Design and construction of an 8-channel transceiver coil array for rat imaging at 9.4 T.

Ultra-high field (UHF) small animal magnetic resonance imaging (MRI) is a crucial tool permitting investigation of metabolic diseases and identification of imaging biomarkers suitable for clinical diagnosis and translation. Radiofrequency (RF) coils are critical components in enabling acquisition of high-quality rat abdomen MRI data. However, efficient RF coils with high-channel count, capable of sensitive and accelerated rat abdomen imaging at 9.4 T, are not available commercially. The SNR of the commonly-used 9.4 T birdcage coil is relatively weak, particularly in the peripheral area of the subject. In addition, the birdcage is not readily to perform parallel imaging due to unavailability of the required multiple channels. Consequently, the extended scanning duration may cause unnecessary hazards to the rat. In this work, an 8-channel transceiver coil array was designed and constructed to provide good image quality and large coverage for rat abdomen imaging at 9.4 T. The structure and the performance of the developed array was optimized and evaluated by numerical electromagnetic simulations and bench tests, respectively. The MR imaging experiments in phantoms and rat models were also performed on a Bruker 9.4 T preclinical MRI system to validate the feasibility of the proposed design. The coil array supports a one-dimensional acceleration factor up to R = 4, providing good parallel imaging capabilities. These results demonstrated that the proposed 8-channel transceiver coil array for rat imaging has the ability to obtain high spatial resolution of rat abdomen anatomical structure images at 9.4 T.

Multinuclear Magnetic Resonance Spectroscopy at Ultra-High-Field: Assessing Human Cerebral Metabolism in Healthy and Diseased States.

The brain is a highly energetic organ. Although the brain can consume metabolic substrates, such as lactate, glycogen, and ketone bodies, the energy metabolism in a healthy adult brain mainly relies on glucose provided via blood. The cerebral metabolism of glucose produces energy and a wide variety of intermediate metabolites. Since cerebral metabolic alterations have been repeatedly implicated in several brain disorders, understanding changes in metabolite levels and corresponding cell-specific neurotransmitter fluxes through different substrate utilization may highlight the underlying mechanisms that can be exploited to diagnose or treat various brain disorders. Magnetic resonance spectroscopy (MRS) is a noninvasive tool to measure tissue metabolism in vivo. 1H-MRS is widely applied in research at clinical field strengths (≤3T) to measure mostly high abundant metabolites. In addition, X-nuclei MRS including, 13C, 2H, 17O, and 31P, are also very promising. Exploiting the higher sensitivity at ultra-high-field (>4T; UHF) strengths enables obtaining unique insights into different aspects of the substrate metabolism towards measuring cell-specific metabolic fluxes in vivo. This review provides an overview about the potential role of multinuclear MRS (1H, 13C, 2H, 17O, and 31P) at UHF to assess the cerebral metabolism and the metabolic insights obtained by applying these techniques in both healthy and diseased states.

Magnetic resonance imaging at 9.4 T: the Maastricht journey.

The 9.4 T scanner in Maastricht is a whole-body magnet with head gradients and parallel RF transmit capability. At the time of the design, it was conceptualized to be one of the best fMRI scanners in the world, but it has also been used for anatomical and diffusion imaging. 9.4 T offers increases in sensitivity and contrast, but the technical ultra-high field (UHF) challenges, such as field inhomogeneities and constraints set by RF power deposition, are exacerbated compared to 7 T. This article reviews some of the 9.4 T work done in Maastricht. Functional imaging experiments included blood oxygenation level-dependent (BOLD) and blood-volume weighted (VASO) fMRI using different readouts. BOLD benefits from shorter T2* at 9.4 T while VASO from longer T1. We show examples of both ex vivo and in vivo anatomical imaging. For many applications, pTx and optimized coils are essential to harness the full potential of 9.4 T. Our experience shows that, while considerable effort was required compared to our 7 T scanner, we could obtain high-quality anatomical and functional data, which illustrates the potential of MR acquisitions at even higher field strengths. The practical challenges of working with a relatively unique system are also discussed.

[Effect of Ganmai Dazao Decoction on ethology of rats with PTSD and its mechanism].

This study aimed to explore the effect of Ganmai Dazao Decoction on the ethology of rats with posttraumatic stress disorder(PTSD) and study the related mechanism through the changes in magnetic resonance imaging and protein expression. Sixty rats were randomly divided into 6 groups, namely the normal group, the model group, the low(1 g·kg~(-1)), medium(2 g·kg~(-1)), and high-dose Ganmai Dazao Decoction groups(4 g·kg~(-1)), and the positive control group(intragastric administration with 10.8 mg·kg~(-1) of fluoxetine), with 10 rats in each group. Two weeks after inducing PTSD by single-prolonged stress(SPS) in rats, the positive control group was given fluoxetine hydrochloride capsule by gavage, the low, medium, and high-dose groups were given Ganmai Dazao Decoction by gavage, and both the normal group and the model group were given the same volume of normal saline by gavage, each for 7 days. The open field experiment, elevated cross elevated maze, forced swimming experiment, and new object recognition test were carried out for the behavioral test. Three rats in each group were selected to detect the expression of neuropeptide receptor Y1(NPY1R) protein in the hippocampus by Western blot. Then, the other three rats in each group were selected to use the 9.4T magnetic resonance imaging experiment to observe the overall structural changes in the brain region and the anisotropy fraction of the hippocampus. The results of the open field experiment showed that the total distance and central distance of rats in the model group were significantly lower than those in the normal group, and the total distance and central distance of rats in the middle and high-dose Ganmai Dazao Decoction groups were higher than those in the model group. The results of the elevated cross maze test showed that medium and high-dose Ganmai Dazao Decoction remarkably increased the number of open arm entries and the residence time of open arm of rats with PTSD. The results of the forced swimming experiment showed that the immobility time in the water of the model group rats was significantly higher than that of the normal group, and Ganmai Dazao Decoction hugely reduced the immobility time in the water of rats with PTSD. The results of the new object recognition test showed that Ganmai Dazao Decoction significantly increased the exploration time of new objects and familiar objects in rats with PTSD. The results of Western blot showed that Ganmai Dazao Decoction significantly reduced the expression of NYP1R protein in the hippocampus of rats with PTSD. The 9.4T magnetic resonance examination found that there was no significant difference in the structural image among the groups. In the functional image, the fractional anisotropy(FA value) of the hippocampus in the model group was significantly lower than that in the normal group. The FA value of the hippocampus in the middle and high-dose Ganmai Dazao Decoction groups was higher than that in the model group. Ganmai Dazao Decoction reduces the injury of hippocampal neurons by inhibiting the expression of NYP1R in the hippocampus of rats with PTSD, thereby improving the nerve function injury of rats with PTSD and playing a neuroprotective role.

Engineered macrophage-biomimetic versatile nanoantidotes for inflammation-targeted therapy against Alzheimer's disease by neurotoxin neutralization and immune recognition suppression.

Immune recognition of excessive neurotoxins by microglia is a trigger for the onset of neuroinflammation in the brain, leading to neurodegeneration in Alzheimer's disease (AD). Blocking active recognition of microglia while removing neurotoxins holds promise for fundamentally alleviating neurotoxin-induced immune responses, but is very challenging. Herein, an engineered macrophage-biomimetic versatile nanoantidote (OT-Lipo@M) is developed for inflammation-targeted therapy against AD by neurotoxin neutralization and immune recognition suppression. Coating macrophage membranes can not only endow OT-Lipo@M with anti-phagocytic and inflammation-tropism capabilities to target inflammatory lesions in AD brain, but also efficiently reduce neurotoxin levels to prevent them from activating microglia. The loaded oxytocin (OT) can be slowly released to downregulate the expression of immune recognition site Toll-like receptor 4 (TLR4) on microglia, inhibiting TLR4-mediated pro-inflammatory signalling cascade. Benefiting from this two-pronged immunosuppressive strategy, OT-Lipo@M exhibits outstanding therapeutic effects on ameliorating cognitive deficits, inhibiting neuronal apoptosis, and enhancing synaptic plasticity in AD mice, accompanied by the delayed hippocampal atrophy and brain microstructural disruption by in vivo 9.4T MR imaging. This work provides new insights into potential AD therapeutics targeting microglia-mediated neuroinflammation at the source.

Effect of Ganmai Dazao Decoction on ethology of rats with PTSD and its mechanism / 中国中药杂志

This study aimed to explore the effect of Ganmai Dazao Decoction on the ethology of rats with posttraumatic stress disorder(PTSD) and study the related mechanism through the changes in magnetic resonance imaging and protein expression. Sixty rats were randomly divided into 6 groups, namely the normal group, the model group, the low(1 g·kg~(-1)), medium(2 g·kg~(-1)), and high-dose Ganmai Dazao Decoction groups(4 g·kg~(-1)), and the positive control group(intragastric administration with 10.8 mg·kg~(-1) of fluoxetine), with 10 rats in each group. Two weeks after inducing PTSD by single-prolonged stress(SPS) in rats, the positive control group was given fluoxetine hydrochloride capsule by gavage, the low, medium, and high-dose groups were given Ganmai Dazao Decoction by gavage, and both the normal group and the model group were given the same volume of normal saline by gavage, each for 7 days. The open field experiment, elevated cross elevated maze, forced swimming experiment, and new object recognition test were carried out for the behavioral test. Three rats in each group were selected to detect the expression of neuropeptide receptor Y1(NPY1R) protein in the hippocampus by Western blot. Then, the other three rats in each group were selected to use the 9.4T magnetic resonance imaging experiment to observe the overall structural changes in the brain region and the anisotropy fraction of the hippocampus. The results of the open field experiment showed that the total distance and central distance of rats in the model group were significantly lower than those in the normal group, and the total distance and central distance of rats in the middle and high-dose Ganmai Dazao Decoction groups were higher than those in the model group. The results of the elevated cross maze test showed that medium and high-dose Ganmai Dazao Decoction remarkably increased the number of open arm entries and the residence time of open arm of rats with PTSD. The results of the forced swimming experiment showed that the immobility time in the water of the model group rats was significantly higher than that of the normal group, and Ganmai Dazao Decoction hugely reduced the immobility time in the water of rats with PTSD. The results of the new object recognition test showed that Ganmai Dazao Decoction significantly increased the exploration time of new objects and familiar objects in rats with PTSD. The results of Western blot showed that Ganmai Dazao Decoction significantly reduced the expression of NYP1R protein in the hippocampus of rats with PTSD. The 9.4T magnetic resonance examination found that there was no significant difference in the structural image among the groups. In the functional image, the fractional anisotropy(FA value) of the hippocampus in the model group was significantly lower than that in the normal group. The FA value of the hippocampus in the middle and high-dose Ganmai Dazao Decoction groups was higher than that in the model group. Ganmai Dazao Decoction reduces the injury of hippocampal neurons by inhibiting the expression of NYP1R in the hippocampus of rats with PTSD, thereby improving the nerve function injury of rats with PTSD and playing a neuroprotective role.

Simulation Study of Radio Frequency Safety and the Optimal Size of a Single-Channel Surface Radio Frequency Coil for Mice at 9.4 T Magnetic Resonance Imaging.

The optimized size of a single-channel surface radio frequency (RF) coil for mouse body images in a 9.4 T magnetic resonance imaging (MRI) system was determined via electromagnetic-field analysis of the signal depth according to the size of a single-channel coil. The single-channel surface RF coils used in electromagnetic field simulations were configured to operate in transmission/reception mode at a frequency of 9.4 T-400 MHz. Computational analysis using the finite-difference time-domain method was used to assess the single-channel surface RF coil by comparing single-channel surface RF coils of varying sizes in terms of |B1|-, |B1+|-, |B1-|- and |E|-field distribution. RF safety for the prevention of burn injuries to small animals was assessed using an analysis of the specific absorption rate. A single-channel surface RF coil with a 20 mm diameter provided optimal B1-field distribution and RF safety, thus confirming that single-channel surface RF coils with ≥25 mm diameter could not provide typical B1-field distribution. A single-channel surface RF coil with a 20 mm diameter for mouse body imaging at 9.4 T MRI was recommended to preserve the characteristics of single-channel surface RF coils, and ensured that RF signals were applied correctly to the target point within RF safety guidelines.

Phosphorus transversal relaxation times and metabolite concentrations in the human brain at 9.4 T.

A method to estimate phosphorus (31 P) transversal relaxation times (T2 s) of coupled spin systems is demonstrated. Additionally, intracellular and extracellular pH and relaxation-corrected metabolite concentrations are reported. Echo time (TE) series of 31 P metabolite spectra were acquired using stimulated echo acquisition mode (STEAM) localization. Spectra were fitted using LCModel with accurately modeled Versatile Simulation, Pulses and Analysis (VeSPA) basis sets accounting for J-evolution of the coupled spin systems. T2 s were estimated by fitting a single exponential two-parameter model across the TE series. Fitted inorganic phosphate frequencies were used to calculate pH, and estimated relaxation times were used to determine the relaxation-corrected brain metabolite concentrations on an assumption of 3 mM γ-ATP. The method was demonstrated in healthy human brain at a field strength of 9.4 T. T2 times of ATP and nicotinamide adenine dinucleotide (NAD) were shortest between 8 and 20 ms, followed by T2 s of inorganic phosphate between 25 and 50 ms, and phosphocreatine with a T2 of 100 ms. Phosphomonoesters and phosphodiesters had the longest T2 s of about 130 ms. The measured T2 s are comparable with literature values and fit in a decreasing trend with increasing field strengths. Calculated pHs and metabolite concentrations are also comparable with literature values.

OTUP workflow: target specific optimization of the transmit k-space trajectory for flexible universal parallel transmit RF pulse design.

PURPOSE: To optimize transmit k-space trajectories for a wide range of excitation targets and to design "universal pTx RF pulses" based on these trajectories. METHODS: Transmit k-space trajectories (stack of spirals and SPINS) were optimized to best match different excitation targets using the parameters of the analytical equations of spirals and SPINS. The performances of RF pulses designed based on optimized and non-optimized trajectories were compared. The optimized trajectories were utilized for universal pulse design. The universal pulse performances were compared with subject specific tailored pulse performances. The OTUP workflow (optimization of transmit k-space trajectories and universal pulse calculation) was tested on three test target excitation patterns. For one target (local excitation of a central area in the human brain) the pulses were tested in vivo at 9.4 T. RESULTS: The workflow produced appropriate transmit k-space trajectories for each test target. Utilization of an optimized trajectory was crucial for the pulse performance. Using unsuited trajectories diminished the performance. It was possible to create target specific universal pulses. However, not every test target is equally well suited for universal pulse design. There was no significant difference in the in vivo performance between subject specific tailored pulses and a universal pulse at 9.4 T. CONCLUSIONS: The proposed workflow further exploited and improved the universal pulse concept by combining it with gradient trajectory optimization for stack of spirals and SPINS. It emphasized the importance of a well suited trajectory for pTx RF pulse design. Universal and tailored pulses performed with a sufficient degree of similarity in simulations and a high degree of similarity in vivo. The implemented OTUP workflow and the B0 /B1+ map data from 18 subjects measured at 9.4 T are available as open source (https://github.com/ole1965/workflow_OTUP.git).

Three-dimensional high-resolution T1 and T2 mapping of whole macaque brain at 9.4 T using magnetic resonance fingerprinting.

PURPOSE: Quantitative T1 and T2 mapping in non-human primates with whole-brain coverage is challenged by the requirement of sub-millimeter resolution and the inhomogeneity of the transmit magnetic field (B1+ ) covering a large field of view. The goal of the current study is to develop a magnetic resonance fingerprinting (MRF) method for simultaneous T1 and T2 mapping of the entire macaque brain within feasible scan time. METHODS: A three-dimensional (3D) MRF sequence with both inversion- and T2 -preparation modules was developed and evaluated on a 9.4 T preclinical scanner. Data acquisition used a 3D stack-of-spirals trajectory, with undersampling along both the in-plane and the through-plane directions. The effect of B1+ inhomogeneity was accounted for by matching the acquired fingerprint to a dictionary simulated with the B1+ factors measured from a separate scan. In vitro and ex vivo studies were performed to evaluate the accuracy and the undersampling capacity of the MRF method. The application of the MRF method for in vivo, brain-wide T1 and T2 mapping was demonstrated on macaques at 4, 6, and 12 years of age. RESULTS: The MRF method enabled highly repeatable T1 and T2 mapping at high spatial resolution (0.35 × 0.35 × 1 mm3 ) with an acceleration factor of 24. In vivo studies showed significant age-related T2 reduction in deep gray nuclei including the globus pallidus, the putamen, and the caudate nucleus. CONCLUSIONS: This study demonstrates the first MRF study for brain-wide, multi-parametric quantification in non-human primates with sub-millimeter resolution.

Value of ultra-high field MRI in patients with suspected focal epilepsy and negative 3 T MRI (EpiUltraStudy): protocol for a prospective, longitudinal therapeutic study.

PURPOSE: Resective epilepsy surgery is a well-established, evidence-based treatment option in patients with drug-resistant focal epilepsy. A major predictive factor of good surgical outcome is visualization and delineation of a potential epileptogenic lesion by MRI. However, frequently, these lesions are subtle and may escape detection by conventional MRI (≤ 3 T). METHODS: We present the EpiUltraStudy protocol to address the hypothesis that application of ultra-high field (UHF) MRI increases the rate of detection of structural lesions and functional brain aberrances in patients with drug-resistant focal epilepsy who are candidates for resective epilepsy surgery. Additionally, therapeutic gain will be addressed, testing whether increased lesion detection and tailored resections result in higher rates of seizure freedom 1 year after epilepsy surgery. Sixty patients enroll the study according to the following inclusion criteria: aged ≥ 12 years, diagnosed with drug-resistant focal epilepsy with a suspected epileptogenic focus, negative conventional 3 T MRI during pre-surgical work-up. RESULTS: All patients will be evaluated by 7 T MRI; ten patients will undergo an additional 9.4 T MRI exam. Images will be evaluated independently by two neuroradiologists and a neurologist or neurosurgeon. Clinical and UHF MRI will be discussed in the multidisciplinary epilepsy surgery conference. Demographic and epilepsy characteristics, along with postoperative seizure outcome and histopathological evaluation, will be recorded. CONCLUSION: This protocol was reviewed and approved by the local Institutional Review Board and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: www.trialregister.nl : NTR7536.

High-resolution MRI of the human palatine tonsil and its schematic anatomic 3D reconstruction.

The palatine tonsils form an important part of the human immune system. Together with the other lymphoid tonsils of Waldeyer's tonsillar ring, they act as the first line of defense against ingested or inhaled pathogens. Although histologically stained sections of the palatine tonsil are widely available, they represent the tissue only in two dimensions and do not provide reference to three-dimensional space. Such a representation of a tonsillar specimen based on imaging data as a 3D anatomical reconstruction is lacking both in scientific publications and especially in textbooks. As a first step in this direction, the objective of the present work was to image a resected tonsil specimen with high spatial resolution in a 9.4 T small-bore pre-clinical MRI and to combine these data with data from the completely sectioned and H&E stained same palatine tonsil. Based on the information from both image modalities, a 3D anatomical sketch was drawn by a scientific graphic artist. In perspective, such studies could help to overcome the difficulty of capturing the spatial extent and arrangement of anatomical structures from 2D images and to establish a link between three-dimensional anatomical preparations and two-dimensional sections or illustrations, as they have been found so far in common textbooks and anatomical atlases.

3D 31 P MRSI of the human brain at 9.4 Tesla: Optimization and quantitative analysis of metabolic images.

PURPOSE: To present 31 P whole brain MRSI with a high spatial resolution to probe quantitative tissue analysis of 31 P MRSI at an ultrahigh field strength of 9.4 Tesla. METHODS: The study protocol included a 31 P MRSI measurement with an effective resolution of 2.47 mL. For SNR optimization, the nuclear Overhauser enhancement at 9.4 Tesla was investigated. A sensitivity correction was achieved by applying a low rank approximation of the γ-adenosine triphosphate signal. Group analysis and regression on individual volunteers were performed to investigate quantitative concentration differences between different tissue types. RESULTS: Differences in gray and white matter tissue 31 P concentrations could be investigated for 12 different 31 P resonances. In addition, the first highly resolved quantitative MRSI images measured at B0 = 9.4 Tesla of 31 P detectable metabolites with high SNR could be presented. CONCLUSION: With an ultrahigh field strength B0 = 9.4 Tesla, 31 P MRSI moves further toward quantitative metabolic imaging, and subtle differences in concentrations between different tissue types can be detected.

In vivo 1 H MR spectroscopy with J-refocusing.

PURPOSE: The goal of this study was to propose a novel localized proton MR spectroscopy (MRS) sequence that reduces signal loss due to J-modulation in the rat brain in vivo. METHODS: Sprague-Dawley rats were studied at 9.4 T. A semi-LASER sequence with evenly distributed echo-time (TE ) was used, and a 90° J-refocusing pulse was inserted at TE /2. Proton spectra were acquired at two TE s (30 and 68 ms), with and without the J-refocused pulse. Data were processed in MATLAB and quantified with LCModel. RESULTS: The J-refocused spectrum acquired at TE = 30 ms did not show any signal losses due to J-modulation and had comparable spectral pattern to the one acquired with semi-LASER using the minimum achievable TE . Higher signal amplitudes for glutamine, γ-aminobutyric acid and glutathione led to more reliable quantification precision for these metabolites. The refocused signal intensities at TE = 68 ms were also unaffected by J-modulation but were smaller than the signals at TE = 30 ms mainly due to transverse T2 relaxation of metabolites. CONCLUSION: The proposed localized MRS sequence will be beneficial in both animal and human MRS studies when using ultra-short TE is not possible while also providing more reliable quantification precision for J-coupled metabolites.

Local excitation universal parallel transmit pulses at 9.4T.

PURPOSE: To demonstrate that the concept of "universal pTx pulses" is applicable to local excitation applications. METHODS: A database of B0 / B1+ maps from eight different subjects was acquired at 9.4T. Based on these maps, universal pulses that aim at local excitation of the visual cortex area in the human brain (with a flip angle of 90° or 7°) were calculated. The remaining brain regions should not experience any excitation. The pulses were designed with an extension of the "spatial domain method." A 2D and a 3D target excitation pattern were tested, respectively. The pulse performance was examined on non-database subjects by Bloch simulations and in vivo at 9.4T using a GRE anatomical MRI and a presaturated TurboFLASH B1+ mapping sequence. RESULTS: The calculated universal pulses show excellent performance in simulations and in vivo on subjects that were not contained in the design database. The visual cortex region is excited, while the desired non-excitation areas produce the only minimal signal. In simulations, the pulses with 3D target pattern show a lack of excitation uniformity in the visual cortex region; however, in vivo, this inhomogeneity can be deemed acceptable. A reduced field of view application of the universal pulse design concept was performed successfully. CONCLUSIONS: The proposed design approach creates universal local excitation pulses for a flip angle of 7° and 90°, respectively. Providing universal pTx pulses for local excitation applications prospectively abandons the need for time-consuming subject-specific B0 / B1+ mapping and pTx-pulse calculation during the scan session.

An upward 9.4 T static magnetic field inhibits DNA synthesis and increases ROS-P53 to suppress lung cancer growth.

Studies have shown that 9.4 Tesla (9.4 T) high-field magnetic resonance imaging (MRI) has obvious advantages in improving image resolution and capacity, but their safety issues need to be further validated before their clinical approval. Meanwhile, emerging experimental evidences show that moderate to high intensity Static Magnetic Fields (SMFs) have some anti-cancer effects. We examined the effects of two opposite SMF directions on lung cancer bearing mice and found when the lung cancer cell-bearing mice were treated with 9.4 T SMFs for 88 h in total, the upward 9.4 T SMF significantly inhibited A549 tumor growth (tumor growth inhibition=41%), but not the downward 9.4 T SMF. In vitro cellular analysis shows that 9.4 T upward SMF treatment for 24 h not only inhibited A549 DNA synthesis, but also significantly increased ROS and P53 levels, and arrested G2 cell cycle. Moreover, the 9.4 T SMF-treatments for 88 h had no severe impairment to the key organs or blood cell count of the mice. Our findings demonstrated the safety of 9.4 T SMF long-term exposure for their future applications in MRI, and revealed the anti-cancer potential of the upward direction 9.4 T SMF.

Optimization of a quadrature birdcage coil for functional imaging of squirrel monkey brain at 9.4T.

A quadrature transmit/receive birdcage coil was optimized for squirrel monkey functional imaging at the high field of 9.4 T. The coil length was chosen to gain maximum coil efficiency/signal-to-noise ratio (SNR) and meanwhile provide enough homogenous RF field in the whole brain area. Based on the numerical simulation results, a 16-rung high-pass birdcage coil with the optimal length of 9 cm was constructed and evaluated on phantom and in vivo experiments. Compared to a general-purpose non-optimized coil, it exhibits approximately 25% in vivo SNR improvement. In addition to the volume coil, details about how to design and construct the associated animal preparation system were provided.

MRI and pathology correlations in the medulla in sudden unexpected death in epilepsy (SUDEP): a postmortem study.

AIMS: Sudden unexpected death in epilepsy (SUDEP) likely arises as a result of autonomic dysfunction around the time of a seizure. In vivo MRI studies report volume reduction in the medulla and other brainstem autonomic regions. Our aim, in a pathology series, is to correlate regional quantitative features on 9.4T MRI with pathology measures in medullary regions. METHODS: Forty-seven medullae from 18 SUDEP, 18 nonepilepsy controls and 11 epilepsy controls were studied. In 16 cases, representing all three groups, ex vivo 9.4T MRI of the brainstem was carried out. Five regions of interest (ROI) were delineated, including the reticular formation zone (RtZ), and actual and relative volumes (RV), as well as T1, T2, T2* and magnetization transfer ratio (MTR) measurements were evaluated on MRI. On serial sections, actual and RV estimates using Cavalieri stereological method and immunolabelling indices for myelin basic protein, synaptophysin and Microtubule associated protein 2 (MAP2) were carried out in similar ROI. RESULTS: Lower relative RtZ volumes in the rostral medulla but higher actual volumes in the caudal medulla were observed in SUDEP (P < 0.05). No differences between groups for T1, T2, T2* and MTR values in any region was seen but a positive correlation between T1 values and MAP2 labelling index in RtZ (P < 0.05). Significantly lower MAP2 LI were noted in the rostral medulla RtZ in epilepsy cases (P < 0.05). CONCLUSIONS: Rostro-caudal alterations of medullary volume in SUDEP localize with regions containing respiratory regulatory nuclei. They may represent seizure-related alterations, relevant to the pathophysiology of SUDEP.

Resolving the omega-3 methyl resonance with long echo time magnetic resonance spectroscopy in mouse adipose tissue at 9.4 T.

Tissue omega-3 (ω-3) content is biologically important to disease; however, its quantification with magnetic resonance spectroscopy in vivo is challenging due to its low concentration. In addition, the ω-3 methyl resonance (≈ 0.98 ppm) overlaps that of the non-ω-3 (≈ 0.90 ppm), even at 9.4 T. We demonstrate that a Point-RESolved Spectroscopy (PRESS) sequence with an echo time (TE) of 109 ms resolves the ω-3 and non-ω-3 methyl peaks at 9.4 T. Sequence efficacy was verified on five oils with differing ω-3 fat content; the ω-3 content obtained correlated with that measured using 16.5 T NMR (R2 = 0.97). The PRESS sequence was also applied to measure ω-3 content in visceral adipose tissue of three different groups (all n = 3) of mice, each of which were fed a different 20% w/w fat diet. The fat portion of the diet consisted of low (1.4%), medium (9.0%) or high (16.4%) ω-3 fat. The sequence was also applied to a control mouse fed a standard chow diet (5.6% w/w fat, which was 5.9% ω-3). Gas chromatography (GC) analysis of excised tissue was performed for each mouse. The ω-3 fat content obtained with the PRESS sequence correlated with the GC measures (R2 = 0.96). Apparent T2 times of methyl protons were assessed by obtaining spectra from the oils and another group of four mice (fed the high ω-3 diet) with TE values of 109 and 399 ms. Peak areas were fit to a mono-exponentially decaying function and the apparent T2 values of the ω-3 and non-ω-3 methyl protons were 906 ± 148 and 398 ± 78 ms, respectively, in the oils. In mice, the values were 410 ± 68 and 283 ± 57 ms for ω-3 and non-ω-3 fats, respectively.

Ultra-High-Resolution in vitro MRI Study of Age-Related Brain Subcortical Susceptibility Alteration in Rhesus Monkeys at 9.4 T.

Iron concentration in the brain has been suggested as a biomarker of pathologic neurodegeneration. However, the iron concentration changes in healthy aging as well. This study aimed to quantify the age-related changes in iron concentration in the gray matter of healthy rhesus monkeys using quantitative susceptibility mapping (QSM). Three-dimensional gradient-echo images of 16 female rhesus monkey brains aged between 2 and 26 years were acquired in vitro. The susceptibilities in the brain regions of the caudate nucleus (Cd), putamen (Pt), globus pallidus (Gp), and substantia nigra (Sn) were analyzed. The susceptibility varied across different brain regions, with higher levels in the Gp and Sn. Susceptibilities in all analyzed brain regions were linearly correlated with age, yet the plateau period as observed in human brains was absent. This is the first in vitro report of the age-related variability of susceptibility in the deep gray matter of rhesus monkey brains at 9.4 T, with an isotropic resolution of 150 µm. Awareness of age-related changes in susceptibility is vital for the establishment of a baseline to facilitate the differentiation of pathologic neurodegeneration from healthy aging in non-human primate studies.