Glioneuronal tumors (GNTs) are an expanding group of primary CNS neoplasms, commonly affecting children, adolescents and young adults. Most GNTs are relatively indolent, low-grade, WHO grade I ...lesions. In the pediatric age group, GNTs have their epicenter in the cerebral cortex and present with seizures. Alterations in the mitogen-activated protein kinase (MAPK) pathway, which regulates cell growth, are implicated in tumorigenesis. Imaging not only plays a key role in the characterization and pre-surgical evaluation of GNTs but is also crucial role in follow-up, especially with the increasing use of targeted inhibitors and immunotherapies. In this chapter, we review the clinical and imaging perspectives of common pediatric GNTs.Glioneuronal tumors (GNTs) are an expanding group of primary CNS neoplasms, commonly affecting children, adolescents and young adults. Most GNTs are relatively indolent, low-grade, WHO grade I lesions. In the pediatric age group, GNTs have their epicenter in the cerebral cortex and present with seizures. Alterations in the mitogen-activated protein kinase (MAPK) pathway, which regulates cell growth, are implicated in tumorigenesis. Imaging not only plays a key role in the characterization and pre-surgical evaluation of GNTs but is also crucial role in follow-up, especially with the increasing use of targeted inhibitors and immunotherapies. In this chapter, we review the clinical and imaging perspectives of common pediatric GNTs.
non-invasive verification of endolymphatic hydrops (ELH) by means of intravenous delayed gadolinium (Gd) enhanced magnetic resonance imaging of the inner ear (iMRI) is rapidly developing into a ...standard clinical tool to investigate peripheral vestibulo-cochlear syndromes. In this context, methodological comparative studies providing standardization and comparability between labs seem even more important, but so far very few are available. One hundred eight participants 75 patients with Meniere's disease (MD; 55.2 ± 14.9 years) and 33 vestibular healthy controls (HC; 46.4 ± 15.6 years) were examined. The aim was to understand (i) how variations in acquisition protocols influence endolymphatic space (ELS) MR-signals; (ii) how ELS quantification methods correlate to each other or clinical data; and finally, (iii) how ELS extent influences MR-signals. Diagnostics included neuro-otological assessment, video-oculography during caloric stimulation, head-impulse test, audiometry, and iMRI. Data analysis provided semi-quantitative (SQ) visual grading and automatic algorithmic quantitative segmentation of ELS area 2D, mm
and volume 3D, mm
using deep learning-based segmentation and volumetric local thresholding. Within the range of 0.1-0.2 mmol/kg Gd dosage and a 4 h ± 30 min time delay, SQ grading and 2D- or 3D-quantifications were independent of signal intensity (SI) and signal-to-noise ratio (SNR; FWE corrected,
< 0.05). The ELS quantification methods used were highly reproducible across raters or thresholds and correlated strongly (0.3-0.8). However, 3D-quantifications showed the least variability. Asymmetry indices and normalized ELH proved the most useful for predicting quantitative clinical data. ELH size influenced SI (cochlear basal turn
< 0.001), but not SNR. SI could not predict the presence of ELH. In conclusion, (1) Gd dosage of 0.1-0.2 mmol/kg after 4 h ± 30 min time delay suffices for ELS quantification. (2) A consensus is needed on a clinical SQ grading classification including a standardized level of evaluation reconstructed to anatomical fixpoints. (3) 3D-quantification methods of the ELS are best suited for correlations with clinical variables and should include both ears and ELS values reported relative or normalized to size. (4) The presence of ELH increases signal intensity in the basal cochlear turn weakly, but cannot predict the presence of ELH.
Abstract
Hippocampal formation (HF) volume loss is a well-established finding in schizophrenia, with select subfields, such as the cornu ammonis and dentate gyrus, being particularly vulnerable. ...These morphologic alterations are related to functional abnormalities and cognitive deficits, which are at the core of the insufficient recovery frequently seen in this illness. To counteract HF volume decline, exercise to improve aerobic fitness is considered as a promising intervention. However, the effects of aerobic fitness levels on HF subfields are not yet established in individuals with schizophrenia. Therefore, our study investigated potential associations between aerobic fitness and HF subfield structure, functional connectivity, and related cognitive impact in a multiparametric research design. In this cross-sectional study, 53 participants diagnosed with schizophrenia (33 men, 20 women; mean SD age, 37.4 11.8 years) underwent brain structural and functional magnetic resonance imaging and assessments of aerobic fitness and verbal memory. Multivariate multiple linear regressions were performed to determine whether aerobic fitness was associated with HF subfield volumes and functional connections. In addition, we explored whether identified associations mediated verbal memory functioning. Significant positive associations between aerobic fitness levels and volumes were demonstrated for most HF subfields, with the strongest associations for the cornu ammonis, dentate gyrus, and subiculum. No significant associations were found for HF functional connectivity or mediation effects on verbal memory. Aerobic fitness may mitigate HF volume loss, especially in the subfields most affected in schizophrenia. This finding should be further investigated in longitudinal studies.
Clinical Trials Registration: The study on which the manuscript is based was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number:
NCT03466112
) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).
Recurrent mutations in chromatin modifiers are specifically prevalent in adolescent or adult patients with Sonic hedgehog-associated medulloblastoma (SHH MB). Here, we report that mutations in the ...acetyltransferase CREBBP have opposing effects during the development of the cerebellum, the primary site of origin of SHH MB. Our data reveal that loss of Crebbp in cerebellar granule neuron progenitors (GNPs) during embryonic development of mice compromises GNP development, in part by downregulation of brain-derived neurotrophic factor (Bdnf). Interestingly, concomitant cerebellar hypoplasia was also observed in patients with Rubinstein-Taybi syndrome, a congenital disorder caused by germline mutations of CREBBP. By contrast, loss of Crebbp in GNPs during postnatal development synergizes with oncogenic activation of SHH signaling to drive MB growth, thereby explaining the enrichment of somatic CREBBP mutations in SHH MB of adult patients. Together, our data provide insights into time-sensitive consequences of CREBBP mutations and corresponding associations with human diseases.
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•CREBBP mutations in human medulloblastoma deplete acetyltransferase activity•Crebbp mutations exert opposing effects during cerebellar development•Embryonal loss of Crebbp impairs normal cerebellar development•Postnatal loss of Crebbp synergizes with Shh to drive growth of medulloblastoma
Merk et al. show that the developmental time frame of CREBBP mutation acquisition in cerebellar granule neurons determines the pathogenic effect of these alterations in the cerebellum. These time-sensitive consequences explain phenotypic differences seen in patients with germline (Rubinstein-Taybi syndrome) or somatic mutations (adult SHH medulloblastoma) of CREBBP.
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•MRI is the modality of choice to image and quantify cerebral perfusion.•Imaging of neonatal brain perfusion is possible using MRI and ultrasound.•Novel ultrafast ultrasound imaging ...allows for excellent spatiotemporal resolution.•Understanding cerebral hemodynamic changes of neonatal adaptation is key.
Abnormal variations of the neonatal brain perfusion can result in long-term neurodevelopmental consequences and cerebral perfusion imaging can play an important role in diagnostic and therapeutic decision-making. To identify at-risk situations, perfusion imaging of the neonatal brain must accurately evaluate both regional and global perfusion. To date, neonatal cerebral perfusion assessment remains challenging. The available modalities such as magnetic resonance imaging (MRI), ultrasound imaging, computed tomography (CT), near-infrared spectroscopy or nuclear imaging have multiple compromises and limitations. Several promising methods are being developed to achieve better diagnostic accuracy and higher robustness, in particular using advanced MRI and ultrasound techniques.
The objective of this state-of-the-art review is to analyze the methodology and challenges of neonatal brain perfusion imaging, to describe the currently available modalities, and to outline future perspectives.
Crossed cerebellar diaschisis (CCD) is the phenomenon of hypoperfusion and hypometabolism of the contralateral cerebellar hemisphere caused by dysfunction of the related supratentorial region. Our ...aim was to analyze its influence on morphologic and functional outcome in acute ischemic stroke. Subjects with stroke caused by a large vessel occlusion of the anterior circulation were selected from an initial cohort of 1644 consecutive patients who underwent multiparametric CT including whole-brain CT perfusion. Two experienced readers evaluated the posterior fossa in terms of CCD absence (CCD−) or presence (CCD+). A total of 156 patients formed the study cohort with 102 patients (65.4%) categorized as CCD− and 54 (34.6%) as CCD+. In linear and logistic regression analyses, no significant association between CCD and final infarction volume (β = −0.440, p = 0.972), discharge mRS ≤ 2 (OR = 1.897, p = 0.320), or 90-day mRS ≤ 2 (OR = 0.531, p = 0.492) was detected. CCD+ patients had larger supratentorial cerebral blood flow deficits (median: 164 ml vs. 115 ml; p = 0.001) compared to CCD−patients. Regarding complications, CCD was associated with a higher rate of parenchymal hematomas (OR = 4.793, p = 0.035). In conclusion, CCD is frequently encountered in acute ischemic stroke caused by large vessel occlusion of the anterior circulation. CCD was associated with the occurrence of parenchymal hematoma in the ipsilateral cerebral infarction but did not prove to significantly influence patient outcome.
To investigate image quality and vascular delineation of multi-detector row computed tomographic (CT) angiography at various kilovoltage settings.
Thirty patients were investigated with a ...standardized CT protocol, with three groups of 10 consecutive patients examined at 80, 120, and 140 kV, respectively. Three blinded readers independently evaluated images and graded image quality parameters, diagnostic confidence, and vascular delineation of intracranial arteries and veins. Vascular CT attenuation values, CT dose indices, and dose length products were assessed quantitatively. For data analysis, a Kruskal-Wallis nonparametric rank F test was used to identify trends and variables that required modeling attention. A proportional odds multinomial regression model was then fit with generalized estimating equations to account for the correlated nature of the data.
Image quality was rated higher with higher kilovoltage settings (P <.001). The severity of imaging artifacts was higher with lower kilovoltage settings (P <.001), while the subjectively rated vessel contrast was lower in the 80-kV group than in the 120-kV group and the 140-kV group (P <.05). Diagnostic confidence was higher in the 120-kV group and 140-kV group (P <.005). Vascular delineation was higher with higher kilovoltage settings for most arterial and venous structures. Differences were more significant for structures in close topographic proximity to bone and for subsegmental arteries and were less significant and, in parts, not significant for the main arterial branches and the large venous sinus. Attenuation values were higher with lower kilovoltage settings (P <.05). The mean dose length product could be reduced from 594 mGy. cm in the 140-kV group to 152 mGy.cm in the 80-kV group.
This multireader study of image quality and vessel delineation with cranial multi-detector row CT angiography at various kilovoltage settings demonstrated a superiority of higher voltages with most pronounced effects for vessels adjacent to bone and subsegmental arteries.
Fetal MR imaging is subject to artifacts including motion, chemical shift, and radiofrequency artifacts. Currently, such artifacts are detected by the MRI operator, a process which is subjective, ...time consuming, and prone to errors. We propose a novel algorithm, RISE-Net, that can consistently, automatically, and objectively detect artifacts in 3D fetal MRI. It makes use of a CNN ensemble approach where the first CNN aims to identify and classify any artifacts in the image, and the second CNN uses regression to determine the severity of the detected artifacts. The main mechanism in RISE-Net is the stacked Residual, Inception, Squeeze and Excitation (RISE) blocks. This classification network achieved an accuracy of 90.34% and a F1 score of 90.39% and outperformed other state-of-the-art architectures, such as VGG-16, Inception, ResNet-50, ReNet-Inception, SE-ResNet, and SE-Inception. The severity regression network had an MSE of 0.083 across all classes. The presented algorithm facilitates rapid and accurate fetal MRI quality assurance that can be implemented into clinical use.
Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) has been widely applied in cognitive neurosciences and advocated as a therapeutic intervention, e.g. in major depressive ...disorder. Although several targets and protocols have been suggested, comparative studies of tDCS parameters, particularly electrode montages and their cortical targets, are still lacking.
This study investigated a priori hypotheses on specific effects of prefrontal-tDCS montages by using multimodal functional magnetic resonance imaging (fMRI) in healthy participants.
28 healthy male participants underwent three common active-tDCS montages and sham tDCS in a pseudo-randomized order, comprising a total of 112 tDCS-fMRI sessions. Active tDCS was applied at 2 mA for 20 min. Before and after tDCS, a resting-state fMRI (RS fMRI) was recorded, followed by a task fMRI with a delayed-response working-memory (DWM) task for assessing cognitive control over emotionally negative or neutral distractors.
After tDCS with a cathode-F3/anode-F4 montage, RS-fMRI connectivity decreased in a medial part of the left PFC. Also, after the same stimulation condition, regional brain activity during DWM retrieval decreased more in this area after negative than after neutral distraction, and responses to the DWM task were faster, independent of distractor type.
The current study does not confirm our a priori hypotheses on direction and localization of polarity-dependent tDCS effects using common bipolar electrode montages over PFC regions, but it provides evidence for montage-specific effects on multimodal neurophysiological and behavioral outcome measures. Systematic research on the actual targets and the respective dose-response relationships of prefrontal tDCS is warranted.
•Large fMRI study in healthy participants investigating prefrontal tDCS targets.•Multimodal (resting-state and task) fMRI for characterizing tDCS effects.•Effects of cathode-F3/anode-F4 tDCS in medial and dorsolateral prefrontal regions.•In parallel, facilitatory effects of same montage on a behavioral level.•Prefrontal-tDCS effects depend on electrode montage.
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