Next-generation MRI scanner designed for ultra-high-resolution human brain imaging at 7 Tesla.

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-1s-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.

The possible influence of third-order shim coils on gradient-magnet interactions: an inter-field and inter-site study.

OBJECTIVE: To assess the possible influence of third-order shim coils on the behavior of the gradient field and in gradient-magnet interactions at 7 T and above. MATERIALS AND METHODS: Gradient impulse response function measurements were performed at 5 sites spanning field strengths from 7 to 11.7 T, all of them sharing the same exact whole-body gradient coil design. Mechanical fixation and boundary conditions of the gradient coil were altered in several ways at one site to study the impact of mechanical coupling with the magnet on the field perturbations. Vibrations, power deposition in the He bath, and field dynamics were characterized at 11.7 T with the third-order shim coils connected and disconnected inside the Faraday cage. RESULTS: For the same whole-body gradient coil design, all measurements differed greatly based on the third-order shim coil configuration (connected or not). Vibrations and gradient transfer function peaks could be affected by a factor of 2 or more, depending on the resonances. Disconnecting the third-order shim coils at 11.7 T also suppressed almost completely power deposition peaks at some frequencies. DISCUSSION: Third-order shim coil configurations can have major impact in gradient-magnet interactions with consequences on potential hardware damage, magnet heating, and image quality going beyond EPI acquisitions.

Peripheral nerve stimulation informed design of a high-performance asymmetric head gradient coil.

PURPOSE: Peripheral nerve stimulation (PNS) limits the image encoding performance of both body gradient coils and the latest generation of head gradients. We analyze a variety of head gradient design aspects using a detailed PNS model to guide the design process of a new high-performance asymmetric head gradient to raise PNS thresholds and maximize the usable image-encoding performance. METHODS: A novel three-layer coil design underwent PNS optimization involving PNS predictions of a series of candidate designs. The PNS-informed design process sought to maximize the usable parameter space of a coil with <10% nonlinearity in a 22 cm region of linearity, a relatively large inner diameter (44 cm), maximum gradient amplitude of 200 mT/m, and a high slew rate of 900 T/m/s. PNS modeling allowed identification and iterative adjustment of coil features with beneficial impact on PNS such as the number of winding layers, shoulder accommodation strategy, and level of asymmetry. PNS predictions for the final design were compared to measured thresholds in a constructed prototype. RESULTS: The final head gradient achieved up to 2-fold higher PNS thresholds than the initial design without PNS optimization and compared to existing head gradients with similar design characteristics. The inclusion of a third intermediate winding layer provided the additional degrees of freedom necessary to improve PNS thresholds without significant sacrifices to the other design metrics. CONCLUSION: Augmenting the design phase of a new high-performance head gradient coil by PNS modeling dramatically improved the usable image-encoding performance by raising PNS thresholds.

A 128-channel receive array for cortical brain imaging at 7 T.

PURPOSE: A 128-channel receive-only array for brain imaging at 7 T was simulated, designed, constructed, and tested within a high-performance head gradient designed for high-resolution functional imaging. METHODS: The coil used a tight-fitting helmet geometry populated with 128 loop elements and preamplifiers to fit into a 39 cm diameter space inside a built-in gradient. The signal-to-noise ratio (SNR) and parallel imaging performance (1/g) were measured in vivo and simulated using electromagnetic modeling. The histogram of 1/g factors was analyzed to assess the range of performance. The array's performance was compared to the industry-standard 32-channel receive array and a 64-channel research array. RESULTS: It was possible to construct the 128-channel array with body noise-dominated loops producing an average noise correlation of 5.4%. Measurements showed increased sensitivity compared with the 32-channel and 64-channel array through a combination of higher intrinsic SNR and g-factor improvements. For unaccelerated imaging, the 128-channel array showed SNR gains of 17.6% and 9.3% compared to the 32-channel and 64-channel array, respectively, at the center of the brain and 42% and 18% higher SNR in the peripheral brain regions including the cortex. For R = 5 accelerated imaging, these gains were 44.2% and 24.3% at the brain center and 86.7% and 48.7% in the cortex. The 1/g-factor histograms show both an improved mean and a tighter distribution by increasing the channel count, with both effects becoming more pronounced at higher accelerations. CONCLUSION: The experimental results confirm that increasing the channel count to 128 channels is beneficial for 7T brain imaging, both for increasing SNR in peripheral brain regions and for accelerated imaging.

Distinct local and brain-wide networks are activated by optogenetic stimulation of neurons specific to each layer of motor cortex.

Primary motor cortex (M1) consists of a stack of interconnected but distinct layers (L1-L6) which affect motor control through large-scale networks. However, the brain-wide functional influence of each layer is poorly understood. We sought to expand our knowledge of these layers' circuitry by combining Cre-driver mouse lines, optogenetics, fMRI, and electrophysiology. Neuronal activities initiated in Drd3 neurons (within L2/3) were mainly confined within M1, while stimulation of Scnn1a, Rbp4, and Ntsr1 neurons (within L4, L5, and L6, respectively) evoked distinct responses in M1 and motor-related subcortical regions, including striatum and motor thalamus. We also found that fMRI responses from targeted stimulations correlated with both local field potentials (LFPs) and spike changes. This study represents a step forward in our understanding of how different layers of primary motor cortex are embedded in brain-wide circuitry.

Highly accelerated submillimeter resolution 3D GRASE with controlled T2 blurring in T2 -weighted functional MRI at 7 Tesla: A feasibility study.

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.

Comparison of BOLD and CBV using 3D EPI and 3D GRASE for cortical layer functional MRI at 7 T.

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.

Virtual slice concept for improved simultaneous multi-slice MRI employing an extended leakage constraint.

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.

Pushing the limits of ultra-high resolution human brain imaging with SMS-EPI demonstrated for columnar level fMRI.

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.

Evaluation of SLIce Dithered Enhanced Resolution Simultaneous MultiSlice (SLIDER-SMS) for human fMRI.

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).

Early cancer diagnoses through BRCA1/2 screening of unselected adult biobank participants.

PurposeThe clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility.MethodsWhole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants. Clinically confirmed variants were disclosed to patient-participants and their clinicians. We queried patient-participants' electronic health records for BRCA1/2-associated cancer diagnoses and risk management that occurred within 12 months after results disclosure, and calculated the percentage of patient-participants of eligible age who had begun risk management.ResultsThirty-seven MyCode patient-participants were unaware of their pathogenic/likely pathogenic BRCA1/2 variant, had not had a BRCA1/2-associated cancer, and had 12 months of follow-up. Of the 33 who were of an age to begin BRCA1/2-associated risk management, 26 (79%) had performed at least one such procedure. Three were diagnosed with an early-stage, BRCA1/2-associated cancer-including a stage 1C fallopian tube cancer-via these procedures.ConclusionScreening for pathogenic BRCA1/2 variants among unselected individuals can lead to occult cancer detection shortly after disclosure. Comprehensive outcomes data generated within our learning healthcare system will aid in determining whether population-wide BRCA1/2 genomic screening programs offer clinical utility.

No clear evidence for correlations between handgrip strength and sexually dimorphic acoustic properties of voices.

OBJECTIVES: Recent research on the signal value of masculine physical characteristics in men has focused on the possibility that such characteristics are valid cues of physical strength. However, evidence that sexually dimorphic vocal characteristics are correlated with physical strength is equivocal. Consequently, we undertook a further test for possible relationships between physical strength and masculine vocal characteristics. METHODS: We tested the putative relationships between White UK (N = 115) and Chinese (N = 106) participants' handgrip strength (a widely used proxy for general upper-body strength) and five sexually dimorphic acoustic properties of voices: fundamental frequency (F0), fundamental frequency's SD (F0-SD), formant dispersion (Df), formant position (Pf), and estimated vocal-tract length (VTL). RESULTS: Analyses revealed no clear evidence that stronger individuals had more masculine voices. CONCLUSIONS: Our results do not support the hypothesis that masculine vocal characteristics are a valid cue of physical strength.

Rapid brain MRI acquisition techniques at ultra-high fields.

Ultra-high-field MRI provides large increases in signal-to-noise ratio (SNR) as well as enhancement of several contrast mechanisms in both structural and functional imaging. Combined, these gains result in a substantial boost in contrast-to-noise ratio that can be exploited for higher-spatial-resolution imaging to extract finer-scale information about the brain. With increased spatial resolution, however, there is a concurrent increased image-encoding burden that can cause unacceptably long scan times for structural imaging and slow temporal sampling of the hemodynamic response in functional MRI - particularly when whole-brain imaging is desired. To address this issue, new directions of imaging technology development - such as the move from conventional 2D slice-by-slice imaging to more efficient simultaneous multislice (SMS) or multiband imaging (which can be viewed as "pseudo-3D" encoding) as well as full 3D imaging - have provided dramatic improvements in acquisition speed. Such imaging paradigms provide higher SNR efficiency as well as improved encoding efficiency. Moreover, SMS and 3D imaging can make better use of coil sensitivity information in multichannel receiver arrays used for parallel imaging acquisitions through controlled aliasing in multiple spatial directions. This has enabled unprecedented acceleration factors of an order of magnitude or higher in these imaging acquisition schemes, with low image artifact levels and high SNR. Here we review the latest developments of SMS and 3D imaging methods and related technologies at ultra-high field for rapid high-resolution functional and structural imaging of the brain. Copyright © 2016 John Wiley & Sons, Ltd.

Dynamics of respiratory and cardiac CSF motion revealed with real-time simultaneous multi-slice EPI velocity phase contrast imaging.

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 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) CSF movement into the cranial cavity and lateral ventricles and a reversal of direction in expiration phase.

Temporally-independent functional modes of spontaneous brain activity.

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.

Functional mapping of the magnocellular and parvocellular subdivisions of human LGN.

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 (7 T and 3 T) 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.

Changes in salivary estradiol predict changes in women's preferences for vocal masculinity.

Although many studies have reported that women's preferences for masculine physical characteristics in men change systematically during the menstrual cycle, the hormonal mechanisms underpinning these changes are currently poorly understood. Previous studies investigating the relationships between measured hormone levels and women's masculinity preferences tested only judgments of men's facial attractiveness. Results of these studies suggested that preferences for masculine characteristics in men's faces were related to either women's estradiol or testosterone levels. To investigate the hormonal correlates of within-woman variation in masculinity preferences further, here we measured 62 women's salivary estradiol, progesterone, and testosterone levels and their preferences for masculine characteristics in men's voices in five weekly test sessions. Multilevel modeling of these data showed that changes in salivary estradiol were the best predictor of changes in women's preferences for vocal masculinity. These results complement other recent research implicating estradiol in women's mate preferences, attention to courtship signals, sexual motivation, and sexual strategies, and are the first to link women's voice preferences directly to measured hormone levels.

Sociosexual attitudes and dyadic sexual desire independently predict women's preferences for male vocal masculinity.

Research suggests that the desire to behave sexually with a partner (dyadic sexual desire) may reflect desire for intimacy whereas solitary sexual desire may reflect pleasure seeking motivations more generally. Because direct reproductive success can only be increased with a sexual partner, we tested whether dyadic sexual desire was a better predictor of women's preferences for lower pitched men's voices (a marker of relatively high reproductive success) than was solitary sexual desire. In Study 1, women (N = 95) with higher dyadic sexual desire scores on the Sexual Desire Inventory-2 preferred masculinized male voices more than did women with lower dyadic sexual desire scores. We did not find a significant relationship between women's vocal masculinity preferences and their solitary sexual desire scores. In Study 2, we tested whether the relationship between voice preferences and dyadic sexual desire scores was related to differences in sociosexual orientation. Women (N = 80) with more positive attitudes towards uncommitted sex had stronger vocal masculinity preferences regardless of whether men's attractiveness was judged for short-term or long-term relationships. Independent of the effect of sociosexual attitudes, dyadic sexual desire positively predicted women's masculinity preferences when assessing men's attractiveness for short-term but not long-term relationships. These effects were independent of women's own relationship status and hormonal contraceptive use. Our results provide further evidence that women's mate preferences may independently reflect individual differences in both sexual desire and openness to short-term relationships, potentially with the ultimate function of maximizing the fitness benefits of women's mate choices.

No evidence that averaging voices influences attractiveness.

Vocal attractiveness influences important social outcomes. While most research on the acoustic parameters that influence vocal attractiveness has focused on the possible roles of sexually dimorphic characteristics of voices, such as fundamental frequency (i.e., pitch) and formant frequencies (i.e., a correlate of body size), other work has reported that increasing vocal averageness increases attractiveness. Here we investigated the roles these three characteristics play in judgments of the attractiveness of male and female voices. In Study 1, we found that increasing vocal averageness significantly decreased distinctiveness ratings, demonstrating that participants could detect manipulations of vocal averageness in this stimulus set and using this testing paradigm. However, in Study 2, we found no evidence that increasing averageness significantly increased attractiveness ratings of voices. In Study 3, we found that fundamental frequency was negatively correlated with male vocal attractiveness and positively correlated with female vocal attractiveness. By contrast with these results for fundamental frequency, vocal attractiveness and formant frequencies were not significantly correlated. Collectively, our results suggest that averageness may not necessarily significantly increase attractiveness judgments of voices and are consistent with previous work reporting significant associations between attractiveness and voice pitch.