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

Introduction: White 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. Methods: To 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. Results: Application 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. Conclusion: fMRI-guided advanced DTI fiber tracking has the potential to provide accurate anatomical and functional information for a more informed therapeutic decision makin

Investigating functional brain connectivity patterns associated with two hypnotic states

While there’s been clinical success and growing research interest in hypnosis, neurobiological underpinnings induced by hypnosis remain unclear. In this fMRI study (which is part of a larger hypnosis project) with 50 hypnosis-experienced participants, we analyzed neural and physiological responses during two hypnosis states, comparing them to non-hypnotic control conditions and to each other. An unbiased whole-brain analysis (multi-voxel- pattern analysis, MVPA), pinpointed key neural hubs in parieto-occipital-temporal areas, cuneal/precuneal and occipital cortices, lingual gyri, and the occipital pole. Comparing directly both hypnotic states revealed depth-dependent connectivity changes, notably in left superior temporal/supramarginal gyri, cuneus, planum temporale, and lingual gyri. Multi-voxel- pattern analysis (MVPA) based seeds were implemented in a seed-to-voxel analysis unveiling region-specific increases and decreases in functional connectivity patterns. Physiologically, the respiration rate significantly slowed during hypnosis. Summarized, these findings foster fresh insights into hypnosis-induced functional connectivity changes and illuminate further knowledge related with the neurobiology of altered consciousness

Illusory Body Ownership Affects the Cortical Response to Vicarious Somatosensation

Fundamental human feelings such as body ownership (“this” body is “my” body) and vicariousness (first-person-like experience of events occurring to others) are based on multisensory integration. Behavioral links between body ownership and vicariousness have been shown, but the neural underpinnings remain largely unexplored. To fill this gap, we investigated the neural effects of altered body ownership on vicarious somatosensation. While recording functional brain imaging data, first, we altered participants’ body ownership by robotically delivering tactile stimulations (“tactile” stroking) in synchrony or not with videos of a virtual hand being brushed (“visual” stroking). Then, we manipulated vicarious somatosensation by showing videos of the virtual hand being touched by a syringe’s plunger (touch) or needle (pain). Only after the alteration of body ownership (synchronous visuo-tactile stroking) and specifically during late epochs of vicarious somatosensation, vicarious pain was associated with lower activation in premotor and anterior cingulate cortices with respect to vicarious touch. At the methodological level, the present study highlights the importance of the neural response’s temporal evolution. At the theoretical level, it shows that the higher-level (cognitive) impact of a lower-level (sensory) body-related processing (visuo-tactile) is not limited to body ownership but also extends to other psychological body-related domains, such as vicarious somatosensation

Gamma-hydroxybutyrate increases brain resting-state functional connectivity of the salience network and dorsal nexus in humans

According to the triple network hypothesis the brain is equipped with three core neurocognitive networks: the default mode (DMN), the salience (SN), and the central executive (CEN) network. Moreover, the so called dorsal nexus, has met growing interest as it is a hub region connecting these three networks. Assessment of resting-state functional connectivity (rsFC) of these networks enables the elucidation of drug-induced brain alterations. Gamma-hydroxybutyrate (GHB) is a GHB/GABA-B receptor agonist that induces a paradoxical state of mixed stimulation and sedation at moderate doses, which makes it a valuable tool to investigate neural signatures of subjective drug effects. Employing a placebo-controlled, double-blind, randomized, cross-over design, we assessed the effects of GHB (35 mg/kg p. o.) in 19 healthy male subjects on DMN-, SN-, CEN-, and dorsal nexus-rsFC measured by functional magnet resonance imaging and applying independent component as well as seed-based analyses, while subjective drug effects were investigated using visual analog scales (VAS). Subjectively, GHB increased VAS ratings of a general drug effect, stimulation, and sedation. Intrinsic DMN-, and CEN-rsFC remained largely unchanged under GHB, but the drug increased SN-DMN-rsFC and SN-dorsal nexus-rsFC, while dorsal nexus-rsFC was reciprocally increased to both the SN (right anterior insula) and to the CEN (right middle frontal gyrus). Increased sedation significantly predicted the observed SN-dorsal nexus-rsFC. In conclusion, GHB generates a unique stimulant/sedative subjective state that is paralleled by a complex pattern of increased functional connectivity encompassing all three core neurocognitive networks of the brain, while increased SN-dorsal nexus-rsFC was demonstrated to be a potential signature of the sedative component of the drug effect

Uniformity and Deviation of Intra-axonal Cross-sectional Area Coverage of the Gray-to-White Matter Interface

Diffusion magnetic resonance imaging (dMRI) is a compelling tool for investigating the structure and geometry of brain tissue based on indirect measurement of the diffusion anisotropy of water. Recent developments in global top-down tractogram optimizations enable the estimation of streamline weights, which characterize the connection between gray matter areas. In this work, the intra-axonal cross-sectional area coverage of the gray-to-white matter interface was examined by intersecting tractography streamlines with cortical regions of interest. The area coverage is the ratio of streamline weights divided by the surface area at the gray-to-white matter interface and assesses the estimated percentage which is covered by intra-axonal space. A high correlation (r = 0.935) between streamline weights and the cortical surface area was found across all regions of interest in all subjects. The variance across different cortical regions exhibits similarities to myelin maps. Additionally, we examined the effect of different diffusion gradient subsets at a lower, clinically feasible spatial resolution. Subsampling of the initial high-resolution diffusion dataset did not alter the tendency of the area coverage at the gray-to-white matter interface across cortical areas and subjects. However, single-shell acquisition schemes with lower b-values lead to a steady increase in area coverage in comparison to the full acquisition scheme at high resolution

Uniformity and deviation of intra-axonal cross-sectional area coverage of the gray-to-white matter interface

Diffusion magnetic resonance imaging (dMRI) is a compelling tool for investigating the structure and geometry of brain tissue based on indirect measurement of the diffusion anisotropy of water. Recent developments in global top-down tractogram optimizations enable the estimation of streamline weights, which characterize the connection between gray matter areas. In this work, the intra-axonal cross-sectional area coverage of the gray-to-white matter interface was examined by intersecting tractography streamlines with cortical regions of interest. The area coverage is the ratio of streamline weights divided by the surface area at the gray-to-white matter interface and assesses the estimated percentage which is covered by intra-axonal space. A high correlation (r = 0.935) between streamline weights and the cortical surface area was found across all regions of interest in all subjects. The variance across different cortical regions exhibits similarities to myelin maps. Additionally, we examined the effect of different diffusion gradient subsets at a lower, clinically feasible spatial resolution. Subsampling of the initial high-resolution diffusion dataset did not alter the tendency of the area coverage at the gray-to-white matter interface across cortical areas and subjects. However, single-shell acquisition schemes with lower b-values lead to a steady increase in area coverage in comparison to the full acquisition scheme at high resolution

Investigation of Cerebral White Matter Changes After Spinal Cord Injury With a Measure of Fiber Density

Remote neurodegenerative changes in supraspinal white matter (WM) can manifest after central lesions such as spinal cord injury (SCI). The majority of diffusion tensor imaging (DTI) studies use traditional metrics such as fractional anisotropy (FA) and mean diffusivity (MD) to investigate microstructural changes in cerebral WM after SCI. However, interpretation of FA readouts is often challenged by inherent limitations of the tensor model. Recent developments in novel diffusion markers, such as fiber density (FD), allows more accurate depictions of WM pathways and has shown more reliable quantification of WM alterations compared to FA in recent studies of neurological diseases. This study investigated if FD provides useful characterization of supraspinal WM integrity after SCI in addition to the traditional DTI readouts. FA, MD, and FD maps were derived from diffusion datasets of 20 patients with chronic SCI and compared with 19 healthy controls (HC). Group differences were investigated across whole brain WM using tract-based spatial statistics and averaged diffusion values of the corticospinal tract (CST) and thalamic radiation (TR) were extracted for comparisons between HC and SCI subgroups. We also related diffusion readouts of the CST and TR with clinical scores of sensorimotor function. To investigate which diffusion markers of the CST and TR delineate HC and patients with SCI a receiver operating characteristic (ROC) analysis was performed. Overall, patients with an SCI showed decreased FA of the TR and CST. ROC analysis differentiated HC and SCI based on diffusion markers of large WM tracts including FD of the TR. Furthermore, patients' motor function was positively correlated with greater microstructural integrity of the CST. While FD showed the strongest correlation, motor function was also associated with FA and MD of the CST. In summary, microstructural changes of supraspinal WM in patients with SCI can be detected using FD as a complementary marker to traditional DTI readouts and correlates with their clinical characteristics. Future DTI studies may benefit from utilizing this novel marker to investigate complex large WM tracts in patient cohorts with varying presentations of SCI or neurodegenerative diseases

In human non-REM sleep, more slow-wave activity leads to less blood flow in the prefrontal cortex

Cerebral blood flow (CBF) is related to integrated neuronal activity of the brain whereas EEG provides a more direct measurement of transient neuronal activity. Therefore, we addressed what happens in the brain during sleep, combining CBF and EEG recordings. The dynamic relationship of CBF with slow-wave activity (SWA; EEG sleep intensity marker) corroborated vigilance state specific (i.e., wake, non-rapid eye movement (NREM) sleep stages N1-N3, wake after sleep) differences of CBF e.g. in the posterior cingulate, basal ganglia, and thalamus, indicating their role in sleep-wake regulation and/or sleep processes. These newly observed dynamic correlations of CBF with SWA - namely a temporal relationship during continuous NREM sleep in individuals - additionally implicate an impact of sleep intensity on the brain's metabolism. Furthermore, we propose that some of the aforementioned brain areas that also have been shown to be affected in disorders of consciousness might therefore contribute to the emergence of consciousness

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

Introduction: White 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. Methods: To 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. Results Application 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. Conclusion: fMRI-guided advanced DTI fiber tracking has the potential to provide accurate anatomical and functional information for a more informed therapeutic decision making

Reconstruction of the human visual system based on DTI fiber tracking

PURPOSE: 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). MATERIALS AND METHODS: Diffusion tensor images were acquired in 10 healthy volunteers. Due to the proximity to bony structures and air-filled spaces of the optic chiasm, a high sensitivity encoding (SENSE) reduction factor was applied to reduce image distortions in this area. To reconstruct the visual system, three different seed areas were chosen separately. The results obtained by the aFM tracking algorithm were compared and validated with known anatomy. RESULTS: The visual system could be reconstructed reproducibly in all subjects and the reconstructed fiber pathways are in good agreement with known anatomy. CONCLUSION: The present work shows that the advanced aFM, which is especially designed for overcoming tracking limitations within areas of extensive fiber crossing, handles the fiber crossing and branching within the optic chiasm and the LGN correctly, thus allowing the reconstruction of the entire human visual fiber pathway, from the intraorbital segment of the optic nerves to the visual cortex