Neurodesk: an accessible, flexible and portable data analysis environment for reproducible neuroimaging.

Neuroimaging research requires purpose-built analysis software, which is challenging to install and may produce different results across computing environments. The community-oriented, open-source Neurodesk platform ( https://www.neurodesk.org/ ) harnesses a comprehensive and growing suite of neuroimaging software containers. Neurodesk includes a browser-accessible virtual desktop, command-line interface and computational notebook compatibility, allowing for accessible, flexible, portable and fully reproducible neuroimaging analysis on personal workstations, high-performance computers and the cloud.

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.

Imaging the columnar functional organization of human area MT+ to axis-of-motion stimuli using VASO at 7 Tesla.

Cortical columns of direction-selective neurons in the motion sensitive area (MT) have been successfully established as a microscopic feature of the neocortex in animals. The same property has been investigated at mesoscale (<1 mm) in the homologous brain area (hMT+, V5) in living humans by using ultra-high field functional magnetic resonance imaging (fMRI). Despite the reproducibility of the selective response to axis-of-motion stimuli, clear quantitative evidence for the columnar organization of hMT+ is still lacking. Using cerebral blood volume (CBV)-sensitive fMRI at 7 Tesla with submillimeter resolution and high spatial specificity to microvasculature, we investigate the columnar functional organization of hMT+ in 5 participants perceiving axis-of-motion stimuli for both blood oxygenation level dependent (BOLD) and vascular space occupancy (VASO) contrast mechanisms provided by the used slice-selective slab-inversion (SS-SI)-VASO sequence. With the development of a new searchlight algorithm for column detection, we provide the first quantitative columnarity map that characterizes the entire 3D hMT+ volume. Using voxel-wise measures of sensitivity and specificity, we demonstrate the advantage of using CBV-sensitive fMRI to detect mesoscopic cortical features by revealing higher specificity of axis-of-motion cortical columns for VASO as compared to BOLD contrast. These voxel-wise metrics also provide further insights on how to mitigate the highly debated draining veins effect. We conclude that using CBV-VASO fMRI together with voxel-wise measurements of sensitivity, specificity and columnarity offers a promising avenue to quantify the mesoscopic organization of hMT+ with respect to axis-of-motion stimuli. Furthermore, our approach and methodological developments are generalizable and applicable to other human brain areas where similar mesoscopic research questions are addressed.

Layer-fMRI VASO with short stimuli and event-related designs at 7 T.

Layers and columns are the dominant processing units in the human (neo)cortex at the mesoscopic scale. While the blood oxygenation dependent (BOLD) signal has a high detection sensitivity, it is biased towards unwanted signals from large draining veins at the cortical surface. The additional fMRI contrast of vascular space occupancy (VASO) has the potential to augment the neuroscientific interpretability of layer-fMRI results by means of capturing complementary information of locally specific changes in cerebral blood volume (CBV). Specifically, VASO is not subject to unwanted sensitivity amplifications of large draining veins. Because of constrained sampling efficiency, it has been mainly applied in combination with efficient block task designs and long trial durations. However, to study cognitive processes in neuroscientific contexts, or probe vascular reactivity, short stimulation periods are often necessary. Here, we developed a VASO acquisition procedure with a short acquisition period and sub-millimeter resolution. During visual event-related stimulation, we show reliable responses in visual cortices within a reasonable number of trials (∼20). Furthermore, the short TR and high spatial specificity of our VASO implementation enabled us to show differences in laminar reactivity and onset times. Finally, we explore the generalizability to a different stimulus modality (somatosensation). With this, we showed that CBV-sensitive VASO provides the means to capture layer-specific haemodynamic responses with high spatio-temporal resolution and is able to be used with event-related paradigms.

Magnetic resonance imaging at 9.4 T: the Maastricht journey.

The 9.4 T scanner in Maastricht is a whole-body magnet with head gradients and parallel RF transmit capability. At the time of the design, it was conceptualized to be one of the best fMRI scanners in the world, but it has also been used for anatomical and diffusion imaging. 9.4 T offers increases in sensitivity and contrast, but the technical ultra-high field (UHF) challenges, such as field inhomogeneities and constraints set by RF power deposition, are exacerbated compared to 7 T. This article reviews some of the 9.4 T work done in Maastricht. Functional imaging experiments included blood oxygenation level-dependent (BOLD) and blood-volume weighted (VASO) fMRI using different readouts. BOLD benefits from shorter T2* at 9.4 T while VASO from longer T1. We show examples of both ex vivo and in vivo anatomical imaging. For many applications, pTx and optimized coils are essential to harness the full potential of 9.4 T. Our experience shows that, while considerable effort was required compared to our 7 T scanner, we could obtain high-quality anatomical and functional data, which illustrates the potential of MR acquisitions at even higher field strengths. The practical challenges of working with a relatively unique system are also discussed.

Concurrent CBF and BOLD FMRI with dual-echo spiral simultaneous multi-slice acquisitions at 7T.

Measurement of cerebral blood flow (CBF) using the Arterial Spin Labeling (ASL) technique is a desirable fMRI approach due to the higher specificity of CBF to the site of neural activation. However, ASL has inherent limitations, such as a low signal-to-noise ratio (SNR) and low coverage/resolution due to the limited readout window following the labeling. Recently, ASL has been implemented at ultra-high field (UHF) strengths in an attempt to mitigate the SNR challenges. Even though ASL intrinsically allows concurrent acquisition of CBF and BOLD contrasts, a compromise in the echo time (TE) for either of the contrasts is inevitable with single-echo acquisitions. Long durations of the Cartesian EPI readout do not allow for multi-echo acquisitions for resolutions ≤2 mm where both contrasts can be acquired at their optimal TE at UHF. With its higher acquisition efficiency, single-shot spiral imaging provides a promising alternative to EPI, and with a dual-echo, out-in trajectory allows both CBF and BOLD contrasts to be acquired at their respective optimal TE. In this work, we implemented a dual-echo spiral out-in ASL sequence with simultaneous multi-slice (SMS) readout for increased coverage, and validated its application to fMRI with a visuomotor paradigm. Conventional Cartesian EPI acquisitions with matched parameters served as a reference. The dual-echo spiral ASL acquisitions resulted in robust CBF and BOLD activations maps. The absolute and relative CBF changes measured with the dual-echo spiral readout were in agreement with previous reports in the literature as well as the reference Cartesian acquisitions. The BOLD response amplitude was higher compared to the Cartesian acquisitions, attributable to a more optimal TE of the second echo. In conclusion, dual-echo spiral out-in SMS acquisition shows promise for concurrent acquisitions of BOLD and non-BOLD contrasts that require a short TE, with no loss in temporal resolution.

Mesoscopic in vivo human T2* dataset acquired using quantitative MRI at 7 Tesla.

Mesoscopic (0.1-0.5 mm) interrogation of the living human brain is critical for advancing neuroscience and bridging the resolution gap with animal models. Despite the variety of MRI contrasts measured in recent years at the mesoscopic scale, in vivo quantitative imaging of T2* has not been performed. Here we provide a dataset containing empirical T2* measurements acquired at 0.35 × 0.35 × 0.35 mm3 voxel resolution using 7 Tesla MRI. To demonstrate unique features and high quality of this dataset, we generate flat map visualizations that reveal fine-scale cortical substructures such as layers and vessels, and we report quantitative depth-dependent T2* (as well as R2*) values in primary visual cortex and auditory cortex that are highly consistent across subjects. This dataset is freely available at https://doi.org/10.17605/OSF.IO/N5BJ7, and may prove useful for anatomical investigations of the human brain, as well as for improving our understanding of the basis of the T2*-weighted (f)MRI signal.

Layer-specific activation in human primary somatosensory cortex during tactile temporal prediction error processing.

The human brain continuously generates predictions of incoming sensory input and calculates corresponding prediction errors from the perceived inputs to update internal predictions. In human primary somatosensory cortex (area 3b), different cortical layers are involved in receiving the sensory input and generation of error signals. It remains unknown, however, how the layers in the human area 3b contribute to the temporal prediction error processing. To investigate prediction error representation in the area 3b across layers, we acquired layer-specific functional magnetic resonance imaging (fMRI) data at 7T from human area 3b during a task of index finger poking with no-delay, short-delay and long-delay touching sequences. We demonstrate that all three tasks increased activity in both superficial and deep layers of area 3b compared to the random sensory input. The fMRI signal was differentially modulated solely in the deep layers rather than the superficial layers of area 3b by the delay time. Compared with the no-delay stimuli, activity was greater in the deep layers of area 3b during the short-delay stimuli but lower during the long-delay stimuli. This difference activity features in the superficial and deep layers suggest distinct functional contributions of area 3b layers to tactile temporal prediction error processing. The functional segregation in area 3b across layers may reflect that the excitatory and inhibitory interplay in the sensory cortex contributions to flexible communication between cortical layers or between cortical areas.

Quantification of cerebral blood volume changes caused by visual stimulation at 3 T using DANTE-prepared dual-echo EPI.

PURPOSE: We investigate the influence of moving blood-attenuation effects when using "delay alternating with nutation for tailored excitation" (DANTE) pulses in conjunction with blood oxygen level dependent (BOLD) of functional MRI (fMRI) at 3 T. Based on the effects of including DANTE pulses, we propose quantification of cerebral blood volume (CBV) changes following functional stimulation. METHODS: Eighteen volunteers in total underwent fMRI scans at 3 T. Seven volunteers were scanned to investigate the effects of DANTE pulses on the fMRI signal. CBV changes in response to visual stimulation were quantified in 11 volunteers using a DANTE-prepared dual-echo EPI sequence. RESULTS: The inflow effects from flowing blood in arteries and draining vein effects from flowing blood in large veins can be suppressed by use of a DANTE preparation module. Using DANTE-prepared dual-echo EPI, we quantitatively measured intravascular-weighted microvascular CBV changes of 25.4%, 29.8%, and 32.6% evoked by 1, 5, and 10 Hz visual stimulation, respectively. The extravascular fraction (∆S/S)extra at TE = 30 ms in total BOLD signal was determined to be 64.8 ± 3.4%, which is in line with previous extravascular component estimation at 3 T. Results show that the microvascular CBV changes are linearly dependent on total BOLD changes at TE = 30 ms with a slope of 0.113, and this relation is independent of stimulation frequency and subject. CONCLUSION: The DANTE preparation pulses can be incorporated into a standard EPI fMRI sequence for the purpose of minimizing inflow effects and reducing draining veins effects in large vessels. Additionally, the DANTE-prepared dual-echo EPI sequence is a promising fast imaging tool for quantification of intravascular-weighted CBV change in the microvascular space at 3 T.

Magnetization transfer weighted EPI facilitates cortical depth determination in native fMRI space.

The increased availability of ultra-high field scanners provides an opportunity to perform fMRI at sub-millimeter spatial scales and enables in vivo probing of laminar function in the human brain. In most previous studies, the definition of cortical layers, or depths, is based on an anatomical reference image that is collected by a different acquisition sequence and exhibits different geometric distortion compared to the functional images. Here, we propose to generate the anatomical image with the fMRI acquisition technique by incorporating magnetization transfer (MT) weighted imaging. Small flip angle binomial pulse trains are used as MT preparation, with a flexible duration (several to tens of milliseconds), which can be applied before each EPI segment without constraining the acquisition length (segment or slice number). The method's feasibility was demonstrated at 7T for coverage of either a small slab or the near-whole brain at 0.8 mm isotropic resolution. Tissue contrast was found to be similar to that obtained with a state-of-art anatomical reference based on MP2RAGE. This MT-weighted EPI image allows an automatic reconstruction of the cortical surface to support laminar analysis in native fMRI space, obviating the need for distortion correction and registration.

Validating layer-specific VASO across species.

Cerebral blood volume (CBV) has been shown to be a robust and important physiological parameter for quantitative interpretation of functional (f)MRI, capable of delivering highly localized mapping of neural activity. Indeed, with recent advances in ultra-high-field (≥7T) MRI hardware and associated sequence libraries, it has become possible to capture non-invasive CBV weighted fMRI signals across cortical layers. One of the most widely used approaches to achieve this (in humans) is through vascular-space-occupancy (VASO) fMRI. Unfortunately, the exact contrast mechanisms of layer-dependent VASO fMRI have not been validated for human fMRI and thus interpretation of such data is confounded. Here we validate the signal source of layer-dependent SS-SI VASO fMRI using multi-modal imaging in a rat model in response to neuronal activation (somatosensory cortex) and respiratory challenge (hypercapnia). In particular VASO derived CBV measures are directly compared to concurrent measures of total haemoglobin changes from high resolution intrinsic optical imaging spectroscopy (OIS). Quantified cortical layer profiling is demonstrated to be in agreement between VASO and contrast enhanced fMRI (using monocrystalline iron oxide nanoparticles, MION). Responses show high spatial localisation to layers of cortical processing independent of confounding large draining veins which can hamper BOLD fMRI studies, (depending on slice positioning). Thus, a cross species comparison is enabled using VASO as a common measure. We find increased VASO based CBV reactivity (3.1 ± 1.2 fold increase) in humans compared to rats. Together, our findings confirm that the VASO contrast is indeed a reliable estimate of layer-specific CBV changes. This validation study increases the neuronal interpretability of human layer-dependent VASO fMRI as an appropriate method in neuroscience application studies, in which the presence of large draining intracortical and pial veins limits neuroscientific inference with BOLD fMRI.

LayNii: A software suite for layer-fMRI.

High-resolution fMRI in the sub-millimeter regime allows researchers to resolve brain activity across cortical layers and columns non-invasively. While these high-resolution data make it possible to address novel questions of directional information flow within and across brain circuits, the corresponding data analyses are challenged by MRI artifacts, including image blurring, image distortions, low SNR, and restricted coverage. These challenges often result in insufficient spatial accuracy of conventional analysis pipelines. Here we introduce a new software suite that is specifically designed for layer-specific functional MRI: LayNii. This toolbox is a collection of command-line executable programs written in C/C++ and is distributed opensource and as pre-compiled binaries for Linux, Windows, and macOS. LayNii is designed for layer-fMRI data that suffer from SNR and coverage constraints and thus cannot be straightforwardly analyzed in alternative software packages. Some of the most popular programs of LayNii contain 'layerification' and columnarization in the native voxel space of functional data as well as many other layer-fMRI specific analysis tasks: layer-specific smoothing, model-based vein mitigation of GE-BOLD data, quality assessment of artifact dominated sub-millimeter fMRI, as well as analyses of VASO data.

Sub-millimeter fMRI reveals multiple topographical digit representations that form action maps in human motor cortex.

The human brain coordinates a wide variety of motor activities. On a large scale, the cortical motor system is topographically organized such that neighboring body parts are represented by neighboring brain areas. This homunculus-like somatotopic organization along the central sulcus has been observed using neuroimaging for large body parts such as the face, hands and feet. However, on a finer scale, invasive electrical stimulation studies show deviations from this somatotopic organization that suggest an organizing principle based on motor actions rather than body part moved. It has not been clear how the action-map organization principle of the motor cortex in the mesoscopic (sub-millimeter) regime integrates into a body map organization principle on a macroscopic scale (cm). Here we developed and applied advanced mesoscopic (sub-millimeter) fMRI and analysis methodology to non-invasively investigate the functional organization topography across columnar and laminar structures in humans. Compared to previous methods, in this study, we could capture locally specific blood volume changes across entire brain regions along the cortical curvature. We find that individual fingers have multiple mirrored representations in the primary motor cortex depending on the movements they are involved in. We find that individual digits have cortical representations up to 3 â€‹mm apart from each other arranged in a column-like fashion. These representations are differentially engaged depending on whether the digits' muscles are used for different motor actions such as flexion movements, like grasping a ball or retraction movements like releasing a ball. This research provides a starting point for non-invasive investigation of mesoscale topography across layers and columns of the human cortex and bridges the gap between invasive electrophysiological investigations and large coverage non-invasive neuroimaging.

Cortical laminar resting-state signal fluctuations scale with the hypercapnic blood oxygenation level-dependent response.

Calibrated functional magnetic resonance imaging can remove unwanted sources of signal variability in the blood oxygenation level-dependent (BOLD) response. This is achieved by scaling, using information from a perfusion-sensitive scan during a purely vascular challenge, typically induced by a gas manipulation or a breath-hold task. In this work, we seek for a validation of the use of the resting-state fluctuation amplitude (RSFA) as a scaling factor to remove vascular contributions from the BOLD response. Given the peculiarity of depth-dependent vascularization in gray matter, BOLD and vascular space occupancy (VASO) data were acquired at submillimeter resolution and averaged across cortical laminae. RSFA from the primary motor cortex was, thus, compared to the amplitude of hypercapnia-induced signal changes (tSDhc ) and with the M factor of the Davis model on a laminar level. High linear correlations were observed for RSFA and tSDhc ( R2 = 0.92 ± 0.06) and somewhat reduced for RSFA and M ( R2 = 0.62 ± 0.19). Laminar profiles of RSFA-normalized BOLD signal changes yielded good agreement with corresponding VASO profiles. Overall, this suggests that RSFA contains strong vascular components and is also modulated by baseline quantities contained in the M factor. We conclude that RSFA may replace the scaling factor tSDhc for normalizing the laminar BOLD response.

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.

Non-BOLD contrast for laminar fMRI in humans: CBF, CBV, and CMRO2.

Functional magnetic resonance imaging (fMRI) using the blood oxygenation level-dependent (BOLD) contrast indirectly probes neuronal activity changes via evoked cerebral blood flow (CBF), cerebral blood volume (CBV) and cerebral metabolic rate of oxygen (CMRO2) changes. The gradient-echo BOLD signal is mostly sensitive to ascending veins in the tissue and to pial veins. Thereby, the achievable spatial specificity to neuronal activation is limited. Furthermore, the non-linear interaction of CBF, CBV and CMRO2 can hamper quantitative interpretations of the BOLD signal across cortical depths with different baseline physiology. Measuring CBF, CBV or CMRO2 directly on a depth-dependent level has the potential to overcome these limitations. Here, we review these candidates of physiologically well-defined contrasts with the particular focus on arterial spin labeling (ASL), vascular space occupancy (VASO) and calibrated fMRI. These methods are reviewed with respect to their fMRI sequence parameter space and the applicability for neuroscientific studies in humans. We show representative results of depth-dependent 'non-BOLD-fMRI' in humans and their spatiotemporal characteristics. We conclude that non-BOLD methods are promising alternatives compared to conventional fMRI as they can provide improved spatial specificity, quantifiability and, hence, physiological interpretability as a function of cortical depth. At submillimeter resolution with inherently low signal-to-noise ratio (SNR), however, their use is still challenging. Nevertheless, we believe that 'non-BOLD-fMRI' is a useful alternative for depth-dependent investigations, by providing valuable insights into neurovascular coupling models that facilitate the interpretability of fMRI for neuroscientific applications.

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.

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.

Optimization of simultaneous multislice EPI for concurrent functional perfusion and BOLD signal measurements at 7T.

PURPOSE: To overcome limitations of previous ultra-high-field arterial spin labeling (ASL) techniques concerning temporal resolution and brain coverage by utilizing the simultaneous multi-slice (SMS) approach. METHODS: An optimized, flow-alternating inversion recovery quantitative imaging of perfusion using a single subtraction II scheme was developed that tackles the challenges of 7 tesla (T) ASL. The implementation of tailored labeling radiofrequency pulses reduced the effect of transmit field ( B1+) inhomogeneities. The proposed approach utilizes an SMS echo-planar imaging (EPI) readout to efficiently achieve large brain coverage. RESULTS: A pulsed ASL (PASL) technique with large brain coverage is described and optimized that can be applied at temporal resolutions below 2.5 s, similar to those achievable at 1.5 and 3T magnetic field strength. The influences of within- and through-slice acceleration factors and reconstruction parameters on perfusion and blood-oxygenation-level-dependent (BOLD)-signal image and temporal signal-to-noise ratio (SNR) are presented. The proposed approach yielded twice the brain coverage as compared to conventional PASL at 7T, without notable loss in image quality. CONCLUSION: The presented SMS EPI PASL at 7T overcomes current limitations in SNR, temporal resolution, and spatial coverage for functional perfusion and BOLD signal as well as baseline perfusion measurements. Magn Reson Med 78:121-129, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Physiological basis of vascular autocalibration (VasA): Comparison to hypercapnia calibration methods.

PURPOSE: The statistical power of functional MRI (fMRI) group studies is significantly hampered by high intersubject spatial and magnitude variance. We recently presented a vascular autocalibration method (VasA) to account for vascularization differences between subjects and hence improve the sensitivity in group studies. Here, we validate the novel calibration method by means of direct comparisons of VasA with more established measures of baseline venous blood volume (and indirectly vascular reactivity), the M-value. METHODS: Seven healthy volunteers participated in two 7 T (T) fMRI experiments to compare M-values with VasA estimates: (i) a hypercapnia experiment to estimate voxelwise M-value maps, and (ii) an fMRI experiment using visual stimulation to estimate voxelwise VasA maps. RESULTS: We show that VasA and M-value calibration maps show the same spatial profile, providing strong evidence that VasA is driven by local variations in vascular reactivity as reflected in the M-value. CONCLUSION: The agreement of vascular reactivity maps obtained with VasA when compared with M-value maps confirms empirically the hypothesis that the VasA method is an adequate tool to account for variations in fMRI response amplitudes caused by vascular reactivity differences in healthy volunteers. VasA can therefore directly account for them and increase the statistical power of group studies. The VasA toolbox is available as a statistical parametric mapping (SPM) toolbox, facilitating its general application. Magn Reson Med, 2016. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.