Ultra-High Field Magnetic Resonance Imaging of the Retrobulbar Optic Nerve, Subarachnoid Space, and Optic Nerve Sheath in Emmetropic and Myopic Eyes.

Purpose: We aimed to image the optic nerve, subarachnoid space and optic nerve sheath in emmetropes and myopes ultra-high field (7-Tesla) magnetic resonance imaging (MRI). We targeted the retrobulbar distance of approximately 3 mm behind the eyeball, an area of clinical interest because of optic nerve sheath distensibility and pressure-related enlargement. Methods: Eleven emmetropes (+0.75 to -0.50D, aged 20-41 years) and 10 myopes (-4.5 to -12D, aged 21-37 years) participated. Cross-sectional area of the optic nerve, subarachnoid space and optic nerve sheath at approximately 3 mm behind the eye were measured from two-dimensional T2-weighted coronal oblique MRI images obtained through the left optic nerve. Axial length of the left eye was measured from T2-weighted axial MRI images. In nine emmetropes and seven myopes, the optic nerve head was imaged with optical coherence tomography to compare retrobulbar and intraocular measures. Results: Retrobulbar optic nerve, subarachnoid space and optic nerve sheath dimensions differed between myopes and emmetropes. Myopes tended to have smaller optic nerve and subarachnoid space. Longer MRI-derived axial length was associated with smaller optic nerve area (P = 0.03). Bruch's membrane opening area did not predict retrobulbar optic nerve area (P = 0.48). Conclusions: This study demonstrates the feasibility of using 7-Tesla MRI to measure optic nerve, subarachnoid space, and optic nerve sheath dimensions behind the eye. In healthy adults, the retrobulbar optic nerve and subarachnoid space size are influenced by the degree of myopia. Translational Relevance: ultra-high field MRI is a practical tool for assessing the morphometry of the optic nerve and surrounding anatomy behind the eye.

MR-EYE: High-Resolution MRI of the Human Eye and Orbit at Ultrahigh Field (7T).

Ultrahigh-field (7T) MRI provides improved contrast and a signal-to-noise gain compared with lower magnetic field strengths. Here, we demonstrate feasibility and optimization of anatomic imaging of the eye and orbit using a dedicated commercial multichannel transmit and receive eye coil. Optimization of participant setup techniques and MRI sequence parameters allowed for improvements in the image resolution and contrast, and the eye and orbit coverage with minimal susceptibility and motion artifacts in a clinically feasible protocol.

Compressed sensing effects on quantitative analysis of undersampled human brain sodium MRI.

PURPOSE: The clinical application of sodium MRI is hampered due to relatively low image quality and associated long acquisition times. Compressed sensing (CS) aims at a reduction of measurement time, but has been found to encompass quantitative estimation bias when used in low SNR x-Nuclei imaging. This work analyses CS in quantitative human brain sodium MRI from undersampled acquisitions and provides recommendations for tissue sodium concentration (TSC) estimation. METHODS: CS reconstructions from 3D radial acquisitions of 5 healthy volunteers were investigated over varying undersampling factors (USFs) and CS penalty weights on different sparsity domains, Wavelet, Discrete Cosine Transform (DCT), and Identity. Resulting images were compared with highly sampled and undersampled NUFFT-based images and evaluated for image quality (i.e. structural similarity), image intensity bias, and its effect on TSC estimates in gray and white matter. RESULTS: Wavelet-based CS reconstructions show highest image quality with stable TSC estimates for most USFs. Up to an USF of 4, images showed good structural detail. DCT and Identity-based CS enable good image quality, however show a bias in TSC with a reduction in estimates across USFs. CONCLUSIONS: The image intensity bias is lowest in Wavelet-based reconstructions and enables an up to fourfold acquisition speed up while maintaining good structural detail. The associated acquisition time reduction can facilitate a translation of sodium MRI into clinical routine.

Extracting more for less: multi-echo MP2RAGE for simultaneous T1 -weighted imaging, T1 mapping, R2∗ mapping, SWI, and QSM from a single acquisition.

PURPOSE: To demonstrate simultaneous T1 -weighted imaging, T1 mapping, R2∗ mapping, SWI, and QSM from a single multi-echo (ME) MP2RAGE acquisition. METHODS: A single-echo (SE) MP2RAGE sequence at 7 tesla was extended to ME with 4 bipolar gradient echo readouts. T1 -weighted images and T1 maps calculated from individual echoes were combined using sum of squares and averaged, respectively. ME-combined SWI and associated minimum intensity projection images were generated with TE-adjusted homodyne filters. A QSM reconstruction pipeline was used, including a phase-offsets correction and coil combination method to properly combine the phase images from the 32 receiver channels. Measurements of susceptibility, R2∗ , and T1 of brain tissue from ME-MP2RAGE were compared with those from standard ME-gradient echo and SE-MP2RAGE. RESULTS: The ME combined T1 -weighted, T1 map, SWI, and minimum intensity projection images showed increased SNRs compared to the SE results. The proposed coil combination method led to QSM results free of phase-singularity artifacts, which were present in the standard adaptive combination method. T1 -weighted, T1 , and susceptibility maps from ME-MP2RAGE were comparable to those obtained from SE-MP2RAGE and ME-gradient echo, whereas R2∗ maps showed increased blurring and reduced SNR. T1 , R2∗ , and susceptibility values of brain tissue from ME-MP2RAGE were consistent with those from SE-MP2RAGE and ME-gradient echo. CONCLUSION: High-resolution structural T1 weighted imaging, T1 mapping, R2∗ mapping, SWI, and QSM can be extracted from a single 8.5-min ME-MP2RAGE acquisition using a customized reconstruction pipeline. This method can be applied to replace separate SE-MP2RAGE and ME-gradient echo acquisitions to significantly shorten total scan time.

Zero-gradient-excitation ramped hybrid encoding (zGRF -RHE) sodium MRI.

PURPOSE: Fast bi-exponential transverse signal decay compounds sodium image quality. This work aims at enhancing image characteristics using a special case of ramped hybrid encoding (RHE). Zero-gradient-excitation (zGRF )-RHE provides (1) gradient-free excitation for high flip angle, artifact-free excitation profiles and (2) gradient ramping during dead-time for the optimization of encoding time (tenc ) to reduce T2* signal decay influence during acquisition. METHODS: Radial zGRF -RHE and standard radial UTE were investigated over a range of receiver bandwidths in simulations, phantom and in vivo brain experiments. Central k-space in zGRF -RHE was acquired through single point measurements at the minimum achievable TE. T2* blurring artifacts and image SNR and CNR were assessed. RESULTS: zGRF -RHE enabled 90° flip angle artifact-free excitation, whereas gradient pre-ramping provided greater tenc efficiency for any readout bandwidths. Experiments confirmed simulation results, revealing sharper edge characteristics particularly at short readout durations (TRO ). Significant SNR improvements of up to 4.8% were observed for longer TRO . CONCLUSION: zGRF -RHE allows for artifact-free high flip angle excitation with time-efficient encoding improving on image characteristics. This hybrid encoding concept with gradient pre-ramping is trajectory independent and can be introduced in any center-out UTE trajectory design.

Feasibility of identifying the ideal locations for motor intention decoding using unimodal and multimodal classification at 7T-fMRI.

Invasive Brain-Computer Interfaces (BCIs) require surgeries with high health-risks. The risk-to-benefit ratio of the procedure could potentially be improved by pre-surgically identifying the ideal locations for mental strategy classification. We recorded high-spatiotemporal resolution blood-oxygenation-level-dependent (BOLD) signals using functional MRI at 7 Tesla in eleven healthy participants during two motor imagery tasks. BCI diagnostic task isolated the intent to imagine movements, while BCI simulation task simulated the neural states that may be yielded in a real-life BCI-operation scenario. Imagination of movements were classified from the BOLD signals in sub-regions of activation within a single or multiple dorsal motor network regions. Then, the participant's decoding performance during the BCI simulation task was predicted from the BCI diagnostic task. The results revealed that drawing information from multiple regions compared to a single region increased the classification accuracy of imagined movements. Importantly, systematic unimodal and multimodal classification revealed the ideal combination of regions that yielded the best classification accuracy at the individual-level. Lastly, a given participant's decoding performance achieved during the BCI simulation task could be predicted from the BCI diagnostic task. These results show the feasibility of 7T-fMRI with unimodal and multimodal classification being utilized for identifying ideal sites for mental strategy classification.

Optimized partial-coverage functional analysis pipeline (OPFAP): a semi-automated pipeline for skull stripping and co-registration of partial-coverage, ultra-high-field functional images.

OBJECTIVE: Ultra-high-field functional MRI (UHF-fMRI) allows for higher spatiotemporal resolution imaging. However, higher-resolution imaging entails coverage limitations. Processing partial-coverage images using standard pipelines leads to sub-optimal results. We aimed to develop a simple, semi-automated pipeline for processing partial-coverage UHF-fMRI data using widely used image processing algorithms. MATERIALS AND METHODS: We developed automated pipelines for optimized skull stripping and co-registration of partial-coverage UHF functional images, using built-in functions of the Centre for Functional Magnetic Resonance Imaging of the Brain's (FMRIB's) Software library (FSL) and advanced normalization tools. We incorporated the pipelines into the FSL's functional analysis pipeline and provide a semi-automated optimized partial-coverage functional analysis pipeline (OPFAP). RESULTS: Compared to the standard pipeline, the OPFAP yielded images with 15 and 30% greater volume of non-zero voxels after skull stripping the functional and anatomical images, respectively (all p = 0.0004), which reflected the conservation of cortical voxels lost when the standard pipeline was used. The OPFAP yielded the greatest Dice and Jaccard coefficients (87 and 80%, respectively; all p < 0.0001) between the co-registered participant gyri maps and the template gyri maps, demonstrating the goodness of the co-registration results. Furthermore, the greatest volume of group-level activation in the most number of functionally relevant regions was observed when the OPFAP was used. Importantly, group-level activations were not observed when using the standard pipeline. CONCLUSION: These results suggest that the OPFAP should be used for processing partial-coverage UHF-fMRI data for detecting high-resolution macroscopic blood oxygenation level-dependent activations.

Spatially dynamic recurrent information flow across long-range dorsal motor network encodes selective motor goals.

Performing voluntary movements involves many regions of the brain, but it is unknown how they work together to plan and execute specific movements. We recorded high-resolution ultra-high-field blood-oxygen-level-dependent signal during a cued ankle-dorsiflexion task. The spatiotemporal dynamics and the patterns of task-relevant information flow across the dorsal motor network were investigated. We show that task-relevant information appears and decays earlier in the higher order areas of the dorsal motor network then in the primary motor cortex. Furthermore, the results show that task-relevant information is encoded in general initially, and then selective goals are subsequently encoded in specifics subregions across the network. Importantly, the patterns of recurrent information flow across the network vary across different subregions depending on the goal. Recurrent information flow was observed across all higher order areas of the dorsal motor network in the subregions encoding for the current goal. In contrast, only the top-down information flow from the supplementary motor cortex to the frontoparietal regions, with weakened recurrent information flow between the frontoparietal regions and bottom-up information flow from the frontoparietal regions to the supplementary cortex were observed in the subregions encoding for the opposing goal. We conclude that selective motor goal encoding and execution rely on goal-dependent differences in subregional recurrent information flow patterns across the long-range dorsal motor network areas that exhibit graded functional specialization.

3D-multi-echo radial imaging of 23 Na (3D-MERINA) for time-efficient multi-parameter tissue compartment mapping.

PURPOSE: This work demonstrates a 3D radial multi-echo acquisition scheme for time-efficient sodium (23 Na) MR-signal acquisition and analysis. Echo reconstructions were used to produce signal-to-noise ratio (SNR)-enhanced 23 Na-images and parameter maps of the biexponential observed transverse relaxation time ( T2*) decay. METHODS: A custom-built sequence for radial multi-echo acquisition was proposed for acquisition of a series of 3D volumetric 23 Na-images. Measurements acquired in a phantom and in vivo human brains were analyzed for SNR enhancement and multi-component T2* estimation. RESULTS: Rapid gradient refocused imaging acquired 38 echoes within a repetition time of 160 ms. Signal averaging of multi-echo time (TE) measurements showed an average brain tissue SNR enhancement of 34% compared to single-TE images across subjects. Phantom and in vivo measurements detected distinguishable signal decay characteristics for fluid and solid media. Mapping results were investigated in phantom and in vivo experiments for sequence timing optimization and signal decay analysis. The T2* mapping results were consistent with previously reported values and facilitated fluid-signal discrimination. CONCLUSION: The proposed method offers an efficient 23 Na-imaging scheme that extends existing 23 Na-MRI sequences by acquiring signal decay information with no increase in time or specific absorption rate. The resultant SNR-enhanced 23 Na-images and estimated T2* signal decay characteristics offer great potential for detailed investigation of tissue compartment characterization and clinical application. Magn Reson Med 79:1950-1961, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

7T-fMRI: Faster temporal resolution yields optimal BOLD sensitivity for functional network imaging specifically at high spatial resolution.

Recent developments in accelerated imaging methods allow faster acquisition of high spatial resolution images. This could improve the applications of functional magnetic resonance imaging at 7 Tesla (7T-fMRI), such as neurosurgical planning and Brain Computer Interfaces (BCIs). However, increasing the spatial and temporal resolution will both lead to signal-to-noise ratio (SNR) losses due to decreased net magnetization per voxel and T1-relaxation effect, respectively. This could potentially offset the SNR efficiency gains made with increasing temporal resolution. We investigated the effects of varying spatial and temporal resolution on fMRI sensitivity measures and their implications on fMRI-based BCI simulations. We compared temporal signal-to-noise ratio (tSNR), observed percent signal change (%∆S), volumes of significant activation, Z-scores and decoding performance of linear classifiers commonly used in BCIs across a range of spatial and temporal resolution images acquired during an ankle-tapping task. Our results revealed an average increase of 22% in %∆S (p=0.006) and 9% in decoding performance (p=0.015) with temporal resolution only at the highest spatial resolution of 1.5×1.5×1.5mm3, despite a 29% decrease in tSNR (p<0.001) and plateaued Z-scores. Further, the volume of significant activation was indifferent (p>0.05) across spatial resolution specifically at the highest temporal resolution of 500ms. These results demonstrate that the overall BOLD sensitivity can be increased significantly with temporal resolution, granted an adequately high spatial resolution with minimal physiological noise level. This shows the feasibility of diffuse motor-network imaging at high spatial and temporal resolution with robust BOLD sensitivity with 7T-fMRI. Importantly, we show that this sensitivity improvement could be extended to an fMRI application such as BCIs.

Quantifying the area-at-risk of myocardial infarction in-vivo using arterial spin labeling cardiac magnetic resonance.

T2-weighted cardiovascular magnetic resonance (T2-CMR) of myocardial edema can quantify the area-at-risk (AAR) following acute myocardial infarction (AMI), and has been used to assess myocardial salvage by new cardioprotective therapies. However, some of these therapies may reduce edema, leading to an underestimation of the AAR by T2-CMR. Here, we investigated arterial spin labeling (ASL) perfusion CMR as a novel approach to quantify the AAR following AMI. Adult B6sv129-mice were subjected to in vivo left coronary artery ligation for 30 minutes followed by 72 hours reperfusion. T2-mapping was used to quantify the edema-based AAR (% of left ventricle) following ischemic preconditioning (IPC) or cyclosporin-A (CsA) treatment. In control animals, the AAR by T2-mapping corresponded to that delineated by histology. As expected, both IPC and CsA reduced MI size. However, IPC, but not CsA, also reduced myocardial edema leading to an underestimation of the AAR by T2-mapping. In contrast, regions of reduced myocardial perfusion delineated by cardiac ASL were able to delineate the AAR when compared to both T2-mapping and histology in control animals, and were not affected by either IPC or CsA. Therefore, ASL perfusion CMR may be an alternative method for quantifying the AAR following AMI, which unlike T2-mapping, is not affected by IPC.

Using the robust principal component analysis algorithm to remove RF spike artifacts from MR images.

PURPOSE: Brief bursts of RF noise during MR data acquisition ("k-space spikes") cause disruptive image artifacts, manifesting as stripes overlaid on the image. RF noise is often related to hardware problems, including vibrations during gradient-heavy sequences, such as diffusion-weighted imaging. In this study, we present an application of the Robust Principal Component Analysis (RPCA) algorithm to remove spike noise from k-space. METHODS: Corrupted k-space matrices were decomposed into their low-rank and sparse components using the RPCA algorithm, such that spikes were contained within the sparse component and artifact-free k-space data remained in the low-rank component. Automated center refilling was applied to keep the peaked central cluster of k-space from misclassification in the sparse component. RESULTS: This algorithm was demonstrated to effectively remove k-space spikes from four data types under conditions generating spikes: (i) mouse heart T1 mapping, (ii) mouse heart cine imaging, (iii) human kidney diffusion tensor imaging (DTI) data, and (iv) human brain DTI data. Myocardial T1 values changed by 86.1 ± 171 ms following despiking, and fractional anisotropy values were recovered following despiking of DTI data. CONCLUSION: The RPCA despiking algorithm will be a valuable postprocessing method for retrospectively removing stripe artifacts without affecting the underlying signal of interest. Magn Reson Med 75:2517-2525, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Diffusion microscopic MRI of the mouse embryo: Protocol and practical implementation in the splotch mouse model.

PURPOSE: Advanced methodologies for visualizing novel tissue contrast are essential for phenotyping the ever-increasing number of mutant mouse embryos being generated. Although diffusion microscopic MRI (µMRI) has been used to phenotype embryos, widespread routine use is limited by extended scanning times, and there is no established experimental procedure ensuring optimal data acquisition. METHODS: We developed two protocols for designing experimental procedures for diffusion µMRI of mouse embryos, which take into account the effect of embryo preparation and pulse sequence parameters on resulting data. We applied our protocols to an investigation of the splotch mouse model as an example implementation. RESULTS: The protocols provide DTI data in 24 min per direction at 75 µm isotropic using a three-dimensional fast spin-echo sequence, enabling preliminary imaging in 3 h (6 directions plus one unweighted measurement), or detailed imaging in 9 h (42 directions plus six unweighted measurements). Application to the splotch model enabled assessment of spinal cord pathology. CONCLUSION: We present guidelines for designing diffusion µMRI experiments, which may be adapted for different studies and research facilities. As they are suitable for routine use and may be readily implemented, we hope they will be adopted by the phenotyping community.

Monitoring systemic amyloidosis using MRI measurements of the extracellular volume fraction.

We report the in vivo evaluation, in a murine model, of MRI measurements of the extracellular volume fraction (ECV) for the detection and monitoring of systemic amyloidosis. A new inducible transgenic model was used, with increased production of mouse serum amyloid A protein controlled by oral administration of doxycycline, that causes both the usual hepatic and splenic amyloidosis and also cardiac deposits. ECV was measured in vivo by equilibrium contrast MRI in the heart and liver of 11 amyloidotic and 10 control mice. There was no difference in the cardiac function between groups, but ECV was significantly increased in the heart, mean (standard deviation) 0.20 (0.05) versus 0.14 (0.04), p < 0.005, and liver, 0.27 (0.04) versus 0.15 (0.04), p < 0.0005, of amyloidotic animals and was strongly correlated with the histological amyloid score, myocardium, ρ = 0.67, p < 0.01; liver, ρ = 0.87, p < 0.01. In a further four mice that received human serum amyloid P component (SAP) followed by anti-human SAP antibody, a treatment to eliminate visceral amyloid deposits, ECV in the liver and spleen returned to baseline after therapy (p < 0.01). MRI measurement of ECV is a sensitive marker of amyloid deposits with potential application for early detection and monitoring therapies promoting their clearance.

Anodal transcranial direct current stimulation increases brain intracellular pH and modulates bioenergetics.

Transcranial direct current stimulation is an emerging treatment for brain disorders but its mode of action is not well understood. We applied 10 min 1 mA anodal transcranial direct current stimulation (tDCS) inside the bore of a 3 T MRI scanner to the left dorsolateral prefrontal cortex of 13 healthy volunteers (aged 19-28 yr) in a blinded, sham-controlled, cross-over design. Brain bioenergetics were measured from the left temporo-frontal region using 31P magnetic resonance spectroscopy before, during and for 20 min following tDCS. Brain pH rose during tDCS and remained elevated afterwards. Phosphomonoesters were significantly decreased while inorganic phosphate (Pi) also fell. Partial-least squares discriminant analysis of the data revealed two significantly different subject groups: one where phosphocreatine (PCr), ATP and Pi fell along with a larger increase in pH and one where PCr and ATP increased along with a smaller increase in pH and a slower and more sustained decrease in Pi. Group membership was predicted by baseline pH and ATP. We interpreted the effects of tDCS as driving two biochemical processes: cellular consumption of ATP causing hydrolysis of PCr via the creatine kinase reaction driving the increase in pH; synthesis of ATP and PCr by mitochondria with concomitant drop in Pi and phosphomonoester levels.

Diffusion tensor parameters and principal eigenvector coherence: relation to b-value intervals and field strength.

Diffusion-weighted MRI images acquired at b-value greater than 1000 s mm(-2) measure the diffusion of a restricted pool of water molecules. High b-value images are accompanied by a reduction in signal-to-noise ratio (SNR) due to the application of large diffusion gradients. By fitting the diffusion tensor model to data acquired at incremental b-value intervals, we determined the effect of SNR on tensor parameters in normal human brains, in vivo. In addition, we also investigated the impact of field strength on the diffusion tensor model. Data were acquired at 1.5 and 3T, at b-values 0, 1000, 2000 and 3000 s mm(-2) in twenty diffusion-sensitised directions. Fractional anisotropy (FA), mean diffusivity (MD) and principal eigenvector coherence (κ) were calculated from diffusion tensors fitted between datasets with b-values 0-1000, 0-2000, 0-3000, 1000-2000 and 2000-3000 s mm(-2). Field strength and b-value effects on diffusion parameters were analysed in white and grey matter regions of interest. Decreases in FA, κ and MD were found with increasing b-value in white matter. Univariate analysis showed a significant increase in FA with increasing field strength in highly organised white matter. These results suggest there are significant differences in diffusion parameters at 1.5 and 3T and that the optimal results, in terms of the highest values of FA in white matter, are obtained at 3T with a maximum b=1000 s mm(-2).

Cardiac arterial spin labeling using segmented ECG-gated Look-Locker FAIR: variability and repeatability in preclinical studies.

MRI is important for the assessment of cardiac structure and function in preclinical studies of cardiac disease. Arterial spin labeling techniques can be used to measure perfusion noninvasively. In this study, an electrocardiogram-gated Look-Locker sequence with segmented k-space acquisition has been implemented to acquire single slice arterial spin labeling data sets in 15 min in the mouse heart. A data logger was introduced to improve data quality by: (1) allowing automated rejection of respiration-corrupted images, (2) providing additional prospective gating to improve consistency of acquisition timing, and (3) allowing the recombination of uncorrupted k-space lines from consecutive data sets to reduce respiration corruption. Finally, variability and repeatability of perfusion estimation within-session, between-session, between-animal, and between image rejection criteria were assessed in mice. The criterion used to reject images from the T(1) fit was shown to affect the perfusion estimation. These data showed that the between-animal coefficient of variability (24%) was greater than the between-session variability (17%) and within-session variability (11%). Furthermore, the magnitude of change in perfusion required to detect differences was 30% (within-session) and 55% (between-session) according to Bland-Altman repeatability analysis. These technique developments and repeatability statistics will provide a platform for future preclinical studies applying cardiac arterial spin labeling.

Multislice cardiac arterial spin labeling using improved myocardial perfusion quantification with simultaneously measured blood pool input function.

PURPOSE: Myocardial blood flow (MBF) is an important indicator of cardiac tissue health, which can be measured using arterial spin labeling. This study aimed to develop a new method of MBF quantification with blood pool magnetization measurement ("bpMBF quantification") that allows multislice cardiac arterial spin labeling. THEORY AND METHODS: A multislice segmented ECG-gated Look-Locker T1 mapping sequence was validated. Quantification of multislice arterial spin labeling is not straightforward due to the large volume of blood inverted following slice-selective inversion. For bpMBF quantification, a direct measurement of the left-ventricle blood pool magnetization was used to approximate the blood input function into the Bloch equations. Simulations and in vivo measurements in the mouse heart were performed to evaluate the bpMBF method. RESULTS: Measurements indicated that blood pool magnetization requires ∼3 s to return to equilibrium following slice-selective inversion. Simulation and in vivo results show that bpMBF quantification is robust to variations in slice-selective thickness and therefore applicable to multislice acquisition, whereas traditional methods are likely to underestimate multislice perfusion. In vivo, single and multislice perfusion values matched well when quantified using bpMBF. CONCLUSION: The first multislice cardiac arterial spin labeling technique has been presented, which can be used for accurate perfusion measurements in studies of cardiac disease.

Structural correlates of active-staining following magnetic resonance microscopy in the mouse brain.

Extensive worldwide efforts are underway to produce knockout mice for each of the ~25,000 mouse genes, which may give new insights into the underlying pathophysiology of neurological disease. Microscopic magnetic resonance imaging (µMRI) is a key method for non-invasive morphological phenotyping, capable of producing high-resolution 3D images of ex-vivo brains, after fixation with an MR contrast agent. These agents have been suggested to act as active-stains, enhancing structures not normally visible on MRI. In this study, we investigated the structural correlates of the MRI agent Gd-DTPA, together with the optimal preparation and scan parameters for contrast-enhanced gradient-echo imaging of the mouse brain. We observed that in-situ preparation was preferential to ex-situ due to the degree of extraction damage. In-situ brains scanned with optimised parameters, enabled images with a high signal-to-noise-ratio (SNR ~30) and comprehensive anatomical delineation. Direct correlation of the MR brain structures to histology, detailed fine histoarchitecture in the cortex, cerebellum, olfactory bulb and hippocampus. Neurofilament staining demonstrated that regions of negative MR contrast strongly correlated to myelinated white-matter structures, whilst structures of more positive MR contrast corresponded to areas with high grey matter content. We were able to identify many sub-regions, particularly within the hippocampus, such as the unmyelinated mossy fibres (stratum lucidum) and their region of synapse in the stratum pyramidale, together with the granular layer of the dentate gyrus, an area of densely packed cell bodies, which was clearly visible as a region of hyperintensity. This suggests that cellular structure influences the site-specific distribution of the MR contrast agent, resulting in local variations in T(2)*, which leads to enhanced tissue discrimination. Our findings provide insights not only into the cellular distribution and mechanism of MR active-staining, but also allow for three dimensional analysis, which enables interpretation of magnetic resonance microscopy brain data and highlights cellular structure for investigation of disease processes in development and disease.

Accelerated cardiac magnetic resonance imaging in the mouse using an eight-channel array at 9.4 Tesla.

MRI has become an important tool to noninvasively assess global and regional cardiac function, infarct size, or myocardial blood flow in surgically or genetically modified mouse models of human heart disease. Constraints on scan time due to sensitivity to general anesthesia in hemodynamically compromised mice frequently limit the number of parameters available in one imaging session. Parallel imaging techniques to reduce acquisition times require coil arrays, which are technically challenging to design at ultrahigh magnetic field strengths. This work validates the use of an eight-channel volume phased-array coil for cardiac MRI in mice at 9.4 T. Two- and three-dimensional sequences were combined with parallel imaging techniques and used to quantify global cardiac function, T(1)-relaxation times and infarct sizes. Furthermore, the rapid acquisition of functional cine-data allowed for the first time in mice measurement of left-ventricular peak filling and ejection rates under intravenous infusion of dobutamine. The results demonstrate that a threefold accelerated data acquisition is generally feasible without compromising the accuracy of the results. This strategy may eventually pave the way for routine, multiparametric phenotyping of mouse hearts in vivo within one imaging session of tolerable duration.