Enhanced delineation of white matter structures of the fixed mouse brain using Gd‐DTPA in microscopic MRI

The purpose of this study was to investigate the effect of gadolinium (III) diethyltriaminepenta‐acetic acid (Gd‐DTPA) mixed with a fixative on the image contrast between the white and gray matter of the perfusion‐fixed mouse brain. A series of microscopic MRI (µMRI) studies using different concentrations of Gd‐DTPA were performed at multiple time points to determine the optimal Gd‐DTPA concentration and fixation time necessary to maximize the contrast‐to‐noise ratio between the white and gray matter with relatively short scan time using a three‐dimensional gradient‐echo pulse sequence. On the basis of the experimental results, high‐resolution (39 µm isotropic) images with excellent contrast‐to‐noise ratio (～50) were acquired in less than 2 h of scan time after the specimen had been soaked in 10 mM Gd‐DTPA for 4 days. Excellent correlation was noted between µMRI and histology in that the µMRI clearly depicted brain regions that were also observed by the Kluver–Barrera stain. The enhanced contrast between the white and gray matter obtained by the proposed µMRI method may facilitate the development of µMRI‐based morphological phenotyping methods for mouse models of neurological disorders. Copyright © 2008 John Wiley & Sons, Ltd.     

Lipid suppression via double inversion recovery with symmetric frequency sweep for robust 2D‐GRAPPA‐accelerated MRSI of the brain at 7 T

This work presents a new approach for high‐resolution MRSI of the brain at 7 T in clinically feasible measurement times. Two major problems of MRSI are the long scan times for large matrix sizes and the possible spectral contamination by the transcranial lipid signal. We propose a combination of free induction decay (FID)‐MRSI with a short acquisition delay and acceleration via in‐plane two‐dimensional generalised autocalibrating partially parallel acquisition (2D‐GRAPPA) with adiabatic double inversion recovery (IR)‐based lipid suppression to allow robust high‐resolution MRSI. We performed Bloch simulations to evaluate the magnetisation pathways of lipids and metabolites, and compared the results with phantom measurements. Acceleration factors in the range 2–25 were tested in a phantom. Five volunteers were scanned to verify the value of our MRSI method in vivo. GRAPPA artefacts that cause fold‐in of transcranial lipids were suppressed via double IR, with a non‐selective symmetric frequency sweep. The use of long, low‐power inversion pulses (100 ms) reduced specific absorption rate requirements. The symmetric frequency sweep over both pulses provided good lipid suppression (>90%), in addition to a reduced loss in metabolite signal‐to‐noise ratio (SNR), compared with conventional IR suppression (52–70%). The metabolic mapping over the whole brain slice was not limited to a rectangular region of interest. 2D‐GRAPPA provided acceleration up to a factor of nine for in vivo FID‐MRSI without a substantial increase in g‐factors (<1.1). A 64 × 64 matrix can be acquired with a common repetition time of ~1.3 s in only 8 min without lipid artefacts caused by acceleration. Overall, we present a fast and robust MRSI method, using combined double IR fat suppression and 2D‐GRAPPA acceleration, which may be used in (pre)clinical studies of the brain at 7 T. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.     

Non‐water‐suppressed short‐echo‐time magnetic resonance spectroscopic imaging using a concentric ring k‐space trajectory

Water‐suppressed MRS acquisition techniques have been the standard MRS approach used in research and for clinical scanning to date. The acquisition of a non‐water‐suppressed MRS spectrum is used for artefact correction, reconstruction of phased‐array coil data and metabolite quantification. Here, a two‐scan metabolite‐cycling magnetic resonance spectroscopic imaging (MRSI) scheme that does not use water suppression is demonstrated and evaluated. Specifically, the feasibility of acquiring and quantifying short‐echo (T_E = 14 ms), two‐dimensional stimulated echo acquisition mode (STEAM) MRSI spectra in the motor cortex is demonstrated on a 3 T MRI system. The increase in measurement time from the metabolite‐cycling is counterbalanced by a time‐efficient concentric ring k‐space trajectory. To validate the technique, water‐suppressed MRSI acquisitions were also performed for comparison. The proposed non‐water‐suppressed metabolite‐cycling MRSI technique was tested for detection and correction of resonance frequency drifts due to subject motion and/or hardware instability, and the feasibility of high‐resolution metabolic mapping over a whole brain slice was assessed. Our results show that the metabolite spectra and estimated concentrations are in agreement between non‐water‐suppressed and water‐suppressed techniques. The achieved spectral quality, signal‐to‐noise ratio (SNR) > 20 and linewidth <7 Hz allowed reliable metabolic mapping of five major brain metabolites in the motor cortex with an in‐plane resolution of 10 × 10 mm² in 8 min and with a Cramér‐Rao lower bound of less than 20% using LCModel analysis. In addition, the high SNR of the water peak of the non‐water‐suppressed technique enabled voxel‐wise single‐scan frequency, phase and eddy current correction. These findings demonstrate that our non‐water‐suppressed metabolite‐cycling MRSI technique can perform robustly on 3 T MRI systems and within a clinically feasible acquisition time.     

Multi‐echo susceptibility‐weighted imaging and histology of open‐field blast‐induced traumatic brain injury in a rat model

Blast‐induced traumatic brain injury is on the rise, predominantly as a result of the use of improvised explosive devices, resulting in undesirable neuropsychological dysfunctions, as demonstrated in both animals and humans. This study investigated the effect of open‐field blast injury on the rat brain using multi‐echo, susceptibility‐weighted imaging (SWI). Multi‐echo SWI provided phase maps with better signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR), making it a sensitive technique for brain injury. Male Sprague‐Dawley rats were subjected to a survivable blast of 180 kPa. The visibility of blood vessels of varying sizes improved with multi‐echo SWI. Reduced signal intensity from major vessels post‐blast indicates increased deoxyhaemoglobin. Relative cerebral blood flow was computed from filtered phase SWI images using inferred changes in oxygen saturation from major blood vessels. Cerebral blood flow decreased significantly at day 3 and day 5 post‐blast compared with that pre‐blast. This was substantiated by the upregulation of β‐amyloid precursor protein (β‐APP), a marker of ischaemia, in the neuronal perikaya of the cerebral cortex, as observed by immunofluorescence, and in the cortical tissue by western blot analysis. Our findings indicate the presence of brain ischaemia in post‐blast acute phase of injury with possible recovery subsequently. Our results from cerebrovascular imaging, histology and staining provide an insight into the ischaemic state of the brain post‐blast and may be useful for prognosis and outcome. Copyright © 2015 John Wiley & Sons, Ltd.     

Whole‐brain perfusion imaging with balanced steady‐state free precession arterial spin labeling

Recently, balanced steady‐state free precession (bSSFP) readout has been proposed for arterial spin labeling (ASL) perfusion imaging to reduce susceptibility artifacts at a relatively high spatial resolution and signal‐to‐noise ratio (SNR). However, the main limitation of bSSFP‐ASL is the low spatial coverage. In this work, methods to increase the spatial coverage of bSSFP‐ASL are proposed for distortion‐free, high‐resolution, whole‐brain perfusion imaging. Three strategies of (i) segmentation, (ii) compressed sensing (CS) and (iii) a hybrid approach combining the two methods were tested to increase the spatial coverage of pseudo‐continuous ASL (pCASL) with three‐dimensional bSSFP readout. The spatial coverage was increased by factors of two, four and six using each of the three approaches, whilst maintaining the same total scan time (5.3 min). The number of segments and/or CS acceleration rate (R) correspondingly increased to maintain the same bSSFP readout time (1.2 s). The segmentation approach allowed whole‐brain perfusion imaging for pCASL‐bSSFP with no penalty in SNR and/or total scan time. The CS approach increased the spatial coverage of pCASL‐bSSFP whilst maintaining the temporal resolution, with minimal impact on the image quality. The hybrid approach provided compromised effects between the two methods. Balanced SSFP‐based ASL allows the acquisition of perfusion images with wide spatial coverage, high spatial resolution and SNR, and reduced susceptibility artifacts, and thus may become a good choice for clinical and neurological studies. Copyright © 2015 John Wiley & Sons, Ltd.     

Spatial location and strength of BOLD activation in high-spatial-resolution fMRI of the motor cortex: a comparison of spin echo and gradient echo fMRI at 7 T

The increased blood oxygenation level‐dependent contrast‐to‐noise ratio at ultrahigh field (7 T) has been exploited in a comparison of the spatial location and strength of activation in high‐resolution (1.5 mm isotropic) gradient echo (GE) and spin echo (SE), echo planar imaging data acquired during the execution of a simple motor task in five subjects. SE data were acquired at six echo times from 30 to 55 ms. Excellent fat suppression was achieved in the SE echo planar images using slice‐selective gradient reversal. Threshold‐free cluster enhancement was used to define regions of interest (ROIs) containing voxels showing significant stimulus‐locked signal changes from the GE and average SE data. These were used to compare the signal changes and spatial locations of activated regions in SE and GE data. T₂ and T₂* values were measured, with means of 48.3 ± 1.1 ms and 36.5 ± 3.4 ms in the SE ROI. In addition, we identified a dark band in SE images of the motor cortex corresponding to a region in which T₂ and T₂* were significantly lower than in the surrounding grey matter. The fractional SE signal change in the ROI was found to vary linearly as a function of TE, with a slope that was dependent on the particular ROI assessed: the mean ΔR₂ value was found to be 0.85 ± 0.11 s^–1 for the SE ROI and ?0.37 ± 0.05 s^–1 for the GE ROI. The fractional signal change relative to the shortest TE revealed that the largest signal change occurred at a TE of 45 ms outside of the dark band. At this TE, the ratio of the fractional signal change in GE and SE data was found to be 0.48 ± 0.05. Phase maps produced from high‐resolution GE images spanning the right motor cortex were used to identify veins. The GE ROI was found to contain 18% more voxels overlying the venous mask than the SE ROI. Copyright © 2011 John Wiley & Sons, Ltd.     

Density‐weighted concentric rings k‐space trajectory for 1H magnetic resonance spectroscopic imaging at 7 T

It has been shown that density‐weighted (DW) k‐space sampling with spiral and conventional phase encoding trajectories reduces spatial side lobes in magnetic resonance spectroscopic imaging (MRSI). In this study, we propose a new concentric ring trajectory (CRT) for DW‐MRSI that samples k‐space with a density that is proportional to a spatial, isotropic Hanning window. The properties of two different DW‐CRTs were compared against a radially equidistant (RE) CRT and an echo‐planar spectroscopic imaging (EPSI) trajectory in simulations, phantoms and in vivo experiments. These experiments, conducted at 7 T with a fixed nominal voxel size and matched acquisition times, revealed that the two DW‐CRT designs improved the shape of the spatial response function by suppressing side lobes, also resulting in improved signal‐to‐noise ratio (SNR). High‐quality spectra were acquired for all trajectories from a specific region of interest in the motor cortex with an in‐plane resolution of 7.5 × 7.5 mm² in 8 min 3 s. Due to hardware limitations, high‐spatial‐resolution spectra with an in‐plane resolution of 5 × 5 mm² and an acquisition time of 12 min 48 s were acquired only for the RE and one of the DW‐CRT trajectories and not for EPSI. For all phantom and in vivo experiments, DW‐CRTs resulted in the highest SNR. The achieved in vivo spectral quality of the DW‐CRT method allowed for reliable metabolic mapping of eight metabolites including N‐acetylaspartylglutamate, γ‐aminobutyric acid and glutathione with Cramér‐Rao lower bounds below 50%, using an LCModel analysis. Finally, high‐quality metabolic mapping of a whole brain slice using DW‐CRT was achieved with a high in‐plane resolution of 5 × 5 mm² in a healthy subject. These findings demonstrate that our DW‐CRT MRSI technique can perform robustly on MRI systems and within a clinically feasible acquisition time.     

A model‐based reconstruction for undersampled radial spin‐echo DTI with variational penalties on the diffusion tensor

Radial spin‐echo diffusion imaging allows motion‐robust imaging of tissues with very low T₂ values like articular cartilage with high spatial resolution and signal‐to‐noise ratio (SNR). However, in vivo measurements are challenging, due to the significantly slower data acquisition speed of spin‐echo sequences and the less efficient k‐space coverage of radial sampling, which raises the demand for accelerated protocols by means of undersampling. This work introduces a new reconstruction approach for undersampled diffusion‐tensor imaging (DTI). A model‐based reconstruction implicitly exploits redundancies in the diffusion‐weighted images by reducing the number of unknowns in the optimization problem and compressed sensing is performed directly in the target quantitative domain by imposing a total variation (TV) constraint on the elements of the diffusion tensor. Experiments were performed for an anisotropic phantom and the knee and brain of healthy volunteers (three and two volunteers, respectively). Evaluation of the new approach was conducted by comparing the results with reconstructions performed with gridding, combined parallel imaging and compressed sensing and a recently proposed model‐based approach. The experiments demonstrated improvements in terms of reduction of noise and streaking artifacts in the quantitative parameter maps, as well as a reduction of angular dispersion of the primary eigenvector when using the proposed method, without introducing systematic errors into the maps. This may enable an essential reduction of the acquisition time in radial spin‐echo diffusion‐tensor imaging without degrading parameter quantification and/or SNR. Copyright © 2015 John Wiley & Sons, Ltd.     

A multi‐compartmental SE‐BOLD interpretation for stimulus‐related signal changes in diffusion‐weighted functional MRI

A new interpretation is proposed for stimulus‐induced signal changes in diffusion‐weighted functional MRI. T₂‐weighted spin‐echo echo‐planar images were acquired at different diffusion‐weightings while visual stimulation was presented to human volunteers. The amplitudes of the positive stimulus‐correlated response and post‐stimulus undershoot (PSU) in the functional time‐courses were found to follow different trends as a function of b‐value. Data were analysed using a three‐compartment signal model, with one compartment being purely vascular and the other two dominated by fast‐ and slow‐diffusing molecules in the brain tissue. The diffusion coefficients of the tissue were assumed to be constant throughout the experiments. It is shown that the stimulus‐induced signal changes can be decomposed into independent contributions originating from each of the three compartments. After decomposition, the fast‐diffusion phase displays a substantial PSU, while the slow‐diffusion phase demonstrates a highly reproducible and stimulus‐correlated time‐course with minimal undershoot. The decomposed responses are interpreted in terms of the spin‐echo blood oxygenation level dependent (SE‐BOLD) effect, and it is proposed that the signal produced by fast‐ and slow‐diffusing molecules reflect a sensitivity to susceptibility changes in arteriole/venule‐ and capillary‐sized vessels, respectively. This interpretation suggests that diffusion‐weighted SE‐BOLD imaging may provide subtle information about the haemodynamic and neuronal responses. Copyright © 2009 John Wiley & Sons, Ltd.     

Triple‐echo steady‐state T2 relaxometry of the human brain at high to ultra‐high fields

Quantitative MRI techniques, such as T₂ relaxometry, have demonstrated the potential to detect changes in the tissue microstructure of the human brain with higher specificity to the underlying pathology than in conventional morphological imaging. At high to ultra‐high field strengths, quantitative MR‐based tissue characterization benefits from the higher signal‐to‐noise ratio traded for either improved resolution or reduced scan time, but is impaired by severe static (B₀) and transmit (B₁) field heterogeneities. The objective of this study was to derive a robust relaxometry technique for fast T₂ mapping of the human brain at high to ultra‐high fields, which is highly insensitive to B₀ and B₁ field variations. The proposed method relies on a recently presented three‐dimensional (3D) triple‐echo steady‐state (TESS) imaging approach that has proven to be suitable for fast intrinsically B₁‐insensitive T₂ relaxometry of rigid targets. In this work, 3D TESS imaging is adapted for rapid high‐ to ultra‐high‐field two‐dimensional (2D) acquisitions. The achieved short scan times of 2D TESS measurements reduce motion sensitivity and make TESS‐based T₂ quantification feasible in the brain. After validation in vitro and in vivo at 3 T, T₂ maps of the human brain were obtained at 7 and 9.4 T. Excellent agreement between TESS‐based T₂ measurements and reference single‐echo spin‐echo data was found in vitro and in vivo at 3 T, and T₂ relaxometry based on TESS imaging was proven to be feasible and reliable in the human brain at 7 and 9.4 T. Although prominent B₀ and B₁ field variations occur at ultra‐high fields, the T₂ maps obtained show no B₀‐ or B₁‐related degradations. In conclusion, as a result of the observed robustness, TESS T₂ may emerge as a valuable measure for the early diagnosis and progression monitoring of brain diseases in high‐resolution 2D acquisitions at high to ultra‐high fields. Copyright © 2014 John Wiley & Sons, Ltd.     

Partitioning k‐space for cylindrical three‐dimensional rapid acquisition with relaxation enhancement imaging in the mouse brain

Three‐dimensional rapid acquisition with relaxation enhancement (RARE) scans require the assignment of each phase encode step in two dimensions to an echo in the echo train. Although this assignment is frequently made across the entire Cartesian grid, collection of only the central cylinder of k‐space by eliminating the corners in each phase encode dimension reduces the scan time by ~22% with negligible impact on image quality. The recipe for the assignment of echoes to grid points for such an acquisition is less straightforward than for the simple full Cartesian acquisition case, and has important implications for image quality. We explored several methods of partitioning k‐space—exploiting angular symmetry in one extreme or emulating a cropped Cartesian acquisition in the other—and acquired three‐dimensional RARE magnetic resonance imaging (MRI) scans of the ex vivo mouse brain. We evaluated each partitioning method for sensitivity to artifacts and then further considered strategies to minimize these through averaging or interleaving of echoes and by empirical phase correction. All scans were collected 16 at a time with multiple‐mouse MRI. Although all schemes considered could be used to generate images, the results indicate that the emulation of a standard Cartesian echo assignment, by partitioning preferentially along one dimension within the cylinder, is more robust to artifacts. Samples at the periphery of the bore showed larger phase deviations and higher sensitivity to artifacts, but images of good quality could still be obtained with an optimized acquisition protocol. A protocol for high‐resolution (40 μm) ex vivo images using this approach is presented, and has been used routinely with a success rate of 99% in over 1000 images.     

Simultaneous multi‐slice spin‐ and gradient‐echo dynamic susceptibility‐contrast perfusion‐weighted MRI of gliomas

Although combined spin‐ and gradient‐echo (SAGE) dynamic susceptibility‐contrast (DSC) MRI can provide perfusion quantification that is sensitive to both macrovessels and microvessels while correcting for T₁‐shortening effects, spatial coverage is often limited in order to maintain a high temporal resolution for DSC quantification. In this work, we combined a SAGE echo‐planar imaging (EPI) sequence with simultaneous multi‐slice (SMS) excitation and blipped controlled aliasing in parallel imaging (blipped CAIPI) at 3 T to achieve both high temporal resolution and whole brain coverage. Two protocols using this sequence with multi‐band (MB) acceleration factors of 2 and 3 were evaluated in 20 patients with treated gliomas to determine the optimal scan parameters for clinical use. ΔR₂*(t) and ΔR₂(t) curves were derived to calculate dynamic signal‐to‐noise ratio (dSNR), ΔR₂*‐ and ΔR₂‐based relative cerebral blood volume (rCBV), and mean vessel diameter (mVD) for each voxel. The resulting SAGE DSC images acquired using MB acceleration of 3 versus 2 appeared visually similar in terms of image distortion and contrast. The difference in the mean dSNR from normal‐appearing white matter (NAWM) and that in the mean dSNR between NAWM and normal‐appearing gray matter were not statistically significant between the two protocols. ΔR₂*‐ and ΔR₂‐rCBV maps and mVD maps provided unique contrast and spatial heterogeneity within tumors.     

Diffusion‐prepared stimulated‐echo turbo spin echo (DPsti‐TSE): An eddy current‐insensitive sequence for three‐dimensional high‐resolution and undistorted diffusion‐weighted imaging

In this study, we present a new three‐dimensional (3D), diffusion‐prepared turbo spin echo sequence based on a stimulated‐echo read‐out (DPsti‐TSE) enabling high‐resolution and undistorted diffusion‐weighted imaging (DWI). A dephasing gradient in the diffusion preparation module and rephasing gradients in the turbo spin echo module create stimulated echoes, which prevent signal loss caused by eddy currents. Near to perfect agreement of apparent diffusion coefficient (ADC) values between DPsti‐TSE and diffusion‐weighted echo planar imaging (DW‐EPI) was demonstrated in both phantom transient signal experiments and phantom imaging experiments. High‐resolution and undistorted DPsti‐TSE was demonstrated in vivo in prostate and carotid vessel wall. 3D whole‐prostate DWI was achieved with four b values in only 6 min. Undistorted ADC maps of the prostate peripheral zone were obtained at low and high imaging resolutions with no change in mean ADC values [(1.60 ± 0.10) × 10^?3 versus (1.60 ± 0.02) × 10^?3 mm²/s]. High‐resolution 3D DWI of the carotid vessel wall was achieved in 12 min, with consistent ADC values [(1.40 ± 0.23) × 10^?3 mm²/s] across different subjects, as well as slice locations through the imaging volume. This study shows that DPsti‐TSE can serve as a robust 3D diffusion‐weighted sequence and is an attractive alternative to the traditional two‐dimensional DW‐EPI approaches.     

Increased brain perfusion contrast with T2‐prepared intravoxel incoherent motion (T2prep IVIM) MRI

The feasibility to measure brain perfusion using intravoxel incoherent motion (IVIM) MRI has been reported recently with currently clinically available technology. The method is intrinsically local and quantitative, but is contaminated by partial volume effects with cerebrospinal fluid (CSF). Signal from CSF can be suppressed by a 180° inversion recovery (180°‐IR) magnetization preparation, but this also leads to strong suppression of blood and brain tissue signal. Here, we take advantage of the different T₂ relaxations of blood and brain relative to CSF, and implement a T₂‐prepared IVIM (T2prep IVIM) inversion recovery acquisition, which permits a recovery of between 43% and 57% of arterial and venous blood magnetization at excitation time compared with the theoretical recovery of between 27% and 30% with a standard 180°‐IR. We acquired standard IVIM (IVIM), T2prep IVIM and dynamic susceptibility contrast (DSC) images at 3 T using a 32‐multichannel receiver head coil in eight patients with known large high‐grade brain tumors. We compared the contrast and contrast‐to‐noise ratio obtained in the corresponding cerebral blood volume images quantitatively, as well as subjectively by two neuroradiologists. Our findings suggest that quantitative cerebral blood volume contrast and contrast‐to‐noise ratio, as well as subjective lesion detection, contrast quality and diagnostic confidence, are increased with T2prep IVIM relative to IVIM and DSC. Copyright © 2014 John Wiley & Sons, Ltd.     

Pushing the limits of high‐resolution functional MRI using a simple high‐density multi‐element coil design

Recent studies have shown that functional MRI (fMRI) can be sensitive to the laminar and columnar organization of the cortex based on differences in the spatial and temporal characteristics of the blood oxygenation level‐dependent (BOLD) signal originating from the macrovasculature and the neuronal‐specific microvasculature. Human fMRI studies at this scale of the cortical architecture, however, are very rare because the high spatial/temporal resolution required to explore these properties of the BOLD signal are limited by the signal‐to‐noise ratio. Here, we show that it is possible to detect BOLD signal changes at an isotropic spatial resolution as high as 0.55 mm at 7 T using a high‐density multi‐element surface coil with minimal electronics, which allows close proximity to the head. The coil comprises of very small, 1 × 2‐cm², elements arranged in four flexible modules of four elements each (16‐channel) that can be positioned within 1 mm from the head. As a result of this proximity, tissue losses were five‐fold greater than coil losses and sufficient to exclude preamplifier decoupling. When compared with a standard 16‐channel head coil, the BOLD sensitivity was approximately 2.2‐fold higher for a high spatial/temporal resolution (1 mm isotropic/0.4 s), multi‐slice, echo planar acquisition, and approximately three‐ and six‐fold higher for three‐dimensional echo planar images acquired with isotropic resolutions of 0.7 and 0.55 mm, respectively. Improvements in parallel imaging performance (geometry factor) were up to around 1.5‐fold with increasing acceleration factor, and improvements in fMRI detectability (temporal signal‐to‐noise ratio) were up to around four‐fold depending on the distance to the coil. Although deeper lying structures may not benefit from the design, most fMRI questions pertain to the neocortex which lies within approximately 4 cm from the surface. These results suggest that the resolution of fMRI (at 7 T) can approximate levels that are closer to the spatial/temporal scale of the fundamental functional organization of the human cortex using a simple high‐density coil design for high sensitivity. Copyright © 2012 John Wiley & Sons, Ltd.     

High-field MRS of the human brain at short TE and TR

In vivo MRS of the human brain at 7 tesla allows identification of a large number of metabolites at higher spatial resolutions than currently possible at lower field strengths. However, several challenges complicate in vivo localization and artifact suppression in MRS at high spatial resolution within a clinically feasible scan time at 7 tesla. Published MRS sequences at 7 tesla suffer from long echo times, inherent signal‐to‐noise ratio (SNR) loss, large chemical shift displacement artifacts or long repetition times because of excessive radiofrequency (RF) power deposition. In the present study a pulse‐acquire sequence was used that does not suffer from these high field drawbacks. A slice selective excitation combined with high resolution chemical shift imaging for in‐plane localization was used to limit chemical shift displacement artifacts. The pulse‐acquire approach resulted in a very short echo time of 1.4 ms. A cost function guided shimming algorithm was developed to constrain frequency offsets in the excited slice, therefore adiabatic frequency selective suppression could be employed to minimize artifacts from high intensity lipids and water signals in the excited slice. The high sensitivity at a TR of 1 s was demonstrated both on a supraventricular slice as well as in an area very close to the skull in the frontal cortex at a nominal spatial resolution of 0.25 cc within a feasible scan time. Copyright © 2011 John Wiley & Sons, Ltd.     

Cell layers and neuropil: contrast‐enhanced MRI of mouse brain in vivo

Contrast‐enhanced T₁‐ and T₂‐weighted MRI at 9.4 T and in‐plane resolutions of 25 and 30 µm has been demonstrated to differentiate between neural tissues in mouse brain in vivo, including granule cell layers, principal cell layers, general neuropil, specialized neuropil and white matter. In T₁‐weighted MRI of the olfactory bulb, hippocampus and cerebellum, contrast obtained by the intracranial administration of gadopentetate dimeglumine (Gd‐DTPA) reflects the extra‐ and intracellular spaces of gray matter in agreement with histological data. General neuropil areas are highlighted, whereas other tissues present with lower signal intensities. The induced contrast is similar to that in plain T₂‐weighted MRI, but offers a 16–30‐fold higher contrast‐to‐noise ratio. Systemic administration of manganese chloride increases the signal‐to‐noise ratio in T₁‐weighted MRI to a significantly greater extent in principal cell layers and specialized neuropil than in granule cell layers, whereas gadolinium‐enhanced MRI indicates no larger intracellular spaces in these tissues. Granule cell layers are enhanced no more than general neuropil by manganese, whereas gadolinium‐enhanced MRI indicates significantly larger intracellular spaces in the cell layers. These discrepancies suggest that the signal increase after manganese administration reflects cellular activity which is disproportionate to the intracellular space. As a result, principal cell layers and specialized neuropil become highlighted, whereas granule cell layers, general neuropil and white matter present with lower signal intensities. Copyright © 2013 John Wiley & Sons, Ltd.     

Implementation of spin‐echo blood oxygen level‐dependent (BOLD) functional MRI in birds

The advent of high‐field MRI systems has allowed the implementation of blood oxygen level‐dependent functional MRI (BOLD fMRI) on small animals. An increased magnetic field improves the signal‐to‐noise ratio and thus allows an improvement in the spatial resolution. However, it also increases susceptibility artefacts in the commonly acquired gradient‐echo images. This problem is particularly prominent in songbird MRI because of the presence of numerous air cavities in the skull of birds. These T₂*‐related image artefacts can be circumvented using spin‐echo BOLD fMRI. In this article, we describe the implementation of spin‐echo BOLD fMRI in zebra finches, a small songbird of 15–25 g, extensively studied in the behavioural neurosciences of birdsong. Because the main topics in this research domain are song perception and song learning, the protocol implemented used auditory stimuli. Despite the auditory nature of the stimuli and the weak contrast‐to‐noise ratio of spin‐echo BOLD fMRI compared with gradient‐echo BOLD fMRI, we succeeded in detecting statistically significant differences in BOLD responses triggered by different stimuli. This study shows that spin‐echo BOLD fMRI is a viable approach for the investigation of auditory processing in the whole brain of small songbirds. It can also be applied to study auditory processing in other small animals, as well as other sensory modalities. Copyright © 2010 John Wiley & Sons, Ltd.     

Orotracheal manganese‐enhanced MRI (MEMRI): An effective approach for lung tumor detection

Lung cancer is a primary cause of cancer deaths worldwide. Timely detection of this pathology is necessary to delay or interrupt lung cancer progression, ultimately resulting in a possible better prognosis for the patient. In this context, magnetic resonance imaging (MRI) is especially promising. Ultra‐short echo time (UTE) MRI sequences, in combination with gadolinium‐based contrast agents, have indeed shown to be especially adapted to the detection of lung neoplastic lesions at submillimeter precision. Manganese‐enhanced MRI (MEMRI) increasingly appears to be a possible effective alternative to gadolinium‐enhanced MRI. In this work, we investigated whether low‐dose MEMRI can effectively target non‐small‐cell lung cancer in rodents, whilst minimizing the potential toxic effect of manganese. Both systemic and orotracheal administration modalities allowed the identification of tumors of submillimeter size, as confirmed by bioluminescence imaging and histology. Equivalent tumor signal enhancements and contrast‐to‐noise ratios were observed with orotracheal administration using 20 times lower doses compared with the more conventional systemic route. This finding is of crucial importance as it supports the observation that higher performances of contrast agents can be obtained using an orotracheal administration route when targeting lung diseases. As a consequence, lower concentrations of contrast media can be employed, reducing the dose and potential safety issues. The non‐detectable accumulation of ionic manganese in the brain and liver following orotracheal administration observed in vivo is extremely encouraging with regard to the safety of the orotracheal protocol with low‐dose Mn²⁺ administration. To our knowledge, this is the first time that a study has clearly allowed the high‐precision detection of lung tumor and its contours via the synergic employment of a strongly T₁‐weighted MRI UTE sequence and ionic manganese, an inexpensive contrast agent. Overall, these results support the growing interest in drug and contrast agent delivery via the airways to target and diagnose several diseases of the lungs.