Spatio-temporal wavelet regularization for parallel MRI reconstruction: application to functional MRI

Parallel MRI is a fast imaging technique that enables the acquisition of highly resolved images in space or/and in time. The performance of parallel imaging strongly depends on the reconstruction algorithm, which can proceed either in the original k-space (GRAPPA, SMASH) or in the image domain (SENSE-like methods). To improve the performance of the widely used SENSE algorithm, 2D- or slice-specific regularization in the wavelet domain has been deeply investigated. In this paper, we extend this approach using 3D-wavelet representations in order to handle all slices together and address reconstruction artifacts which propagate across adjacent slices. The gain induced by such extension (3D-Unconstrained Wavelet Regularized -SENSE: 3D-UWR-SENSE) is validated on anatomical image reconstruction where no temporal acquisition is considered. Another important extension accounts for temporal correlations that exist between successive scans in functional MRI (fMRI). In addition to the case of 2D+t acquisition schemes addressed by some other methods like kt-FOCUSS, our approach allows us to deal with 3D+t acquisition schemes which are widely used in neuroimaging. The resulting 3D-UWR-SENSE and 4D-UWR-SENSE reconstruction schemes are fully unsupervised in the sense that all regularization parameters are estimated in the maximum likelihood sense on a reference scan. The gain induced by such extensions is illustrated on both anatomical and functional image reconstruction, and also measured in terms of statistical sensitivity for the 4D-UWR-SENSE approach during a fast event-related fMRI protocol. Our 4D-UWR-SENSE algorithm outperforms the SENSE reconstruction at the subject and group levels (15 subjects) for different contrasts of interest (eg, motor or computation tasks) and using different parallel acceleration factors (R=2 and R=4) on 2x2x3mm3 EPI images.Comment: arXiv admin note: substantial text overlap with arXiv:1103.353

Mitigating susceptibility-induced distortions in high-resolution 3DEPI fMRI at 7T

Geometric distortion is a major limiting factor for spatial specificity in high-resolution fMRI using EPI readouts and is exacerbated at higher field strengths due to increased B0 field inhomogeneity. Prominent correction schemes are based on B0 field-mapping or acquiring reverse phase-encoded (reversed-PE) data. However, to date, comparisons of these techniques in the context of fMRI have only been performed on 2DEPI data, either at lower field or lower resolution. In this study, we investigate distortion compensation in the context of sub-millimetre 3DEPI data at 7T. B0 field-mapping and reversed-PE distortion correction techniques were applied to both partial coverage BOLD-weighted and whole brain MT-weighted 3DEPI data with matched distortion. Qualitative assessment showed overall improvement in cortical alignment for both correction techniques in both 3DEPI fMRI and whole-brain MT-3DEPI datasets. The distortion-corrected MT-3DEPI images were quantitatively evaluated by comparing cortical alignment with an anatomical reference using dice coefficient (DC) and correlation ratio (CR) measures. These showed that B0 field-mapping and reversed-PE methods both improved correspondence between the MT-3DEPI and anatomical data, with more substantial improvements consistently obtained using the reversed-PE approach. Regional analyses demonstrated that the largest benefit of distortion correction, and in particular of the reversed-PE approach, occurred in frontal and temporal regions where susceptibility-induced distortions are known to be greatest, but had not led to complete signal dropout. In conclusion, distortion correction based on reversed-PE data has shown the greater capacity for achieving faithful alignment with anatomical data in the context of high-resolution fMRI at 7T using 3DEPI

Ultra-high spatial resolution BOLD fMRI in humans using combined segmented-accelerated VFA-FLEET with a recursive RF pulse design

Purpose To alleviate the spatial encoding limitations of single-shot EPI by developing multi-shot segmented EPI for ultra-high-resolution fMRI with reduced ghosting artifacts from subject motion and respiration. Methods Segmented EPI can reduce readout duration and reduce acceleration factors, however, the time elapsed between segment acquisitions (on the order of seconds) can result in intermittent ghosting, limiting its use for fMRI. Here, "FLEET" segment ordering--where segments are looped over before slices--was combined with a variable flip angle progression (VFA-FLEET) to improve inter-segment fidelity and maximize signal for fMRI. Scaling a sinc pulse's flip angle for each segment (VFA-FLEET-Sinc) produced inconsistent slice profiles and ghosting, therefore, a recursive Shinnar-Le Roux (SLR) RF pulse design was developed (VFA-FLEET-SLR) to generate unique pulses for every segment that together produce consistent slice profiles and signals. Results The temporal stability of VFA-FLEET-SLR was compared against conventional-segmented EPI and VFA-FLEET-Sinc at 3 T and 7 T. VFA-FLEET-SLR showed reductions in both intermittent and stable ghosting compared to conventional-segmented and VFA-FLEET-Sinc, resulting in improved image quality with a minor trade-off in temporal SNR. Combining VFA-FLEET-SLR with acceleration, we achieved a 0.6-mm isotropic acquisition at 7 T--without zoomed imaging or partial Fourier--demonstrating reliable detection of BOLD responses to a visual stimulus. To counteract the increased repetition time from segmentation, simultaneous multi-slice VFA-FLEET-SLR was demonstrated using RF-encoded controlled aliasing. Conclusions VFA-FLEET with a recursive RF pulse design supports acquisitions with low levels of artifact and spatial blur, enabling fMRI at previously inaccessible spatial resolutions with a "full-brain" field of view.Comment: 51 pages (including supplement), 8 main figures, 6 supporting figures. For supporting videos (8), please visit https://github.com/aveberman/vfa-fleet. Note: this work has been accepted for publication at Magnetic Resonance in Medicin

Simultaneous in vivo positron emission tomography and magnetic resonance imaging

Positron emission tomography (PET) and magnetic resonance imaging (MRI) are widely used in vivo imaging technologies with both clinical and biomedical research applications. The strengths of MRI include high-resolution, high-contrast morphologic imaging of soft tissues; the ability to image physiologic parameters such as diffusion and changes in oxygenation level resulting from neuronal stimulation; and the measurement of metabolites using chemical shift imaging. PET images the distribution of biologically targeted radiotracers with high sensitivity, but images generally lack anatomic context and are of lower spatial resolution. Integration of these technologies permits the acquisition of temporally correlated data showing the distribution of PET radiotracers and MRI contrast agents or MR-detectable metabolites, with registration to the underlying anatomy. An MRI-compatible PET scanner has been built for biomedical research applications that allows data from both modalities to be acquired simultaneously. Experiments demonstrate no effect of the MRI system on the spatial resolution of the PET system and <10% reduction in the fraction of radioactive decay events detected by the PET scanner inside the MRI. The signal-to-noise ratio and uniformity of the MR images, with the exception of one particular pulse sequence, were little affected by the presence of the PET scanner. In vivo simultaneous PET and MRI studies were performed in mice. Proof-of-principle in vivo MR spectroscopy and functional MRI experiments were also demonstrated with the combined scanner

Vascular artefacts in fMRI of early visual cortex: The effects of resolution and field strength

Large draining veins residing on the cortical surface are recognised as a major problem in fMRI measurements, leading to the displacement, distortion, and reduction in spatial localisation of signals. This is detrimental to the application of fMRI in advanced human brain imaging, such as in retinotopic mapping, where the BOLD signal becomes obscured by the artefacts from nearby draining veins (venous artefacts). There is consensus that at an increased magnetic field strength, the sensitivity to the contributions from these draining veins reduces, which promises the ability to capture measurements at greater sensitivity and specificity. With the advent of fMRI hardware and technologies, there is a great interest in understanding cortical layer-specific neuronal response that had been previously obscured due to the domination of signal change caused by venous artefacts. This forms the basis of support for fMRI at ultra-high magnetic field strength, with the conventional wisdom that the reduced sensitivity to macrovasculature (including draining veins) that comes with higher magnetic field strength can increase the sensitivity to underlying responses that closely reflect neuronal activation. However, this is debatable. Instead, there are instances where human neuronal response profiles displayed a pattern that seemed indicative of synaptic activities even without using ultra-high magnetic field strength. Recent trends in moving to ultra-high magnetic field strengths, especially for depth-dependent fMRI, beget the questions – is ultra-high magnetic field strength really necessary, and can it resolve the artefacts from draining veins? To elucidate these questions, this thesis aims to test the venous artefact and its impact on underlying signals across spatial resolutions and magnetic field strengths, focusing on the quality of the retinotopic organisation of the early visual cortex. The first experimental study was conducted to test the venous artefact and its impact on fMRI signals across the grey matter using high-resolution (isotropic resolution of 1 mm) fMRI images collected at 3 T. Using two surface reconstruction packages, the findings established that venous artefact occurs at the cortical surface and spreads within the grey matter. In this study, the ability of high-resolution fMRI at 3 T to conduct depth-dependent analyses was demonstrated. The second experimental study delves into the role of spatial resolution in the depth-dependent analysis of venous artefacts and their impact. The 1 mm 3 T fMRI images were spatially smoothed to simulate two additional sets of lower-effective resolution images. Here, the results found consistency in the venous artefact but a reduction in the venous effects. This suggests that at lower spatial resolutions, the venous artefact exists, but its impact on underlying signals is concealed. The third experiment incorporates two sets of 7 T fMRI images, with spatial resolutions of 1.6 mm and 0.8 mm, to test the venous artefacts at ultra-high magnetic field strength. The results showed evidence that venous artefacts remained prominent at 7 T. This study was extended into a comparative study by including the 3 T fMRI images used in the first study. Here, the generalisability of the venous artefact was established at 3 T and 7 T, as well as across various spatial resolutions. Finally, the fourth experiment explored a non- BOLD contrast, postulated to be less sensitive to contributions from the draining veins. In this study, VASO-fMRI was conducted with a spatial resolution of 1.1 mm and at 7 T to test the venous artefact and its impact. A reduction in the venous artefact and its impact was demonstrated. However, VASO images were found insufficient to inform the retinotopic organisation of the early visual cortex due to higher noise and lower signals, but they can be beneficial when used in conjunction with BOLD images. In summary, this thesis established the competence of high-resolution fMRI at 3 T for depth-dependent analysis. This suggests that the artefacts arising from draining veins can be avoided by avoiding surfaces or locations that are in proximity to these veins. Furthermore, this thesis sheds light on the generalisability of the venous artefact across magnetic field strengths and spatial resolutions. Finally, the results from the VASO-fMRI study demonstrated how VASO retinotopic mapping could benefit BOLD retinotopic mapping, especially when the BOLD response is highly polluted with macrovasculature

The nonhuman primate neuroimaging and neuroanatomy project

Multi-modal neuroimaging projects such as the Human Connectome Project (HCP) and UK Biobank are advancing our understanding of human brain architecture, function, connectivity, and their variability across individuals using high-quality non-invasive data from many subjects. Such efforts depend upon the accuracy of non-invasive brain imaging measures. However, ‘ground truth’ validation of connectivity using invasive tracers is not feasible in humans. Studies using nonhuman primates (NHPs) enable comparisons between invasive and non-invasive measures, including exploration of how “functional connectivity” from fMRI and “tractographic connectivity” from diffusion MRI compare with long-distance connections measured using tract tracing. Our NonHuman Primate Neuroimaging & Neuroanatomy Project (NHP_NNP) is an international effort (6 laboratories in 5 countries) to: (i) acquire and analyze high-quality multi-modal brain imaging data of macaque and marmoset monkeys using protocols and methods adapted from the HCP; (ii) acquire quantitative invasive tract-tracing data for cortical and subcortical projections to cortical areas; and (iii) map the distributions of different brain cell types with immunocytochemical stains to better define brain areal boundaries. We are acquiring high-resolution structural, functional, and diffusion MRI data together with behavioral measures from over 100 individual macaques and marmosets in order to generate non-invasive measures of brain architecture such as myelin and cortical thickness maps, as well as functional and diffusion tractography-based connectomes. We are using classical and next-generation anatomical tracers to generate quantitative connectivity maps based on brain-wide counting of labeled cortical and subcortical neurons, providing ground truth measures of connectivity. Advanced statistical modeling techniques address the consistency of both kinds of data across individuals, allowing comparison of tracer-based and non-invasive MRI-based connectivity measures. We aim to develop improved cortical and subcortical areal atlases by combining histological and imaging methods. Finally, we are collecting genetic and sociality-associated behavioral data in all animals in an effort to understand how genetic variation shapes the connectome and behavior

Neural Representations of Visual Motion Processing in the Human Brain Using Laminar Imaging at 9.4 Tesla

During natural behavior, much of the motion signal falling into our eyes is due to our own movements. Therefore, in order to correctly perceive motion in our environment, it is important to parse visual motion signals into those caused by self-motion such as eye- or head-movements and those caused by external motion. Neural mechanisms underlying this task, which are also required to allow for a stable perception of the world during pursuit eye movements, are not fully understood. Both, perceptual stability as well as perception of real-world (i.e. objective) motion are the product of integration between motion signals on the retina and efference copies of eye movements. The central aim of this thesis is to examine whether different levels of cortical depth or distinct columnar structures of visual motion regions are differentially involved in disentangling signals related to self-motion, objective, or object motion. Based on previous studies reporting segregated populations of voxels in high level visual areas such as V3A, V6, and MST responding predominantly to either retinal or extra- retinal (‘real’) motion, we speculated such voxels to reside within laminar or columnar functional units. We used ultra-high field (9.4T) fMRI along with an experimental paradigm that independently manipulated retinal and extra-retinal motion signals (smooth pursuit) while controlling for effects of eye-movements, to investigate whether processing of real world motion in human V5/MT, putative MST (pMST), and V1 is associated to differential laminar signal intensities. We also examined motion integration across cortical depths in human motion areas V3A and V6 that have strong objective motion responses. We found a unique, condition specific laminar profile in human area V6, showing reduced mid-layer responses for retinal motion only, suggestive of an inhibitory retinal contribution to motion integration in mid layers or alternatively an excitatory contribution in deep and superficial layers. We also found evidence indicating that in V5/MT and pMST, processing related to retinal, objective, and pursuit motion are either integrated or colocalized at the scale of our resolution. In contrast, in V1, independent functional processes seem to be driving the response to retinal and objective motion on the one hand, and to pursuit signals on the other. The lack of differential signals across depth in these regions suggests either that a columnar rather than laminar segregation governs these functions in these areas, or that the methods used were unable to detect differential neural laminar processing. Furthermore, the thesis provides a thorough analysis of the relevant technical modalities used for data acquisition and data analysis at ultra-high field in the context of laminar fMRI. Relying on our technical implementations we were able to conduct two high-resolution fMRI experiments that helped us to further investigate the laminar organization of self-induced and externally induced motion cues in human high-level visual areas and to form speculations about the site and the mechanisms of their integration

Microstructural imaging of the human brain with a 'super-scanner': 10 key advantages of ultra-strong gradients for diffusion MRI

The key component of a microstructural diffusion MRI 'super-scanner' is a dedicated high-strength gradient system that enables stronger diffusion weightings per unit time compared to conventional gradient designs. This can, in turn, drastically shorten the time needed for diffusion encoding, increase the signal-to-noise ratio, and facilitate measurements at shorter diffusion times. This review, written from the perspective of the UK National Facility for In Vivo MR Imaging of Human Tissue Microstructure, an initiative to establish a shared 300 mT/m-gradient facility amongst the microstructural imaging community, describes ten advantages of ultra-strong gradients for microstructural imaging. Specifically, we will discuss how the increase of the accessible measurement space compared to a lower-gradient systems (in terms of Δ, b-value, and TE) can accelerate developments in the areas of 1) axon diameter distribution mapping; 2) microstructural parameter estimation; 3) mapping micro-vs macroscopic anisotropy features with gradient waveforms beyond a single pair of pulsed-gradients; 4) multi-contrast experiments, e.g. diffusion-relaxometry; 5) tractography and high-resolution imaging in vivo and 6) post mortem; 7) diffusion-weighted spectroscopy of metabolites other than water; 8) tumour characterisation; 9) functional diffusion MRI; and 10) quality enhancement of images acquired on lower-gradient systems. We finally discuss practical barriers in the use of ultra-strong gradients, and provide an outlook on the next generation of 'super-scanners'