Christian Schwarzbauer

Optimisation of the 3D MDEFT sequence for anatomical brain imaging: Technical implications at 1.5 and 3 T

An algorithm for the optimisation of 3D Modified Driven Equilibrium Fourier Transform (MDEFT) sequences for T1-weighted anatomical brain imaging is presented. Imaging parameters are optimised for a clinical whole body scanner and a clinical head scanner operating at 1.5 and 3 T, respectively. In vivo studies show that the resulting sequences allow for the whole brain acquisition of anatomical scans with an isotropic resolution of 1 mm and high contrast-to-noise ratio (CNR) in an acceptable scan time of 12 min. Typical problems related to the scanner-specific hardware configurations are discussed in detail, especially the occurrence of flow artefacts in images acquired with head transmit coils and the enhancement of scalp intensities in images acquired with phased array receive coils. It is shown both theoretically and experimentally that these problems can be avoided by using spin tagging and fat saturation.

Undirected graphs of frequency-dependent functional connectivity in whole brain networks

We explored properties of whole brain networks based on multivariate spectral analysis of human functional magnetic resonance imaging (fMRI) time-series measured in 90 cortical and subcortical subregions in each of five healthy volunteers studied in the (no-task) resting state. We note that undirected graphs representing conditional independence between multivariate time-series can be more readily approached in the frequency domain than the time domain. Estimators of partial coherency and normalized partial mutual information φ, an integrated measure of partial coherence over an arbitrary frequency band, are applied. Using these tools, we replicate the prior observations that bilaterally homologous brain regions tend to be strongly connected and functional connectivity is generally greater at low frequencies [0.0004, 0.1518 Hz]. We also show that long-distance intrahemispheric connections between regions of prefrontal and parietal cortex were more salient at low frequencies than at frequencies greater than 0.3 Hz, whereas many local or short-distance connections, such as those comprising segregated dorsal and ventral paths in posterior cortex, were also represented in the graph of high-frequency connectivity. We conclude that the partial coherency spectrum between a pair of human brain regional fMRI time-series depends on the anatomical distance between regions: long-distance (greater than 7 cm) edges represent conditional dependence between bilaterally symmetric neocortical regions, and between regions of prefrontal and parietal association cortex in the same hemisphere, are predominantly subtended by low-frequency components.

Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder

To date, electroconvulsive therapy (ECT) is the most potent treatment in severe depression. Although ECT has been successfully applied in clinical practice for over 70 years, the underlying mechanisms of action remain unclear. We used functional MRI and a unique data-driven analysis approach to examine functional connectivity in the brain before and after ECT treatment. Our results show that ECT has lasting effects on the functional architecture of the brain. A comparison of pre- and posttreatment functional connectivity data in a group of nine patients revealed a significant cluster of voxels in and around the left dorsolateral prefrontal cortical region (Brodmann areas 44, 45, and 46), where the average global functional connectivity was considerably decreased after ECT treatment (P < 0.05, family-wise error-corrected). This decrease in functional connectivity was accompanied by a significant improvement (P < 0.001) in depressive symptoms; the patients’ mean scores on the Montgomery Asberg Depression Rating Scale pre- and posttreatment were 36.4 (SD = 4.9) and 10.7 (SD = 9.6), respectively. The findings reported here add weight to the emerging “hyperconnectivity hypothesis” in depression and support the proposal that increased connectivity may constitute both a biomarker for mood disorder and a potential therapeutic target.

Subanesthetic isoflurane affects task-induced brain activation in a highly specific manner: a functional magnetic resonance imaging study

Background Functional magnetic resonance imaging of blood oxygenation level–dependent signal changes offers a very promising approach to investigate activated neural networks during anesthesia. Methods Sixteen healthy male volunteers, assigned into two groups of eight subjects (isoflurane group, control group), were investigated by functional magnetic resonance imaging during different experimental conditions. The isoflurane group successively breathed air (baseline condition), isoflurane in air (0.42 vol% inspiratory; isoflurane condition) and air again (recovery condition) while performing a visual search task, whereas the control group breathed air during all experimental conditions. Functional magnetic resonance images were acquired during the entire experimental session. In addition, reaction times and error rates were recorded. Results A significant isoflurane-related decrease (z > 3.1 corresponding to P < 0.001) in task-induced brain activation was found in three distinct cortical regions: the right anterio-superior insula (Talairach coordinates: x = 32, y = 22, z = 8) and the banks of the left and right intraparietal sulcus (Talairach coordinates: x = −34, y = −36, z = 32; x = 22, y = −60, z = 41, respectively). Subcortical structures (lateral geniculate nucleus) and the primary cortices (motor cortex, visual cortex) were not affected. All measured parameters indicated a nearly complete recovery of the affected networks within 5 min. Conclusions Our findings indicate that subanesthetic isoflurane affected task-induced activation in specific neural networks rather than causing a global decrease in functional activation.

Perirhinal cortex activity during visual object discrimination: An event-related fMRI study

Previous fMRI studies have demonstrated preferential involvement of the perirhinal cortex and hippocampus in tasks of object and spatial memory, respectively. Here we investigated whether similar activity would also be present when object and spatial discrimination was assessed in the absence of explicit declarative memory demands. On each trial in the scanner, participants were presented simultaneously with two arrays of objects and were asked to indicate whether both arrays were identical, differed with respect to the identity of one object or differed with respect to the spatial arrangement of the objects. It was found that the detection of an object identity change was associated with significant right perirhinal cortex activity. We suggest that this perirhinal activity indicates a role of this structure in processes beyond declarative memory, for example, short-term visual working memory or higher order perception. Significantly greater hippocampal activity was not, however, observed during the spatial arrangement condition, perhaps due to the relatively low spatial processing demands of this task.

Evaluating an acoustically quiet EPI sequence for use in fMRI studies of speech and auditory processing

Echoplanar MRI is associated with significant acoustic noise, which can interfere with the presentation of auditory stimuli, create a more challenging listening environment, and increase discomfort felt by participants. Here we investigate a scanning sequence that significantly reduces the amplitude of acoustic noise associated with echoplanar imaging (EPI). This is accomplished using a constant phase encoding gradient and a sinusoidal readout echo train to produce a narrow-band acoustic frequency spectrum, which is adapted to the scanners frequency response function by choosing an optimum gradient switching frequency. To evaluate the effect of these nonstandard parameters we conducted a speech experiment comparing four different EPI sequences: Quiet, Sparse, Standard, and Matched Standard (using the same readout duration as Quiet). For each sequence participants listened to sentences and signal-correlated noise (SCN), which provides an unintelligible amplitude-matched control condition. We used BOLD sensitivity maps to quantify sensitivity loss caused by the longer EPI readout duration used in the Quiet and Matched Standard EPI sequences. We found that the Quiet sequence provided more robust activation for SCN in primary auditory areas and comparable activation in frontal and temporal regions for Sentences > SCN, but less sentence-related activity in inferotemporal cortex. The increased listening effort associated with the louder Standard sequence relative to the Quiet sequence resulted in increased activation in the left temporal and inferior parietal cortices. Together, these results suggest that the Quiet sequence is suitable, and perhaps preferable, for many auditory studies. However, its applicability depends on the specific brain regions of interest.

A qualitative test of the balloon model for BOLD-based MR signal changes at 3T

The aim of this study was to adapt the balloon model for BOLD‐based MR signal changes to a magnetic field strength of 3T and to examine its validity. The simultaneous measurement of BOLD and diffusion‐weighted BOLD responses was performed. The amplitude of the BOLD peak was found to be similar for all subjects when a short visual stimulus of 6 sec was used. The rise‐time to the BOLD peak and the shape and depth of the poststimulus undershoot varied significantly. A fit of the experimental BOLD responses was found to be possible by use of parameters within a reasonable physiological range. The relations between these parameters and their influence on the modeled BOLD responses is discussed. A prediction of the balloon model is the occurrence of a BOLD overshoot, i.e., a lag between the changes of the blood volume and the blood flow after the start of the stimulation. Experimental evidence for the existence of a BOLD overshoot is presented. Magn Reson Med 46:891–899, 2001.

Investigating the dependence of BOLD contrast on oxidative metabolism

Most functional magnetic resonance imaging (fMRI) studies are based on measuring the changes in the blood oxygenation level–dependent (BOLD) contrast that arise from a complex interplay between cerebral hemodynamics and oxidative metabolism. To separate these effects, we consecutively applied two different stimuli: visual stimulation (black/white checkerboard alternating with a frequency of 8 Hz) and hypercapnia (inspiration of 5% co2). Changes in cerebral blood flow (ΔCBF) and the effective transverse relaxation time (T*2) were measured in an interleaved manner by combining a previously described spin‐labeling technique with BOLD‐based fMRI. In six healthy volunteers, T*2 was significantly longer during hypercapnia than during visual stimulation, whereas the corresponding ΔCBF values were the same at the given level of significance (P < 0.01). This finding is explained by a significant increase in oxygen consumption under visual stimulation. The average T*2 changes in the visual cortex related to cerebral hemodynamics and oxidative metabolism were 10.6 ± 3.0% and −4.7 ± 1.2%, respectively, resulting in a net increase of 5.9 ± 2.3%. Although the hemodynamic effect is dominant, the increase in oxidative metabolism gives rise to a significant decrease in BOLD contrast. The calculated average change in the cerebral metabolic rate of oxygen (CMRo2), 4.4 ± 1.1% (N = 6), is in excellent agreement with previous results obtained by positron emission tomography. Magn Reson Med 41:537–543, 1999.

Investigating brain response to music: A comparison of different fMRI acquisition schemes

Functional magnetic resonance imaging (fMRI) in auditory experiments is a challenge, because the scanning procedure produces considerable noise that can interfere with the auditory paradigm. The noise might either mask the auditory material presented, or interfere with stimuli designed to evoke emotions because it sounds loud and rather unpleasant. Therefore, scanning paradigms that allow interleaved auditory stimulation and image acquisition appear to be advantageous. The sparse temporal sampling (STS) technique uses a very long repetition time in order to achieve a stimulus presentation in the absence of scanner noise. Although only relatively few volumes are acquired for the resulting data sets, there have been recent studies where this method has furthered remarkable results. A new development is the interleaved silent steady state (ISSS) technique. Compared with STS, this method is capable of acquiring several volumes in the time frame between the auditory trials (while the magnetization is kept in a steady state during stimulus presentation). In order to draw conclusions about the optimum fMRI procedure with auditory stimulation, different echo-planar imaging (EPI) acquisition schemes were compared: Continuous scanning, STS, and ISSS. The total acquisition time of each sequence was adjusted to about 12.5 min. The results indicate that the ISSS approach exhibits the highest sensitivity in detecting subtle activity in sub-cortical brain regions.

Vascular component analysis of hyperoxic and hypercapnic BOLD contrast

Hyperoxia or hypercapnia provides a useful experimental tool to systematically alter the blood oxygenation level dependent (BOLD) contrast. Typical applications include calibrated functional magnetic resonance imaging (fMRI), BOLD sensitivity mapping, vessel size imaging or cerebrovascular reactivity mapping. This article describes a novel biophysical model of hyperoxic and hypercapnic BOLD contrast, which accounts for the magnetic susceptibility effects of molecular oxygen that is dissolved in blood and tissue, in addition to the well-established effects caused by the paramagnetic properties of deoxyhaemoglobin. Furthermore, the concept of vascular component analysis (VCA) is introduced and is shown to provide a computationally efficient tool for investigating the vascular specificity of hyperoxic and hypercapnic BOLD contrast. A theoretical investigation of gradient and spin echo BOLD contrast based on computer simulations was performed to compare three different conditions (hypercapnia induced by breathing 6% CO2, hyperoxia induced by breathing 100% O2, and simultaneous hypercapnia and hyperoxia induced by breathing carbogen, i.e. 5% CO2 in 95% CO2) with baseline (breathing air). Simulations were carried out for different levels of metabolic oxygen extraction fraction (OEF) ranging from 0 to 0.5. The key findings can be summarised as follows: (i) for hyperoxia the susceptibility of dissolved O2 may lead to a significant arterial BOLD contrast; (ii) under normoxic conditions the susceptibility of dissolved O2 is negligible; (iii) an almost complete loss of BOLD sensitivity may occur at lower OEF values in all parts of the vascular tree, whereas hyperoxic BOLD sensitivity is largely maintained; (iv) under hyperoxic conditions, a transition from positive to negative BOLD contrast occurs with decreasing OEF values. These findings have important implications for experimental applications of hyperoxic and hypercapnic BOLD contrast and may enable new clinical applications in ischemic stroke and other forms of acquired brain injury.