Magnetic resonance microscopy of collagen mineralization

A model mineralizing system was subjected to magnetic resonance microscopy to investigate how water proton transverse (T₂) relaxation times and magnetization transfer ratios can be applied to monitor collagen mineralization. In our model system, a collagen sponge was mineralized with polymer-stabilized amorphous calcium carbonate. The lower hydration and water proton T₂ values of collagen sponges during the initial mineralization phase were attributed to the replacement of the water within the collagen fibrils by amorphous calcium carbonate. The significant reduction in T₂ values by day 6 (p < 0.001) was attributed to the appearance of mineral crystallites, which were also detected by x-ray diffraction and scanning electron microscopy. In the second phase, between days 6 and 13, magnetic resonance microscopy properties appear to plateau as amorphous calcium carbonate droplets began to coalesce within the intrafibrillar space of collagen. In the third phase, after day 15, the amorphous mineral phase crystallized, resulting in a reduction in the absolute intensity of the collagen diffraction pattern. We speculate that magnetization transfer ratio values for collagen sponges, with similar collagen contents, increased from 0.25 ± 0.02 for control strips to a maximum value of 0.31 ± 0.04 at day 15 (p = 0.03) because mineral crystals greatly reduce the mobility of the collagen fibrils.     

Magnetic resonance microscopy of chick embryos in ovo

Magnetic resonance imaging (MRI) of the live 11-day chick embryo with special radiofrequency coils and 3-D imaging methods has produced contiguous 1.25-mm-thick slices with 200-microns pixel resolution, permitting definition of cardiac chambers, cerebral ventricles, spinal cord, liver, and lungs. It was the objective of this study to image younger chick embryos in ovo with higher spatial resolution through the application of implanted radiofrequency coils. Fertilized Arbor Acre eggs were windowed at 9, 6, and 4 days. Circular coils 18 mm in diameter tuned to 85.5 MHz were suspended around the developing embryo. The eggs were sealed with tape and maintained at 37 degrees C during the imaging procedure. MRI was performed in a 2.0-Tesla GE system utilizing a 3-D Fourier transform acquisition in sagittal and axial planes with a partial saturation sequence (TR = 400 ms, TE = 27 ms). Approximately 1 hour of imaging time was required to obtain 16 contiguous 600-microns-thick slices with 50-microns pixel resolution. Embryos remained viable through the imaging procedure. Embryos were photographed, fixed, and cleared for correlative anatomical study. Vitelline vessels, dorsal aorta, aortic arches, cardinal veins, and cardiac chambers were identified as areas of decreased signal intensity. Cerebral ventricles and the vitreous portion of the eye have signal intensities that are less than adjacent neural, scleral, and lens tissue. Further refinements in MR instrumentation and imaging sequences promise improvements in resolution and offer the potential for sequential observations of the intact embryo.     

Ensuring oxygenation of carrot cell cultures in a Couette viscometer during investigation of shear effects

Mathematical simulation and experimental measurement of dissolved O₂ were performed for extended (up to 8 h) shear testing of Daucus carota (carrot) cell cultures in a conventional Couette viscometer (0.625 mm annulus). The results suggest O₂ depletion below critical levels for cell growth may occur. A novel design modification incorporating an O₂-permeable silicone-layer spun cast on a porous ceramic bowl was devised. It significantly improved oxygenation of the cell cultures, keeping dissolved O₂ near saturation.     

Magnetic resonance microscopy for the quantitative analysis of trabecular bone architecture

A major concern for long-term spaceflight is the effect of microgravity on bone structure and mass as a loss of cortical and trabecular bone volume and density, both of which can lead to decreased bone strength and an increased risk of bone fracture. Detailed analysis of the three-dimensional structure of trabecular bone, and its relation to bone strength has become feasible only recently using high-resolution 3D imaging techniques. In particular, magnetic resonance microscopy (MRM) has proved to be particularly useful for the ex vivo evaluation of the complex architecture of trabecular bone. In this study, we describe the use of two different MRM-based methods for the quantitative evaluation of the three-dimensional structure of trabecular bone explants and for the prediction of their biomechanical properties. The in vivo application of such methods is also discussed.     

Model-independent relationships between hematocrit,blood viscosity,and yield stress derived from Couette viscometry data

This paper describes a procedure, based on Tikhonov regularization, for obtaining the shear rate function or equivalently the viscosity function of blood from Couette viscometry data. For data sets that include points where the sample in the annulus is partially sheared the yield stress of blood will also be obtained. For data sets that do not contain partially sheared points, provided the shear stress is sufficiently low, a different method of estimating the yield stress is proposed. Both the shear rate function and yield stress obtained in this investigation are independent of any rheological model of blood. This procedure is applied to a large set of Couette viscometer data taken from the literature. Results in the form of shear rate and viscosity functions and yield stress are presented for a wide range of hematocrits and are compared against those reported by the originators of the data and against independently measured shear properties of blood.     

Magnetic resonance microscopy at 14 Tesla and correlative histopathology of human brain tumor tissue

Magnetic Resonance Microscopy (MRM) can provide high microstructural detail in excised human lesions. Previous MRM images on some experimental models and a few human samples suggest the large potential of the technique. The aim of this study was the characterization of specific morphological features of human brain tumor samples by MRM and correlative histopathology. We performed MRM imaging and correlative histopathology in 19 meningioma and 11 glioma human brain tumor samples obtained at surgery. To our knowledge, this is the first MRM direct structural characterization of human brain tumor samples. MRM of brain tumor tissue provided images with 35 to 40 μm spatial resolution. The use of MRM to study human brain tumor samples provides new microstructural information on brain tumors for better classification and characterization. The correlation between MRM and histopathology images allowed the determination of image parameters for critical microstructures of the tumor, like collagen patterns, necrotic foci, calcifications and/or psammoma bodies, vascular distribution and hemorrhage among others. Therefore, MRM may help in interpreting the Clinical Magnetic Resonance images in terms of cell biology processes and tissue patterns. Finally, and most importantly for clinical diagnosis purposes, it provides three-dimensional information in intact samples which may help in selecting a preferential orientation for the histopathology slicing which contains most of the informative elements of the biopsy. Overall, the findings reported here provide a new and unique microstructural view of intact human brain tumor tissue. At this point, our approach and results allow the identification of specific tissue types and pathological features in unprocessed tumor samples.     

Structure of a VEGF-VEGF receptor complex determined by electron microscopy

Receptor tyrosine kinases are activated upon ligand-induced dimerization. Here we show that the monomeric extracellular domain of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2) has a flexible structure. Binding of VEGF to membrane-distal immunoglobulin-like domains causes receptor dimerization and promotes further interaction between receptor monomers through the membrane-proximal immunoglobulin-like domain 7. By this mechanism, ligand-induced dimerization of VEGFR-2 can be communicated across the membrane, activating the intracellular tyrosine kinase domains.     

Hematocrit,viscosity and velocity distributions of aggregating and non-aggregating blood in a bifurcating microchannel

Microscale blood flow is characterised by heterogeneous distributions of hematocrit, viscosity and velocity. In microvascular bifurcations, cells are unevenly distributed between the branches, and this effect can be amplified in subsequent branches depending on a number of parameters. We propose an approach to infer hematocrit profiles of human blood flowing through a bifurcating microchannel. The influence of aggregation, induced by the addition of Dextran 2000 to the samples, is also considered. Averaged values indicate plasma skimming, particularly in the presence of red blood cell (RBC) aggregation. Using an empirical model, the hematocrit profiles are used to estimate local relative viscosity distributions. Simulations are used to predict how the non-uniform viscosity influences the velocity profiles. Comparing these data to velocity profiles of RBCs measured using particle image velocimetry provides validation of the model. It is observed that aggregation blunts velocity profiles after a long straight section of channel. Downstream of the bifurcation, skewing of the velocity profiles is detected, which is enhanced by aggregation. The proposed methodology is capable of providing hitherto unreported information on important aspects of microscale blood rheology.     

Magnetic resonance cholangiopancreatography and a problem in diagnosis of hepatopancreatoduodenal diseases

Based on the findings of 54 magnetic resonance studies, the authors used 19 of them authors to study the types of normalcy. A role of the new noninvasive technique magnetic resonance cholangiopancreatography (MRCPG) in the diagnosis of hepatopancreatoduodenal diseases is assessed. The potentialities of MRCPG in the detection of most common diseases and malformations of the biliary system are demonstrated. Comparative studies of MRCPG and endoscopic retrograde cholangiopancreatography (ERCPG) were conducted in 18 cases. The paper shows a methodological approach to MRCPG and analyzes the studies by describing the MR semiotics of major diseases. Emphasis is laid on how it is important to combine routine MRI and MRCPG in certain diagnostic situations. The authors consider that MRCPG is able to replace X-ray endoscopic studies and primarily ERCPG in diagnostic terms, by reserving their therapeutical functions for itself. MRCPG has great potentialities that, require further investigations and analysis.     

Size and settling velocity distributions of flocs in the Tamar estuary during a tidal cycle

Data extracted from video recordings of individual estuarine flocs near the estuary bed during the advance and retreat of the salt intrusion show changes in size and settling velocity distributions. The recordings were taken using INSSEV —IN Situ SEttling Velocity instrument. Size coupled with effective density variations due to both changes in floc structure and ambient salinity result in changes in the settling velocity during the tidal cycle. In particular, just after high water slack, the appearance of high settling velocity medium size flocs and individual particles suggest that the lower density flocs have been broken up by the intense vertical shear in the currents caused by the salt wedge intrusion. Current shear is shown to have a significant influence on floc effective density.     

Magnetic resonance imaging and magnetic resonance spectroscopy in a patient with amyotrophic lateral sclerosis and frontotemporal dementia

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have been investigated in a single neurodegenerative disease manifesting as either amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) alone, but have not been examined in combined disorders such as ALS with FTD (ALS-FTD). To our knowledge, this study is the first attempt to demonstrate relationship between MRI abnormalities and MR spectroscopic metabolite changes of the motor cortex, frontal white matter and corticospinal tract in a patient with the diagnosis of ALS with probable upper motor neuron signs (ALS-PUMNS) and FTD. Patient presented underwent MRI of the brain and MRS. The ratio of N-acetylaspartate (NAA) to creatine (Cr), choline to Cr, myo-inositol (ml) to Cr and glutamate-glutamine (Glx) to Cr were derived from peak area measurement. Spectra from the right motor cortex, frontal white matter and corticospinal tract were obtained. MR images were evaluated for sulcus centralis enlargement, corticospinal tract hyperintensity and frontal lobes atrophy. Spectra showed reduced NAA/Cr and Glx/Cr ratio, yet the ratio of Cho/Cr exhibited significant elevation. MR images revealed sulcus centralis enlargement, high signal intensity of corticospinal tract and atrophy of both frontal lobes. Proton spectroscopic metabolic changes in a current patient fully correlate with previously reported MRS metabolic changes in ALS alone. Surprisingly, normal ml (glial marker) values have been found in almost all measured voxels of interest except in the frontal white matter. These findings differ from the previous findings in ALS or FTD alone. In conclusion, these findings support the concept that ALS, FTD and ALS-FTD may represent different manifestations of a single pathological continuum.     

Magnetic resonance imaging in personalized medicine

正Continued biomedical advances and increased demands on quality health care have led to a new era of personalized medicine—a concept of medicine that uses specific information to an individual to help diagnose disease,plan treatment,assess treatment efficacy,and/or predict prognosis.This concept has evolved from the idea ofpatient-centered care,which intends to shift the focus of health care from diseases to patients(Abujudeh et al.,2016).Medical imaging is essential in the practice of modern medicine,and its role in personalized medicine has never been greater.In particular,magnetic resonance(MR)     

Scaling in biological nuclear magnetic resonance spectral distributions

A statistical analysis of the distribution of the eigenvalues of the chemical shift interaction as detected by nuclear magnetic resonance (NMR) spectroscopy in large biological systems is presented in the light of random matrix theory. A power law dependence is experimentally observed for the distribution of the number of eigenvalues, N, of the shielding hamiltonian with epsilon i less than or equal to E as a function of the energy E. From this cumulative distribution of energy levels, N(E), we also obtain a density of states rho(E). The exponent of the energy variation of N(E) and rho(E) are correlated with the dimensionality of the molecular system. A crossover in the values of the exponents is found in passing from low to higher energy in the spectra. Our method classifies and reduces the chemical shift data base of proteins and also demonstrates a degree of regularity in seemingly irregular spectral patterns.     

Magnetic resonance microscopy of prenatal dolphins (Mammalia, Odontoceti, Delphinidae) - Ontogenetic and phylogenetic implications

The structure of two preserved prenatal dolphins were visualized by 3D MR microscopy (isotropic nominal resolution up to 78.1 μm), which is a high-resolution 3D magnetic resonance imaging (MRI) technique. To determine the benefits and limitations of this method, the acquired 3D datasets were segmented manually and compared to histological sections of different specimens in corresponding developmental stages. The MR images visualize the external and internal morphology of both prenatal dolphins in detail. Various organ systems with their main components are clearly documented in the images, allowing a complete segmentation of the specimens and the calculation of volumes and surface areas of different organ systems. Due to its non-invasive character and the detailed imaging within its resolution range, MR microscopy proves to be a valuable tool in developmental biology for the visualization of the inner architecture of rare and delicate museum specimens, such as the small dolphin embryo and fetus examined. In these two prenatal dolphins, the profound structural modifications at the transition from the embryonic to the fetal stage reflect the adaptations of the mammalian bauplan to the requirements of a holaquatic cetacean life-style. However, the developmental pattern and sequence of the emerging tissues and organs in prenatal life do not resemble the hypothesized evolution of the structural and functional adaptations found in the fossil record.     

Stress distributions and material properties determined in articular cartilage from MRI-based finite strains

The noninvasive measurement of finite strains in biomaterials and tissues by magnetic resonance imaging (MRI) enables mathematical estimates of stress distributions and material properties. Such methods allow for non-contact and patient-specific modeling in a manner not possible with traditional mechanical testing or finite element techniques. Here, we employed three constitutive (i.e. linear Hookean, and nonlinear Neo-Hookean and Mooney-Rivlin) relations with known loading conditions and MRI-based finite strains to estimate stress patterns and material properties in the articular cartilage of tibiofemoral joints. Displacement-encoded MRI was used to determine two-dimensional finite strains in juvenile porcine joints, and an iterative technique estimated stress distributions and material properties with defined constitutive relations. Stress distributions were consistent across all relations, although the stress magnitudes varied. Material properties for femoral and tibial cartilage were found to be consistent with those reported in literature. Further, the stress estimates from Hookean and Neo-Hookean, but not Mooney-Rivlin, relations agreed with finite element-based simulations. A nonlinear Neo-Hookean relation provided the most appropriate model for the characterization of complex and spatially dependent stresses using two-dimensional MRI-based finite strain. These results demonstrate the feasibility of a new and computationally efficient technique incorporating MRI-based deformation with mathematical modeling to non-invasively evaluate the mechanical behavior of biological tissues and materials.