Histological Properties of a Chemically Fixed Human Embryo Visualized with Quantitative Susceptibility Mapping.

A chemically fixed Carnegie stage 23 (approximately 56 days of gestation) human embryo specimen was imaged using 3D spin-echo and gradient-echo sequences in a static magnetic field strength of 4.74T, and a quantitative susceptibility map was calculated using the 3D gradient-echo image. The acquired 3D microscopic images (90 µm cube voxel size) clarified the relationship between R2 (transverse relaxation rate), R2* (apparent transverse relaxation rate), and magnetic susceptibility in the heart, liver, kidney, and spinal cord. The results suggested that the R2* and magnetic susceptibility in each tissue were probably due to paramagnetic iron ions originating from erythrocytes. The large R2* (~130 s-1) and magnetic susceptibility (~0.122 ppm) in the liver were attributed to its hemopoietic function. A large magnetic susceptibility (~0.116 ppm) was also observed in the spinal cord, but we conclude that more detailed future studies are needed.

Nonlinear Gradient Field Mapping Using a Spherical Grid Phantom for 3 and 7 Tesla MR Imaging Systems Equipped with High-performance Gradient Coils.

Recent high-performance gradient coils are fabricated mainly at the expense of spatial linearity. In this study, we measured the spatial nonlinearity of the magnetic field generated by the gradient coils of two MRI systems with high-performance gradient coils. The nonlinearity of the gradient fields was measured using 3D gradient echo sequences and a spherical phantom with a built-in lattice structure. The spatial variation of the gradient field was approximated to the 3rd order polynomials. The coefficients of the polynomials were calculated using the steepest descent method. The geometric distortion of the acquired 3D MR images was corrected using the polynomials and compared with the 3D images corrected using the harmonic functions provided by the MRI venders. As a result, it was found that the nonlinearity correction formulae provided by the vendors were insufficient and needed to be verified or corrected using a geometric phantom such as used in this study.

Coronary artery established through amniote evolution.

Coronary arteries are a critical part of the vascular system and provide nourishment to the heart. In humans, even minor defects in coronary arteries can be lethal, emphasizing their importance for survival. However, some teleosts survive without coronary arteries, suggesting that there may have been some evolutionary changes in the morphology and function of coronary arteries in the tetrapod lineage. Here, we propose that the true ventricular coronary arteries were newly established during amniote evolution through remodeling of the ancestral coronary vasculature. In mouse (Mus musculus) and Japanese quail (Coturnix japonica) embryos, the coronary arteries unique to amniotes are established by the reconstitution of transient vascular plexuses: aortic subepicardial vessels (ASVs) in the outflow tract and the primitive coronary plexus on the ventricle. In contrast, amphibians (Hyla japonica, Lithobates catesbeianus, Xenopus laevis, and Cynops pyrrhogaster) retain the ASV-like vasculature as truncal coronary arteries throughout their lives and have no primitive coronary plexus. The anatomy and development of zebrafish (Danio rerio) and chondrichthyans suggest that their hypobranchial arteries are ASV-like structures serving as the root of the coronary vasculature throughout their lives. Thus, the ventricular coronary artery of adult amniotes is a novel structure that has acquired a new remodeling process, while the ASVs, which occur transiently during embryonic development, are remnants of the ancestral coronary vessels. This evolutionary change may be related to the modification of branchial arteries, indicating considerable morphological changes underlying the physiological transition during amniote evolution.

Coronary arteries are tasked with supplying the heart with oxygenated blood and nutrients. Any blockage or developmental problem in these blood vessels can have severe and sometimes lethal consequences. Due to their importance for health, researchers have extensively studied how coronary arteries form in humans and mice; a more limited range of studies have also looked at their equivalent in zebrafish. However, little is known about these structures develop in animals such as birds, amphibians, or other groups of fish. This makes it difficult to retrace the evolutionary processes that have given rise to the coronary arteries we are familiar with in mammals. To address this knowledge gap, Mizukami et al. set out to compare blood vessel development around the heart of mammals, birds, amphibians, and fish. To do this, they performed detailed anatomical studies of blood vessel structure at different stages of development in mice as well as quail, frogs and newts, zebrafish and sharks. In both mice and quail, small arterial subepicardial vessels (or ASVs) emerged early in development around the heart; these subsequently reorganised and remodelled themselves to give rise to the 'true' coronary arteries characteristic of the mature heart. Frogs and newts also developed similar ASV-like structures; however, unlike their mammalian and bird equivalents, these vessels did not reorganise, instead being retained into adulthood. In fish, blood vessel development resembled that of amphibians, suggesting that the coronary artery-like structures seen in some fish are an 'ancestral' form of ASVs, rather than the equivalent of the mature coronary arteries in mammals and birds. This work sheds light on the evolutionary processes shaping essential structures in the heart. In the future, Mizukami et al. hope that this knowledge will help develop a greater range of experimental animal models for studying heart disease and potential treatments.

Implementation of the QRAPMASTER data analysis using dictionary matching and quantitative evaluation of the magnetization transfer effect.

PURPOSE: To clarify the magnetization transfer (MT) effect on T1 and T2 values obtained with the QRAPMASTER sequence. METHODS: A phantom consisting of MnCl2 aqueous solution with various proton relaxation times and a chicken breast sample was imaged with the QRAPMASTER sequence and a multislice multiple spin-echo (MSMSE) sequence that was the basis of the QRAPMASTER sequence using a 1.5 T MRI system. T1 values were calculated by data matching using the dictionary dataset created by a Bloch image simulation of the QRAPMASTER sequence. T2 values were calculated by data matching using the dictionary dataset created by a Bloch image simulation of the MSMSE sequence. The MT effect on the images acquired with the QRAPMASTER and MSMSE sequences was calculated by numerically solving Bloch equations using a two-pool model. RESULTS: The linearity and accuracy of the regression lines between the T1 values measured by the QRAPMASTER sequence and those measured by the standard method excluding the T1 values of the chicken breast sample was excellent (R = 0.9969-0.9986, slope = 1.0065-1.016) for consecutive four slices including the central slice. The linearity of the regression lines for the T2 values of all samples was good (R = 0.963-0.985) for the four slices. The accuracy of the regression line was not good (slope = 0.674-0.758), which was mainly due to the effect of eddy currents. The large deviation of the T1 values of the chicken breast sample from the regression line was semi-quantitatively reproduced by the Bloch simulation for the two-pool model. CONCLUSION: This study demonstrated that the T1 value of a biological sample obtained by the QRAPMASTER sequence was shortened by the MT effect.

Bloch Simulation of a Three-point Dixon Experiment Using a Four-dimensional Numerical Phantom.

A 4D numerical phantom, which is defined in the 3D spatial axes and the resonance frequency axis, is indispensable for Bloch simulations of biological tissues with complex distribution of materials. In this study, a 4D numerical phantom was created using MR image datasets of a biological sample containing water and fat, and the Bloch simulations were performed using the 4D numerical phantom. As a result, 3D images of the sample containing water and fat were successfully reproduced, which demonstrated the usefulness of the concept of the 4D numerical phantom.

Development of a method for the Bloch image simulation of biological tissues.

PURPOSE: The purpose of this study is to develop a method for the Bloch image simulation of biological tissues including various chemical components and T2* distribution. METHODS: The nuclear spins in the object material were modeled as a spectral intensity function Sr→ω defined by superposition of Lorentz functions with various central precession frequencies and the half width of 1/(πT2'), where 1/T2' is a relaxation rate attributable to microscopic field inhomogeneity in a voxel. Four-dimensional numerical phantoms were created to simulate Sr→ω and used for MRI simulations of the phantoms containing water and fat protons. Single slice multiple (16) gradient-echo sequences (ΔTE = 2.2 and 1.384 ms) were used for experiments at 1.5 T and 3 T and MRI simulations to evaluate the validity of the approach. RESULTS: Experimentally measured image intensities of the multiple gradient-echo imaging sequences were well reproduced by the MRI simulations. The correlation coefficients between the experimentally measured image intensities and those numerically simulated were 0.9895 to 0.9992 for the 4-component phantom at 1.5 T and 0.9580 to 0.9996 for the 7-component phantom at 3 T. CONCLUSION: T2* and chemical shift effects were successfully implemented in the MRI simulator (BlochSolver). Because this approach can be applied to other MRI simulators, the method developed in this study is useful for MRI simulation of biological tissues containing water and fat protons.

Dynamics of xylem and phloem sap flow in an outdoor zelkova tree visualized by magnetic resonance imaging.

Xylem and phloem sap flows in an intact, young Japanese zelkova tree (Zelkova serrata (Thunb.) Makino) growing outdoors were measured using magnetic resonance imaging (MRI). Two propagator-based sequences were developed for q-space imaging: pulse field gradient (PFG) with spin echo (PFG-SE) and stimulated echo (PFG-STE), which were used for xylem and phloem flow measurements, respectively. The data evaluation methods were improved to image fast xylem flow and slow phloem flow. Measurements were taken every 2-3 h for several consecutive days in August 2016, and diurnal changes in xylem and phloem sap flows in a cross-section of the trunk were quantified at a resolution of 1 mm2. During the day, apparent xylem flow volume exhibited a typical diurnal pattern following a vapor pressure deficit. The velocity mapping of xylem sap flow across the trunk cross section revealed that the greatest flow volume was found in current-year earlywood that had differentiated in April-May. The combined xylem flow in the 1- and 2-year-old annual rings also contributed to one-third of total sap flow. In the phloem, downward sap flow did not exhibit diurnal changes. This novel application of MRI in visualization of xylem and phloem sap flow by MRI is a promising tool for in vivo study of water transport in mature trees.

An Accurate Dictionary Creation Method for MR Fingerprinting Using a Fast Bloch Simulator.

This study proposes an accurate method for creating a dictionary for magnetic resonance fingerprinting (MRF) using a fast Bloch image simulator. An MRF sequence based on a fast imaging with steady precession sequence and a numerical phantom were used for dictionary generation. Cartesian and spiral readout gradients were used for the Bloch image simulation. The validity and usefulness of the method for accurate dictionary creation were demonstrated by MRF parameter maps obtained by pattern matching with the dictionaries generated by the proposed method.

A Fast GPU-optimized 3D MRI Simulator for Arbitrary k-space Sampling.

PURPOSE: To develop a fast 3D MRI simulator for arbitrary k-space sampling using a graphical processing unit (GPU) and demonstrate its performance by comparing simulation and experimental results in a real MRI system. MATERIALS AND METHODS: A fast 3D MRI simulator using a GeForce GTX 1080 GPU (NVIDIA Corporation, Santa Clara, CA, USA) was developed using C++ and the CUDA 8.0 platform (NVIDIA Corporation). The unique advantage of this simulator was that it could use the same pulse sequence as used in the experiment. The performance of the MRI simulator was measured using two GTX 1080 GPUs and 3D Cones sequences. The MRI simulation results for 3D non-Cartesian sampling trajectories like 3D Cones sequences using a numerical 3D phantom were compared with the experimental results obtained with a real MRI system and a real 3D phantom. RESULTS: The performance of the MRI simulator was about 3800-4900 gigaflops for 128- to 4-shot 3D Cones sequences with 2563 voxels, which was about 60% of the performance of the previous MRI simulator optimized for Cartesian sampling calculated for a Cartesian sampling gradient-echo sequence with 2563 voxels. The effects of the static magnetic field inhomogeneity, radio-frequency field inhomogeneity, gradient field nonlinearity, and fast repetition times on the MR images were reproduced in the simulated images as observed in the experimental images. CONCLUSION: The 3D MRI simulator developed for arbitrary k-space sampling optimized using GPUs is a powerful tool for the development and evaluation of advanced imaging sequences including both Cartesian and non-Cartesian k-space sampling.

3D Cones Acquisition of Human Extremity Imaging Using a 1.5T Superconducting Magnet and an Unshielded Gradient Coil Set.

We developed ultrashort echo-time (UTE) imaging sequences with 3D Cones trajectories for a home-built compact MRI system using a 1.5T superconducting magnet and an unshielded gradient coil set. We achieved less than 7 min imaging time and obtained clear in vivo images of a human forearm with a TE of 0.4 ms. We concluded that UTE imaging using 3D Cones acquisition was successfully implemented in our 1.5T MRI system.

Magnetic Resonance Microscopy of Chemically Fixed Human Embryos Performed in University of Tsukuba Since 1999 to 2015.

Magnetic resonance (MR) microscopy of chemically fixed human embryos performed in University of Tsukuba since 1999 to 2015 was reviewed. More than 1,000 chemically fixed human embryos stored in the Congenital Anomaly Research Center of Kyoto University were used throughout the MR microscopy project, which was divided into three terms. In the first term (1999-2005), 3D MR images of 1,204 embryo specimens were acquired with 128 × 128 × 256 voxels by a super-parallel MR microscope using a 2.35 T horizontal-bore superconducting magnet. In the second term (2005-2006), 3D MR images of seven embryo specimens were acquired with 256 × 256 × 512 voxels by an MR microscope using a 9.4 T vertical wide-bore superconducting magnet. In the third term (2013-2015), 3D MR images of a Carnegie Stage (CS) 21 specimen were acquired with 512 × 512 × 1024 voxels by an MR microscope using a 4.7 T vertical wide-bore superconducting magnet and nuclear magnetic resonance parameters of a CS23 specimen were measured with 128 × 128 × 256-256 × 256 × 512 voxels by an MR microscope using a 9.4 T vertical narrow-bore superconducting magnet. Based on the results obtained in this project, the author has proposed the future MR microscopy project in which a number of embryo specimens will be imaged with 256 × 256 × 512-512 × 512 × 1024 voxels using a newly designed super-parallel MR microscope. Anat Rec, 301:987-997, 2018. © 2018 Wiley Periodicals, Inc.

Deletion of both p62 and Nrf2 spontaneously results in the development of nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is one of the leading causes of chronic liver disease worldwide. However, details of pathogenetic mechanisms remain unknown. Deletion of both p62/Sqstm1 and Nrf2 genes spontaneously led to the development of NASH in mice fed a normal chow and was associated with liver tumorigenesis. The pathogenetic mechanism (s) underlying the NASH development was investigated in p62:Nrf2 double-knockout (DKO) mice. DKO mice showed massive hepatomegaly and steatohepatitis with fat accumulation and had hyperphagia-induced obesity coupled with insulin resistance and adipokine imbalance. They also showed dysbiosis associated with an increased proportion of gram-negative bacteria species and an increased lipopolysaccharide (LPS) level in feces. Intestinal permeability was elevated in association with both epithelial damage and decreased expression levels of tight junction protein zona occludens-1, and thereby LPS levels were increased in serum. For Kupffer cells, the foreign body phagocytic capacity was decreased in magnetic resonance imaging, and the proportion of M1 cells was increased in DKO mice. In vitro experiments showed that the inflammatory response was accelerated in the p62:Nrf2 double-deficient Kupffer cells when challenged with a low dose of LPS. Diet restriction improved the hepatic conditions of NASH in association with improved dysbiosis and decreased LPS levels. The results suggest that in DKO mice, activation of innate immunity by excessive LPS flux from the intestines, occurring both within and outside the liver, is central to the development of hepatic damage in the form of NASH.

Three-dimensional models of the segmented human fetal brain generated by magnetic resonance imaging.

Recent advances in imaging technology have enabled us to obtain more detailed images of the human fetus in a nondestructive and noninvasive manner. Through detailed images, elaborate three-dimensional (3D) models of the developing brain can be reconstructed. The segmentation of the developing brain has been determined by serial sections. Therefore, in this study, we attempted to develop a 3D model of the fetal brain using magnetic resonance image (MRI). MR images from 19 specimens (11 embryonic specimens and eight fetal specimens from 5.2 to 225 mm in crown rump length) were used to reconstruct 3D models of regionalized developing brains. From this analysis, we succeeded in registering a maximum of nine landmarks on MR images and reconstructing 19 sequential models of the regionalized developing brain. To confirm the validity of the landmarks, we also compared our results with three serial sections from the Kyoto Collection; the same morphological characteristics were observed on both serial sections and MRI. The morphological minutiae could be found on MR images, and regionalized models of the developing brain could be reconstructed. These results will be useful for clinical diagnosis of living fetuses in utero.

Spiral MRI on a 9.4T Vertical-bore Superconducting Magnet Using Unshielded and Self-shielded Gradient Coils.

Spiral MRI sequences were developed for a 9.4T vertical standard bore (54 mm) superconducting magnet using unshielded and self-shielded gradient coils. Clear spiral images with 64-shot scan were obtained with the self-shielded gradient coil, but severe shading artifacts were observed for the spiral-scan images acquired with the unshielded gradient coil. This shading artifact was successfully corrected with a phase-correction technique using reference scans that we developed based on eddy current field measurements. We therefore concluded that spiral imaging sequences can be installed even for unshielded gradient coils if phase corrections are performed using the reference scans.

BlochSolver: A GPU-optimized fast 3D MRI simulator for experimentally compatible pulse sequences.

A magnetic resonance imaging (MRI) simulator, which reproduces MRI experiments using computers, has been developed using two graphic-processor-unit (GPU) boards (GTX 1080). The MRI simulator was developed to run according to pulse sequences used in experiments. Experiments and simulations were performed to demonstrate the usefulness of the MRI simulator for three types of pulse sequences, namely, three-dimensional (3D) gradient-echo, 3D radio-frequency spoiled gradient-echo, and gradient-echo multislice with practical matrix sizes. The results demonstrated that the calculation speed using two GPU boards was typically about 7 TFLOPS and about 14 times faster than the calculation speed using CPUs (two 18-core Xeons). We also found that MR images acquired by experiment could be reproduced using an appropriate number of subvoxels, and that 3D isotropic and two-dimensional multislice imaging experiments for practical matrix sizes could be simulated using the MRI simulator. Therefore, we concluded that such powerful MRI simulators are expected to become an indispensable tool for MRI research and development.

Oval gradient coils for an open magnetic resonance imaging system with a vertical magnetic field.

Existing open magnetic resonance imaging (MRI) systems use biplanar gradient coils for the spatial encoding of signals. We propose using novel oval gradient coils for an open vertical-field MRI. We designed oval gradients for a 0.3T open MRI system and showed that such a system could outperform a traditional biplanar gradient system while maintaining adequate gradient homogeneity and subject accessibility. Such oval gradient coils would exhibit high efficiency, low inductance and resistance, and high switching capability. Although the designed oval Y and Z coils showed more heat dissipation and less cooling capability than biplanar coils with the same gap, they showed an efficient heat-dissipation path to the surrounding air, which would alleviate the heat problem. The performance of the designed oval-coil system was demonstrated experimentally by imaging a human hand.

Analysis of Rhizome Development in Oryza longistaminata, a Wild Rice Species.

Vegetative reproduction is a form of asexual propagation in plants. A wide range of plants develop rhizomes, modified stems that grow underground horizontally, as a means of vegetative reproduction. In rhizomatous species, despite their distinct developmental patterns, both rhizomes and aerial shoots derive from axillary buds. Therefore, it is of interest to understand the basis of rhizome initiation and development. Oryza longistaminata, a wild rice species, develops rhizomes. We analyzed bud initiation and growth of O. longistaminata rhizomes using various methods of morphological observation. We show that, unlike aerial shoot buds that contain a few leaves only, rhizome buds initiate several leaves and bend to grow at right angles to the original rhizome. Rhizomes are maintained in the juvenile phase irrespective of the developmental phase of the aerial shoot. Stem elongation and reproductive transition are tightly linked in the aerial shoots, but are uncoupled in the rhizome. Our findings indicate that developmental programs operate independently in the rhizomes and aerial shoots. Temporal modification of the developmental pathways that are common to rhizomes and aerial shoots may be the source of developmental plasticity. Furthermore, the creation of new developmental systems appears to be necessary for rhizome development.

Echo-Planar Imaging for a 9.4 Tesla Vertical-Bore Superconducting Magnet Using an Unshielded Gradient Coil.

Echo-planar imaging (EPI) sequences were developed for a 9.4 Tesla vertical standard bore (~54 mm) superconducting magnet using an unshielded gradient coil optimized for live mice imaging and a data correction technique with reference scans. Because EPI requires fast switching of intense magnetic field gradients, eddy currents were induced in the surrounding metallic materials, e.g., the room temperature bore, and this produced serious artifacts on the EPI images. We solved the problem using an unshielded gradient coil set of proper size (outer diameter = 39 mm, inner diameter = 32 mm) with time control of the current rise and reference scans. The obtained EPI images of a phantom and a plant sample were almost artifact-free and demonstrated the promise of our approach.

Development of an outdoor MRI system for measuring flow in a living tree.

An outdoor MRI system for noninvasive, long-term measurements of sap flow in a living tree in its natural environment has been developed. An open-access, 0.2 T permanent magnet with a 160 mm gap was combined with a radiofrequency probe, planar gradient coils, electromagnetic shielding, several electrical units, and a waterproofing box. Two-dimensional cross-sectional images were acquired for a ring-porous tree, and the anatomical structures, including xylem and phloem, were identified. The MRI flow measurements demonstrated the diurnal changes in flow velocity in the stem on a per-pixel basis. These results demonstrate that our outdoor MRI system is a powerful tool for studies of water transport in outdoor trees.

Morphometric human embryonic brain features according to developmental stage.

OBJECTIVES: The present study investigated linear, area, and volume measurements of human brain samples according to Carnegie stages (CS) in an attempt to select suitable morphometric features that reflect embryonic development. METHODS: Using magnetic resonance imaging, we measured seven linear segments, three separate areas, and three regional volumes in 101 samples between CS13 and 23. Brain volume was determined via manual segmentation of the magnetic resonance image, whereby a formula was generated to estimate the volume of each linear measurement. RESULTS: All parameters correlated with crown-rump length. Bitemporal length and mesencephalic height increased linearly according to the CS, and a high correlation between bitemporal length and both whole-brain (r = 0.98) and prosencephalon (r = 0.99) volumes was found when brain cavity volume was excluded. CONCLUSION: Morphometric data related to human embryonic stages are valuable for correcting and comparing sonographic data. The present approach may contribute to improvements in prenatal diagnostics by enabling the selection of more suitable measurements during early embryonic stages. © 2016 John Wiley & Sons, Ltd.