Cortical lamina-dependent blood volume changes in human brain at 7T

Cortical layer-dependent high (sub-millimeter) resolution functional magnetic resonance imaging (fMRI) in human or animal brain can be used to address questions regarding the functioning of cortical circuits, such as the effect of different afferent and efferent connectivities on activity in specific cortical layers. The sensitivity of gradient echo (GE) blood oxygenation level-dependent (BOLD) responses to large draining veins reduces its local specificity and can render the interpretation of the underlying laminar neural activity impossible. The application of the more spatially specific cerebral blood volume (CBV)-based fMRI in humans has been hindered by the low sensitivity of the noninvasive modalities available. Here, a vascular space occupancy (VASO) variant, adapted for use at high field, is further optimized to capture layer-dependent activity changes in human motor cortex at sub-millimeter resolution. Acquired activation maps and cortical profiles show that the VASO signal peaks in gray matter at 0.8–1.6 mm depth, and deeper compared to the superficial and vein-dominated GE-BOLD responses. Validation of the VASO signal change versus well-established iron-oxide contrast agent based fMRI methods in animals showed the same cortical profiles of CBV change, after normalization for lamina-dependent baseline CBV. In order to evaluate its potential of revealing small lamina-dependent signal differences due to modulations of the input-output characteristics, layer-dependent VASO responses were investigated in the ipsilateral hemisphere during unilateral finger tapping. Positive activation in ipsilateral primary motor cortex and negative activation in ipsilateral primary sensory cortex were observed. This feature is only visible in high-resolution fMRI where opposing sides of a sulcus can be investigated independently because of a lack of partial volume effects. Based on the results presented here, we conclude that VASO offers good reproducibility, high sensitivity and lower sensitivity than GE-BOLD to changes in larger vessels, making it a valuable tool for layer-dependent fMRI studies in humans

Advances in image acquisition and filtering for MRI neuroimaging at 7 tesla

Performing magnetic resonance imaging at high magnetic field strength promises many improvements over low fields that are of direct benefit in functional neuroimaging. This includes the possibility of improved signal-to-noise levels, and increased BOLD functional contrast and spatial specificity. However, human MRI at 7T and above suffers from unique engineering challenges that limit the achievable gains. In this thesis, three technological developments are introduced, all of which address separate issues associated with functional magnetic resonance neuroimaging at very high magnetic field strengths. First, the image homogeneity problem is addressed by investigating methods of RF shimming — modifying the excitation portion of the MRI experiment for use with multi-channel RF coils. It is demonstrated that in 2D MRI experiments, shimming on a slice-by slice basis allows utilization of an extra degree of freedom available from the slice dimension, resulting in significant gains in image homogeneity and reduced RF power requirements. After acceptable images are available, we move to address complications of high field imaging that manifest in the fMRI time series. In the second paper, the increased physiological noise present in BOLD time series at high field is addressed with a unique data-driven noise regressor scheme based upon information in the phase component of the MRI signal. It is demonstrated that this method identifies and removes a significant portion of physiological signals, and performs as good or better than other popular data driven methods that use only the magnitude signal information. Lastly, the BOLD phase signal is again leveraged to address the confounding role of veins in resting state BOLD fMRI experiments. The phase regressor technique (previously developed by Dr. Menon) is modified and applied to resting state fMRI to remove macro vascular contributions in the datasets, leading to changes in spatial extent and connectivity of common resting state networks on single subjects and at the group level

Temporal SNR characteristics in segmented 3D-EPI at 7T.

Three-dimensional segmented echo planar imaging (3D-EPI) is a promising approach for high-resolution functional magnetic resonance imaging, as it provides an increased signal-to-noise ratio (SNR) at similar temporal resolution to traditional multislice 2D-EPI readouts. Recently, the 3D-EPI technique has become more frequently used and it is important to better understand its implications for fMRI. In this study, the temporal SNR characteristics of 3D-EPI with varying numbers of segments are studied. It is shown that, in humans, the temporal variance increases with the number of segments used to form the EPI acquisition and that for segmented acquisitions, the maximum available temporal SNR is reduced compared to single shot acquisitions. This reduction with increased segmentation is not found in phantom data and thus likely due to physiological processes. When operating in the thermal noise dominated regime, fMRI experiments with a motor task revealed that the 3D variant outperforms the 2D-EPI in terms of temporal SNR and sensitivity to detect activated brain regions. Thus, the theoretical SNR advantage of a segmented 3D-EPI sequence for fMRI only exists in a low SNR situation. However, other advantages of 3D-EPI, such as the application of parallel imaging techniques in two dimensions and the low specific absorption rate requirements, may encourage the use of the 3D-EPI sequence for fMRI in situations with higher SNR

FMRI resting slow fluctuations correlate with the activity of fast cortico-cortical physiological connections

Recording of slow spontaneous fluctuations at rest using functional magnetic resonance imaging (fMRI) allows distinct long-range cortical networks to be identified. The neuronal basis of connectivity as assessed by resting-state fMRI still needs to be fully clarified, considering that these signals are an indirect measure of neuronal activity, reflecting slow local variations in de-oxyhaemoglobin concentration. Here, we combined fMRI with multifocal transcranial magnetic stimulation (TMS), a technique that allows the investigation of the causal neurophysiological interactions occurring in specific cortico-cortical connections. We investigated whether the physiological properties of parieto-frontal circuits mapped with short-latency multifocal TMS at rest may have some relationship with the resting-state fMRI measures of specific resting-state functional networks (RSNs). Results showed that the activity of fast cortico-cortical physiological interactions occurring in the millisecond range correlated selectively with the coupling of fMRI slow oscillations within the same cortical areas that form part of the dorsal attention network, i.e., the attention system believed to be involved in reorientation of attention. We conclude that resting-state fMRI ongoing slow fluctuations likely reflect the interaction of underlying physiological cortico-cortical connections

Optimized simultaneous ASL and BOLD functional imaging of the whole brain

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106990/1/jmri24273.pd

A novel method of combining blood oxygenation and blood flow sensitive magnetic resonance imaging techniques to measure the cerebral blood flow and oxygen metabolism responses to an unknown neural stimulus.

Simultaneous implementation of magnetic resonance imaging methods for Arterial Spin Labeling (ASL) and Blood Oxygenation Level Dependent (BOLD) imaging makes it possible to quantitatively measure the changes in cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO(2)) that occur in response to neural stimuli. To date, however, the range of neural stimuli amenable to quantitative analysis is limited to those that may be presented in a simple block or event related design such that measurements may be repeated and averaged to improve precision. Here we examined the feasibility of using the relationship between cerebral blood flow and the BOLD signal to improve dynamic estimates of blood flow fluctuations as well as to estimate metabolic-hemodynamic coupling under conditions where a stimulus pattern is unknown. We found that by combining the information contained in simultaneously acquired BOLD and ASL signals through a method we term BOLD Constrained Perfusion (BCP) estimation, we could significantly improve the precision of our estimates of the hemodynamic response to a visual stimulus and, under the conditions of a calibrated BOLD experiment, accurately determine the ratio of the oxygen metabolic response to the hemodynamic response. Importantly we were able to accomplish this without utilizing a priori knowledge of the temporal nature of the neural stimulus, suggesting that BOLD Constrained Perfusion estimation may make it feasible to quantitatively study the cerebral metabolic and hemodynamic responses to more natural stimuli that cannot be easily repeated or averaged

Dopamine-induced dissociation of BOLD and neural activity in macaque visual cortex

Neuromodulators determine how neural circuits process information during cognitive states such as wakefulness, attention, learning, and memory [1]. fMRI can provide insight into their function and dynamics, but their exact effect on BOLD responses remains unclear [2, 3 and 4], limiting our ability to interpret the effects of changes in behavioral state using fMRI. Here, we investigated the effects of dopamine (DA) injections on neural responses and haemodynamic signals in macaque primary visual cortex (V1) using fMRI (7T) and intracortical electrophysiology. Aside from DA’s involvement in diseases such as Parkinson’s and schizophrenia, it also plays a role in visual perception [5, 6, 7 and 8]. We mimicked DAergic neuromodulation by systemic injection of L-DOPA and Carbidopa (LDC) or by local application of DA in V1 and found that systemic application of LDC increased the signal-to-noise ratio (SNR) and amplitude of the visually evoked neural responses in V1. However, visually induced BOLD responses decreased, whereas cerebral blood flow (CBF) responses increased. This dissociation of BOLD and CBF suggests that dopamine increases energy metabolism by a disproportionate amount relative to the CBF response, causing the reduced BOLD response. Local application of DA in V1 had no effect on neural activity, suggesting that the dopaminergic effects are mediated by long-range interactions. The combination of BOLD-based and CBF-based fMRI can provide a signature of dopaminergic neuromodulation, indicating that the application of multimodal methods can improve our ability to distinguish sensory processing from neuromodulatory effects

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

All that glitters is not BOLD: inconsistencies in functional MRI

The blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal is a widely-accepted marker of brain activity. The acquisition parameters (APs) of fMRI aim at maximizing the signals related to neuronal activity while minimizing unrelated signal fluctuations. Currently, a diverse set of APs is used to acquire BOLD fMRI data. Here we demonstrate that some fMRI responses are alarmingly inconsistent across APs, ranging from positive to negative, or disappearing entirely, under identical stimulus conditions. These discrepancies, resulting from non-BOLD effects masquerading as BOLD signals, have remained largely unnoticed because studies rarely employ more than one set of APs. We identified and characterized non-BOLD responses in several brain areas, including posterior cingulate cortex and precuneus, as well as AP-dependence of both the signal time courses and of seed-based functional networks, noticing that AP manipulation can inform about the origin of the measured signals.Peer reviewe