Rapid submillimeter QSM and R2* mapping using interleaved multishot 3D-EPI at 7 and 3 Tesla.

PURPOSE: To explore the high signal-to-noise ratio (SNR) efficiency of interleaved multishot 3D-EPI with standard image reconstruction for fast and robust high-resolution whole-brain quantitative susceptibility (QSM) and R 2 ∗ $$ {R}_2^{\ast } $$ mapping at 7 and 3T. METHODS: Single- and multi-TE segmented 3D-EPI is combined with conventional CAIPIRINHA undersampling for up to 72-fold effective gradient echo (GRE) imaging acceleration. Across multiple averages, scan parameters are varied (e.g., dual-polarity frequency-encoding) to additionally correct for B 0 $$ {\mathrm{B}}_0 $$ -induced artifacts, geometric distortions and motion retrospectively. A comparison to established GRE protocols is made. Resolutions range from 1.4 mm isotropic (1 multi-TE average in 36 s) up to 0.4 mm isotropic (2 single-TE averages in approximately 6 min) with whole-head coverage. RESULTS: Only 1-4 averages are needed for sufficient SNR with 3D-EPI, depending on resolution and field strength. Fast scanning and small voxels together with retrospective corrections result in substantially reduced image artifacts, which improves susceptibility and R 2 ∗ $$ {R}_2^{\ast } $$ mapping. Additionally, much finer details are obtained in susceptibility-weighted image projections through significantly reduced partial voluming. CONCLUSION: Using interleaved multishot 3D-EPI, single-TE and multi-TE data can readily be acquired 10 times faster than with conventional, accelerated GRE imaging. Even 0.4 mm isotropic whole-head QSM within 6 min becomes feasible at 7T. At 3T, motion-robust 0.8 mm isotropic whole-brain QSM and R 2 ∗ $$ {R}_2^{\ast } $$ mapping with no apparent distortion in less than 7 min becomes clinically feasible. Stronger gradient systems may allow for even higher effective acceleration rates through larger EPI factors while maintaining optimal contrast.

Fast 3D fMRI acquisition with high spatial resolutions over a reduced FOV.

PURPOSE: To develop and demonstrate a fast 3D fMRI acquisition technique with high spatial resolution over a reduced FOV, named k-t 3D reduced FOV imaging (3D-rFOVI). METHODS: Based on 3D gradient-echo EPI, k-t 3D-rFOVI used a 2D RF pulse to reduce the FOV in the in-plane phase-encoding direction, boosting spatial resolution without increasing echo train length. For image acceleration, full sampling was applied in the central k-space region along the through-slab direction (kz) for all time frames, while randomized undersampling was used in outer kz regions at different time frames. Images were acquired at 3T and reconstructed using a method based on partial separability. fMRI detection sensitivity of k-t 3D-rFOVI was quantitively analyzed with simulation data. Human visual fMRI experiments were performed to evaluate k-t 3D-rFOVI and compare it with a commercial multiband EPI sequence. RESULTS: The simulation data showed that k-t 3D-rFOVI can detect 100% of fMRI activations with an acceleration factor (R) of 2 and ˜80% with R = 6. In the human fMRI data acquired with 1.5-mm spatial resolution and 800-ms volume TR (TRvol), k-t 3D-rFOVI with R = 4 detected 46% more activated voxels in the visual cortex than the multiband EPI. Additional fMRI experiments showed that k-t 3D-rFOVI can achieve TRvol of 480 ms with R = 6, while reliably detecting visual activation. CONCLUSIONS: k-t 3D-rFOVI can simultaneously achieve a high spatial resolution (1.5-mm isotropically) and short TRvol (480-ms) at 3T. It offers a robust acquisition technique for fast fMRI studies over a focused brain volume.

Three-dimensional EPI with shot-selective CAIPIRIHANA for rapid high-resolution quantitative susceptibility mapping at 3 T.

PURPOSE: QSM provides insight into healthy brain aging and neuropathologies such as multiple sclerosis (MS), traumatic brain injuries, brain tumors, and neurodegenerative diseases. Phase data for QSM are usually acquired from 3D gradient-echo (3D GRE) scans with long acquisition times that are detrimental to patient comfort and susceptible to patient motion. This is particularly true for scans requiring whole-brain coverage and submillimeter resolutions. In this work, we use a multishot 3D echo plannar imaging (3D EPI) sequence with shot-selective 2D CAIPIRIHANA to acquire high-resolution, whole-brain data for QSM with minimal distortion and blurring. METHODS: To test clinical viability, the 3D EPI sequence was used to image a cohort of MS patients at 1-mm isotropic resolution at 3 T. Additionally, 3D EPI data of healthy subjects were acquired at 1-mm, 0.78-mm, and 0.65-mm isotropic resolution with varying echo train lengths (ETLs) and compared with a reference 3D GRE acquisition. RESULTS: The appearance of the susceptibility maps and the susceptibility values for segmented regions of interest were comparable between 3D EPI and 3D GRE acquisitions for both healthy and MS participants. Additionally, all lesions visible in the MS patients on the 3D GRE susceptibility maps were also visible on the 3D EPI susceptibility maps. The interplay among acquisition time, resolution, echo train length, and the effect of distortion on the calculated susceptibility maps was investigated. CONCLUSION: We demonstrate that the 3D EPI sequence is capable of rapidly acquiring submillimeter resolutions and providing high-quality, clinically relevant susceptibility maps.

Whole-cerebrum guanidino and amide CEST mapping at 3 T by a 3D stack-of-spirals gradient echo acquisition.

PURPOSE: To develop a 3D, high-sensitivity CEST mapping technique based on the 3D stack-of-spirals (SOS) gradient echo readout, the proposed approach was compared with conventional acquisition techniques and evaluated for its efficacy in concurrently mapping of guanidino (Guan) and amide CEST in human brain at 3 T, leveraging the polynomial Lorentzian line-shape fitting (PLOF) method. METHODS: Saturation time and recovery delay were optimized to achieve maximum CEST time efficiency. The 3DSOS method was compared with segmented 3D EPI (3DEPI), turbo spin echo, and gradient- and spin-echo techniques. Image quality, temporal SNR (tSNR), and test-retest reliability were assessed. Maps of Guan and amide CEST derived from 3DSOS were demonstrated on a low-grade glioma patient. RESULTS: The optimized recovery delay/saturation time was determined to be 1.4/2 s for Guan and amide CEST. In addition to nearly doubling the slice number, the gradient echo techniques also outperformed spin echo sequences in tSNR: 3DEPI (193.8 ± 6.6), 3DSOS (173.9 ± 5.6), and GRASE (141.0 ± 2.7). 3DSOS, compared with 3DEPI, demonstrated comparable GuanCEST signal in gray matter (GM) (3DSOS: [2.14%-2.59%] vs. 3DEPI: [2.15%-2.61%]), and white matter (WM) (3DSOS: [1.49%-2.11%] vs. 3DEPI: [1.64%-2.09%]). 3DSOS also achieves significantly higher amideCEST in both GM (3DSOS: [2.29%-3.00%] vs. 3DEPI: [2.06%-2.92%]) and WM (3DSOS: [2.23%-2.66%] vs. 3DEPI: [1.95%-2.57%]). 3DSOS outperforms 3DEPI in terms of scan-rescan reliability (correlation coefficient: 3DSOS: 0.58-0.96 vs. 3DEPI: -0.02 to 0.75) and robustness to motion as well. CONCLUSION: The 3DSOS CEST technique shows promise for whole-cerebrum CEST imaging, offering uniform contrast and robustness against motion artifacts.

Improved test-retest reliability of R 2 * $$ {\mathrm{R}}_2

PURPOSE: This study aimed to evaluate the potential of 3D EPI for improving the reliability of T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted data and quantification of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ decay rate and susceptibility (χ) compared with conventional gradient-echo (GRE)-based acquisition. METHODS: Eight healthy subjects in a wide age range were recruited. Each subject received repeated scans for both GRE and EPI acquisitions with an isotropic 1 mm resolution at 3 T. Maps of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and χ were quantified, and their interscan differences were used to evaluate the test-retest reliability. Interprotocol differences of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and χ between GRE and EPI were also measured voxel by voxel and in selected regions of interest to test the consistency between the two acquisition methods. RESULTS: The quantifications of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and χ using EPI protocols showed increased test-retest reliability with higher EPI factors up to 5 as performed in the experiment and were consistent with those based on GRE. CONCLUSION: The result suggests that multishot multi-echo 3D EPI can be a useful alternative acquisition method for T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted MRI and quantification of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and χ with reduced scan time, improved test-retest reliability, and similar accuracy compared with commonly used 3D GRE.

Susceptibility-based imaging aids accurate distinction of pediatric-onset MS from myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) and pediatric-onset multiple sclerosis (POMS) share clinical and magnetic resonance imaging (MRI) features but differ in prognosis and management. Early POMS diagnosis is essential to avoid disability accumulation. Central vein sign (CVS), paramagnetic rim lesions (PRLs), and central core lesions (CCLs) are susceptibility-based imaging (SbI)-related signs understudied in pediatric populations that may help discerning POMS from MOGAD. METHODS: T2-FLAIR and SbI (three-dimensional echoplanar imaging (3D-EPI)/susceptibility-weighted imaging (SWI) or similar) were acquired on 1.5T/3T scanners. Two readers assessed CVS-positive rate (%CVS+), and their average score was used to build a receiver operator curve (ROC) assessing the ability to discriminate disease type. PRLs and CCLs were identified using a consensual approach. RESULTS: The %CVS+ distinguished 26 POMS cases (mean age 13.7 years, 63% females, median EDSS 1.5) from 14 MOGAD cases (10.8 years, 35% females, EDSS 1.0) with ROC = 1, p < 0.0001, (cutoff 41%). PRLs were only detectable in POMS participants (mean 2.1±2.3, range 1-10), discriminating the two conditions with a sensitivity of 69% and a specificity of 100%. CCLs were more sensitive (81%) but less specific (71.43%). CONCLUSION: The %CVS+ and PRLs are highly specific markers of POMS. After proper validation on larger multicenter cohorts, consideration should be given to including such imaging markers for diagnosing POMS at disease onset.

Three-dimensional echo-shifted EPI with simultaneous blip-up and blip-down acquisitions for correcting geometric distortion.

PURPOSE: EPI with blip-up/down acquisition (BUDA) can provide high-quality images with minimal distortions by using two readout trains with opposing phase-encoding gradients. Because of the need for two separate acquisitions, BUDA doubles the scan time and degrades the temporal resolution when compared to single-shot EPI, presenting a major challenge for many applications, particularly fMRI. This study aims at overcoming this challenge by developing an echo-shifted EPI BUDA (esEPI-BUDA) technique to acquire both blip-up and blip-down datasets in a single shot. METHODS: A 3D esEPI-BUDA pulse sequence was designed by using an echo-shifting strategy to produce two EPI readout trains. These readout trains produced a pair of k-space datasets whose k-space trajectories were interleaved with opposite phase-encoding gradient directions. The two k-space datasets were separately reconstructed using a 3D SENSE algorithm, from which time-resolved B0 -field maps were derived using TOPUP in FSL and then input into a forward model of joint parallel imaging reconstruction to correct for geometric distortion. In addition, Hankel structured low-rank constraint was incorporated into the reconstruction framework to improve image quality by mitigating the phase errors between the two interleaved k-space datasets. RESULTS: The 3D esEPI-BUDA technique was demonstrated in a phantom and an fMRI study on healthy human subjects. Geometric distortions were effectively corrected in both phantom and human brain images. In the fMRI study, the visual activation volumes and their BOLD responses were comparable to those from conventional 3D echo-planar images. CONCLUSION: The improved imaging efficiency and dynamic distortion correction capability afforded by 3D esEPI-BUDA are expected to benefit many EPI applications.

Improved test-retest reliability of R2* and susceptibility quantification using multi-shot multi-echo 3D EPI.

This study aimed to evaluate the potential of 3D echo-planar imaging (EPI) for improving the reliability of T2*-weighted (T2*w) data and quantification of R2* decay rate and susceptibility (χ) compared to conventional gradient echo (GRE)-based acquisition. Eight healthy subjects in a wide age range were recruited. Each subject received repeated scans for both GRE and EPI acquisitions with an isotropic 1 mm resolution at 3 T. Maps of R2* and χ were quantified and compared using their inter-scan difference to evaluate the test-retest reliability. Inter-protocol differences of R2* and χ between GRE and EPI were also measured voxel by voxel and in selected ROIs to test the consistency between the two acquisition methods. The quantifications of R2* and χ using EPI protocols showed increased test-retest reliability with higher EPI factors up to 5 as performed in the experiment and were consistent with those based on GRE. This result suggested multi-shot multi-echo 3D EPI can be a useful alternative acquisition method for T2*w MRI and quantification of R2* and χ with reduced scan time, improved test-retest reliability and similar accuracy compared to commonly used 3D GRE.

Combining arterial blood contrast with BOLD increases fMRI intracortical contrast.

BOLD fMRI is widely applied in human neuroscience but is limited in its spatial specificity due to a cortical-depth-dependent venous bias. This reduces its localization specificity with respect to neuronal responses, a disadvantage for neuroscientific research. Here, we modified a submillimeter BOLD protocol to selectively reduce venous and tissue signal and increase cerebral blood volume weighting through a pulsed saturation scheme (dubbed Arterial Blood Contrast) at 7 T. Adding Arterial Blood Contrast on top of the existing BOLD contrast modulated the intracortical contrast. Isolating the Arterial Blood Contrast showed a response free of pial-surface bias. The results suggest that Arterial Blood Contrast can modulate the typical fMRI spatial specificity, with important applications in in-vivo neuroscience.

Self-navigated prospective motion correction for 3D-EPI acquisition.

PURPOSE: Although 3D EPI is more susceptible to motion artifacts than 2D EPI, it presents some benefits for functional MRI, including the absence of spin-history artifacts, greater potential for parallel imaging acceleration, and better functional sensitivity in high-resolution imaging. Here we present a self-navigated 3D-EPI sequence suitable for prospective motion-corrected functional MRI without additional hardware or pulses. METHODS: For each volume acquisition, the first 24 of the 52 partitions being acquired are accumulated to a new feedback block that was added to the image reconstruction pipeline. After zero-filling the remaining partitions, the feedback block constructs a volumetric self-navigator (vSNav), co-registers it to the reference vSNav acquired during the first volume acquisition, and sends motion estimates to the sequence. The sequence then updates its FOV and acquires subsequent partitions with the adjusted FOV, until the next update is received. The sequence was validated without and with intentional motion in phantom and in vivo on a 3T Skyra. RESULTS: For phantom scans, the FOV was updated 0.704 s after acquisition of the vSNav partitions, and for in vivo scans after 0.768 s. Both phantom and in vivo data demonstrated stable motion estimates in the absence of motion. For in vivo acquisitions, prospective head-pose estimates using the vSNav's and retrospective estimates with FLIRT (FMRIB's Linear Image Registration Tool) agreed to within 0.23 mm (< 10% of the slice thickness) and 0.14° in all directions. CONCLUSION: Depending when motion occurs during a volume acquisition, the proposed method fully corrects the FOV and recovers image quality within one volume acquisition.

A local multi-transmit coil combined with a high-density receive array for cerebellar fMRI at 7 T.

The human cerebellum is involved in a wide array of functions, ranging from motor control to cognitive control, and as such is of great neuroscientific interest. However, its function is underexplored in vivo, due to its small size, its dense structure and its placement at the bottom of the brain, where transmit and receive fields are suboptimal. In this study, we combined two dense coil arrays of 16 small surface receive elements each with a transmit array of three antenna elements to improve BOLD sensitivity in the human cerebellum at 7 T. Our results showed improved B1+ and SNR close to the surface as well as g-factor gains compared with a commercial coil designed for whole-head imaging. This resulted in improved signal stability and large gains in the spatial extent of the activation close to the surface (<3.5 cm), while good performance was retained deeper in the cerebellum. Modulating the phase of the transmit elements of the head coil to constructively interfere in the cerebellum improved the B1+ , resulting in a temporal SNR gain. Overall, our results show that a dedicated transmit array along with the SNR gains of surface coil arrays can improve cerebellar imaging, at the cost of a decreased field of view and increased signal inhomogeneity.

Segmented K-space blipped-controlled aliasing in parallel imaging for high spatiotemporal resolution EPI.

PURPOSE: A segmented k-space blipped-controlled aliasing in parallel imaging (skipped-CAIPI) sampling strategy for EPI is proposed, which allows for a flexible choice of EPI factor and phase encode bandwidth independent of the controlled aliasing in parallel imaging (CAIPI) sampling pattern. THEORY AND METHODS: With previously proposed approaches, exactly two EPI trajectories were possible given a specific CAIPI pattern, either with slice gradient blips (blipped-CAIPI) or following a shot-selective CAIPI approach (higher resolution). Recently, interleaved multi-shot segmentation along shot-selective CAIPI trajectories has been applied for high-resolution anatomical imaging. For more flexibility and a broader range of applications, we propose segmentation along any blipped-CAIPI trajectory. Thus, all EPI factors and phase encode bandwidths available with traditional segmented EPI can be combined with controlled aliasing. RESULTS: Temporal SNR maps of moderate-to-high-resolution time series acquisitions at varying undersampling factors demonstrate beneficial sampling alternatives to blipped-CAIPI or shot-selective CAIPI. Rapid high-resolution scans furthermore demonstrate SNR-efficient and motion-robust structural imaging with almost arbitrary EPI factor and minimal noise penalty. CONCLUSION: Skipped-CAIPI sampling increases protocol flexibility for high spatiotemporal resolution EPI. In terms of SNR and efficiency, high-resolution functional or structural scans benefit vastly from a free choice of the CAIPI pattern. Even at moderate resolutions, the independence of sampling pattern, TE, and image matrix size is valuable for optimized functional protocol design. Although demonstrated with 3D-EPI, skipped-CAIPI is also applicable with simultaneous multislice EPI.

Pushing functional MRI spatial and temporal resolution further: High-density receive arrays combined with shot-selective 2D CAIPIRINHA for 3D echo-planar imaging at 7 T.

To be able to examine dynamic and detailed brain functions, the spatial and temporal resolution of 7 T MRI needs to improve. In this study, it was investigated whether submillimeter multishot 3D EPI fMRI scans, acquired with high-density receive arrays, can benefit from a 2D CAIPIRINHA sampling pattern, in terms of noise amplification (g-factor), temporal SNR and fMRI sensitivity. High-density receive arrays were combined with a shot-selective 2D CAIPIRINHA implementation for multishot 3D EPI sequences at 7 T. In this implementation, in contrast to conventional inclusion of extra kz gradient blips, specific EPI shots are left out to create a CAIPIRINHA shift and reduction of scan time. First, the implementation of the CAIPIRINHA sequence was evaluated with a standard receive setup by acquiring submillimeter whole brain T2 *-weighted anatomy images. Second, the CAIPIRINHA sequence was combined with high-density receive arrays to push the temporal resolution of submillimeter 3D EPI fMRI scans of the visual cortex. Results show that the shot-selective 2D CAIPIRINHA sequence enables a reduction in scan time for 0.5 mm isotropic 3D EPI T2 *-weighted anatomy scans by a factor of 4 compared with earlier reports. The use of the 2D CAIPIRINHA implementation in combination with high-density receive arrays, enhances the image quality of submillimeter 3D EPI scans of the visual cortex at high acceleration as compared to conventional SENSE. Both the g-factor and temporal SNR improved, resulting in a method that is more sensitive to the fMRI signal. Using this method, it is possible to acquire submillimeter single volume 3D EPI scans of the visual cortex in a subsecond timeframe. Overall, high-density receive arrays in combination with shot-selective 2D CAIPIRINHA for 3D EPI scans prove to be valuable for reducing the scan time of submillimeter MRI acquisitions.

Self-navigation for 3D multishot EPI with data-reference.

PURPOSE: In this study, we sought to develop a self-navigation strategy for improving the reconstruction of diffusion weighted 3D multishot echo planar imaging (EPI). We propose a method for extracting the phase correction information from the acquisition itself, eliminating the need for a 2D navigator, further accelerating the acquisition. METHODS: In-vivo acquisitions at 3T with 0.9 mm and 1.5 mm isotropic resolutions were used to evaluate the performance of the self-navigation strategy. Sensitivity to motion was tested using a large difference in pitch position of the head. Using a multishell diffusion weighted acquisition, tractography results were obtained at (0.9 mm)3 to validate the quality with conventional acquisition. RESULTS: The use of 3D multislab EPI with self-navigation enables 3D diffusion-weighted spin echo EPI acquisitions that have the same efficiency as 2D single-shot acquisition. For matched acquisition time the image signal-to-noise ratio (SNR) between 3D and 2D acquisition is shown to be comparable for whole-brain coverage with (1.5 mm)3 resolution and for (0.9 mm)3 resolution the 3D acquisition has higher SNR than what can be obtained with 2D acquisitions using current state-of-art multiband techniques. The self-navigation technique was shown to be stable under inter-volume motion. In tractography analysis, the higher resolution afforded by our technique enabled clear delineation of the tapetum and posterior corona radiata. CONCLUSION: The proposed self-navigation approach utilized a self-consistent phase in 3D diffusion weighted acquisitions. Its efficiency and stability were demonstrated for a plurality of common acquisitions. The proposed self-navigation approach allows for faster acquisition of 3D multishot EPI desirable for large field of view and/or higher resolution.

Bayesian population receptive field modeling in human somatosensory cortex.

Somatosensation is fundamental to our ability to sense our body and interact with the world. Our body is continuously sampling the environment using a variety of receptors tuned to different features, and this information is routed up to primary somatosensory cortex. Strikingly, the spatial organization of the peripheral receptors in the body are well maintained, with the resulting representation of the body in the brain being referred to as the somatosensory homunculus. Recent years have seen considerable advancements in the field of high-resolution fMRI, which have enabled an increasingly detailed examination of the organization and properties of this homunculus. Here we combined advanced imaging techniques at ultra-high field (7T) with a recently developed Bayesian population receptive field (pRF) modeling framework to examine pRF properties in primary somatosensory cortex. In each subject, vibrotactile stimulation of the fingertips (i.e., the peripheral mechanoreceptors) modulated the fMRI response along the post-central gyrus and these signals were used to estimate pRFs. We found the pRF center location estimates to be in accord with previous work as well as evidence of other properties in line with the underlying neurobiology. Specifically, as expected from the known properties of cortical magnification, we find a larger representation of the index finger compared to the other stimulated digits (middle, index, little). We also show evidence that the little finger is marked by the largest pRF sizes, and that pRF size increases from anterior to posterior regions of S1. The ability to estimate somatosensory pRFs in humans provides an unprecedented opportunity to examine the neural mechanisms underlying somatosensation and is critical for studying how the brain, body, and environment interact to inform perception and action.

Whole-brain snapshot CEST imaging at 7 T using 3D-EPI.

PURPOSE: The aim of this work is to develop a fast and robust CEST sequence in order to allow the acquisition of a whole-brain imaging volume after a single preparation block (snapshot acquisition). METHODS: A 3D-CEST sequence with an optimized 3D-EPI readout module was developed, which acquires the complete k-space data following a single CEST preparation for 1 saturation offset. Whole-brain mapping of the Z-spectrum with 2 mm isotropic resolution is achieved at 68 saturation frequencies in 5 minutes (4.33 s per offset). We analyzed the B1 distribution in order to optimize B1 correction and to provide accurate CEST quantification across the whole brain. RESULTS: We obtained maps for 3 different CEST contrasts from 4 healthy subjects. Based on our B1 distribution analysis, we conclude that 3 B1 sampling points allow for sufficient compensation of B1 variations across most of the brain. Two brain regions, the cerebellum and the temporal lobes, are difficult to quantify at 7 T due to very low B1 that was achieved in these regions. CONCLUSIONS: The proposed sequence enables robust acquisition of 2 mm isotropic whole-brain CEST maps at 7 Tesla within a total scan time of 16 minutes.

Determining the optimal postlabeling delay for arterial spin labeling using subject-specific estimates of blood velocity in the carotid artery.

BACKGROUND: Arterial spin labeling with 3D acquisition requires determining a single postlabeling delay (PLD) value. PLD affects the signal-to-noise ratio (SNR) per unit time as well as quantitative cerebral blood flow (CBF) values due to its bearing on the presence of a vascular signal. PURPOSE: To search for an optimal PLD for pseudocontinuous arterial spin labeling (pCASL) using patient-specific carotid artery blood velocity measurements. STUDY TYPE: Prospective. SUBJECTS: A control group of 11 volunteers with no known pathology. Corroboration was through a separate group of six volunteers and a noncontrol group of five sickle cell disease (SCD) patients. FIELD STRENGTH/SEQUENCE: Pseudocontinuous arterial spin labeling with 3D nonsegmented echo planar imaging acquisition at 3T. ASSESSMENT: A perfusion-based measure was determined over a range of PLDs for each of 11 volunteers. A third-order polynomial was used to find the optimal PLD where the defined measure was maximum. This was plotted against the corresponding carotid artery velocity to determine a relationship between the perfusion measure and velocity. Corroboration was done using a group of six volunteers and a noncontrol group of five patients with SCD. PLD was determined from the carotid artery velocity and derived relationship and compared with optimal PLD obtained from measured perfusion over a range of PLD values. Error between the perfusion measure at predicted and measured optimal PLD was determined. STATISTICAL TESTS: Chi-squared goodness of fit; Pearson correlation; Bland-Altman. RESULTS: Carotid artery velocity was 63.8 ± 6.6 cm/s (53.1 ≤ v ≤ 72.3 cm/s) while optimal PLD was 1374 ± 226.5 msec (1102 ≤ PLD ≤ 1787 msec) across the 11 volunteers. PLD as a function of carotid velocity was determined to be PLD = -31.94. v + 3410 msec (Pearson correlation -0.93). In six volunteers, mean error between the perfusion measure at predicted and measured optimal PLD was 1.35%. Pearson correlation between the perfusion measure at the predicted PLD and the measure obtained experimentally was r = 0.96 (P < 0.001). Bland-Altman revealed a slight bias of 1.3%. For the test case of five SCD patients, the mean error was 1.3%. DATA CONCLUSION: Carotid artery velocity was used to determine optimal PLD for pCASL with 3D acquisition. The derived relationship was used to predict optimal PLD and the associated perfusion measure, which was found to be accurate when compared with its measured counterpart. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:951-960.

Ultra-high resolution blood volume fMRI and BOLD fMRI in humans at 9.4 T: Capabilities and challenges.

Functional mapping of cerebral blood volume (CBV) changes has the potential to reveal brain activity with high localization specificity at the level of cortical layers and columns. Non-invasive CBV imaging using Vascular Space Occupancy (VASO) at ultra-high magnetic field strengths promises high spatial specificity but poses unique challenges in human applications. As such, 9.4 T B1+ and B0 inhomogeneities limit efficient blood tagging, while the specific absorption rate (SAR) constraints limit the application of VASO-specific RF pulses. Moreover, short T2* values at 9.4 T require short readout duration, and long T1 values at 9.4 T can cause blood-inflow contaminations. In this study, we investigated the applicability of layer-dependent CBV-fMRI at 9.4 T in humans. We addressed the aforementioned challenges by combining multiple technical advancements: temporally alternating pTx B1+ shimming parameters, advanced adiabatic RF-pulses, 3D-EPI signal readout, optimized GRAPPA acquisition and reconstruction, and stability-optimized RF channel combination. We found that a combination of suitable advanced methodology alleviates the challenges and potential artifacts, and that VASO fMRI provides reliable measures of CBV change across cortical layers in humans at 9.4 T. The localization specificity of CBV-fMRI, combined with the high sensitivity of 9.4 T, makes this method an important tool for future studies investigating cortical micro-circuitry in humans.

High spatio-temporal resolution in functional MRI with 3D echo planar imaging using cylindrical excitation and a CAIPIRINHA undersampling pattern.

PURPOSE: The combination of 3D echo planar imaging (3D-EPI) with a 2D-CAIPIRINHA undersampling scheme provides high flexibility in the optimization for spatial or temporal resolution. This flexibility can be increased further with the addition of a cylindrical excitation pulse, which exclusively excites the brain regions of interest. Here, 3D-EPI was combined with a 2D radiofrequency pulse to reduce the brain area from which signal is generated, and hence, allowing either reduction of the field of view or reduction of parallel imaging noise amplification. METHODS: 3D-EPI with cylindrical excitation and 4 × 3-fold undersampling in a 2D-CAIPIRINHA sampling scheme was used to generate functional MRI (fMRI) data with either 2-mm or 0.9-mm in-plane resolution and 1.1-s temporal resolution over a 5-cm diameter cylinder placed over both temporal lobes for an auditory fMRI experiment. RESULTS: Significant increases in image signal-to-noise ratio (SNR) and temporal SNR (tSNR) were found for both 2-mm isotropic data and the high-resolution protocol when using the cylindrical excitation pulse. Both protocols yielded highly significant blood oxygenation level-dependent responses for the presentation of natural sounds. CONCLUSION: The higher tSNR of the cylindrical excitation 3D-EPI data makes this sequence an ideal choice for high spatiotemporal resolution fMRI acquisitions. Magn Reson Med 79:2589-2596, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Techniques for blood volume fMRI with VASO: From low-resolution mapping towards sub-millimeter layer-dependent applications.

Quantitative cerebral blood volume (CBV) fMRI has the potential to overcome several specific limitations of BOLD fMRI. It provides direct physiological interpretability and promises superior localization specificity in applications of sub-millimeter resolution fMRI applications at ultra-high magnetic fields (7T and higher). Non-invasive CBV fMRI using VASO (vascular space occupancy), however, is inherently limited with respect to its data acquisition efficiency, restricting its imaging coverage and achievable spatial and temporal resolution. This limitation may be reduced with recent advanced acceleration and reconstruction strategies that allow two-dimensional acceleration, such as in simultaneous multi-slice (SMS) 2D-EPI or 3D-EPI in combination with CAIPIRINHA field-of-view shifting. In this study, we sought to determine the functional sensitivity and specificity of these readout strategies with VASO over a broad range of spatial resolutions; spanning from low spatial resolution (3mm) whole-cortex to sub-millimeter (0.75mm) slab-of-cortex (for cortical layer-dependent applications). In the thermal-noise-dominated regime of sub-millimeter resolutions, 3D-EPI-VASO provides higher temporal stability and sensitivity to detect changes in CBV compared to 2D-EPI-VASO. In this regime, 3D-EPI-VASO unveils task activation located in the cortical laminae with little contamination from surface veins, in contrast to the cortical surface weighting of GE-BOLD fMRI. In the physiological-noise-dominated regime of lower resolutions, however, 2D-SMS-VASO shows superior performance compared to 3D-EPI-VASO. Due to its superior sensitivity at a layer-dependent level, 3D-EPI VASO promises to play an important role in future neuroscientific applications of layer-dependent fMRI.