Stefan Hetzer

Brain tissue properties differentiate between motor and limbic basal ganglia circuits

Despite advances in understanding basic organizational principles of the human basal ganglia, accurate in vivo assessment of their anatomical properties is essential to improve early diagnosis in disorders with corticosubcortical pathology and optimize target planning in deep brain stimulation. Main goal of this study was the detailed topological characterization of limbic, associative, and motor subdivisions of the subthalamic nucleus (STN) in relation to corresponding corticosubcortical circuits. To this aim, we used magnetic resonance imaging and investigated independently anatomical connectivity via white matter tracts next to brain tissue properties. On the basis of probabilistic diffusion tractography we identified STN subregions with predominantly motor, associative, and limbic connectivity. We then computed for each of the nonoverlapping STN subregions the covariance between local brain tissue properties and the rest of the brain using high‐resolution maps of magnetization transfer (MT) saturation and longitudinal (R1) and transverse relaxation rate (R2*). The demonstrated spatial distribution pattern of covariance between brain tissue properties linked to myelin (R1 and MT) and iron (R2*) content clearly segregates between motor and limbic basal ganglia circuits. We interpret the demonstrated covariance pattern as evidence for shared tissue properties within a functional circuit, which is closely linked to its function. Our findings open new possibilities for investigation of changes in the established covariance pattern aiming at accurate diagnosis of basal ganglia disorders and prediction of treatment outcome. Hum Brain Mapp 35:5083–5092, 2014.

3D GRASE Pulsed Arterial Spin Labeling at Multiple Inflow Times in Patients with Long Arterial Transit Times: Comparison with Dynamic Susceptibility-Weighted Contrast-Enhanced MRI at 3 Tesla

Pulsed arterial spin labeling (PASL) at multiple inflow times (multi-TIs) is advantageous for the measurement of brain perfusion in patients with long arterial transit times (ATTs) as in steno-occlusive disease, because bolus-arrival-time can be measured and blood flow measurements can be corrected accordingly. Owing to its increased signal-to-noise ratio, a combination with a three-dimensional gradient and spin echo (GRASE) readout allows acquiring a sufficient number of multi-TIs within a clinically feasible acquisition time of 5 minutes. We compared this technique with the clinical standard dynamic susceptibility-weighted contrast-enhanced imaging—magnetic resonance imaging in patients with unilateral stenosis >70% of the internal carotid or middle cerebral artery (MCA) at 3 Tesla. We performed qualitative (assessment by three expert raters) and quantitative (region of interest (ROI)/volume of interest (VOI) based) comparisons. In 43 patients, multi-TI PASL-GRASE showed perfusion alterations with moderate accuracy in the qualitative analysis. Quantitatively, moderate correlation coefficients were found for the MCA territory (ROI based: r=0.52, VOI based: r=0.48). In the anterior cerebral artery (ACA) territory, a readout related right-sided susceptibility artifact impaired correlation (ROI based: r=0.29, VOI based: r=0.34). Arterial transit delay artifacts were found only in 12% of patients. In conclusion, multi-TI PASL-GRASE can correct for arterial transit delay in patients with long ATTs. These results are promising for the transfer of ASL to the clinical practice.

Stereoscopic depth increases intersubject correlations of brain networks

Three-dimensional movies presented via stereoscopic displays have become more popular in recent years aiming at a more engaging viewing experience. However, neurocognitive processes associated with the perception of stereoscopic depth in complex and dynamic visual stimuli remain understudied. Here, we investigate the influence of stereoscopic depth on both neurophysiology and subjective experience. Using multivariate statistical learning methods, we compare the brain activity of subjects when freely watching the same movies in 2D and in 3D. Subjective reports indicate that 3D movies are more strongly experienced than 2D movies. On the neural level, we observe significantly higher intersubject correlations of cortical networks when subjects are watching 3D movies relative to the same movies in 2D. We demonstrate that increases in intersubject correlations of brain networks can serve as neurophysiological marker for stereoscopic depth and for the strength of the viewing experience.

Perfusion alters stiffness of deep gray matter

Viscoelastic properties of the brain reflect tissue architecture at multiple length scales. However, little is known about the relation between vital tissue functions, such as perfusion, and the macroscopic mechanical properties of cerebral tissue. In this study, arterial spin labelling is paired with magnetic resonance elastography to investigate the relationship between tissue stiffness and cerebral blood flow (CBF) in the in vivo human brain. The viscoelastic modulus, |G*|, and CBF were studied in deep gray matter (DGM) of 14 healthy male volunteers in the following sub-regions: putamen, nucleus accumbens, hippocampus, thalamus, globus pallidus, and amygdala. CBF was further normalized by vessel area data to obtain the flux rate q which is proportional to the perfusion pressure gradient. The striatum (represented by putamen and nucleus accumbens) was distinct from the other DGM regions by displaying markedly higher stiffness and perfusion values. q was a predictive marker for DGM stiffness as analyzed by linear regression |G*| = q·(4.2 ± 0.6)kPa·s + (0.80 ± 0.06)kPa (R2 = 0.92, P = 0.006). These results suggest a high sensitivity of MRE in DGM to perfusion pressure. The distinct mechano-vascular properties of striatum tissue, as compared to the rest of DGM, may reflect elevated perfusion pressure, which could explain the well-known susceptibility of the putamen to hemorrhages.

Increasing the spatial resolution and sensitivity of magnetic resonance elastography by correcting for subject motion and susceptibility-induced image distortions

To improve the resolution of elasticity maps by adapting motion and distortion correction methods for phase‐based magnetic resonance imaging (MRI) contrasts such as magnetic resonance elastography (MRE), a technique for measuring mechanical tissue properties in vivo.

Correction for Susceptibility Distortions Increases the Performance of Arterial Spin Labeling in Patients with Cerebrovascular Disease

Arterial spin labeling (ASL) is an MRI technique to measure cerebral blood flow (CBF) without the need of exogenous contrast agents and is thus a promising alternative to the clinical standard dynamic susceptibility‐weighted contrast‐enhanced (DSC) perfusion imaging. Latest international guidelines encourage its application in the clinical setting. However, susceptibility‐induced image distortions impair ASL with fast readout modules (eg Echo Planar Imaging, EPI; gradient and spin echo, GRASE). In the present study, we investigated the benefit of a distortion correction for ASL compared to DSC.

Center-out echo-planar spectroscopic imaging with correction of gradient-echo phase and time shifts

A procedure to prevent the formation of image and spectral Nyquist ghosts in echo‐planar spectroscopic imaging is introduced. It is based on a novel Cartesian center‐out echo‐planar spectroscopic imaging trajectory, referred to as EPSICO, and combined with a correction of the gradient‐echo phase and time shifts. Processing of homogenous sets of forward and reflected echoes is no longer necessary, resulting in an optimized spectral width. The proposed center‐out trajectory passively prevents the formation of Nyquist ghosts by privileging the acquisition of the center k‐space line with forward echoes at the beginning of an echo‐planar spectroscopic imaging dwell time and by ensuring that all k‐space lines and their respective complex conjugates are acquired at equal time intervals. With the proposed procedure, concentrations of N‐acetyl aspartate, creatine, choline, glutamate, and myo‐inositol were reliably determined in human white matter at 3 T. Magn Reson Med, 2013.

Stress-induced brain activity, brain atrophy, and clinical disability in multiple sclerosis

Significance Psychological stress is linked to multiple sclerosis (MS) severity (e.g., to a heightened risk of brain lesion development). The exact mechanisms underlying this association are unknown. To investigate the link between brain activity induced by mild psychological stress and MS disease parameters, we conducted a mental arithmetic neuroimaging task involving performance feedback in MS patients and healthy controls and related the brain activity signals to clinical disability and brain volume. In patients, motor and cognitive impairment were related to activity in the insular cortex. Brain volume was related to activity in overlapping cerebellar areas in patients and controls. This overlap suggests that the link between activity and volume cannot reflect a passive response to clinical disability alone. Prospective clinical studies support a link between psychological stress and multiple sclerosis (MS) disease severity, and peripheral stress systems are frequently dysregulated in MS patients. However, the exact link between neurobiological stress systems and MS symptoms is unknown. To evaluate the link between neural stress responses and disease parameters, we used an arterial-spin–labeling functional MRI stress paradigm in 36 MS patients and 21 healthy controls. Specifically, we measured brain activity during a mental arithmetic paradigm with performance-adaptive task frequency and performance feedback and related this activity to disease parameters. Across all participants, stress increased heart rate, perceived stress, and neural activity in the visual, cerebellar and insular cortex areas compared with a resting condition. None of these responses was related to cognitive load (task frequency). Consistently, although performance and cognitive load were lower in patients than in controls, stress responses did not differ between groups. Insula activity elevated during stress compared with rest was negatively linked to impairment of pyramidal and cerebral functions in patients. Cerebellar activation was related negatively to gray matter (GM) atrophy (i.e., positively to GM volume) in patients. Interestingly, this link was also observed in overlapping areas in controls. Cognitive load did not contribute to these associations. The results show that our task induced psychological stress independent of cognitive load. Moreover, stress-induced brain activity reflects clinical disability in MS. Finally, the link between stress-induced activity and GM volume in patients and controls in overlapping areas suggests that this link cannot be caused by the disease alone.