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Increasing the concentration of oxygen dissolved in water is known to increase the recovery rate (R1 = 1/T1) of longitudinal magnetization (T1 relaxation). Direct T1 changes in response to precise hyperoxic gas challenges have not yet been quantified and the actual effect of increasing arterial oxygen concentration on the T1 of brain parenchyma remains unclear. The aim of this work was to use quantitative T1 mapping to measure tissue T1 changes in response to precisely targeted hyperoxic respiratory challenges ranging from baseline end-tidal oxygen (PetO 2 ) to approximately 500 mmHg. We did not observe measureable T1 changes in either gray matter or white matter parenchymal tissue. The T1 of peripheral cerebrospinal fluid located within the sulci, however, was reduced as a function of PetO 2 . No significant T1 changes were observed in the ventricular cerebrospinal fluid under hyperoxia. Our results indicate that care should be taken to distinguish actual T1 changes from those which may be related to partial volume effects with cerebrospinal fluid, or regions with increased fluid content such as edema when examining hyperoxia-induced changes in T1 using methods based on T1-weighted imaging.

Purpose: Owing to variability in vascular dynamics across cerebral cortex, blood-oxygenation-level-dependent (BOLD) spatial and temporal characteristics should vary as a function of cortical-depth. Here, the positive response, initial dip (ID), and post-stimulus undershoot (PSU) of the BOLD response in human visual cortex are investigated as a function of cortical depth and stimulus duration at 7 Tesla (T)., Methods: Gradient-echo echo-planar-imaging BOLD fMRI with high spatial and temporal resolution was performed in 7 healthy volunteers and measurements of the ID, PSU, and positive BOLD response were made as a function of cortical depth and stimulus duration (0.5-8 s). Exploratory analyses were applied to understand whether functional mapping could be achieved using the ID, rather than positive, BOLD signal characteristics, Results: The ID was largest in outer cortical layers, consistent with previously reported upstream propagation of vasodilation along the diving arterioles in animals. The positive BOLD signal and PSU showed different relationships across the cortical depth with respect to stimulus duration., Conclusion: The ID and PSU were measured in humans at 7T and exhibited similar trends to those recently reported in animals. Furthermore, while evidence is provided for the ID being a potentially useful feature for better understanding BOLD signal dynamics, such as laminar neurovascular coupling, functional mapping based on the ID is extremely difficult., (© 2014 Wiley Periodicals, Inc.)

High resolution BOLD fMRI has the potential to map activation patterns of small neuronal populations at the scale of cortical columns. However, BOLD fMRI does not measure neuronal activity, but only a correlate thereof, since it measures blood dynamics. To confirm that BOLD activation maps reflect neuronal population activity patterns, a direct comparison with neuro-electrophysiological data from the same cortical patch is necessary. Here, we compare BOLD activation patterns obtained with fMRI at 7 T to electrophysiological patterns obtained with implanted high density electrocorticography (ECoG) grids in the same patch of human sensorimotor cortex, and with similar resolution (1.5mm). We used high spatially sampled high-frequency broadband (HFB) power from ECoG, which reflects local neuronal population activity. The spatial distribution of 7 T BOLD activation matched the spatial distribution of ECoG HFB-power changes in the covered patch of sensorimotor cortex. BOLD fMRI activation foci were located within 1-3mm of the HFB-power ECoG foci. Both methods distinguished individual finger movement activation within a 1cm cortical patch, revealing a topographical medial to lateral layout for the little finger to index to thumb. These findings demonstrate that the BOLD signal at 7 T is strongly correlated with the underlying electrophysiology, and is capable of discriminating patterns of neuronal population activity at a millimeter scale. The results further indicate the utility of 7 T fMRI for investigation of intra-area organization of function and network dynamics., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Cerebrovascular reactivity (CVR) is a mechanism responsible for maintaining stable perfusion pressure within the brain via smooth muscle mediated modulations of vascular tone. The amplitude of cerebral blood flow (CBF) change in response to a stimulus has been evaluated using Blood Oxygen Level Dependent (BOLD) MRI, however the relationship between the stimulus and the measured signal remains unclear. CVR measured invasively in animal models and using blood-velocity based measurements in humans has demonstrated a sigmoidal relationship between cerebral blood flow and CO2 partial pressure. Using an ultra-high magnetic field strength (7T) MRI scanner and a computer controlled gas delivery system, we examined the regional and voxel-wise CVR response in relation to a targeted progressively increasing hypo- to hypercapnic stimulus. The aim of this study was to assess the non-linearity/sigmoidal behavior of the CVR response at varying arterial CO2 (PaCO2) levels. We find that a sigmoidal model provides a better description of the BOLD signal response to increasing PaCO2 than a linear model. A distinct whole-brain and gray matter BOLD-CVR signal plateau was observed in both voxel-wise and regional analysis. Furthermore, we demonstrate that a progressively increasing stimulus in combination with a sigmoidal response model can be used to obtain CVR values and provides additional physiologically relevant information (such as linear and non-linear response domains, and maximum response amplitudes) that may be more difficult to obtain from blocked CVR experiments. Considering these results, we propose an alternative way in which to define CVR based on the derivative of the BOLD-CVR response curve, which can potentially be used to differentiate between healthy and diseased vascular states., (Copyright © 2014 Elsevier Inc. All rights reserved.)

High-field gradient-echo (GE) BOLD fMRI enables very high resolution imaging, and has great potential for detailed investigations of brain function. However, as spatial resolution increases, confounds due to signal from non-capillary vessels increasingly impact the fidelity of GE BOLD fMRI signals. Here we report on an assessment of the microvascular weighting of the GE BOLD response across the cortical depth in human cortex using spin-echo fMRI which is thought to be dominated by microvasculature (albeit not completely). BOLD responses were measured with a hemodynamic impulse response (HRF) obtained from the spin-echo (SE) and gradient-echo (GE) BOLD contrast using very short stimuli (0.25 s) and a fast event-related functional paradigm. We show that the onset (≈ 1.25 s) and the rising slope of the GE and SE HRFs are strikingly similar for voxels in deep gray matter presumably containing the most metabolically demanding neurons (layers III-IV). This finding provides a strong indication that the onset of the GE HRF in deep gray matter is predominantly associated with microvasculature.

Mapping the longitudinal relaxation time (T(1)) of brain tissue is of great interest for both clinical research and MRI sequence development. For an unambiguous interpretation of in vivo variations in T(1) images, it is important to understand the degree of variability that is associated with the quantitative T(1) parameter. This paper presents a general framework for estimating the uncertainty in quantitative T(1) mapping by combining a slice-shifted multi-slice inversion recovery EPI technique with the statistical wild-bootstrap approach. Both simulations and experimental analyses were performed to validate this novel approach and to evaluate the estimated T(1) uncertainty in several brain regions across four healthy volunteers. By estimating the T(1) uncertainty, it is shown that the variation in T(1) within anatomic regions for similar tissue types is larger than the uncertainty in the measurement. This indicates that heterogeneity of the inspected tissue and/or partial volume effects can be the main determinants for the observed variability in the estimated T(1) values. The proposed approach to estimate T(1) and its uncertainty without the need for repeated measurements may also prove to be useful for calculating effect sizes that are deemed significant when comparing group differences., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Synchrony measurements of spontaneous low-frequency blood oxygenation level-dependent (BOLD) fluctuations are increasingly being used to investigate spatial regions of functional connectivity. Although information regarding BOLD-BOLD synchrony between different regions is frequently reported, the relationship between spontaneous activity and behavioral state, and the association of spontaneous signal synchrony and evoked response, are less well characterized. The purpose of this study is to exploit the higher signal-to-noise ratio and in turn available spatial resolution at 7.0 T to understand the relationship between synchrony, measured as Pearson's R value, and amplitude, measured as signal standard deviation over time, in sensorimotor cortex for four separate behavioral states: eyes closed resting (EC), eyes open fixation (EO), EO with constant right hand fist clench (EO-F) and EO with 6 s off/6 s on (0.083 Hz) right hand finger tapping (EO-T). BOLD (TE/TR = 25/3,000 ms; 100 time points) scans were performed in healthy volunteers (7.0 T; 4 M/3 F; right-handed) at high spatial resolution = 1.6 × 1.6 × 1.6 mm3 . Results (z > 5; P < 0.05; low-pass filtering <0.067 Hz) reveal that synchrony is highest in the EC state (R = 0.35 ± 0.07) and reduces for EO (R = 0.26 ± 0.07), EO-F (R = 0.23 ± 0.07; P < 0.05), and EO-T (R = 0.12 ± 0.04; P < 0.05) conditions. Amplitude was highest in the EC condition and only reduced significantly (P < 0.05) for the EO-T condition. Synchrony within sensorimotor cortex correlated with evoked finger-tapping response magnitude (R = 0.81; P = 0.03), suggesting that spontaneous signal synchrony may be a predictor of evoked BOLD response magnitude and may account for intersubject variability in sensorimotor cortex., (Copyright © 2011 Wiley Periodicals, Inc.)

Dutch speakers with agrammatic Broca's aphasia are known to have problems with the production of finite verbs in main clauses. This performance pattern has been accounted for in terms of the specific syntactic complexity of the Dutch main clause structure, which requires an extra syntactic operation (Verb Second), relative to the basic Subject-Object-Verb order surfacing in Dutch subordinate clauses. We report an fMRI study into the question whether this syntactic complexity is reflected in increased brain activation correlated with the production of Dutch main clause word order, in speakers without language impairment. Nineteen healthy subjects performed a covert sentence completion task, during which main and subordinate clauses were alternately elicited in a block design. Results show a left middle to superior frontal cluster of activation correlated to production of Verb-Second over Verb-Final clauses, with no activation in the opposite contrast. This activation pattern is counter to what might be expected from the frequency distribution of main and subordinate clauses. We conclude that the Verb-Second deviation from the basic Dutch SOV word order costs extra neural resources and that this also underlies the agrammatic problems with the production of finite verbs in Dutch main clauses.