Philipp Staempfli

Resolving fiber crossing using advanced fast marching tractography based on diffusion tensor imaging.

Magnetic resonance diffusion tensor tractography is a powerful tool for the non-invasive depiction of the white matter architecture in the human brain. However, due to limitations in the underlying tensor model, the technique is often unable to reconstruct correct trajectories in heterogeneous fiber arrangements, such as axonal crossings. A novel tractography method based on fast marching (FM) is proposed which is capable of resolving fiber crossings and also permits trajectories to branch. It detects heterogeneous fiber arrangements by incorporating information from the entire diffusion tensor. The FM speed function is adapted to the local tensor characteristics, allowing in particular to maintain the front evolution direction in crossing situations. In addition, the FMs discretization error is reduced by increasing the number of considered possible front evolution directions. The performance of the technique is demonstrated in artificial data and in the healthy human brain. Comparisons with standard FM tractography and conventional line propagation algorithms show that, in the presence of interfering structures, the proposed method is more accurate in reconstructing trajectories. The in vivo results illustrate that the elucidated major white matter pathways are consistent with known anatomy and that multiple crossings and tract branching are handled correctly.

Combining fMRI and DTI: a framework for exploring the limits of fMRI-guided DTI fiber tracking and for verifying DTI-based fiber tractography results.

A powerful, non-invasive technique for estimating and visualizing white matter tracts in the human brain in vivo is white matter fiber tractography that uses magnetic resonance diffusion tensor imaging. The success of this method depends strongly on the capability of the applied tracking algorithm and the quality of the underlying data set. However, DTI-based fiber tractography still lacks standardized validation. In the present work, a combined fMRI/DTI study was performed, both to develop a setup for verifying fiber tracking results using fMRI-derived functional connections and to explore the limitations of fMRI based DTI fiber tracking. Therefore, a minor fiber bundle that features several fiber crossings and intersections was examined: The striatum and its connections to the primary motor cortex were examined by using two approaches to derive the somatotopic organization of the striatum. First, an fMRI-based somatotopic map of the striatum was reconstructed, based on fMRI activations that were provoked by unilateral motor tasks. Second, fMRI-guided DTI fiber tracking was performed to generate DTI-based somatotopic maps, using a standard line propagation and an advanced fast marching algorithm. The results show that the fiber connections reconstructed by the advanced fast marching algorithm are in good agreement with known anatomy, and that the DTI-revealed somatotopy is similar to the fMRI somatotopy. Furthermore, the study illustrates that the combination of fMRI with DTI can supply additional information in order to choose reasonable seed regions for generating functionally relevant networks and to validate reconstructed fibers.

Impact of fMRI-guided advanced DTI fiber tracking techniques on their clinical applications in patients with brain tumors

IntroductionWhite matter tractography based on diffusion tensor imaging has become a well-accepted non-invasive tool for exploring the white matter architecture of the human brain in vivo. There exist two main key obstacles for reconstructing white matter fibers: firstly, the implementation and application of a suitable tracking algorithm, which is capable of reconstructing anatomically complex fascicular pathways correctly, as, e.g., areas of fiber crossing or branching; secondly, the definition of an appropriate tracking seed area for starting the reconstruction process. Large intersubject, anatomical variations make it difficult to define tracking seed areas based on reliable anatomical landmarks. An accurate definition of seed regions for the reconstruction of a specific neuronal pathway becomes even more challenging in patients suffering from space occupying pathological processes as, e.g., tumors due to the displacement of the tissue and the distortion of anatomical landmarks around the lesion.MethodsTo resolve the first problem, an advanced tracking algorithm, called advanced fast marching, was applied in this study. The second challenge was overcome by combining functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) in order to perform fMRI-guided accurate definition of appropriate seed areas for the DTI fiber tracking. In addition, the performance of the tasks was controlled by a MR-compatible power device.ResultsApplication of this combined approach to eight healthy volunteers and exemplary to three tumor patients showed that it is feasible to accurately reconstruct relevant fiber tracts belonging to a specific functional system.ConclusionfMRI-guided advanced DTI fiber tracking has the potential to provide accurate anatomical and functional information for a more informed therapeutic decision making.

Conflict monitoring and error processing: new insights from simultaneous EEG-fMRI

Error processing and conflict monitoring are essential executive functions for goal directed actions and adaptation to conflicting information. Although medial frontal regions such as the anterior cingulate cortex (ACC) and the pre-supplementary motor area (pre-SMA) are known to be involved in these functions, there is still considerable heterogeneity regarding their spatio-temporal activations. The timing of these functions has been associated with two separable event-related potentials (ERPs) usually localized to the medial frontal wall, one during error processing (ERN--error related negativity) and one during conflict monitoring (N2). In this study we aimed to spatially and temporally dissociate conflict and error processing using simultaneously recorded EEG and fMRI data from a modified Flanker task in healthy adults. We demonstrate a spatial dissociation of conflict monitoring and error processing along the medial frontal wall, with selective conflict level dependent activation of the SMA/pre-SMA. Activation to error processing was located in the ACC, rostral cingulate zone (RCZ) and pre-SMA. The EEG-informed fMRI analysis revealed that stronger ERN amplitudes are associated with increased activation in a large coherent cluster comprising the ACC, RCZ and pre-SMA, while N2 amplitudes increased with activation in the pre-SMA. Conjunction analysis of EEG-informed fMRI revealed common activation of ERN and N2 in the pre-SMA and divergent activation in the RCZ. No conjoint activation between error processing and conflict monitoring was found with standard fMRI analysis along the medial frontal wall. Our fMRI findings clearly demonstrate that conflict monitoring and error processing are spatially dissociable along the medial frontal wall. Moreover, the overlap of ERN- and N2-informed fMRI activation in the pre-SMA provides new evidence that these ERP components share conflict related processing functions and are thus not completely separable.

Reconstruction of the human visual system based on DTI fiber tracking.

To apply and to evaluate the newly developed advanced fast marching algorithm (aFM) in vivo by reconstructing the human visual pathway, which is characterized by areas of extensive fiber crossing and branching, i.e., the optic chiasm and the lateral geniculate nucleus (LGN).

Preliminary experience with visualization of intracortical fibers by focused high-resolution diffusion tensor imaging

BACKGROUND AND PURPOSE: The inherent low anisotropy of gray matter and the lack of adequate imaging sensitivity and resolution has, so far, impeded depiction of axonal fibers to their intracortical origin or termination. We tested the hypothesis that an experimental approach with high-resolution diffusion tensor imaging (DTI) provides anisotropic data for fiber tractography with sufficient sensitivity to visualize in vivo the fine distribution of white matter bundles at the intracortical level. MATERIALS AND METHODS: We conducted phantom measurements of signal-to-noise ratio (SNR) and obtained diffusion tensor maps of the occipital lobe in 6 healthy volunteers using a dedicated miniature phased array detector at 3T. We reconstructed virtual fibers using a standard tracking algorithm. RESULTS: The coil array provided a SNR of 8.0 times higher at the head surface compared with a standard quadrature whole head coil. Diffusion tensor maps could be obtained with an in-plane resolution of 0.58 × 0.58 mm2. The axonal trajectories reconstructed from the diffusion data penetrate into the cortical ribbon perpendicular to the pial surface. This is the expected pattern for the terminations of thalamocortical afferent fibers to the middle layers of the occipital cortex and is consistent with the known microstructural organization of the mammalian cerebral cortex. CONCLUSION: High-resolution DTI reveals intracortical anisotropy with a distinct parallel geometrical order, perpendicular to the pial surface, consistent with structures that may be identified as the terminal afferents in cortical gray matter.

Construction of a temperature-controlled diffusion phantom for quality control of diffusion measurements

To construct a temperature‐controlled diffusion phantom with known diffusion properties and geometry in order to facilitate the comparison and optimization of diffusion sequences with the objective of increasing the precision of experimentally derived diffusion parameters.

Gamma-Hydroxybutyrate Increases Resting-State Limbic Perfusion and Body and Emotion Awareness in Humans

Gamma-hydroxybutyrate (GHB) is a GHB-/GABA-B receptor agonist inducing a broad spectrum of subjective effects including euphoria, disinhibition, and enhanced vitality. It is used as treatment for neuropsychiatric disorders including narcolepsy and alcohol withdrawal, but is also a drug of abuse. Non-medical users report enhancement of body and emotion awareness during intoxication. However, the neuronal underpinnings of such awareness alterations under GHB are unknown so far. The assessment of regional cerebral blood flow (rCBF) by pharmacological magnetic resonance imaging (phMRI) enables the elucidation of drug-induced functional brain alterations. Thus, we assessed the effects of GHB (35 mg/kg p.o.) in 17 healthy males on rCBF and subjective drug effects, using a placebo-controlled, double-blind, randomized, cross-over design employing arterial spin labeling phMRI. Compared to placebo, GHB increased subjective ratings for body and emotion awareness, and for dizziness (p<0.01–0.001, Bonferroni-corrected). A whole-brain analysis showed increased rCBF in the bilateral anterior cingulate cortex (ACC) and the right anterior insula under GHB (p<0.05, cluster-corrected). ACC and insula rCBF are correlated with relaxation, and body and emotion awareness (p<0.05–0.001, uncorrected). Interaction analyses revealed that GHB-induced increase of body awareness was accompanied by increased rCBF in ACC, whereas relaxation under GHB was accompanied by elevated rCBF in right anterior insula (p<0.05, uncorrected). In conclusion, enhancement of emotion and body awareness, and increased perfusion of insula and ACC bears implications both for the properties of GHB as a drug of abuse as well as for its putative personalized potential for specific therapeutic indications in affective disorders.

Neural underpinnings of prosexual effects induced by gamma-hydroxybutyrate in healthy male humans

Gamma-hydroxybutyrate (GHB) is a GHB-/GABAB-receptor agonist currently used as treatment for narcolepsy but also as a drug of abuse. Non-medical GHB users have repeatedly reported prosexual effects including libido-enhancement and lowering of attractiveness standards for partner selection. Here, we examined the putative prosexual effects of oral GHB in healthy males in two experiments both employing randomized, placebo-controlled, double-blind, balanced, and cross-over study designs. In experiment I, subjective effects of 20 and 35mg/kg GHB vs. placebo were tested in 32 participants using the Sexual Arousal and Desire Inventory. In experiment II, brain reactivity towards erotic vs. neutral pictures was investigated in 15 participants using functional magnetic resonance imaging after 35mg/kg GHB vs. placebo. In experiment I, prosexual effects of GHB were shown by increased SADI ratings regarding physiological, evaluative, and motivational aspects of sexual arousal. In experiment II, erotic visual stimuli activated the bilateral insula, nucleus accumbens (NAcc), fusiform gyrus, thalamus, and left occipital pole under placebo. After GHB administration, even sexually neutral pictures of persons induced subjective sexual arousal and increased activation of the bilateral NAcc and right anterior cingulate cortex, which significantly correlated (left NAcc by trend). Moreover, a psychophysiological interaction analysis showed that GHB increased connectivity between NAcc and ventromedial prefrontal cortex during processing of visual erotic cues, i.e., in the condition in which subjective sexual arousal was highest. Our data show that GHB stimulates hedonic sexual functioning and lowers the threshold for erotic perception, which is related to increased susceptibility of mesolimbic reward pathways.

Two dose investigation of the 5-HT-agonist psilocybin on relative and global cerebral blood flow

Abstract Psilocybin, the active compound in psychedelic mushrooms, is an agonist of various serotonin receptors. Seminal psilocybin positron emission tomography (PET) research suggested regional increases in glucose metabolism in frontal cortex (hyperfrontality). However, a recent arterial spin labeling (ASL) study suggests psilocybin may lead to hypo‐perfusion in various brain regions. In this placebo‐controlled, double‐blind study we used pseudo‐continuous ASL (pCASL) to measure perfusion changes, with and without adjustment for global brain perfusion, after two doses of oral psilocybin (low dose: 0.160 mg/kg; high dose: 0.215 mg/kg) in two groups of healthy controls (n = 29 in both groups, total N = 58) during rest. We controlled for sex and age and used family‐wise error corrected p values in all neuroimaging analyses. Both dose groups reported profound subjective drug effects as measured by the Altered States of Consciousness Rating Scale (5D‐ASC) with the high dose inducing significantly larger effects in four out of the 11 scales. After adjusting for global brain perfusion, psilocybin increased relative perfusion in distinct right hemispheric frontal and temporal regions and bilaterally in the anterior insula and decreased perfusion in left hemispheric parietal and temporal cortices and left subcortical regions. Whereas, psilocybin significantly reduced absolute perfusion in frontal, temporal, parietal, and occipital lobes, and bilateral amygdalae, anterior cingulate, insula, striatal regions, and hippocampi. Our analyses demonstrate consistency with both the hyperfrontal hypothesis of psilocybin and the more recent study demonstrating decreased perfusion, depending on analysis method. Importantly, our data illustrate that relative changes in perfusion should be understood and interpreted in relation to absolute signal variations. HighlightsOral psilocybin decreases absolute cerebral blood flow in healthy participants.When evaluating relative changes, psilocybin produces hyperfrontal effects.Our results may clarify an existing discrepancy in the current literature.Our results highlight the importance of evaluating regional and global CBF.