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The corticospinal tract (CST) is a critically important white matter fiber tract in the human brain that enables control of voluntary movements of the body. The CST exhibits a somatotopic organization, which means that the motor neurons that control specific body parts are arranged in order within the CST. Diffusion magnetic resonance imaging (MRI) tractography is increasingly used to study the anatomy of the CST. However, despite many advances in tractography algorithms over the past decade, modern, state-of-the-art methods still face challenges. In this study, we compare the performance of six widely used tractography methods for reconstructing the CST and its somatotopic organization. These methods include constrained spherical deconvolution (CSD) based probabilistic (iFOD1) and deterministic (SD-Stream) methods, unscented Kalman filter (UKF) tractography methods including multi-fiber (UKF2T) and single-fiber (UKF1T) models, the generalized q-sampling imaging (GQI) based deterministic tractography method, and the TractSeg method. We investigate CST somatotopy by dividing the CST into four subdivisions per hemisphere that originate in the leg, trunk, hand, and face areas of the primary motor cortex. A quantitative and visual comparison is performed using diffusion MRI data (N = 100 subjects) from the Human Connectome Project. Quantitative evaluations include the reconstruction rate of the eight anatomical subdivisions, the percentage of streamlines in each subdivision, and the coverage of the white matter-gray matter (WM-GM) interface. CST somatotopy is further evaluated by comparing the percentage of streamlines in each subdivision to the cortical volumes for the leg, trunk, hand, and face areas. Overall, UKF2T has the highest reconstruction rate and cortical coverage. It is the only method with a significant positive correlation between the percentage of streamlines in each subdivision and the volume of the corresponding motor cortex. However, our experimental results show that all compared tractography methods are biased toward generating many trunk streamlines (ranging from 35.10% to 71.66% of total streamlines across methods). Furthermore, the coverage of the WM-GM interface in the largest motor area (face) is generally low (under 40%) for all compared tractography methods. Different tractography methods give conflicting results regarding the percentage of streamlines in each subdivision and the volume of the corresponding motor cortex, indicating that there is generally no clear relationship, and that reconstruction of CST somatotopy is still a large challenge. Overall, we conclude that while current tractography methods have made progress toward the well-known challenge of improving the reconstruction of the lateral projections of the CST, the overall problem of performing a comprehensive CST reconstruction, including clinically important projections in the lateral (hand and face areas) and medial portions (leg area), remains an important challenge for diffusion MRI tractography., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Purpose: Brain shift that occurs during neurosurgery disturbs the brain's anatomy. Prediction of the brain shift is essential for accurate localisation of the surgical target. Biomechanical models have been envisaged as a possible tool for such predictions. In this study, we created a framework to automate the workflow for predicting intra-operative brain deformations., Methods: We created our framework by uniquely combining our meshless total Lagrangian explicit dynamics (MTLED) algorithm for computing soft tissue deformations, open-source software libraries and built-in functions within 3D Slicer, an open-source software package widely used for medical research. Our framework generates the biomechanical brain model from the pre-operative MRI, computes brain deformation using MTLED and outputs results in the form of predicted warped intra-operative MRI., Results: Our framework is used to solve three different neurosurgical brain shift scenarios: craniotomy, tumour resection and electrode placement. We evaluated our framework using nine patients. The average time to construct a patient-specific brain biomechanical model was 3 min, and that to compute deformations ranged from 13 to 23 min. We performed a qualitative evaluation by comparing our predicted intra-operative MRI with the actual intra-operative MRI. For quantitative evaluation, we computed Hausdorff distances between predicted and actual intra-operative ventricle surfaces. For patients with craniotomy and tumour resection, approximately 95% of the nodes on the ventricle surfaces are within two times the original in-plane resolution of the actual surface determined from the intra-operative MRI., Conclusion: Our framework provides a broader application of existing solution methods not only in research but also in clinics. We successfully demonstrated the application of our framework by predicting intra-operative deformations in nine patients undergoing neurosurgical procedures., (© 2023. The Author(s).)

Purpose: We present SlicerDMRI, an open-source software suite that enables research using diffusion magnetic resonance imaging (dMRI), the only modality that can map the white matter connections of the living human brain. SlicerDMRI enables analysis and visualization of dMRI data and is aimed at the needs of clinical research users. SlicerDMRI is built upon and deeply integrated with 3D Slicer, a National Institutes of Health-supported open-source platform for medical image informatics, image processing, and three-dimensional visualization. Integration with 3D Slicer provides many features of interest to cancer researchers, such as real-time integration with neuronavigation equipment, intraoperative imaging modalities, and multimodal data fusion. One key application of SlicerDMRI is in neurosurgery research, where brain mapping using dMRI can provide patient-specific maps of critical brain connections as well as insight into the tissue microstructure that surrounds brain tumors., Patients and Methods: In this article, we focus on a demonstration of SlicerDMRI as an informatics tool to enable end-to-end dMRI analyses in two retrospective imaging data sets from patients with high-grade glioma. Analyses demonstrated here include conventional diffusion tensor analysis, advanced multifiber tractography, automated identification of critical fiber tracts, and integration of multimodal imagery with dMRI., Results: We illustrate the ability of SlicerDMRI to perform both conventional and advanced dMRI analyses as well as to enable multimodal image analysis and visualization. We provide an overview of the clinical rationale for each analysis along with pointers to the SlicerDMRI tools used in each., Conclusion: SlicerDMRI provides open-source and clinician-accessible research software tools for dMRI analysis. SlicerDMRI is available for easy automated installation through the 3D Slicer Extension Manager.

Purpose: In image-guided surgery for glioma removal, neurosurgeons usually plan the resection on images acquired before surgery and use them for guidance during the subsequent intervention. However, after the surgical procedure has begun, the preplanning images become unreliable due to the brain shift phenomenon, caused by modifications of anatomical structures and imprecisions in the neuronavigation system. To obtain an updated view of the resection cavity, a solution is to collect intraoperative data, which can be additionally acquired at different stages of the procedure in order to provide a better understanding of the resection. A spatial mapping between structures identified in subsequent acquisitions would be beneficial. We propose here a fully automated segmentation-based registration method to register ultrasound (US) volumes acquired at multiple stages of neurosurgery., Methods: We chose to segment sulci and falx cerebri in US volumes, which remain visible during resection. To automatically segment these elements, first we trained a convolutional neural network on manually annotated structures in volumes acquired before the opening of the dura mater and then we applied it to segment corresponding structures in different surgical phases. Finally, the obtained masks are used to register US volumes acquired at multiple resection stages., Results: Our method reduces the mean target registration error (mTRE) between volumes acquired before the opening of the dura mater and during resection from 3.49 mm (± 1.55 mm) to 1.36 mm (± 0.61 mm). Moreover, the mTRE between volumes acquired before opening the dura mater and at the end of the resection is reduced from 3.54 mm (± 1.75 mm) to 2.05 mm (± 1.12 mm)., Conclusion: The segmented structures demonstrated to be good candidates to register US volumes acquired at different neurosurgical phases. Therefore, our solution can compensate brain shift in neurosurgical procedures involving intraoperative US data.

Purpose: Protoporphyrin (PpIX) fluorescence allows discrimination of tumor and normal brain tissue during neurosurgery. A handheld fluorescence (HHF) probe can be used for spectroscopic measurement of 5-ALA-induced PpIX to enable objective detection compared to visual evaluation of fluorescence. However, current technology requires that the surgeon either views the measured values on a screen or employs an assistant to verbally relay the values. An auditory feedback system was developed and evaluated for communicating measured fluorescence intensity values directly to the surgeon., Methods: The auditory display was programmed to map the values measured by the HHF probe to the playback of tones that represented three fluorescence intensity ranges and one error signal. Ten persons with no previous knowledge of the application took part in a laboratory evaluation. After a brief training period, participants performed measurements on a tray of 96 wells of liquid fluorescence phantom and verbally stated the perceived measurement values for each well. The latency and accuracy of the participants' verbal responses were recorded. The long-term memorization of sound function was evaluated in a second set of 10 participants 2-3 and 7-12 days after training., Results: The participants identified the played tone accurately for 98% of measurements after training. The median response time to verbally identify the played tones was 2 pulses. No correlation was found between the latency and accuracy of the responses, and no significant correlation with the musical proficiency of the participants was observed on the function responses. Responses for the memory test were 100% accurate., Conclusion: The employed auditory display was shown to be intuitive, easy to learn and remember, fast to recognize, and accurate in providing users with measurements of fluorescence intensity or error signal. The results of this work establish a basis for implementing and further evaluating auditory displays in clinical scenarios involving fluorescence guidance and other areas for which categorized auditory display could be useful.

Diffusion MRI (dMRI) is the only noninvasive method for mapping white matter connections in the brain. We describe SlicerDMRI, a software suite that enables visualization and analysis of dMRI for neuroscientific studies and patient-specific anatomic assessment. SlicerDMRI has been successfully applied in multiple studies of the human brain in health and disease, and here, we especially focus on its cancer research applications. As an extension module of the 3D Slicer medical image computing platform, the SlicerDMRI suite enables dMRI analysis in a clinically relevant multimodal imaging workflow. Core SlicerDMRI functionality includes diffusion tensor estimation, white matter tractography with single and multi-fiber models, and dMRI quantification. SlicerDMRI supports clinical DICOM and research file formats, is open-source and cross-platform, and can be installed as an extension to 3D Slicer (www.slicer.org). More information, videos, tutorials, and sample data are available at dmri.slicer.org Cancer Res; 77(21); e101-3. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: Change detection is a critical component in the diagnosis and monitoring of many slowly evolving pathologies., Objective: This article describes a semiautomatic monitoring approach using longitudinal medical images. We test the method on brain scans of patients with meningioma, which experts have found difficult to monitor because the tumor evolution is very slow and may be obscured by artifacts related to image acquisition., Methods: We describe a semiautomatic procedure targeted toward identifying difficult-to-detect changes in brain tumor imaging. The tool combines input from a medical expert with state-of-the-art technology. The software is easy to calibrate and, in less than 5 minutes, returns the total volume of tumor change in mm. We test the method on postgadolinium, T1-weighted magnetic resonance images of 10 patients with meningioma and compare our results with experts' findings. We also perform benchmark testing with synthetic data., Results: Our experiments indicated that experts' visual inspections are not sensitive enough to detect subtle growth. Measurements based on experts' manual segmentations were highly accurate but also labor intensive. The accuracy of our approach was comparable to the experts' results. However, our approach required far less user input and generated more consistent measurements., Conclusion: The sensitivity of experts' visual inspection is often too low to detect subtle growth of meningiomas from longitudinal scans. Measurements based on experts' segmentation are highly accurate but generally too labor intensive for standard clinical settings. We described an alternative metric that provides accurate and robust measurements of subtle tumor changes while requiring a minimal amount of user input.

Background: Diffusion tensor imaging (DTI) infers the trajectory and location of large white matter tracts by measuring the anisotropic diffusion of water. DTI data may then be analyzed and presented as tractography for visualization of the tracts in 3 dimensions. Despite the important information contained in tractography images, usefulness for neurosurgical planning has been limited by the inability to define which are critical structures within the mass of demonstrated fibers and to clarify their relationship to the tumor., Objective: To develop a method to allow the interactive querying of tractography data sets for surgical planning and to provide a working software package for the research community., Methods: The tool was implemented within an open source software project. Echo-planar DTI at 3 T was performed on 5 patients, followed by tensor calculation. Software was developed that allowed the placement of a dynamic seed point for local selection of fibers and for fiber display around a segmented structure, both with tunable parameters. A neurosurgeon was trained in the use of software in < 1 hour and used it to review cases., Results: Tracts near tumor and critical structures were interactively visualized in 3 dimensions to determine spatial relationships to lesion. Tracts were selected using 3 methods: anatomical and functional magnetic resonance imaging-defined regions of interest, distance from the segmented tumor volume, and dynamic seed-point spheres., Conclusion: Interactive tractography successfully enabled inspection of white matter structures that were in proximity to lesions, critical structures, and functional cortical areas, allowing the surgeon to explore the relationships between them.

User interaction is required for reliable segmentation of brain tumors in clinical practice and in clinical research. By incorporating current research tools, 3D Slicer provides a set of interactive, easy to use tools that can be efficiently used for this purpose. One of the modules of 3D Slicer is an interactive editor tool, which contains a variety of interactive segmentation effects. Use of these effects for fast and reproducible segmentation of a single glioblastoma from magnetic resonance imaging data is demonstrated. The innovation in this work lies not in the algorithm, but in the accessibility of the algorithm because of its integration into a software platform that is practical for research in a clinical setting.

Rationale and Objectives: To perform a retrospective, quantitative assessment of the anatomic relationship between intra-axial, supratentorial, primary brain tumors, and adjacent white matter fiber tracts based on anatomic and diffusion tensor magnetic resonance imaging (MRI). We hypothesized that white matter infiltration may be common among different types of tumor., Material and Methods: Preoperative, anatomic (T1- and T2-weighted), and LINESCAN diffusion tensor MRI were obtained in 12 patients harboring supratentorial gliomas (World Health Organization [WHO] Grades II and III). The two imaging modalities were rigidly registered. The tumors were manually segmented from the T1- and T2-weighted MRI, and their volume calculated. A three-dimensional tractography was performed in each case. A second segmentation and volume measurement was performed on the tumor regions intersecting adjacent white matter fiber tracts. Statistical methods included summary statistics to examine the fraction of tumor volume infiltrating adjacent white matter., Results: There were five patients with low-grade oligodendroglioma (WHO Grade II), one with low-grade mixed oligoastrocytoma (WHO Grade II), one with ganglioglioma, two with low-grade astrocytoma (WHO Grade II), and three with anaplastic astrocytoma (WHO Grade III). We identified white matter tracts infiltrated by tumor in all 12 cases. The median tumor volume (+/- standard deviation) in our patient population was 42.5 +/- 28.9 mL. The median tumor volume (+/- standard deviation) infiltrating white matter fiber tracts was 5.2 +/- 9.9 mL. The median percentage of tumor volume infiltrating white matter fiber tracts was 21.4% +/- 9.7%., Conclusions: The information provided by diffusion tensor imaging combined with anatomic MRI might be useful for neurosurgical planning and intraoperative guidance. Our results confirm previous reports that extensive white matter infiltration by primary brain tumors is a common occurrence. However, prospective, large population studies are required to definitively clarify this issue, and how infiltration relates to histologic tumor type, tumor size, and location.

We present a new algorithm to register 3-D preoperative magnetic resonance (MR) images to intraoperative MR images of the brain which have undergone brain shift. This algorithm relies on a robust estimation of the deformation from a sparse noisy set of measured displacements. We propose a new framework to compute the displacement field in an iterative process, allowing the solution to gradually move from an approximation formulation (minimizing the sum of a regularization term and a data error term) to an interpolation formulation (least square minimization of the data error term). An outlier rejection step is introduced in this gradual registration process using a weighted least trimmed squares approach, aiming at improving the robustness of the algorithm. We use a patient-specific model discretized with the finite element method in order to ensure a realistic mechanical behavior of the brain tissue. To meet the clinical time constraint, we parallelized the slowest step of the algorithm so that we can perform a full 3-D image registration in 35 s (including the image update time) on a heterogeneous cluster of 15 personal computers. The algorithm has been tested on six cases of brain tumor resection, presenting a brain shift of up to 14 mm. The results show a good ability to recover large displacements, and a limited decrease of accuracy near the tumor resection cavity.

Objective: Medical classification accuracy studies often yield continuous data based on predictive models for treatment outcomes. A popular method for evaluating the performance of diagnostic tests is the receiver operating characteristic (ROC) curve analysis. The main objective was to develop a global statistical hypothesis test for assessing the goodness-of-fit (GOF) for parametric ROC curves via the bootstrap., Design: A simple log (or logit) and a more flexible Box-Cox normality transformations were applied to untransformed or transformed data from two clinical studies to predict complications following percutaneous coronary interventions (PCIs) and for image-guided neurosurgical resection results predicted by tumor volume, respectively. We compared a non-parametric with a parametric binormal estimate of the underlying ROC curve. To construct such a GOF test, we used the non-parametric and parametric areas under the curve (AUCs) as the metrics, with a resulting p value reported., Results: In the interventional cardiology example, logit and Box-Cox transformations of the predictive probabilities led to satisfactory AUCs (AUC=0.888; p=0.78, and AUC=0.888; p=0.73, respectively), while in the brain tumor resection example, log and Box-Cox transformations of the tumor size also led to satisfactory AUCs (AUC=0.898; p=0.61, and AUC=0.899; p=0.42, respectively). In contrast, significant departures from GOF were observed without applying any transformation prior to assuming a binormal model (AUC=0.766; p=0.004, and AUC=0.831; p=0.03), respectively., Conclusions: In both studies the p values suggested that transformations were important to consider before applying any binormal model to estimate the AUC. Our analyses also demonstrated and confirmed the predictive values of different classifiers for determining the interventional complications following PCIs and resection outcomes in image-guided neurosurgery.

During neurosurgical procedures the objective of the neurosurgeon is to achieve the resection of as much diseased tissue as possible while achieving the preservation of healthy brain tissue. The restricted capacity of the conventional operating room to enable the surgeon to visualize critical healthy brain structures and tumor margin has lead, over the past decade, to the development of sophisticated intraoperative imaging techniques to enhance visualization. However, both rigid motion due to patient placement and nonrigid deformations occurring as a consequence of the surgical intervention disrupt the correspondence between preoperative data used to plan surgery and the intraoperative configuration of the patient's brain. Similar challenges are faced in other interventional therapies, such as in cryoablation of the liver, or biopsy of the prostate. We have developed algorithms to model the motion of key anatomical structures and system implementations that enable us to estimate the deformation of the critical anatomy from sequences of volumetric images and to prepare updated fused visualizations of preoperative and intraoperative images at a rate compatible with surgical decision making. This paper reviews the experience at Brigham and Women's Hospital through the process of developing and applying novel algorithms for capturing intraoperative deformations in support of image guided therapy.

We present a new algorithm to register 3D pre-operative Magnetic Resonance (MR) images with intra-operative MR images of the brain. This algorithm relies on a robust estimation of the deformation from a sparse set of measured displacements. We propose a new framework to compute iteratively the displacement field starting from an approximation formulation (minimizing the sum of a regularization term and a data error term) and converging toward an interpolation formulation (least square minimization of the data error term). The robustness of the algorithm is achieved through the introduction of an outliers rejection step in this gradual registration process. We ensure the validity of the deformation by the use of a biomechanical model of the brain specific to the patient, discretized with the finite element method. The algorithm has been tested on six cases of brain tumor resection, presenting a brain shift up to 13 mm.

In this paper we present a new algorithm for 3D medical image segmentation. The algorithm is versatile, fast, relatively simple to implement, and semi-automatic. It is based on minimizing a global energy defined from a learned non-parametric estimation of the statistics of the region to be segmented. Implementation details are discussed and source code is freely available as part of the 3D Slicer project. In addition, a new unified set of validation metrics is proposed. Results on artificial and real MRI images show that the algorithm performs well on large brain structures both in terms of accuracy and robustness to noise.

We introduce a method for combining fiber tracking from diffusion-tensor (DT) imaging with cortical gray matter parcellation from structural high-spatial-resolution 3D spoiled gradient-recalled acquisition in the steady state images. We applied this method to a tumor case to determine the impact of the tumor on white matter architecture. We conclude that this new method for combining structural and DT imaging data is useful for understanding cortical connectivity and the localization of fiber tracts and their relationship with cortical anatomy and brain abnormalities.

The validity of brain tumour segmentation is an important issue in image processing because it has a direct impact on surgical planning. We examined the segmentation accuracy based on three two-sample validation metrics against the estimated composite latent gold standard, which was derived from several experts' manual segmentations by an EM algorithm. The distribution functions of the tumour and control pixel data were parametrically assumed to be a mixture of two beta distributions with different shape parameters. We estimated the corresponding receiver operating characteristic curve, Dice similarity coefficient, and mutual information, over all possible decision thresholds. Based on each validation metric, an optimal threshold was then computed via maximization. We illustrated these methods on MR imaging data from nine brain tumour cases of three different tumour types, each consisting of a large number of pixels. The automated segmentation yielded satisfactory accuracy with varied optimal thresholds. The performances of these validation metrics were also investigated via Monte Carlo simulation. Extensions of incorporating spatial correlation structures using a Markov random field model were considered., (Copyright 2004 John Wiley & Sons, Ltd.)

Rationale and Objectives: To examine a statistical validation method based on the spatial overlap between two sets of segmentations of the same anatomy., Materials and Methods: The Dice similarity coefficient (DSC) was used as a statistical validation metric to evaluate the performance of both the reproducibility of manual segmentations and the spatial overlap accuracy of automated probabilistic fractional segmentation of MR images, illustrated on two clinical examples. Example 1: 10 consecutive cases of prostate brachytherapy patients underwent both preoperative 1.5T and intraoperative 0.5T MR imaging. For each case, 5 repeated manual segmentations of the prostate peripheral zone were performed separately on preoperative and on intraoperative images. Example 2: A semi-automated probabilistic fractional segmentation algorithm was applied to MR imaging of 9 cases with 3 types of brain tumors. DSC values were computed and logit-transformed values were compared in the mean with the analysis of variance (ANOVA)., Results: Example 1: The mean DSCs of 0.883 (range, 0.876-0.893) with 1.5T preoperative MRI and 0.838 (range, 0.819-0.852) with 0.5T intraoperative MRI (P < .001) were within and at the margin of the range of good reproducibility, respectively. Example 2: Wide ranges of DSC were observed in brain tumor segmentations: Meningiomas (0.519-0.893), astrocytomas (0.487-0.972), and other mixed gliomas (0.490-0.899)., Conclusion: The DSC value is a simple and useful summary measure of spatial overlap, which can be applied to studies of reproducibility and accuracy in image segmentation. We observed generally satisfactory but variable validation results in two clinical applications. This metric may be adapted for similar validation tasks.

Rationale and Objectives: The accuracy of diagnostic test and imaging segmentation is important in clinical practice because it has a direct impact on therapeutic planning. Statistical validations of classification accuracy was conducted based on parametric receiver operating characteristic analysis, illustrated on three radiologic examples,, Materials and Methods: Two parametric models were developed for diagnostic or imaging data. Example 1: A semi-automated fractional segmentation algorithm was applied to magnetic resonance imaging of nine cases of brain tumors. The tumor and background pixel data were assumed to have bi-beta distributions. Fractional segmentation was validated against an estimated composite pixel-wise gold standard based on multi-reader manual segmentations. Example 2: The predictive value of 100 cases of spiral computed tomography of ureteral stone sizes, distributed as bi-normal after a non-linear transformation, under two treatment options received. Example 3: One hundred eighty cases had prostate-specific antigen levels measured in a prospective clinical trial. Radical prostatectomy was performed in all to provide a binary gold standard of local and advanced cancer stages. Prostate-specific antigen level was transformed and modeled by bi-normal distributions. In all examples, areas under the receiver operating characteristic curves were computed. RESULTS. The areas under the receiver operating characteristic curves were: Example 1: Fractional segmentation of magnetic resonance imaging of brain tumors: meningiomas (0.924-0.984); astrocytomas (0.786-0.986); and other low-grade gliomas (0.896-0.983). Example 3: Ureteral stone size for treatment planning (0.813). Example 2: Prostate-specific antigen for staging prostate cancer (0.768)., Conclusion: All clinical examples yielded fair to excellent accuracy. The validation metric area under the receiver operating characteristic curves may be generalized to evaluating the performances of several continuous classifiers related to imaging.