- NMR spectroscopy and applications
- Advanced Neuroimaging Techniques and Applications
- Advanced MRI Techniques and Applications
- Advanced NMR Techniques and Applications
- Electron Spin Resonance Studies
- Pluripotent Stem Cells Research
- Planarian Biology and Electrostimulation
- Electrochemical Analysis and Applications
- Microstructure and Mechanical Properties of Steels
- MRI in cancer diagnosis
- Ultrasound and Hyperthermia Applications
- Neural dynamics and brain function
- Radiation Therapy and Dosimetry
- Neuroscience and Neuropharmacology Research
- Photoacoustic and Ultrasonic Imaging
- Lipoproteins and Cardiovascular Health
- Neuroscience and Neural Engineering
- Lipid Membrane Structure and Behavior
- 3D Printing in Biomedical Research
- Electromagnetic Fields and Biological Effects
- Diffusion Coefficients in Liquids
- Caveolin-1 and cellular processes
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2019-2024
National Institutes of Health
2018-2024
Wellcome Centre for Integrative Neuroimaging
2020-2024
University of Oxford
2020-2024
Eunice Kennedy Shriver Center
2020
National Institute of Biomedical Imaging and Bioengineering
2018
Carnegie Mellon University
2018
We develop magnetic resonance (MR) methods for real-time measurement of tissue microstructure and membrane permeability live fixed excised neonatal mouse spinal cords. Diffusion exchange MR measurements are performed using the strong static gradient produced by a single-sided permanent magnet. Using delipidation methods, we show that water diffusion is restricted solely lipid membranes. Most signal can be assigned to in which far from The remaining 25% on length scales roughly micron or...
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...
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,...
Diffusion exchange spectroscopy (DEXSY) is a multidimensional NMR technique that can reveal how water molecules between compartments within heterogeneous media, such as biological tissue. Data from DEXSY experiments typically processed using numerical inverse Laplace transforms (ILTs) to produce diffusion-diffusion spectrum. A tacit assumption of this ILT approach the signal behavior Gaussian—i.e., spin echo intensity decays exponentially with degree diffusion weighting. The assumptions...
Contrary to prevailing views, recent work suggests that steady-state water exchange between the intra- and extracellular space is driven, in part, by active metabolic processes. To support these findings, we investigate whether exhibits multiexponential behavior consistent with distinct We find a bimodal distribution of times live neural tissue, only faster peak being reduced upon introduction sodium-potassium pump inhibitor, thus supporting existence exchange. Furthermore, describe...
Time-dependent diffusion behavior is probed over sub-millisecond timescales in a single shot using nuclear magnetic resonance static gradient time-incremented echo train acquisition (SG-TIETA) framework. The method extends the Carr-Purcell-Meiboom-Gill cycle under field by discretely incrementing π-pulse spacings to simultaneously avoid off-resonance effects and probe range of (50-500 µs). Pulse are optimized based on derived ruleset. remaining pulse inaccuracy examined found be consistent...
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...
Diffusion-weighted imaging (DWI) and intrinsic optical signal (IOS) are both used to measure neural tissue structure function. Here we demonstrate with simultaneous real-time low-field, high-gradient MR microscopy that DW signals IOS share a similar contrast mechanism, most likely the ratio between intracellular extracellular volume. Signals monitor how cells affected respond adverse conditions, providing novel insight into pathological mechanisms links
Motivation: To understand the mechanisms of water exchange. Goal(s): determine extent that DEXSY-based exchange measurements depend on changes to tissue microstructure (e.g., cellular swelling/shrinking). Approach: NMR ADC, rate and light microscopy intrinsic optical signal (IOS) are acquired simultaneously in real time viable dead ex vivo neural during potassium osmotic perturbations. Results: In samples, exchange, IOS similarly affected. however, some perturbations affect differently than...
Motivation: Exchange is an important effect in diffusion MR of the brain but remains difficult to quantify using conventional methods and signal models due parameter degeneracy. Goal(s): To develop demonstrate robust measurement exchange mouse brain. Approach: A method based on double encoding was previously developed probe isolated from other effects, yielding time measurements. We apply this vivo for first time. Results: report a fast approximately 38 ms as compared 146 fixed sample,...
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...
We develop magnetic resonance (MR) methods for measuring real-time changes of tissue microstructure and membrane permeability live fixed neural tissue. Diffusion exchange MR measurements are performed using the large static gradient produced by a single-sided permanent magnet. Using delipidation methods, we show that water diffusion is restricted solely lipid membranes. Most signal can be assigned to in which far from The remaining 25% on length scales roughly micron or less, near within...
Abstract Previous studies reported that alternating electric fields (EFs) in the intermediate frequency (100 – 300 kHz) and low intensity (1 3 V/cm) regime — termed “Tumor Treating Fields” (TTFields) have a specific, anti-proliferative effect on glioblastoma multiforme (GBM) cells. However, mechanism(s) of action remain(s) incompletely understood, hindering clinical adoption treatments based TTFields. To advance study such treatment vitro , we developed an inductive device to deliver EFs...
Currently, no MRI method exists to non-invasively and absolutely measure cellular activity. One approach is quantify steady-state transmembrane water exchange rates. Diffusion Exchange Spectroscopy (DEXSY) directly encodes for of endogenous components. Using DEXSY-based methods implemented on a low-field, high-gradient MR system, we show in viable ex vivo neonatal mouse spinal cord samples that the rate at which exchanges across cell membranes decreases drastically after perturbation known...
The diffusion MR signal in complex tissue such as gray matter exhibits non-Gaussian attenuation due to exchange and restrictions. Existing models typically ignore one or both effects by assuming Gaussian negligible exchange. We propose a more rigorous model that incorporates effects. Subsequently, an acquisition scheme utilizing equal double encodings ($$$b_1=b_2$$$) at various mixing times, single with the same total weighting $$$b=b_1+b_2$$$, is designed independently characterize of...
We propose a new functional MR method based on steady-state transmembrane water exchange rate measurements with diffusion spectroscopy (DEXSY). Rapid DEXSY methods are implemented low-field system strong static gradient to test for an active component of in ex vivo neonatal mouse spinal cords. Temperature-dependent Arrhenius activation energies significantly greater viable “live” samples than the same after fixation, suggesting connection ATP-driven enzymatic processes....
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 reliable method assess absolute basal activity or activity-dependent changes non-invasively. We propose a novel, high temporal resolution low-field, high-gradient diffusion exchange NMR capable directly measuring cellular metabolic via rate constant...