Measurement of activation-related changes in cerebral blood volume: VASO with single-shot HASTE acquisition

Object The recently developed vascular space occupancy (VASO) fMRI technique is gaining popularity as it facilitates the measurement of cerebral blood volume (CBV) changes concomitant with brain activation, without the use of contrast agents. Thus far, VASO fMRI has only been used in conjunction with a GE-EPI (gradient-echo echo planar imaging) sequence, which is proceeded by an inversion recovery (IR) experiment to selectively null the blood signal. The use of GE-EPI has potential disadvantages: (a) the non-zero TE may lead to BOLD contamination and (b) images suffer from the EPI-typical inhomogeneity artefacts

Asymmetric representation of aversive prediction errors in Pavlovian threat conditioning

Learning to predict threat is important for survival. Such learning may be driven by differences between expected and encountered outcomes, termed prediction errors (PEs). While PEs are crucial for reward learning, the role of putative PE signals in aversive learning is less clear. Here, we used functional magnetic resonance imaging in humans to investigate neural PE signals. Four cues, each with a different probability of being followed by an aversive outcome, were presented multiple times. We found that neural activity only at omission - but not at occurrence - of predicted threat related to PEs in the medial prefrontal cortex. More expected omission was associated with higher neural activity. In no brain region did neural activity fulfill necessary computational criteria for full signed PE representation. Our result suggests that, different from reward learning, aversive learning may not be primarily driven by PE signals in one single brain region

In vivo imaging of the nucleus of the solitary tract with Magnetization Transfer at 7 Tesla

The nucleus of the solitary tract (NTS) is a nuclei complex with, among others, a high concentration of noradrenergic neurons (including the noradrenergic subnuclei named A1 and A2) in the medulla. The NTS regulates several cognitive, neuroendocrine and autonomic functions. No method currently exists to anatomically visualize the NTS in vivo. Several noradrenergic and dopaminergic nuclei have been successfully imaged using Magnetization Transfer (MT) contrast manipulation. We therefore hypothesized that an efficient, high-resolution MT-weighted sequence at 7 T might successfully image the NTS. In this study, we found a hyperintensity, similar to hyperintensities found in other noradrenergic and dopaminergic nuclei, consistent with the expected NTS location, and specific to the MT-weighted images. The localization of the hyperintensity was found to be consistent between individuals and slices and in good correspondence to a histological atlas and a meta-analytic map of fMRI-based NTS activation. We conclude that the method may, for the first time, achieve NTS imaging in vivo and within a clinically-feasible acquisition time. To facilitate NTS research at lower field strengths, an NTS template was created and made publicly available

Using multi-echo simultaneous multi-slice (SMS) EPI to improve functional MRI of the subcortical nuclei of the basal ganglia at ultra-high field (7T)

The nuclei of the basal ganglia pose a special problem for functional MRI, especially at ultra-high field, because T2* variations between different regions result in suboptimal BOLD sensitivity when using gradient-echo echo-planar imaging (EPI). Specifically, the iron-rich lentiform nucleus of the basal ganglia, including the putamen and globus pallidus, suffers from substantial signal loss when imaging is performed using conventional single-echo EPI with echo times optimized for the cortex. Multi-echo EPI acquires several echoes at different echo times for every imaging slice, allowing images to be reconstructed with a weighting of echo times that is optimized individually for each voxel according to the underlying tissue or T2* properties. Here we show that multi-echo simultaneous multi-slice (SMS) EPI can improve functional activation of iron-rich subcortical regions while maintaining sensitivity within cortical areas. Functional imaging during a motor task known to elicit strong activations in the cortex and the subcortex (basal ganglia) was performed to compare the performance of multi-echo SMS EPI to single-echo SMS EPI. Notably within both the caudate nucleus and putamen of the basal ganglia, multi-echo SMS EPI yielded higher tSNR (an average 84% increase) and CNR (an average 58% increase), an approximate 3-fold increase in supra-threshold voxels, and higher t-values (an average 39% increase). The degree of improvement in the group level t-statistics was negatively correlated to the underlying T2* of the voxels, such that the shorter the T2*, as in the iron-rich nuclei of the basal ganglia, the higher the improvement of t-values in the activated region

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 ​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

A Specialized Multi-Transmit Head Coil for High Resolution fMRI of the Human Visual Cortex at 7T

PURPOSE: To design, construct and validate radiofrequency (RF) transmit and receive phased array coils for high-resolution visual cortex imaging at 7 Tesla. METHODS: A 4 channel transmit and 16 channel receive array was constructed on a conformal polycarbonate former. Transmit field efficiency and homogeneity were simulated and validated, along with the Specific Absorption Rate, using [Image: see text] mapping techniques and electromagnetic simulations. Receiver signal-to-noise ratio (SNR), temporal SNR (tSNR) across EPI time series, g-factors for accelerated imaging and noise correlations were evaluated and compared with a commercial 32 channel whole head coil. The performance of the coil was further evaluated with human subjects through functional MRI (fMRI) studies at standard and submillimeter resolutions of upto 0.8mm isotropic. RESULTS: The transmit and receive sections were characterized using bench tests and showed good interelement decoupling, preamplifier decoupling and sample loading. SNR for the 16 channel coil was ∼ 1.5 times that of the commercial coil in the human occipital lobe, and showed better g-factor values for accelerated imaging. fMRI tests conducted showed better response to Blood Oxygen Level Dependent (BOLD) activation, at resolutions of 1.2mm and 0.8mm isotropic. CONCLUSION: The 4 channel phased array transmit coil provides homogeneous excitation across the visual cortex, which, in combination with the dual row 16 channel receive array, makes for a valuable research tool for high resolution anatomical and functional imaging of the visual cortex at 7T

Functional cerebral blood volume mapping with simultaneous multi-slice acquisition

The aim of this study is to overcome the current limits of brain coverage available with multi-slice echo planar imaging (EPI) for vascular space occupancy (VASO) mapping. By incorporating simultaneous multi-slice (SMS) EPI image acquisition into slice-saturation slab-inversion VASO (SS-SI VASO), many more slices can be acquired for non-invasive functional measurements of blood volume responses. Blood-volume-weighted VASO and gradient echo blood oxygenation level-dependent (GE-BOLD) data were acquired in humans at 7 T with a 32-channel head coil. SMS-VASO was applied in three scenarios: A) high-resolution acquisition of spatially distant brain areas in the visuo-motor network (V1/V5/M1/S1); B) high-resolution acquisition of an imaging slab covering the entire M1/S1 hand regions; and C) low-resolution acquisition with near whole-brain coverage. The results show that the SMS-VASO sequence provided images enabling robust detection of blood volume changes in up to 20 slices with signal readout durations shorter than 150 ms. High-resolution application of SMS-VASO revealed improved specificity of VASO to GM tissue without contamination from large draining veins compared to GE-BOLD in the visual cortex and in the sensory-motor cortex. It is concluded that VASO fMRI with SMS-EPI allows obtaining a reasonable three-dimensional coverage not achievable with standard VASO during the short time period when blood magnetization is approximately nulled. Due to the increased brain coverage and better spatial specificity to GM tissue of VASO compared to GE-BOLD signal, the proposed method may play an important role in high-resolution human fMRI at 7 T

High-resolution CBV-fMRI allows mapping of laminar activity and connectivity of cortical input and output in human M1

Layer-dependent fMRI allows measurements of information flow in cortical circuits, as afferent and efferent connections terminate in different cortical layers. However, it is unknown to what level human fMRI is specific and sensitive enough to reveal directional functional activity across layers. To answer this question, we developed acquisition and analysis methods for blood-oxygen-level-dependent (BOLD) and cerebral-blood-volume (CBV)-based laminar fMRI and used these to discriminate four different tasks in the human motor cortex (M1). In agreement with anatomical data from animal studies, we found evidence for somatosensory and premotor input in superficial layers of M1 and for cortico-spinal motor output in deep layers. Laminar resting-state fMRI showed directional functional connectivity of M1 with somatosensory and premotor areas. Our findings demonstrate that CBV-fMRI can be used to investigate cortical activity in humans with unprecedented detail, allowing investigations of information flow between brain regions and outperforming conventional BOLD results that are often buried under vascular biases

Volumetric imaging with homogenised excitation and static field at 9.4 T

Objectives: To overcome the challenges of B and RF excitation inhomogeneity at ultra-high field MRI, a workflow for volumetric B and flip-angle homogenisation was implemented on a human 9.4 T scanner. Materials and methods: Imaging was performed with a 9.4 T human MR scanner (Siemens Medical Solutions, Erlangen, Germany) using a 16-channel parallel transmission system. B- and B-mapping were done using a dual-echo GRE and transmit phase-encoded DREAM, respectively. B shims and a small-tip-angle-approximation kT-points pulse were calculated with an off-line routine and applied to acquire T- and T -weighted images with MPRAGE and 3D EPI, respectively. Results: Over six in vivo acquisitions, the B-distribution in a region-of-interest defined by a brain mask was reduced down to a full-width-half-maximum of 0.10\ua0±\ua00.01\ua0ppm (39\ua0±\ua02\ua0Hz). Utilising the kT-points pulses, the normalised RMSE of the excitation was decreased from CP-mode’s 30.5\ua0±\ua00.9 to 9.2\ua0±\ua00.7\ua0% with all B \ua0voids eliminated. The SNR inhomogeneities and contrast variations in the T- and T -weighted volumetric images were greatly reduced which led to successful tissue segmentation of the T-weighted image. Conclusion: A 15-minute B- and flip-angle homogenisation workflow, including the B- and B-map acquisitions, was successfully implemented and enabled us to reduce intensity and contrast variations as well as echo-planar image distortions in 9.4 T images

Fast spin echo sequences for BOLD functional MRI

At higher field strengths, spin echo (SE) functional MRI (fMRI) is an attractive alternative to gradient echo (GE) as the increased weighting towards the microvasculature results in intrinsically better localization of the BOLD signal. Images are free of signal voids but the commonly used echo planar imaging (EPI) sampling scheme causes geometric distortions, and T2* effects often contribute considerably to the signal changes measured upon brain activation. Multiply refocused SE sequences such as fast spin echo (FSE) are essentially artifact free but their application to fast fMRI is usually hindered due to high energy deposition, and long sampling times. In the work presented here, a combination of parallel imaging and partial Fourier acquisition is used to shorten FSE acquisition times to near those of conventional SE-EPI, permitting sampling of eight slices (matrix 64  ×  64) per second. Signal acquisition is preceded by a preparation experiment that aims at increasing the relative contribution of extravascular dynamic averaging to the BOLD signal. Comparisons are made with conventional SE-EPI using a visual stimulation paradigm. While the observed signal changes are approximately 30% lower, most likely due to the absence of T2* contamination, activation size and t-scores are comparable for both methods, suggesting that HASTE fMRI is a viable alternative, particularly if distortion free images are required. Our data also indicate that the BOLD post-stimulus undershoot is most probably attributable to persistent elevated oxygen metabolism rather than to delayed vascular compliance