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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.

To increase granularity in human neuroimaging science, we designed and built a next-generation 7 Tesla magnetic resonance imaging scanner to reach ultra-high resolution by implementing several advances in hardware. To improve spatial encoding and increase the image signal-to-noise ratio, we developed a head-only asymmetric gradient coil (200 mT m −1 , 900 T m −1 s −1 ) with an additional third layer of windings. We integrated a 128-channel receiver system with 64- and 96-channel receiver coil arrays to boost signal in the cerebral cortex while reducing g-factor noise to enable higher accelerations. A 16-channel transmit system reduced power deposition and improved image uniformity. The scanner routinely performs functional imaging studies at 0.35–0.45 mm isotropic spatial resolution to reveal cortical layer functional activity, achieves high angular resolution in diffusion imaging and reduces acquisition time for both functional and structural imaging. A combination of hardware developments has increased the achievable spatial resolution in 7 Tesla human neuroimaging to about 0.4 mm.

We evaluate residual aliasing among simultaneously excited and acquired slices in slice accelerated multiband (MB) echo planar imaging (EPI). No in-plane accelerations were used in order to maximize and evaluate achievable slice acceleration factors at 3T. We propose a novel leakage (L-) factor to quantify the effects of signal leakage between simultaneously acquired slices. With a standard 32-channel receiver coil at 3T, we demonstrate that slice acceleration factors of up to eight (MB=8) with blipped controlled aliasing in parallel imaging (CAIPI), in the absence of in-plane accelerations, can be used routinely with acceptable image quality and integrity for whole brain imaging. Spectral analyses of single-shot fMRI time series demonstrate that temporal fluctuations due to both neuronal and physiological sources were distinguishable and comparable up to slice-acceleration factors of nine (MB=9). The increased temporal efficiency could be employed to achieve, within a given acquisition period, higher spatial resolution, increased fMRI statistical power, multiple TEs, faster sampling of temporal events in a resting state fMRI time series, increased sampling of q-space in diffusion imaging, or more quiet time during a scan. [Display omitted] •High slice accelerations using multiband (MB) GRE-EPI with blipped CAIPI.•Acceptable MB factors up to 8 with a 32-channel receiver coil at 3T.•Neuronal and physiological sources are distinguishable at high MB factors.•Leakage (L-) factor evaluates residual aliasing among simultaneously acquired slices.•High temporal efficiency with MB-EPI benefits various applications.

Recent work has established that cerebral blood flow is regulated at a spatial scale that can be resolved by high field fMRI to show cortical columns in humans. While cortical columns represent a cluster of neurons with similar response properties (spanning from the pial surface to the white matter), important information regarding neuronal interactions and computational processes is also contained within a single column, distributed across the six cortical lamina. A basic understanding of underlying neuronal circuitry or computations may be revealed through investigations of the distribution of neural responses at different cortical depths. In this study, we used T(2)-weighted imaging with 0.7 mm (isotropic) resolution to measure fMRI responses at different depths in the gray matter while human subjects observed images with either recognizable or scrambled (physically impossible) objects. Intact and scrambled images were partially occluded, resulting in clusters of activity distributed across primary visual cortex. A subset of the identified clusters of voxels showed a preference for scrambled objects over intact; in these clusters, the fMRI response in middle layers was stronger during the presentation of scrambled objects than during the presentation of intact objects. A second experiment, using stimuli targeted at either the magnocellular or the parvocellular visual pathway, shows that laminar profiles in response to parvocellular-targeted stimuli peak in more superficial layers. These findings provide new evidence for the differential sensitivity of high-field fMRI to modulations of the neural responses at different cortical depths.

MRI pulse sequences designed to increase the speed and spatial resolution of fMRI have always been a hot topic. Here, we review and chronicle the history behind some of the pulse sequence ideas that have contributed not only to the enhancement of fMRI acquisition but also to diffusion imaging. (i) Partial Fourier EPI allows lengthening echo trains for higher spatial resolution while maintaining optimal TE and BOLD sensitivity. (ii) Inner-volume EPI renamed zoomed-EPI, achieves extremely high spatial resolution and has been applied to fMRI at 7Tesla to resolve cortical layer activity and columnar level fMRI. (iii) An early non-BOLD approach while unsuccessful for fMRI created a diffusion sequence of bipolar pulses called ‘twice refocused spin echo’ now widely used for high-resolution DTI and HARDI neuronal fiber track imaging. (iv) Multiplexed EPI shortens TR to a few hundred milliseconds, increasing sampling rates and statistical power in fMRI.

Resting-state functional magnetic resonance imaging has become a powerful tool for the study of functional networks in the brain. Even \"at rest,\" the brain's different functional networks spontaneously fluctuate in their activity level; each network's spatial extent can therefore be mapped by finding temporal correlations between its different subregions. Current correlation-based approaches measure the average functional connectivity between regions, but this average is less meaningful for regions that are part of multiple networks; one ideally wants a network model that explicitly allows overlap, for example, allowing a region's activity pattern to reflect one network's activity some of the time, and another network's activity at other times. However, even those approaches that do allow overlap have often maximized mutual spatial independence, which may be suboptimal if distinct networks have significant overlap. In this work, we identify functionally distinct networks by virtue of their temporal independence, taking advantage of the additional temporal richness available via improvements in functional magnetic resonance imaging sampling rate. We identify multiple \"temporal functional modes,\" including several that subdivide the default-mode network (and the regions anticorrelated with it) into several functionally distinct, spatially overlapping, networks, each with its own pattern of correlations and anticorrelations. These functionally distinct modes of spontaneous brain activity are, in general, quite different from resting-state networks previously reported, and may have greater biological interpretability.

The magnocellular (M) and parvocellular (P) subdivisions of primate LGN are known to process complementary types of visual stimulus information, but a method for noninvasively defining these subdivisions in humans has proven elusive. As a result, the functional roles of these subdivisions in humans have not been investigated physiologically. To functionally map the M and P subdivisions of human LGN, we used high-resolution fMRI at high field (7T and 3T) together with a combination of spatial, temporal, luminance, and chromatic stimulus manipulations. We found that stimulus factors that differentially drive magnocellular and parvocellular neurons in primate LGN also elicit differential BOLD fMRI responses in human LGN and that these responses exhibit a spatial organization consistent with the known anatomical organization of the M and P subdivisions. In test–retest studies, the relative responses of individual voxels to M-type and P-type stimuli were reliable across scanning sessions on separate days and across sessions at different field strengths. The ability to functionally identify magnocellular and parvocellular regions of human LGN with fMRI opens possibilities for investigating the functions of these subdivisions in human visual perception, in patient populations with suspected abnormalities in one of these subdivisions, and in visual cortical processing streams arising from parallel thalamocortical pathways. •Functional mapping of the M and P subdivisions of human LGN with 7T and 3T fMRI•Stimuli based on electrophysiology in non-human primates allow human LGN mapping•Spatial organization of M-like and P-like voxels consistent with known LGN anatomy•Reliable M/P maps across test–retest sessions for individual subjects

Functional magnetic resonance imaging (fMRI) allows studying human brain function non-invasively up to the spatial resolution of cortical columns and layers. Most fMRI acquisitions rely on the blood oxygenation level dependent (BOLD) contrast employing T(*) 2 weighted 2D multi-slice echo-planar imaging (EPI). At ultra-high magnetic field (i.e., 7 T and above), it has been shown experimentally and by simulation, that T2 weighted acquisitions yield a signal that is spatially more specific to the site of neuronal activity at the cost of functional sensitivity. This study compared two T2 weighted imaging sequences, inner-volume 3D Gradient-and-Spin-Echo (3D-GRASE) and 2D Spin-Echo EPI (SE-EPI), with evaluation of their imaging point-spread function (PSF), functional specificity, and functional sensitivity at sub-millimeter resolution. Simulations and measurements of the imaging PSF revealed that the strongest anisotropic blurring in 3D-GRASE (along the second phase-encoding direction) was about 60% higher than the strongest anisotropic blurring in 2D SE-EPI (along the phase-encoding direction). In a visual paradigm, the BOLD sensitivity of 3D-GRASE was found to be superior due to its higher temporal signal-to-noise ratio (tSNR). High resolution cortical depth profiles suggested that the contrast mechanisms are similar between the two sequences, however, 2D SE-EPI had a higher surface bias owing to the higher T(*) 2 contribution of the longer in-plane EPI echo-train for full field of view compared to the reduced field of view of zoomed 3D-GRASE.

We evaluate residual aliasing among simultaneously excited and acquired slices in slice accelerated multiband (MB) echo planar imaging (EPI). No in-plane accelerations were used in order to maximize and evaluate achievable slice acceleration factors at 3 T. We propose a novel leakage (L-) factor to quantify the effects of signal leakage between simultaneously acquired slices. With a standard 32-channel receiver coil at 3 T, we demonstrate that slice acceleration factors of up to eight (MB=8) with blipped controlled aliasing in parallel imaging (CAIPI), in the absence of in-plane accelerations, can be used routinely with acceptable image quality and integrity for whole brain imaging. Spectral analyses of single-shot fMRI time series demonstrate that temporal fluctuations due to both neuronal and physiological sources were distinguishable and comparable up to slice-acceleration factors of nine (MB=9). The increased temporal efficiency could be employed to achieve, within a given acquisition period, higher spatial resolution, increased fMRI statistical power, multiple TEs, faster sampling of temporal events in a resting state fMRI time series, increased sampling of q-space in diffusion imaging, or more quiet time during a scan.

Cerebrospinal fluid (CSF) dynamics have been mostly studied with cardiac-gated phase contrast MRI combining signal from many cardiac cycles to create cine-phase sampling of one time-averaged cardiac cycle. The relative effects of cardiac and respiratory changes on CSF movement are not well understood. There is possible respiration-driven movement of CSF in ventricles, cisterns, and subarachnoid spaces which has not been characterized with velocity measurements. To date, commonly used cine-phase contrast techniques of velocity imaging inherently cannot detect respiratory velocity changes since cardiac-gated data acquired over several minutes randomizes respiratory phase contributions. We have developed an extremely fast, real-time, and quantitative MRI technique to image CSF velocity in simultaneous multi-slice (SMS) echo planar imaging (EPI) acquisitions of 3 or 6 slice levels simultaneously over 30s and observe 3D spatial distributions of CSF velocity. Measurements were made in 10 subjects utilizing a respiratory belt to record respiratory phases and visual cues to instruct subjects on breathing rates. A protocol is able to measure velocity within regions of brain and basal cisterns covered with 24 axial slices in 4minutes, repeated for 3 velocity directions. These measurements were performed throughout the whole brain, rather than in selected line regions so that a global view of CSF dynamics could be visualized. Observations of cardiac and breathing-driven CSF dynamics show bidirectional respiratory motion occurs primarily along the central axis through the basal cisterns and intraventricular passageways and to a lesser extent in the peripheral Sylvian fissure with little CSF motion present in subarachnoid spaces. During inspiration phase, there is upward (inferior to superior) CSF movement into the cranial cavity and lateral ventricles and a reversal of direction in expiration phase. •Real-time imaging of CSF velocity cardiac and respiratory components•Novel technique is simultaneous multi-slice (SMS) phase contrast (PC) EPI•Respiratory driven CSF velocity for the first time is observed in direction and magnitude•Inspiration phase CSF movement is directed upwards through the foramen magnum into the basal cisterns and into the ventricular system.•Expiration phase direction is reversed giving bidirectional respiratory motion