Deep brain stimulation electrodes may rotate after implantation-an animal study.

Directional deep brain stimulation (dDBS) electrodes allow to steer the electrical field in a specific direction. When implanted with torque, they may rotate for a certain time after implantation. The aim of this study was to evaluate whether and to which degree leads rotate in the first 24 h after implantation using a sheep brain model. dDBS electrodes were implanted in 14 sheep heads and 3D rotational fluoroscopy (3D-RF) scans were acquired to visualize the orientation of the electrode leads. Electrode leads were clockwise rotated just above the burr holes (180° n = 6, 360° n = 6, 2 controls) and 3D-RF scans were again acquired after 3, 6, 13, 17, and 24 h, respectively. One hundred eighty degree rotated electrodes showed an initial rotation of 83.5° (range: 35.4°-128.3°) and a rotation of 114.0° (range: 57°-162°) after 24 h. With 360° torsion, mean initial rotation was 201° (range: 3.3°-321.4°) and mean rotation after 24 h 215.7° (range 31.9°-334.7°), respectively. Direct postoperative imaging may not be accurate for determining the rotation of dDBS electrodes if torque is present.

Alterations of intracerebral connectivity in epilepsy patients with secondary bilateral synchrony.

INTRODUCTION: The aim of our study was to evaluate intracerebral network changes in epilepsy patients demonstrating secondary bilateral synchrony (SBS) in EEG by applying a new Diffusion Tensor Imaging (DTI) method using an energy-based global tracking algorithm. MATERIALS AND METHODS: 10 MRI negative epilepsy patients demonstrating SBS in 10-20 surface EEG were included. EEG findings were analyzed for irritative zones characterized by focal interictal epileptiform discharges (IEDs) triggering SBS. In addition, DTI including an energy-based global tracking algorithm was applied to analyze fiber tract alterations in irritative zones. To measure the deviation of a certain cortical connection in comparison to healthy controls, normalized differences of fiber tract streamline counts (SC) and their p-values were evaluated in comparison to corresponding fibers of the control group. RESULTS: In 6 patients the irritative zone initiating SBS was located in the frontal lobe, in 3 patients in the temporal lobe and in 1 patient in the region surrounding the right central sulcus. All patients demonstrated significantly altered SC in brain lobes where the irritative zone triggering SBS was located (p ≤ 0.05). Seven out of 10 patients demonstrated SC alterations in tracts connecting brain lobes between the ipsilateral and the contralateral hemisphere (p ≤ 0.05). CONCLUSION: Our data demonstrate that alterations in fiber tracts in irritative zones triggering SBS are not necessarily associated with intracerebral lesions visible in high resolution MRI. Our study gives evidence that diffusion tensor imaging is a promising non-invasive additive tool for intracerebral network analyses even in MRI-negative epilepsy patients.

Ventral tegmental area connections to motor and sensory cortical fields in humans.

In humans, sensorimotor cortical areas receive relevant dopaminergic innervation-although an anatomic description of the underlying fiber projections is lacking so far. In general, dopaminergic projections towards the cortex originate within the ventral tegmental area (VTA) and are organized in a meso-cortico-limbic system. Using a DTI-based global tractography approach, we recently characterized the superolateral branch of the medial forebrain bundle (slMFB), a prominent pathway providing dopaminergic (and other transmitters) innervation for the pre-frontal cortex (Coenen et al., NeuroImage Clin 18:770-783, 2018). To define the connections between VTA and sensory-motor cortical fields that should contain dopaminergic fibers, we use the slMFB as a key structure to lead our fiber selection procedure: using a similar tracking-seed and tractography algorithm, we describe a dorsal extension of this slMFB that covers sensorimotor fields that are dorsally appended to pre-frontal cortical areas. This "motorMFB", that connects the VTA to sensorimotor cortical fields, can be further segregated into three sub-bundles with a seed-based fiber-selection strategy: A PFC bundle that is attendant to the pre-frontal cortex, passes the lateral VTA, runs through the border zone between the posterior and lateral ventral thalamic nucleus, and involves the pre- and postcentral gyrus. An MB bundle that is attendant to the mammillary bodies runs directly through the medial VTA, passes the lateral ventral thalamic nucleus, and involves the pre- and postcentral gyrus as well as the supplementary motor area (SMA) and the dorsal premotor cortex (dPMC). Finally, a BC bundle that is attendant to the brainstem and cerebellum runs through the lateral VTA, passes the anterior ventral thalamic nucleus, and covers the SMA, pre-SMA, and the dPMC. We, furthermore, included a fiber tracking of the well-defined dentato-rubro-thalamic tract (DRT) that is known to lie in close proximity with respect to fiber orientation and projection areas. As expected, the tract is characterized by a decussation at the ponto-mesencephal level and a projection covering the superior-frontal and precentral cortex. In addition to the physiological role of these particular bundles, the physiological and pathophysiological impact of dopaminergic signaling within sensorimotor cortical fields becomes discussed. However, some limitations have to be taken into account in consequence of the method: the transmitter content, the directionality, and the occurrence of interposed synaptic contacts cannot be specified.

Comparison of automated and visual DWI ASPECTS in acute ischemic stroke.

BACKGROUND AND PURPOSE: To assess intra-and inter-rater agreement of the ASPECTS (Alberta Stroke Program Early CT Score) based on diffusion-weighted MRI and to compare it with fully - automated methods (eASPECTS). METHODS: DWI-ASPECTS of scans of 96 patients with acute ischemic stroke was rated by 2 experts. Automated methods based on thresholding the affected volumes of a coregistered atlas, and a regression tree learning method were established. Intra-rater, inter-rater and human-rater vs. automated methods agreements were investigated based on the intraclass correlation coefficients (ICC) and Bland Altman plots. RESULTS: Intra-rater agreement was good for both raters (ICC of 0.91 and 0.93). Inter-rater agreement was worse (ICC = 0.86) indicating a slight bias between both raters. Agreement with automated methods ranged from 0.81 to 0.87. Root-mean-squared deviation was 0.89 and 0.69 for the human raters and ranged from 0.95 to 1.24 for the automated methods. CONCLUSIONS: Agreement values are on the same order or higher compared to a literature review of CT-based ASPECTS. Automated methods perform slightly worse than human expert ratings, but they still have enough power to determine the DWI-ASPECTS with good precision in a clinical setting.

[Big data and artificial intelligence for diagnostic decision support in atypical dementia]. / "Big Data" und künstliche Intelligenz zur Diagnoseunterstützung bei atypischer Demenz.

The differential diagnosis of atypical dementia remains difficult. The use of positron emission tomography (PET) still represents the gold standard for imaging diagnostics. According to the current evidence, however, magnetic resonance imaging (MRI) is almost equal to fluorodeoxyglucose (FDG)-PET, but only when using new big data and machine learning methods. In cases of atypical dementia, especially in younger patients and for follow-up, MRI is preferable to computed tomography (CT). In the clinical routine, promising MRI procedures are e. g. the automated volumetry of anatomical 3D images, as well as a non-contrast-enhanced MRI perfusion method, called arterial spin labeling (ASL). Because of the rapidly growing amount of biomarker data, there is a need for computer-aided big data analyses and artificial intelligence. Based on fast analyses of the diverse and rapidly increasing amount of clinical, imaging, epidemiological, molecular genetic and economic data, new knowledge on the pathogenesis, prevention and treatment can be generated. Technical availability, homogenization of the underlying data and the availability of large reference data are the basis for the widespread establishment of promising analytical methods.

[Imaging in acute ischemic stroke using automated postprocessing algorithms]. / Bildgebung beim akuten ischämischen Schlaganfall unter Verwendung automatisierter Analysealgorithmen.

There are several automated analytical methods to detect thromboembolic vascular occlusions, the infarct core and the potential infarct-endangered tissue (tissue at risk) by means of multimodal computed tomography (CT) and magnetic resonance imaging (MRI). The infarct core is more reliably visualized by diffusion-weighted imaging (DWI) MRI or CT perfusion than by native CT. The extent of tissue at risk and endangerment can only be estimated; however, it seems essential whether "tissue at risk" actually exists. To ensure consistent patient care, uniform imaging protocols should be acquired in the referring hospital and thrombectomy center and the collected data should be standardized and automatically evaluated and presented. Whether patients with a large infarct core and with or without tissue at risk or patients with large vessel occlusion (LVO) but low NIHSS benefit from thrombectomy has to be evaluated in controlled clinical trials using standardized imaging protocols. A promising, potentially time-saving approach is also native CT and CT angiography using a flat-panel detector angiography system for assessment of vessel occlusion and leptomeningeal collaterals.

Temporal lobe epilepsy due to meningoencephaloceles into the greater sphenoid wing: a consequence of idiopathic intracranial hypertension?

PURPOSE: Antero-inferior temporal lobe meningoencephaloceles are a rare, but increasingly recognized cause of drug-resistant temporal lobe epilepsy (TLE). In order to evaluate whether these lesions are related to idiopathic intracranial hypertension (IIH), we analyzed clinical and MRI findings of a cohort of patients undergoing presurgical work-up. METHODS: Seizure onset in the anterior temporal lobe was proven by EEG electrodes in 22 patients, and in 21 patients, anterior temporal lobectomy (mostly with sparing of the hippocampus) was performed. MRI signs of IIH (in particular empty sella) and the volumes of the ventricles and external CSF spaces were determined and related to the body mass index (BMI) and clinical outcome. RESULTS: Six of seven obese (BMI > 30 kg/m2) compared to four of 15 non-obese patients had partial empty or empty sella (p = 0.007). Bilateral lesions were found in all obese and 11 patients. Seizure freedom (Engel class 1A) was achieved in 12 of 21 patients (5 obese compared to 7 non-obese patients). BMI was related to the volume of the external CSF spaces (r = 0.467), and age at seizure onset was higher in obese patients. CONCLUSION: Roughly a third of patients with temporal lobe epilepsy due to antero-inferior meningoencephaloceles is obese and has MRI signs of idiopathic intracranial hypertension.

Longitudinal Volume Quantification of Deep Medullary Veins in Patients with Cerebral Venous Sinus Thrombosis : Venous Volume Assessment in Cerebral Venous Sinus Thrombosis Using SWI.

PURPOSE: Susceptibility-weighted imaging (SWI) visualizes small cerebral veins with high sensitivity and could, thus, enable quantification of hemodynamics of deep medullary veins. We aimed to evaluate volume changes of deep medullary veins in patients with acute cerebral venous sinus thrombosis (CVST) over time in comparison to healthy controls. METHODS: All magnetic resonance imaging (MRI) experiments were executed at 3 T using a 32-channel head coil. Based on SWI and semiautomatic postprocessing (statistical parametric mapping [SPM8] and ANTs), the volume of deep medullary veins was quantified in 14 patients with acute CVST at baseline and the 6­month follow-up, as well as in 13 healthy controls undergoing repeated MRI examination with an interscan interval of at least 1 month. RESULTS: Deep medullary venous volume change over time was significantly different between healthy controls and patient groups (p < 0.001). Patients with superior sagittal sinus thrombosis (SSST) showed a significant decline from baseline to follow-up measurements (9.8 ± 4.9 ml versus 7.5 ± 4.2 ml; p = 0.02), whereas in patients with transverse sinus thrombosis (TST) and healthy controls no significant volume changes were observable. CONCLUSIONS: Venous volume quantification was feasible and reproducible both in healthy volunteers and in patients. The decrease of venous volume in patients over time represents improvement of venous drainage, reduction of congestion, and normalization of microcirculation due to treatment. Thus, quantification of venous microcirculation could be valuable for estimation of prognosis and guidance of CVST therapy in the future.

Bilateral cingulum fiber reductions in temporal lobe epilepsy with unilateral hippocampal sclerosis.

PURPOSE: To evaluate whether white matter tracts within the Papez circuit are altered in patients with unilateral hippocampal sclerosis (HS). METHODS: Twenty patients with histologically proven unilateral HS and 20 age-matched controls were studied with a 3T Epilepsy-dedicated MRI protocol including a MPRAGE sequence for hippocampus volumetry and a diffusion tensor imaging (DTI) sequence (61 diffusion-encoding directions, 2×2×2mm3 voxels) for diffusion tensor tractography (DTT). An energy-based global tracking algorithm was used to calculate streamline counts (SC) and fractional anisotropy (FA) of cingulate, fornix, and mammillo-thalamic tracts, respectively. RESULTS: Sclerotic hippocampi were significantly smaller compared to the contralateral side and to age-matched controls. Cingulum SC but not FA were reduced on the hippocampal sclerosis (258+81.0) and contralateral side (271+85.6) compared to age-matched controls (447+138). CONCLUSION: Focusing on white matter tracts of the Papez circuit we showed that in patients with intractable temporal lobe epilepsy unilateral hippocampal sclerosis is associated with a bilateral reduction of cingulum association fibers projecting from the cingulate gyrus to the parahippocampal gyrus.

Determining the Orientation of Directional Deep Brain Stimulation Electrodes Using 3D Rotational Fluoroscopy.

BACKGROUND AND PURPOSE: New deep brain stimulation leads with electrode contacts that are split along their circumference allow steering of the electrical field in a predefined direction. However, imaging-assisted directional stimulation requires detailed knowledge of the exact orientation of the electrode array. The purpose of this study was to evaluate whether this information can be obtained by rotational 3D fluoroscopy. MATERIALS AND METHODS: Two directional leads were inserted into a 3D-printed plaster skull filled with gelatin. The torsion of the lead tip versus the lead at the burr-hole level was investigated. Then, 3 blinded raters evaluated 12 3D fluoroscopies with random lead orientations. They determined the lead orientation considering the x-ray marker only and considering the overlap of the gaps between the contact segments. Intraclass correlation coefficients and an extended version of the Bland-Altman plot were used to determine interrater reliability and agreement of the measurements of the different raters. RESULTS: Electrode torsion of up to 35° could be demonstrated. Evaluation of the lead rotation considering the x-ray marker only revealed limits of agreement of ±9.37° and an intraclass correlation coefficient of 0.9975. In addition, taking into account the lines resulting from overlapping of the gaps between the electrode segments, the limits of agreement to the mean were ±2.44° and an intraclass correlation coefficient of 0.9998. CONCLUSIONS: In directional deep brain stimulation systems, rotational 3D fluoroscopy combined with the described evaluation method allows for determining the exact orientation of the leads, enabling the full potential of imaging-assisted personalized programming.

[Idiopathic intracranial hypertension]. / Idiopathische intrakranielle Hypertension.

This review describes the clinical findings as well as thes diagnostic and therapeutic options for idiopathic intracranial hypertension (pseudotumor cerebri). Furthermore, the pathophysiological concepts are discussed. Idiopathic intracranial hypertension is characterized by signs and symptoms of raised intracranial pressure with no established pathogenesis. Common symptoms include headaches, visual loss and pulsatile tinnitus. Treatment has two major goals: the alleviation of headaches and the preservation of vision. Weight loss and acetazolamide are the cornerstones in the treatment of the disorder. Drainage of cerebrospinal fluid, optic nerve sheath fenestration and stent angioplasty of a sinus stenosis can be employed in severe cases.

Spinal diffusion tensor tractography for differentiation of intramedullary tumor-suspected lesions.

BACKGROUND AND PURPOSE: Primary MRI diagnosis of spinal intramedullary tumor-suspected lesions can be challenging and often requires spinal biopsy or resection with a substantial risk of neurological deficits. We evaluated whether Diffusion Tensor Imaging (DTI) tractography can facilitate the differential diagnosis. MATERIALS AND METHODS: Twenty-five consecutive patients with an intramedullary tumor-suspected lesion considered for spinal surgery were studied with a Diffusion-weighted multi-shot read out segmented EPI sequence (RESOLVE). White matter tracts ("streamlines") were calculated using the FACT algorithm and visually co-registered to a T2-weighted 3D sequence. The fused images were assessed concerning spinal streamline appearance as normal, displaced or terminated. Definite diagnosis was verified by histological analysis or further clinical work-up. RESULTS: All patients with normal appearing streamlines (n=6) showed an acute inflammatory demyelinating pathology in the further clinical work-up. In 10 patients streamline displacing lesions were found from which 5 patients underwent a surgical treatment with histologically confirmed low-grade tumors like ependymomas and pilocytic astrocytomas. In nine patients streamlines were terminated, from which 6 patients received a histology proven diagnoses with a more heterogenous spectrum (3 cases of high grade tumor, 1 case of low grade tumor with intralesional hemorrhage and 2 cases with gliosis but no tumor cells). CONCLUSION: Using multi-shot DTI spinal tractography acute inflammatory lesions can be differentiated from other tumorous intramedullary lesions. The entity diagnosis of spinal tumors seems to be more challenging, primarily due to the variety of factors like invasivity, expansion or intralesional hemorrhage.

Reliability of cerebral vein volume quantification based on susceptibility-weighted imaging.

INTRODUCTION: Susceptibility-weighted imaging (SWI) visualizes even small cerebral veins and might, therefore, be valuable in monitoring neurological diseases affecting cerebral veins. Since it is generally difficult to evaluate individual results of quantitative MRI measurements, an automatic approach would be highly appreciated to assist the diagnostic process. The aim of this study was to evaluate the rescan and reanalysis reliability using an automatic venous volumetric approach based on SWI in healthy controls. METHODS: SWI was performed in ten healthy controls undergoing MRI examinations using a 32-channel head coil at 3 T five times on five different days. To test for rescan and reanalysis variability, the deep cerebral vein volume was quantified using ANTs and SPM8. RESULTS: Total volumes of cerebral deep veins measured during five MRI scans in ten individuals (n = 50 scans) showed intra-individual volume changes ranging from 0.07 to 1.03 ml (mean variability = 10.2 %). Automatic reanalyses revealed exactly the same results in all scans. CONCLUSION: Automatic SWI-based cerebral vein volumetry shows acceptable rescan-and excellent reanalyses-reliability in healthy volunteers. Therefore, this approach might be beneficial in intra-individual follow-up studies of neurological diseases affecting the cerebral venous system.

Facing the Time Window in Acute Ischemic Stroke: The Infarct Core.

BACKGROUND: Increasing numbers needed to treat within the first hours after ischemic stroke onset indicate a strong time dependency of the viability of brain tissue. However, this time dependency is not reflected in recent randomized controlled trials of endovascular stroke treatment. This study evaluates whether and to which extent a time dependency exists in patients with embolic carotid T or M1 occlusions within the first 6 h of stroke onset. METHODS: Patient data were retrieved from the Freiburg stroke data bank. Time from onset to acquisition of the diffusion weighted images (DWIs) varied between 49 and 357 min. Ischemic lesions were semiautomatically segmented on apparent diffusion coefficient maps with a threshold of 600 × 10 (- 6) mm(2)/s. Occlusion location and thrombus length were determined with magnetic resonance angiography, T2*, and more recently susceptibility weighted image (SWI) sequences. A hyperintense vessel sign in FLAIR images as a possible surrogate for collaterals was also identified. RESULTS: A total of 155 patients with occlusions of the carotid T (n = 26), proximal M1 segment (n = 44), and distal M1 segment (n = 85) of the middle cerebral artery between 2011 and 2015 were included. Infarct volumes varied from 0.3 to 180.2 mL. Infarct size did not correlate with stroke onset to DWI times. Infarct volumes also did not associate with different locations of vessel occlusion, thrombus length, presence of the hyperintense vessel sign and initial infarct growth. CONCLUSION: We found no significant time dependency of the viability of brain tissue with embolic carotid T or M1 occlusions between 1 and 6 h after stroke onset. The early infarction volume is thus probably determined in the hyperacute phase by the quality of leptomeningeal collaterals and comparatively stable in this time period.

Microstructural effects of a neuro-modulating drug evaluated by diffusion tensor imaging.

In a longitudinal mouse study we evaluated whether diffusion tensor imaging (DTI) can monitor microstructural changes after administration of the neuromodulating drug EPO and whether erythropoietin (EPO) has an effect on cognitive performance. Twelve mice (2 groups with 6 mice each) were scanned in a 7T Bruker Biospin animal scanner with a highly resolved DTI sequence before and 16 days after intraperitoneal injections of EPO or saline. All mice underwent behavioral testing (Morris water maze) and histologic evaluation of hippocampal and corpus callosum cell proliferation and oligodendrogenesis. Whole brain DTI analysis showed significant Trace, RD and AD decrease within the dentate gyrus, subiculum, primary motor, somatosensory, and supplementary somatosensory areas and FA increase in the hippocampus, corpus callosum, and fimbria fornix in EPO treated mice only. ROI-based DTI analysis showed significant Trace and RD decrease and FA increase only in the corpus callosum of EPO treated mice, whereas in the dentate gyrus significant Trace, RD, and AD decrease occurred in both, EPO- and control-group. Behavioral tests showed that EPO treated mice performed better and learned faster than controls. Histologically, the number of BrdU-positive nuclei and optical density of DCX-labeled juvenile neurons significantly increased within the dentate gyrus, corpus callosum and fimbria fornix and the number of NG2-positive oligodendrocyte progenitors in corpus callosum and fimbria fornix, respectively. In conclusion we were able to monitor microstructural changes with DTI and showed EPO treatment-related alterations correlating with enhanced dentate gyrus and corpus callosum cell proliferation and better learning capabilities.

Tractography of Association Fibers Associated with Language Processing.

INTRODUCTION: Several major association fiber tracts are known to be part of the language processing system. There is evidence that high angular diffusion-based MRI is able to separate these fascicles in a constant way. In this study, we wanted to proof this thesis using a novel whole brain "global tracking" approach and to test for possible lateralization. METHODS: Global tracking was performed in six healthy right-handed volunteers for the arcuate fascicle (AF), the medial longitudinal fascicle (MdLF), the inferior fronto-occipital fascicle (IFOF), and the inferior longitudinal fascicle (ILF). These fiber tracts were characterized quantitatively using the number of streamlines (SL) and the mean fractional anisotropy (FA). RESULTS: We were able to characterize the AF, the MdLF, the IFOF, and the ILF consistently in six healthy volunteers using global tracking. A left-sided dominance (LI > 0.2) for the AF was found in all participants. The MdLF showed a left-sided dominance in four participants (one female, three male). Regarding the FA, no lateralization (LI > 0.2) could be shown in any of the fascicles. CONCLUSION: Using a novel global tracking algorithm we confirmed that the courses of the primary language processing associated fascicles can consistently be differentiated. Additionally we were able to show a streamline-based left-sided lateralization in the AF of all right-handed healthy subjects.

Presurgical MR Imaging in Epilepsy.

Primary goal of magnetic resonance imaging in epilepsy patients is to detect epileptogenic lesions with small lesions best detectable on a 3D FLAIR SPACE sequence with 1 mm(3) voxels. Morphometric analysis of 3D T1-weighted data sets helps to find subtle lesions and may reveal the true extent of a lesion. In further presurgical work-up, language lateralization and spatial relationship of epileptogenic lesions to eloquent cortex and white matter tracts must be evaluated. With clear left lateralization language, fMRI is sufficient; in atypical lateralizations, Wada test and electrical stimulation mapping may be added. Primary motor cortex and corticospinal tract on one and visual cortex and optic radiation on the other side are displayed with fMRI and diffusion tensor tractography. For the corticospinal tract a "global" tracking algorithm, for the optic radiation including Meyer' loop, which may be damaged in anterior temporal lobe resections, a probabilistic algorithm is best suited.