The Feasibility and Accuracy of Holographic Navigation with Laser Crosshair Simulator Registration on a Mixed-Reality Display.

Addressing conventional neurosurgical navigation systems' high costs and complexity, this study explores the feasibility and accuracy of a simplified, cost-effective mixed reality navigation (MRN) system based on a laser crosshair simulator (LCS). A new automatic registration method was developed, featuring coplanar laser emitters and a recognizable target pattern. The workflow was integrated into Microsoft's HoloLens-2 for practical application. The study assessed the system's precision by utilizing life-sized 3D-printed head phantoms based on computed tomography (CT) or magnetic resonance imaging (MRI) data from 19 patients (female/male: 7/12, average age: 54.4 ± 18.5 years) with intracranial lesions. Six to seven CT/MRI-visible scalp markers were used as reference points per case. The LCS-MRN's accuracy was evaluated through landmark-based and lesion-based analyses, using metrics such as target registration error (TRE) and Dice similarity coefficient (DSC). The system demonstrated immersive capabilities for observing intracranial structures across all cases. Analysis of 124 landmarks showed a TRE of 3.0 ± 0.5 mm, consistent across various surgical positions. The DSC of 0.83 ± 0.12 correlated significantly with lesion volume (Spearman rho = 0.813, p < 0.001). Therefore, the LCS-MRN system is a viable tool for neurosurgical planning, highlighting its low user dependency, cost-efficiency, and accuracy, with prospects for future clinical application enhancements.

Single-Center Experience in Microsurgical Resection of Acoustic Neurinomas and the Benefit of Microscope-Based Augmented Reality.

Background and Objectives: Microsurgical resection with intraoperative neuromonitoring is the gold standard for acoustic neurinomas (ANs) which are classified as T3 or T4 tumors according to the Hannover Classification. Microscope-based augmented reality (AR) can be beneficial in cerebellopontine angle and lateral skull base surgery, since these are small areas packed with anatomical structures and the use of this technology enables automatic 3D building of a model without the need for a surgeon to mentally perform this task of transferring 2D images seen on the microscope into imaginary 3D images, which then reduces the possibility of error and provides better orientation in the operative field. Materials and Methods: All patients who underwent surgery for resection of ANs in our department were included in this study. Clinical outcomes in terms of postoperative neurological deficits and complications were evaluated, as well as neuroradiological outcomes for tumor remnants and recurrence. Results: A total of 43 consecutive patients (25 female, median age 60.5 ± 16 years) who underwent resection of ANs via retrosigmoid osteoclastic craniotomy with the use of intraoperative neuromonitoring (22 right-sided, 14 giant tumors, 10 cystic, 7 with hydrocephalus) by a single surgeon were included in this study, with a median follow up of 41.2 ± 32.2 months. A total of 18 patients underwent subtotal resection, 1 patient partial resection and 24 patients gross total resection. A total of 27 patients underwent resection in sitting position and the rest in semi-sitting position. Out of 37 patients who had no facial nerve deficit prior to surgery, 19 patients were intact following surgery, 7 patients had House Brackmann (HB) Grade II paresis, 3 patients HB III, 7 patients HB IV and 1 patient HB V. Wound healing deficit with cerebrospinal fluid (CSF) leak occurred in 8 patients (18.6%). Operative time was 317.3 ± 99 min. One patient which had recurrence and one further patient with partial resection underwent radiotherapy following surgery. A total of 16 patients (37.2%) underwent resection using fiducial-based navigation and microscope-based AR, all in sitting position. Segmented objects of interest in AR were the sigmoid and transverse sinus, tumor outline, cranial nerves (CN) VII, VIII and V, petrous vein, cochlea and semicircular canals and brain stem. Operative time and clinical outcome did not differ between the AR and the non-AR group. However, use of AR improved orientation in the operative field for craniotomy planning and microsurgical resection by identification of important neurovascular structures. Conclusions: The single-center experience of resection of ANs showed a high rate of gross total (GTR) and subtotal resection (STR) with low recurrence. Use of AR improves intraoperative orientation and facilitates craniotomy planning and AN resection through early improved identification of important anatomical relations to structures of the inner auditory canal, venous sinuses, petrous vein, brain stem and the course of cranial nerves.

Surgical Treatment of Calcified Thoracic Herniated Disc Disease via the Transthoracic Approach with the Use of Intraoperative Computed Tomography (iCT) and Microscope-Based Augmented Reality (AR).

Background and Objectives: The aim of this study is to present our experience in the surgical treatment of calcified thoracic herniated disc disease via a transthoracic approach in the lateral position with the use of intraoperative computed tomography (iCT) and augmented reality (AR). Materials and Methods: All patients who underwent surgery for calcified thoracic herniated disc via a transthoracic transpleural approach at our Department using iCT and microscope-based AR were included in the study. Results: Six consecutive patients (five female, median age 53.2 ± 6.4 years) with calcified herniated thoracic discs (two patients Th 10-11 level, two patients Th 7-8, one patient Th 9-10, one patient Th 11-12) were included in this case series. Indication for surgery included evidence of a calcified thoracic disc on magnet resonance imaging (MRI) and CT with spinal canal stenosis of >50% of diameter, intractable pain, and neurological deficits, as well as MRI-signs of myelopathy. Five patients had paraparesis and ataxia, and one patient had no deficit. All surgeries were performed in the lateral position via a transthoracic transpleural approach (Five from left side). CT for automatic registration was performed following the placement of the reference array, with a high registration accuracy. Microscope-based AR was used, with segmented structures of interest such as vertebral bodies, disc space, herniated disc, and dural sac. Mean operative time was 277.5 ± 156 min. The use of AR improved orientation in the operative field for identification, and tailored the resection of the herniated disc and the identification of the course of dural sac. A control-iCT scan confirmed the complete resection in five patients and incomplete resection of the herniated disc in one patient. In one patient, complications occurred, such as postoperative hematoma, and wound healing deficit occurred. Mean follow-up was 22.9 ± 16.5 months. Five patients improved following surgery, and one patient who had no deficits remained unchanged. Conclusions: Optimal surgical therapy in patients with calcified thoracic disc disease with compression of dural sac and myelopathy was resectioned via a transthoracic transpleural approach. The use of iCT-based registration and microscope-based AR significantly improved orientation in the operative field and facilitated safe resection of these lesions.

Correlation of MR-Based Metabolomics and Molecular Profiling in the Tumor Microenvironment of Temozolomide-Treated Orthotopic GL261 Glioblastoma in Mice.

The tumor microenvironment in glioblastoma (GB) is considered to be "cold", i.e., the fraction of cytotoxic T cells, for instance, is low. Instead, macrophages are the major immune cell population in GB, which stem either from tissue response (resident microglia) or recruitment of macrophages from the periphery, thereby undergoing tumor-dependent "imprinting" mechanisms by which macrophages can adapt a tumor-supportive phenotype. In this regard, it is important to describe the nature of macrophages associated with GB, in particular under therapy conditions using the gold standard chemotherapy drug temozolomide (TMZ). Here, we explored the suitability of combining information from in vivo magnetic resonance spectroscopic (MRS) approaches (metabolomics) with in vitro molecular analyses to assess therapy response and characterize macrophage populations in mouse GB using an isogenic GL261 model. For macrophage profiling, expression levels of matrix metalloproteinases (MMPs) and A disintegrin and metalloproteinases (ADAMs) were determined, since their gene products affect macrophage-tumor cell communication by extensive cleavage of immunomodulatory membrane proteins, such as PD-L1. In tumor mice with an overall therapy response, expression of genes encoding the proteases ADAM8, ADAM10, and ADAM17 was increased and might contribute to the immunosuppressive phenotype of GB and immune cells. In tumors responding to therapy, expression levels of ADAM8 were upregulated by TMZ, and higher levels of PD-L1 were correlated significantly. Using a CRISPR/Cas9 knockout of ADAM8 in GL261 cells, we demonstrated that soluble PD-L1 (sPD-L1) is only generated in the presence of ADAM8. Moreover, primary macrophages from WT and ADAM8-deficient mice showed ADAM8-dependent release of sPD-L1, independent of the macrophage polarization state. Since ADAM8 expression is induced in responding tumors and PD-L1 shedding is likely to decrease the anti-tumor activities of T-cells, we conclude that immunotherapy resistance is caused, at least in part, by the increased presence of proteases, such as ADAM8.

Augmented Reality to Compensate for Navigation Inaccuracies.

This study aims to report on the capability of microscope-based augmented reality (AR) to evaluate registration and navigation accuracy with extracranial and intracranial landmarks and to elaborate on its opportunities and obstacles in compensation for navigation inaccuracies. In a consecutive single surgeon series of 293 patients, automatic intraoperative computed tomography-based registration was performed delivering a high initial registration accuracy with a mean target registration error of 0.84 ± 0.36 mm. Navigation accuracy is evaluated by overlaying a maximum intensity projection or pre-segmented object outlines within the recent focal plane onto the in situ patient anatomy and compensated for by translational and/or rotational in-plane transformations. Using bony landmarks (85 cases), there was two cases where a mismatch was seen. Cortical vascular structures (242 cases) showed a mismatch in 43 cases and cortex representations (40 cases) revealed two inaccurate cases. In all cases, with detected misalignment, a successful spatial compensation was performed (mean correction: bone (6.27 ± 7.31 mm), vascular (3.00 ± 1.93 mm, 0.38° ± 1.06°), and cortex (5.31 ± 1.57 mm, 1.75° ± 2.47°)) increasing navigation accuracy. AR support allows for intermediate and straightforward monitoring of accuracy, enables compensation of spatial misalignments, and thereby provides additional safety by increasing overall accuracy.

ADAM8 affects glioblastoma progression by regulating osteopontin-mediated angiogenesis.

Glioblastoma multiforme (GBM) is the most aggressive type of brain cancer with a median survival of only 15 months. To complement standard treatments including surgery, radiation and chemotherapy, it is essential to understand the contribution of the GBM tumor microenvironment. Brain macrophages and microglia particularly contribute to tumor angiogenesis, a major hallmark of GBM. ADAM8, a metalloprotease-disintegrin strongly expressed in tumor cells and associated immune cells of GBMs, is related to angiogenesis and correlates with poor clinical prognosis. However, the specific contribution of ADAM8 to GBM tumorigenesis remains elusive. Knockdown of ADAM8 in U87 glioma cells led to significantly decreased angiogenesis and tumor volumes of these cells after stereotactic injection into striate body of mice. We found that the angiogenic potential of ADAM8 in GBM cells and in primary macrophages is mediated by the regulation of osteopontin (OPN), an important inducer of tumor angiogenesis. By in vitro cell signaling analyses, we demonstrate that ADAM8 regulates OPN via JAK/STAT3 pathway in U87 cells and in primary macrophages. As ADAM8 is a dispensable protease for physiological homeostasis, we conclude that ADAM8 could be a tractable target to modulate angiogenesis in GBM with minor side-effects.

The Marburg-Münster Affective Disorders Cohort Study (MACS): A quality assurance protocol for MR neuroimaging data.

Large, longitudinal, multi-center MR neuroimaging studies require comprehensive quality assurance (QA) protocols for assessing the general quality of the compiled data, indicating potential malfunctions in the scanning equipment, and evaluating inter-site differences that need to be accounted for in subsequent analyses. We describe the implementation of a QA protocol for functional magnet resonance imaging (fMRI) data based on the regular measurement of an MRI phantom and an extensive variety of currently published QA statistics. The protocol is implemented in the MACS (Marburg-Münster Affective Disorders Cohort Study, http://for2107.de/), a two-center research consortium studying the neurobiological foundations of affective disorders. Between February 2015 and October 2016, 1214 phantom measurements have been acquired using a standard fMRI protocol. Using 444 healthy control subjects which have been measured between 2014 and 2016 in the cohort, we investigate the extent of between-site differences in contrast to the dependence on subject-specific covariates (age and sex) for structural MRI, fMRI, and diffusion tensor imaging (DTI) data. We show that most of the presented QA statistics differ severely not only between the two scanners used for the cohort but also between experimental settings (e.g. hardware and software changes), demonstrate that some of these statistics depend on external variables (e.g. time of day, temperature), highlight their strong dependence on proper handling of the MRI phantom, and show how the use of a phantom holder may balance this dependence. Site effects, however, do not only exist for the phantom data, but also for human MRI data. Using T1-weighted structural images, we show that total intracranial (TIV), grey matter (GMV), and white matter (WMV) volumes significantly differ between the MR scanners, showing large effect sizes. Voxel-based morphometry (VBM) analyses show that these structural differences observed between scanners are most pronounced in the bilateral basal ganglia, thalamus, and posterior regions. Using DTI data, we also show that fractional anisotropy (FA) differs between sites in almost all regions assessed. When pooling data from multiple centers, our data show that it is a necessity to account not only for inter-site differences but also for hardware and software changes of the scanning equipment. Also, the strong dependence of the QA statistics on the reliable placement of the MRI phantom shows that the use of a phantom holder is recommended to reduce the variance of the QA statistics and thus to increase the probability of detecting potential scanner malfunctions.

Enabling Navigation and Augmented Reality in the Sitting Position in Posterior Fossa Surgery Using Intraoperative Ultrasound.

Despite its broad use in cranial and spinal surgery, navigation support and microscope-based augmented reality (AR) have not yet found their way into posterior fossa surgery in the sitting position. While this position offers surgical benefits, navigation accuracy and thereof the use of navigation itself seems limited. Intraoperative ultrasound (iUS) can be applied at any time during surgery, delivering real-time images that can be used for accuracy verification and navigation updates. Within this study, its applicability in the sitting position was assessed. Data from 15 patients with lesions within the posterior fossa who underwent magnetic resonance imaging (MRI)-based navigation-supported surgery in the sitting position were retrospectively analyzed using the standard reference array and new rigid image-based MRI-iUS co-registration. The navigation accuracy was evaluated based on the spatial overlap of the outlined lesions and the distance between the corresponding landmarks in both data sets, respectively. Image-based co-registration significantly improved (p < 0.001) the spatial overlap of the outlined lesion (0.42 ± 0.30 vs. 0.65 ± 0.23) and significantly reduced (p < 0.001) the distance between the corresponding landmarks (8.69 ± 6.23 mm vs. 3.19 ± 2.73 mm), allowing for the sufficient use of navigation and AR support. Navigated iUS can therefore serve as an easy-to-use tool to enable navigation support for posterior fossa surgery in the sitting position.

Microstructure predicts non-motor outcomes following deep brain stimulation in Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) effectively treats motor and non-motor symptoms in advanced Parkinson's disease (PD). As considerable interindividual variability of outcomes exists, neuroimaging-based biomarkers, including microstructural metrics, have been proposed to anticipate treatment response. In this prospective open-label study, we sought to detect microstructural properties of brain areas associated with short-term non-motor outcomes following STN-DBS. Thirty-seven PD patients underwent diffusion MRI and clinical assessments at preoperative baseline and 6-month follow-up. Whole brain voxel-wise analysis assessed associations between microstructural metrics and non-motor outcomes. Intact microstructure within specific areas, including the right insular cortex, right putamen, right cingulum, and bilateral corticospinal tract were associated with greater postoperative improvement of non-motor symptom burden. Furthermore, microstructural properties of distinct brain regions were associated with postoperative changes in sleep, attention/memory, urinary symptoms, and apathy. In conclusion, diffusion MRI could support preoperative patient counselling by identifying patients with above- or below-average non-motor responses.

Structural connectivity of low-frequency subthalamic stimulation for improving stride length in Parkinson's disease.

BACKGROUND: A reduction in stride length is considered a key characteristic of gait kinematics in Parkinson's disease (PD) and has been identified as a predictor of falls. Although low-frequency stimulation (LFS) has been suggested as a method to improve gait characteristics, the underlying structural network is not well understood. OBJECTIVE: This study aims to investigate the structural correlates of changes in stride length during LFS (85 Hz). METHODS: Objective gait performance was retrospectively evaluated in 19 PD patients who underwent deep brain stimulation (DBS) at 85 Hz and 130 Hz. Individual DBS contacts and volumes of activated tissue (VAT) were computed using preoperative magnetic resonance imaging (MRI) and postoperative computed tomography (CT) scans. Structural connectivity profiles to predetermined cortical and mesencephalic areas were estimated using a normative connectome. RESULTS: LFS led to a significant improvement in stride length compared to 130 Hz stimulation. The intersection between VAT and the associative subregion of the subthalamic nucleus (STN) was associated with an improvement in stride length and had structural connections to the supplementary motor area, prefrontal cortex, and pedunculopontine nucleus. Conversely, we found that a lack of improvement was linked to stimulation volumes connected to cortico-diencephalic fibers bypassing the STN dorsolaterally. The robustness of the connectivity model was verified through leave-one-patient-out, 5-, and 10-fold cross cross-validation paradigms. CONCLUSION: These findings offer new insights into the structural connectivity that underlies gait changes following LFS. Targeting the non-motor subregion of the STN with LFS on an individual level may present a potential therapeutic approach for PD patients with gait disorders.

Head model dataset for mixed reality navigation in neurosurgical interventions for intracranial lesions.

Mixed reality navigation (MRN) technology is emerging as an increasingly significant and interesting topic in neurosurgery. MRN enables neurosurgeons to "see through" the head with an interactive, hybrid visualization environment that merges virtual- and physical-world elements. Offering immersive, intuitive, and reliable guidance for preoperative and intraoperative intervention of intracranial lesions, MRN showcases its potential as an economically efficient and user-friendly alternative to standard neuronavigation systems. However, the clinical research and development of MRN systems present challenges: recruiting a sufficient number of patients within a limited timeframe is difficult, and acquiring low-cost, commercially available, medically significant head phantoms is equally challenging. To accelerate the development of novel MRN systems and surmount these obstacles, the study presents a dataset designed for MRN system development and testing in neurosurgery. It includes CT and MRI data from 19 patients with intracranial lesions and derived 3D models of anatomical structures and validation references. The models are available in Wavefront object (OBJ) and Stereolithography (STL) formats, supporting the creation and assessment of neurosurgical MRN applications.

Case report: Unilateral GPi DBS in secondary myoclonus-dystonia syndrome after acute disseminated encephalomyelitis.

Introduction: Deep brain stimulation (DBS) is an established and effective therapy for movement disorders. Here, we present a case of secondary myoclonus-dystonia syndrome following acute disseminated encephalomyelitis (ADEM) in childhood, which was alleviated by DBS. Using a patient-specific connectome analysis, we sought to characterise the fibres and circuits affected by stimulation. Case report: We report a case of a 20-year-old man with progressive dystonia, myoclonic jerks, and impaired concentration following childhood ADEM. Motor assessments utilising the Unified Myoclonus Rating Scale (UMRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) revealed a greater improvement in dystonia compared to myoclonus following adjustments of DBS parameters. These adjustments were based on visualisation of electrode position and volume of tissue activated (VTA) 3 years after surgery. A patient-specific connectome analysis using the VTA as a region of interest revealed fibre tracts connecting to the cerebello-thalamo-cortical network and the superior frontal gyrus in addition to basal ganglia circuits as particularly effective. Conclusion: Globus pallidus internus (GPi) DBS shows promise as a treatment for secondary myoclonus-dystonia syndromes. Personalised structural considerations, tailored to individual symptoms and clinical characteristics, can provide significant benefits. Patient-specific connectome analysis, specifically, offers insights into the structures involved and may enable a favourable treatment response.

A Novel Registration Method for a Mixed Reality Navigation System Based on a Laser Crosshair Simulator: A Technical Note.

Mixed Reality Navigation (MRN) is pivotal in augmented reality-assisted intelligent neurosurgical interventions. However, existing MRN registration methods face challenges in concurrently achieving low user dependency, high accuracy, and clinical applicability. This study proposes and evaluates a novel registration method based on a laser crosshair simulator, evaluating its feasibility and accuracy. A novel registration method employing a laser crosshair simulator was introduced, designed to replicate the scanner frame's position on the patient. The system autonomously calculates the transformation, mapping coordinates from the tracking space to the reference image space. A mathematical model and workflow for registration were designed, and a Universal Windows Platform (UWP) application was developed on HoloLens-2. Finally, a head phantom was used to measure the system's target registration error (TRE). The proposed method was successfully implemented, obviating the need for user interactions with virtual objects during the registration process. Regarding accuracy, the average deviation was 3.7 ± 1.7 mm. This method shows encouraging results in efficiency and intuitiveness and marks a valuable advancement in low-cost, easy-to-use MRN systems. The potential for enhancing accuracy and adaptability in intervention procedures positions this approach as promising for improving surgical outcomes.

Microscope-Based Augmented Reality with Intraoperative Computed Tomography-Based Navigation for Resection of Skull Base Meningiomas in Consecutive Series of 39 Patients.

BACKGROUND: The aim of surgery for skull base meningiomas is maximal resection with minimal damage to the involved cranial nerves and cerebral vessels; thus, implementation of technologies for improved orientation in the surgical field, such as neuronavigation and augmented reality (AR), is of interest. METHODS: Included in the study were 39 consecutive patients (13 male, 26 female, mean age 64.08 ± 13.5 years) who underwent surgery for skull base meningiomas using microscope-based AR and automatic patient registration using intraoperative computed tomography (iCT). RESULTS: Most common were olfactory meningiomas (6), cavernous sinus (6) and clinoidal (6) meningiomas, meningiomas of the medial (5) and lateral (5) sphenoid wing and meningiomas of the sphenoidal plane (5), followed by suprasellar (4), falcine (1) and middle fossa (1) meningiomas. There were 26 patients (66.6%) who underwent gross total resection (GTR) of the meningioma. Automatic registration applying iCT resulted in high accuracy (target registration error, 0.82 ± 0.37 mm). The effective radiation dose of the registration iCT scans was 0.58 ± 1.05 mSv. AR facilitated orientation in the resection of skull base meningiomas with encasement of cerebral vessels and compression of the optic chiasm, as well as in reoperations, increasing surgeon comfort. No injuries to critical neurovascular structures occurred. Out of 35 patients who lived to follow-up, 33 could ambulate at their last presentation. CONCLUSION: A microscope-based AR facilitates surgical orientation for resection of skull base meningiomas. Registration accuracy is very high using automatic registration with intraoperative imaging.

Navigated Intraoperative 3D Ultrasound in Glioblastoma Surgery: Analysis of Imaging Features and Impact on Extent of Resection.

Background: Neuronavigation is routinely used in glioblastoma surgery, but its accuracy decreases during the operative procedure due to brain shift, which can be addressed utilizing intraoperative imaging. Intraoperative ultrasound (iUS) is widely available, offers excellent live imaging, and can be fully integrated into modern navigational systems. Here, we analyze the imaging features of navigated i3D US and its impact on the extent of resection (EOR) in glioblastoma surgery. Methods: Datasets of 31 glioblastoma resection procedures were evaluated. Patient registration was established using intraoperative computed tomography (iCT). Pre-operative MRI (pre-MRI) and pre-resectional ultrasound (pre-US) datasets were compared regarding segmented tumor volume, spatial overlap (Dice coefficient), the Euclidean distance of the geometric center of gravity (CoG), and the Hausdorff distance. Post-resectional ultrasound (post-US) and post-operative MRI (post-MRI) tumor volumes were analyzed and categorized into subtotal resection (STR) or gross total resection (GTR) cases. Results: The mean patient age was 59.3 ± 11.9 years. There was no significant difference in pre-resectional segmented tumor volumes (pre-MRI: 24.2 ± 22.3 cm3; pre-US: 24.0 ± 21.8 cm3). The Dice coefficient was 0.71 ± 0.21, the Euclidean distance of the CoG was 3.9 ± 3.0 mm, and the Hausdorff distance was 12.2 ± 6.9 mm. A total of 18 cases were categorized as GTR, 10 cases were concordantly classified as STR on MRI and ultrasound, and 3 cases had to be excluded from post-resectional analysis. In four cases, i3D US triggered further resection. Conclusion: Navigated i3D US is reliably adjunct in a multimodal navigational setup for glioblastoma resection. Tumor segmentations revealed similar results in i3D US and MRI, demonstrating the capability of i3D US to delineate tumor boundaries. Additionally, i3D US has a positive influence on the EOR, allows live imaging, and depicts brain shift.

Use of Neuronavigation and Augmented Reality in Transsphenoidal Pituitary Adenoma Surgery.

The aim of this study was to report on the clinical experience with microscope-based augmented reality (AR) in transsphenoidal surgery compared to the classical microscope-based approach. AR support was established using the head-up displays of the operating microscope, with navigation based on fiducial-/surface- or automatic intraoperative computed tomography (iCT)-based registration. In a consecutive single surgeon series of 165 transsphenoidal procedures, 81 patients underwent surgery without AR support and 84 patients underwent surgery with AR support. AR was integrated straightforwardly within the workflow. ICT-based registration increased AR accuracy significantly (target registration error, TRE, 0.76 ± 0.33 mm) compared to the landmark-based approach (TRE 1.85 ± 1.02 mm). The application of low-dose iCT protocols led to a significant reduction in applied effective dosage being comparable to a single chest radiograph. No major vascular or neurological complications occurred. No difference in surgical time was seen, time to set-up patient registration prolonged intraoperative preparation time on average by twelve minutes (32.33 ± 13.35 vs. 44.13 ± 13.67 min), but seems justifiable by the fact that AR greatly and reliably facilitated surgical orientation and increased surgeon comfort and patient safety, not only in patients who had previous transsphenoidal surgery but also in cases with anatomical variants. Automatic intraoperative imaging-based registration is recommended.

Radiogenomic Predictors of Recurrence in Glioblastoma-A Systematic Review.

Glioblastoma, as the most aggressive brain tumor, is associated with a poor prognosis and outcome. To optimize prognosis and clinical therapy decisions, there is an urgent need to stratify patients with increased risk for recurrent tumors and low therapeutic success to optimize individual treatment. Radiogenomics establishes a link between radiological and pathological information. This review provides a state-of-the-art picture illustrating the latest developments in the use of radiogenomic markers regarding prognosis and their potential for monitoring recurrence. Databases PubMed, Google Scholar, and Cochrane Library were searched. Inclusion criteria were defined as diagnosis of glioblastoma with histopathological and radiological follow-up. Out of 321 reviewed articles, 43 articles met these inclusion criteria. Included studies were analyzed for the frequency of radiological and molecular tumor markers whereby radiogenomic associations were analyzed. Six main associations were described: radiogenomic prognosis, MGMT status, IDH, EGFR status, molecular subgroups, and tumor location. Prospective studies analyzing prognostic features of glioblastoma together with radiological features are lacking. By reviewing the progress in the development of radiogenomic markers, we provide insights into the potential efficacy of such an approach for clinical routine use eventually enabling early identification of glioblastoma recurrence and therefore supporting a further personalized monitoring and treatment strategy.

The Metalloprotease-Disintegrin ADAM8 Alters the Tumor Suppressor miR-181a-5p Expression Profile in Glioblastoma Thereby Contributing to Its Aggressiveness.

Glioblastoma (GBM) as the most common and aggressive brain tumor is characterized by genetic heterogeneity, invasiveness, radio-/chemoresistance, and occurrence of GBM stem-like cells. The metalloprotease-disintegrin ADAM8 is highly expressed in GBM tumor and immune cells and correlates with poor survival. In GBM, ADAM8 affects intracellular kinase signaling and increases expression levels of osteopontin/SPP1 and matrix metalloproteinase 9 (MMP9) by an unknown mechanism. Here we explored whether microRNA (miRNA) expression levels could be regulators of MMP9 expression in GBM cells expressing ADAM8. Initially, we identified several miRNAs as dysregulated in ADAM8-deficient U87 GBM cells. Among these, the tumor suppressor miR-181a-5p was significantly upregulated in ADAM8 knockout clones. By inhibiting kinase signaling, we found that ADAM8 downregulates expression of miR-181a-5p via activation of signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) signaling suggesting an ADAM8-dependent silencing of miR-181a-5p. In turn, mimic miR-181a-5p transfection caused decreased cell proliferation and lower MMP9 expression in GBM cells. Furthermore, miR-181a-5p was detected in GBM cell-derived extracellular vesicles (EVs) as well as patient serum-derived EVs. We identified miR-181a-5p downregulating MMP9 expression via targeting the MAPK pathway. Analysis of patient tissue samples (n=22) revealed that in GBM, miR-181a-5p is strongly downregulated compared to ADAM8 and MMP9 mRNA expression, even in localized tumor areas. Taken together, we provide evidence for a functional axis involving ADAM8/miR-181a-5p/MAPK/MMP9 in GBM tumor cells.

Fiber tractography of the optic radiations: impact of diffusion model, voxel shape and orientation.

BACKGROUND: Reliable visualization of the optic radiations (OR) is of major importance in tumor surgery close to the OR to prevent permanent visual field deficits. Diffusion tensor imaging (DTI) based fiber tractography (FT) has become a standard tool to visualize major white matter tracts and to support the prevention of postoperative deficits. Nevertheless, FT of the OR is notoriously challenging due to its high neuroanatomical complexity. METHODS: To improve FT of the OR we analyzed the effect of a more complex diffusion model and the effect of different voxel shapes and orientations. MRI data of 21 healthy subjects was acquired using isometric and anisometric voxel sizes and standard and adapted slice angulation. FT was performed using the DTI based approach and an orientation distribution function (ODF) based approach. Results were visually inspected, and fiber tract volumes were compared. RESULTS: DTI based FT led to poor results, failing to reconstruct plausible tracts at all in up to 26.11% of all cases. The ODF based approach resulted in more compound and solid tracts showing also significantly larger tract volumes. Voxel shape or orientation did not influence DTI, but ODF based FT. Isometric or anisometric voxels with standard slice orientation revealed highest tract volumes. Adapted orientation in combination with anisometric voxels led to significantly smaller tract volumes. CONCLUSIONS: Plausible tractography of the OR can be achieved using ODF based fiber tracking within a clinically feasible timeframe. Voxel shape and orientation seem to be of minor importance and might be kept to isometric voxel for flexible application of FT.

Diffusion Kurtosis Imaging Fiber Tractography of Major White Matter Tracts in Neurosurgery.

Diffusion tensor imaging (DTI)-based fiber tractography is routinely used in clinical applications to visualize major white matter tracts, such as the corticospinal tract (CST), optic radiation (OR), and arcuate fascicle (AF). Nevertheless, DTI is limited due to its capability of resolving intra-voxel multi-fiber populations. Sophisticated models often require long acquisition times not applicable in clinical practice. Diffusion kurtosis imaging (DKI), as an extension of DTI, combines sophisticated modeling of the diffusion process with short acquisition times but has rarely been investigated in fiber tractography. In this study, DTI- and DKI-based fiber tractography of the CST, OR, and AF was investigated in healthy volunteers and glioma patients. For the CST, significantly larger tract volumes were seen in DKI-based fiber tractography. Similar results were obtained for the OR, except for the right OR in patients. In the case of the AF, results of both models were comparable with DTI-based fiber tractography showing even significantly larger tract volumes in patients. In the case of the CST and OR, DKI-based fiber tractography contributes to advanced visualization under clinical time constraints, whereas for the AF, other models should be considered.