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Image registration is a fundamental medical image analysis task, and a wide variety of approaches have been proposed. However, only a few studies have comprehensively compared medical image registration ap- proaches on a wide range of clinically relevant tasks. This limits the development of registration methods, the adoption of research advances into practice, and a fair benchmark across competing approaches. The Learn2Reg challenge addresses these limitations by providing a multi- task medical image registration data set for comprehen- sive characterisation of deformable registration algorithms. A continuous evaluation will be possible at https:// learn2reg.grand-challenge.org. Learn2Reg covers a wide range of anatomies (brain, abdomen, and thorax), modalities (ultrasound, CT, MR), availability of annotations, as well as intra- and inter-patient registration evaluation. We established an easily accessible framework for training and validation of 3D registration methods, which enabled the compilation of results of over 65 individual method submissions from more than 20 unique teams. We used a complementary set of metrics, including robustness, ac- curacy, plausibility, and runtime, enabling unique insight into the current state-of-the-art of medical image regis- tration. This paper describes datasets, tasks, evaluation methods and results of the challenge, as well as results of further analysis of transferability to new datasets, the importance of label supervision, and resulting bias. While no single approach worked best across all tasks, many methodological aspects could be identified that push the performance of medical image registration to new state- of-the-art performance. Furthermore, we demystified the common belief that conventional registration methods have to be much slower than deep-learning-based methods.

Simple Summary Neurosurgical decisions for patients with glioblastoma depend on tumor characteristics in the preoperative MR scan. Currently, this is based on subjective estimates or manual tumor delineation in the absence of a standard for reporting. We compared tumor features of 1596 patients from 13 institutions extracted from manual segmentations by a human rater and from automated segmentations generated by a machine learning model. The automated segmentations were in excellent agreement with manual segmentations and are practically equivalent regarding tumor features that are potentially relevant for neurosurgical purposes. Standard reports can be generated by open access software, enabling comparison between surgical cohorts, multicenter trials, and patient registries. Abstract Treatment decisions for patients with presumed glioblastoma are based on tumor characteristics available from a preoperative MR scan. Tumor characteristics, including volume, location, and resectability, are often estimated or manually delineated. This process is time consuming and subjective. Hence, comparison across cohorts, trials, or registries are subject to assessment bias. In this study, we propose a standardized Glioblastoma Surgery Imaging Reporting and Data System (GSI-RADS) based on an automated method of tumor segmentation that provides standard reports on tumor features that are potentially relevant for glioblastoma surgery. As clinical validation, we determine the agreement in extracted tumor features between the automated method and the current standard of manual segmentations from routine clinical MR scans before treatment. In an observational consecutive cohort of 1596 adult patients with a first time surgery of a glioblastoma from 13 institutions, we segmented gadolinium-enhanced tumor parts both by a human rater and by an automated algorithm. Tumor features were extracted from segmentations of both methods and compared to assess differences, concordance, and equivalence. The laterality, contralateral infiltration, and the laterality indices were in excellent agreement. The native and normalized tumor volumes had excellent agreement, consistency, and equivalence. Multifocality, but not the number of foci, had good agreement and equivalence. The location profiles of cortical and subcortical structures were in excellent agreement. The expected residual tumor volumes and resectability indices had excellent agreement, consistency, and equivalence. Tumor probability maps were in good agreement. In conclusion, automated segmentations are in excellent agreement with manual segmentations and practically equivalent regarding tumor features that are potentially relevant for neurosurgical purposes. Standard GSI-RADS reports can be generated by open access software.

Meningiomas are the most common type of primary brain tumor, accounting for approximately 30% of all brain tumors. A substantial number of these tumors are never surgically removed but rather monitored over time. Automatic and precise meningioma segmentation is therefore beneficial to enable reliable growth estimation and patient-specific treatment planning. In this study, we propose the inclusion of attention mechanisms over a U-Net architecture: (i) Attention-gated U-Net (AGUNet) and (ii) Dual Attention U-Net (DAUNet), using a 3D MRI volume as input. Attention has the potential to leverage the global context and identify features' relationships across the entire volume. To limit spatial resolution degradation and loss of detail inherent to encoder-decoder architectures, we studied the impact of multi-scale input and deep supervision components. The proposed architectures are trainable end-to-end and each concept can be seamlessly disabled for ablation studies. The validation studies were performed using a 5-fold cross validation over 600 T1-weighted MRI volumes from St. Olavs University Hospital, Trondheim, Norway. For the best performing architecture, an average Dice score of 81.6% was reached for an F1-score of 95.6%. With an almost perfect precision of 98%, meningiomas smaller than 3ml were occasionally missed hence reaching an overall recall of 93%. Leveraging global context from a 3D MRI volume provided the best performances, even if the native volume resolution could not be processed directly. Overall, near-perfect detection was achieved for meningiomas larger than 3ml which is relevant for clinical use. In the future, the use of multi-scale designs and refinement networks should be further investigated to improve the performance. A larger number of cases with meningiomas below 3ml might also be needed to improve the performance for the smallest tumors., 16 pages, 5 figures, 3 tables. Submitted to Artificial Intelligence in Medicine

Objective To determine the diagnostic accuracy of routine clinico-radiological workup for a population-based selection of intracranial tumours. Methods In this prospective cohort study, we included consecutive adult patients who underwent a primary surgical intervention for a suspected intracranial tumour between 2015 and 2019 at a single-neurosurgical centre. The treating team estimated the expected diagnosis prior to surgery using predefined groups. The expected diagnosis was compared to final histopathology and the accuracy of preoperative clinico-radiological diagnosis (sensitivity, specificity, positive and negative predictive values) was calculated. Results 392 patients were included in the data analysis, of whom 319 underwent a primary surgical resection and 73 were operated with a diagnostic biopsy only. The diagnostic accuracy varied between different tumour types. The overall sensitivity, specificity and diagnostic mismatch rate of clinico-radiological diagnosis was 85.8%, 97.7% and 4.0%, respectively. For gliomas (including differentiation between low-grade and high-grade gliomas), the same diagnostic accuracy measures were found to be 82.2%, 97.2% and 5.6%, respectively. The most common diagnostic mismatch was between low-grade gliomas, high-grade gliomas and metastases. Accuracy of 90.2% was achieved for differentiation between diffuse low-grade gliomas and high-grade gliomas. Conclusions The current accuracy of a preoperative clinico-radiological diagnosis of brain tumours is high. Future non-invasive diagnostic methods need to outperform our results in order to add much value in a routine clinical setting in unselected patients.

Simple Summary Neurosurgical decisions for patients with glioblastoma depend on visual inspection of a preoperative MR scan to determine the tumor characteristics. To avoid subjective estimates and manual tumor delineation, automatic methods and standard reporting are necessary. We compared and extensively assessed the performances of two deep learning architectures on the task of automatic tumor segmentation. A total of 1887 patients from 14 institutions, manually delineated by a human rater, were compared to automated segmentations generated by neural networks. The automated segmentations were in excellent agreement with the manual segmentations, and external validity, as well as generalizability were demonstrated. Together with automatic tumor feature computation and standardized reporting, our Glioblastoma Surgery Imaging Reporting And Data System (GSI-RADS) exhibited the potential for more accurate data-driven clinical decisions. The trained models and software are open-source and open-access, enabling comparisons among surgical cohorts, multicenter trials, and patient registries. Abstract For patients with presumed glioblastoma, essential tumor characteristics are determined from preoperative MR images to optimize the treatment strategy. This procedure is time-consuming and subjective, if performed by crude eyeballing or manually. The standardized GSI-RADS aims to provide neurosurgeons with automatic tumor segmentations to extract tumor features rapidly and objectively. In this study, we improved automatic tumor segmentation and compared the agreement with manual raters, describe the technical details of the different components of GSI-RADS, and determined their speed. Two recent neural network architectures were considered for the segmentation task: nnU-Net and AGU-Net. Two preprocessing schemes were introduced to investigate the tradeoff between performance and processing speed. A summarized description of the tumor feature extraction and standardized reporting process is included. The trained architectures for automatic segmentation and the code for computing the standardized report are distributed as open-source and as open-access software. Validation studies were performed on a dataset of 1594 gadolinium-enhanced T1-weighted MRI volumes from 13 hospitals and 293 T1-weighted MRI volumes from the BraTS challenge. The glioblastoma tumor core segmentation reached a Dice score slightly below 90%, a patientwise F1-score close to 99%, and a 95th percentile Hausdorff distance slightly below 4.0 mm on average with either architecture and the heavy preprocessing scheme. A patient MRI volume can be segmented in less than one minute, and a standardized report can be generated in up to five minutes. The proposed GSI-RADS software showed robust performance on a large collection of MRI volumes from various hospitals and generated results within a reasonable runtime.

Due to the lack of reliable prognostic tools, prognostication and surgical decisions largely rely on the neurosurgeons’ clinical prediction skills. The aim of this study was to assess the accuracy of neurosurgeons’ prediction of survival in patients with high-grade glioma and explore factors possibly associated with accurate predictions. In a prospective single-center study, 199 patients who underwent surgery for high-grade glioma were included. After surgery, the operating surgeon predicted the patient’s survival using an ordinal prediction scale. A survival curve was used to visualize actual survival in groups based on this scale, and the accuracy of clinical prediction was assessed by comparing predicted and actual survival. To investigate factors possibly associated with accurate estimation, a binary logistic regression analysis was performed. The surgeons were able to differentiate between patients with different lengths of survival, and median survival fell within the predicted range in all groups with predicted survival 24 months, median survival was shorter than predicted. The overall accuracy of surgeons’ survival estimates was 41%, and over- and underestimations were done in 34% and 26%, respectively. Consultants were 3.4 times more likely to accurately predict survival compared to residents (p = 0.006). Our findings demonstrate that although especially experienced neurosurgeons have rather good predictive abilities when estimating survival in patients with high-grade glioma on the group level, they often miss on the individual level. Future prognostic tools should aim to beat the presented clinical prediction skills.

Deep convolutional neural networks (CNNs) are the current state-of-the-art for digital analysis of histopathological images. The large size of whole-slide microscopy images (WSIs) requires advanced memory handling to read, display and process these images. There are several open-source platforms for working with WSIs, but few support deployment of CNN models. These applications use third-party solutions for inference, making them less user-friendly and unsuitable for high-performance image analysis. To make deployment of CNNs user-friendly and feasible on low-end machines, we have developed a new platform, FastPathology, using the FAST framework and C++. It minimizes memory usage for reading and processing WSIs, deployment of CNN models, and real-time interactive visualization of results. Runtime experiments were conducted on four different use cases, using different architectures, inference engines, hardware configurations and operating systems. Memory usage for reading, visualizing, zooming and panning a WSI were measured, using FastPathology and three existing platforms. FastPathology performed similarly in terms of memory to the other C++ based application, while using considerably less than the two Java-based platforms. The choice of neural network model, inference engine, hardware and processors influenced runtime considerably. Thus, FastPathology includes all steps needed for efficient visualization and processing of WSIs in a single application, including inference of CNNs with real-time display of the results. Source code, binary releases and test data can be found online on GitHub at https://github.com/SINTEFMedtek/FAST-Pathology/., 12 pages, 4 figures, submitted to IEEE Access

International audience; Because of the deformation of the brain during neurosurgery, intraoperative imaging can be used to visualize the actual location of the brain structures. These images are used for image-guided navigation as well as determining whether the resection is complete and localizing the remaining tumor tissue. Intraoperative ultrasound (iUS) is a convenient modality with short acquisition times. However, iUS images are difficult to interpret because of the noise and artifacts. In particular, tumor tissue is difficult to distinguish from healthy tissue and it is very difficult to delimit tumors in iUS images. In this paper, we propose an automatic method to segment low grade brain tumors in iUS images using a 2-D and 3-D U-Net. We trained the networks on three folds with twelve training cases and five test cases each. The obtained results are promising, with a median Dice score of 0.72. The volume differences between the estimated and ground truth segmentations were similar to the intra-rater volume differences. While these results are preliminary, they suggest that deep learning methods can be successfully applied to tumor segmentation in intraoperative images.

With the recent developments in machine learning and modern graphics processing units (GPUs), there is a marked shift in the way intra-operative ultrasound (iUS) images can be processed and presented during surgery. Real-time processing of images to highlight important anatomical structures combined with in-situ display, has the potential to greatly facilitate the acquisition and interpretation of iUS images when guiding an operation. In order to take full advantage of the recent advances in machine learning, large amounts of high-quality annotated training data are necessary to develop and validate the algorithms. To ensure efficient collection of a sufficient number of patient images and external validity of the models, training data should be collected at several centers by different neurosurgeons, and stored in a standard format directly compatible with the most commonly used machine learning toolkits and libraries. In this paper, we argue that such effort to collect and organize large-scale multi-center datasets should be based on common open source software and databases. We first describe the development of existing open-source ultrasound based neuronavigation systems and how these systems have contributed to enhanced neurosurgical guidance over the last 15 years. We review the impact of the large number of projects worldwide that have benefited from the publicly available datasets “Brain Images of Tumors for Evaluation” (BITE) and “Retrospective evaluation of Cerebral Tumors” (RESECT) that include MR and US data from brain tumor cases. We also describe the need for continuous data collection and how this effort can be organized through the use of a well-adapted and user-friendly open-source software platform that integrates both continually improved guidance and automated data collection functionalities. Copyright © 2021 Reinertsen, Collins and Drouin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Introduction According to the stem cell theory, two neurogenic niches in the adult human brain may harbor cells that initiate the formation of gliomas: The larger subventricular zone (SVZ) and the subgranular zone (SGZ) in the hippocampus. We wanted to explore whether defining molecular markers in low-grade gliomas (LGG; WHO grade II) are related to distance to the neurogenic niches. Methods Patients treated at two Norwegian university hospitals with population-based referral were included. Eligible patients had histopathological verified supratentorial low-grade glioma. IDH mutational status and 1p19q co-deletion status was retrospectively assessed. 159 patients were included, and semi-automatic tumor segmentation was done from pre-treatment T2-weighted (T2W) or Fluid-Attenuated Inversion Recovery (FLAIR) images. 3D maps showing the anatomical distribution of the tumors were then created for each of the three molecular subtypes (IDH mutated/1p19q co-deleted, IDH mutated and IDH wild-type). Both distance from tumor center and tumor border to the neurogenic niches were recorded. Results In this population-based cohort of previously untreated low-grade gliomas, we found that low-grade gliomas are more often found closer to the SVZ than the SGZ, but IDH wild-type tumors are more often found near SGZ. Conclusion Our study suggests that the stem cell origin of IDH wild-type and IDH mutated low-grade gliomas may be different.

Background Malignant transformation represents the natural evolution of diffuse low-grade gliomas (LGG). This is a catastrophic event, causing neurocognitive symptoms, intensified treatment and premature death. However, little is known concerning the spatial distribution of malignant transformation in patients with LGG. Materials and methods Patients histopathological diagnosed with LGG and subsequent radiological malignant transformation were identified from two different institutions. We evaluated the spatial distribution of malignant transformation with (1) visual inspection and (2) segmentations of longitudinal tumor volumes. In (1) a radiological transformation site Results We included 43 patients in the clinical evaluation, and 36 patients had MRIs scans available for longitudinal segmentations. Prior to malignant transformation, residual radiological tumor volumes were > 10 ml in 93% of patients. The transformation site was considered local in 91% of patients by clinical assessment. Patients treated with radiotherapy prior to transformation had somewhat lower rate of local transformations (83%). Based upon the segmentations, the transformation was local in 92%. We did not observe any particular pattern of transformations in examined molecular subgroups. Conclusion Malignant transformation occurs locally and within the T2w hyperintensities in most patients. Although LGG is an infiltrating disease, this data conceptually strengthens the role of loco-regional treatments in patients with LGG.

International audience

Purpose The aim of this paper is to show how a specialized planning and guidance application called Fraxinus, can be built on top of the CustusX platform (www.custusx.org), which is an open source image-guided intervention software platform. Fraxinus has been customized to meet the clinical needs in navigated bronchoscopy. Methods The application requirements for Fraxinus were defined in close collaboration between research scientists, software developers and clinicians (pulmonologists), and built on top of CustusX. Its superbuild system downloads specific versions of the required libraries and builds them for the application in question, including the selected plugins. New functionality is easily added through the plugin framework. The build process enables the creation of specialized applications, adding additional documentation and custom configurations. The toolkit’s libraries offer building blocks for image-guided applications. An iterative development process was applied, where the clinicians would test and provide feedback during the entire process. Results Fraxinus has been developed and is released as an open source planning and guidance application built on top of CustusX. It is highly specialized for bronchoscopy. The proposed workflow is adapted to the different steps in this procedure. The user interface of CustusX has been modified to enhance information, quality assurance and user friendliness with the intention to increase the overall yield for the patient. As the workflow of the procedure is relatively constant, some actions are predicted and automatically performed by the application, according to the requirements from the clinicians. Conclusions The CustusX platform facilitates development of new and specialized applications. The toolkit supports the process and makes important extension and injection points available for customization. © 2019 Lervik Bakeng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License

In brain tumor surgery, the quality and safety of the procedure can be impacted by intra-operative tissue deformation, called brain shift. Brain shift can move the surgical targets and other vital structures such as blood vessels, thus invalidating the pre-surgical plan. Intra-operative ultrasound (iUS) is a convenient and cost-effective imaging tool to track brain shift and tumor resection. Accurate image registration techniques that update pre-surgical MRI based on iUS are crucial but challenging. The MICCAI Challenge 2018 for Correction of Brain shift with Intra-Operative UltraSound (CuRIOUS2018) provided a public platform to benchmark MRI-iUS registration algorithms on newly released clinical datasets. In this work, we present the data, setup, evaluation, and results of CuRIOUS 2018, which received 6 fully automated algorithms from leading academic and industrial research groups. All algorithms were first trained with the public RESECT database, and then ranked based on test dataset of 10 additional cases with identical data curation and annotation protocols as the RESECT database. The article compares the results of all participating teams and discusses the insights gained from the challenge, as well as future work., Comment: This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessible

Background Tumor location is important for surgical decision making. Particular attention is paid to regions that contain sensorimotor and language functions, but it is unknown if these are the most important regions from the patients' perspective. Objective To develop an atlas for depicting and assessing the potential importance of tumor location for perioperative health-related quality of life (HRQoL) in patients with newly diagnosed high-grade glioma. Methods Patient-reported HRQoL data and semi-automatically segmented preoperative 3D MRI-images were combined in 170 patients. The images were registered to a standardized space where the individual tumors were given the values and color intensity of the corresponding HRQoL. Descriptive brain maps of HRQoL, defined quantitative analyses, and voxel-based lesion symptom mapping comparing patients with tumors in different locations were made. Results There was no statistical difference in overall perioperative HRQoL between patients with tumors located in left or right hemisphere, between patients with tumors in different lobes, or between patients with tumors located in non-eloquent, near eloquent, or eloquent areas. Patients with tumors involving the internal capsule, and patients with preoperative motor symptoms and postoperative motor deficits, reported significantly worse overall HRQoL-scores. Conclusions The impact of anatomical tumor location on overall perioperative HRQoL seems less than frequently believed, and the distinction between critical and less critical brain regions seems more unclear according to the patients than perhaps when judged by physicians. However, worse HRQoL was found in patients with tumors in motor-related regions, indicating that these areas are crucial also from the patients' perspective., Highlights • The impact of tumor location on patient-reported overall quality of life is low. • There is no “dominant hemisphere” from the patients' perspective. • Motor related regions seem to be most crucial for the patients.

Objective In glioma operations, we sought to analyze sensitivity, specificity, and predictive values of intraoperative 3-dimensional ultrasound (US) for detecting residual tumor compared with early postoperative magnetic resonance imaging (MRI). Factors possibly associated with radiologic complete resection were also explored. Methods One hundred forty-four operations for diffuse supratentorial gliomas were included prospectively in an unselected, population-based, single-institution series. Operating surgeons answered a questionnaire immediately after surgery, stating whether residual tumor was seen with US at the end of resection and rated US image quality (e.g., good, medium, poor). Extent of surgical resection was estimated from preoperative and postoperative MRI. Results Overall specificity was 85% for “no tumor remnant” seen in US images at the end of resection compared with postoperative MRI findings. Sensitivity was 46%, but tumor remnants seen on MRI were usually small (median, 1.05 mL) in operations with false-negative US findings. Specificity was highest in low-grade glioma operations (94%) and lowest in patients who had undergone prior radiotherapy (50%). Smaller tumor volume and superficial location were factors significantly associated with gross total resection in a multivariable logistic regression analysis, whereas good ultrasound image quality did not reach statistical significance (P = 0.061). Conclusions The specificity of intraoperative US is good, but sensitivity for detecting the last milliliter is low compared with postoperative MRI. Tumor volume and tumor depth are the predictors of achieving gross total resection, although ultrasound image quality was not. © 2018. This is the authors’ accepted and refereed manuscript to the article. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

Generating MR-derived growth pattern models for glioblastoma multiforme (GBM) has been an attractive approach in neuro-oncology, suggesting a distinct pattern of lesion spread with a tendency in growing along the white matter (WM) fibre direction for the invasive component. However, the direction of growth is not much studied in vivo. In this study, we sought to study the dominant directions of tumour expansion/shrinkage pre-treatment. We examined fifty-six GBMs at two time-points: at radiological diagnosis and as part of the pre-operative planning, both with contrast-enhanced T1-weighted MRIs. The tumour volumes were semi-automatically segmented. A non-linear registration resulting in a deformation field characterizing the changes between the two time points was used together with the segmented tumours to determine the dominant directions of tumour change. To compute the degree of alignment between tumour growth vectors and WM fibres, an angle map was calculated. Our results demonstrate that tumours tend to grow predominantly along the WM, as evidenced by the dominant vector population with the maximum alignments. Our findings represent a step forward in investigating the hypothesis that tumour cells tend to migrate preferentially along the WM. © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)

Purpose In brain tumor surgeries, maximum removal of cancerous tissue without compromising normal brain functions can improve the patient’s survival rate and therapeutic benefits. To achieve this, diffusion MRI and intra-operative ultrasound (iUS) can be highly instrumental. While diffusion MRI allows the visualization of white matter tracts and helps define the resection plan to best preserve the eloquent areas, iUS can effectively track the brain shift after craniotomy that often renders the pre-surgical plan invalid, ensuring the accuracy and safety of the intervention. Unfortunately, brain shift correction using iUS and automatic registration has never been shown for brain tractography so far despite its rising significance in brain tumor resection. Methods We employed a correlation-ratio-based nonlinear registration algorithm to account for brain shift through MRI–iUS registration and used the recovered deformations to warp both the brain anatomy and tractography seen in pre-surgical plans. The overall technique was demonstrated retrospectively on four patients who underwent iUS-guided low-grade brain gliomas resection. Results Through qualitative and quantitative evaluations, the preoperative MRI and iUS scans were well realigned after nonlinear registration, and the deformed brain tumor volumes and white matter tracts showed large displacements away from the pre-surgical plans. Conclusions We are the first to demonstrate the technique to track nonlinear deformation of brain tractography using real clinical MRI and iUS data, and the results confirm the need for updating white matter tracts due to tissue shift during surgery. Nonlinear deformation of tractography in ultrasound-guided low-grade gliomas resection This is a post-peer-review, pre-copyedit version of an article published in International Journal of Computer Assisted Radiology and Surgery. Locked until 3 January 2019 due to copyright restrictions. The final authenticated version is available online at: http://dx.doi.org/ 0.1007/s11548-017-1699-x .

Background Unreliable neuronavigation owing to inaccurate patient-to-image registration and brain shift is a major problem in conventional magnetic resonance imaging–guided neurosurgery. We performed a prospective intraoperative validation of a system for fully automatic correction of this inaccuracy based on intraoperative three-dimensional ultrasound and magnetic resonance imaging-to-ultrasound registration. Methods The system was tested intraoperatively in 13 tumor resection cases, and performance was evaluated intraoperatively and postoperatively. Results Intraoperatively, the system was accurate enough for tumor resection guidance in 9 of 13 cases. Manually placed anatomic landmarks showed improvement of alignment from 5.12 mm to 2.72 mm (median) after intraoperative correction. Postoperatively, the limitations of the current system were identified and modified for the system to be sufficiently accurate in all cases. Conclusions Automatic and accurate correction of spatially unreliable neuronavigation is feasible within the constraints of surgery. The current limitations of the system were also identified and addressed. © 2018. This is the authors’ accepted and refereed manuscript to the article. Locked until 11.9.2019 due to copyright restrictions. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

Purpose In neurosurgery, reliable information about blood vessel anatomy and flow direction is important to identify, characterize, and avoid damage to the vasculature. Due to ultrasound Doppler angle dependencies and the complexity of the vascular architecture, clinically valuable 3-D flow direction information is currently not available. In this paper, we aim to clinically validate and demonstrate the intraoperative use of a fully automatic method for estimation of 3-D blood flow direction from freehand 2-D Doppler ultrasound. Methods A 3-D vessel model is reconstructed from 2-D Doppler ultrasound and used to determine the vessel architecture. The blood flow direction is then estimated automatically using the model in combination with Doppler velocity data. To enable testing and validation during surgery, the method was implemented as part of the open-source navigation system CustusX (www.custusx.org). Results Ten patients were included prospectively. Data from four patients were processed postoperatively, and data from six patients were processed intraoperatively. In total, the blood flow direction was estimated for 48 different blood vessels with a success rate of 98%. Conclusions In this work, we have shown that the proposed method is suitable for fully automatic estimation of the blood flow direction in intracranial vessels during neurosurgical interventions. The method has the potential to make the understanding of the complex vascular anatomy and flow pattern more intuitive for the surgeon. The method is compatible with intraoperative use, and results can be presented within the limited time frame where they still are of clinical interest. This is a post-peer-review, pre-copyedit version of an article published in [International Journal of Computer Assisted Radiology and Surgery] Locked until 13.3.2019 due to copyright restrictions. The final authenticated version is available online at: https://doi.org/10.1007/s11548-018-1711-0

Purpose CustusX is an image-guided therapy (IGT) research platform dedicated to intraoperative navigation and ultrasound imaging. In this paper, we present CustusX as a robust, accurate, and extensible platform with full access to data and algorithms and show examples of application in technological and clinical IGT research. Methods CustusX has been developed continuously for more than 15 years based on requirements from clinical and technological researchers within the framework of a well-defined software quality process. The platform was designed as a layered architecture with plugins based on the CTK/OSGi framework, a superbuild that manages dependencies and features supporting the IGT workflow. We describe the use of the system in several different clinical settings and characterize major aspects of the system such as accuracy, frame rate, and latency. Results The validation experiments show a navigation system accuracy of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$

Objectives Molecular markers provide valuable information about treatment response and prognosis in patients with low-grade gliomas (LGG). In order to make this important information available prior to surgery the aim of this study was to explore if molecular status in LGG can be discriminated by preoperative magnetic resonance imaging (MRI). Patients and methods All patients with histopathologically confirmed LGG with available molecular status who had undergone a preoperative standard clinical MRI protocol using a 3T Siemens Skyra scanner during 2008–2015 were retrospectively identified. Based on Haralick texture parameters and the segmented LGG FLAIR volume we explored if it was possible to predict molecular status. Results In total 25 patients (nine women, average age 44) fulfilled the inclusion parameters. The textural parameter homogeneity could discriminate between LGG patients with IDH mutation (0.12, IQR 0.10-0.15) and IDH wild type (0.07, IQR 0.06-0.09, p = 0.005). None of the other four analyzed texture parameters (energy, entropy, correlation and inertia) were associated with molecular status. Using ROC curves, the area under curve for predicting IDH mutation was 0.905 for homogeneity, 0.840 for tumor volume and 0.940 for the combined parameters of tumor volume and homogeneity. We could not predict molecular status using the four other chosen texture parameters (energy, entropy, correlation and inertia). Further, we could not separate LGG with IDH mutation with or without 1p19q codeletion. Conclusions In this preliminary study using Haralick texture parameters based on preoperative clinical FLAIR sequence, the homogeneity parameter could separate IDH mutated LGG from IDH wild type LGG. Combined with tumor volume, these diagnostic properties seem promising. © 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).

One of the main limitations of today’s navigation systems for spine surgery is that they often are not available until after the bone surface has been exposed. Also, they lack the capability of soft tissue imaging, both preoperatively and intraoperatively. The use of ultrasound has been proposed to overcome these limitations. By registering preoperative magnetic resonance (MR) images to intraoperative percutaneous ultrasound images, navigation can start even before incision. We therefore present a method for registration of MR images to ultrasound images of the spine. The method is feature-based and consists of two steps: segmentation of the bone surfaces from both the ultrasound images and the MR images, followed by rigid registration using a modified version of the Iterative Closest Point algorithm. The method was tested on data from a healthy volunteer, and the data set was successfully segmented and registered with an accuracy of \(3.67\pm 0.38\) mm.

International audience; PURPOSE: We describe and validate a novel hybrid nonlinear vessel registration algorithm for intra-operative updating of preoperative magnetic resonance (MR) images using Doppler ultrasound (US) images acquired on the dura for the correction of brain-shift and registration inaccuracies. We also introduce an US vessel appearance simulator that generates vessel images similar in appearance to that acquired with US from MR angiography data. METHODS: Our registration uses the minimum amount of preprocessing to extract vessels from the raw volumetric images. This prevents the removal of important registration information and minimizes the introduction of artifacts that may affect robustness, while reducing the amount of extraneous information in the image to be processed, thus improving the convergence speed of the algorithm. We then completed 3 rounds of validation for our vessel registration method for robustness and accuracy using (i) a large number of synthetic trials generated with our US vessel simulator, (ii) US images acquired from a real physical phantom made from polyvinyl alcohol cryogel, and (iii) real clinical data gathered intra-operatively from 3 patients. RESULTS: Resulting target registration errors (TRE) of less than 2.5 mm are achieved in more than 90 % of the synthetic trials when the initial TREs are less than 20 mm. TREs of less than 2 mm were achieved when the technique was applied to the physical phantom, and TREs of less than 3 mm were achieved on clinical data. CONCLUSIONS: These test trials show that the proposed algorithm is not only accurate but also highly robust to noise and missing vessel segments when working with US images acquired in a wide range of real-world conditions.