Quantifying mixing using magnetic resonance imaging

Mixing is a unit operation that combines two or more components into a homogeneous mixture. This work involves mixing two viscous liquid streams using an in-line static mixer. The mixer is a split-and-recombine design that employs shear and extensional flow to increase the interfacial contact between the components. A prototype split-and-recombine (SAR) mixer was constructed by aligning a series of thin laser-cut Poly (methyl methacrylate) (PMMA) plates held in place in a PVC pipe. Mixing in this device is illustrated in the photograph in Fig. 1. Red dye was added to a portion of the test fluid and used as the minor component being mixed into the major (undyed) component. At the inlet of the mixer, the injected layer of tracer fluid is split into two layers as it flows through the mixing section. On each subsequent mixing section, the number of horizontal layers is duplicated. Ultimately, the single stream of dye is uniformly dispersed throughout the cross section of the device. Using a non-Newtonian test fluid of 0.2% Carbopol and a doped tracer fluid of similar composition, mixing in the unit is visualized using magnetic resonance imaging (MRI). MRI is a very powerful experimental probe of molecular chemical and physical environment as well as sample structure on the length scales from microns to centimeters. This sensitivity has resulted in broad application of these techniques to characterize physical, chemical and/or biological properties of materials ranging from humans to foods to porous media (1, 2). The equipment and conditions used here are suitable for imaging liquids containing substantial amounts of NMR mobile (1)H such as ordinary water and organic liquids including oils. Traditionally MRI has utilized super conducting magnets which are not suitable for industrial environments and not portable within a laboratory (Fig. 2). Recent advances in magnet technology have permitted the construction of large volume industrially compatible magnets suitable for imaging process flows. Here, MRI provides spatially resolved component concentrations at different axial locations during the mixing process. This work documents real-time mixing of highly viscous fluids via distributive mixing with an application to personal care products.     

Investigation of fluid flow patterns in a hollow fiber module using magnetic resonance velocity imaging

Summary Magnetic Resonance Imaging (MRI) was used to obtain new information about fluid flow patterns in hollow fiber reactors. Significant changes in inlet flow distribution were observed as a function of Reynolds number. Images taken at the tube bundle entrance and exit showed that maldistribution of flow persists throughout the module. Furthermore, the results suggest that individual fibers act in a mixed degree as feeders or collectors depending upon radial position. These effects must be considered when modelling or designing hollow fiber reactors.     

In-vivo studies of mammary development in the goat using magnetic resonance imaging (MRI)

Mammary development and regression were measured in goats in vivo using magnetic resonance imaging (MRI). Measurements were made during the first and second cycles of pregnancy, lactation and involution. In primiparous goats, and exponential pattern of growth was evident during gestation and for the first 2 weeks of lactation. Parenchyma volume correlated significantly with milk yield across goats during early lactation, and across stage of lactation within goats. Milking was discontinued in Week 26 of the first lactation. Involution was characterized by an initial accumulation of fluid (over 2 days) followed by reabsorption; parenchyma volume did not decrease significantly until the 3rd week of involution, which was also the time at which these goats were mated to start their second gestation. Their udders still contained significant quantities of fluid (40-60% of the gross volume), but parenchyma volume was also greater (by 4.7-fold) than in goats beginning their first gestation. By Week 15 of gestation there was no longer a parity difference in parenchyma; the udders of first-gestation goats had grown significantly, but those of second-gestation goats had not. Conversely, between gestation Week 15 and lactation Week 2 mammary growth was significantly more rapid in the second cycle, such that the udder was larger at the start of the second lactation.     

Computed tomography and magnetic resonance imaging studies of Latimeria chalumnae

Synopsis Recent radiologic imaging techniques (CT[Computed Tomography] and MRI[Magnetic Resonance Imaging]) were used to investigate the cranial anatomy of the coelacanth Latimeria chalumnae. The non-invasive CT and MRI techniques were performed successfully on a 1.45 m female specimen. This specimen had been frozen a year earlier for future research; the CT was conducted on the frozen animal, whereas the MRI method was performed immediately after thawing. The CT technique provides information about differential density of the organism (especially informative with respect to hard tissues, bone and cartilage), whereas three different types of MRI (proton resonance T₁, T₂ and flash) distinguish cartilage, muscles, and different connective tissues. A total of 381 CT cross sections (2 mm thick with 1 mm of overlap) through the head region were used in a computerized three-dimensional reconstruction program to address questions concerning cranial morphology. The results obtained from these radiologic imaging techniques confirmed most of the basic anatomy known from traditional dissections. However, the morphology of complex structures. such as the cartilaginous processes of the neurocranium, and the integration of the branchial arches and palate can only now be described more accurately.     

Structural changes of hip osteoarthritis using magnetic resonance imaging

Introduction

Few data are available concerning structural changes at the hip observed by magnetic resonance imaging (MRI) in people with or without hip osteoarthritis (OA). The aim of this study was to compare cartilage volume and the presence of cartilage defects and bone marrow lesions (BMLs) in participants with and without diagnosed hip OA.

Methods

Femoral head cartilage volume was measured by MRI for 141 community-based persons with no diagnosed hip OA, and 19 with diagnosed hip OA. Cartilage defects and BMLs were regionally scored at the femoral head and acetabulum.

Results

Compared with those without diagnosed hip OA, people with diagnosed hip OA had less femoral head cartilage volume (1763 mm³ versus 3343 mm³; p <0.001) and more prevalent cartilage defects and BMLs (all p ≤0.05) at all sites other than the central inferomedial region of the femoral head. In those with no diagnosed hip OA, cartilage defects in the anterior and central superolateral region of the femoral head were associated with reduced femoral head cartilage volume (all p ≤0.02). Central superolateral BMLs at all sites were associated with reduced femoral head cartilage volume (all p ≤0.003), with a similar trend occurring when BMLs were located in the anterior region of the hip (all p ≤0.08).

Conclusions

Compared with community-based adults with no diagnosed hip OA, people with diagnosed hip OA have less femoral head cartilage volume and a higher prevalence of cartilage defects and BMLs. For people with no diagnosed hip OA, femoral head cartilage volume was reduced where cartilage defects and/or BMLs were present in the anterior and central superolateral regions of the hip joint. Cartilage defects and BMLs present in the anterior and central superolateral regions may represent early structural damage in the pathogenesis of hip OA.     

Quantification of left and right ventricular kinetic energy using four-dimensional intracardiac magnetic resonance imaging flow measurements

We aimed to quantify kinetic energy (KE) during the entire cardiac cycle of the left ventricle (LV) and right ventricle (RV) using four-dimensional phase-contrast magnetic resonance imaging (MRI). KE was quantified in healthy volunteers (n = 9) using an in-house developed software. Mean KE through the cardiac cycle of the LV and the RV were highly correlated (r(2) = 0.96). Mean KE was related to end-diastolic volume (r(2) = 0.66 for LV and r(2) = 0.74 for RV), end-systolic volume (r(2) = 0.59 and 0.68), and stroke volume (r(2) = 0.55 and 0.60), but not to ejection fraction (r(2) < 0.01, P = not significant for both). Three KE peaks were found in both ventricles, in systole, early diastole, and late diastole. In systole, peak KE in the LV was lower (4.9 ± 0.4 mJ, P = 0.004) compared with the RV (7.5 ± 0.8 mJ). In contrast, KE during early diastole was higher in the LV (6.0 ± 0.6 mJ, P = 0.004) compared with the RV (3.6 ± 0.4 mJ). The late diastolic peaks were smaller than the systolic and early diastolic peaks (1.3 ± 0.2 and 1.2 ± 0.2 mJ). Modeling estimated the proportion of KE to total external work, which comprised ～0.3% of LV external work and 3% of RV energy at rest and 3 vs. 24% during peak exercise. The higher early diastolic KE in the LV indicates that LV filling is more dependent on ventricular suction compared with the RV. RV early diastolic filling, on the other hand, may be caused to a higher degree of the return of the atrioventricular plane toward the base of the heart. The difference in ventricular geometry with a longer outflow tract in the RV compared with the LV explains the higher systolic KE in the RV.     

Radiation dosimetry using Fricke-infused gels and magnetic resonance imaging

We have witnessed the advancements of MRI-Fricke-infused gel dosimetry since its commencing in 1984. Over the years, many efforts have been spent to improve the method's efficacy, i.e., to improve its dose-response sensitivity, reproducibility and measurement accuracy. In this article, we give a review of the development of this relatively new dosimetric method. An example of applying this method to gamma knife stereotactic radiosurgery dose distribution mapping is also given.     

Nuclear magnetic resonance imaging in studies of gravitropism in soil mixtures

Gravitropic responses of oat coleoptiles were measured in different growth media; humid air, natural soil and artificial soil (glass beads). The oat coleoptiles in soil and glass beads were monitored by NMR imaging, while those in humid air were imaged in darkness with an infrared-sensitive charge-coupled device (CCD) camera. The present study shows for the first time that gravitropic experiments can be performed in artificial soil using NMR imaging as a convenient and suitable recording method. Not only was it possible to follow the gravitropic curvatures in natural soil, but the artificial soil allowed plant images of sufficient spatial and temporal resolution to be recorded. The advantages of using artificial soil in magnetic resonance imaging studies are that the iron content of glass beads is very low compared with natural soil, and that the artificial soil matrix can easily be standardized with regard to particle size distribution and nutrient content. Two types of glass beads were used, the diameter of the small and the large beads being 300–400 and 420–840 μm, respectively. The growth rate of the coleoptiles in soil and in big beads was roughly the same and only slightly lower than in humid air, whereas small beads reduced the growth rate by approx. 16%. The bending rate of the coleoptiles during the gravitropic response was reduced by c. 65% in soil and 75% in bead mixtures relative to bending in air. It should be noted, however, that the maximum curvature of the coleoptile tip was of the same order in all cases, about 35°. This value may represent the largest possible curvature of the organ. The potential of NMR imaging to study how plant organs penetrate the soil under the influence of gravitropism, mechanical impedance and thigmotropism is also discussed.     

Screening of ligands for redox-active europium using magnetic resonance imaging

We report a screening procedure to predict ligand coordination to Eu^II and Eu^III using magnetic resonance imaging in which bright images indicate complexation and dark images indicate no complexation. Here, paramagnetic Gd^III is used as a surrogate for Eu^III in the screening procedure to enable detection with magnetic resonance imaging. The screening procedure was tested using a set of eight ligands with known coordination to Eu^II and Eu^III, and results were found to be consistent with expected binding. Validation of the screening procedure with known coordination chemistry enables use with new ligands in the future.     

Regional measurements of pulmonary edema by using magnetic resonance imaging

Athree-dimensional magnetic resonance imaging (MRI) method to measurepulmonary edema and lung microvascular barrier permeability wasdeveloped and compared with conventional methods in nine mongrel dogs.MRIs were obtained covering the entire lungs. Injury was induced byinjection of oleic acid (0.021-0.048 ml/kg) into a jugularcatheter. Imaging followed for 0.75-2 h. Extravascular lung waterand permeability-related parameters were measured from multiple-indicator dilution curves. Edema was measured as magnetic resonance signal-to-noise ratio (SNR). Postinjury wet-to-dry lung weight ratio was 5.30 ± 0.38 (n = 9). Extravascular lung water increased from 2.03 ± 1.11 to 3.00 ± 1.45 ml/g(n = 9, P < 0.01). Indicatordilution studies yielded parameters characterizing capillary exchangeof urea and butanediol: the product of the square root of equivalentdiffusivity of escape from the capillary and capillary surface area(D^1/2S)and the capillary permeability-surface area product(PS). The ratio ofD^1/2Sfor urea toD^1/2Sfor butanediol increased from 0.583 ± 0.027 to 0.852 ± 0.154 (n = 9, P < 0.05). Whole lung SNR atbaseline, before injury, correlated withD^1/2Sand PS ratios (both P < 0.02). By using rate of SNR change, the mismatch of transcapillaryfiltration flow and lymph clearance was estimated to be0.2-1.8 ml/min. The filtration coefficient was estimated fromthese values. Results indicate that pulmonary edema formation duringoleic acid injury can be imaged regionally and quantified globally, andthe results suggest possible regional quantification by usingthree-dimensional MRI.

     

Integrated lymphography using fluorescence imaging and magnetic resonance imaging in intact mice

We assessed lymph drainage in living mice by an integrated imaging method using fluorescence imaging (FLI) and magnetic resonance imaging (MRI). Mice were subcutaneously injected with quantum dots and gadofluorine 8 into the right rear footpad. They were fixed on a transparent flat plate and underwent FLI and MRI successively. Small markers were attached to the mouse surface for spatial coregistration, and image fusion of FLIs and MRIs was performed. Two-dimensional fluorescence reflectance imaging was used for FLI. FLI and MRI provided generally consistent results and demonstrated lymphatic flow to the popliteal, sacral, and iliac lymph nodes in most mice and to the renal, inguinal, and lumbar-aortic lymph nodes in some mice. On the fusion images, the locations of the lymph nodes in the mouse trunk were in good agreement between FLI and MRI, indicating successful spatial registration even for the deep structures. The popliteal node tended to be visualized a little farther caudally in FLI than in MRI, presumably because the overlying tissues were thicker in the cranial portion. Integrated FLI/MRI lymphography with image fusion appears to be a useful tool for analysis of the murine lymphatic system.     

Plaque imaging and characterization using magnetic resonance imaging: towards molecular assessment

Identification of high-risk atherosclerotic lesions prone to rupture and thrombosis may greatly decrease the morbidity and mortality associated with atherosclerosis. High-resolution magnetic resonance imaging (MRI) has recently emerged as one of the most promising techniques for the non-invasive study of atherothrombotic disease, as it can characterize plaque composition and monitor its progression. The development of MRI contrast agents that specifically target components of the atherosclerotic plaque may enable non-invasive detection of high-risk lesions. This review discusses the use of high-resolution MRI for plaque detection and characterization and the potentials of "Molecular Imaging" using a variety of molecules present in atherosclerotic plaques that may serve as targets for specific contrast agents to allow the identification of high-risk atherosclerotic lesions in-vivo. Ultimately, such agents may enable treatment of "high-risk" patients prior to lesion progression and occurrence of complications.     

In vivo visualization of gene expression using magnetic resonance imaging

High-resolution in vivo imaging of gene expression is not possible in opaque animals by existing techniques. Here we present a new approach for obtaining such images by magnetic resonance imaging (MRI) using an MRI contrast agent that can indicate reporter gene expression in living animals. We have prepared MRI contrast agents in which the access of water to the first coordination sphere of a chelated paramagnetic ion is blocked with a substrate that can be removed by enzymatic cleavage. Following cleavage, the paramagnetic ion can interact directly with water protons to increase the MR signal. Here, we report an agent where galactopyranose is the blocking group. This group renders the MRI contrast agent sensitive to expression of the commonly used marker gene, beta-galactosidase. To cellular resolution, regions of higher intensity in the MR image correlate with regions expressing marker enzyme. These results offer the promise of in vivo mapping of gene expression in transgenic animals and validate a general approach for constructing a family of MRI contrast agents that respond to biological activity.     

Differentiation between hemosiderin- and ferritin-bound brain iron using nuclear magnetic resonance and magnetic resonance imaging.

MRI is an optimal clinical (research) tool to provide information on brain morphology and pathology and to detect metal ions that possess intrinsic magnetic properties. Non-heme iron is abundantly present in the brain in three different forms: "low molecular weight" complexes, iron bound to "medium molecular weight complexes" metalloproteins such as transferrin, and "high molecular weight" complexes as ferritin and hemosiderin. The total amount and form of iron may differ in health and disease, and MRI can possibly quantify and monitor such changes. Ferritin-bound iron is the main storage form of iron and is present predominantly in the extrapyramidal nuclei where its amounts normally increase as a function of age. Ferritin is water soluble and shortens both, T1 and T2 relaxation, with as result a signal change on the MR images. Hemosiderin, a degradation product of ferritin, is water-insoluble with a stronger T2 shortening effect than ferritin. The larger cluster size of hemosiderin and its water-insolubility also explain a lack of significant T1-shortening effect on T1-weighted images. Using both in vitro specimens and intact brain tissue in vivo we demonstrate here that MRI may be able to distinguish between ferritin- and hemosiderin-bound iron.     

Principles of magnetic resonance imaging

This article aims to provide an educational document of magnetic resonance imaging principles for applied biomedical users of the technology. Basic principles are illustrated using simple experimental models on a preclinical imaging system.     

Velocity profiles in stenosed tube models using magnetic resonance imaging

A time-of-flight MRI velocity measurement technique is evaluated against corresponding LDV measurements in a constriction tube model over a range of physiologic flow conditions. Results from this study show that MR displacement images can: 1) be obtained within both laminar and turbulent jets (maximum stenotic Re approximately equal to 4,200), 2) measure mean jet velocities up to 172 cm/s, and, 3) detect low forward and reverse stenosis (0 less than or equal to L/D less than or equal to 2). Regions between the jet termination point and re-establishment of laminar flow (Re greater than or equal to 1500, greater than or equal to 1000, and greater than or equal to 110 downstream of 40, 60, and 80 percent stenosis, respectively) cannot presently be detected by this technique.     

Denoising functional magnetic resonance imaging time-series using anisotropic spatial averaging

We propose a novel iterative scheme for adaptive smoothing of functional MR images. The method estimates a signal model at every voxel in the time-series, which is subsequently used in determining the weights of the smoothing kernel. The method does not require any information about the test hypothesis and is well-suited as a preprocessing step for both hypothesis-driven and data-driven analysis techniques. We demonstrate the performance of the proposed method by applying it to preprocess both simulated and real fMRI data. The method is found to effectively suppress the noise while preserving the shapes of the active brain regions.     

Quantitative imaging of cell-permeable magnetic resonance contrast agents using x-ray fluorescence

The inability to transduce cellular membranes is a limitation of current magnetic resonance imaging probes used in biologic and clinical settings. This constraint confines contrast agents to extracellular and vascular regions of the body, drastically reducing their viability for investigating processes and cycles in developmental biology. Conversely, a contrast agent with the ability to permeate cell membranes could be used in visualizing cell patterning, cell fate mapping, gene therapy, and, eventually, noninvasive cancer diagnosis. Therefore, we describe the synthesis and quantitative imaging of four contrast agents with the capability to cross cell membranes in sufficient quantity for detection. Each agent is based on the conjugation of a Gd(III) chelator with a cellular transduction moiety. Specifically, we coupled Gd(III)-diethylenetriaminepentaacetic acid DTPA and Gd(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with an 8-amino acid polyarginine oligomer and an amphipathic stilbene molecule, 4-amino-4'-(N,N-dimethylamino)stilbene. The imaging modality that provided the best sensitivity and spatial resolution for direct detection of the contrast agents is synchrotron radiation x-ray fluorescence (SR-XRF). Unlike optical microscopy, SR-XRF provides two-dimensional images with resolution 10(3) better than (153)Gd gamma counting, without altering the agent by organic fluorophore conjugation. The transduction efficiency of the intracellular agents was evaluated by T(1) analysis and inductively coupled plasma mass spectrometry to determine the efficacy of each chelate-transporter combination.