Multiparametric prenatal imaging characterization of fetal brain edema in Chiari II malformation might help to select candidates for fetal surgery.

OBJECTIVE: To identify brain edema in fetuses with Chiari II malformation using a multiparametric approach including structural T2-weighted, diffusion tensor imaging (DTI) metrics, and MRI-based radiomics. METHODS: A single-center retrospective review of MRI scans obtained in fetuses with Chiari II was performed. Brain edema cases were radiologically identified using the following MR criteria: brain parenchymal T2 prolongation, blurring of lamination, and effacement of external CSF spaces. Fractional anisotropy (FA) values were calculated from regions of interest (ROI), including hemispheric parenchyma, internal capsule, and corticospinal tract, and compared group-wise. After 1:1 age matching and manual single-slice 2D segmentation of the fetal brain parenchyma using ITK-Snap, radiomics features were extracted using pyradiomics. Areas under the curve (AUCs) of the features regarding discriminating subgroups were calculated. RESULTS: Ninety-one fetuses with Chiari II underwent a total of 101 MRI scans at a median gestational age of 24.4 weeks and were included. Fifty scans were visually classified as Chiari II with brain edema group and showed significantly reduced external CSF spaces compared to the nonedema group (9.8 vs. 18.3 mm, p < 0.001). FA values of all used ROIs were elevated in the edema group (p < 0.001 for all ROIs). The 10 most important radiomics features showed an AUC of 0.81 (95%CI: 0.71, 0.91) for discriminating between Chiari II fetuses with and without edema. CONCLUSIONS: Brain edema in fetuses with Chiari II is common and radiologically detectable on T2-weighted fetal MRI sequences, and DTI-based FA values and radiomics features provide further evidence of microstructure differences between subgroups with and without edema. CLINICAL RELEVANCE STATEMENT: A more severe phenotype of fetuses with Chiari II malformation is characterized by prenatal brain edema and more postnatal clinical morbidity and disability. Fetal brain edema is a promising prenatal MR imaging biomarker candidate for optimizing the risk-benefit evaluation of selection for fetal surgery. KEY POINTS: Brain edema of fetuses prenatally diagnosed with Chiari II malformation is a common, so far unknown, association. DTI metrics and radiomics confirm microstructural differences between the brains of Chiari II fetuses with and without edema. Fetal brain edema may explain worse motor outcomes in this Chiari II subgroup, who may substantially benefit from fetal surgery.

Perceptual sequence learning is more severely impaired than motor sequence learning in patients with chronic cerebellar stroke.

Patients with cerebellar stroke are impaired in procedural learning. Several different learning mechanisms contribute to procedural learning in healthy individuals. The aim was to compare the relative share of different learning mechanisms in patients and healthy controls. Ten patients with cerebellar stroke and 12 healthy controls practiced a visuomotor serial reaction time task. Learning blocks with high stimulus-response compatibility were exercised repeatedly; in between these, participants performed test blocks with the same or a different (mirror-inverted or unrelated) stimulus sequence and/or the same or a different (mirror-inverted) stimulus-response allocation. This design allowed to measure the impact of motor learning and perceptual learning independently and to separate both mechanisms from the learning of stimulus-response pairs. Analysis of the learning blocks showed that, as expected, both patients and controls improved their performance over time, although patients remained significantly slower. Analysis of the test blocks revealed that controls showed significant motor learning as well as significant visual perceptual learning, whereas cerebellar patients showed only significant motor learning. Healthy participants were able to use perceptual information for procedural learning even when the rule linking stimuli and responses had been changed, whereas patients with cerebellar lesions could not recruit this perception-based mechanism. Therefore, the cerebellum appears involved in the accurate processing of perceptual information independent from prelearned stimulus-response mappings.

Transitory ischemic attack associated with a rare fenestration of the cervical segment of the internal carotid artery: a case report.

BACKGROUND: Fenestration of the cervical segment of the internal carotid artery is a very rare finding, and its origin is still not fully understood. Explanations of its genesis range from dissections leading to the fenestration to the more common interpretation as a developmental vascular variant. However, most reported cases were symptomatic and presented with dissections, where even endovascular treatment of the fenestration of the cervical segment of the internal carotid artery became necessary. Here we report a case of a fenestration of the cervical segment of the internal carotid artery suffering a transitory ischemic attack and local pain in absence of any sign of dissection. CASE PRESENTATION: A 62-year-old Caucasian male patient was admitted to our institution because of an episode of amaurosis fugax, initially accompanied with headache. Magnetic resonance imaging revealed an intact fenestration of the cervical segment of the internal carotid artery on the symptomatic side. With antiplatelet therapy, all symptoms vanished within 2 months of the initial event. CONCLUSIONS: Our findings support the interpretation of a fenestration of the cervical segment of the internal carotid artery as a developmental vascular variant, but also suggest a substantial risk for dissection and ischemic stroke. Even in case of an accidental finding, clinicians should be aware of this. At least in this case, antiplatelet therapy seemed beneficial.

Flow dynamics in acute ischemic stroke due to embolic occlusion of a fetal posterior cerebral artery treated with endovascular thrombectomy - report of two cases.

The fetal variant of the posterior cerebral artery (fPCA) conserves a major blood flow from the anterior to the posterior cerebral circulation via a strong persistent caudal portion of the embryonic internal carotid artery. We present two cases where endovascular treatment in acute ischemic stroke was complicated by this flow diversion. Though direct thrombectomy of the fPCA using a stent retriever was feasible and successful in both cases outcome remained unfavourable due to a continuous redirection of embolic material into the posterior circulation. Knowledge of flow dynamics in a fPCA is important for endovascular treatment in acute ischemic stroke.

MOG antibody associated disease (MOGAD) presenting with extensive brain stem encephalitis: A case report.

Background: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a relatively new entity of demyelinating diseases, clinically presenting with optic neuritis, transverse myelitis, or encephalic symptoms. Typical radiological features include demyelinating cerebral and spinal lesions, cortical involvement, leptomeningeal enhancement, or tumefactive lesions. Here we present a rare case of a young patient with extensive brain stem lesion on the MRI while exhibiting nystagmus, singultus and somnolence. Case presentation: A 30-year-old male patient presented initially with fever and impaired consciousness, but furthermore developed nystagmus, singultus and tetraparesis during the following week. Repeated MRI examinations revealed extensive brain stem edema with notable bilateral affection of the cerebellar peduncles and the pons. Antiviral and antibiotic treatment was changed to intravenous corticosteroids and immunoglobulins as soon as the diagnosis of MOGAD was established by testing serum and cerebrospinal fluid positive for MOG specific antibodies. MRI alterations vanished completely over time with a delayed, nearly complete clinical recovery of our patient. Conclusion: Brain stem affection in MOGAD is rare. However, in patients presenting with an unclear brain stem encephalitis the possibility of MOGAD should be considered and tested using MOG antibodies. In case of a positive testing treatment with steroids and immunoglobulins seems recommendable.

Reversible cytotoxic oedema in the splenium of the corpus callosum related to tetracycline therapy.

We report a symptomatic girl with reversible circumscribed cytotoxic oedema in the splenium of the corpus callosum (CC) that occurred, to our knowledge, for the first time in relation to tetracycline treatment. After stopping tetracycline therapy the girl recovered completely and the CC lesion, clearly visible on diffusion-weighted MR imaging (DWI), disappeared. Reversible circumscribed cytotoxic oedema (CCO) of the splenium of the CC is a well-defined entity that is found to be associated with administration of antiepileptic drugs, alterations in therapy using arginin-vasopressin and metronidazole or infections with influenza and rotavirus. CCO of splenium of the CC is clearly visible on DWI, shows no enhancement after administration of contrast medium and is completely reversible in most cases.

Disparity of time-contrast curves generated by various types of power injectors used in magnetic resonance imaging.

The profiles of time-contrast (TC) -curves from popular MRI injectors derived at the injection site of the attached tube-line system were compared. Variations of TC-profiles were previously reported to potentially influence image quality in time critical MRI measurements. TC-curves from five injectors obtained during commonly used injection protocols were assessed according to representative quality criteria: (1) correlation strength between a fitted boxcar function and the TC-curve (cBCF) and (2) difference between true and expected injection time (dBIT). Additionally, the impact from technical injector properties: pump type, line volume, maximum injection power and type of contrast medium (CM) on the TC-profiles was evaluated. Injectors using a piston-syrinx (PS) mechanism for CM-injection performed significantly better than those working with a peristaltic roller pump (RP) technique. Besides injection mechanism, line filling volume showed a strong influence on the final TC-curves, where larger filling volumes induced worse cBCF- and dBIT-results. Therefore, to achieve an optimal bolus in clinical MRI use of a PS-injector seems recommendable. Besides their pump mechanism, RP-injectors appeared additionally hampered by their high volume line systems, pointing out an unfavourable coinicidence of these technical features in RP-injectors. This should be considered, particularly, in comparative or time-critical MRI-studies.

Glucocorticoids in the treatment of children with acute lymphoblastic leukemia and hodgkin's disease: a pilot study on the adverse psychological reactions and possible associations with neurobiological, endocrine, and genetic markers.

PURPOSE: We did a controlled study to assess adverse psychological reactions (APR) associated with high-dose glucocorticoid therapy and tried to detect somatic correlates for the observed reactions. PATIENTS AND METHODS: Our study included 37 patients with acute lymphoblastic leukemia (ALL) and 11 patients with Morbus Hodgkin (MH) disease, who were treated with high-dose glucocorticoid therapy, and 26 control patients with other types of malignancies. APRs were assessed with a standardized measure via parent-report. Patients with ALL and MH were further analyzed for signs of neuronal cell death in the cerebrospinal fluid, polymorphisms of the glucocorticoid receptor gene, as well as cortisol, adrenocorticorticotropic hormone, and dehydroepiandrosterone sulfate blood levels. RESULTS: Fifty-four percent of ALL, 36% of MH, and 23% of control patients developed APR in the first few weeks of therapy. Approximately 3.5 months later, the majority of patients with ALL showed no APR, similar to control patients. Patients demonstrating a higher, nonsuppressible secretion of cortisol and/or adrenocorticorticotropic hormone during glucocorticoid therapy were found to be more likely to develop APR. No sign of neuronal cell destruction and no correlation of APR with specific glucocorticoid receptor polymorphisms were found. CONCLUSION: Our results suggest that the development of APR due to glucocorticoid therapy is measurable and correlates with hormonal reaction patterns.

A Quantitative Comparison of Clinically Employed Parameters in the Assessment of Acute Cerebral Ischemia Using Dynamic Susceptibility Contrast Magnetic Resonance Imaging.

Purpose: Perfusion magnetic resonance imaging (P-MRI) is part of the mismatch concept employed for therapy decisions in acute ischemic stroke. Using dynamic susceptibility contrast (DSC) MRI the time-to-maximum (Tmax) parameter is quite popular, but its inconsistently defined computation, arterial input function (AIF) selection, and the applied deconvolution method may introduce bias into the assessment. Alternatively, parameter free methods, namely, standardized time-to-peak (stdTTP), zf-score, and standardized-zf (stdZ) are also available, offering consistent calculation procedures without the need of an AIF or deconvolution. Methods: Tmax was compared to stdTTP, zf-, and stdZ to evaluate robustness of infarct volume estimation in 66 patients, using data from two different sites and MR systems (i.e., 1.5T vs. 3T; short TR (= 689 ms) vs. medium TR (= 1,390 ms); bolus dose 0.1 or 0.2 ml/kgBW, respectively). Results: Quality factors (QF) for Tmax were 0.54 ± 0.18 (sensitivity), 0.90 ± 0.06 (specificity), and 0.87 ± 0.05 (accuracy). Though not significantly different, best specificity (0.93 ± 0.05) and accuracy (0.90 ± 0.04) were found for stdTTP with a sensitivity of 0.56 ± 0.17. Other tested parameters performed not significantly worse than Tmax and stdTTP, but absolute values of QFs were slightly lower, except for zf showing the highest sensitivity (0.72 ± 0.16). Accordingly, in ROC-analysis testing the parameter performance to predict the final infarct volume, stdTTP and zf showed the best performance. The odds for stdTTP to obtain the best prediction of the final infarct size, was 6.42 times higher compared to all other parameters (odds-ratio test; p = 2.2*10-16). Conclusion: Based on our results, we suggest to reanalyze data from large cohort studies using the parameters presented here, particularly stdTTP and zf-score, to further increase consistency of perfusion assessment in acute ischemic stroke.

Normalised time-to-peak-distribution curves correlate with cerebral white matter hyperintensities - Could this improve early diagnosis?

Parameter-free assessment of the time-to-peak (TTP) histogram, termed 'TTP-distribution curve' (TDC), of dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) was introduced as a robust method to evaluate cerebral perfusion. TDC-assessment works fully automatically without the need of an arterial input function, thereby providing full comparability between different measurements. In the investigated sample of 106 patients, a strong dependency of TDC on the hemodynamic state of cerebral microvessels and the arterio-venous bolus-transit time [Formula: see text] was demonstrated. Accordingly, TDC-derived [Formula: see text] was 3.3-3.7 s for control patients and 4.4 s for cerebral small vessel disease patients. Measurements of associated bolus spread velocities ν and accelerations [Formula: see text] additionally revealed a direct effect from spin-spin relaxation time T2-weighted white matter hyperintensity volume, considered to indicate microangiopathy in cerebral small vessel disease, on the TDC-measurements. This strongly supports the prevailing hypothesis that cerebral small vessel disease directly influences DSC-measurements, where the degree could be estimated from an analysis of TDC. While this may be used to correct DSC-parameters for undesirable effects from cerebral small vessel disease, it could also serve to potentially identify patients at risk for cerebral small vessel disease at an early stage, since a subset of patients without yet significant WHM-volume, but clearly altered hemodynamics in TDC-measurements, was identified in this study.

Protoneus-sequence: extended fluid-attenuated inversion recovery MR imaging without and with contrast enhancement.

Fluid-attenuated inversion recovery imaging (=flair imaging) is widely used as primary screening sequence in various investigation protocols, due to its high lesion contrast and sensitivity in detection of parenchymatous and leptomeningeal disease. An additional increase of sensitivity for detection of lesions may be achieved by contrast-enhanced flair imaging. Based on flair imaging a dual-echo inversion recovery imaging sequence (=proton echo usage [=protoneus] - sequence) was developed, which could significantly extend the possibilities of conventional flair imaging.

Big Data Approaches for the Analysis of Large-Scale fMRI Data Using Apache Spark and GPU Processing: A Demonstration on Resting-State fMRI Data from the Human Connectome Project.

Technologies for scalable analysis of very large datasets have emerged in the domain of internet computing, but are still rarely used in neuroimaging despite the existence of data and research questions in need of efficient computation tools especially in fMRI. In this work, we present software tools for the application of Apache Spark and Graphics Processing Units (GPUs) to neuroimaging datasets, in particular providing distributed file input for 4D NIfTI fMRI datasets in Scala for use in an Apache Spark environment. Examples for using this Big Data platform in graph analysis of fMRI datasets are shown to illustrate how processing pipelines employing it can be developed. With more tools for the convenient integration of neuroimaging file formats and typical processing steps, big data technologies could find wider endorsement in the community, leading to a range of potentially useful applications especially in view of the current collaborative creation of a wealth of large data repositories including thousands of individual fMRI datasets.

Identification of Voxels Confounded by Venous Signals Using Resting-State fMRI Functional Connectivity Graph Community Identification.

Identifying venous voxels in fMRI datasets is important to increase the specificity of fMRI analyses to microvasculature in the vicinity of the neural processes triggering the BOLD response. This is, however, difficult to achieve in particular in typical studies where magnitude images of BOLD EPI are the only data available. In this study, voxelwise functional connectivity graphs were computed on minimally preprocessed low TR (333 ms) multiband resting-state fMRI data, using both high positive and negative correlations to define edges between nodes (voxels). A high correlation threshold for binarization ensures that most edges in the resulting sparse graph reflect the high coherence of signals in medium to large veins. Graph clustering based on the optimization of modularity was then employed to identify clusters of coherent voxels in this graph, and all clusters of 50 or more voxels were then interpreted as corresponding to medium to large veins. Indeed, a comparison with SWI reveals that 75.6±5.9% of voxels within these large clusters overlap with veins visible in the SWI image or lie outside the brain parenchyma. Some of the remaining differences between the two modalities can be explained by imperfect alignment or geometric distortions between the two images. Overall, the graph clustering based method for identifying venous voxels has a high specificity as well as the additional advantages of being computed in the same voxel grid as the fMRI dataset itself and not needing any additional data beyond what is usually acquired (and exported) in standard fMRI experiments.

fMRI measurements of amygdala activation are confounded by stimulus correlated signal fluctuation in nearby veins draining distant brain regions.

Imaging the amygdala with functional MRI is confounded by multiple averse factors, notably signal dropouts due to magnetic inhomogeneity and low signal-to-noise ratio, making it difficult to obtain consistent activation patterns in this region. However, even when consistent signal changes are identified, they are likely to be due to nearby vessels, most notably the basal vein of rosenthal (BVR). Using an accelerated fMRI sequence with a high temporal resolution (TR = 333 ms) combined with susceptibility-weighted imaging, we show how signal changes in the amygdala region can be related to a venous origin. This finding is confirmed here in both a conventional fMRI dataset (TR = 2000 ms) as well as in information of meta-analyses, implying that "amygdala activations" reported in typical fMRI studies are likely confounded by signals originating in the BVR rather than in the amygdala itself, thus raising concerns about many conclusions on the functioning of the amygdala that rely on fMRI evidence alone.

Abciximab reduces monocyte tissue factor in carotid angioplasty and stenting.

BACKGROUND AND PURPOSE: Abciximab, a nonselective glycoprotein IIb/IIIa inhibitor, was shown to reduce peri-interventional stroke rate in carotid stenting. We evaluated the effect of adjunct abciximab therapy on monocyte-platelet cross talk and neurological deficit in unprotected carotid stenting and compared its efficacy with distal filter protection. METHODS: Fifty patients were randomized to either standard antithrombotic therapy (n=30) consisting of aspirin, clopidogrel, and heparin or adjunct bolus (0.25 mg/kg) and 12-hour infusion (0.125 microg x kg(-1) x min(-1)) of abciximab (n=20). A third cohort of patients was stented with filter protection (n=30). Monocyte-platelet aggregate formation and monocyte tissue factor expression were determined by whole blood flow cytometry, and F1.2 generation and soluble CD40 ligand (sCD40L) were determined by immunoassay. RESULTS: The incidence of peri-interventional ischemic episodes (23% versus 10%; P=0.2) and the number of de novo ischemic lesions detected by diffusion-weighted MRI (47% versus 30%; P=0.17) were not significantly different between standard antithrombotic therapy and adjunct abciximab but were reduced with filter protection (P=0.023). However, the number of transient ischemic attacks was lower (P=0.05) and the National Institutes of Health Stroke Score rapidly decreased in patients with adjunct abciximab. This clinical improvement was paralleled by a reduction in the postinterventional percentage of activated monocyte-platelet aggregates (CD62P+/CD14+; P=0.018) and the number of tissue factor-positive monocytes (TF+/CD14+; P=0.005). Both abciximab and filter protection suppressed F1.2 generation and significantly reduced sCD40L. CONCLUSIONS: Abciximab limits thrombus propagation and thrombus stabilization after carotid stenting by reducing monocyte-platelet cross talk and sCD40L. Although abciximab seems inferior to filter devices in peri-interventional cerebral protection, it may be considered in patients who do not allow placement of protection devices.

Standardized time to peak in ischemic and regular cerebral tissue measured with perfusion MR imaging.

BACKGROUND AND PURPOSE: Standardized time to peak (stdTTP) enables a quick quantification of time to peak measurements. An stdTTP /=7 seconds indicates critically perfused tissue. We verified this stdTTP in acute ischemia (within the first 6 hours after the onset of symptoms), when perfusion is critical, and after 24-72 hours. METHODS: Combined diffusion-weighted imaging (DWI) and perfusion MR imaging was performed in 20 consecutive patients with acute cerebral ischemia. Distributions of stdTTP >/=7 and /=7 seconds. StdTTP of about 80% of voxels was /=7 seconds and resulting infarct (r(2)=0.86). CONCLUSION: StdTTP is reciprocal in regions with and without ischemic injury. An stdTTP >/=7 seconds (regular range) is strongly correlated with resulting infarct and reflects critical perfusion with a high probability of ischemic tissue injury in acute ischemia, whereas this is unlikely in regions with stdTTP

Successful revascularization of acute carotid stent thrombosis by facilitated thrombolysis.

A 64-year-old woman undergoing protected carotid artery stent placement developed acute stent thrombosis despite pretreatment with combined antiplatelet therapy. A reduced dose of recombinant tissue plasminogen activator and a half-dose bolus of abciximab were administered intra-arterially via superselective catherization followed by systemic intravenous infusion of abciximab for 12 hours. Control angiography showed complete restoration of blood flow paralleled by neurologic improvement.

Improved quantification of cerebral hemodynamics using individualized time thresholds for assessment of peak enhancement parameters derived from dynamic susceptibility contrast enhanced magnetic resonance imaging.

PURPOSE: Assessment of cerebral ischemia often employs dynamic susceptibility contrast enhanced magnetic resonance imaging (DSC-MRI) with evaluation of various peak enhancement time parameters. All of these parameters use a single time threshold to judge the maximum tolerable peak enhancement delay that is supposed to reliably differentiate sufficient from critical perfusion. As the validity of this single threshold approach still remains unclear, in this study, (1) the definition of a threshold on an individual patient-basis, nevertheless (2) preserving the comparability of the data, was investigated. METHODS: The histogram of time-to-peak (TTP) values derived from DSC-MRI, the so-called TTP-distribution curve (TDC), was modeled using a double-Gaussian model in 61 patients without severe cerebrovascular disease. Particular model-based zf-scores were used to describe the arterial, parenchymal and venous bolus-transit phase as time intervals Ia,p,v. Their durations (delta Ia,p,v), were then considered as maximum TTP-delays of each phase. RESULTS: Mean-R2 for the model-fit was 0.967. Based on the generic zf-scores the proposed bolus transit phases could be differentiated. The Ip-interval reliably depicted the parenchymal bolus-transit phase with durations of 3.4 s-10.1 s (median = 4.3s), where an increase with age was noted (∼30 ms/year). CONCLUSION: Individual threshold-adjustment seems rational since regular bolus-transit durations in brain parenchyma obtained from the TDC overlap considerably with recommended critical TTP-thresholds of 4 s-8 s. The parenchymal transit time derived from the proposed model may be utilized to individually correct TTP-thresholds, thereby potentially improving the detection of critical perfusion.

Scanning fast and slow: current limitations of 3 Tesla functional MRI and future potential.

Functional MRI at 3T has become a workhorse for the neurosciences, e.g., neurology, psychology, and psychiatry, enabling non-invasive investigation of brain function and connectivity. However, BOLD-based fMRI is a rather indirect measure of brain function, confounded by physiology related signals, e.g., head or brain motion, brain pulsation, blood flow, intermixed with susceptibility differences close or distant to the region of neuronal activity. Even though a plethora of preprocessing strategies have been published to address these confounds, their efficiency is still under discussion. In particular, physiological signal fluctuations closely related to brain supply may mask BOLD signal changes related to "true" neuronal activation. Here we explore recent technical and methodological advancements aimed at disentangling the various components, employing fast multiband vs. standard EPI, in combination with fast temporal ICA. Our preliminary results indicate that fast (TR <0.5 s) scanning may help to identify and eliminate physiologic components, increasing tSNR and functional contrast. In addition, biological variability can be studied and task performance better correlated to other measures. This should increase specificity and reliability in fMRI studies. Furthermore, physiological signal changes during scanning may then be recognized as a source of information rather than a nuisance. As we are currently still undersampling the complexity of the brain, even at a rather coarse macroscopic level, we should be very cautious in the interpretation of neuroscientific findings, in particular when comparing different groups (e.g., age, sex, medication, pathology, etc.). From a technical point of view our goal should be to sample brain activity at layer specific resolution with low TR, covering as much of the brain as possible without violating SAR limits. We hope to stimulate discussion toward a better understanding and a more quantitative use of fMRI.