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

Multiplexed Echo Planar Imaging for Sub-Second Whole Brain FMRI and Fast Diffusion Imaging

Echo planar imaging (EPI) is an MRI technique of particular value to neuroscience, with its use for virtually all functional MRI (fMRI) and diffusion imaging of fiber connections in the human brain. EPI generates a single 2D image in a fraction of a second; however, it requires 2–3 seconds to acquire multi-slice whole brain coverage for fMRI and even longer for diffusion imaging. Here we report on a large reduction in EPI whole brain scan time at 3 and 7 Tesla, without significantly sacrificing spatial resolution, and while gaining functional sensitivity. The multiplexed-EPI (M-EPI) pulse sequence combines two forms of multiplexing: temporal multiplexing (m) utilizing simultaneous echo refocused (SIR) EPI and spatial multiplexing (n) with multibanded RF pulses (MB) to achieve m×n images in an EPI echo train instead of the normal single image. This resulted in an unprecedented reduction in EPI scan time for whole brain fMRI performed at 3 Tesla, permitting TRs of 400 ms and 800 ms compared to a more conventional 2.5 sec TR, and 2–4 times reductions in scan time for HARDI imaging of neuronal fibertracks. The simultaneous SE refocusing of SIR imaging at 7 Tesla advantageously reduced SAR by using fewer RF refocusing pulses and by shifting fat signal out of the image plane so that fat suppression pulses were not required. In preliminary studies of resting state functional networks identified through independent component analysis, the 6-fold higher sampling rate increased the peak functional sensitivity by 60%. The novel M-EPI pulse sequence resulted in a significantly increased temporal resolution for whole brain fMRI, and as such, this new methodology can be used for studying non-stationarity in networks and generally for expanding and enriching the functional information

High-Field fMRI for Human Applications: An Overview of Spatial Resolution and Signal Specificity

In the last decade, dozens of 7 Tesla scanners have been purchased or installed around the world, while 3 Tesla systems have become a standard. This increased interest in higher field strengths is driven by a demonstrated advantage of high fields for available signal-to-noise ratio (SNR) in the magnetic resonance signal. Functional imaging studies have additional advantages of increases in both the contrast and the spatial specificity of the susceptibility based BOLD signal. One use of this resultant increase in the contrast to noise ratio (CNR) for functional MRI studies at high field is increased image resolution. However, there are many factors to consider in predicting exactly what kind of resolution gains might be made at high fields, and what the opportunity costs might be. The first part of this article discusses both hardware and image quality considerations for higher resolution functional imaging. The second part draws distinctions between image resolution, spatial specificity, and functional specificity of the fMRI signals that can be acquired at high fields, suggesting practical limitations for attainable resolutions of fMRI experiments at a given field, given the current state of the art in imaging techniques. Finally, practical resolution limitations and pulse sequence options for studies in human subjects are considered

Multishot versus Single-Shot Pulse Sequences in Very High Field fMRI: A Comparison Using Retinotopic Mapping

High-resolution functional MRI is a leading application for very high field (7 Tesla) human MR imaging. Though higher field strengths promise improvements in signal-to-noise ratios (SNR) and BOLD contrast relative to fMRI at 3 Tesla, these benefits may be partially offset by accompanying increases in geometric distortion and other off-resonance effects. Such effects may be especially pronounced with the single-shot EPI pulse sequences typically used for fMRI at standard field strengths. As an alternative, one might consider multishot pulse sequences, which may lead to somewhat lower temporal SNR than standard EPI, but which are also often substantially less susceptible to off-resonance effects. Here we consider retinotopic mapping of human visual cortex as a practical test case by which to compare examples of these sequence types for high-resolution fMRI at 7 Tesla. We performed polar angle retinotopic mapping at each of 3 isotropic resolutions (2.0, 1.7, and 1.1 mm) using both accelerated single-shot 2D EPI and accelerated multishot 3D gradient-echo pulse sequences. We found that single-shot EPI indeed led to greater temporal SNR and contrast-to-noise ratios (CNR) than the multishot sequences. However, additional distortion correction in postprocessing was required in order to fully realize these advantages, particularly at higher resolutions. The retinotopic maps produced by both sequence types were qualitatively comparable, and showed equivalent test/retest reliability. Thus, when surface-based analyses are planned, or in other circumstances where geometric distortion is of particular concern, multishot pulse sequences could provide a viable alternative to single-shot EPI

Simultaneous Multislice (SMS) Imaging Techniques

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Structured low-rank methods for robust 3D multi-shot EPI

Magnetic resonance imaging (MRI) has inherently slow acquisition speed, and Echo-Planar Imaging (EPI), as an efficient acquisition scheme, has been widely used in functional magnetic resonance imaging (fMRI) where an image series with high temporal resolution is needed to measure neuronal activity. Recently, 3D multi-shot EPI which samples data from an entire 3D volume with repeated shots has been drawing growing interest for fMRI with its high isotropic spatial resolution, particularly at ultra-high fields. However, compared to single-shot EPI, multi-shot EPI is sensitive to any inter-shot instabilities, e.g., subject movement and even physiologically induced field fluctuations. These inter-shot inconsistencies can greatly negate the theoretical benefits of 3D multi-shot EPI over conventional 2D multi-slice acquisitions. Structured low-rank image reconstruction which regularises under-sampled image reconstruction by exploiting the linear dependencies in MRI data has been successfully demonstrated in a variety of applications. In this thesis, a structured low-rank reconstruction method is optimised for 3D multi-shot EPI imaging together with a dedicated sampling pattern termed seg-CAIPI, in order to enhance the robustness to physiological fluctuations and improve the temporal stability of 3D multi-shot EPI for fMRI at 7T. Moreover, a motion compensated structured low-rank reconstruction framework is also presented for robust 3D multi-shot EPI which further takes into account inter-shot instabilities due to bulk motion. Lastly, this thesis also investigates into the improvement of structured low-rank reconstruction from an algorithmic perspective and presents the locally structured low-rank reconstruction scheme

Does higher sampling rate (multiband + SENSE) improve group statistics - An example from social neuroscience block design at 3T

Multiband (MB) or Simultaneous multi-slice (SMS) acquisition schemes allow the acquisition of MRI signals from more than one spatial coordinate at a time. Commercial availability has brought this technique within the reach of many neuroscientists and psychologists. Most early evaluation of the performance of MB acquisition employed resting state fMRI or the most basic tasks. In this study, we tested whether the advantages of using MB acquisition schemes generalize to group analyses using a cognitive task more representative of typical cognitive neuroscience applications. Twenty-three subjects were scanned on a Philips 3 ​T scanner using five sequences, up to eight-fold acceleration with MB-factors 1 to 4, SENSE factors up to 2 and corresponding TRs of 2.45s down to 0.63s, while they viewed (i) movie blocks showing complex actions with hand object interactions and (ii) control movie blocks without hand object interaction. Data were processed using a widely used analysis pipeline implemented in SPM12 including the unified segmentation and canonical HRF modelling. Using random effects group-level, voxel-wise analysis we found that all sequences were able to detect the basic action observation network known to be recruited by our task. The highest t-values were found for sequences with MB4 acceleration. For the MB1 sequence, a 50% bigger voxel volume was needed to reach comparable t-statistics. The group-level t-values for resting state networks (RSNs) were also highest for MB4 sequences. Here the MB1 sequence with larger voxel size did not perform comparable to the MB4 sequence. Altogether, we can thus recommend the use of MB4 (and SENSE 1.5 or 2) on a Philips scanner when aiming to perform group-level analyses using cognitive block design fMRI tasks and voxel sizes in the range of cortical thickness (e.g. 2.7 ​mm isotropic). While results will not be dramatically changed by the use of multiband, our results suggest that MB will bring a moderate but significant benefit

fMRI protocol optimization for simultaneously studying small subcortical and cortical areas at 7 ​T

Most fundamental cognitive processes rely on brain networks that include both cortical and subcortical structures. Studying such networks using functional magnetic resonance imaging (fMRI) requires a data acquisition protocol that provides blood-oxygenation-level dependent (BOLD) sensitivity across the entire brain. However, when using standard single echo, echo planar imaging protocols, researchers face a tradeoff between BOLD-sensitivity in cortex and in subcortical areas. Multi echo protocols avoid this tradeoff and can be used to optimize BOLD-sensitivity across the entire brain, at the cost of an increased repetition time. Here, we empirically compare the BOLD-sensitivity of a single echo protocol to a multi echo protocol. Both protocols were designed to meet the specific requirements for studying small, iron rich subcortical structures (including a relatively high spatial resolution and short echo times), while retaining coverage and BOLD-sensitivity in cortical areas. The results indicate that both sequences lead to similar BOLD-sensitivity across the brain at 7 ​T