Hans Hoogduin

In vivo three-dimensional whole-brain pulsed steady-state chemical exchange saturation transfer at 7 T

Chemical exchange saturation transfer (CEST) is a technique to indirectly detect pools of exchangeable protons through the water signal. To increase its applicability to human studies, it is needed to develop sensitive pulse sequences for rapidly acquiring whole‐organ images while adhering to stringent amplifier duty cycle limitations and specific absorption rate restrictions. In addition, the interfering effects of direct water saturation and conventional magnetization transfer contrast complicate CEST quantification and need to be reduced as much as possible. It is shown that for protons exchanging with rates of less than 50–100 Hz, such as imaged in amide proton transfer experiments, these problems can be addressed by using a three‐dimensional steady state pulsed acquisition of limited B1 strength (∼1 μT). Such an approach exploits the fact that the direct water saturation width, magnetization transfer contrast magnitude, and specific absorption rate increase strongly with B1, while the size of the CEST effect for such protons depends minimally on B1. A short repetition time (65 ms) steady‐state sequence consisting of a brief saturation pulse (25 ms) and a segmented echo‐planar imaging train allowed acquisition of a three‐dimensional whole‐brain volume in approximately 11 s per saturation frequency, while remaining well within specific absorption rate and duty cycle limits. Magnetization transfer contrast was strongly reduced, but substantial saturation effects were found at frequencies upfield from water, which still confound the use of magnetization transfer asymmetry analysis. Fortunately, the limited width of the direct water saturation signal could be exploited to fit it with a Lorentzian function allowing CEST quantification. Amide proton transfer effects ranged between 1.5% and 2.5% in selected white and grey matter regions. This power and time‐efficient 3D pulsed CEST acquisition scheme should aid endogenous CEST quantification at both high and low fields. Magn Reson Med, 2011.

Cortical depth-dependent temporal dynamics of the BOLD response in the human brain

Recent animal studies at high field have shown that blood oxygen level-dependent (BOLD) contrast can be specific to the laminar vascular architecture of the cortex, by differences in its temporal dynamics in reference to cortical depth. In this study, we characterize the temporal dynamics of the hemodynamic response (HDR) across cortical depth in the human primary motor and visual cortex, at 7T and using very short stimuli and with high spatial and temporal resolution. We find that the shape and temporal dynamics of the HDR changed in an orderly manner across cortical depth. Compared with the pial vasculature, HDRs in deeper gray matter are significantly faster in onset time (by ∼ 0.5 second) and peak time (∼2 seconds), and are narrower (by ∼1 second) and with smaller amplitude, in line with the known vascular organization across cortical depth and the transit of deoxygenated blood through the vasculature. The width of the HDR in deeper gray matter was as short as 2.1 seconds, indicating that neurovascular coupling takes place at a shorter timescale than previously reported in the human brain. These findings open the possibility to probe layer-specific hemodynamics and neurovascular coupling mechanisms in human gray matter.

Blood oxygenation level-dependent (BOLD) total and extravascular signal changes and ΔR2* in human visual cortex at 1.5, 3.0 and 7.0 T.

The characterisation of the extravascular (EV) contribution to the blood oxygenation level‐dependent (BOLD) effect is important for understanding the spatial specificity of BOLD contrast and for modelling approaches that aim to extract quantitative metabolic parameters from the BOLD signal. Using bipolar crusher gradients, total (b = 0 s/mm2) and predominantly EV (b = 100 s/mm2) gradient echo BOLD ΔR2* and signal changes (ΔS/S) in response to visual stimulation (flashing checkerboard; f = 8 Hz) were investigated sequentially (within < 3 h) at 1.5, 3.0 and 7.0 T in the same subgroup of healthy volunteers (n = 7) and at identical spatial resolutions (3.5 × 3.5 × 3.5 mm3). Total ΔR2* (z‐score analysis) values were −0.61 ± 0.10 s−1 (1.5 T), −0.74 ± 0.05 s−1 (3.0 T) and −1.37 ± 0.12 s−1 (7.0 T), whereas EV ΔR2* values were −0.28 ± 0.07 s−1 (1.5 T), −0.52 ± 0.07 s−1 (3.0 T) and −1.25 ± 0.11 s−1 (7.0 T). Although EV ΔR2* increased linearly with field, as expected, it was found that EV ΔS/S increased less than linearly with field in a manner that varied with TE choice. Furthermore, unlike ΔR2*, total and EV ΔS/S did not converge at 7.0 T. These trends were similar whether a z‐score analysis or occipital lobe‐based region‐of‐interest approach was used for voxel selection. These findings suggest that calibrated BOLD approaches may benefit from an EV ΔR2* measurement as opposed to a ΔS/S measurement at a single TE. Copyright

BOLD matches neuronal activity at the mm scale: A combined 7 T fMRI and ECoG study in human sensorimotor cortex

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.

High‐field MRS of the human brain at short TE and TR

In vivo MRS of the human brain at 7 tesla allows identification of a large number of metabolites at higher spatial resolutions than currently possible at lower field strengths. However, several challenges complicate in vivo localization and artifact suppression in MRS at high spatial resolution within a clinically feasible scan time at 7 tesla. Published MRS sequences at 7 tesla suffer from long echo times, inherent signal‐to‐noise ratio (SNR) loss, large chemical shift displacement artifacts or long repetition times because of excessive radiofrequency (RF) power deposition. In the present study a pulse‐acquire sequence was used that does not suffer from these high field drawbacks. A slice selective excitation combined with high resolution chemical shift imaging for in‐plane localization was used to limit chemical shift displacement artifacts. The pulse‐acquire approach resulted in a very short echo time of 1.4 ms. A cost function guided shimming algorithm was developed to constrain frequency offsets in the excited slice, therefore adiabatic frequency selective suppression could be employed to minimize artifacts from high intensity lipids and water signals in the excited slice. The high sensitivity at a TR of 1 s was demonstrated both on a supraventricular slice as well as in an area very close to the skull in the frontal cortex at a nominal spatial resolution of 0.25 cc within a feasible scan time. Copyright

Fast design of local N-gram-specific absorption rate-optimized radiofrequency pulses for parallel transmit systems.

Designing multidimensional radiofrequency pulses for clinical application must take into account the local specific absorption rate (SAR) as controlling the global SAR does not guarantee suppression of hot spots. The maximum peak SAR, averaged over an N grams cube (local NgSAR), must be kept under certain safety limits. Computing the SAR over a three‐dimensional domain can require several minutes and implementing this computation in a radiofrequency pulse design algorithm could slow down prohibitively the numerical process. In this article, a fast optimization algorithm is designed acting on a limited number of control points, which are strategically selected locations from the entire domain. The selection is performed by comparing the largest eigenvalues and the corresponding eigenvectors of the matrices which locally describe the tissues amount of heating. The computation complexity is dramatically reduced. An additional critical step to accelerate the computations is to apply a multi shift conjugate gradient algorithm. Two transmit array setups are studied: a two channel 3 T birdcage body coil and a 12‐channel 7 T transverse electromagnetic (TEM) head coil. In comparison with minimum power radiofrequency pulses, it is shown that a reduction of 36.5% and 35%, respectively, in the local NgSAR can be achieved within short, clinically feasible, computation times. Magn Reson Med, 2012.

BOLD Consistently Matches Electrophysiology in Human Sensorimotor Cortex at Increasing Movement Rates: A Combined 7T fMRI and ECoG Study on Neurovascular Coupling

Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is widely used to measure human brain function and relies on the assumption that hemodynamic changes mirror the underlying neuronal activity. However, an often reported saturation of the BOLD response at high movement rates has led to the notion of a mismatch in neurovascular coupling. We combined BOLD fMRI at 7T and intracranial electrocorticography (ECoG) to assess the relationship between BOLD and neuronal population activity in human sensorimotor cortex using a motor task with increasing movement rates. Though linear models failed to predict BOLD responses from the task, the measured BOLD and ECoG responses from the same tissue were in good agreement. Electrocorticography explained almost 80% of the mismatch between measured- and model-predicted BOLD responses, indicating that in human sensorimotor cortex, a large portion of the BOLD nonlinearity with respect to behavior (movement rate) is well predicted by electrophysiology. The results further suggest that other reported examples of BOLD mismatch may be related to neuronal processes, rather than to neurovascular uncoupling.

Investigating the non-linearity of the BOLD cerebrovascular reactivity response to targeted hypo/hypercapnia at 7 T

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.

Examining the regional and cerebral depth-dependent BOLD cerebrovascular reactivity response at 7 T

Changes in cerebral blood flow (CBF) in response to hypercapnia induced changes in vascular tone, known as cerebrovascular reactivity (CVR), can be measured using the Blood Oxygenation Level Dependent (BOLD) MR contrast. We examine regional differences in the BOLD-CVR response to a progressively increasing hypercapnic stimulus as well as regional BOLD characteristics for the return to baseline normocapnia. CVR across 9 subjects was highest in the cerebral lobes and deep gray matter. Peak CVR in these regions was measured at 3.6±1.6mmHg above baseline end-tidal CO2. White matter CVR was generally reduced compared to that of the gray matter (peak white matter CVR was ~48% lower). A positive relationship between the end-tidal CO2 value at which peak CVR was measured and white matter depth is observed. Furthermore, the time required for the BOLD signal to return to baseline after cessation of the hypercapnic stimulus, was also related to white matter depth; the return, expressed as a time constant, was ~25% longer in white matter. To explain the observed differences in regional CVR response, a model is proposed that takes into account the local architecture of the cerebrovascular, which can result in changes in regional blood flow distribution as a function of end-tidal CO2.

Cortical depth dependence of the BOLD initial dip and poststimulus undershoot in human visual cortex at 7 Tesla

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).