Impact of turbulence-induced asymmetric propagators on the accuracy of phase-contrast velocimetry

Phase-contrast magnetic resonance velocimetry (PC-MRI) has been widely used to investigate flow properties in numerous systems. In a horizontal cylindrical pipe (3mm diameter), we investigated the accuracy of PC-MRI as the flow transitioned from laminar to turbulent flow (Reynolds number 352 to 2708). We focus primarily on velocimetry errors introduced by skewed intra-voxel displacement distributions, a consequence of PC-MRI theory assuming symmetric distributions. We demonstrated how rapid fluctuations in the velocity field, can produce broad asymmetric intravoxel displacement distributions near the wall. Depending on the shape of the distribution, this resulted in PC-MRI measurements under-estimating (positive skewness) or over-estimating (negative skewness) the true mean intravoxel velocity, which could have particular importance to clinical wall shear stress measurements. The magnitude of these velocity errors was shown to increase with the variance and decrease with the kurtosis of the intravoxel displacement distribution. These experimental results confirm our previous theoretical analysis, which gives a relationship for PC-MRI velocimetry errors, as a function of the higher moments of the intravoxel displacement distribution (skewness, variance, and kurtosis) and the experimental parameters q and Δ. This suggests that PC-MRI errors in such unsteady/turbulent flow conditions can potentially be reduced by employing lower q values or shorter observation times Δ

Quantitative histopathologic assessment of perfusion MRI as a marker of glioblastoma cell infiltration in and beyond the peritumoral edema region

Background: Conventional MRI fails to detect regions of glioblastoma cell infiltration beyond the contrast‐enhanced T1 solid tumor region, with infiltrating tumor cells often migrating along host blood vessels. Purpose: To quantitatively and qualitatively analyze the correlation between perfusion MRI signal and tumor cell density in order to assess whether local perfusion perturbation could provide a useful biomarker of glioblastoma cell infiltration. Study Type: Animal model. Subjects: Mice bearing orthotopic glioblastoma xenografts generated from a patient‐derived glioblastoma cell line. Field Strength/Sequences: 7T perfusion images acquired using a high signal‐to‐noise ratio (SNR) multiple boli arterial spin labeling sequence were compared with conventional MRI (T1/T2 weighted, contrast‐enhanced T1, diffusion‐weighted, and apparent diffusion coefficient). Assessment: Immunohistochemistry sections were stained for human leukocyte antigen (probing human‐derived tumor cells). To achieve quantitative MRI‐tissue comparison, multiple histological slices cut in the MRI plane were stacked to produce tumor cell density maps acting as a “ground truth.” Statistical Tests: Sensitivity, specificity, accuracy, and Dice similarity indices were calculated and a two‐tailed, paired t‐test used for statistical analysis. Results: High comparison test results (Dice 0.62–0.72, Accuracy 0.86–0.88, Sensitivity 0.51–0.7, and Specificity 0.92–0.97) indicate a good segmentation for all imaging modalities and highlight the quality of the MRI tissue assessment protocol. Perfusion imaging exhibits higher sensitivity (0.7) than conventional MRI (0.51–0.61). MRI/histology voxel‐to‐voxel comparison revealed a negative correlation between tumor cell infiltration and perfusion at the tumor margins (P = 0.0004). Data Conclusion: These results demonstrate the ability of perfusion imaging to probe regions of low tumor cell infiltration while confirming the sensitivity limitations of conventional imaging modalities. The quantitative relationship between tumor cell density and perfusion identified in and beyond the edematous T2 hyperintensity region surrounding macroscopic tumor could be used to detect marginal tumor cell infiltration with greater accuracy

Accuracy of phase-contrast velocimetry in systems with skewed intravoxel velocity distributions

Phase contrast velocimetry (PCV) has been widely used to investigate flow properties in numerous systems. Several authors have reported errors in velocity measurements and have speculated on the sources, which have ranged from eddy current effects to acceleration artefacts. An often overlooked assumption in the theory of PCV, which may not be met in complex or unsteady flows, is that the intravoxel displacement distributions (propagators) are symmetric. Here, the effect of the higher moments of the displacement distribution (variance, skewness and kurtosis) on the accuracy of PCV is investigated experimentally and theoretically. Phase and propagator measurements are performed on tailored intravoxel distributions, achieved using a simple phantom combined with a single large voxel. Asymmetric distributions (Skewness ≠ 0) are shown to generate important phase measurement errors that lead to significant velocimetry errors. Simulations of the phase of the spin vector sum, based on experimentally measured propagators, are shown to quantitatively reproduce the relationship between measured phase and experimental parameters. These allow relating the observed velocimetry errors to a discrepancy between the average phase of intravoxel spins considered in PCV theory and the vector phase actually measured by a PFG experiment. A theoretical expression is derived for PCV velocimetry errors as a function of the moments of the displacement distribution. Positively skewed distributions result in an underestimation of the true mean velocity, while negatively skewed distributions result in an overestimation. The magnitude of these errors is shown to increase with the variance and decrease with the kurtosis of the intravoxel displacement distribution

The effect of displacement distribution asymmetry on the accuracy of phase-shift velocimetry in porous media

Phase-shift velocimetry provided by pulsed magnetic field gradient experiments is the fastest magnetic resonance technique for measuring velocity. However, critical issues have been reported when studying flow through porous media. These lead to inaccurate velocimetry results, with no clear explanation emerging. In this work we investigate the effect of asymmetries in the distribution of intra-voxel displacements on the accuracy of phase-shift velocimetry. This is particularly relevant to flow through porous media, where the presence of stagnant pores or differential flow is known to result in asymmetric displacement distributions. Here, tailored intra-voxel distributions are achieved using a simple phantom combined with a single large voxel. Combining experimental results with simulations, we demonstrate that the presence of asymmetries in the intra-voxel displacement distributions, common in studies of porous materials, can lead to important velocimetry errors

A novel small molecule inhibitor of MRCK prevents radiation-driven invasion in glioblastoma

Glioblastoma (GBM) is an aggressive and incurable primary brain tumor that causes severe neurological, cognitive, and psychological symptoms. Symptoms are caused and exacerbated by the infiltrative properties of GBM cells, which enable them to pervade the healthy brain and disrupt normal function. Recent research has indicated that, while radiotherapy (RT) remains the most effective component of multimodality therapy for GBM patients, it can provoke a more infiltrative phenotype in GBM cells that survive treatment. Here we demonstrate an essential role of the actin-myosin regulatory kinase myotonic dystrophy kinase-related CDC42- binding kinase (MRCK) in mediating the pro-invasive effects of radiation. MRCK-mediated invasion occurred via downstream signaling to effector molecules MYPT1 and MLC2. MRCK was activated by clinically relevant doses per fraction of radiation, and this activation was concomitant with an increase in GBM cell motility and invasion. Furthermore, ablation of MRCK activity either by RNAi or by inhibition with the novel small molecule inhibitor BDP-9066 prevented radiation-driven increases in motility both in vitro and in a clinically relevant orthotopic xenograft model of GBM. Crucially, treatment with BDP-9066 in combination with RT significantly increased survival in this model and markedly reduced infiltration of the contralateral cerebral hemisphere

Adaptive Manufacturing for Healthcare During the COVID-19 Emergency and Beyond

During the COVID-19 pandemic, global health services have faced unprecedented demands. Many key workers in health and social care have experienced crippling shortages of personal protective equipment, and clinical engineers in hospitals have been severely stretched due to insufficient supplies of medical devices and equipment. Many engineers who normally work in other sectors have been redeployed to address the crisis, and they have rapidly improvised solutions to some of the challenges that emerged, using a combination of low-tech and cutting-edge methods. Much publicity has been given to efforts to design new ventilator systems and the production of 3D-printed face shields, but many other devices and systems have been developed or explored. This paper presents a description of efforts to reverse engineer or redesign critical parts, specifically a manifold for an anaesthesia station, a leak port, plasticware for COVID-19 testing, and a syringe pump lock box. The insights obtained from these projects were used to develop a product lifecycle management system based on Aras Innovator, which could with further work be deployed to facilitate future rapid response manufacturing of bespoke hardware for healthcare. The lessons learned could inform plans to exploit distributed manufacturing to secure back-up supply chains for future emergency situations. If applied generally, the concept of distributed manufacturing could give rise to “21st century cottage industries” or “nanofactories,” where high-tech goods are produced locally in small batches

Accurate phase-shift velocimetry in rock

AbstractSpatially resolved Pulsed Field Gradient (PFG) velocimetry techniques can provide precious information concerning flow through opaque systems, including rocks. This velocimetry data is used to enhance flow models in a wide range of systems, from oil behaviour in reservoir rocks to contaminant transport in aquifers. Phase-shift velocimetry is the fastest way to produce velocity maps but critical issues have been reported when studying flow through rocks and porous media, leading to inaccurate results. Combining PFG measurements for flow through Bentheimer sandstone with simulations, we demonstrate that asymmetries in the molecular displacement distributions within each voxel are the main source of phase-shift velocimetry errors. We show that when flow-related average molecular displacements are negligible compared to self-diffusion ones, symmetric displacement distributions can be obtained while phase measurement noise is minimised. We elaborate a complete method for the production of accurate phase-shift velocimetry maps in rocks and low porosity media and demonstrate its validity for a range of flow rates. This development of accurate phase-shift velocimetry now enables more rapid and accurate velocity analysis, potentially helping to inform both industrial applications and theoretical models

Magnetic resonance studies of transport and reaction in vortical flow

This thesis explores the coupling of autocatalytic reactions, such as the oscillating Belousov- Zhabotinsky reaction, with vortical flows produced in a Couette cell. Similarly to many Reaction-Diffusion-Advection (RDA) systems found in nature, the resulting systems are characterised by chemical cycles maintained out of equilibrium by transport processes involving complex flow properties, such as periodicity and vorticity. In this project, an integrated approach was developed, combining optical and magnetic resonance techniques with modelling, to study transport and reaction in vortical flows. Flow structure and molecular displacements within stationary and translating vortices were investigated using a combination of magnetic resonance (MR) velocity and diffusion mapping with MR propagator experiments. A model based on MR experimental data was developed to simulate molecular displacements and provide quantitative information on micro-mixing and long time-scale axial dispersion. Simulations of molecular displacements allow linkage of molecular transport with the propagation of chemical waves travelling through vortical flows. The macroscopic patterns arising from these RDA systems, in combination with modelling results, allowed understanding coupling mechanisms between flow and chemistry and characterising inter- and intra- vortex mixing. Finally, MR imaging of chemical waves was shown to compare well with molecular displacement simulations, providing with a means for characterising the interplay of flow and chemistry in reactive flow systems

Multiple boli arterial spin labelling for high signal-to-noise rodent brain perfusion imaging

Purpose: A systematic method is proposed for optimizing a promising preclinical arterial spin labeling (ASL) sequence based on the use of a train of adiabatic radiofrequency pulses labeling successive boli of blood water. Methods: The sequence optimization is performed and evaluated using brain imaging experiments in mice and in rats. It involves the investigation of several parameters, ranging from the number of adiabatic pulses and labeling duration to the properties of the adiabatic hyperbolic secant pulses (ie, amplitude and frequency modulation). Results: Species-dependent parameters are identified, allowing for robust fast optimization protocols to be introduced. The resulting optimized multiple boli ASL (mbASL) sequence provides with significantly higher average signal-to-noise ratios (SNR) per voxel volume than currently encountered in ASL studies (278 mm−3 in mice and 172 mm−3 in rats). Comparing with the commonly used flow-sensitive alternating inversion recovery technique (FAIR), mbASL-to-FAIR SNR ratios reach 203% for mice and 725% for rats. Conclusion: When properly optimized, mbASL can offer a robust, high SNR ASL alternative for rodent brain perfusion studies