Intraoperative confocal laser endomicroscopy during 5-aminolevulinic acid-guided glioma surgery: significant considerations for resection at the tumor margin.

OBJECTIVE: Because gliomas have poorly defined tumor margins, the ability to achieve maximal resection is limited. To better discern these margins, fluorescence-guided surgery has been used to aid maximal safe resection. The authors describe their experience with the simultaneous use of intraoperative fluorescein sodium (FNa) confocal laser endomicroscopy (CLE) and operating microscope 5-aminolevulinic acid (5-ALA) fluorescence imaging for glioma resection to improve CLE use for better margin discrimination. METHODS: FNa CLE and 5-ALA wide-field imaging were used in 33 patients with gliomas. CLE imaging was enhanced with the use of a telesurgical pathology software platform that enables real-time conversation between the operating neurosurgeons and the pathologists located remotely. CLE was used for imaging tumor regions that were subjectively regarded as tumor margins under normal visualization with the operative microscope. After FNa CLE imaging, 5-ALA wide-field imaging was performed in the same regions. Tissue was biopsied at imaging locations, and interpretations of FNa CLE and 5-ALA wide-field imaging were compared to those of permanent histological sections. RESULTS: Eighty-eight deep- and superficial-margin regions of interest (ROIs) were imaged with FNa CLE and 5-ALA imaging. Most of the ROIs interpreted by the neuropathologist as infiltrative glioma based on FNa CLE imaging lacked 5-ALA-induced fluorescence. Permanent histological sections from the corresponding regions were concordant with the interpretation of FNa CLE images in 57 of 88 (65%) ROIs and with the interpretation of 5-ALA imaging in 43 of 88 (49%) ROIs. The sensitivity and specificity of FNa CLE for the interpretation of tumor margins were 73% and 41%, respectively, and those of 5-ALA were 38% and 82%, respectively. Positive and negative predictive values for CLE were 79% and 33%, respectively, and those for 5-ALA were 86% and 31%, respectively. CONCLUSIONS: Conventional intraoperative evaluation of tumor margins, based on MRI and wide-field fluorescence imaging, can underestimate the invasiveness of gliomas. FNa CLE showed higher accuracy in detecting regions with infiltrating tumors than intraoperative 5-ALA imaging. Future considerations should include more rigorous comparisons of FNa CLE imaging and 5-ALA-guided resections on a larger cohort of patients.

Resection versus biopsy in patients with glioblastoma (RESBIOP study): study protocol for an international multicentre prospective cohort study (ENCRAM 2202).

INTRODUCTION: There are no guidelines or prospective studies defining the optimal surgical treatment for glioblastomas in older patients (≥70 years), for those with a limited functioning performance at presentation (Karnofsky Performance Scale ≤70) or for those with tumours in certain locations (midline, multifocal). Therefore, the decision between resection and biopsy is varied, among neurosurgeons internationally and at times even within an institution. This study aims to compare the effects of maximal tumour resection versus tissue biopsy on survival, functional, neurological and quality of life outcomes in these patient subgroups. Furthermore, it evaluates which modality would maximise the potential to undergo adjuvant treatment. METHODS AND ANALYSIS: This study is an international, multicentre, prospective, two-arm cohort study of an observational nature. Consecutive patients with glioblastoma will be treated with resection or biopsy and matched with a 1:1 ratio. Primary endpoints are (1) overall survival and (2) proportion of patients that have received adjuvant treatment with chemotherapy and radiotherapy. Secondary endpoints are (1) proportion of patients with National Institute of Health Stroke Scale deterioration at 6 weeks, 3 months and 6 months after surgery; (2) progression-free survival (PFS); (3) quality of life at 6 weeks, 3 months and 6 months after surgery and (4) frequency and severity of serious adverse events. The total duration of the study is 5 years. Patient inclusion is 4 years; follow-up is 1 year. ETHICS AND DISSEMINATION: The study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media. TRIAL REGISTRATION NUMBER: NCT06146725.

Single versus multiple fraction stereotactic radiosurgery for medium-sized brain metastases (4-14 cc in volume): reducing or fractionating the radiosurgery dose?

Background and purpose: Stereotactic radiosurgery (SRS) of brain metastases (BM) and resection cavities is a widely used and effective treatment modality. Based on target lesion size and anatomical location, single fraction SRS (SF-SRS) or multiple fraction SRS (MF-SRS) are applied. Current clinical recommendations conditionally recommend either reduced dose SF-SRS or MF-SRS for medium-sized BM (2-2.9 cm in diameter). Despite excellent local control rates, SRS carries the risk of radionecrosis (RN). The purpose of this study was to assess the 12-months local control (LC) rate and 12-months RN rate of this specific patient population. Materials and methods: This single-center retrospective study included 54 patients with medium-sized intact BM (n=28) or resection cavities (n=30) treated with either SF-SRS or MF-SRS. Follow-up MRI was used to determine LC and RN using a modification of the "Brain Tumor Reporting and Data System" (BT-RADS) scoring system. Results: The 12-month LC rate following treatment of intact BM was 66.7% for SF-SRS and 60.0% for MF-SRS (p=1.000). For resection cavities, the 12-month LC rate was 92.9%% after SF-SRS and 46.2% after MF-SRS (p=0.013). For intact BM, RN rate was 17.6% for SF-SRS and 20.0% for MF-SRS (p=1.000). For resection cavities, RN rate was 28.6% for SF-SRS and 20.0% for MF-SRS (p=1.000). Conclusion: Patients with intact BM showed no statistically significant differences in 12-months LC and RN rate following SF-SRS or MF-SRS. In patients with resection cavities the 12-months LC rate was significantly better following SF-SRS, with no increase in the RNFS.

Velocity and pattern of growth of intracranial meningiomas.

OBJECTIVE: The authors' aim was to assess the velocity and pattern of growth of meningiomas and to correlate the kinetics of tumor growth with their previously reported two-item radiological risk stratification and CNS WHO grade (5th edition, 2021). METHODS: The authors performed a serial volumetric analysis of meningiomas diagnosed radiologically at their institution between 2003 and 2015. The primary endpoint was velocity of diametric expansion (VDE), which represents the slope of the linear regression of the mean tumor diameter against time. For the secondary analysis, they categorized the growth patterns as linear or exponential by fitting time-volume curves to a linear and exponential function. Three radiological risk categories based on T2-weighted iso/hyperintensity and absence of calcifications were compared: low risk (T2-weighted hypointense), intermediate-risk (T2-weighted iso/hyperintense with calcifications), and high-risk (T2-weighted iso/hyperintense without calcifications) tumors. RESULTS: For the entire cohort of 240 meningiomas, the median (IQR) VDE was 0.33 (0.00-0.71) mm/year. Distribution of VDE differed significantly among radiological risk categories (0.49 vs 0.35 vs 0.05 mm/year, p < 0.001). High-risk and intermediate-risk tumors more frequently tended to grow exponentially compared to low-risk tumors (43.8% vs 37.0% vs 8.3%, p = 0.067). The authors found no correlation of growth velocity with CNS WHO grade in their cohort (1.30 mm/year for CNS WHO grade 1 vs 4.01 mm/year for CNS WHO grade 2, p = 0.185). CONCLUSIONS: A radiological risk assessment using two parameters-T2-weighted signal iso/hyperintensity and absence of calcifications-allows estimation of growth velocity and characteristics of untreated intracranial meningiomas. Only high-risk tumors exhibit the potential for rapid growth. However, rapid tumor growth does not indicate a higher CNS WHO grade per se.

Characterization of Polarimetric Properties in Various Brain Tumor Types Using Wide-Field Imaging Mueller Polarimetry.

Neuro-oncological surgery is the primary brain cancer treatment, yet it faces challenges with gliomas due to their invasiveness and the need to preserve neurological function. Hence, radical resection is often unfeasible, highlighting the importance of precise tumor margin delineation to prevent neurological deficits and improve prognosis. Imaging Mueller polarimetry, an effective modality in various organ tissues, seems a promising approach for tumor delineation in neurosurgery. To further assess its use, we characterized the polarimetric properties by analysing 45 polarimetric measurements of 27 fresh brain tumor samples, including different tumor types with a strong focus on gliomas. Our study integrates a wide-field imaging Mueller polarimetric system and a novel neuropathology protocol, correlating polarimetric and histological data for accurate tissue identification. An image processing pipeline facilitated the alignment and overlay of polarimetric images and histological masks. Variations in depolarization values were observed for grey and white matter of brain tumor tissue, while differences in linear retardance were seen only within white matter of brain tumor tissue. Notably, we identified pronounced optical axis azimuth randomization within tumor regions. This study lays the foundation for machine learning-based brain tumor segmentation algorithms using polarimetric data, facilitating intraoperative diagnosis and decision making.

SUPRAMAX-study: supramaximal resection versus maximal resection for glioblastoma patients: study protocol for an international multicentre prospective cohort study (ENCRAM 2201).

INTRODUCTION: A greater extent of resection of the contrast-enhancing (CE) tumour part has been associated with improved outcomes in glioblastoma. Recent results suggest that resection of the non-contrast-enhancing (NCE) part might yield even better survival outcomes (supramaximal resection, SMR). Therefore, this study evaluates the efficacy and safety of SMR with and without mapping techniques in high-grade glioma (HGG) patients in terms of survival, functional, neurological, cognitive and quality of life outcomes. Furthermore, it evaluates which patients benefit the most from SMR, and how they could be identified preoperatively. METHODS AND ANALYSIS: This study is an international, multicentre, prospective, two-arm cohort study of observational nature. Consecutive glioblastoma patients will be operated with SMR or maximal resection at a 1:1 ratio. Primary endpoints are (1) overall survival and (2) proportion of patients with National Institute of Health Stroke Scale deterioration at 6 weeks, 3 months and 6 months postoperatively. Secondary endpoints are (1) residual CE and NCE tumour volume on postoperative T1-contrast and FLAIR (Fluid-attenuated inversion recovery) MRI scans; (2) progression-free survival; (3) receipt of adjuvant therapy with chemotherapy and radiotherapy; and (4) quality of life at 6 weeks, 3 months and 6 months postoperatively. The total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year. ETHICS AND DISSEMINATION: The study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media.

Cortico-cortical evoked potentials of language tracts in minimally invasive glioma surgery guided by Penfield stimulation.

OBJECTIVE: We investigated the feasibility of recording cortico-cortical evoked potentials (CCEPs) in patients with low- and high-grade glioma. We compared CCEPs during awake and asleep surgery, as well as those stimulated from the functional Broca area and recorded from the functional Wernicke area (BtW), and vice versa (WtB). We also analyzed CCEP properties according to tumor location, histopathology, and aphasia. METHODS: We included 20 patients who underwent minimally invasive surgery in an asleep-awake-asleep setting. Strip electrode placement was guided by classical Penfield stimulation of positive language sites and fiber tracking of the arcuate fascicle. CCEPs were elicited with alternating monophasic single pulses of 1.1 Hz frequency and recorded as averaged signals. Intraoperatively, there was no post-processing of the signal. RESULTS: Ninety-seven CCEPs from 19 patients were analyzed. There was no significant difference in CCEP properties when comparing awake versus asleep, nor BtW versus WtB. CCEP amplitude and latency were affected by tumor location and histopathology. CCEP features after tumor resection correlated with short- and long-term postoperative aphasia. CONCLUSION: CCEP recordings are feasible during minimally invasive surgery. CCEPs might be surrogate markers for altered connectivity of the language tracts. SIGNIFICANCE: This study may guide the incorporation of CCEPs into intraoperative neurophysiological monitoring.

Near-real-time Mueller polarimetric image processing for neurosurgical intervention.

PURPOSE: Wide-field imaging Mueller polarimetry is a revolutionary, label-free, and non-invasive modality for computer-aided intervention; in neurosurgery, it aims to provide visual feedback of white matter fibre bundle orientation from derived parameters. Conventionally, robust polarimetric parameters are estimated after averaging multiple measurements of intensity for each pair of probing and detected polarised light. Long multi-shot averaging, however, is not compatible with real-time in vivo imaging, and the current performance of polarimetric data processing hinders the translation to clinical practice. METHODS: A learning-based denoising framework is tailored for fast, single-shot, noisy acquisitions of polarimetric intensities. Also, performance-optimised image processing tools are devised for the derivation of clinically relevant parameters. The combination recovers accurate polarimetric parameters from fast acquisitions with near-real-time performance, under the assumption of pseudo-Gaussian polarimetric acquisition noise. RESULTS: The denoising framework is trained, validated, and tested on experimental data comprising tumour-free and diseased human brain samples in different conditions. Accuracy and image quality indices showed significant ( p < 0.05 ) improvements on testing data for a fast single-pass denoising versus the state-of-the-art and high polarimetric image quality standards. The computational time is reported for the end-to-end processing. CONCLUSION: The end-to-end image processing achieved real-time performance for a localised field of view ( ≈ 6.5 mm 2 ). The denoised polarimetric intensities produced visibly clear directional patterns of neuronal fibre tracts in line with reference polarimetric image quality standards; directional disruption was kept in case of neoplastic lesions. The presented advances pave the way towards feasible oncological neurosurgical translations of novel, label-free, interventional feedback.

Intraoperative Neurophysiologic Monitoring and Mapping During Surgery on Intramedullary Spinal Cord Tumors in Children and Adolescents.

SUMMARY: Surgical resection of intramedullary spinal cord tumors carries significant risks of neurologic deficits, especially in cases of infiltrative tumors. In pediatric patients, this type of surgery may be associated with a high risk of poor neurologic outcome. Intraoperative neurophysiologic monitoring has been adopted as part of the clinical routine by many centers as a useful adjunct for intraoperative assessment of neurologic integrity. To what extent intraoperative neurophysiologic mapping strategies may further support intraoperative decision-making is still a matter of debate. Here, we report on a small cohort of five pediatric patients in whom mapping with the double-train paradigm was used to identify the dorsal column and corticospinal tract and to guide the surgical resection. We also discuss the possible benefits and challenges regarding the available literature.

Simultaneous multi-region detection of GABA+ and Glx using 3D spatially resolved SLOW-editing and EPSI-readout at 7T.

GABA+ and Glx (glutamate and glutamine) are widely studied metabolites, yet the commonly used magnetic resonance spectroscopy (MRS) techniques have significant limitations, including sensitivity to B0 and B1+-inhomogeneities, limited bandwidth of MEGA-pulses, high SAR which is accentuated at 7T. To address these limitations, we propose SLOW-EPSI method, employing a large 3D MRSI coverage and achieving a high resolution down to 0.26 ml. Simulation results demonstrate the robustness of SLOW-editing for both GABA+ and Glx against B0 and B1+-inhomogeneities within the range of [-0.3, +0.3] ppm and [40 %, 250 %], respectively. Two protocols, both utilizing a 70 mm thick FOV slab, were employed to target distinct brain regions in vivo, differentiated by their orientation: transverse and tilted. Protocol 1 (n = 11) encompassed 5 locations (cortical gray matter, white matter, frontal lobe, parietal lobe, and cingulate gyrus). Protocol 2 (n = 5) involved 9 locations (cortical gray matter, white matter, frontal lobe, occipital lobe, cingulate gyrus, caudate nucleus, hippocampus, putamen, and inferior thalamus). Quantitative analysis of GABA+ and Glx was conducted in a stepwise manner. First, B1+/B1--inhomogeneities were corrected using water reference data. Next, GABA+ and Glx values were calculated employing spectral fitting. Finally, the GABA+ level for each selected region was compared to the global Glx within the same subject, generating the GABA+/Glx_global ratio. Our findings from two protocols indicate that the GABA+/Glx_global level in cortical gray matter was approximately 16 % higher than in white matter. Elevated GABA+/Glx_global levels acquired with protocol 2 were observed in specific regions such as the caudate nucleus (0.118±0.067), putamen (0.108±0.023), thalamus (0.092±0.036), and occipital cortex (0.091±0.010), when compared to the cortical gray matter (0.079±0.012). Overall, our results highlight the effectiveness of SLOW-EPSI as a robust and efficient technique for accurate measurements of GABA+ and Glx at 7T. In contrast to previous SVS and 2D-MRSI based editing sequences with which only one or a limited number of brain regions can be measured simultaneously, the method presented here measures GABA+ and Glx from any brain area and any arbitrarily shaped volume that can be flexibly selected after the examination. Quantification of GABA+ and Glx across multiple brain regions through spectral fitting is achievable with a 9-minute acquisition. Additionally, acquisition times of 18-27 min (GABA+) and 9-18 min (Glx) are required to generate 3D maps, which are constructed using Gaussian fitting and peak integration.

Intraoperative in vivo confocal laser endomicroscopy imaging at glioma margins: can we detect tumor infiltration?

OBJECTIVE: Confocal laser endomicroscopy (CLE) is a US Food and Drug Administration-cleared intraoperative real-time fluorescence-based cellular resolution imaging technology that has been shown to image brain tumor histoarchitecture rapidly in vivo during neuro-oncological surgical procedures. An important goal for successful intraoperative implementation is in vivo use at the margins of infiltrating gliomas. However, CLE use at glioma margins has not been well studied. METHODS: Matching in vivo CLE images and tissue biopsies acquired at glioma margin regions of interest (ROIs) were collected from 2 institutions. All images were reviewed by 4 neuropathologists experienced in CLE. A scoring system based on the pathological features was implemented to score CLE and H&E images from each ROI on a scale from 0 to 5. Based on the H&E scores, all ROIs were divided into a low tumor probability (LTP) group (scores 0-2) and a high tumor probability (HTP) group (scores 3-5). The concordance between CLE and H&E scores regarding tumor probability was determined. The intraclass correlation coefficient (ICC) and diagnostic performance were calculated. RESULTS: Fifty-six glioma margin ROIs were included for analysis. Interrater reliability of the scoring system was excellent when used for H&E images (ICC [95% CI] 0.91 [0.86-0.94]) and moderate when used for CLE images (ICC [95% CI] 0.69 [0.40-0.83]). The ICCs (95% CIs) of the LTP group (0.68 [0.40-0.83]) and HTP group (0.68 [0.39-0.83]) did not differ significantly. The concordance between CLE and H&E scores was 61.6%. The sensitivity and specificity values of the scoring system were 79% and 37%. The positive predictive value (PPV) and negative predictive value were 65% and 53%, respectively. Concordance, sensitivity, and PPV were greater in the HTP group than in the LTP group. Specificity was higher in the newly diagnosed group than in the recurrent group. CONCLUSIONS: CLE may detect tumor infiltration at glioma margins. However, it is not currently dependable, especially in scenarios where low probability of tumor infiltration is expected. The proposed scoring system has excellent intrinsic interrater reliability, but its interrater reliability is only moderate when used with CLE images. These results suggest that this technology requires further exploration as a method for consistent actionable intraoperative guidance with high dependability across the range of tumor margin scenarios. Specific-binding and/or tumor-specific fluorophores, a CLE image atlas, and a consensus guideline for image interpretation may help with the translational utility of CLE.

Overcoming chemotherapy resistance in low-grade gliomas: A computational approach.

Low-grade gliomas are primary brain tumors that arise from glial cells and are usually treated with temozolomide (TMZ) as a chemotherapeutic option. They are often incurable, but patients have a prolonged survival. One of the shortcomings of the treatment is that patients eventually develop drug resistance. Recent findings show that persisters, cells that enter a dormancy state to resist treatment, play an important role in the development of resistance to TMZ. In this study we constructed a mathematical model of low-grade glioma response to TMZ incorporating a persister population. The model was able to describe the volumetric longitudinal dynamics, observed in routine FLAIR 3D sequences, of low-grade glioma patients acquiring TMZ resistance. We used the model to explore different TMZ administration protocols, first on virtual clones of real patients and afterwards on virtual patients preserving the relationships between parameters of real patients. In silico clinical trials showed that resistance development was deferred by protocols in which individual doses are administered after rest periods, rather than the 28-days cycle standard protocol. This led to median survival gains in virtual patients of more than 15 months when using resting periods between two and three weeks and agreed with recent experimental observations in animal models. Additionally, we tested adaptive variations of these new protocols, what showed a potential reduction in toxicity, but no survival gain. Our computational results highlight the need of further clinical trials that could obtain better results from treatment with TMZ in low grade gliomas.

Incidence, therapy, and outcome in the management of chronic subdural hematoma in Switzerland: a population-based multicenter cohort study.

Background: Chronic subdural hematoma (cSDH) is a disease affecting mainly elderly individuals. The reported incidence ranges from 2.0/100,000 to 58 per 100,000 person-years when only considering patients who are over 70 years old, with an overall incidence of 8.2-14.0 per 100,000 persons. Due to an estimated doubling of the population above 65 years old between 2000 and 2030, cSDH will become an even more significant concern. To gain an overview of cSDH hospital admission rates, treatment, and outcome, we performed this multicenter national cohort study of patients requiring surgical treatment of cSDH. Methods: A multicenter cohort study included patients treated in 2013 in a Swiss center accredited for residency. Demographics, medical history, symptoms, and medication were recorded. Imaging at admission was evaluated, and therapy was divided into burr hole craniostomy (BHC), twist drill craniostomy (TDC), and craniotomy. Patients' outcomes were dichotomized into good (mRS, 0-3) and poor (mRS, 4-6) outcomes. A two-sided t-test for unpaired variables was performed, while a chi-square test was performed for categorical variables, and a p-value of <0.05 was considered to be statistically significant. Results: A total of 663 patients were included. The median age was 76 years, and the overall incidence rate was 8.2/100,000. With age, the incidence rate increased to 64.2/100,000 in patients aged 80-89 years. The most prevalent symptoms were gait disturbance in 362 (58.6%) of patients, headache in 286 (46.4%), and focal neurological deficits in 252 (40.7%). CSDH distribution was unilateral in 478 (72.1%) patients, while 185 presented a bilateral hematoma with no difference in the outcome. BHC was the most performed procedure for 758 (97.3%) evacuations. CSDH recurrence was noted in 104 patients (20.1%). A good outcome was seen in almost 81% of patients. Factors associated with poor outcomes were age, GCS and mRS on admission, and the occurrence of multiple deficits present at the diagnosis of the cSDH. Conclusion: As the first multicenter national cohort-based study analyzing the disease burden of cSDH, our study reveals that the hospital admission rate of cSDH was 8.2/100,000, while with age, it rose to 64.2/100,000. A good outcome was seen in 81% of patients, who maintained the same quality of life as before the surgery. However, the mortality rate was 4%.

Evaluating automated longitudinal tumor measurements for glioblastoma response assessment.

Automated tumor segmentation tools for glioblastoma show promising performance. To apply these tools for automated response assessment, longitudinal segmentation, and tumor measurement, consistency is critical. This study aimed to determine whether BraTumIA and HD-GLIO are suited for this task. We evaluated two segmentation tools with respect to automated response assessment on the single-center retrospective LUMIERE dataset with 80 patients and a total of 502 post-operative time points. Volumetry and automated bi-dimensional measurements were compared with expert measurements following the Response Assessment in Neuro-Oncology (RANO) guidelines. The longitudinal trend agreement between the expert and methods was evaluated, and the RANO progression thresholds were tested against the expert-derived time-to-progression (TTP). The TTP and overall survival (OS) correlation was used to check the progression thresholds. We evaluated the automated detection and influence of non-measurable lesions. The tumor volume trend agreement calculated between segmentation volumes and the expert bi-dimensional measurements was high (HD-GLIO: 81.1%, BraTumIA: 79.7%). BraTumIA achieved the closest match to the expert TTP using the recommended RANO progression threshold. HD-GLIO-derived tumor volumes reached the highest correlation between TTP and OS (0.55). Both tools failed at an accurate lesion count across time. Manual false-positive removal and restricting to a maximum number of measurable lesions had no beneficial effect. Expert supervision and manual corrections are still necessary when applying the tested automated segmentation tools for automated response assessment. The longitudinal consistency of current segmentation tools needs further improvement. Validation of volumetric and bi-dimensional progression thresholds with multi-center studies is required to move toward volumetry-based response assessment.

Impact of corpus callosum fiber tract crossing on polarimetric images of human brain histological sections: ex vivo studies in transmission configuration.

Significance: Imaging Mueller polarimetry is capable to trace in-plane orientation of brain fiber tracts by detecting the optical anisotropy of white matter of healthy brain. Brain tumor cells grow chaotically and destroy this anisotropy. Hence, the drop in scalar retardance values and randomization of the azimuth of the optical axis could serve as the optical marker for brain tumor zone delineation. Aim: The presence of underlying crossing fibers can also affect the values of scalar retardance and the azimuth of the optical axis. We studied and analyzed the impact of fiber crossing on the polarimetric images of thin histological sections of brain corpus callosum. Approach: We used the transmission Mueller microscope for imaging of two-layered stacks of thin sections of corpus callosum tissue to mimic the overlapping brain fiber tracts with different fiber orientations. The decomposition of the measured Mueller matrices was performed with differential and Lu-Chipman algorithms and completed by the statistical analysis of the maps of scalar retardance, azimuth of the optical axis, and depolarization. Results: Our results indicate the sensitivity of Mueller polarimetry to different spatial arrangement of brain fiber tracts as seen in the maps of scalar retardance and azimuth of optical axis of two-layered stacks of corpus callosum sections The depolarization varies slightly (<15%) with the orientation of the optical axes in both corpus callosum stripes, but its value increases by 2.5 to 3 times with the stack thickness. Conclusions: The crossing brain fiber tracts measured in transmission induce the drop in values of scalar retardance and randomization of the azimuth of the optical axis at optical path length of 15 µm. It suggests that the presence of nerve fibers crossing within the depth of few microns will be also detected in polarimetric maps of brain white matter measured in reflection configuration.

How much space is needed for decompressive surgery in malignant middle cerebral artery infarction: Enabling single-stage surgery.

Introduction: Decompressive hemicraniectomy (DCE) is routinely performed for intracranial pressure control after malignant middle cerebral artery (MCA) infarction. Decompressed patients are at risk of traumatic brain injury and the syndrome of the trephined until cranioplasty. Cranioplasty after DCE is itself associated with high complication rates. Single-stage surgical strategies may eliminate the need for follow-up surgery while allowing for safe brain expansion and protection from environmental factors. Research question: Assess the volume needed for safe expansion of the brain to enable single-stage surgery. Materials and methods: We performed a retrospective radiological and volumetric analysis of all patients that had DCE in our clinic between January 2009 and December 2018 and met inclusion criteria. We investigated prognostic parameters in perioperative imaging and assessed clinical outcome. Results: Of 86 patients with DCE, 44 fulfilled the inclusion criteria. Median brain swelling was 75.35 mL (8.7-151.2 mL). Median bone flap volume was 113.3 mL (73.34-146.1 mL). Median brain swelling was 1.62 mm below the previous outer rim of the skull (5.3 mm to -2.19 mm). In 79.6% of the patients, the volume of removed bone alone was equivalent to or larger than the additional intracranial volume needed for brain swelling. Discussion and conclusion: The space provided by removal of the bone alone was sufficient to match the expansion of the injured brain after malignant MCA infarction in the vast majority of our patientsA subgaleal space-expanding flap with a minimal offset can provide protection from trauma and atmospheric pressure without compromising brain expansion.

Radiomics and machine learning for predicting the consistency of benign tumors of the central nervous system: A systematic review.

PURPOSE: Predicting the consistency of benign central nervous system (CNS) tumors prior to surgery helps to improve surgical outcomes. This review summarizes and analyzes the literature on using radiomics and/or machine learning (ML) for consistency prediction. METHOD: The Medical Literature Analysis and Retrieval System Online (MEDLINE) database was screened for studies published in English from January 1st 2000. Data was extracted according to the PRISMA guidelines and quality of the studies was assessed in compliance with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). RESULTS: Eight publications were included focusing on pituitary macroadenomas (n = 5), pituitary adenomas (n = 1), and meningiomas (n = 2) using a retrospective (n = 6), prospective (n = 1), and unknown (n = 1) study design with a total of 763 patients for the consistency prediction. The studies reported an area under the curve (AUC) of 0.71-0.99 for their respective best performing model regarding the consistency prediction. Of all studies, four articles validated their models internally whereas none validated their models externally. Two articles stated making data available on request with the remaining publications lacking information with regard to data availability. CONCLUSIONS: The research on consistency prediction of CNS tumors is still at an early stage regarding the use of radiomics and different ML techniques. Best-practice procedures regarding radiomics and ML need to be followed more rigorously to facilitate the comparison between publications and, accordingly, the possible implementation into clinical practice in the future.

Effects of formalin fixation on polarimetric properties of brain tissue: fresh or fixed?

Significance: Imaging Mueller polarimetry (IMP) appears as a promising technique for real-time delineation of healthy and neoplastic tissue during neurosurgery. The training of machine learning algorithms used for the image post-processing requires large data sets typically derived from the measurements of formalin-fixed brain sections. However, the success of the transfer of such algorithms from fixed to fresh brain tissue depends on the degree of alterations of polarimetric properties induced by formalin fixation (FF). Aim: Comprehensive studies were performed on the FF induced changes in fresh pig brain tissue polarimetric properties. Approach: Polarimetric properties of pig brain were assessed in 30 coronal thick sections before and after FF using a wide-field IMP system. The width of the uncertainty region between gray and white matter was also estimated. Results: The depolarization increased by 5% in gray matter and remained constant in white matter following FF, whereas the linear retardance decreased by 27% in gray matter and by 28% in white matter after FF. The visual contrast between gray and white matter and fiber tracking remained preserved after FF. Tissue shrinkage induced by FF did not have a significant effect on the uncertainty region width. Conclusions: Similar polarimetric properties were observed in both fresh and fixed brain tissues, indicating a high potential for transfer learning.

Robustness of the wide-field imaging Mueller polarimetry for brain tissue differentiation and white matter fiber tract identification in a surgery-like environment: an ex vivo study.

During neurooncological surgery, the visual differentiation of healthy and diseased tissue is often challenging. Wide-field imaging Muller polarimetry (IMP) is a promising technique for tissue discrimination and in-plane brain fiber tracking in an interventional setup. However, the intraoperative implementation of IMP requires realizing imaging in the presence of remanent blood, and complex surface topography resulting from the use of an ultrasonic cavitation device. We report on the impact of both factors on the quality of polarimetric images of the surgical resection cavities reproduced in fresh animal cadaveric brains. The robustness of IMP is observed under adverse experimental conditions, suggesting a feasible translation of IMP for in vivo neurosurgical applications.