2D 1H sLASER Long-TE and 3D 31P Chemical Shift Imaging at 3 T for Monitoring Fasting-Induced Changes in Brain Tumor Tissue.

BACKGROUND: Emerging evidence suggests that fasting could play a key role in cancer treatment. Its metabolic effects on gliomas require further investigation. PURPOSE: To design a multi-voxel 1H/31P MR-spectroscopic imaging (MRSI) protocol for noninvasive metabolic monitoring of cerebral, fasting-induced changes on an individual patient/tumor level, and to assess its technical reliability/reproducibility. STUDY TYPE: Prospective. POPULATION: MRS phantom. Twenty-two patients (mean age = 61, 6 female) with suspected WHO grade II-IV glioma examined before and after 72-hour-fasting prior to biopsy/resection. FIELD STRENGTH/SEQUENCE: 3-T, 1H decoupled 3D 31P MRSI, 2D 1H sLASER MRSI at an echo time of 144 msec, 2D 1H MRSI (as water reference), T1-weighted, T1-weighted contrast-enhanced, T2-weighted, and FLAIR. sLASER and PRESS sequences were used for phantom measurements. ASSESSMENT: Phantom measurements and spectral simulations were performed with various echo-times for protocol optimization. In vivo spectral analyses were conducted using LCModel and AMARES, obtaining quality/fitting parameters (linewidth, signal-to-noise-ratio, and uncertainty measures of fitting) and metabolite intensities. The volume of glioma sub-regions was calculated and correlated with MRS findings. Ex-vivo spectra of necrotic tumor tissues were obtained using high-resolution magic-angle spinning (HR-MAS) technique. STATISTICAL TESTS: Wilcoxon signed-rank test, Bland-Altman plots, and coefficient of variation were used for repeatability analysis of quality/fitting parameters and metabolite concentrations. Spearman ρ correlation for the concentration of ketone bodies with volumes of glioma sub-regions was determined. A P-value <0.05 was considered statistically significant. RESULTS: 1H and 31P repeatability measures were highly consistent between the two sessions. ß-hydroxybutyrate and acetoacetate were detectable (fitting-uncertainty <50%) in glioma sub-regions of all patients who completed the 72-hour-fasting cycle. ß-hydroxybutyrate accumulation was significantly correlated with the necrotic/non-enhancing tumor core volume (ρ = 0.81) and validated using ex-vivo 1H HR-MAS. DATA CONCLUSION: We propose a comprehensive MRS protocol that may be used for monitoring cerebral, fasting-induced changes in patients with glioma. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 4.

Benchmarking palliative care practices in neurooncology: a german perspective.

PURPOSE: To benchmark palliative care practices in neurooncology centers across Germany, evaluating the variability in palliative care integration, timing, and involvement in tumor board discussions. This study aims to identify gaps in care and contribute to the discourse on optimal palliative care strategies. METHODS: A survey targeting both German Cancer Society-certified and non-certified university neurooncology centers was conducted to explore palliative care frameworks and practices for neurooncological patients. The survey included questions on palliative care department availability, involvement in tumor boards, timing of palliative care integration, and use of standardized screening tools for assessing palliative burden and psycho-oncological distress. RESULTS: Of 57 centers contacted, 46 responded (81% response rate). Results indicate a dedicated palliative care department in 76.1% of centers, with palliative specialists participating in tumor board discussions at 34.8% of centers. Variability was noted in the initiation of palliative care, with early integration at the diagnosis stage in only 30.4% of centers. The survey highlighted a significant lack of standardized spiritual care assessments and minimal use of advanced care planning. Discrepancies were observed in the documentation and treatment of palliative care symptoms and social complaints, underscoring the need for comprehensive care approaches. CONCLUSION: The study highlights a diverse landscape of palliative care provision within German neurooncology centers, underscoring the need for more standardized practices and early integration of palliative care. It suggests the necessity for standardized protocols and guidelines to enhance palliative care's quality and uniformity, ultimately improving patient-centered care in neurooncology.

MR imaging profile and histopathological characteristics of tumour vasculature, cell density and proliferation rate define two distinct growth patterns of human brain metastases from lung cancer.

PURPOSE: Non-invasive prediction of the tumour of origin giving rise to brain metastases (BMs) using MRI measurements obtained in radiological routine and elucidating the biological basis by matched histopathological analysis. METHODS: Preoperative MRI and histological parameters of 95 BM patients (female, 50; mean age 59.6 ± 11.5 years) suffering from different primary tumours were retrospectively analysed. MR features were assessed by region of interest (ROI) measurements of signal intensities on unenhanced T1-, T2-, diffusion-weighted imaging and apparent diffusion coefficient (ADC) normalised to an internal reference ROI. Furthermore, we assessed BM size and oedema as well as cell density, proliferation rate, microvessel density and vessel area as histopathological parameters. RESULTS: Applying recursive partitioning conditional inference trees, only histopathological parameters could stratify the primary tumour entities. We identified two distinct BM growth patterns depending on their proliferative status: Ki67high BMs were larger (p = 0.02), showed less peritumoural oedema (p = 0.02) and showed a trend towards higher cell density (p = 0.05). Furthermore, Ki67high BMs were associated with higher DWI signals (p = 0.03) and reduced ADC values (p = 0.004). Vessel density was strongly reduced in Ki67high BM (p < 0.001). These features differentiated between lung cancer BM entities (p ≤ 0.03 for all features) with SCLCs representing predominantly the Ki67high group, while NSCLCs rather matching with Ki67low features. CONCLUSION: Interpretable and easy to obtain MRI features may not be sufficient to predict directly the primary tumour entity of BM but seem to have the potential to aid differentiating high- and low-proliferative BMs, such as SCLC and NSCLC.

Path to success: female leaders in German neurosurgery.

Despite advances in gender equality, only 6% of German neurosurgical departments are currently led by women. With regard to their pioneering work and the importance of their role model effect, we aimed at reporting on the career pathways of the present and former female chairs of neurosurgical departments in Germany. We approached current and former female chairs in German neurosurgery and gathered descriptive information on their ways into leadership positions through structured interviews. Data were obtained from 16/22 (72.7%) female neurosurgical chairs, aged between 44 and 82 years. They completed their training within 6.5 ± 0.6 years, and it took them further 14.5 ± 5.9 years between training completion and chair acquisition. Having obtained their chair positions between 1993 and 2020, six (37.5%) of them have retired or changed career tracks. Of ten (62.5%) chairs still practicing, two are directors of university departments. Twelve (75.0%) hold professorships. Nine chairs (56.3%) are married, eight (50.0%) having children. Five chairs reported having experienced gender-based discrimination. Twelve had a male mentor or role model, two had a female role model, while only one had a female mentor. This study characterizes the to date small number of female neurosurgical chairs in Germany and their paths to neurosurgical leadership positions. In future, these should become historical in order to perceive the presence of women in leadership positions as self-evident normality, reflecting our society. However, further analyses comparing paths of both female and male neurosurgical chairs are necessary to explore gender-based differences in achieving neurosurgical leadership positions.

Immune profile and radiological characteristics of progressive multifocal leukoencephalopathy.

BACKGROUND AND PURPOSE: Progressive multifocal leukoencephalopathy (PML) constitutes a severe disease with increasing incidence, mostly in the context of immunosuppressive therapies. A detailed understanding of immune response in PML appears critical for the treatment strategy. The aim was a comprehensive immunoprofiling and radiological characterization of magnetic resonance imaging (MRI) defined PML variants. METHODS: All biopsy-confirmed PML patients (n = 15) treated in our department between January 2004 and July 2019 were retrospectively analysed. Data from MRI, histology as well as detailed clinical and outcome data were collected. The MRI-defined variants of classical (cPML) and inflammatory (iPML) PML were discriminated based on the intensity of gadolinium enhancement. In these PML variants, intensity and localization (perivascular vs. parenchymal) of inflammation in MRI and histology as well as the cellular composition by immunohistochemistry were assessed. The size of the demyelinating lesions was correlated with immune cell infiltration. RESULTS: Patients with MRI-defined iPML showed a stronger intensity of inflammation with an increased lymphocyte infiltration on histological level. Also, iPML was characterized by a predominantly perivascular inflammation. However, cPML patients also demonstrated certain inflammatory tissue alterations. Infiltration of CD163-positive microglia and macrophage (M/M) subtypes correlated with PML lesion size. CONCLUSIONS: The non-invasive MRI-based discrimination of PML variants allows for an estimation of inflammatory tissue alterations, although exhibiting limitations in MRI-defined cPML. The association of a distinct phagocytic M/M subtype with the extent of demyelination might reflect disease progression.

Concurrent CNS tumors and multiple sclerosis: retrospective single-center cohort study and lessons for the clinical management.

INTRODUCTION: The concurrent presence of both central nervous system (CNS) tumors and multiple sclerosis (MS) poses various diagnostic and therapeutic pitfalls and makes the clinical management of such patients challenging. METHODS: In this retrospective, single-center cohort study, we searched our clinical databases (2006-2019) for patients with concurrent CNS tumors and MS and described their disease courses. Age at diagnosis of the respective disease and probabilities for MS disease activity events (DAEs) with vs. without prior tumor-specific therapy were tested pairwise using t-test for dependent samples and exact binomial test. RESULTS: N = 16 patients with concurrent CNS tumors and MS were identified. MS diagnosis preceded the CNS oncological diagnosis by an average of 9 years (p = 0.004). More DAEs occurred in patients without prior chemotherapy (83.3%) than in patients with prior chemotherapy (16.7%; p = 0.008). This effect did not reach significance for patients with prior radiation therapy/radiosurgery (66.7% vs. 33.3%, p = 0.238). The average interval between DAEs and the last documented lymphopenia was 32.25 weeks. CONCLUSIONS: This study describes the clinical and demographic features of patients with concurrent CNS tumors and MS and suggests several practical approaches to their clinical management. Our findings suggest that adding a disease-modifying MS therapy to the regimen of patients treated with chemotherapy is necessary only if the patient suffers from a highly active, aggressive course of MS. In view of the lack of prospective trials, individual risk assessments should remain the foundation of the decision on MS treatment in concurrent CNS tumor diseases.

Implementation of the "No ICU - Unless" approach in postoperative neurosurgical management in times of COVID-19.

Following elective craniotomy, patients routinely receive 24-h monitoring in an intensive care unit (ICU). However, the benefit of intensive care monitoring and treatment in these patients is discussed controversially. This study aimed to evaluate the complication profile of a "No ICU - Unless" strategy and to compare this strategy with the standardized management of post-craniotomy patients in the ICU. Two postoperative management strategies were compared in a matched-pair analysis: The first cohort included patients who were managed in the normal ward postoperatively ("No ICU - Unless" group). The second cohort contained patients routinely admitted to the ICU (control group). Outcome parameters contained detailed complication profile, length of hospital and ICU stay, duration to first postoperative mobilization, number of unplanned imaging before scheduled postoperative imaging, number and type of intensive care interventions, as well as pre- and postoperative modified Rankin scale (mRS). Patient characteristics and clinical course were analyzed using electronic medical records. The No ICU - Unless (NIU) group consisted of 96 patients, and the control group consisted of 75 patients. Complication rates were comparable in both cohorts (16% in the NIU group vs. 17% in the control group; p = 0.123). Groups did not differ significantly in any of the outcome parameters examined. The length of hospital stay was shorter in the NIU group but did not reach statistical significance (average 5.8 vs. 6.8 days; p = 0.481). There was no significant change in the distribution of preoperative (p = 0.960) and postoperative (p = 0.425) mRS scores in the NIU and control groups. Routine postoperative ICU management does not reduce postoperative complications and does not affect the surgical outcome of patients after elective craniotomies. Most postoperative complications are detected after a 24-h observation period. This approach may represent a potential strategy to prevent the overutilization of ICU capacities while maintaining sufficient postoperative care for neurosurgical patients.

Proposed definition of competencies for surgical neuro-oncology training.

OBJECTIVE: The aim of this work is to define competencies and entrustable professional activities (EPAs) to be imparted within the framework of surgical neuro-oncological residency and fellowship training as well as the education of medical students. Improved and specific training in surgical neuro-oncology promotes neuro-oncological expertise, quality of surgical neuro-oncological treatment and may also contribute to further development of neuro-oncological techniques and treatment protocols. Specific curricula for a surgical neuro-oncologic education have not yet been established. METHODS: We used a consensus-building approach to propose skills, competencies and EPAs to be imparted within the framework of surgical neuro-oncological training. We developed competencies and EPAs suitable for training in surgical neuro-oncology. RESULT: In total, 70 competencies and 8 EPAs for training in surgical neuro-oncology were proposed. EPAs were defined for the management of the deteriorating patient, the management of patients with the diagnosis of a brain tumour, tumour-based resections, function-based surgical resections of brain tumours, the postoperative management of patients, the collaboration as a member of an interdisciplinary and/or -professional team and finally for the care of palliative and dying patients and their families. CONCLUSIONS AND RELEVANCE: The present work should subsequently initiate a discussion about the proposed competencies and EPAs and, together with the following discussion, contribute to the creation of new training concepts in surgical neuro-oncology.

Single-shot bevacizumab for cerebral radiation injury.

BACKGROUND: Cerebral radiation injury, including subacute radiation reactions and later stage radiation necrosis, is a severe side effect of brain tumor radiotherapy. A protocol of four infusions of the monoclonal antibody bevacizumab has been shown to be a highly effective treatment. However, bevacizumab is costly and can cause severe complications including thrombosis, bleeding and gastrointestinal perforations. METHODS: We performed a retrospective analysis of patients treated in our clinic for cerebral radiation injury who received only a singular treatment with bevacizumab. Single-shot was defined as a singular administration of bevacizumab without a second administration during an interval of at least 6 weeks. RESULTS: We identified 11 patients who had received a singular administration of bevacizumab to treat cerebral radiation injury. Prior radiation had been administered to treat gliomas (ten patients) or breast cancer brain metastases (one patient). 9 of 10 patients with available MRIs showed a marked reduction of edema at first follow-up. Discontinuation of Dexamethasone was possible in 6 patients and a significant dose reduction could be achieved in all other patients. One patient developed pulmonary artery embolism 2 months after bevacizumab administration. The median time to treatment failure of any cause was 3 months. CONCLUSIONS: Single-shot bevacizumab therefore has meaningful activity in cerebral radiation injury, but durable control is rarely achieved. In patients where a complete protocol of four infusions with bevacizumab is not feasible due to medical contraindications or lack of reimbursement, single-shot bevacizumab treatment may be considered.

Low-Frequency Oscillations Code Speech during Verbal Working Memory.

The way the human brain represents speech in memory is still unknown. An obvious characteristic of speech is its evolvement over time. During speech processing, neural oscillations are modulated by the temporal properties of the acoustic speech signal, but also acquired knowledge on the temporal structure of language influences speech perception-related brain activity. This suggests that speech could be represented in the temporal domain, a form of representation that the brain also uses to encode autobiographic memories. Empirical evidence for such a memory code is lacking. We investigated the nature of speech memory representations using direct cortical recordings in the left perisylvian cortex during delayed sentence reproduction in female and male patients undergoing awake tumor surgery. Our results reveal that the brain endogenously represents speech in the temporal domain. Temporal pattern similarity analyses revealed that the phase of frontotemporal low-frequency oscillations, primarily in the beta range, represents sentence identity in working memory. The positive relationship between beta power during working memory and task performance suggests that working memory representations benefit from increased phase separation.SIGNIFICANCE STATEMENT Memory is an endogenous source of information based on experience. While neural oscillations encode autobiographic memories in the temporal domain, little is known on their contribution to memory representations of human speech. Our electrocortical recordings in participants who maintain sentences in memory identify the phase of left frontotemporal beta oscillations as the most prominent information carrier of sentence identity. These observations provide evidence for a theoretical model on speech memory representations and explain why interfering with beta oscillations in the left inferior frontal cortex diminishes verbal working memory capacity. The lack of sentence identity coding at the syllabic rate suggests that sentences are represented in memory in a more abstract form compared with speech coding during speech perception and production.

The ability to return to work: a patient-centered outcome parameter following glioma surgery.

BACKGROUND: With refinements in diagnosis and therapy of gliomas, the importance of survival time as the sole outcome parameter has decreased, and patient-centered outcome parameters have gained interest. Pursuing a profession is an indispensable component of human happiness. The aim of this study was to analyze the professional outcomes besides their neuro-oncological and functional evaluation after surgery for gliomas in eloquent areas. METHODS: We assessed neuro-oncological and functional outcomes of patients with gliomas WHO grades II and III undergoing surgery between 2012 and 2018. All patients underwent routine follow-up and adjuvant treatment. Treatment and survival parameters were collected prospectively. Repercussions of the disease on the patients' professional status, socio-economic situation, and neurocognitive function were evaluated retrospectively with questionnaires. RESULTS: We analyzed data of 58 patients with gliomas (WHO II: 9; III: 49). Median patient age was 35.8 years (range 21-63 years). Awake surgery techniques were applied in 32 patients (55.2%). Gross total and subtotal tumor resections were achieved in 33 (56.9%) and 17 (29.3%) patients, respectively, whereas in 8 patients (13.8%) resection had to remain partial. Most patients (n = 46; 79.3%) received adjuvant treatment. Median follow up was 43.8 months (range 11-82 months). After treatment 41 patients (70.7%) were able to resume a working life. Median time until returning to work was 8.0 months (range 0.2-22.0 months). To be younger than 40 at the time of the surgery was associated with a higher probability to return to work (p < .001). Multivariable regression analysis showed that patient age < 40 years as well as occupational group and self-reported fatigue were factors independently associated with the ability to return to work. CONCLUSION: The ability to resume professional activities following brain tumor surgery is an important patient-oriented outcome parameter. We found that the majority of patients with gliomas were able to return to work following surgical and adjuvant treatment. Preservation of neurological function is of utmost relevance for individual patients´ quality of life.

Contrast enhancing spots as a new pattern of late onset pseudoprogression in glioma patients.

INTRODUCTION: Magnet resonance imaging (MRI) of gliomas is assessed by Response Assessment in Neuro-Oncology Criteria (RANO), which define new contrast-enhancing lesions as a sign for tumor recurrence. Pseudoprogression after radiotherapy may mimic tumor progression in MRI but is usually limited to the first months after irradiation. We noted a late onset pattern of new contrast-enhancing spots (NCES) appearing years after radiotherapy. METHODS: We prospectively collected 23 glioma patients with 26 NCES (three patients had two separate NCES events) between 2014 and 2016 in our weekly tumor board without further selection by diagnosis, molecular markers or pretreatment. RESULTS: Retrospective analysis revealed a homogeneous collective of young patients (median age of 49 years at NCES) with mainly IDH-mutated glioma (61%). Initial histology showed 26% glioblastoma, 52% grade III and 22% grade II glioma. NCES occurred at late follow-up with a median of 52 months after tumor diagnosis and 30 months after the last radiotherapy. The majority of NCES regressed spontaneously within a median of 10 months (n = 11) or remained stable without further therapy with a median follow-up of 26 months (n = 7). Only 4 NCES developed MRI morphologically into tumor recurrence. Two NCES were resected without any histopathological proof of tumor recurrence, and in 2 other cases NCES were defined as ischemic stroke or radionecrosis. CONCLUSION: We hypothesize that the late onset phenomenon of NCES predominantly represents a form of radiation-induced vasculopathy that is different from early pseudoprogression and should be considered especially in younger patients with IDH-mutated glioma before initiation of new therapy.

Influence of pregnancy on glioma patients.

BACKGROUND: Data about the influence of pregnancy on progression-free survival and overall survival of glioma patients are sparse and controversial. We aimed at providing further evidence on this relation. METHODS: The course of 18 glioma patients giving birth to 23 children after tumor surgery was reviewed and compared to the course of 18 nulliparous female patients matched for tumor diagnosis including molecular markers, extent of resection, and tumor location. RESULTS: Tumor pathology was astrocytoma, oligodendroglioma, and ependymoma in 9, 6, and 3 patients, respectively. Time interval between tumor resection and delivery was 5.3 ± 4.4 years. All newborns were healthy after uneventful deliveries. Tumor progression was diagnosed before pregnancy in 4 patients and during pregnancy in 1 patient, and 4 patients displayed progressive disease 31.0 ± 11 months after delivery. Three of these latter patients underwent second surgery, whereas resection of recurrent tumor had been performed in 2 women before pregnancy. Among nulliparous patients, 9 women suffered from tumor progression, resulting in re-operation in 7 patients and/or further adjuvant treatment in 6 cases. Progression-free survival did not differ between patients with and patients without children (p = 0.4). Moreover, in both groups, median overall survival was not reached after a mean follow-up period of 9.7 ± 5.7 years in glioma patients who gave birth to a child and 8.9 ± 4.2 years in nulliparous glioma patients. CONCLUSION: Pregnancy does not seem to influence the clinical course of glioma patients. Likewise, glioma seems not to have an impact on delivered children's health.

Dexamethasone-induced leukocytosis is associated with poor survival in newly diagnosed glioblastoma.

Despite its well-characterized side effects, dexamethasone is widely used in the pre-, peri- and postoperative neurosurgical setting due to its effective relief of tumor-induced symptoms through the reduction of tumor-associated edema. However, some patients show laboratory-defined dexamethasone induced elevation of white blood cell count, and its impact on glioblastoma progression is unknown. We retrospectively analyzed 113 patients with newly diagnosed glioblastoma to describe the incidence, risk factors and clinical features of dexamethasone-induced leukocytosis in primary glioblastoma patients. We further conducted an immunohistochemical analysis of the granulocyte and lymphocyte tumor-infiltration in the available corresponding histological sections. Patient age was identified to be a risk factor for the development of dexamethasone-induced leukocytosis (p < 0.05). The presence of dexamethasone-induced leukocytosis decreased overall survival (HR 2.25 95% CI [1.15-4.38]; p < 0.001) and progression-free survival (HR 2.23 95% CI [1.09-4.59]; p < 0.01). Furthermore, patients with dexamethasone-induced leukocytosis had significantly reduced CD15 + granulocytic- (p < 0.05) and CD3 + lymphocytic tumour infiltration (p < 0.05). We identified a subgroup of glioblastoma patients that are at particularly high risk for poor outcome upon dexamethasone treatment. Therefore, restrictive dosage or other edema reducing substances should be considered in patients with dexamethasone-induced leukocytosis.

Pre- and early postoperative GFAP serum levels in glioma and brain metastases.

SUBJECT: To date there is no established tumor marker for the clinical follow-up of glioblastoma, WHO grade IV, (GBM) which constitutes the most frequent and malignant primary brain tumor. However, since there is promising data that the serum glial fibrillary acidic protein (sGFAP) may serve as a biomarker for glial brain tumors, this prospective study aimed at evaluating the diagnostic relevance of perioperative changes in sGFAP levels for the assessment of residual glial tumor tissue in patients undergoing surgery of intracerebral tumors. METHODS: Serum GFAP was measured using an electrochemiluminometric immunoassay (ElecsysR GFAP prototype test, Roche Diagnostics, Penzberg/Germany) in 32 prospectively recruited patients between September 2009 and August 2010. Twenty-five were diagnosed with glioma and seven with brain metastases (BM). We assessed sGFAP levels prior to and at different time points during the early postoperative phase until patient discharge. RESULTS: There were only significant differences in the pre-operative sGFAP levels of patients with gliomas compared to BM (0.18 vs. 0.08 µg/l; p = 0.0198, Welch's t-Test). Even though there was an increase of sGFAP after surgery, there were no significant differences between glioma and BM patients at any other time point. Peak sGFAP levels where reached on postoperative day 1 followed by a slight decrease, but not reaching pre-operative levels until postop day 7. There was no significant correlation between postoperative glioma tumor volume and sGFAP levels in univariate analyses. CONCLUSION: According to our data sGFAP does not appear to be suitable to detect residual glioma tissue in the acute postoperative phase.

Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging.

OBJECTIVE: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers. METHODS: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery. RESULTS: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI. CONCLUSION: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of ≤ 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET. IMPORTANCE OF THE STUDY: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.

Combination of 5-ALA and iMRI in re-resection of recurrent glioblastoma.

Background Tumour resection plays a role in the initial treatment but also in the setting of recurrent glioblastoma (rGBM). To achieve maximum resection, 5-aminolevulinic acid (5-ALA) and intraoperative MRI (iMRI) are used as surgical tools. Aiming at complete tumour re-resection, we started combining iMRI with 5-ALA to find out if this leads to better surgical results. Methods We performed tumour resections in seven patients with rGBM, combining 5-ALA (20 mg/kg bodyweight) with iMRI (0.15 T). Radiologically complete resections were intended in all seven patients. We assessed intraoperative fluorescence findings and compared these with intraoperative imaging. All patients had early postoperative MRI (3 T) to verify final iMRI scans and received adjuvant treatment according to interdisciplinary tumour board decision. Results Median patient age was 63 years. Median KPS score was 90, and median tumour volume was 8.2 cm(3). In six of seven patients (85%), 5-ALA induced fluorescence of tumour-tissue was detected intraoperatively. All tumours were good to visualise with iMRI and contrast media. One patient received additional resection of residual contrast enhancing tissue on intraoperative imaging, which did not show fluorescence. Radiologically complete resections according to early postoperative MRI were achieved in all patients. Median survival since second surgery was 7.6 months and overall survival since diagnosis was 27.8 months. Conclusions 5-ALA and iMRI are important surgical tools to maximise tumour resection also in rGBM. However, not all rGBMs exhibit fluorescence after 5-ALA administration. We propose the combined use of 5-ALA and iMRI in the surgery of rGBM.

Brain surface reformatted imaging (BSRI) for intraoperative neuronavigation in brain tumor surgery.

BACKGROUND: For safe resection of lesions situated in or near eloquent brain regions, determination of their spatial and functional relationship is crucial. Since functional magnetic resonance imaging and intraoperative neurophysiological mapping are not available in all neurosurgical departments, we aimed to evaluate brain surface reformatted imaging (BSRI) as an additional display mode for neuronavigation. METHODS: Eight patients suffering from perirolandic tumors were preoperatively studied with MRI and navigated transcranial magnetic stimulation (nTMS). Afterwards, the MRI was automatically transformed into BSR images in neuronavigation software (Brainlab, Brainlab AG, Feldkirchen, Germany). One experienced neuroradiologist, one experienced neurosurgeon, and two residents determined hand representation areas ipsilateral to each tumor on two-dimensional (2D) MR images and on BSR images. All results were compared to results from intraoperative direct cortical mapping of the hand motor cortex and to preoperative nTMS results. RESULTS: Findings from nTMS and intraoperative direct cortical mapping of the hand motor cortex were congruent in all cases. Hand representation areas were correctly determined on BSR images in 81.3 % and on 2D-MR images in 93.75 % (p = 0.26). In a subgroup analysis, experienced observers showed more familiarity with BSRI than residents (96.9 vs. 84.4 % correct results, p = 0.19), with an equal error rate for 2D-MRI. The time required to define hand representation areas was significantly shorter using BSRI than using standard MRI (mean 27.4 vs. 40.4 s, p = 0.04). CONCLUSIONS: With BSRI, a new method for neuronavigation is now available, allowing fast and easy intraoperative localization of distinct brain regions.

Disturbance in cerebral blood microcirculation and hypoxic-ischemic microenvironment are associated with the development of brain metastasis.

Brain metastases (BM) constitute an increasing challenge in oncology due to their impact on neurological function, limited treatment options, and poor prognosis. BM occur through extravasation of circulating tumor cells across the blood-brain barrier. However, the extravasation processes are still poorly understood. We here propose a brain colonization process which mimics infarction-like microenvironmental reactions, that is dependent on Angiopoietin (Ang-2) and vascular endothelial growth factor (VEGF). In this study, intracardiac BM models were used, and cerebral blood microcirculation was monitored by 2-photon microscopy through a cranial window. BM formation was observed using cranial magnetic resonance, bioluminescent imaging, and post-mortem autopsy. Ang-2/VEGF targeting strategies and Ang-2 gain-of-function (GOF) mice were employed to interfere with BM formation. In addition, vascular and stromal factors as well as clinical outcome were analyzed in BM patients. Blood vessel occlusions by cancer cells were detected, accompanied by significant disturbances of cerebral blood microcirculation, and focal stroke-like histological signs. Cerebral endothelial cells showed an elevated Ang-2 expression both in mouse and human BM. Ang-2 GOF resulted in an increased BM burden. Combined anti-Ang-2/anti-VEGF therapy led to a decrease in brain metastasis size and number. Ang-2 expression in tumor vessels of established human brain metastases negatively correlated with survival. Our observations revealed a relationship between disturbance of cerebral blood microcirculation and brain metastasis formation. This suggests that vessel occlusion by tumor cells facilitates brain metastatic extravasation and seeding, while combined inhibition of microenvironmental effects of Ang-2 and VEGF prevent the outgrowth of macrometastases.