Brain Maturation Patterns on Normalized FLAIR MR Imaging in Children and Adolescents.

BACKGROUND AND PURPOSE: Signal analysis of FLAIR sequences is gaining momentum for studying neurodevelopment and brain maturation, but FLAIR intensity varies across scanners and needs to be normalized. This study aimed to establish normative values for standardized FLAIR intensity in the pediatric brain. MATERIALS AND METHODS: A new automated algorithm for signal normalization was used to standardize FLAIR intensity across scanners and subjects. Mean intensity was extracted from GM, WM, deep GM, and cortical GM regions. Regression curves were fitted across the pediatric age range, and ANOVA was used to investigate intensity differences across age groups. Correlations between intensity and regional volume were also examined. RESULTS: We analyzed 429 pediatric FLAIR sequences in children 2-19 years of age with a median age of 11.2 years, including 199 males and 230 females. WM intensity had a parabolic relationship with age, with significant differences between various age groups (P < .05). GM and cortical GM intensity increased over the pediatric age range, with significant differences between early childhood and adolescence (P < .05). There were no significant relationships between volume and intensity in early childhood, while there were significant positive and negative correlations (P < .05) in WM and GM, respectively, for increasing age groups. Only the oldest age group showed significant differences between males and females (P < .05). CONCLUSIONS: This work presents a FLAIR intensity standardization algorithm to normalize intensity across large data sets, which allows FLAIR intensity to be used to compare regions and individuals as a surrogate measure of the developing pediatric brain.

T2-FLAIR Mismatch Sign in Pediatric Low-Grade Glioma.

BACKGROUND AND PURPOSE: No qualitative imaging feature currently predicts molecular alterations of pediatric low-grade gliomas with high sensitivity or specificity. The T2-FLAIR mismatch sign predicts IDH-mutated 1p19q noncodeleted adult gliomas with high specificity. We aimed to assess the significance of the T2-FLAIR mismatch sign in pediatric low-grade gliomas. MATERIALS AND METHODS: Pretreatment MR images acquired between January 2001 and August 2018 in pediatric patients with pediatric low-grade gliomas were retrospectively identified. Inclusion criteria were the following: 1) 0-18 years of age, 2) availability of molecular information in histopathologically confirmed cases, and 3) availability of preoperative brain MR imaging with non-motion-degraded T2-weighted and FLAIR sequences. Spinal cord tumors were excluded. RESULTS: Three hundred forty-nine patients were included (187 boys; mean age, 8.7 [SD, 4.8] years; range, 0.5-17.7 years). KIAA1549-B-Raf proto-oncogene (BRAF) fusion and BRAF p.V600E mutation were the most common molecular markers (n = 148, 42%, and n = 73, 20.7%, respectively). The T2-FLAIR mismatch sign was present in 25 patients (7.2%). Of these, 9 were dysembryoplastic neuroepithelial tumors; 8, low-grade astrocytomas; 5, diffuse astrocytomas; 1, a pilocytic astrocytoma; 1, a glioneuronal tumor; and 1, an angiocentric glioma. None of the 25 T2-FLAIR mismatch pediatric low-grade gliomas were BRAF p.V600E-mutated. Fourteen of 25 pediatric low-grade gliomas with the T2-FLAIR mismatch sign had rare molecular alterations, while the molecular subtype was unknown for 11 tumors. CONCLUSIONS: The T2-FLAIR mismatch sign was not observed in the common molecular alterations, BRAF p.V600E-mutated and KIAA1549-BRAF fused pediatric low-grade gliomas, while it was encountered in pediatric low-grade gliomas with rare pediatric molecular alterations.

Decreased Craniocervical CSF Flow in Patients with Normal Pressure Hydrocephalus: A Pilot Study.

BACKGROUND AND PURPOSE: Normal pressure hydrocephalus is characterized by systolic peaks of raised intracranial pressure, possibly due to a reduced compliance of the spinal CSF spaces. This concept of a reduced spinal CSF buffer function may be reflected by a low cervical CSF outflow from the cranium. The aim of this study was to investigate craniospinal CSF flow rates by phase-contrast MR imaging in patients with normal pressure hydrocephalus. MATERIALS AND METHODS: A total of 42 participants were included in this prospective study, consisting of 3 study groups: 1) 10 patients with normal pressure hydrocephalus (mean age, 74 [SD, 6] years, with proved normal pressure hydrocephalus according to current scientific criteria); 2) eighteen age-matched healthy controls (mean age, 71 [SD, 5] years); and 3) fourteen young healthy controls (mean age, 21 [SD, 2] years, for investigation of age-related effects). Axial phase-contrast MR imaging was performed, and the maximal systolic CSF and total arterial blood flow rates were measured at the level of the upper second cervical vertebra and compared among all study groups (2-sample unpaired t test). RESULTS: The maximal systolic CSF flow rate was significantly decreased in patients with normal pressure hydrocephalus compared with age-matched and young healthy controls (53 [SD, 40] mL/m; 329 [SD, 175] mL/m; 472 [SD, 194] mL/m; each P < .01), whereas there were no significant differences with regard to maximal systolic arterial blood flow (1160 [SD, 404] mL/m; 1470 [SD, 381] mL/m; 1400 [SD, 254] mL/m; each P > .05). CONCLUSIONS: The reduced maximal systolic craniospinal CSF flow rate in patients with normal pressure hydrocephalus may be reflective of a reduced compliance of the spinal CSF spaces and an ineffective spinal CSF buffer function. Systolic craniospinal CSF flow rates are an easily obtainable MR imaging-based measure that may support the diagnosis of normal pressure hydrocephalus.

Features of Visually AcceSAble Rembrandt Images: Interrater Reliability in Pediatric Brain Tumors.

BACKGROUND AND PURPOSE: At present, no evidence-based lexicon exists for pediatric intracranial tumors. The Visually AcceSAble Rembrandt Images terminology describes reproducible MR imaging features of adult gliomas for prediction of tumor grade, molecular markers, and survival. Our aim was to assess the interrater reliability of the pre-resection features of Visually AcceSAble Rembrandt Images in pediatric brain tumors. MATERIALS AND METHODS: Fifty consecutive pre-resection brain MR imaging examinations of pediatric intracranial neoplasms were independently reviewed by 3 neuroradiologists. The intraclass correlation coefficient for continuous variables and the Krippendorf alpha were used to evaluate the interrater agreement. Subgroup analysis was performed for 30 gliomas. RESULTS: Parameters with almost perfect agreement (α > .8) included tumor location (F1) and proportion of enhancing tumor (F5). Parameters with substantial agreement (α = .61-.80) were side of tumor epicenter (F2), involvement of eloquent brain (F3), enhancement quality (F4), proportion of non-contrast-enhancing tumor (F6), and deep white matter invasion (F21). The other parameters showed either moderate (α = .41-.60; n = 11), fair (α = .21-.40; n = 5), or slight agreement (α = 0-.20; n = 1). Subgroup analysis of 30 gliomas showed almost perfect agreement for tumor location (F1), involvement of eloquent brain (F3), and proportion of enhancing tumor (F5); and substantial agreement for side of tumor epicenter (F2), enhancement quality (F4), proportion of noncontrast enhancing tumor (F6), cysts (F8), thickness of enhancing margin (F11), and deep white matter invasion (F21). The intraclass correlation coefficient for measurements in the axial plane was excellent in both the main group (0.984 [F29] and 0.982 [F30]) and the glioma subgroup (0.973 [F29] and 0.973 [F30]). CONCLUSIONS: Nine features of Visually AcceSAble Rembrandt Images have an acceptable interrater agreement in pediatric brain tumors. For the subgroup of pediatric gliomas, 11 features of Visually AcceSAble Rembrandt Images have an acceptable interrater agreement. The low degree of reproducibility of the remainder of the features necessitates the use of features tailored to the pediatric age group and is likely related to the more heterogeneous imaging morphology of pediatric brain tumors.

Longitudinal Assessment of Enhancing Foci of Abnormal Signal Intensity in Neurofibromatosis Type 1.

BACKGROUND AND PURPOSE: Patients with neurofibromatosis 1 are at increased risk of developing brain tumors, and differentiation from contrast-enhancing foci of abnormal signal intensity can be challenging. We aimed to longitudinally characterize rare, enhancing foci of abnormal signal intensity based on location and demographics. MATERIALS AND METHODS: A total of 109 MR imaging datasets from 19 consecutive patients (7 male; mean age, 8.6 years; range, 2.3-16.8 years) with neurofibromatosis 1 and a total of 23 contrast-enhancing parenchymal lesions initially classified as foci of abnormal signal intensity were included. The mean follow-up period was 6.5 years (range, 1-13.8 years). Enhancing foci of abnormal signal intensity were followed up with respect to presence, location, and volume. Linear regression analysis was performed. RESULTS: Location, mean peak volume, and decrease in enhancing volume over time of the 23 lesions were as follows: 10 splenium of the corpus callosum (295 mm3, 5 decreasing, 3 completely resolving, 2 surgical intervention for change in imaging appearance later confirmed to be gangliocytoma and astrocytoma WHO II), 1 body of the corpus callosum (44 mm3, decreasing), 2 frontal lobe white matter (32 mm3, 1 completely resolving), 3 globus pallidus (50 mm3, all completely resolving), 6 cerebellum (206 mm3, 3 decreasing, 1 completely resolving), and 1 midbrain (34 mm3). On average, splenium lesions began to decrease in size at 12.2 years, posterior fossa lesions at 17.1 years, and other locations at 9.4 years of age. CONCLUSIONS: Albeit very rare, contrast-enhancing lesions in patients with neurofibromatosis 1 may regress over time. Follow-up MR imaging aids in ascertaining regression. The development of atypical features should prompt further evaluation for underlying tumors.

Radiomics of Pediatric Low-Grade Gliomas: Toward a Pretherapeutic Differentiation of BRAF-Mutated and BRAF-Fused Tumors.

BACKGROUND AND PURPOSE: B-Raf proto-oncogene, serine/threonine kinase (BRAF) status has important implications for prognosis and therapy of pediatric low-grade gliomas. Currently, BRAF status classification relies on biopsy. Our aim was to train and validate a radiomics approach to predict BRAF fusion and BRAF V600E mutation. MATERIALS AND METHODS: In this bi-institutional retrospective study, FLAIR MR imaging datasets of 115 pediatric patients with low-grade gliomas from 2 children's hospitals acquired between January 2009 and January 2016 were included and analyzed. Radiomics features were extracted from tumor segmentations, and the predictive model was tested using independent training and testing datasets, with all available tumor types. The model was selected on the basis of a grid search on the number of trees, opting for the best split for a random forest. We used the area under the receiver operating characteristic curve to evaluate model performance. RESULTS: The training cohort consisted of 94 pediatric patients with low-grade gliomas (mean age, 9.4 years; 45 boys), and the external validation cohort comprised 21 pediatric patients with low-grade gliomas (mean age, 8.37 years; 12 boys). A 4-fold cross-validation scheme predicted BRAF status with an area under the curve of 0.75 (SD, 0.12) (95% confidence interval, 0.62-0.89) on the internal validation cohort. By means of the optimal hyperparameters determined by 4-fold cross-validation, the area under the curve for the external validation was 0.85. Age and tumor location were significant predictors of BRAF status (P values = .04 and <.001, respectively). Sex was not a significant predictor (P value = .96). CONCLUSIONS: Radiomics-based prediction of BRAF status in pediatric low-grade gliomas appears feasible in this bi-institutional exploratory study.

Animal tissue-based quantitative comparison of dual-energy CT to SPR conversion methods using high-resolution gel dosimetry.

Dual-energy computed tomography (DECT) has been shown to allow for more accurate ion therapy treatment planning by improving the estimation of tissue stopping power ratio (SPR) relative to water, among other tissue properties. In this study, we measured and compared the accuracy of SPR values derived using both dual- and single-energy CT (SECT) based on different published conversion algorithms. For this purpose, a phantom setup containing either fresh animal soft tissue samples (beef, pork) and a water reference or tissue equivalent plastic materials was designed and irradiated in a clinical proton therapy facility. Dosimetric polymer gel was positioned downstream of the samples to obtain a three-dimensional proton range distribution with high spatial resolution. The mean proton range in gel for each tissue relative to the water sample was converted to a SPR value. Additionally, the homogeneous samples were probed with a variable water column encompassed by two ionization chambers to benchmark the SPR accuracy of the gel dosimetry. The SPR values measured with both methods were consistent with a mean deviation of 0.2%, but the gel dosimetry captured range variations up to 5 mm within individual samples.Across all fresh tissue samples the SECT approach yielded significantly greater mean absolute deviations from the SPR deduced using gel range measurements, with an average difference of 1.2%, compared to just 0.3% for the most accurate DECT-based algorithm. These results show a significant advantage of DECT over SECT for stopping power prediction in a realistic setting, and for the first time allow to compare a large set of methods under the same conditions.

VOLT: a novel open-source pipeline for automatic segmentation of endolymphatic space in inner ear MRI.

BACKGROUND: Objective and volumetric quantification is a necessary step in the assessment and comparison of endolymphatic hydrops (ELH) results. Here, we introduce a novel tool for automatic volumetric segmentation of the endolymphatic space (ELS) for ELH detection in delayed intravenous gadolinium-enhanced magnetic resonance imaging of inner ear (iMRI) data. METHODS: The core component is a novel algorithm based on Volumetric Local Thresholding (VOLT). The study included three different data sets: a real-world data set (D1) to develop the novel ELH detection algorithm and two validating data sets, one artificial (D2) and one entirely unseen prospective real-world data set (D3). D1 included 210 inner ears of 105 patients (50 male; mean age 50.4 ± 17.1 years), and D3 included 20 inner ears of 10 patients (5 male; mean age 46.8 ± 14.4 years) with episodic vertigo attacks of different etiology. D1 and D3 did not differ significantly concerning age, gender, the grade of ELH, or data quality. As an artificial data set, D2 provided a known ground truth and consisted of an 8-bit cuboid volume using the same voxel-size and grid as real-world data with different sized cylindrical and cuboid-shaped cutouts (signal) whose grayscale values matched the real-world data set D1 (mean 68.7 ± 7.8; range 48.9-92.8). The evaluation included segmentation accuracy using the Sørensen-Dice overlap coefficient and segmentation precision by comparing the volume of the ELS. RESULTS: VOLT resulted in a high level of performance and accuracy in comparison with the respective gold standard. In the case of the artificial data set, VOLT outperformed the gold standard in higher noise levels. Data processing steps are fully automated and run without further user input in less than 60 s. ELS volume measured by automatic segmentation correlated significantly with the clinical grading of the ELS (p < 0.01). CONCLUSION: VOLT enables an open-source reproducible, reliable, and automatic volumetric quantification of the inner ears' fluid space using MR volumetric assessment of endolymphatic hydrops. This tool constitutes an important step towards comparable and systematic big data analyses of the ELS in patients with the frequent syndrome of episodic vertigo attacks. A generic version of our three-dimensional thresholding algorithm has been made available to the scientific community via GitHub as an ImageJ-plugin.

Running effects on cognition and plasticity (ReCaP): study protocol of a longitudinal examination of multimodal adaptations of marathon running.

Regular moderate physical activity (PA) has been linked to beneficial adaptations in various somatic diseases (e.g. cancer, endocrinological disorders) and a reduction in all-cause mortality from several cardiovascular and neuropsychiatric diseases. This study was designed to investigate acute and prolonged exercise-induced cardio- and neurophysiological responses in endurance runners competing in the Munich Marathon. ReCaP (Running effects on Cognition and Plasticity) is a multimodal and longitudinal experimental study. This study included 100 participants (20-60 years). Six laboratory visits were included during the 3-month period before and the 3-month period after the Munich marathon. The multimodal assessment included laboratory measurements, cardiac and cranial imaging (MRI scans, ultrasound/echocardiography) and neurophysiological methods (EEG and TMS/tDCS), and vessel-analysis (e.g. retinal vessels and wave-reflection analyses) and neurocognitive measurements. The ReCaP study was designed to examine novel exercise-induced cardio- and neurophysiological responses to marathon running at the behavioral, functional and morphological levels. This study will expand our understanding of exercise-induced adaptations and will lead to more individually tailored therapeutic options.

[Magnetic resonance imaging of the brain in neonates and infants]. / Magnetresonanztomographie des Gehirns bei Säuglingen und Kleinkindern.

Magnetic resonance imaging (MRI) is increasingly being used for infants and small children due to rapid sequence protocols, broader scanner availability and good monitoring possibilities. The sequence protocol should always be adapted to the individual clinical needs of the infant or toddler. For some clinical indications, such as control of ventricular width in children with shunted hydrocephalus, ultrafast protocols can be used with a scanning time of just a few minutes. For more complex clinical questions, more extensive sequence protocols are warranted. Particularly for neonates and using a rapid investigation protocol, MRI examinations can very often be performed without sedation. The necessity of using gadolinium-based contrast agents has to be critically deliberated in infants and neonates and has to be exactly tailored to the clinical needs. In many cases MRI examinations of the brain in infants and neonates do not require gadolinium-based contrast agents.

A probabilistic atlas of the human inner ear's bony labyrinth enables reliable atlas-based segmentation of the total fluid space.

Intravenous contrast agent-enhanced magnetic resonance imaging of the endolymphatic space (ELS) of the inner ear permits direct, in-vivo, non-invasive visualization of labyrinthine structures and thus verification of endolymphatic hydrops (ELH). However, current volumetric assessment approaches lack normalization. The aim of this study was to develop a probabilistic atlas of the inner ear's bony labyrinth as a first step towards an automated and reproducible volume-based quantification of the ELS. The study included three different datasets: a source dataset (D1) to build the probabilistic atlas and two testing sets (D2, D3). D1 included 24 right-handed patients (12 females; mean age 51.5 ± 3.9 years) and D2 5 patients (3 female; mean age 48.8 ± 5.01 years) with vestibular migraine without ELH or any measurable vestibular deficits. D3 consisted of five patients (one female; mean age 46 ± 5.2 years) suffering from unilateral Menière's disease and ELH. Data processing comprised three steps: preprocessing using an affine and deformable fusion registration pipeline, computation of an atlas for the left and right inner ear using a label-assisted approach, and validation of the atlas based on localizing and segmenting previously unseen ears. The three-dimensional probabilistic atlas of the inner ear's bony labyrinth consisted of the internal acoustic meatus and inner ears (including cochlea, otoliths, and semicircular canals) for both sides separately. The analyses showed a high level of agreement between the atlas-based segmentation and the manual gold standard with an overlap of 89% for the right ear and 86% for the left ear (measured by dice scores). This probabilistic in vivo atlas of the human inner ear's bony labyrinth and thus of the inner ear's total fluid space for both ears represents a necessary step towards a normalized, easily reproducible and reliable volumetric quantification of the perilymphatic and endolymphatic space in view of MR volumetric assessment of ELH. The proposed atlas lays the groundwork for state-of-the-art approaches (e.g., deep learning) and will be provided to the scientific community.

Beyond binary parcellation of the vestibular cortex - A dataset.

The data-set presented in this data article is supplementary to the original publication, doi:10.1016/j.neuroimage.2018.05.018 (Kirsch et al., 2018). Named article describes handedness-dependent organizational patterns of functional subunits within the human vestibular cortical network that were revealed by functional magnetic resonance imaging (fMRI) connectivity parcellation. 60 healthy volunteers (30 left-handed and 30 right-handed) were examined on a 3T MR scanner using resting state fMRI. The multisensory (non-binary) nature of the human (vestibular) cortex was addressed by using masked binary and non-binary variations of independent component analysis (ICA). The data have been made publicly available via github (https://github.com/RainerBoegle/BeyondBinaryParcellationData).

Comparison of 18F-GE-180 and dynamic 18F-FET PET in high grade glioma: a double-tracer pilot study.

BACKGROUND: PET represents a valuable tool for glioma imaging. In addition to amino acid tracers such as 18F-FET, PET targeting the 18-kDa mitochondrial translocator-protein (TSPO) is of high interest for high-grade glioma (HGG) imaging due to its upregulation in HGG cells. 18F-GE-180, a novel TSPO ligand, has shown a high target-to-background contrast in HGG. Therefore, we intra-individually compared its uptake characteristics to dynamic 18F-FET PET and contrast-enhanced MRI in patients with HGG. METHODS: Twenty HGG patients (nine IDH-wildtype, 11 IDH-mutant) at initial diagnosis (n = 8) or recurrence (n = 12) were consecutively included and underwent 18F-GE-180 PET, dynamic 18F-FET PET, and MRI. The maximal tumour-to-background ratios (TBRmax) and biological tumour volumes (BTV) were evaluated in 18F-GE-180 and 18F-FET PET. Dynamic 18F-FET PET analysis included the evaluation of minimal time-to-peak (TTPmin). In MRI, the volume of contrast-enhancement was delineated (VOLCE). Volumes were spatially correlated using the Sørensen-Dice coefficient. RESULTS: The median TBRmax tended to be higher in 18F-GE-180 PET compared to 18F-FET PET [4.58 (2.33-8.95) vs 3.89 (1.56-7.15); p = 0.062] in the overall group. In subgroup analyses, IDH-wildtype gliomas showed a significantly higher median TBRmax in 18F-GE-180 PET compared to 18F-FET PET [5.45 (2.56-8.95) vs 4.06 (1.56-4.48); p = 0.008]; by contrast, no significant difference was observed in IDH-mutant gliomas [3.97 (2.33-6.81) vs 3.79 (2.01-7.15) p = 1.000]. Only 5/20 cases showed higher TBRmax in 18F-FET PET compared to 18F-GE-180 PET, all of them being IDH-mutant gliomas. No parameter in 18F-GE-180 PET correlated with TTPmin (p > 0.05 each). There was a tendency towards higher median BTVGE-180 [32.1 (0.4-236.0) ml] compared to BTVFET [19.3 (0.7-150.2) ml; p = 0.062] with a moderate spatial overlap [median Sørensen-Dice coefficient 0.55 (0.07-0.85)]. In MRI, median VOLCE [9.7 (0.1-72.5) ml] was significantly smaller than both BTVFET and BTVGE180 (p < 0.001 each), leading to a poor spatial correlation with BTVGE-180 [0.29 (0.01-0.48)] and BTVFET [0.38 (0.01-0.68)]. CONCLUSION: PET with 18F-GE-180 and 18F-FET provides differing imaging information in HGG dependent on the IDH-mutational status, with diverging spatial overlap and vast exceedance of contrast-enhancement in MRI. Combined PET imaging might reveal new insights regarding non-invasive characterization of tumour heterogeneity and might influence patients' management.

Handedness-dependent functional organizational patterns within the bilateral vestibular cortical network revealed by fMRI connectivity based parcellation.

Current evidence points towards a vestibular cortex that involves a multisensory bilateral temporo-parietal-insular network with a handedness-dependent hemispheric lateralization. This study aimed to identify handedness-dependent organizational patterns of (lateralized and non-lateralized) functional subunits within the human vestibular cortex areas. 60 healthy volunteers (30 left-handed and 30 right-handed) were examined on a 3T MR scanner using resting state functional MRI (fMRI). The data was analyzed in four major steps using a functional connectivity based parcellation (fCBP) approach: (1) independent component analysis (ICA) on a whole brain level to identify different resting state networks (RSN); (2) creation of a vestibular informed mask from four whole brain ICs that included reference coordinates of the vestibular network extracted from meta-analyses of vestibular neuroimaging experiments; (3) Re-ICA confined to the vestibular informed mask; (4) cross-correlation of the activated voxels within the vestibular subunits (parcels) to each other (P-to-P) and to the whole-brain RSN (P-to-RSN). This approach disclosed handedness-dependency, inter-hemispheric symmetry, the scale of connectedness to major whole brain RSN and the grade of spatial overlap of voxels within parcels (common/unique) as meaningful discriminatory organizational categories within the vestibular cortex areas. This network consists of multiple inter-hemisphere symmetric (not lateralized), well-connected (many RSN-assignments) multisensory areas (or hubs; e.g., superior temporal gyrus, temporo-parietal intersection) organized around an asymmetric (lateralized, "dominant") and functionally more specialized (few RSN-assignments) core region in the parieto-insular cortex. The latter is in the middle, posterior and inferior insula. In conclusion, the bilateral cortical vestibular network contains not only a handedness-dependent lateralized central region concentrated in the right hemisphere in right-handers and left hemisphere in left-handers, but also surrounding inter-hemisphere symmetric multisensory vestibular areas that seem to be functionally influenced by their neighboring sensory systems (e.g., temporo-parietal intersection by the visual system). One may speculate that the development of an asymmetrical organized vestibular subsystem reflects a more recent phylogenetic evolution of various multisensory vestibular functions. The right hemispheric dominance of spatial orientation and its disorders, spatial neglect and pusher syndrome, may serve as examples.

TSPO PET with [18F]GE-180 sensitively detects focal neuroinflammation in patients with relapsing-remitting multiple sclerosis.

PURPOSE: Expression of the translocator protein (TSPO) is upregulated in activated macrophages/microglia and is considered to be a marker of neuroinflammation. We investigated the novel TSPO ligand [18F]GE-180 in patients with relapsing-remitting multiple sclerosis (RRMS) to determine the feasibility of [18F]GE-180 PET imaging in RRMS patients and to assess its ability to detect active inflammatory lesions in comparison with the current gold standard, contrast-enhanced magnetic resonance imaging (MRI). METHODS: Nineteen RRMS patients were prospectively included in this study. All patients underwent TSPO genotyping and were classified as high-affinity, medium-affinity or low-affinity binders (HAB/MAB/LAB). PET scans were performed after administration of 189 ± 12 MBq [18F]GE-180, and 60-90 min summation images were used for visual analysis and assessment of standardized uptake values (SUV). The frontal nonaffected cortex served as a pseudoreference region (PRR) for evaluation of SUV ratios (SUVR). PET data were correlated with MRI signal abnormalities, i.e. T2 hyperintensity or contrast enhancement (CE). When available, previous MRI data were used to follow the temporal evolution of individual lesions. RESULTS: Focal lesions were identified as hot spots by visual inspection. Such lesions were detected in 17 of the 19 patients and overall 89 [18F]GE-180-positive lesions were found. TSPO genotyping revealed 11 patients with HAB status, 5 with MAB status and 3 with LAB status. There were no associations between underlying binding status (HAB, MAB and LAB) and the signal intensity in either lesions (SUVR 1.87 ± 0.43, 1.95 ± 0.48 and 1.86 ± 0.80, respectively; p = 0.280) or the PRR (SUV 0.36 ± 0.03, 0.40 ± 0.06 and 0.37 ± 0.03, respectively; p = 0.990). Of the 89 [18F]GE-180-positive lesions, 70 showed CE on MRI, while the remainder presented as T2 lesions without CE. SUVR were significantly higher in lesions with CE than in those without (2.00 ± 0.53 vs. 1.60 ± 0.15; p = 0.001). Notably, of 19 [18F]GE-180-positive lesions without CE, 8 previously showed CE, indicating that [18F]GE-180 imaging may be able to detect lesional activity that is sustained beyond the blood-brain barrier breakdown. CONCLUSION: [18F]GE-180 PET can detect areas of focal macrophage/microglia activation in patients with RRMS in lesions with and without CE on MRI. Therefore, [18F]GE-180 PET imaging is a sensitive and quantitative approach to the detection of active MS lesions. It may provide information beyond contrast-enhanced MRI and is readily applicable to all patients. [18F]GE-180 PET imaging is therefore a promising new tool for the assessment of focal inflammatory activity in MS.

[Imaging of locally advanced prostate cancer : Importance of ultrasound and especially MRI]. / Bildgebung des lokal fortgeschrittenen Prostatakarzinoms : Die Bedeutung von Ultraschall und insbesondere MRT.

Prostate cancer is the most common male malignant tumor in Germany, which thus places growing demands on differentiated imaging and risk-adapted therapeutic approaches. Multiparametric MRI (mpMRI) of the prostate enables reliable detection of clinically significant cancers and is currently the leading imaging modality for the detection, characterization, and local staging of prostate cancer. According to the German S3 guideline, mpMRI of the prostate is currently primarily recommended in patients with previous negative TRUS biopsies and persisting tumor suspicion. The serial use of mpMRI in the pretherapeutic setting can support individual therapy planning of patients with locally advanced prostate cancer in the near future.

[Migraine in children and adolescents-brain and muscle? : Another example of why children are not small adults]. / Migräne im Kindes- und Jugendalter ­ Gehirn und Muskel? : Warum Kinder einmal mehr keine kleinen Erwachsenen sind.

Migraine as primary headache is a life-long disease which is relevant for the quality of life and is based on complex genetics. It often starts in childhood with symptoms typical for the specific age. These show different nuances compared to the migraine symptoms in adults, for example, regarding (bilateral/unilateral) localization of the acute migraine headache. Only over the course of years-during adolescence and young adulthood-do the more specific symptoms as defined by the International Classification of Headache Disorders (ICHD 3 beta) develop. In this article we focus on the clinical specifics of children and adolescents with migraine. We elaborately refer to the trigeminocervical complex (TCC) because it forms a conceptual bridge for the understanding of migraine, for psychoeducation, and for therapeutic options. We pragmatically discuss options and limits of treatments.