Frontal adenosine triphosphate markers from 31P MRS are associated with cognitive performance in healthy older adults: preliminary findings.

Aging is associated with declines in mitochondrial efficiency and energy production which directly impacts the availability of adenosine triphosphate (ATP), which contains high energy phosphates critical for a variety of cellular functions. Previous phosphorous magnetic resonance spectroscopy (31P MRS) studies demonstrate cerebral ATP declines with age. The purpose of this study was to explore the functional relationships of frontal and posterior ATP levels with cognition in healthy aging. Here, we measured frontal and posterior ATP levels using 31P MRS at 3 Tesla (3 T) and assessed cognition using the Montreal Cognitive Assessment (MoCA) in 30 healthy older adults. We found that greater frontal, but not posterior, ATP levels were significantly associated with better MoCA performance. This relationship remained significant after controlling for age, sex, years of education, and brain atrophy. In conclusion, our findings indicate that cognition is related to ATP in the frontal cortex. These preliminary findings may have important implications in the search for non-invasive markers of in vivo mitochondrial function and the impact of ATP availability on cognition. Future studies are needed to confirm the functional significance of regional ATP and cognition across the lifespan.

Quantification approaches for magnetic resonance imaging following intravenous gadolinium injection: A window into brain-wide glymphatic function.

The glymphatic system is a brain-wide network of perivascular pathways along which cerebrospinal fluid and interstitial fluid rapidly exchange, facilitating solute and waste clearance from the brain parenchyma. The characterization of this exchange process in humans has relied primarily upon serial magnetic resonance imaging following intrathecal gadolinium-based contrast agent injection. However, less invasive approaches are needed. Here, we administered a gadolinium-based contrast agent intravenously in eight healthy participants and acquired magnetic resonance imaging scans prior to and 30, 90, 180, and 360 min post contrast injection. Using a region-of-interest approach, we observed that peripheral tissues and blood vessels exhibited high enhancement at 30 min after contrast administration, likely reflecting vascular and peripheral interstitial distribution of the gadolinium-based contrast agent. Ventricular, grey matter and white matter enhancement peaked at 90 min, declining thereafter. Using k-means clustering, we identify distinct distribution volumes reflecting the leptomeningeal perivascular network, superficial grey matter and deep grey/white matter that exhibit a sequential enhancement pattern consistent with parenchymal contrast enhancement via the subarachnoid cerebrospinal fluid compartment. We also outline the importance of correcting for (otherwise automatic) autoscaling of signal intensities, which could potentially lead to misinterpretation of gadolinium-based contrast agent distribution kinetics. In summary, we visualize and quantify delayed tissue enhancement following intravenous administration of gadolinium-based contrast agent in healthy human participants.

A natural history study to track brain and spinal cord changes in individuals with Friedreich's ataxia: TRACK-FA study protocol.

INTRODUCTION: Drug development for neurodegenerative diseases such as Friedreich's ataxia (FRDA) is limited by a lack of validated, sensitive biomarkers of pharmacodynamic response in affected tissue and disease progression. Studies employing neuroimaging measures to track FRDA have thus far been limited by their small sample sizes and limited follow up. TRACK-FA, a longitudinal, multi-site, and multi-modal neuroimaging natural history study, aims to address these shortcomings by enabling better understanding of underlying pathology and identifying sensitive, clinical trial ready, neuroimaging biomarkers for FRDA. METHODS: 200 individuals with FRDA and 104 control participants will be recruited across seven international study sites. Inclusion criteria for participants with genetically confirmed FRDA involves, age of disease onset ≤ 25 years, Friedreich's Ataxia Rating Scale (FARS) functional staging score of ≤ 5, and a total modified FARS (mFARS) score of ≤ 65 upon enrolment. The control cohort is matched to the FRDA cohort for age, sex, handedness, and years of education. Participants will be evaluated at three study visits over two years. Each visit comprises of a harmonized multimodal Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) scan of the brain and spinal cord; clinical, cognitive, mood and speech assessments and collection of a blood sample. Primary outcome measures, informed by previous neuroimaging studies, include measures of: spinal cord and brain morphometry, spinal cord and brain microstructure (measured using diffusion MRI), brain iron accumulation (using Quantitative Susceptibility Mapping) and spinal cord biochemistry (using MRS). Secondary and exploratory outcome measures include clinical, cognitive assessments and blood biomarkers. DISCUSSION: Prioritising immediate areas of need, TRACK-FA aims to deliver a set of sensitive, clinical trial-ready neuroimaging biomarkers to accelerate drug discovery efforts and better understand disease trajectory. Once validated, these potential pharmacodynamic biomarkers can be used to measure the efficacy of new therapeutics in forestalling disease progression. CLINICAL TRIAL REGISTRATION: ClinicalTrails.gov Identifier: NCT04349514.

Nonparametric 5D D-R2 distribution imaging with single-shot EPI at 21.1 T: Initial results for in vivo rat brain.

In vivo human diffusion MRI is by default performed using single-shot EPI with greater than 50-ms echo times and associated signal loss from transverse relaxation. The individual benefits of the current trends of increasing B0 to boost SNR and employing more advanced signal preparation schemes to improve the specificity for selected microstructural properties eventually may be cancelled by increased relaxation rates at high B0 and echo times with advanced encoding. Here, initial attempts to translate state-of-the-art diffusion-relaxation correlation methods from 3 T to 21.1 T are made to identify hurdles that need to be overcome to fulfill the promises of both high SNR and readily interpretable microstructural information.

Extended Ischemic Recovery After Implantation of Human Mesenchymal Stem Cell Aggregates Indicated by Sodium MRI at 21.1 T.

Extended therapeutic application remains a significant issue in the use of stem cell therapies to treat ischemic stroke. Along these lines, neurological recovery in a rodent model of ischemic stroke was evaluated following implantation of human mesenchymal stem cell aggregates (hMSC-agg), labeled with micron-sized particles of iron oxide, directly into the lateral ventricle contralateral to the ischemic lesion hemisphere. Longitudinally, disease progression and response to hMSC-agg therapy were assessed by 1H and 23Na magnetic resonance imaging (MRI) at 21.1 T to investigate cellular localization, migration, and recovery over an extended timeframe. MRI provides quantifiable metrics of tissue status through sodium distributions in addition to traditional proton imaging. Quantitative 23Na MRI revealed a significant decrease of sodium concentrations following hMSC aggregate implantation, indicating recovery of homeostasis. This result correlates positively with extended neurological recovery assessed by behavioral analysis and immunohistochemistry. These findings demonstrate the potential of implanted hMSC aggregate therapy to provide extended treatment for ischemic stroke, as well as the robustness of MRI for monitoring such approaches. This method potentially can be translated to a clinical setting for the assessment of extended cell therapy efficacy.

Transcranial stimulation of alpha oscillations up-regulates the default mode network.

The default mode network (DMN) is the most-prominent intrinsic connectivity network, serving as a key architecture of the brain's functional organization. Conversely, dysregulated DMN is characteristic of major neuropsychiatric disorders. However, the field still lacks mechanistic insights into the regulation of the DMN and effective interventions for DMN dysregulation. The current study approached this problem by manipulating neural synchrony, particularly alpha (8 to 12 Hz) oscillations, a dominant intrinsic oscillatory activity that has been increasingly associated with the DMN in both function and physiology. Using high-definition alpha-frequency transcranial alternating current stimulation (α-tACS) to stimulate the cortical source of alpha oscillations, in combination with simultaneous electroencephalography and functional MRI (EEG-fMRI), we demonstrated that α-tACS (versus Sham control) not only augmented EEG alpha oscillations but also strengthened fMRI and (source-level) alpha connectivity within the core of the DMN. Importantly, increase in alpha oscillations mediated the DMN connectivity enhancement. These findings thus identify a mechanistic link between alpha oscillations and DMN functioning. That transcranial alpha modulation can up-regulate the DMN further highlights an effective noninvasive intervention to normalize DMN functioning in various disorders.

Olfactory bulb-targeted quantum dot (QD) bioconjugate and Kv1.3 blocking peptide improve metabolic health in obese male mice.

The olfactory system is a driver of feeding behavior, whereby olfactory acuity is modulated by the metabolic state of the individual. The excitability of the major output neurons of the olfactory bulb (OB) can be modulated through targeting a voltage-dependent potassium channel, Kv1.3, which responds to changes in metabolic factors such as insulin, glucose, and glucagon-like peptide-1. Because gene-targeted deletion or inhibition of Kv1.3 in the periphery has been found to increase energy metabolism and decrease body weight, we hypothesized that inhibition of Kv1.3 selectively in the OB could enhance excitability of the output neurons to evoke changes in energy homeostasis. We thereby employed metal-histidine coordination to self-assemble the Kv1.3 inhibitor margatoxin (MgTx) to fluorescent quantum dots (QDMgTx) as a means to label cells in vivo and test changes in neuronal excitability and metabolism when delivered to the OB. Using patch-clamp electrophysiology to measure Kv1.3 properties in heterologously expressed cells and native mitral cells in OB slices, we found that QDMgTx had a fast rate of inhibition, but with a reduced IC50, and increased action potential firing frequency. QDMgTx was capable of labeling cloned Kv1.3 channels but was not visible when delivered to native Kv1.3 in the OB. Diet-induced obese mice were observed to reduce body weight and clear glucose more quickly following osmotic mini-pump delivery of QDMgTx/MgTx to the OB, and following MgTx delivery, they increased the use of fats as fuels (reduced respiratory exchange ratio). These results suggest that enhanced excitability of bulbar output neurons can drive metabolic responses.

Comparative study on contrast enhancement of Magnevist and Magnevist-loaded nanoparticles in pancreatic cancer PDX model monitored by MRI.

BACKGROUND: The aim of this study was to compare contrast enhancement of Magnevist® (gadopentate dimeglumine (Mag)) to that of PEGylated Magnevist®-loaded liposomal nanoparticles (Mag-Lnps) in pancreatic cancer patient-derived xenograft (PDX) mouse model via magnetic resonance imaging (MRI). METHODS: Mag-Lnps formulated by thin-film hydration and extrusion was characterized for the particle size and zeta potential. A 21.1 T vertical magnet was used for all MRI. The magnet was equipped with a Bruker Advance console and ParaVision 6.1 acquisitions software. Mag-Lnps phantoms were prepared and imaged with a 10-mm birdcage coil. For in vivo imaging, animals were sedated and injected with a single dose (4 mg/kg) of Mag or Mag-Lnps with Mag equivalent dose. Using a 33-mm inner diameter birdcage coil, T 1 maps were acquired, and signal to noise ratio (SNR) measured for 2 h. RESULTS: Mag-Lnps phantoms showed a remarkable augmentation in contrast with Mag increment. However, in in vivo imaging, no significant difference in contrast was observed between Mag and MRI. While Mag-Lnps was observed to have fairly high tumor/muscle (T/M) ratio in the first 30 min, free Mag exhibited higher T/M ratio over the time-period between 30 and 120 min. Overall, there was no statistically significant difference between Mag and Mag-Lnp in rating MR image quality. Low payload of Mag entrapment by Lnps and restricted access of water (protons) to Mag-Lnps may have affected the performance of Mag-Lnps as an effective contrast agent. CONCLUSION: This study showed no significance difference in MRI contrast between Mag and Mag-Lnp pancreatic cancer PDX mouse models.

Fast chemical exchange saturation transfer imaging based on PROPELLER acquisition and deep neural network reconstruction.

PURPOSE: To develop a method for fast chemical exchange saturation transfer (CEST) imaging. METHODS: The periodically rotated overlapping parallel lines enhanced reconstruction (PROPELLER) sampling scheme was introduced to shorten the acquisition time. Deep neural network was employed to reconstruct CEST contrast images. Numerical simulation and experiments on a creatine phantom, hen egg, and in vivo tumor rat brain were performed to test the feasibility of this method. RESULTS: The results from numerical simulation and experiments show that there is no significant difference between reference images and CEST-PROPELLER reconstructed images under an acceleration factor of 8. CONCLUSION: Although the deep neural network is trained entirely on synthesized data, it works well on reconstructing experimental data. The proof of concept study demonstrates that the combination of the PROPELLER sampling scheme and the deep neural network enables considerable acceleration of saturated image acquisition and may find applications in CEST MRI.

Amplified detection of phosphocreatine and creatine after supplementation using CEST MRI at high and ultrahigh magnetic fields.

Creatine is an important metabolite involved in muscle contraction. Administration of exogenous creatine (Cr) or phosphocreatine (PCr) has been used for improving exercise performance and protecting the heart during surgery including during valve replacements, coronary artery bypass grafting and repair of congenital heart defects. In this work we investigate whether it is possible to use chemical exchange saturation transfer (CEST) MRI to monitor uptake and clearance of exogenous creatine and phosphocreatine following supplementation. We were furthermore interested in determining the limiting conditions for distinguishing between creatine (1.9 ppm) and phosphocreatine (2.6 ppm) signals at ultra-high fields (21 T) and determine their concentrations could be reliably obtained using Bloch equation fits of the experimental CEST spectra. We have tested these items by performing CEST MRI of hind limb muscle and kidneys at 11.7 T and 21.1 T both before and after intravenous administration of PCr. We observed up to 4% increase in contrast in the kidneys at 2.6 ppm which peaked ~30 min after administration and a relative ratio of 1.3 in PCr:Cr signal. Overall, these results demonstrate the feasibility of independent monitoring of PCr and Cr concentration changes using CEST MRI.

Magnetic resonance electrical property mapping at 21.1 T: a study of conductivity and permittivity in phantoms, ex vivo tissue and in vivo ischemia.

Electrical properties (EP), namely conductivity and permittivity, can provide endogenous contrast for tissue characterization. Using electrical property tomography (EPT), maps of EP can be generated from conventional MRI data. This report investigates the feasibility and accuracy of EPT at 21.1 T for multiple RF coils and modes of operation using phantoms. Additionally, it demonstrates the EP of the in vivo rat brain with and without ischemia. Helmholtz-based EPT was implemented in its Full-form, which demands the complex [Formula: see text] field, and a simplified form requiring either just the [Formula: see text] field phase for conductivity or the [Formula: see text] field magnitude for permittivity. Experiments were conducted at 21.1 T using birdcage and saddle coils operated in linear or quadrature transceive mode, respectively. EPT approaches were evaluated using a phantom, ex and in vivo Sprague-Dawley rats under naïve conditions and ischemic stroke via transient middle cerebral artery occlusion. Different conductivity reconstruction approaches applied to the phantom displayed average errors of 12%-73% to the target acquired from dielectric probe measurements. Permittivity reconstructions showed higher agreement and an average 3%-8% error to the target depending on reconstruction approach. Conductivity and permittivity of ex and in vivo rodent brain were measured. Elevated EP in the ischemia region correlated with the increased sodium content and the influx of water intracellularly following ischemia in the lesion were detected. The Full-form technique generated from the linear birdcage provided the best accuracy for EP of the phantom. Phase-based conductivity and magnitude-based permittivity mapping provided reasonable estimates but also demonstrated the limitations of Helmholtz-based EPT at 21.1 T. Permittivity reconstruction was improved significantly over lower fields, suggesting a novel metric for in vivo brain studies. EPT applied to ischemic rat brain proved sensitivity to physiological changes, motivating the future application of more advanced reconstruction approaches.

Multiparametric classification of sub-acute ischemic stroke recovery with ultrafast diffusion, 23 Na, and MPIO-labeled stem cell MRI at 21.1 T.

MRI leverages multiple modes of contrast to characterize stroke. High-magnetic-field systems enhance the performance of these MRI measurements. Previously, we have demonstrated that individually sodium and stem cell tracking metrics are enhanced at ultrahigh field in a rat model of stroke, and we have developed robust single-scan diffusion-weighted imaging approaches that utilize spatiotemporal encoding (SPEN) of the apparent diffusion coefficient (ADC) for these challenging field strengths. Here, we performed a multiparametric study of middle cerebral artery occlusion (MCAO) biomarker evolution focusing on comparison of these MRI biomarkers for stroke assessment during sub-acute recovery in rat MCAO models at 21.1 T. T2 -weighted MRI was used as the benchmark for identification of the ischemic lesion over the course of the study. The number of MPIO-induced voids measured by gradient-recalled echo, the SPEN measurement of ADC, and 23 Na MRI values were determined in the ischemic area and contralateral hemisphere, and relative performances for stroke classification were compared by receiver operator characteristic analysis. These measurements were associated with unique time-dependent trajectories during stroke recovery that changed the sensitivity and specificity for stroke monitoring during its evolution. Advantages and limitations of these contrasts, and the use of ultrahigh field for multiparametric stroke assessment, are discussed.

Aggregation of human mesenchymal stem cells enhances survival and efficacy in stroke treatment.

Human mesenchymal stem cells (hMSCs) have been shown to enhance stroke lesion recovery by mediating inflammation and tissue repair through secretion of trophic factors. However, low cell survival and reduced primitive stem cell function of culture-expanded hMSCs are the major challenges limiting hMSC therapeutic efficacy in stroke treatment. In this study, we report the effects of short-term preconditioning of hMSCs via three-dimensional (3D) aggregation on stroke lesion recovery after intra-arterial (IA) transplantation of 3D aggregate-derived hMSCs (Agg-D hMSCs) in a transient middle cerebral artery occlusion (MCAO) stroke model. Compared with two-dimensional (2D) monolayer culture, Agg-D hMSCs exhibited increased resistance to ischemic stress, secretory function and therapeutic outcome. Short-term preconditioning via 3D aggregation reconfigured hMSC energy metabolism and altered redox cycle, which activated the PI3K/AKT pathway and enhanced resistance to in vitro oxidative stress. Analysis of transplanted hMSCs in MCAO rats using ultra-high-field magnetic resonance imaging at 21.1 T showed increased hMSC persistence and stroke lesion reduction by sodium (23Na) imaging in the Agg-D hMSC group compared with 2D hMSC control. Behavioral analyses further revealed functional improvement in MCAO animal treated with Agg-D hMSCs compared with saline control. Together, the results demonstrated the improved outcome for Agg-D hMSCs in the MCAO model and suggest short-term 3D aggregation as an effective preconditioning strategy for hMSC functional enhancement in stroke treatment.

Cationic carrier peptide enhances cerebrovascular targeting of nanoparticles in Alzheimer's disease brain.

Accumulation of amyloid beta (Aß) peptides in the cerebral vasculature, referred to as cerebral amyloid angiopathy (CAA), is widely observed in Alzheimer's disease (AD) brain and was shown to accelerate cognitive decline. There is no effective method for detecting cerebrovascular amyloid (CVA) and treat CAA. The targeted nanoparticles developed in this study effectively migrated from the blood flow to the vascular endothelium as determined by using quartz crystal microbalance with dissipation monitoring (QCM-D) technology. We also improved the stability, and blood-brain barrier (BBB) transcytosis of targeted nanoparticles by coating them with a cationic BBB penetrating peptide (K16ApoE). The K16ApoE-Targeted nanoparticles demonstrated specific targeting of vasculotropic DutchAß40 peptide accumulated in the cerebral vasculature. Moreover, K16ApoE-Targeted nanoparticles demonstrated significantly greater uptake into brain and provided specific MRI contrast to detect brain amyloid plaques.

Fluorine-19 MRI at 21.1 T: enhanced spin-lattice relaxation of perfluoro-15-crown-5-ether and sensitivity as demonstrated in ex vivo murine neuroinflammation.

OBJECTIVE: Fluorine MR would benefit greatly from enhancements in signal-to-noise ratio (SNR). This study examines the sensitivity gain of 19F MR that can be practically achieved when moving from 9.4 to 21.1 T. MATERIALS AND METHODS: We studied perfluoro-15-crown-5-ether (PFCE) at both field strengths (B0), as a pure compound, in the form of nanoparticles (NP) as employed to study inflammation in vivo, as well as in inflamed tissue. Brains, lymph nodes (LNs) and spleens were obtained from mice with experimental autoimmune encephalomyelitis (EAE) that had been administered PFCE NPs. All samples were measured at both B0 with 2D-RARE and 2D-FLASH using 19F volume radiofrequency resonators together. T1 and T2 of PFCE were measured at both B0 strengths. RESULTS: Compared to 9.4 T, an SNR gain of > 3 was observed for pure PFCE and > 2 for PFCE NPs at 21.1 T using 2D-FLASH. A dependency of 19F T1 and T2 relaxation on B0 was demonstrated. High spatially resolved 19F MRI of EAE brains and LNs at 21.1 T revealed signals not seen at 9.4 T. DISCUSSION: Enhanced SNR and T1 shortening indicate the potential benefit of in vivo 19F MR at higher B0 to study inflammatory processes with greater detail.

Effects of labeling human mesenchymal stem cells with superparamagnetic iron oxides on cellular functions and magnetic resonance contrast in hypoxic environments and long-term monitoring.

Ischemia, which involves decreased blood flow to a region and a corresponding deprivation of oxygen and nutrients, can be induced as a consequence of stroke or heart attack. A prevalent disease that affects many individuals worldwide, ischemic stroke results in functional and cognitive impairments, as neural cells in the brain receive inadequate nourishment and encounter inflammation and various other detrimental toxic factors that lead to their death. Given the scarce treatments for this disease in the clinic such as the administration of tissue plasminogen activator, which is only effective in a limited time window after the occurrence of stroke, it will be necessary to develop new strategies to ameliorate or prevent stroke-induced brain damage. Cell-based therapies appear to be a promising solution for treating ischemic stroke and many other ischemia-associated and neurodegenerative maladies. Particularly, human mesenchymal stem cells (hMSCs) are of interest for cell transplantation in stroke, given their multipotency, accessibility, and reparative abilities. To determine the fate and survival of hMSC, which will be imperative for successful transplantation therapies, these cells may be monitored using magnetic resonance imaging and transfected with superparamagnetic iron oxide (SPIO), a contrast agent that facilitates the detection of these hMSCs. This review encompasses pertinent research and findings to reveal the effects of SPIO on hMSC functions in the context of transplantation in ischemic environments and over extended time periods. This paper is a review article. Referred literature in this paper has been listed in the references section. The data sets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.

Cellular and molecular responses to acute cocaine treatment in neuronal-like N2a cells: potential mechanism for its resistance in cell death.

Cocaine is a highly abused drug that causes psychiatric and neurological problems. Its entry into neurons could alter cell-biochemistry and contribute in the manifestation of early pathological symptoms. We have previously shown the acute cocaine effects in rat C6 astroglia-like cells and found that these cells were highly sensitive to cocaine in terms of manifesting certain pathologies known to underlie psychological disorders. The present study was aimed to discern acute cocaine effects on the early onset of various changes in Neuro-2a (N2a) cells. Whole-cell patch-clamp recording of differentiated cells displayed the functional voltage-gated Na+ and K+ channels, which demonstrated the neuronal characteristics of the cells. Treatment of these cells with acute cocaine (1 h) at in vivo (nM to µM) and in vitro (mM) concentrations revealed that the cells remained almost 100% viable. Cocaine administration at 6.25 µM or 4 mM doses significantly reduced the inward currents but had no significant effect on outward currents, indicating the Na+ channel-blocking activity of cocaine. While no morphological change was observed at in vivo doses, treatment at in vitro doses altered the morphology, damaged the neurites, and induced cytoplasmic vacuoles; furthermore, general mitochondrial activity and membrane potential were significantly decreased. Mitochondrial dysfunction enabled the cells switch to anaerobic glycolysis, evidenced by dose-dependent increases in lactate and H2S, resulting unaltered ATP level in the cells. Further investigation on the mechanism of action unfolded that the cell's resistance to cocaine was through the activation of nuclear factor E2-related factor-2 (Nrf-2) gene and subsequent increase of antioxidants (glutathione [GSH], catalase and GSH peroxidase [GPx]). The data clearly indicate that the cells employed a detoxifying strategy against cocaine. On a broader perspective, we envision that extrapolating the knowledge of neuronal resistance to central nervous system (CNS) diseases could delay their onset or progression.

Brain investigations of rodent disease models by chemical exchange saturation transfer at 21.1 T.

This study explores opportunities opened up by ultrahigh fields for in vivo saturation transfer brain magnetic resonance imaging experiments. Fast spin-echo images weighted by chemical exchange saturation transfer (CEST) effects were collected on Sprague-Dawley rats at 21.1 T, focusing on two neurological models. One involved a middle cerebral artery occlusion emulating ischemic stroke; the other involved xenografted glioma cells that were followed over the course of several days as they developed into brain tumors. A remarkably strong saturation-derived contrast was observed for the growing tumors when calculating magnetization transfer ratios at c. 3.8 ppm. This large contrast originated partially from an increase in the contribution of the amide CEST effect, but mostly from strong decreases in the Overhauser and magnetization transfer contributions to the upfield region, whose differential attenuations could be clearly discerned thanks to the ultrahigh field. The high spectral separation arising at 21.1 T also revealed numerous CEST signals usually overlapping at lower fields. Ischemic lesions were also investigated but, remarkably, magnetization and saturation transfer contrasts were nearly absent when computing transfer asymmetries using either high or low saturation power schemes. These behaviors were consistently observed at 24 hours post-occlusion, regardless of the data processing approach assayed. Considerations related to how various parameters defining these experiments depend on the magnetic field, primarily chemical shifts and T1 values, are discussed.

Dynamic sodium imaging at ultra-high field reveals progression in a preclinical migraine model.

Under the hypothesis that increased extracellular sodium induces sustained neuronal excitability with the onset and progression of migraine, this study evaluates dynamic in vivo Na fluxes in the brain of a preclinical rodent analogue of migraine. Ultra-high field Na magnetic resonance imaging (MRI) at 21.1 T has demonstrated potential to quantify sodium concentrations with good spatial and temporal resolution after the onset of central sensitization. Sprague-Dawley male rats with implanted intraperitoneal lines were studied by MRI before and after an in situ injection of 10 mg/kg of nitroglycerin (NTG) vs vehicle and saline controls. Slice-selective Na images were acquired using a multislice free induction decay-based chemical shift imaging sequence with resolution of 1.1 × 1.1 × 3 mm for a 9-minute acquisition. A total of 27 repeated scans were acquired over 1 hour of baseline scanning and longitudinally up to 3 hours after injection. Increases of Na MRI signal in the brainstem, extracerebral cerebrospinal fluid, and cisterna magna were evident almost immediately after NTG injection, gaining significance from controls in 36 minutes. The cerebellum and third ventricle also showed sustained trends of increased Na, with the former gaining significance at over 2 hours after NTG injection. The data provide evidence of an early change in sodium concentration, markedly in posterior fossa cerebrospinal fluid and brainstem regions. Further study of fluctuations of sodium concentration and their modulation with treatments could help understand the dynamic features of migraine, locate a putative migraine generator, and guide development of therapeutic measures to correct the disturbance of sodium homeostasis.

Li Distribution Heterogeneity in Solid Electrolyte Li10GeP2S12 upon Electrochemical Cycling Probed by 7Li MRI.

All-solid-state rechargeable batteries embody the promise for high energy density, increased stability, and improved safety. However, their success is impeded by high resistance for mass and charge transfer at electrode-electrolyte interfaces. Li deficiency has been proposed as a major culprit for interfacial resistance, yet experimental evidence is elusive due to the challenges associated with noninvasively probing the Li distribution in solid electrolytes. In this Letter, three-dimensional 7Li magnetic resonance imaging (MRI) is employed to examine Li distribution homogeneity in solid electrolyte Li10GeP2S12 within symmetric Li/Li10GeP2S12/Li batteries. 7Li MRI and the derived histograms reveal Li depletion from the electrode-electrolyte interfaces and increased heterogeneity of Li distribution upon electrochemical cycling. Significant Li loss at interfaces is mitigated via facile modification with a poly(ethylene oxide)/bis(trifluoromethane)sulfonimide Li salt thin film. This study demonstrates a powerful tool for noninvasively monitoring the Li distribution at the interfaces and in the bulk of all-solid-state batteries as well as a convenient strategy for improving interfacial stability.