A combined approach of Computational Fluid Dynamic (CFD) and flow Magnetic Resonance Imaging (flo... more A combined approach of Computational Fluid Dynamic (CFD) and flow Magnetic Resonance Imaging (flow MRI) is used for a highly accurate study of flow phenomena within textiles. Preliminary simulations and experimental data demonstrate the potential of these synergistic techniques. Three-dimensional MRI techniques measure binary pixel intensities in a 3D Cartesian coordinate system. Transformation of these data measured for woven textiles in a CFD compatible computer aided design (CAD) format is feasible, however in many instances the spatial resolution of the MRI technique may not be sufficient to provide data to be used in highly accurate CFD simulations. A flow cell with conditions optimized for both techniques is in development and initial studies of (i) a phantom sample and (ii) simple woven fabrics are under preparation.
The use of virtual prototypes for the prediction of relevant flow related parameters is well esta... more The use of virtual prototypes for the prediction of relevant flow related parameters is well established in many industries such as the automotive industry. For the development of technical textiles an analogous approach is anticipated as being beneficial. However, so far the complex geometry of textiles consisting of a very large number of filaments has impeded this approach. We utilize this approach for the first time investigating a fabric, which is used during the paper forming process. The most challenging aspect for the simulation is the the process of geometry creation by use of single filaments together with the indispensable simplifications for a currently marketed fabric. Meshes of different sizes up 20 million cells have been generated and results from CFD calculations will be displayed together with an analysis of the numerical accuracy. The individual relevance of the simulation experiments will be discussed. Physical experiments at ambient temperature of laminar water flow through the same fabric under comparable conditions with a Reynolds Number of 15 based on pipe diameter of 9.0 mm and pipe volume flow rate averaged velocity magnitude of 0.00172 m/s were performed. The Reynolds Number based on the diameter of the different filaments of 0.2 mm up to 0.45 mm is approx. between 0.34 and 0.77. The experimental set up using Magnetic Resonance Imaging (MRI) will be explained. The use of this experimental approach as a means to validate the results of the simulation will be critically evaluated.
A synergistic approach using techniques of Computational Fluid Dynamics (CFD) and Nuclear Magneti... more A synergistic approach using techniques of Computational Fluid Dynamics (CFD) and Nuclear Magnetic Resonance Imaging (MRI) is used to study textile-relevant flow phenomena on a microscopic scale. Technical textiles as used in paper producing machinery have been studied using both CFD and MRI. So far the combined approach using both methods provides a consistent picture regarding the pathway of fluid flow through these textiles. Further studies are concerned with the spontaneous imbibition of fluids in textiles (wicking), which is largely influenced by the textile micro-structure. A setup has been developed to observe the spatial and temporal fluid distribution during a wicking process by means of Magnetic Resonance Imaging. GOALS
PROJECT GOALS: To understand and quantify moisture transport in textile structures so that novel/... more PROJECT GOALS: To understand and quantify moisture transport in textile structures so that novel/improved materials for fluid management and novel/improved drying processes may be developed. Magnetic resonance imaging (MRI) and other techniques are being used to investigate moisture transport in textiles. MRI revealed that moisture distribution in carpet is significantly influenced by the vacuum extraction procedure. Industrially relevant through-flow drying of carpet has been simulated on a laboratory through-flow dryer (LTFD) as well as inside a MRI scanner. The effects of the moisture distribution and the air flow direction on through-flow drying of unbacked tufted carpet are being studied. Methods to achieve faster drying via increased carpet air permeability are being developed. Based on experimental results obtained using LTFD, the potential to improve drying in constant rate and falling rate drying periods is being explored. Anisotropic wicking of fabrics is being studied. Tw...
Carbon molecular sieve (CMS) membranes have impressive separation properties; however, both chemi... more Carbon molecular sieve (CMS) membranes have impressive separation properties; however, both chemical and morphology structures need to be understood better. Here we characterize CMS with the simplest polyimide (PI) PMDA/pPDA (PMDA=Pyromellitic Dianhydride, pPDA= p -Phenylenediamine), using FTIR, solid state 15 N-NMR, 13 C-NMR, XPS, XRD, and Raman spectra to study chemical structure. We also compare gas separation properties for this CMS to a CMS derived from a more conventional polyimide precursor. The detailed characterization shows the presence of aromatic pyridinic, pyrrolic rings as well as graphitic, pyridonic components and a few other groups in both CMS types derived from the very different precursors. The CMS morphologies, while related to precursor and pyrolysis temperature details, show similarities consistent with a physical picture comprising distributed molecular sieving plate-like structures. These results assist in understanding diverse CMS membrane separation performance.
To examine multi‐component relaxation modelling for quantification of on‐ and off‐resonance relax... more To examine multi‐component relaxation modelling for quantification of on‐ and off‐resonance relaxation signals in multi‐echo ultra‐short echo time (UTE) data of human Achilles tendon (AT) and compare bias and dispersion errors of model parameters to that of the bi‐component model.
Effective drug delivery in brain tumors remains a major challenge in oncology. Although local hyp... more Effective drug delivery in brain tumors remains a major challenge in oncology. Although local hyperthermia and stimuli-responsive delivery systems, such as thermosensitive liposomes, represent promising strategies to locally enhance drug delivery in solid tumors and improve outcomes, their application in intracranial malignancies remains unexplored. We hypothesized that the combined abilities of closed-loop trans-skull Magnetic Resonance Imaging guided Focused Ultrasound (MRgFUS) hyperthermia with those of thermosensitive drugs can alleviate challenges in drug delivery and improve survival in gliomas. Methods: To conduct our investigations, we first designed a closed loop MR-guided Focused Ultrasound (MRgFUS) system for localized trans-skull hyperthermia (ΔT < 0.5 °C) in rodents and established safety thresholds in healthy mice. To assess the abilities of the developed system and proposed therapeutic strategy for FUS-triggered chemotherapy release we employed thermosensitive liposomal Dox (TSL-Dox) and tested it in two different glioma tumor models (F98 in rats and GL261 in mice). To quantify Dox delivery and changes in the transvascular transport dynamics in the tumor microenvironment we combined fluorescent microscopy, dynamic contrast enhanced MRI (DCE-MRI), and physiologically based pharmacokinetic (PBPK) modeling. Lastly, to assess the therapeutic efficacy of the system and of the proposed therapeutic strategy we performed a survival study in the GL261 glioma bearing mice. Results: The developed closed-loop trans-skull MRgFUS-hyperthermia system that operated at 1.7 MHz, a frequency that maximized the brain (FUS-focus) to skull temperature ratio in mice, was able to attain and maintain the desired focal temperature within a narrow range. Histological evidence (H&E and Nissl) suggests that focal temperature at 41.5 ± 0.5 °C for 10 min is below the threshold for tissue damage. Quantitative analysis of doxorubicin delivery from TSLs with MRgFUS-hyperthermia demonstrated 3.5-fold improvement in cellular uptake in GL261 glioma mouse tumors (p < 0.001) and 5-fold increase in delivery in F98 glioma rat tumors (p < 0.05), as compared to controls (TSL-Dox-only). Moreover, PBPK modeling of drug transport that was calibrated using the experimental data indicated that thermal stress could lead to significant improvement in the transvascular transport (2.3-fold increase in the vessel diffusion coefficient; P < 0.001), in addition to promoting targeted Dox release. Prospective experimental investigations with DCE-MRI during FUS-hyperthermia, supported these findings and provided evidence that moderate thermal stress (≈41 °C for up to 10 min) can promote acute changes in the vascular transport dynamics in the brain tumor microenvironment (Ktrans value for control vs. FUS was 0.0097 and 0.0148 min-1, respectively; p = 0.026). Crucially, survival analysis demonstrated significant improvement in the survival in the TSL-Dox-FUS group as compared to TSL-Dox-only group (p < 0.05), providing supporting evidence on the therapeutic potential of the proposed strategy. Conclusions: Our investigations demonstrated that spatially controlled thermal stress can be attained and sustained in the mouse brain, using a trans-skull closed-loop MRgFUS system, and used to promote the effective delivery of chemotherapy in gliomas from thermosensitive drugs. This system also allowed us to conduct mechanistic investigations that resulted in the refinement of our understanding on the role of thermal stress in augmenting mass and drug transport in brain tumors. Overall, our study established a new paradigm for effective drug delivery in brain tumors based on closed-loop ultrasound-mediated thermal stress and thermosensitive drugs.
Here we report that a covalent organic framework (COF), which contains 2,5-di(imine)-substituted ... more Here we report that a covalent organic framework (COF), which contains 2,5-di(imine)-substituted 1,4-dihydroxybenzene (diiminol) moieties, undergoes color changes in the presence of solvents or solvent vapor that are rapid, passive, reversible, and easily detectable by the naked eye. A new visible absorption band appears in the presence of polar solvents, especially water, suggesting reversible conversion to another species. This reversibility is attributed to the ability of the diiminol to rapidly tautomerize to an iminol/cis-ketoenamine and its inability to doubly tautomerize to a diketoenamine. Density functional theory (DFT) calculations suggest similar energies for the two tautomers in the presence of water, but the diiminol is much more stable in its absence. Time-dependent DFT calculations confirm that the iminol/cis-ketoenamine absorbs at longer wavelength than the diiminol and indicate that this absorption has significant charge-transfer character. A colorimetric humidity sensing device constructed from an oriented thin film of the COF responded quickly to water vapor and was stable for months. These results suggest that tautomerization-induced electronic structure changes can be exploited in COF platforms to give rapid, reversible sensing in systems that exhibit long-term stability.
This paper introduces two experimental studies of capillary impregnation across fiber tows. The f... more This paper introduces two experimental studies of capillary impregnation across fiber tows. The first experimental technique embeds four to five flow detection sensors into a fiber tow at radial locations from the outside to the center of the tow to track the motion of fluid from outside to the center of the tow with time. The second technique based on Magnetic Resonance Imaging (MRI) is a non-intrusive tracking of the flow front as it impregnates the fiber tow. The techniques are compared and contrasted to identify their advantages and limitations. An analytical model that ignores the backpressure of the entrapped air grossly under predicts the saturation time for the tow as compared with the experiments. In order to explain this discrepancy, we include the effect of entrapped air in the analytic model, which slows down the capillary flow. However, other effects such as non-uniform fiber volume fraction within the tow and the ease with which the entrapped air can escape from the to...
A combined approach of Computational Fluid Dynamic (CFD) and flow Magnetic Resonance Imaging (flo... more A combined approach of Computational Fluid Dynamic (CFD) and flow Magnetic Resonance Imaging (flow MRI) is used for a highly accurate study of flow phenomena within textiles. Preliminary simulations and experimental data demonstrate the potential of these synergistic techniques. Three-dimensional MRI techniques measure binary pixel intensities in a 3D Cartesian coordinate system. Transformation of these data measured for woven textiles in a CFD compatible computer aided design (CAD) format is feasible, however in many instances the spatial resolution of the MRI technique may not be sufficient to provide data to be used in highly accurate CFD simulations. A flow cell with conditions optimized for both techniques is in development and initial studies of (i) a phantom sample and (ii) simple woven fabrics are under preparation.
The use of virtual prototypes for the prediction of relevant flow related parameters is well esta... more The use of virtual prototypes for the prediction of relevant flow related parameters is well established in many industries such as the automotive industry. For the development of technical textiles an analogous approach is anticipated as being beneficial. However, so far the complex geometry of textiles consisting of a very large number of filaments has impeded this approach. We utilize this approach for the first time investigating a fabric, which is used during the paper forming process. The most challenging aspect for the simulation is the the process of geometry creation by use of single filaments together with the indispensable simplifications for a currently marketed fabric. Meshes of different sizes up 20 million cells have been generated and results from CFD calculations will be displayed together with an analysis of the numerical accuracy. The individual relevance of the simulation experiments will be discussed. Physical experiments at ambient temperature of laminar water flow through the same fabric under comparable conditions with a Reynolds Number of 15 based on pipe diameter of 9.0 mm and pipe volume flow rate averaged velocity magnitude of 0.00172 m/s were performed. The Reynolds Number based on the diameter of the different filaments of 0.2 mm up to 0.45 mm is approx. between 0.34 and 0.77. The experimental set up using Magnetic Resonance Imaging (MRI) will be explained. The use of this experimental approach as a means to validate the results of the simulation will be critically evaluated.
A synergistic approach using techniques of Computational Fluid Dynamics (CFD) and Nuclear Magneti... more A synergistic approach using techniques of Computational Fluid Dynamics (CFD) and Nuclear Magnetic Resonance Imaging (MRI) is used to study textile-relevant flow phenomena on a microscopic scale. Technical textiles as used in paper producing machinery have been studied using both CFD and MRI. So far the combined approach using both methods provides a consistent picture regarding the pathway of fluid flow through these textiles. Further studies are concerned with the spontaneous imbibition of fluids in textiles (wicking), which is largely influenced by the textile micro-structure. A setup has been developed to observe the spatial and temporal fluid distribution during a wicking process by means of Magnetic Resonance Imaging. GOALS
PROJECT GOALS: To understand and quantify moisture transport in textile structures so that novel/... more PROJECT GOALS: To understand and quantify moisture transport in textile structures so that novel/improved materials for fluid management and novel/improved drying processes may be developed. Magnetic resonance imaging (MRI) and other techniques are being used to investigate moisture transport in textiles. MRI revealed that moisture distribution in carpet is significantly influenced by the vacuum extraction procedure. Industrially relevant through-flow drying of carpet has been simulated on a laboratory through-flow dryer (LTFD) as well as inside a MRI scanner. The effects of the moisture distribution and the air flow direction on through-flow drying of unbacked tufted carpet are being studied. Methods to achieve faster drying via increased carpet air permeability are being developed. Based on experimental results obtained using LTFD, the potential to improve drying in constant rate and falling rate drying periods is being explored. Anisotropic wicking of fabrics is being studied. Tw...
Carbon molecular sieve (CMS) membranes have impressive separation properties; however, both chemi... more Carbon molecular sieve (CMS) membranes have impressive separation properties; however, both chemical and morphology structures need to be understood better. Here we characterize CMS with the simplest polyimide (PI) PMDA/pPDA (PMDA=Pyromellitic Dianhydride, pPDA= p -Phenylenediamine), using FTIR, solid state 15 N-NMR, 13 C-NMR, XPS, XRD, and Raman spectra to study chemical structure. We also compare gas separation properties for this CMS to a CMS derived from a more conventional polyimide precursor. The detailed characterization shows the presence of aromatic pyridinic, pyrrolic rings as well as graphitic, pyridonic components and a few other groups in both CMS types derived from the very different precursors. The CMS morphologies, while related to precursor and pyrolysis temperature details, show similarities consistent with a physical picture comprising distributed molecular sieving plate-like structures. These results assist in understanding diverse CMS membrane separation performance.
To examine multi‐component relaxation modelling for quantification of on‐ and off‐resonance relax... more To examine multi‐component relaxation modelling for quantification of on‐ and off‐resonance relaxation signals in multi‐echo ultra‐short echo time (UTE) data of human Achilles tendon (AT) and compare bias and dispersion errors of model parameters to that of the bi‐component model.
Effective drug delivery in brain tumors remains a major challenge in oncology. Although local hyp... more Effective drug delivery in brain tumors remains a major challenge in oncology. Although local hyperthermia and stimuli-responsive delivery systems, such as thermosensitive liposomes, represent promising strategies to locally enhance drug delivery in solid tumors and improve outcomes, their application in intracranial malignancies remains unexplored. We hypothesized that the combined abilities of closed-loop trans-skull Magnetic Resonance Imaging guided Focused Ultrasound (MRgFUS) hyperthermia with those of thermosensitive drugs can alleviate challenges in drug delivery and improve survival in gliomas. Methods: To conduct our investigations, we first designed a closed loop MR-guided Focused Ultrasound (MRgFUS) system for localized trans-skull hyperthermia (ΔT < 0.5 °C) in rodents and established safety thresholds in healthy mice. To assess the abilities of the developed system and proposed therapeutic strategy for FUS-triggered chemotherapy release we employed thermosensitive liposomal Dox (TSL-Dox) and tested it in two different glioma tumor models (F98 in rats and GL261 in mice). To quantify Dox delivery and changes in the transvascular transport dynamics in the tumor microenvironment we combined fluorescent microscopy, dynamic contrast enhanced MRI (DCE-MRI), and physiologically based pharmacokinetic (PBPK) modeling. Lastly, to assess the therapeutic efficacy of the system and of the proposed therapeutic strategy we performed a survival study in the GL261 glioma bearing mice. Results: The developed closed-loop trans-skull MRgFUS-hyperthermia system that operated at 1.7 MHz, a frequency that maximized the brain (FUS-focus) to skull temperature ratio in mice, was able to attain and maintain the desired focal temperature within a narrow range. Histological evidence (H&E and Nissl) suggests that focal temperature at 41.5 ± 0.5 °C for 10 min is below the threshold for tissue damage. Quantitative analysis of doxorubicin delivery from TSLs with MRgFUS-hyperthermia demonstrated 3.5-fold improvement in cellular uptake in GL261 glioma mouse tumors (p < 0.001) and 5-fold increase in delivery in F98 glioma rat tumors (p < 0.05), as compared to controls (TSL-Dox-only). Moreover, PBPK modeling of drug transport that was calibrated using the experimental data indicated that thermal stress could lead to significant improvement in the transvascular transport (2.3-fold increase in the vessel diffusion coefficient; P < 0.001), in addition to promoting targeted Dox release. Prospective experimental investigations with DCE-MRI during FUS-hyperthermia, supported these findings and provided evidence that moderate thermal stress (≈41 °C for up to 10 min) can promote acute changes in the vascular transport dynamics in the brain tumor microenvironment (Ktrans value for control vs. FUS was 0.0097 and 0.0148 min-1, respectively; p = 0.026). Crucially, survival analysis demonstrated significant improvement in the survival in the TSL-Dox-FUS group as compared to TSL-Dox-only group (p < 0.05), providing supporting evidence on the therapeutic potential of the proposed strategy. Conclusions: Our investigations demonstrated that spatially controlled thermal stress can be attained and sustained in the mouse brain, using a trans-skull closed-loop MRgFUS system, and used to promote the effective delivery of chemotherapy in gliomas from thermosensitive drugs. This system also allowed us to conduct mechanistic investigations that resulted in the refinement of our understanding on the role of thermal stress in augmenting mass and drug transport in brain tumors. Overall, our study established a new paradigm for effective drug delivery in brain tumors based on closed-loop ultrasound-mediated thermal stress and thermosensitive drugs.
Here we report that a covalent organic framework (COF), which contains 2,5-di(imine)-substituted ... more Here we report that a covalent organic framework (COF), which contains 2,5-di(imine)-substituted 1,4-dihydroxybenzene (diiminol) moieties, undergoes color changes in the presence of solvents or solvent vapor that are rapid, passive, reversible, and easily detectable by the naked eye. A new visible absorption band appears in the presence of polar solvents, especially water, suggesting reversible conversion to another species. This reversibility is attributed to the ability of the diiminol to rapidly tautomerize to an iminol/cis-ketoenamine and its inability to doubly tautomerize to a diketoenamine. Density functional theory (DFT) calculations suggest similar energies for the two tautomers in the presence of water, but the diiminol is much more stable in its absence. Time-dependent DFT calculations confirm that the iminol/cis-ketoenamine absorbs at longer wavelength than the diiminol and indicate that this absorption has significant charge-transfer character. A colorimetric humidity sensing device constructed from an oriented thin film of the COF responded quickly to water vapor and was stable for months. These results suggest that tautomerization-induced electronic structure changes can be exploited in COF platforms to give rapid, reversible sensing in systems that exhibit long-term stability.
This paper introduces two experimental studies of capillary impregnation across fiber tows. The f... more This paper introduces two experimental studies of capillary impregnation across fiber tows. The first experimental technique embeds four to five flow detection sensors into a fiber tow at radial locations from the outside to the center of the tow to track the motion of fluid from outside to the center of the tow with time. The second technique based on Magnetic Resonance Imaging (MRI) is a non-intrusive tracking of the flow front as it impregnates the fiber tow. The techniques are compared and contrasted to identify their advantages and limitations. An analytical model that ignores the backpressure of the entrapped air grossly under predicts the saturation time for the tow as compared with the experiments. In order to explain this discrepancy, we include the effect of entrapped air in the analytic model, which slows down the capillary flow. However, other effects such as non-uniform fiber volume fraction within the tow and the ease with which the entrapped air can escape from the to...
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Papers by Johannes Leisen