Simulation‐based optimization and experimental comparison of intracranial T2‐weighted DANTE‐SPACE vessel wall imaging at 3T and 7T

Purpose: T2‐weighted DANTE‐SPACE (Delay Alternating with Nutation for Tailored Excitation — Sampling Perfection with Application optimized Contrasts using different flip angle Evolution) sequences facilitate non‐invasive intracranial vessel wall imaging at 7T through simultaneous suppression of blood and CSF. However, the achieved vessel wall delineation depends closely on the selected sequence parameters, and little information is available about the performance of the sequence using more widely available 3T MRI. Therefore, in this paper a comprehensive DANTE‐SPACE simulation framework is used for the optimization and quantitative comparison of T2‐weighted DANTE‐SPACE at both 7T and 3T. Methods: Simulations are used to propose optimized sequence parameters at both 3T and 7T. At 7T, an additional protocol which uses a parallel transmission (pTx) shim during the DANTE preparation for improved suppression of inflowing blood is also proposed. Data at both field strengths using optimized and literature protocols are acquired and quantitatively compared in six healthy volunteers. Results: At 7T, more vessel wall signal can be retained while still achieving sufficient CSF suppression by using fewer DANTE pulses than described in previous implementations. The use of a pTx shim during DANTE at 7T provides a modest further improvement to the inner vessel wall delineation. At 3T, aggressive DANTE preparation is required to achieve CSF suppression, resulting in reduced vessel wall signal. As a result, the achievable vessel wall definition at 3T is around half that of 7T. Conclusion: Simulation‐based optimization of DANTE parameters facilitates improved T2‐weighted DANTE‐SPACE contrasts at 7T. The improved vessel definition of T2‐weighted DANTE‐SPACE at 7T makes DANTE preparation more suitable for T2‐weighted VWI at 7T than at 3T

Optimization of Undersampling Parameters for 3D Intracranial Compressed Sensing MR Angiography at 7 Tesla

Purpose: 3D Time-of-flight (TOF) MR Angiography (MRA) can accurately visualize the intracranial vasculature, but is limited by long acquisition times. Compressed sensing (CS) reconstruction can be used to substantially accelerate acquisitions. The quality of those reconstructions depends on the undersampling patterns used in the acquisitions. In this work, optimized sets of undersampling parameters using various acceleration factors for Cartesian 3D TOF-MRA are established. Methods: Fully-sampled datasets acquired at 7T were retrospectively undersampled using variable-density Poisson-disk sampling with various autocalibration region sizes, polynomial orders, and acceleration factors. The accuracy of reconstructions from the different undersampled datasets was assessed using the vessel-masked structural similarity index. Results were compared for four imaging volumes, acquired from two different subjects. Optimized undersampling parameters were validated using additional prospectively undersampled datasets. Results: For all acceleration factors, using a fully-sampled calibration area of 12x12 k-space lines and a polynomial order of around 2-2.4 resulted in the highest image quality. The importance of sampling parameter optimization was found to increase for higher acceleration factors. The results were consistent across resolutions and regions of interest with vessels of varying sizes and tortuosity. In prospectively undersampled acquisitions, using optimized undersampling parameters resulted in a 7.2% increase in the number of visible small vessels at R = 7.2. Conclusion: The image quality of CS TOF-MRA can be improved by appropriate choice of undersampling parameters. The optimized sets of parameters are independent of the acceleration factor.Comment: Manuscript to be submitted to Magnetic Resonance in Medicin

Lack of effect of citalopram on magnetic resonance spectroscopy measures of glutamate and glutamine in frontal cortex of healthy volunteers

Magnetic resonance spectroscopy (MRS) is a non-invasive imaging technique that can provide localised measures of brain chemistry in vivo. We previously found that healthy volunteers receiving the selective serotonin reuptake inhibitor, citalopram, daily for 1 week showed higher levels of a combined measure of glutamate and glutamine (Glx) in occipital cortex than those receiving placebo. The aim of this study was to assess if a similar effect could be detected in the frontal brain region. Twenty-three healthy volunteers randomised to receive either citalopram 20 mg or a placebo capsule daily for 7–10 days were studied and scanned using a 3T Varian INOVA system before and at the end of treatment. Standard short-TE (echo time) PRESS (Point-resolved spectroscopy) (TE = 26 ms) and PRESS-J spectra were acquired from a single 8-cm3 voxel in a frontal region incorporating anterior cingulate cortex. Glutamate and total Glx levels were quantified both relative to creatine and as absolute levels. Relative to placebo, citalopram produced no change in Glx or glutamate alone at the end of the study. Similarly, no effect was seen on other MRS measures studied: myo-inositol, choline, N-acetylaspartate and creatine. These data suggest that the effects of serotonin reuptake to modify cortical glutamatergic MRS measures may be regionally specific. This supports the potential for MRS in assessing neuroanatomically specific serotonin-glutamate interactions in the human brain

A method for determining venous contribution to BOLD contrast sensory activation

While BOLD contrast reflects haemodynamic changes within capillaries serving neural tissue, it also has a venous component. Studies that have determined the relation of large blood vessels to the activation map indicate that veins are the source of the largest response, and the most delayed in time. It would be informative if the location of these large veins could be extracted from the properties of the functional responses, since vessels are not visible in BOLD contrast images. The present study describes a method for investigating whether measures taken from the functional response can reliably predict vein location, or at least be useful in down-weighting the venous contribution to the activation response, and illustrates this method using data from one subject. We combined fMRI at 3 Tesla with high-resolution anatomical imaging and MR venography to test whether the intrinsic properties of activation time courses corresponded to tissue type. Measures were taken from a gamma fit to the functional response. Mean magnitude showed a significant effect of tissue type (P veins ≈ grey matter > white matter. Mean delays displayed the same ranking across tissue types (P grey matter. However, measures for all tissue types were distributed across an overlapping range. A logistic regression model correctly discriminated 72% of the veins from grey matter in the absence of independent information of macroscopic vessels (ROC=0.72). Whilst tissue classification was not perfect for this subject, weighting the T contrast by the predicted probabilities materially reduced the venous component to the activation map

Intra-amniotic delivery of CFTR-expressing adenovirus does not reverse cystic fibrosis phenotype in inbred CFTR-knockout mice

This article is available open access through the publisher’s website at the link below. Copyright © 2008 The American Society of Gene Therapy.Due to its early onset and severe prognosis, cystic fibrosis (CF) has been suggested as a candidate disease for in utero gene therapy. In 1997, a study was published claiming that to how transient prenatal expression of CF transmembrane conductance regulator (CFTR) from an in utero –injected adenovirus vector could achieve permanent reversal of the CF intestinal pathology in adult CF knockout mice, despite the loss of CFTR transgene expression by birth. This would imply that the underlying cause of CF is a prenatal defect for which lifelong cure can be achieved by transient prenatal expression of CFTR. Despite criticism at the time of publication, no independent verification of this contentious finding has been published so far. This is vital for the development of future therapeutic strategies as it may determine whether CF gene therapy should be performed prenatally or postnatally. We therefore reinvestigated this finding with an identical adenoviral vector and a knockout CF mouse line (CftrtmlCam) with a completely inbred genetic background to eliminate any effects due to genetic variation. After delivery of the CFTR-expressing adenovirus to the fetal mouse, both vector DNA and transgenic CFTR expression were detected in treated animals postpartum but statistically no significant difference in survival was observed between the Cftr–/– mice treated with the CFTR-adenovirus and those treated with the control vector.Sport Aiding Medical Research for Kids, the Cystic Fibrosis Trust, and the Katharine Dormandy Trust

Comparing different analysis methods for quantifying the MRI amide proton transfer (APT) effect in hyperacute stroke patients

Amide proton transfer (APT) imaging is a pH mapping method based on the chemical exchange saturation transfer phenomenon that has potential for penumbra identification following stroke. The majority of the literature thus far has focused on generating pH‐weighted contrast using magnetization transfer ratio asymmetry analysis instead of quantitative pH mapping. In this study, the widely used asymmetry analysis and a model‐based analysis were both assessed on APT data collected from healthy subjects (n = 2) and hyperacute stroke patients (n = 6, median imaging time after onset = 2 hours 59 minutes). It was found that the model‐based approach was able to quantify the APT effect with the lowest variation in grey and white matter (≤ 13.8 %) and the smallest average contrast between these two tissue types (3.48 %) in the healthy volunteers. The model‐based approach also performed quantitatively better than the other measures in the hyperacute stroke patient APT data, where the quantified APT effect in the infarct core was consistently lower than in the contralateral normal appearing tissue for all the patients recruited, with the group average of the quantified APT effect being 1.5 ± 0.3 % (infarct core) and 1.9 ± 0.4 % (contralateral). Based on the fitted parameters from the model‐based analysis and a previously published pH and amide proton exchange rate relationship, quantitative pH maps for hyperacute stroke patients were generated, for the first time, using APT imaging

BOLD Temporal Dynamics of Rat Superior Colliculus and Lateral Geniculate Nucleus following Short Duration Visual Stimulation

Background: The superior colliculus (SC) and lateral geniculate nucleus (LGN) are important subcortical structures for vision. Much of our understanding of vision was obtained using invasive and small field of view (FOV) techniques. In this study, we use non-invasive, large FOV blood oxygenation level-dependent (BOLD) fMRI to measure the SC and LGN's response temporal dynamics following short duration (1 s) visual stimulation. Methodology/Principal Findings: Experiments are performed at 7 tesla on Sprague Dawley rats stimulated in one eye with flashing light. Gradient-echo and spin-echo sequences are used to provide complementary information. An anatomical image is acquired from one rat after injection of monocrystalline iron oxide nanoparticles (MION), a blood vessel contrast agent. BOLD responses are concentrated in the contralateral SC and LGN. The SC BOLD signal measured with gradient-echo rises to 50% of maximum amplitude (PEAK) 0.2±0.2 s before the LGN signal (p<0.05). The LGN signal returns to 50% of PEAK 1.4±1.2 s before the SC signal (p<0.05). These results indicate the SC signal rises faster than the LGN signal but settles slower. Spin-echo results support these findings. The post-MION image shows the SC and LGN lie beneath large blood vessels. This subcortical vasculature is similar to that in the cortex, which also lies beneath large vessels. The LGN lies closer to the large vessels than much of the SC. Conclusions/Significance: The differences in response timing between SC and LGN are very similar to those between deep and shallow cortical layers following electrical stimulation, which are related to depth-dependent blood vessel dilation rates. This combined with the similarities in vasculature between subcortex and cortex suggest the SC and LGN timing differences are also related to depth-dependent dilation rates. This study shows for the first time that BOLD responses in the rat SC and LGN following short duration visual stimulation are temporally different. © 2011 Lau et al

Reliability of multi-site UK Biobank MRI brain phenotypes for the assessment of neuropsychiatric complications of SARS-CoV-2 infection: The COVID-CNS travelling heads study.

Funder: National Institute for Health Research (NIHR)INTRODUCTION: Magnetic resonance imaging (MRI) of the brain could be a key diagnostic and research tool for understanding the neuropsychiatric complications of COVID-19. For maximum impact, multi-modal MRI protocols will be needed to measure the effects of SARS-CoV-2 infection on the brain by diverse potentially pathogenic mechanisms, and with high reliability across multiple sites and scanner manufacturers. Here we describe the development of such a protocol, based upon the UK Biobank, and its validation with a travelling heads study. A multi-modal brain MRI protocol comprising sequences for T1-weighted MRI, T2-FLAIR, diffusion MRI (dMRI), resting-state functional MRI (fMRI), susceptibility-weighted imaging (swMRI), and arterial spin labelling (ASL), was defined in close approximation to prior UK Biobank (UKB) and C-MORE protocols for Siemens 3T systems. We iteratively defined a comparable set of sequences for General Electric (GE) 3T systems. To assess multi-site feasibility and between-site variability of this protocol, N = 8 healthy participants were each scanned at 4 UK sites: 3 using Siemens PRISMA scanners (Cambridge, Liverpool, Oxford) and 1 using a GE scanner (King's College London). Over 2,000 Imaging Derived Phenotypes (IDPs), measuring both data quality and regional image properties of interest, were automatically estimated by customised UKB image processing pipelines (S2 File). Components of variance and intra-class correlations (ICCs) were estimated for each IDP by linear mixed effects models and benchmarked by comparison to repeated measurements of the same IDPs from UKB participants. Intra-class correlations for many IDPs indicated good-to-excellent between-site reliability. Considering only data from the Siemens sites, between-site reliability generally matched the high levels of test-retest reliability of the same IDPs estimated in repeated, within-site, within-subject scans from UK Biobank. Inclusion of the GE site resulted in good-to-excellent reliability for many IDPs, although there were significant between-site differences in mean and scaling, and reduced ICCs, for some classes of IDP, especially T1 contrast and some dMRI-derived measures. We also identified high reliability of quantitative susceptibility mapping (QSM) IDPs derived from swMRI images, multi-network ICA-based IDPs from resting-state fMRI, and olfactory bulb structure IDPs from T1, T2-FLAIR and dMRI data. CONCLUSION: These results give confidence that large, multi-site MRI datasets can be collected reliably at different sites across the diverse range of MRI modalities and IDPs that could be mechanistically informative in COVID brain research. We discuss limitations of the study and strategies for further harmonisation of data collected from sites using scanners supplied by different manufacturers. These acquisition and analysis protocols are now in use for MRI assessments of post-COVID patients (N = 700) as part of the ongoing COVID-CNS study

The Influence of Spatial Registration on Detection of Cerebral Asymmetries Using Voxel-Based Statistics of Fractional Anisotropy Images and TBSS

The sensitivity of diffusion tensor imaging (DTI) for detecting microstructural white matter alterations has motivated the application of voxel-based statistics (VBS) to fractional anisotropy (FA) images (FA-VBS). However, detected group differences may depend on the spatial registration method used. The objective of this study was to investigate the influence of spatial registration on detecting cerebral asymmetries in FA-VBS analyses with reference to data obtained using Tract-Based Spatial Statistics (TBSS). In the first part of this study we performed FA-VBS analyses using three single-contrast and one multi-contrast registration: (i) whole-brain registration based on T2 contrast, (ii) whole-brain registration based on FA contrast, (iii) individual-hemisphere registration based on FA contrast, and (iv) a combination of (i) and (iii). We then compared the FA-VBS results with those obtained from TBSS. We found that the FA-VBS results depended strongly on the employed registration approach, with the best correspondence between FA-VBS and TBSS results when approach (iv), the “multi-contrast individual-hemisphere” method was employed. In the second part of the study, we investigated the spatial distribution of residual misregistration for each registration approach and the effect on FA-VBS results. For the FA-VBS analyses using the three single-contrast registration methods, we identified FA asymmetries that were (a) located in regions prone to misregistrations, (b) not detected by TBSS, and (c) specific to the applied registration approach. These asymmetries were considered candidates for apparent FA asymmetries due to systematic misregistrations associated with the FA-VBS approach. Finally, we demonstrated that the “multi-contrast individual-hemisphere” approach showed the least residual spatial misregistrations and thus might be most appropriate for cerebral FA-VBS analyses

Optimized EPI for fMRI studies of the orbitofrontal cortex: compensation of susceptibility-induced gradients in the readout direction

Object Most functional magnetic resonance imaging (fMRI) studies record the blood oxygen leveldependent (BOLD) signal using gradient-echo echo-planar imaging (GE EPI). EPI can suffer from substantial BOLD sensitivity loss caused by magnetic field inhomogeneities. Here, BOLD sensitivity losses due to susceptibility- induced gradients in the readout (RO) direction are characterized and a compensation approach is developed