RF pulse with an excitation center frequency at 10.3 ppm and an excitation bandwidth of 2 ppm was used for DF 1 H MRS acquisition. RESULTS: In all participants, we observed new resonances at 9.7, 10.1, 10.3, and 10.9 ppm in the DF 1 H MRS. Phantom experiments at 37°C strongly suggest the new resonance at 9.7 ppm could be from H2-proton of the nicotinamide rings in nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) while the resonance at 10.1 ppm could be attributed to the indole -NH proton of L-tryptophan. We observed that the resonances at 10.1 and 10.9 ppm are significantly suppressed when the water resonance is saturated, indicating that these peaks have either 1 H chemical exchange or cross-relaxation with water. Conversely, the resonances at 9.7 and 10.3 ppm exhibit moderate signal reduction in the presence of water saturation. CONCLUSION: We have identified new proton resonances in vivo in human calf muscle occurring at chemical shifts of 9.7, 10.1, 10.3, and 10.9 ppm. These preliminary results are promising for investigating the role of NR/NMN and L-tryptophan metabolism in understanding the de novo and salvage pathways of NAD+ synthesis in skeletal muscle.