Early Intravenous Magnesium Sulfate and Its Impact on Cerebral Vasospasm as well as Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage: A Retrospective Matched Case-Control Analysis.

BACKGROUND: Magnesium sulfate (MgSO4) is a potential neuroprotective agent for patients with aneurysmal subarachnoid hemorrhage (SAH). We analyzed the effect of early application of intraoperative intravenous MgSO4 and compared cerebral vasospasm (CV), delayed cerebral ischemia (DCI), and neurological outcome in 2 patient cohorts. METHODS: A retrospective matched-pair analysis from patients at a single center in Germany was performed without (group A) and with (group B) MgSO4 application <24 hours after diagnosis. Pairs were matched according to the known risk factors for DCI and CV (age, Fisher grade, smoking, severity of SAH). Incidence of CV and DCI and neurological outcome using the modified Rankin Scale score 3 and 12 months after SAH were recorded. RESULTS: The inclusion criteria were met by 196 patients. After risk stratification, 48 patients were included in the final analysis (age 54.2 ± 8.1 years; 30 women and 18 men) and were assigned to group A (n = 24) or group B (n = 24). CV occurred less frequently in group B (33%) than in group A (46%). Likewise, DCI was present in 13% in group B compared with 42% in group A. After 12 months, 22 patients in group B had a favorable functional outcome (modified Rankin Scale score 0-3) compared with 15 patients in group A. CONCLUSIONS: In this study, the incidence of CV and DCI was lower in patients receiving intravenous MgSO4 within 24 hours after aneurysmal SAH onset. Favorable functional outcome was more likely in the MgSO4 group after 12 months of follow-up.

Comprehensive 7 T CEST: A clinical MRI protocol covering multiple exchange rate regimes.

Chemical exchange saturation transfer (CEST) is a magnetic resonance (MR) imaging method providing molecular image contrasts based on indirect detection of low concentrated solutes. Previous CEST studies focused predominantly on the imaging of single CEST exchange regimes (e.g., slow, intermediate or fast exchanging groups). In this work, we aim to establish a so-called comprehensive CEST protocol for 7 T, covering the different exchange regimes by three saturation B1 amplitude regimes: low, intermediate and high. We used the results of previous publications and our own simulations in pulseq-CEST to produce a 7 T CEST protocol that has sensitivity to these three B1 regimes. With postprocessing optimization (simultaneous mapping of water shift and B1, B0-fitting, multiple interleaved mode saturation B1 correction, neural network employment (deepCEST) and analytical input feature reduction), we are able to shorten our initially 40 min protocol to 15 min and generate six CEST contrast maps simultaneously. With this protocol, we measured four healthy subjects and one patient with a brain tumor. We established a comprehensive CEST protocol for clinical 7 T MRI, covering three different B1 amplitude regimes. We were able to reduce the acquisition time significantly by more than 50%, while still maintaining decent image quality and contrast in healthy subjects and one patient with a tumor. Our protocol paves the way to perform comprehensive CEST studies in clinical scan times for hypothesis generation regarding molecular properties of certain pathologies, for example, ischemic stroke or high-grade brain tumours.

Deep histopathology genotype-phenotype analysis of focal cortical dysplasia type II differentiates between the GATOR1-altered autophagocytic subtype IIa and MTOR-altered migration deficient subtype IIb.

Focal cortical dysplasia type II (FCDII) is the most common cause of drug-resistant focal epilepsy in children. Herein, we performed a deep histopathology-based genotype-phenotype analysis to further elucidate the clinico-pathological and genetic presentation of FCDIIa compared to FCDIIb. Seventeen individuals with histopathologically confirmed diagnosis of FCD ILAE Type II and a pathogenic variant detected in brain derived DNA whole-exome sequencing or mTOR gene panel sequencing were included in this study. Clinical data were directly available from each contributing centre. Histopathological analyses were performed from formalin-fixed, paraffin-embedded tissue samples using haematoxylin-eosin and immunohistochemistry for NF-SMI32, NeuN, pS6, p62, and vimentin. Ten individuals carried loss-of-function variants in the GATOR1 complex encoding genes DEPDC5 (n = 7) and NPRL3 (n = 3), or gain-of-function variants in MTOR (n = 7). Whereas individuals with GATOR1 variants only presented with FCDIIa, i.e., lack of balloon cells, individuals with MTOR variants presented with both histopathology subtypes, FCDIIa and FCDIIb. Interestingly, 50% of GATOR1-positive cases showed a unique and predominantly vacuolizing phenotype with p62 immunofluorescent aggregates in autophagosomes. All cases with GATOR1 alterations had neurosurgery in the frontal lobe and the majority was confined to the cortical ribbon not affecting the white matter. This pattern was reflected by subtle or negative MRI findings in seven individuals with GATOR1 variants. Nonetheless, all individuals were seizure-free after surgery except four individuals carrying a DEPDC5 variant. We describe a yet underrecognized genotype-phenotype correlation of GATOR1 variants with FCDIIa in the frontal lobe. These lesions were histopathologically characterized by abnormally vacuolizing cells suggestive of an autophagy-altered phenotype. In contrast, individuals with FCDIIb and brain somatic MTOR variants showed larger lesions on MRI including the white matter, suggesting compromised neural cell migration.

Status epilepticus in patients with glioblastoma: Clinical characteristics, risk factors, and epileptological outcome.

PURPOSE: Epilepsy is a common comorbidity in patients with glioblastoma, however, clinical data on status epilepticus (SE) in these patients is sparse. We aimed to investigate the risk factors associated with the occurrence and adverse outcomes of SE in glioblastoma patients. METHODS: We retrospectively analysed electronic medical records of patients with de-novo glioblastoma treated at our institution between 01/2006 and 01/2020 and collected data on patient, tumour, and SE characteristics. RESULTS: In the final cohort, 292/520 (56.2 %) patients developed seizures, with 48 (9.4 % of the entire cohort and 16.4 % of patients with epilepsy, PWE) experiencing SE at some point during the course of their disease. SE was the first symptom of the tumour in 6 cases (1.2 %) and the first manifestation of epilepsy in 18 PWE (6.2 %). Most SE episodes occurred postoperatively (n = 37, 77.1 %). SE occurrence in PWE was associated with postoperative seizures and drug-resistant epilepsy. Adverse outcome (in-house mortality or admission to palliative care, 10/48 patients, 20.8 %), was independently associated with higher status epilepticus severity score (STESS) and Charlson Comorbidity Index (CCI), but not tumour progression. 32/48 SE patients (66.7 %) were successfully treated with first- and second-line agents, while escalation to third-line agents was successful in 6 (12.5 %) cases. CONCLUSION: Our data suggests a link between the occurrence of SE, postoperative seizures, and drug-resistant epilepsy. Despite the dismal oncological prognosis, SE was successfully treated in 79.2 % of the cases. Higher STESS and CCI were associated with adverse SE outcomes.

Cerebral lesions sites in neurosarcoidosis: a lesion mapping study.

BACKGROUND AND PURPOSE: Sarcoidosis is a granulomatous disease of unknown etiology affecting the central nervous system in up to 15% of the patients. Diagnosis of neurosarcoidosis is very challenging due to the heterogeneity of its clinical manifestation. This study intended to evaluate the distribution of cerebral lesion sites and the potential presence of specific lesion clusters in neurosarcoidosis patients using voxel-based lesion symptom mapping (VLSM). METHODS: Patients with neurosarcoidosis were retrospectively identified and included between 2011 and 2022. Cerebral lesion sites were correlated voxel-wise with presence and absence of neurosarcoidosis using non-parametric permutation test. Multiple sclerosis patients served as controls for the VLSM-analysis. RESULTS: Thirty-four patients (mean age 52 ± 15 years) of whom 13 were diagnosed with possible, 19 with probable and 2 with confirmed neurosarcoidosis were identified. Lesion overlap of neurosarcoidosis patients demonstrated a distribution of white matter lesions in all brain areas, with a periventricular predilection similar to multiple sclerosis. In contrast to multiple sclerosis controls, no propensity for lesions in proximity of the corpus callosum was observed. Neurosarcoidosis lesions appeared smaller and lesion volume was lower in the neurosarcoidosis cohort. The VLSM analysis showed minor associations between neurosarcoidosis and damaged voxels in the bilateral frontobasal cortex. CONCLUSIONS: The VLSM analysis yielded significant associations in the bilateral frontal cortex, suggesting that leptomeningeal inflammatory disease with following cortical involvement is a quite specific feature in neurosarcoidosis. Lesion load was lower in neurosarcoidosis than in multiple sclerosis. However, no specific pattern of subcortical white matter lesions in neurosarcoidosis was revealed.

Time-dependent risk factors for epileptic seizures in glioblastoma patients: A retrospective analysis of 520 cases.

OBJECTIVE: Epilepsy is a common comorbidity of glioblastoma. Seizures may occur in various phases of the disease. We aimed to assess potential risk factors for seizures in accordance with the point in time at which they occurred. METHODS: We retrospectively analyzed medical files of adult patients with de novo glioblastoma treated at our institution between January 2006 and January 2020. We categorized seizures as preoperative seizures (POS), early postoperative seizures (EPS; before initiation of radio[chemo]therapy [RCT]), seizures during radiotherapy (SDR; during or <30 days after RCT), and posttherapeutic seizures (PTS; ≥30 days after completion of RCT). We addressed associations between patients' characteristics and their seizures. RESULTS: In the final cohort (N = 520), 292 patients experienced seizures. POS, EPS, SDR, and/or PTS occurred in 29.6% (154/520), 6.0% (31/520), 13.8% (70/509), and 36.1% (152/421) of patients, respectively. POS occurred more frequently in patients with higher Karnofsky Performance Scale scores (odds ratio [OR] = 3.27, p = .001) and tumor location in the temporal lobe (OR = 1.51, p = .034). None of the parameters we analyzed was related to the occurrence of EPS. SDR were independently associated with tumor location (parietal lobe, OR = 1.86, p = .027) and POS, but not EPS, and were independent of RCT. PTS were independently associated with tumor progression (OR = 2.32, p < .001) and with occurrence of SDR (OR = 3.36, p < .001), and negatively correlated with temporal lobe location (OR = .58, p < .014). In patients with tumors exclusively located in the temporal lobe, complete tumor resection was associated with a decreased risk of postoperative seizures. SIGNIFICANCE: Seizures in glioblastoma patients have various, time-dependent risk factors. Temporal lobe localization was a risk factor for preoperative seizures; surgery may have had a protective effect in these patients. RCT did not have dose-dependent pro- or anticonvulsive effects. PTS were associated with tumor progression.

Snapshot CEST++: Advancing rapid whole-brain APTw-CEST MRI at 3 T.

APTw CEST MRI suffers from long preparation times and consequently long acquisition times (~5 min). Recently, a consensus on the preparation module for clinical APTw CEST at 3 T was found in the community, and we present a fast whole-brain APTw CEST MRI sequence following this consensus preparation of pulsed RF irradiation of 2 s duration at 90% RF duty-cycle and a B1,rms of 2 µT. After optimization of the snapshot CEST approach for APTw imaging regarding flip angle, voxel size and frequency offset sampling, we extend it by undersampled GRE acquisition and compressed sensing reconstruction. This allows 2 mm isotropic whole-brain APTw imaging for clinical research at 3 T below 2 min. With this sequence, a fast snapshot APTw imaging method is now available for larger clinical studies of brain tumors.

Surgical planning, histopathology findings and postoperative outcome in MR-negative extra-temporal epilepsy using intracranial EEG, functional imaging, magnetoencephalography, neuronavigation and intraoperative MRI.

OBJECTIVE: MRI-negative drug-resistant epilepsy presents a challenge when it comes to surgical planning, and surgical outcome is worse than in cases with an identified lesion. Although increasing implementation of more powerful MRI scanners and artificial intelligence has led to the detection of previously unrecognizable lesions, in some cases even postoperative pathological evaluation of electrographically epileptogenic zones shows no structural alterations. While in temporal lobe epilepsy a standardized resection approach can usually be performed, the surgical management of extra-temporal lesions is always individual. Here we present a strategy for treating patients with extra-temporal MRI-negative epilepsy focus and report our histological findings and patient outcome. METHODS: Patients undergoing epilepsy surgery in the Department of Neurosurgery at the University Hospital Erlangen between 2012 and 2020 were included in the study. Inclusion criteria were: (1) failure to identify a structural lesion on preoperative high-resolution 3 Tesla MRI with a standardized epilepsy protocol and (2) preoperative intracranial EEG (iEEG) diagnostics. RESULTS: We identified 8 patients corresponding to the inclusion criteria. Second look MRI analysis by an experienced neuroradiologist including the most recent analysis algorithm utilized in our clinic revealed a possible lesion in two patients. One of the patients with a clear focal cortical dysplasia (FCD) finding on a second look was excluded from further analysis. Of the other 7 patients, in one patient iEEG was performed with subdural electrodes, whereas the other 6 were evaluated with depth electrodes. MEG was performed preoperatively in all but one patient. An MEG focus was implemented in resection planning in 3 patients. FDG PET was performed in all, but only implemented in one patient. Histopathological evaluation revealed one non-lesional case, 4 cases of FCD and 2 cases with mild developmental malformation. All patients were free from permanent neurological deficits and presented with Engel 1A or 1B outcome on the last follow-up. CONCLUSION: We demonstrate that extra-temporal MRI-negative epilepsy can be treated successfully provided an extensive preoperative planning is performed. The most important diagnostic was stereo-EEG, whereas additional data from MEG was helpful and FDG PET was rarely useful in our cohort.

DeepCEST 7 T: Fast and homogeneous mapping of 7 T CEST MRI parameters and their uncertainty quantification.

PURPOSE: In this work, we investigated the ability of neural networks to rapidly and robustly predict Lorentzian parameters of multi-pool CEST MRI spectra at 7 T with corresponding uncertainty maps to make them quickly and easily available for routine clinical use. METHODS: We developed a deepCEST 7 T approach that generates CEST contrasts from just 1 scan with robustness against B1 inhomogeneities. The input data for a neural feed-forward network consisted of 7 T in vivo uncorrected Z-spectra of a single B1 level, and a B1 map. The 7 T raw data were acquired using a 3D snapshot gradient echo multiple interleaved mode saturation CEST sequence. These inputs were mapped voxel-wise to target data consisting of Lorentzian amplitudes generated conventionally by 5-pool Lorentzian fitting of normalized, denoised, B0 - and B1 -corrected Z-spectra. The deepCEST network was trained with Gaussian negative log-likelihood loss, providing an uncertainty quantification in addition to the Lorentzian amplitudes. RESULTS: The deepCEST 7 T network provides fast and accurate prediction of all Lorentzian parameters also when only a single B1 level is used. The prediction was highly accurate with respect to the Lorentzian fit amplitudes, and both healthy tissues and hyperintensities in tumor areas are predicted with a low uncertainty. In corrupted cases, high uncertainty indicated wrong predictions reliably. CONCLUSION: The proposed deepCEST 7 T approach reduces scan time by 50% to now 6:42 min, but still delivers both B0 - and B1 -corrected homogeneous CEST contrasts along with an uncertainty map, which can increase diagnostic confidence. Multiple accurate 7 T CEST contrasts are delivered within seconds.

Linear projection-based chemical exchange saturation transfer parameter estimation.

Isolated evaluation of multiparametric in vivo chemical exchange saturation transfer (CEST) MRI often requires complex computational processing for both correction of B0 and B1 inhomogeneity and contrast generation. For that, sufficiently densely sampled Z-spectra need to be acquired. The list of acquired frequency offsets largely determines the total CEST acquisition time, while potentially representing redundant information. In this work, a linear projection-based multiparametric CEST evaluation method is introduced that offers fast B0 and B1 inhomogeneity correction, contrast generation and feature selection for CEST data, enabling reduction of the overall measurement time. To that end, CEST data acquired at 7 T in six healthy subjects and in one brain tumor patient were conventionally evaluated by interpolation-based inhomogeneity correction and Lorentzian curve fitting. Linear regression was used to obtain coefficient vectors that directly map uncorrected data to corrected Lorentzian target parameters. L1-regularization was applied to find subsets of the originally acquired CEST measurements that still allow for such a linear projection mapping. The linear projection method allows fast and interpretable mapping from acquired raw data to contrast parameters of interest, generalizing from healthy subject training data to unseen healthy test data and to the tumor patient dataset. The L1-regularization method shows that a fraction of the acquired CEST measurements is sufficient to preserve tissue contrasts, offering up to a 2.8-fold reduction of scan time. Similar observations as for the 7-T data can be made for data from a clinical 3-T scanner. Being a fast and interpretable computation step, the proposed method is complementary to neural networks that have recently been employed for similar purposes. The scan time acceleration offered by the L1-regularization ("CEST-LASSO") constitutes a step towards better applicability of multiparametric CEST protocols in a clinical context.

Effects of Hippocampal Sparing Radiotherapy on Brain Microstructure-A Diffusion Tensor Imaging Analysis.

Hippocampal-sparing radiotherapy (HSR) is a promising approach to alleviate cognitive side effects following cranial radiotherapy. Microstructural brain changes after irradiation have been demonstrated using Diffusion Tensor Imaging (DTI). However, evidence is conflicting for certain parameters and anatomic structures. This study examines the effects of radiation on white matter and hippocampal microstructure using DTI and evaluates whether these may be mitigated using HSR. A total of 35 tumor patients undergoing a prospective randomized controlled trial receiving either conventional or HSR underwent DTI before as well as 6, 12, 18, 24, and 30 (±3) months after radiotherapy. Fractional Anisotropy (FA), Mean Diffusivity (MD), Axial Diffusivity (AD), and Radial Diffusivity (RD) were measured in the hippocampus (CA), temporal, and frontal lobe white matter (TL, FL), and corpus callosum (CC). Longitudinal analysis was performed using linear mixed models. Analysis of the entire patient collective demonstrated an overall FACC decrease and RDCC increase compared to baseline in all follow-ups; ADCC decreased after 6 months, and MDCC increased after 12 months (p ≤ 0.001, 0.001, 0.007, 0.018). ADTL decreased after 24 and 30 months (p ≤ 0.004, 0.009). Hippocampal FA increased after 6 and 12 months, driven by a distinct increase in ADCA and MDCA, with RDCA not increasing until 30 months after radiotherapy (p ≤ 0.011, 0.039, 0.005, 0.040, 0.019). Mean radiation dose correlated positively with hippocampal FA (p < 0.001). These findings may indicate complex pathophysiological changes in cerebral microstructures after radiation, insufficiently explained by conventional DTI models. Hippocampal microstructure differed between patients undergoing HSR and conventional cranial radiotherapy after 6 months with a higher ADCA in the HSR subgroup (p ≤ 0.034).

Deep learning for brain metastasis detection and segmentation in longitudinal MRI data.

PURPOSE: Brain metastases (BM) occur frequently in patients with metastatic cancer. Early and accurate detection of BM is essential for treatment planning and prognosis in radiation therapy. Due to their tiny sizes and relatively low contrast, small BM are very difficult to detect manually. With the recent development of deep learning technologies, several res earchers have reported promising results in automated brain metastasis detection. However, the detection sensitivity is still not high enough for tiny BM, and integration into clinical practice in regard to differentiating true metastases from false positives (FPs) is challenging. METHODS: The DeepMedic network with the binary cross-entropy (BCE) loss is used as our baseline method. To improve brain metastasis detection performance, a custom detection loss called volume-level sensitivity-specificity (VSS) is proposed, which rates metastasis detection sensitivity and specificity at a (sub)volume level. As sensitivity and precision are always a trade-off, either a high sensitivity or a high precision can be achieved for brain metastasis detection by adjusting the weights in the VSS loss without decline in dice score coefficient for segmented metastases. To reduce metastasis-like structures being detected as FP metastases, a temporal prior volume is proposed as an additional input of DeepMedic. The modified network is called DeepMedic+ for distinction. Combining a high-sensitivity VSS loss and a high specificity loss for DeepMedic+, the majority of true positive metastases are confirmed with high specificity, while additional metastases candidates in each patient are marked with high sensitivity for detailed expert evaluation. RESULTS: Our proposed VSS loss improves the sensitivity of brain metastasis detection, increasing the sensitivity from 85.3% for DeepMedic with BCE to 97.5% for DeepMedic with VSS. Alternatively, the precision is improved from 69.1% for DeepMedic with BCE to 98.7% for DeepMedic with VSS. Comparing DeepMedic+ with DeepMedic with the same VSS loss, 44.4% of the FP metastases are reduced in the high-sensitivity model and the precision reaches 99.6% for the high-specificity model. The mean dice coefficient for all metastases is about 0.81. With the ensemble of the high-sensitivity and high-specificity models, on average only 1.5 FP metastases per patient need further check, while the majority of true positive metastases are confirmed. CONCLUSIONS: Our proposed VSS loss and temporal prior improve brain metastasis detection sensitivity and precision. The ensemble learning is able to distinguish high confidence true positive metastases from metastases candidates that require special expert review or further follow-up, being particularly well-fit to the requirements of expert support in real clinical practice. This facilitates metastasis detection and segmentation for neuroradiologists in diagnostic and radiation oncologists in therapeutic clinical applications.

High-speed flat-detector computed tomography for temporal bone imaging and postoperative control of cochlear implants.

PURPOSE: Flat-detector computed tomography (FD-CT) is the standard for cochlear implant (CI) imaging. FD-CT systems differ in technical characteristics. Our aim was an evaluation of two different FD-CT generations with different protocols and hardware regarding image quality, radiation dose, and scan time. METHODS: Two temporal bone specimens (- / + CI = TB0/TB1) were scanned using three different scanners: two FD-CT systems with different scanning protocols (standard FD-CT: 20 s 70 kV, 20 s 109 kV; high-speed FD-CT [HS-FD-CT]: 7 s 109 kV, 9 s 109 kV, 14 s 72 kV) and MS-CT (5 s 120 kV). Acquired datasets were evaluated in consensus reading regarding qualitative and quantitative parameters: addressing CI- and cochlea-specific parameters, cochlea delineation, lamina spiralis ossea visibility, distinction of single CI electrodes, determination of intracochlear implant position, stapes delineation, and mastoidal septation were assessed. Addressing protocol-specific parameters, radiation dose (dose-length-product/DLP), and scan time were assessed. RESULTS: Two HS-FD-CT protocols (14 s/9 s) provide higher or equivalent diagnostic information regarding CI- and cochlea-specific parameters compared to both standard FD-CT protocols. The fastest HS-FD-CT protocol (7 s)-providing inferior diagnostic information compared to all other FD-CT protocols-still exceeds MS-CT. The highest DLP was recorded for the 14 s HS-FD-CT protocol (TB1 = 956 mGycm); the lowest DLPs were recorded for the 7 s HS-FD-CT protocol (TB0 = 188 mGycm) and for MS-CT (TB0 = 138 mGycm), respectively. HS-FD-CT allows a significant reduction of scan time compared to standard FD-CT. CONCLUSION: High-speed FD-CT improves visualization of temporal bone anatomy and postoperative assessment of CIs by combining excellent image quality, fast scan time, and reasonable radiation exposure.

Association between tissue hypoxia, perfusion restrictions, and microvascular architecture alterations with lesion-induced impairment of neurovascular coupling.

Functional magnetic resonance imaging (fMRI) has been mainly utilized for the preoperative localization of eloquent cortical areas. However, lesion-induced impairment of neurovascular coupling (NVC) in the lesion border zone may lead to false-negative fMRI results. The purpose of this study was to determine physiological factors impacting the NVC. Twenty patients suffering from brain lesions were preoperatively examined using multimodal neuroimaging including fMRI, magnetoencephalography (MEG) during language or sensorimotor tasks (depending on lesion location), and a novel physiologic MRI approach for the combined quantification of oxygen metabolism, perfusion state, and microvascular architecture. Congruence of brain activity patterns between fMRI and MEG were found in 13 patients. In contrast, we observed missing fMRI activity in perilesional cortex that demonstrated MEG activity in seven patients, which was interpreted as lesion-induced impairment of NVC. In these brain regions with impaired NVC, physiologic MRI revealed significant brain tissue hypoxia, as well as significantly decreased macro- and microvascular perfusion and microvascular architecture. We demonstrated that perilesional hypoxia with reduced vascular perfusion and architecture is associated with lesion-induced impairment of NVC. Our physiologic MRI approach is a clinically applicable method for preoperative risk assessment for the presence of false-negative fMRI results and may prevent severe postoperative functional deficits.

Physiological MRI of microvascular architecture, neovascularization activity, and oxygen metabolism facilitate early recurrence detection in patients with IDH-mutant WHO grade 3 glioma.

PURPOSE: This study aimed to determine the diagnostic performance of physiological MRI biomarkers including microvascular perfusion and architecture, neovascularization activity, tissue oxygen metabolism, and tension for recurrence detection of IDH-mutant WHO grade 3 glioma. METHODS: Sixty patients with IDH-mutant WHO grade 3 glioma who received overall 288 follow-up MRI examinations at 3 Tesla after standard treatment were retrospectively evaluated. A conventional MRI protocol was extended with a physiological MRI approach including vascular architecture mapping and quantitative blood-oxygen-level-dependent imaging which required 7 min extra data acquisition time. Custom-made MATLAB software was used for the calculation of MRI biomarker maps of microvascular perfusion and architecture, neovascularization activity, tissue oxygen metabolism, and tension. Statistical procedures included receiver operating characteristic analysis. RESULTS: Overall, 34 patients showed recurrence of the WHO grade 3 glioma; of these, in 15 patients, recurrence was detected one follow-up examination (averaged 160 days) earlier by physiological MRI data than by conventional MRI. During this time period, the tumor volume increased significantly (P = 0.001) on average 7.4-fold from 1.5 to 11.1 cm3. Quantitative analysis of MRI biomarkers demonstrated microvascular but no macrovascular hyperperfusion in early recurrence. Neovascularization activity (AUC = 0.833), microvascular perfusion (0.682), and oxygen metabolism (0.661) showed higher diagnostic performance for early recurrence detection of WHO grade 3 glioma compared to conventional MRI including cerebral blood volume (0.649). CONCLUSION: This study demonstrated that the targeted assessment of microvascular features and tissue oxygen tension as an early sign of neovascularization activity provided valuable information for recurrence diagnostic of WHO grade 3 glioma.

Extended salvage surgery after high-dose chemoradiation therapy for tumors in the cervico-thoracic junction with invasion of the chest wall and the spine: a case series.

The treatment of malignant tumors localized in the upper thoracic cavity and involving the spine at the cervico-thoracic junction (CTJ) is challenging. We report on three patients with malignant tumors invading the thoracic inlet and the spine at the CTJ. All three patients underwent radical tumor resection and 360° spine fusion following the posterior pedicle screw instrumentation and anterior vertebrectomy combined with implantation of an expandable titanium cage. Postoperatively, a mild paresis with hypesthesia of the ipsilateral arm occurred in one patient because of brachial plexus involvement. Two patients were still alive at last follow-up after 83 and 143 months, the third patient succumbed to tumor progression 13 months after extended salvage surgery. We display the possibilities of extended 'salvage' therapy in well-selected patients that were deemed hopeless regarding neurological function, biomechanical stability and tumor control after multiple courses of combined radio-chemotherapy.

MEG Node Degree Differences in Patients with Focal Epilepsy vs. Controls-Influence of Experimental Conditions.

Drug-resistant epilepsy can be most limiting for patients, and surgery represents a viable therapy option. With the growing research on the human connectome and the evidence of epilepsy being a network disorder, connectivity analysis may be able to contribute to our understanding of epilepsy and may be potentially developed into clinical applications. In this magnetoencephalographic study, we determined the whole-brain node degree of connectivity levels in patients and controls. Resting-state activity was measured at five frequency bands in 15 healthy controls and 15 patients with focal epilepsy of different etiologies. The whole-brain all-to-all imaginary part of coherence in source space was then calculated. Node degree was determined and parcellated and was used for further statistical evaluation. In comparison to controls, we found a significantly higher overall node degree in patients with lesional and non-lesional epilepsy. Furthermore, we examined the conditions of high/reduced vigilance and open/closed eyes in controls, to analyze whether patient node degree levels can be achieved. We evaluated intraclass-correlation statistics (ICC) to evaluate the reproducibility. Connectivity and specifically node degree analysis could present new tools for one of the most common neurological diseases, with potential applications in epilepsy diagnostics.

Pulseq-CEST: Towards multi-site multi-vendor compatibility and reproducibility of CEST experiments using an open-source sequence standard.

PURPOSE: As the field of CEST grows, various novel preparation periods using different parameters are being introduced. At the same time, large, multisite clinical studies require clearly defined protocols, especially across different vendors. Here, we propose a CEST definition standard using the open Pulseq format for a shareable, simple, and exact definition of CEST protocols. METHODS: We present the benefits of such a standard in three ways: (1) an open database on GitHub, where fully defined, human-readable CEST protocols can be shared; (2) an open-source Bloch-McConnell simulation to test and optimize CEST preparation periods in silico; and (3) a hybrid MR sequence that plays out the CEST preparation period and can be combined with any existing readout module. RESULTS: The exact definition of the CEST preparation period, in combination with the flexible simulation, leads to a good match between simulations and measurements. The standard allowed finding consensus on three amide proton transfer-weighted protocols that could be compared in healthy subjects and a tumor patient. In addition, we could show coherent multisite results for a sophisticated CEST method, highlighting the benefits regarding protocol sharing and reproducibility. CONCLUSION: With Pulseq-CEST, we provide a straightforward approach to standardize, share, simulate, and measure different CEST preparation schemes, which are inherently completely defined.

Evaluation After Cochlear Implant Surgery : Correlation of Clinical Outcome and Imaging Findings using Flat-detector CT.

PURPOSE: Assessment of the cochlear implant (CI) electrode array position using flat-detector computed tomography (FDCT) to test dependence of postoperative outcome on intracochlear electrode position. METHODS: A total of 102 patients implanted with 107 CIs underwent FDCT. Electrode position was rated as 1) scala tympani, 2) scala vestibuli, 3) scalar dislocation and 4) no deconvolution. Two independent neuroradiologists rated all image data sets twice and the scalar position was verified by a third neuroradiologist. Presurgical and postsurgical speech audiometry by the Freiburg monosyllabic test was used to evaluate auditory outcome after 6 months of speech rehabilitation. RESULTS: Electrode array position was assessed by FDCT in 107 CIs. Of the electrodes 60 were detected in the scala tympani, 21 in the scala vestibuli, 24 electrode arrays showed scalar dislocation and 2 electrodes were not placed in an intracochlear position. There was no significant difference in rehabilitation outcomes between scala tympani and scala vestibuli inserted patients. Rehabilitation was also possible in patients with dislocated electrodes. CONCLUSION: The use of FDCT is a reliable diagnostic method to determine the position of the electrode array. In our study cohort, the electrode position had no significant impact on postoperative outcome except for non-deconvoluted electrode arrays.