CAT on MOUSE: Control and automation of temperature for single‐sided NMR instruments such as NMR‐MOUSE

Magnetic Resonance in Chemistry, Journal Year: 2023, Volume and Issue: 62(4), P. 252 - 258

Published: June 21, 2023

Temperature-dependent experiments are a rapidly growing area of interest for low-field NMR. In this work, we present new device wide-range temperature control single-sided NMR instruments. The presented device, called CAT, is simple to build, inexpensive, and easy modify accommodate different samples. We the capabilities using freezing study acetic acid/water mixtures. Additionally, stability over long measurement times. believe that by introducing such with an open-source design, allow researchers use it in wide range applications fully incorporate variable-temperature studies world

Language: Английский

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In vivoMapping of Cellular Resolution Neuropathology in Brain Ischemia by Diffusion MRI

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 10, 2023

Abstract Non-invasive mapping of cellular pathology can provide critical diagnostic and prognostic information. Recent developments in diffusion MRI have produced new tools for examining tissue microstructure at a level well below the imaging resolution. Here, we report use time ( t )-dependent kurtosis DKI) to simultaneously assess morphology transmembrane permeability cells their processes context pathological changes hypoxic-ischemic brain (HI) injury. Through Monte Carlo simulations cell culture organoid imaging, demonstrate feasibility measuring effective size based on peak tail DKI curves. In mouse model HI, vivo 11.7T detects marked shift longer edema, suggesting swelling beading associated with astrocytic neuronal neurites. Furthermore, observed faster decrease injured regions, reflecting increased membrane that was upregulated water exchange upon astrocyte activation acute stage as necrosis disrupted integrity subacute stage. Such information, unavailable conventional single t, predict salvageable tissues. For proof-of-concept, 3T an ischemic stroke patient suggested region. This work therefore demonstrates potential detection microstructural after injury using clinically translatable protocol.

Language: Английский

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Comparison of three magnetic resonance imaging measures of brain iron in healthy and cocaine use disorder participants

NMR in Biomedicine, Journal Year: 2023, Volume and Issue: 37(3)

Published: Nov. 27, 2023

Abstract Several magnetic resonance imaging (MRI) measures for quantifying endogenous nonheme brain iron have been proposed. These correspond to distinct physical properties with varying sensitivities and specificities iron. Moreover, they may depend not only on tissue concentration, but also the intravoxel spatial pattern of deposition, which is complex in many regions. Here, three MRI , field correlation (MFC), susceptibility are compared several deep gray matter regions both healthy participants (HPs) individuals cocaine use disorder (CUD). Their concordance assessed from their correlations each other relative dependencies age. In addition, associations between microstructure adjacent white investigated by calculating diffusion internal capsule, cognition determined using results a battery standardized tests relevant CUD. It found that all strongly correlated considered regions, coefficients substantially less than one indicating important differences. The age qualitatively similar most except red nucleus, where has significantly stronger . Weak moderate seen cognitive measures, strongest being obtained differ little HP CUD groups, although lower nucleus group. For comparisons made, behave similarly respects, notable quantitative suggested these differences be, part, attributable higher sensitivity deposition MFC susceptibility. This supported sharp contrast values globus pallidus those nucleus. observed scores point possible connections iron, microstructure, cognition.

Language: Английский

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Molecular localization and exchange kinetics in pharmaceutical liposome and mRNA lipoplex nanoparticle products determined by small angle X-ray scattering and pulsed field gradient NMR diffusion measurements

European Journal of Pharmaceutics and Biopharmaceutics, Journal Year: 2024, Volume and Issue: 201, P. 114380 - 114380

Published: July 1, 2024

We have used pulsed field gradient (PFG)-NMR diffusion experiments, also known as DOSY, in combination with small angle X-ray scattering measurements to investigate structure and molecular exchange dynamics between pharmaceutical lipid nanoparticles the bulk phase. Using liposomes lipoplexes formed after complexation of messenger mRNA test systems, information on encapsulated water molecules, lipids excipients was obtained. The fraction, having a diffusivity similar that liposomes, could be clearly identified quantified by NMR measurements. unilamellar liposome membranes allowed fast while sucrose, an osmolyte model solute, showed very slow exchange. Upon interactions topological transition from vesicular lamellar organization took place, where inserted repeating bilayer stacks. In lipoplexes, fraction tightly bound molecules present, influenced additional presence sucrose. This extended dynamic coherencies inside nanoparticle products, provided combined application SAXS PFG-NMR measurements, can valuable for evaluation quality comparability nanoscaled pharmaceuticals.

Language: Английский

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The Diffusion Exchange Ratio (DEXR): A minimal sampling of diffusion exchange spectroscopy to probe exchange, restriction, and time-dependence

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 6, 2024

Abstract Water exchange is increasingly recognized as an important biological process that can affect the study of tissue using diffusion MR. Methods to measure exchange, however, remain immature opposed those used characterize restriction, with no consensus on optimal pulse sequence(s) or signal model(s). In general, trend has been towards data-intensive fitting highly parameterized models. We take opposite approach and show a judicious sub-sample spectroscopy (DEXSY) data be robustly quantify well in data-efficient manner. This sampling produces ratio two points per mixing time: (i) one point equal weighting both encoding periods, which gives maximal contrast, (ii) same total just first period, for normalization. call this quotient Diffusion EXchange Ratio (DEXR). Furthermore, we it probe time-dependent by estimating velocity autocorrelation function (VACF) over intermediate long times (∼ 2 − 500 ms). provide comprehensive theoretical framework design DEXR experiments case static constant gradients. Data from Monte Carlo simulations acquired fixed viable ex vivo neonatal mouse spinal cord permanent magnet system are presented test validate approach. cord, report following apparent parameters 6 points: τ k = 17 ± 4 ms, f NG 0.71 0.01, R eff 1.10 0.01 μ m, 0.21 0.06 m/ms, correspond time, restricted non-Gaussian fraction, effective spherical radius, permeability, respectively. For VACF, long-time, power-law scaling ≈ t 2.4 , approximately consistent disordered domains 3-D. Overall, method shown efficient, capable providing valuable quantitative metrics minimal MR data.

Language: Английский

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Hydrophysiology NMR reveals mechanisms of steady-state water exchange in neural tissue

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 13, 2024

SUMMARY Water molecules exchange incessantly across cell membranes and among different environments within the cell, but it is not known what dominant transport pathways are whether they active or passive. We have developed realtime NMR hydrophysiology methods to study steady-state water diffusion in viable ex vivo neonatal mouse spinal cord samples. find that linked tonicity maintained by transport. Exchange slows following sodium–potassium pump inhibition recovers a normal rate after adding extracellular osmolytes. Additional information from apparent coefficients (ADC) differentiates inactive samples regardless of tonicity. Data modeling suggest multisite mechanism which modulates pathway between fast transmembrane slow intracellular exchange. The has high activation energy does require ions, suggesting this likely occurs through lipid bilayer rather than channels cotransporters. These may one day be translated clinical MRI scanners determine features cellular state . steady exchange, homeostasis, spectroscopy, DEXSY, tissue microstructure, porous media, membrane permeability, low-field single-sided NMR, coefficient, ADC, gray matter

Language: Английский

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In vivohuman neurite exchange imaging (NEXI) at 500 mT/m diffusion gradients

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

Evaluating tissue microstructure and membrane integrity in the living human brain through diffusion-water exchange imaging is challenging due to requirements for a high signal-to-noise ratio short diffusion times dictated by relatively fast processes. The goal of this work was demonstrate feasibility vivo micro-geometries water within gray matter using state-of-the-art Connectome 2.0 scanner equipped with an ultra-high-performance gradient system (maximum strength=500 mT/m, maximum slew rate=600 T/m/s). We performed MRI measurements 15 healthy volunteers at multiple (13-30 ms) b -values up 17.5 ms/μm 2 . anisotropic Kärger model applied estimate time between intra-neurite extracellular matter. estimated across cortical ribbon around (median±interquartile range) 13±8 ms on 2.0, substantially faster than that measured protocol compatible 1.0-alike systems same cohort. Our investigation suggested NEXI estimation 1.0 more prone residual noise floor biases small time-dependent signal contrasts when (≤20 ms). Furthermore, spatial variation observed cortex, where motor somatosensory cortex visual exhibit longer compared other regions. Non-linear fitting accelerated 100 GPU-based pipeline conventional CPU-based approach. This study highlighted importance chosen measures address Rician dMRI data, which can have substantial impact require extra attention comparing results various hardware setups. 500 mT/m gradients enables high-sensitivity global be about 13 1.0Spatially varying were cortexA GPU-accelerated tool developed speed parameter timesThe narrow pulse approximation used neurite does not affect performance systems.

Language: Английский

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In vivo assessment of the influence of general anaesthetics on transmembrane water cycling in the brain

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 24, 2024

This study presents the first in vivo measurement of transcytolemmal water exchange brain using a novel Magnetic Resonance technique. We extend previous applications Chemical Exchange Saturation Transfer (CEST) to examine across cellular membranes late-stage chicken embryo brains. The immature blood-brain barrier at this stage allows Gadolinium-Based Contrast Agents (GBCAs) penetrate brain’s interstitial space, sensitizing CEST effect between intra- and extracellular environments. rates were measured awake under different anaesthetic regimens, including isoflurane ketamine/xylazine. Results show that is dominated by activity-dependent mechanisms, with anaesthesia reducing over an order magnitude. These findings suggest anaesthetics may impact neuronal glial function interfering active transport potentially altering homeostasis. highlights utility MRI for studying dynamic biological processes vivo.

Language: Английский

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