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The Neuroradiology Journal Aug 2016The effect of respiratory gating on the major diffusion-imaging metrics and that of cardiac gating on mean kurtosis (MK) are not known. For evaluation of whether the...
The effect of respiratory gating on the major diffusion-imaging metrics and that of cardiac gating on mean kurtosis (MK) are not known. For evaluation of whether the major diffusion-imaging metrics-MK, fractional anisotropy (FA), and mean diffusivity (MD) of the brain-varied between gated and non-gated acquisitions, respiratory-gated, cardiac-gated, and non-gated diffusion-imaging of the brain were performed in 10 healthy volunteers. MK, FA, and MD maps were constructed for all acquisitions, and the histograms were constructed. The normalized peak height and location of the histograms were compared among the acquisitions by use of Friedman and post hoc Wilcoxon tests. The effect of the repetition time (TR) on the diffusion-imaging metrics was also tested, and we corrected for its variation among acquisitions, if necessary. The results showed a shift in the peak location of the MK and MD histograms to the right with an increase in TR (p ≤ 0.01). The corrected peak location of the MK histograms, the normalized peak height of the FA histograms, the normalized peak height and the corrected peak location of the MD histograms varied significantly between the gated and non-gated acquisitions (p < 0.05). These results imply an influence of respiration and cardiac pulsation on the major diffusion-imaging metrics. The gating conditions must be kept identical if reproducible results are to be achieved.
Topics: Adult; Anisotropy; Brain; Cardiac-Gated Imaging Techniques; Diffusion; Diffusion Tensor Imaging; Female; Healthy Volunteers; Humans; Image Interpretation, Computer-Assisted; Male; Respiration; Young Adult
PubMed: 27073115
DOI: 10.1177/1971400916643337 -
NMR in Biomedicine Feb 2020Motion is a major confound in diffusion-weighted imaging (DWI) in the body, and it is a common cause of image artefacts. The effects are particularly severe in cardiac...
Motion is a major confound in diffusion-weighted imaging (DWI) in the body, and it is a common cause of image artefacts. The effects are particularly severe in cardiac applications, due to the nonrigid cyclical deformation of the myocardium. Spin echo-based DWI commonly employs gradient moment-nulling techniques to desensitise the acquisition to velocity and acceleration, ie, nulling gradient moments up to the 2nd order (M2-nulled). However, current M2-nulled DWI scans are limited to encode diffusion along a single direction at a time. We propose a method for designing b-tensors of arbitrary shapes, including planar, spherical, prolate and oblate tensors, while nulling gradient moments up to the 2nd order and beyond. The design strategy comprises initialising the diffusion encoding gradients in two encoding blocks about the refocusing pulse, followed by appropriate scaling and rotation, which further enables nulling undesired effects of concomitant gradients. Proof-of-concept assessment of in vivo mean diffusivity (MD) was performed using linear and spherical tensor encoding (LTE and STE, respectively) in the hearts of five healthy volunteers. The results of the M2-nulled STE showed that (a) the sequence was robust to cardiac motion, and (b) MD was higher than that acquired using standard M2-nulled LTE, where diffusion-weighting was applied in three orthogonal directions, which may be attributed to the presence of restricted diffusion and microscopic diffusion anisotropy. Provided adequate signal-to-noise ratio, STE could significantly shorten estimation of MD compared with the conventional LTE approach. Importantly, our theoretical analysis and the proposed gradient waveform design may be useful in microstructure imaging beyond diffusion tensor imaging where the effects of motion must be suppressed.
Topics: Animals; Diffusion; Diffusion Tensor Imaging; Heart; Humans; Motion; Phantoms, Imaging; Spin Labels; Swine
PubMed: 31765063
DOI: 10.1002/nbm.4213 -
Proceedings of the National Academy of... Oct 2022Remitted waves are used for sensing and imaging in diverse diffusive media from the Earth's crust to the human brain. Separating the source and detector increases the...
Remitted waves are used for sensing and imaging in diverse diffusive media from the Earth's crust to the human brain. Separating the source and detector increases the penetration depth of light, but the signal strength decreases rapidly, leading to a poor signal-to-noise ratio. Here, we show, experimentally and numerically, that wavefront shaping a laser beam incident on a diffusive sample enables an enhancement of remission by an order of magnitude at depths of up to 10 transport mean free paths. We develop a theoretical model which predicts the maximal remission enhancement. Our analysis reveals a significant improvement in the sensitivity of remitted waves to local changes of absorption deep inside diffusive media. This work illustrates the potential of coherent wavefront control for noninvasive diffuse wave imaging applications, such as diffuse optical tomography and functional near-infrared spectroscopy.
Topics: Brain; Diffusion; Humans; Signal-To-Noise Ratio
PubMed: 36191199
DOI: 10.1073/pnas.2207089119 -
Magnetic Resonance in Medicine Aug 2020We investigate the importance of high gradient-amplitude and high slew-rate on oscillating gradient spin echo (OGSE) diffusion imaging for human brain imaging and...
PURPOSE
We investigate the importance of high gradient-amplitude and high slew-rate on oscillating gradient spin echo (OGSE) diffusion imaging for human brain imaging and evaluate human brain imaging with OGSE on the MAGNUS head-gradient insert (200 mT/m amplitude and 500 T/m/s slew rate).
METHODS
Simulations with cosine-modulated and trapezoidal-cosine OGSE at various gradient amplitudes and slew rates were performed. Six healthy subjects were imaged with the MAGNUS gradient at 3T with OGSE at frequencies up to 100 Hz and b = 450 s/mm . Comparisons were made against standard pulsed gradient spin echo (PGSE) diffusion in vivo and in an isotropic diffusion phantom.
RESULTS
Simulations show that to achieve high frequency and b-value simultaneously for OGSE, high gradient amplitude, high slew rates, and high peripheral nerve stimulation limits are required. A strong linear trend for increased diffusivity (mean: 8-19%, radial: 9-27%, parallel: 8-15%) was observed in normal white matter with OGSE (20 Hz to 100 Hz) as compared to PGSE. Linear fitting to frequency provided excellent correlation, and using a short-range disorder model provided radial long-term diffusivities of D = 911 ± 72 µm /s, D = 1519 ± 164 µm /s, and D = 640 ± 111 µm /s and correlation lengths of l = 0.802 ± 0.156 µm, l = 0.837 ± 0.172 µm, and l = 0.780 ± 0.174 µm. Diffusivity changes with OGSE frequency were negligible in the phantom, as expected.
CONCLUSION
The high gradient amplitude, high slew rate, and high peripheral nerve stimulation thresholds of the MAGNUS head-gradient enables OGSE acquisition for in vivo human brain imaging.
Topics: Brain; Diffusion; Diffusion Magnetic Resonance Imaging; Humans; Neuroimaging; Phantoms, Imaging
PubMed: 32011027
DOI: 10.1002/mrm.28180 -
Journal of Dental Research Jul 2019The temporomandibular joint (TMJ) disc nutrient environment profoundly affects cell energy metabolism, proliferation, and biosynthesis. Due to technical challenges of in...
The temporomandibular joint (TMJ) disc nutrient environment profoundly affects cell energy metabolism, proliferation, and biosynthesis. Due to technical challenges of in vivo measurements, the human TMJ disc extracellular nutrient environment under load, which depends on metabolic rates, solute diffusion, and disc morphometry, remains unknown. Therefore, the study objective was to predict the TMJ disc nutrient environment under loading conditions using combined experimental and computational modeling approaches. Specifically, glucose consumption and lactate production rates of porcine TMJ discs were measured under varying tissue culture conditions ( = 40 discs), and mechanical strain-dependent glucose and lactate diffusivities were measured using a custom diffusion chamber ( = 6 discs). TMJ anatomy and loading area were obtained from magnetic resonance imaging of healthy human volunteers ( = 11, male, 30 ± 9 y). Using experimentally determined nutrient metabolic rates, solute diffusivities, TMJ anatomy, and loading areas, subject-specific finite element (FE) models were developed to predict the 3-dimensional nutrient profiles in unloaded and loaded TMJ discs (unloaded, 0% strain, 20% strain). From the FE models, glucose, lactate, and oxygen concentration ranges for unloaded healthy human TMJ discs were 0.6 to 4.0 mM, 0.9 to 5.0 mM, and 0% to 6%, respectively, with steep gradients in the anterior and posterior bands. Sustained mechanical loading significantly reduced nutrient levels ( < 0.001), with a critical zone in which cells may die representing approximately 13.5% of the total disc volume. In conclusion, this study experimentally determined TMJ disc metabolic rates, solute diffusivities, and disc morphometry, and through subject-specific FE modeling, revealed critical interactions between mechanical loading and nutrient supply and metabolism for the in vivo human TMJ disc. The results suggest that TMJ disc homeostasis may be vulnerable to pathological loading (e.g., clenching, bruxism), which impedes nutrient supply. Given difficulties associated with direct in vivo measurements, this study provides a new approach to systematically investigate homeostatic and degenerative mechanisms associated with the TMJ disc.
Topics: Adult; Animals; Biomechanical Phenomena; Diffusion; Energy Metabolism; Glucose; Humans; Lactic Acid; Male; Nutrients; Oxygen; Stress, Mechanical; Swine; Temporomandibular Joint Disc; Young Adult
PubMed: 31126205
DOI: 10.1177/0022034519851044 -
BMC Biology Sep 2021Knowledge on the localization and mobility of enzymes inside bacterial cells is scarce, but important for understanding spatial regulation of metabolism. The four...
BACKGROUND
Knowledge on the localization and mobility of enzymes inside bacterial cells is scarce, but important for understanding spatial regulation of metabolism. The four central enzymes (Rib enzymes) of the riboflavin (RF) biosynthesis pathway in the Gram positive model bacterium Bacillus subtilis have been studied extensively in vitro, especially the heavy RF synthase, a large protein complex with a capsid structure formed by RibH and an encapsulated RibE homotrimer, which mediates substrate-channeling. However, little is known about the behavior and mobility of these enzymes in vivo.
RESULTS
We have investigated the localization and diffusion of the Rib enzymes in the cytoplasm of B. subtilis. By characterizing the diffusion of Rib enzymes in live cells using single particle tracking (SPT) we provide evidence for confined diffusion at the cell poles and otherwise Brownian motion. A majority of RibH particles showed clear nucleoid occlusion and a high degree of confined motion, which is largely abolished after treatment with Rifampicin, revealing that confinement is dependent on active transcription. Contrarily, RibE is mostly diffusive within the cell, showing only 14% encapsulation by RibH nanocompartments. By localizing different diffusive populations within single cells, we find that fast diffusion occurs mostly across the nucleoids located in the cell centers, while the slower, confined subdiffusion occurs at the crowded cell poles.
CONCLUSIONS
Our results provide evidence for locally different motion of active enzymes within the bacterial cytoplasm, setting up metabolic compartmentalization mostly at the poles of cells.
Topics: Bacillus subtilis; Cytoplasm; Diffusion; Intracellular Space; Riboflavin
PubMed: 34474681
DOI: 10.1186/s12915-021-01083-4 -
Proceedings of the National Academy of... Aug 2022Some dividing cells sense their shape by becoming polarized along their long axis. Cell polarity is controlled in part by polarity proteins, like Rho GTPases, cycling...
Some dividing cells sense their shape by becoming polarized along their long axis. Cell polarity is controlled in part by polarity proteins, like Rho GTPases, cycling between active membrane-bound forms and inactive cytosolic forms, modeled as a "wave-pinning" reaction-diffusion process. Does shape sensing emerge from wave pinning? We show that wave pinning senses the cell's long axis. Simulating wave pinning on a curved surface, we find that high-activity domains migrate to peaks and troughs of the surface. For smooth surfaces, a simple rule of minimizing the domain perimeter while keeping its area fixed predicts the final position of the domain and its shape. However, when we introduce roughness to our surfaces, shape sensing can be disrupted, and high-activity domains can become localized to locations other than the global peaks and valleys of the surface. On rough surfaces, the domains of the wave-pinning model are more robust in finding the peaks and troughs than the minimization rule, although both can become trapped in steady states away from the peaks and valleys. We can control the robustness of shape sensing by altering the Rho GTPase diffusivity and the domain size. We also find that the shape-sensing properties of cell polarity models can explain how domains localize to curved regions of deformed cells. Our results help to understand the factors that allow cells to sense their shape-and the limits that membrane roughness can place on this process.
Topics: Cell Polarity; Cell Shape; Diffusion; Models, Biological; rho GTP-Binding Proteins
PubMed: 35905323
DOI: 10.1073/pnas.2121302119 -
Journal of Mathematical Biology May 2023A stochastic hierarchical model for the evolution of low grade gliomas is proposed. Starting with the description of cell motion using a piecewise diffusion Markov...
A stochastic hierarchical model for the evolution of low grade gliomas is proposed. Starting with the description of cell motion using a piecewise diffusion Markov process (PDifMP) at the cellular level, we derive an equation for the density of the transition probability of this Markov process based on the generalised Fokker-Planck equation. Then, a macroscopic model is derived via parabolic limit and Hilbert expansions in the moment equations. After setting up the model, we perform several numerical tests to study the role of the local characteristics and the extended generator of the PDifMP in the process of tumour progression. The main aim focuses on understanding how the variations of the jump rate function of this process at the microscopic scale and the diffusion coefficient at the macroscopic scale are related to the diffusive behaviour of the glioma cells and to the onset of malignancy, i.e., the transition from low-grade to high-grade gliomas.
Topics: Humans; Stochastic Processes; Markov Chains; Probability; Diffusion; Glioma
PubMed: 37147527
DOI: 10.1007/s00285-023-01909-5 -
Proceedings of the National Academy of... Nov 2018Using a microscopic theory to analyze experiments, we demonstrate that enzymes are active matter. Superresolution fluorescence measurements-performed across four orders...
Using a microscopic theory to analyze experiments, we demonstrate that enzymes are active matter. Superresolution fluorescence measurements-performed across four orders of magnitude of substrate concentration, with emphasis on the biologically relevant regime around or below the Michaelis-Menten constant-show that catalysis boosts the motion of enzymes to be superdiffusive for a few microseconds, enhancing their effective diffusivity over longer timescales. Occurring at the catalytic turnover rate, these fast ballistic leaps maintain direction over a duration limited by rotational diffusion, driving enzymes to execute wormlike trajectories by piconewton forces performing work of a few against viscosity. The boosts are more frequent at high substrate concentrations, biasing the trajectories toward substrate-poor regions, thus exhibiting antichemotaxis, demonstrated here experimentally over a wide range of aqueous concentrations. Alternative noncatalytic, passive mechanisms that predict chemotaxis, cross-diffusion, and phoresis, are critically analyzed. We examine the physical interpretation of our findings, speculate on the underlying mechanism, and discuss the avenues they open with biological and technological implications. These findings violate the classical paradigm that chemical reaction and motility are distinct processes, and suggest reaction-motion coupling as a general principle of catalysis.
Topics: Biocatalysis; Catalysis; Chemotaxis; Diffusion; Enzymes; Hydrodynamics; Kinetics
PubMed: 30385635
DOI: 10.1073/pnas.1814180115 -
Biophysical Journal Oct 2022Fluorescence recovery after photobleaching (FRAP) is a widely used biological experiment to study the kinetics of molecules that react and move randomly. Since the...
Fluorescence recovery after photobleaching (FRAP) is a widely used biological experiment to study the kinetics of molecules that react and move randomly. Since the development of FRAP in the 1970s, many reaction-diffusion models have been used to interpret FRAP data. However, intracellular molecules are widely observed to move by anomalous subdiffusion instead of normal diffusion. In this article, we extend a popular reaction-diffusion model of FRAP to the case of subdiffusion modeled by a fractional diffusion equation. By analyzing this reaction-subdiffusion model, we show that FRAP data are consistent with both diffusive and subdiffusive motion in many scenarios. We illustrate this general result by fitting our model to FRAP data from glucocorticoid receptors in a cell nucleus. We further show that the assumed model of molecular motion (normal diffusion or subdiffusion) strongly impacts the biological parameter values inferred from a given experimentally observed FRAP curve. We additionally analyze our model in three simplified parameter regimes and discuss parameter identifiability for varying subdiffusion exponents.
Topics: Fluorescence Recovery After Photobleaching; Receptors, Glucocorticoid; Diffusion; Kinetics; Motion
PubMed: 36127879
DOI: 10.1016/j.bpj.2022.09.015