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 30 seconds 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 4 minutes, 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 direction) CSF movement into the cranial cavity and into the lateral ventricles and a reversed direction in expiration phase.

Purpose: Simultaneous multi-slice (SMS) echo planar imaging (EPI) is incorporated into two-dimensional (2D) arterial spin labeling (ASL) imaging to produce more slices for measuring perfusion in a larger region of the brain than currently possible with multi-slice EPI. Methods: Pulsed ASL (PASL) preparations using FAIR and QUIPSS II techniques were combined with SMS-EPI. Testing was performed in four subjects at 3 Tesla. Multiband slice acceleration factors (MB) from MB-2 to MB-5 using 40 averages were evaluated. Comparisons were made quantitatively to PASL 2D EPI and qualitatively to PASL 3D GRASE. Results: In the 12 slice data set, spatial SNR for the perfusion weighted images averaged across subjects was 3.28 and 3.44 for the two sequential MB-1 acquisitions as control comparison, 3.25 for MB-2 and 2.98 for MB-3. The temporal SNR averaged 1.01 and 0.99 for MB-1, 0.89 for MB-2, and 0.78 for MB-3. For whole-brain spatial coverage, the 20 slice data sets could be acquired in narrower time windows, from 874 ms using EPI (MB-1) down to 196 ms using MB-5. SMS-EPI ASL differed from 3D GRASE ASL, which can use background suppression and has less susceptibility artifact as a CPMG SE sequence. Conclusion: SMS-EPI has a major advantage over EPI-based ASL imaging by increasing slice coverage without lengthening the acquisition time window.

Purpose Functional MRI (fMRI) at the mesoscale of cortical layers and columns requires both sensitivity and specificity, the latter of which can be compromised if the imaging method is affected by vascular artifacts, particularly cortical draining veins at the pial surface. Recent studies have shown that cerebral blood volume (CBV) imaging is more specific to the actual laminar locus of neural activity than BOLD imaging using standard gradient‐echo EPI sequences. Gradient and spin‐echo (GRASE) BOLD imaging has also shown greater specificity when compared with standard gradient‐echo EPI BOLD. Here we directly compare CBV and BOLD contrasts in high‐resolution imaging of the primary motor cortex for laminar functional MRI in four combinations of signal labeling, CBV using slice‐selective slab‐inversion vascular space occupancy (VASO) and BOLD, each with 3D gradient‐echo EPI and zoomed 3D‐GRASE image readouts. Methods Activations were measured using each sequence and contrast combination during a motor task. Activation profiles across cortical depth were measured to assess the sensitivity and specificity (pial bias) of each method. Results Both CBV imaging using gradient‐echo 3D‐EPI and BOLD imaging using 3D‐GRASE show similar specificity and sensitivity and are therefore useful tools for mesoscopic functional MRI in the human cortex. The combination of GRASE and VASO did not demonstrate high levels of sensitivity, nor show increased specificity. Conclusion Three‐dimensional EPI with VASO contrast and 3D‐GRASE with BOLD contrast both demonstrate sufficient sensitivity and specificity for laminar functional MRI to be used by neuroscientists in a wide range of investigations of depth‐dependent neural circuitry in the human brain.

Encoding higher spatial resolution in simultaneous multi-slice (SMS) EPI is highly dependent on gradient performance, high density receiver coil arrays and pulse sequence optimization. We simulate gradient amplitude and slew rate determination of EPI imaging performance in terms of minimum TE, echo spacing (ES) and spatial resolution. We discuss the effects of image zooming in pulse sequences that have been used for sub-millimeter resolutions and the trade-offs in using partial Fourier and parallel imaging to reduce TE, PSF and ES. Using optimizations for SMS EPI pulse sequences with available gradient and receiver hardware, experimental results in ultra-high resolution (UHR) (0.45-0.5mm isotropic) SMS-EPI fMRI and mapping ocular dominance columns (ODC) in human brain at 0.5 mm isotropic resolution are demonstrated. We discuss promising future directions of UHR fMRI.

Purpose To achieve highly accelerated submillimeter resolution T2‐weighted functional MRI at 7T by developing a three‐dimensional gradient and spin echo imaging (GRASE) with inner‐volume selection and variable flip angles (VFA). Methods GRASE imaging has disadvantages in that (a) k‐space modulation causes T2 blurring by limiting the number of slices and (b) a VFA scheme results in partial success with substantial SNR loss. In this work, accelerated GRASE with controlled T2 blurring is developed to improve a point spread function (PSF) and temporal signal‐to‐noise ratio (tSNR) with a large number of slices. To this end, the VFA scheme is designed by minimizing a trade‐off between SNR and blurring for functional sensitivity, and a new GRASE‐optimized random encoding, which takes into account the complex signal decays of T2 and T2∗ weightings, is proposed by achieving incoherent aliasing for constrained reconstruction. Numerical and experimental studies were performed to validate the effectiveness of the proposed method over regular and VFA GRASE (R‐ and V‐GRASE). Results The proposed method, while achieving 0.8 mm isotropic resolution, functional MRI compared to R‐ and V‐GRASE improves the spatial extent of the excited volume up to 36 slices with 52%‐68% full width at half maximum (FWHM) reduction in PSF but approximately 2‐ to 3‐fold mean tSNR improvement, thus resulting in higher BOLD activations. Conclusions We successfully demonstrated the feasibility of the proposed method in T2‐weighted functional MRI. The proposed method is especially promising for cortical layer‐specific functional MRI.

PurposeFunctional MRI (fMRI) at the mesoscale of cortical layers and columns requires both sensitivity and specificity, which can be compromised if the imaging method is affected by vascular artifacts, particularly cortical draining veins at the pial surface. Recent studies have shown that cerebral blood volume (CBV) imaging is more specific to the actual laminar locus of neural activity than BOLD imaging when using standard gradient-echo (GE) EPI sequences. Gradient and Spin Echo (GRASE) BOLD imaging has also shown greater specificity when compared with GE-BOLD.MethodsHere we directly compare CBV and BOLD contrasts in high-resolution imaging of the primary motor cortex for laminar fMRI in four combinations of signal labeling, VASO (CBV) and BOLD with 3D GE-EPI and zoomed 3D GRASE image readouts.ResultsWe find that both CBV imaging using EPI-VASO and BOLD imaging using GRASE-BOLD, show similar specificity and sensitivity and are thus useful tools for mesoscopic fMRI in the human cortex.ConclusionThese techniques demonstrate sufficient sensitivity and specificity to allow layer-fMRI to be used by neuroscientists in a wide range of investigations of depth-dependent neural circuitry in the human brain.

High isotropic resolution fMRI is challenging primarily due to long repetition times (TR) and insufficient SNR, especially at lower field strengths. Recently, Simultaneous Multi-Slice (SMS) imaging with blipped-CAIPI has substantially reduced scan time and improved SNR efficiency of fMRI. Similarly, super-resolution techniques utilizing sub- voxel spatial shifts in the slice direction have increased both resolution and SNR efficiency. Here we demonstrate the synergistic combination of SLIce Dithered Enhanced Resolution (SLIDER) and SMS for high-resolution, high-SNR whole brain fMRI in comparison to standard resolution fMRI data as well as high-resolution data. With SLIDER-SMS, high spatial frequency information is recovered (unaliased) even in absence of super-resolution deblurring algorithms. Additionally we find that BOLD CNR (as measured by t-value in a visual checkerboard paradigm) is improved by as much as 100% relative to traditionally acquired high- resolution data. Using this gain in CNR, we are able to obtain unprecedented nominally isotropic resolutions at 3T (0.66 mm) and 7T (0.45 mm).

Purpose: To develop a novel, simultaneous multi-slice (SMS) reconstruction that extends an inter-slice leakage constraint to intra-slice aliasing with a virtual slice concept for artifact reduction. Methods: Inter-slice leakage constraint has been used for SMS reconstruction that mitigates leakage artifacts from the adjacent slices. In this work, the leakage constraint is extended to more general framework that includes SMS and parallel MRI as special cases by viewing intra-slice aliasing artifacts from undersampling as virtual slices while imposing data fidelity to ensure the measurement consistency. In this way, the reconstruction makes it feasible to directly estimate the individual slices from the undersampled SMS acquisition as a one-step method. The performance of the extended method is evaluated with data acquired using 2D GRE and EPI sequences. Results: Compared to a two-step method that performs slice unaliasing followed by inplane unaliasing, the proposed one-step method reduces aliasing artifacts by employing the extended leakage constraint while lowering the noise amplification by improving the conditioning for the inverse problem. Conclusions: The proposed one-step method takes advantage of virtual slices as additional encoding power for improved image quality. We successfully demonstrated that the proposed one-step method minimizes a trade-off between aliasing artifacts and amplified noises over the two-step method. K E Y W O R D Smagnetic resonance imaging, parallel MRI, simultaneous multi-slice, slice leakage, virtual slice