Water exchange rates measure active transport and homeostasis in neural tissue

PNAS Nexus, Journal Year: 2023, Volume and Issue: 2(3)

Published: Feb. 27, 2023

For its size, the brain is most metabolically active organ in body. Most of energy demand used to maintain stable homeostatic physiological conditions. Altered homeostasis and states are hallmarks many diseases disorders. Yet there currently no direct reliable method assess absolute basal activity cells tissue noninvasively without exogenous tracers or contrast agents. We propose a novel low-field, high-gradient diffusion exchange nuclear magnetic resonance (NMR) capable directly measuring cellular metabolic via rate constant for water across cell membranes. Exchange rates 140±16 s -1 under normal conditions viable ex vivo neonatal mouse spinal cords. High repeatability samples suggest that values intrinsic tissue. Using temperature drug (ouabain) perturbations, we find majority coupled transport by sodium-potassium pump. show this sensitive primarily provides distinct functional information. In contrast, apparent coefficient (ADC) measured with submillisecond times microstructure but not activity. Water appears independently regulated from microstructural oxygenation changes reported ADC T1 relaxation measurements an oxygen-glucose deprivation model stroke; remain 30-40 min before dropping levels similar effect ouabain never completely recovering when oxygen glucose restored.

Language: Английский

---

Cerebellar imaging with diffusion magnetic resonance imaging: approaches, challenges, and potential

Current Opinion in Behavioral Sciences, Journal Year: 2024, Volume and Issue: 56, P. 101353 - 101353

Published: Feb. 8, 2024

Diffusion magnetic resonance imaging (dMRI) is sensitive to the mobility of water in tissue and cell geometry organization central nervous system — providing unique insight into both local microstructure white matter connectivity. Most dMRI methods were developed for studying cerebral but can provide useful information about cerebellar gray matter. However, small size intricate structure cerebellum poses challenges dMRI. In this review, we discuss these challenges, recent advancements methodology, insights from applications novel methods. While many limitations still remain should be considered conclusions regarding connectivity, carefully designed experiments analyses new behavioral pathological aspects function.

Language: Английский

---

Diffusion MRI with pulsed and free gradient waveforms: Effects of restricted diffusion and exchange

NMR in Biomedicine, Journal Year: 2022, Volume and Issue: 36(1)

Published: Sept. 8, 2022

Monitoring time dependence with diffusion MRI yields observables sensitive to compartment sizes (restricted diffusion) and membrane permeability (water exchange). However, restricted exchange have opposite effects on the diffusion-weighted signal, which can lead errors in parameter estimates. In this work, we propose a signal representation that incorporates of both up second order b-value is compatible gradient waveforms arbitrary shape. The features mappings from waveform two scalars separately control sensitivity restriction exchange. We demonstrate these span two-dimensional space be used choose selectively probe or exchange, eliminating correlation between phenomena. found specific but unconventional shapes provide an advantage over conventional pulsed oscillating acquisitions. also show parametrization into understand protocols other approaches For example, variation mixing filter-exchange imaging corresponds our exchange-weighting scalar at fixed value restriction-weighting scalar. proposed was evaluated using Monte Carlo simulations identical parallel cylinders hexagonal random packing as well gamma-distributed radii. Results showed approach interval 4-12 μm rates simulated range 0 20 s-1 , there extracellular geometry. presented theory constitutes simple intuitive description how influence guide protocol design capable separating effects.

Language: Английский

---

Diffusion MRI with free gradient waveforms on a high-performance gradient system: Probing restriction and exchange in the human brain

NeuroImage, Journal Year: 2023, Volume and Issue: 283, P. 120409 - 120409

Published: Oct. 13, 2023

The dependence of the diffusion MRI signal on time carries signatures restricted and exchange. Here we seek to highlight these in human brain by performing experiments using free gradient waveforms that are selectively sensitive two effects. We examine six healthy volunteers both strong ultra-strong gradients (80, 200 300 mT/m). In an experiment featuring a large set with different sensitivities exchange (150 samples), our results reveal unique time-dependence grey white matter, where former is characterised latter predominantly exhibits diffusion. Furthermore, show independently varying can be used map brain. consistently find matter at least twice as fast across all subjects strengths. shortest times observed this study were cerebellar cortex (115 ms). also assess feasibility future clinical applications method work, grey-white contrast obtained 25-minute mT/m protocol preserved 4-minute 10-minute 80 protocol. Our work underlines utility for detecting due vivo, which may potentially serve tool studying diseased tissue.

Language: Английский

---

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

Journal of Magnetic Resonance, Journal Year: 2024, Volume and Issue: 366, P. 107745 - 107745

Published: Aug. 6, 2024

Language: Английский

---

Low-field, high-gradient NMR shows diffusion contrast consistent with localization or motional averaging of water near surfaces

Magnetic Resonance Letters, Journal Year: 2023, Volume and Issue: 3(2), P. 90 - 107

Published: April 9, 2023

Nuclear magnetic resonance (NMR) measurements of water diffusion have been extensively used to probe microstructure in porous materials, such as biological tissue, however primarily using pulsed gradient spin echo (PGSE) methods. Low-field single-sided NMR systems built-in static gradients (SG) much stronger than typical PGSE maximum strengths, which allows for the signal attenuation at extremely high b-values be explored. Here, we perform SG (SGSE) and stimulated (SGSTE) on cells, tissues, gels. Measurements fixed live neonatal mouse spinal cord, lobster ventral nerve starved yeast cells all show multiexponential a scale b with significant fractions observed × D0 ≫ 1 400 ms/μm2. These persistent trend surface-to-volume ratios these systems, expected from media theory. An exception found case vs. cords was attributed faster exchange or permeability millisecond timescale. Data suggests existence multiple processes neural may relevant modeling time-dependent gray matter. The multi-exponential is protons not macromolecules because it remains proportional normalized when specimen washed D2O. that persists also drastically reduced after delipidation, indicating originates lipid membranes restrict diffusion. stretched exponential character appears mono-exponential viewed (b×D0)1/3, suggesting originate localization motional averaging near sub-micron length scales. To try disambiguate two contributions, curves were compared varying temperatures. While align normalizing them scale, they separate scale. This supports source non-Gaussian displacements, but this interpretation still provisional due possible confounds heterogeneity, exchange, relaxation. types gel phantoms designed mimic extracellular matrix, one charged functional groups synthesized polyacrylic acid (PAC) another uncharged polyacrylamide (PAM), both exhibit 1, potentially interacting macromolecules. preliminary finding motivate future research into contrast mechanisms tissue low-field, high-gradient NMR.

Language: Английский

---

Diffusion MRI with double diffusion encoding and variable mixing times disentangles water exchange from transient kurtosis

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 13, 2025

Abstract Double diffusion encoding (DDE) makes MRI sensitive to a wide range of microstructural features, and the acquired data can be analysed using different approaches. Correlation tensor imaging (CTI) uses DDE resolve three components diffusional kurtosis: isotropic, anisotropic, microscopic kurtosis. The kurtosis is estimated from contrast between single (SDE) parallel signals at same b-value. Another approach multi-Gaussian exchange (MGE), which employs measure exchange. Sensitivity obtained by contrasting SDE CTI MGE exploit signal quantify exchange, this study investigates interplay these two quantities. We perform Monte Carlo simulations in geometries with varying levels behaviour parameters MGE. conclude that rate intercompartmental transient individual compartments are distinct sources In an attempt disentangle sources, we propose heuristic representation referred as tMGE (MGE incorporating kurtosis) accounts for both effects exploiting signatures mixing time: causes slow dependence on time while arguably has much faster dependence. find applying multiple times orthogonal may enable estimation well

Language: Английский

---

Restriction-induced time-dependent transcytolemmal water exchange: Revisiting the Kӓrger exchange model

Journal of Magnetic Resonance, Journal Year: 2024, Volume and Issue: 367, P. 107760 - 107760

Published: Aug. 30, 2024

The Kӓrger model and its derivatives have been widely used to incorporate transcytolemmal water exchange rate, an essential characteristic of living cells, into analyses diffusion MRI (dMRI) signals from tissues. consists two homogeneous exchanging components coupled by rate constant assumes measurements are made with sufficiently long time slow exchange. Despite successful applications, it remains unclear whether these assumptions generally valid for practical dMRI sequences biological In particular, barrier-induced restrictions produce inhomogeneous magnetization distributions in relatively large-sized compartments such as cancer violating the above assumptions. effects this inhomogeneity usually overlooked. We performed computer simulations quantify how restriction effects, which images edge enhancements at compartment boundaries, influence different variants Kӓrger-model. results show that enhancement effect will larger, time-dependent estimates rates e.g., tumors large cell sizes (>10 μm), resulting overestimations previously reported. Moreover, stronger gradients, longer gradient durations, larger sizes, all cause more pronounced effects. This helps us better understand feasibility Kärger estimating tissue types provides useful guidance on signal acquisition methods may mitigate effect. work also indicates need correct overestimated obtained assuming Kärger-model.

Language: Английский

---

Diffusional kurtosis time dependence and the water exchange rate for the multi‐compartment Kärger model

Magnetic Resonance in Medicine, Journal Year: 2023, Volume and Issue: 91(3), P. 1122 - 1135

Published: Nov. 13, 2023

Abstract Purpose To demonstrate an analytic formula giving the time dependence of diffusional kurtosis for Kärger model (KM) with arbitrary number exchanging compartments and its application in estimating mean KM water exchange rate. Theory Methods The general is derived from a power series solution multi‐compartment KM. A lower bound on rate established observation that always logarithmically convex function time. Both are illustrated numerical calculations. also applied to previously published data both brain tumors. Results given by sum which each term associated eigenvector matrix. determined most negative value logarithmic derivative respect In cerebral cortex, found vary 15 76 s −1 , depending experimental details, while tumors considered, it varies 2 4 . Conclusion has simple allows be directly experiment. This may useful tissues complex microstructure difficult explicitly.

Language: Английский

---

Meningioma microstructure assessed by diffusion MRI: An investigation of the source of mean diffusivity and fractional anisotropy by quantitative histology

NeuroImage Clinical, Journal Year: 2023, Volume and Issue: 37, P. 103365 - 103365

Published: Jan. 1, 2023

Mean diffusivity (MD) and fractional anisotropy (FA) from diffusion MRI (dMRI) have been associated with cell density tissue across tumors, but it is unknown whether these associations persist at the microscopic level. To quantify degree to which anisotropy, as determined histology, account for intra-tumor variability of MD FA in meningioma tumors. Furthermore, clarify other histological features additional dMRI parameters. We performed ex-vivo 200 μm isotropic resolution imaging 16 excised tumor samples. Diffusion tensor (DTI) was used map FA, well in-plane (FAIP). Histology images were analyzed terms nuclei (CD) structure (SA; obtained analysis) separately a regression analysis predict FAIP, respectively. A convolutional neural network (CNN) also trained parameters histology patches. The association between out-of-sample (R2OS) on level within-sample R2 Regions where poorly predicted identify apart CD SA that could influence Cell assessed by explained mesoscopic (200 μm), median R2OS = 0.04 (interquartile range 0.01–0.26). Structure more variation FAIP (median 0.31, 0.20–0.42). Samples low exhibited variations throughout samples thus explainable variability, however, this not case MD. Across clearly (R2 0.60) 0.81), In 37% (6 out 16), did explain when compared CNN. Tumor vascularization, psammoma bodies, microcysts, cohesivity bias prediction based solely CD. Our results support high presence elongated aligned structures, otherwise. tumors does within tumor, means or values locally may always reflect density. Features beyond need be considered interpreting

Language: Английский

---