Alexander Geißler

Clinical fMRI: Evidence for a 7 T benefit over 3 T

Despite there being an increasing number of installations of ultra high field MR systems (> 3 T) in clinical environments, no functional patient investigations have yet examined possible benefits for functional diagnostics. Here we performed presurgical localization of the primary motor hand area on 3 T and 7 T Siemens scanners with identical investigational procedures and comparable system specific sequence optimizations. Results from 17 patients showed significantly higher functional sensitivity of the 7 T system measured via percent signal change, mean t-values, number of suprathreshold voxels and contrast to noise ratio. On the other hand, 7 T data suffered from a significant increase of artifacts (ghosting, head motion). We conclude that ultra high field systems provide a clinically relevant increase of functional sensitivity for patient investigations.

Does clinical memory fMRI provide a comprehensive map of medial temporal lobe structures

Successful clinical application of fMRI tasks requires reliable knowledge about the brain structures mapped by the task. With memory fMRI, diverging evidence exists concerning the location of major signal sources as well as hippocampal contributions. To clarify these issues, we investigated a frequently applied memory test (home town walking) in 33 patients with unilateral medial temporal lobe pathology, comparing healthy and diseased hemispheres. We focused on a detailed investigation of individual fMRI maps on non-transformed high-resolution functional images. Results show a clear dominance of activations around the collateral sulcus, corresponding to parahippocampal and entorhinal cortex activities. Hippocampus activity was absent in the vast majority of patients. The diseased hemispheres showed lower activation than the healthy hemispheres. We conclude that (1) the investigated memory test may be successfully applied for evaluation of the parahippocampal cortex, (2) the hippocampus is not reliably mapped by the task, and (3) the methods described for investigation of individual high-resolution functional images allow generation of application profiles for clinical fMRI tasks.

FMRI correlates of apraxia in Parkinson's disease patients OFF medication

Impairment of hand dexterity in Parkinsons disease (PD) is usually attributed to bradykinesia. Recently, behavioral studies illustrated that decreased dexterity might also be due to limb-kinetic apraxia (LkA), as demonstrated by impaired performance in a coin rotation task. Here, we provide a first investigation on whether functional magnetic resonance imaging (fMRI) may reveal specific brain activation patterns for PD patients with impaired performance in a coin rotation task. We compared coin rotation as an apraxia task to simple finger tapping as a bradykinesia task in ten PD patients OFF medication and matched healthy controls. In addition to a tendency for general overactivation, PD patients showed a perirolandic dissociation with precentral overactivation and postcentral underactivation. This finding significantly separated PD patients from healthy controls.

New Type of Cortical Neuroplasticity After Nerve Repair in Brachial Plexus Lesions

BACKGROUND In brachial plexus avulsion, a recent technique connects the ending of the disrupted musculocutaneous nerve to the side of the intact phrenic nerve to regain elbow flexion. This requires the phrenic nerve to perform a new double function: independent control of breathing and elbow flexion. Neuroplastic changes associated with acquisition of double nerve functions have not yet been investigated. OBJECTIVE To evaluate neuroplastic changes associated with acquisition of double nerve functions in a monofunctional nerve (phrenic nerve). DESIGN Clinical and functional magnetic resonance imaging investigations during arm movements, forced inspiration, and motor control tasks. SETTING Investigations at the Medical University of Vienna, Vienna, Austria. PARTICIPANTS Three healthy control subjects, 2 patients with phrenic nerve end-to-side coaptation, and 1 control patient with C7 end-to-end coaptation (same clinical presentation but phrenic nerve unchanged). RESULTS Clinical documentation showed that both patients with phrenic nerve end-to-side coaptation were able to control the diaphragm and the biceps independently via the same phrenic nerve. In contrast to all controls, both patients with phrenic nerve end-to-side coaptation activated the cortical diaphragm areas with flexion of the diseased arm. CONCLUSION Our functional magnetic resonance imaging data indicate that the patients cortical diaphragm areas reorganize in such a way that independent control of breathing and elbow flexion is possible with the same neuronal population.

Finger dexterity deficits in Parkinson's disease and somatosensory cortical dysfunction

INTRODUCTION The patho-physiological basis for finger dexterity deficits in Parkinsons disease (PD) is controversial. Previously, bradykinesia was regarded as the major mechanism. However, recent research suggested limb-kinetic apraxia as an important component of impaired fine motor skills in PD. In contrast to bradykinesia, limb-kinetic apraxia only marginally responds to dopaminergic treatment. Here we investigate the novel hypothesis that the dexterity deficits are related to an intrinsic dysfunction of primary somatosensory cortex (S1), which is not reversible by dopaminergic medication. METHODS Applying a standard and approved dexterity task (coin rotation), brain activation networks were investigated using functional magnetic resonance imaging in PD patients both ON and OFF medication and matched healthy controls. RESULTS PD patients both ON and OFF medication showed impaired S1 activation relative to controls (p < 0.05; region of interest based analysis). The impaired S1 activation remained unchanged by dopaminergic medication. Despite the considerable clinical deficit, no other brain area showed impaired activation. In contrast, structures of the basal ganglia--motor cortex loop responded to dopaminergic medication. Behaviorally, dexterity performance both ON and OFF was significantly (p < 0.05) reduced relative to controls. CONCLUSIONS Our results provide first evidence that dexterity deficits in PD are related to an S1 dysfunction which is insensitive to dopaminergic treatment.

Differential functional benefits of ultra highfield MR systems within the language network

Several investigations have shown limitations of fMRI reliability with the current standard field strengths. Improvement is expected from ultra highfield systems but studies on possible benefits for cognitive networks are lacking. Here we provide an initial investigation on a prominent and clinically highly-relevant cognitive function: language processing in individual brains. 26 patients evaluated for presurgical language localization were investigated with a standardized overt language fMRI paradigm on both 3 T and 7 T MR scanners. During data acquisition and analysis we made particular efforts to minimize effects not related to static magnetic field strength differences. Six measures relevant for functional activation showed a large dissociation between essential language network nodes: although in Wernickes area 5/6 measures indicated a benefit of ultra highfield, in Brocas area no comparison was significant. The most important reason for this discrepancy was identified as being an increase in susceptibility-related artifacts in inferior frontal brain areas at ultra high field. We conclude that functional UHF benefits are evident, however these depend crucially on the brain region investigated and the ability to control local artifacts.

Comparing the microvascular specificity of the 3- and 7-T BOLD response using ICA and susceptibility-weighted imaging

In functional MRI it is desirable for the blood-oxygenation level dependent (BOLD) signal to be localized to the tissue containing activated neurons rather than the veins draining that tissue. This study addresses the dependence of the specificity of the BOLD signal – the relative contribution of the BOLD signal arising from tissue compared to venous vessels – on magnetic field strength. To date, studies of specificity have been based on models or indirect measures of BOLD sensitivity such as signal to noise ratio and relaxation rates, and assessment has been made in isolated vein and tissue voxels. The consensus has been that ultra-high field systems not only significantly increase BOLD sensitivity but also specificity, that is, there is a proportionately reduced signal contribution from draining veins. Specificity was not quantified in prior studies, however, due to the difficulty of establishing a reliable network of veins in the activated volume. In this study we use a map of venous vessel networks extracted from 7 T high resolution Susceptibility-Weighted Images to quantify the relative contributions of micro- and macro-vasculature to functional MRI results obtained at 3 and 7 T. High resolution measurements made here minimize the contribution of physiological noise and Independent Component Analysis (ICA) is used to separate activation from technical, physiological, and motion artifacts. ICA also avoids the possibility of timing-dependent bias from different micro- and macro-vasculature responses. We find a significant increase in the number of activated voxels at 7 T in both the veins and the microvasculature – a BOLD sensitivity increase – with the increase in the microvasculature being higher. However, the small increase in sensitivity at 7 T was not significant. For the experimental conditions of this study, our findings do not support the hypothesis of an increased specificity of the BOLD response at ultra-high field.

An fMRI Marker for Peripheral Nerve Regeneration

Final outcome after surgical repair of peripheral nerve transections varies. Here, we present the first longitudinal functional magnetic resonance imaging (fMRI) obserof cortical somatosensory reorganization patterns after surgery. A 43-year-old man presented with isolated complete transecof the right median nerve and underwent immediate epineural end-to-end coaptation. Applying standardized vibrotactile median nerve stimulation, 3 T brain activation maps were evaluated at 1, 7, 15 weeks and 1 year after surgery. Initially, the affected hemisphere showed no primary activation but increased frontoparietal activity. After 1 year, primary activation had recovered, and frontoparietal activity was decreased relative to the nonaffected hemisphere. Based on these longitudinal fMRI patterns, we propose a new marker for restoration of somatosensory function, which may not be provided by electrophysiological methods.

Between- and within-site variability of fMRI localizations

This study provides first data about the spatial variability of fMRI sensorimotor localizations when investigating the same subjects at different fMRI sites. Results are comparable to a previous patient study. We found a median between‐site variability of about 6 mm independent of task (motor or sensory) and experimental standardization (high or low). An intraclass correlation coefficient analysis using data quality measures indicated a major influence of the fMRI site on variability. In accordance with this, within‐site localization variability was considerably lower (about 3 mm). We conclude that the fMRI site is a considerable confound for localization of brain activity. However, when performed by experienced clinical fMRI experts, brain pathology does not seem to have a relevant impact on the reliability of fMRI localizations. Hum Brain Mapp 37:2151–2160, 2016.

Robust presurgical functional MRI at 7 T using response consistency: Presurgical fMRI at 7 T Using Response Consistency

Functional MRI is valuable in presurgical planning due to its non‐invasive nature, repeatability, and broad availability. Using ultra‐high field MRI increases the specificity and sensitivity, increasing the localization reliability and reducing scan time. Ideally, fMRI analysis for this application should identify unreliable runs and work even if the patient deviates from the prescribed task timing or if there are changes to the hemodynamic response due to pathology. In this study, a model‐free analysis method—UNBIASED—based on the consistency of fMRI responses over runs was applied, to ultra‐high field fMRI localizations of the hand area. Ten patients with brain tumors and epilepsy underwent 7 Tesla fMRI with multiple runs of a hand motor task in a block design. FMRI data were analyzed with the proposed approach (UNBIASED) and the conventional General Linear Model (GLM) approach. UNBIASED correctly identified and excluded fMRI runs that contained little or no activation. Generally, less motion artifact contamination was present in UNBIASED than in GLM results. Some cortical regions were identified as activated in UNBIASED but not GLM results. These were confirmed to show reproducible delayed or transient activation, which was time‐locked to the task. UNBIASED is a robust approach to generating activation maps without the need for assumptions about response timing or shape. In presurgical planning, UNBIASED can complement model‐based methods to aid surgeons in making prudent choices about optimal surgical access and resection margins for each patient, even if the hemodynamic response is modified by pathology. Hum Brain Mapp 38:3163–3174, 2017.