Tractostorm: The what, why, and how of tractography dissection reproducibility.

Investigative studies of white matter (WM) brain structures using diffusion MRI (dMRI) tractography frequently require manual WM bundle segmentation, often called "virtual dissection." Human errors and personal decisions make these manual segmentations hard to reproduce, which have not yet been quantified by the dMRI community. It is our opinion that if the field of dMRI tractography wants to be taken seriously as a widespread clinical tool, it is imperative to harmonize WM bundle segmentations and develop protocols aimed to be used in clinical settings. The EADC-ADNI Harmonized Hippocampal Protocol achieved such standardization through a series of steps that must be reproduced for every WM bundle. This article is an observation of the problematic. A specific bundle segmentation protocol was used in order to provide a real-life example, but the contribution of this article is to discuss the need for reproducibility and standardized protocol, as for any measurement tool. This study required the participation of 11 experts and 13 nonexperts in neuroanatomy and "virtual dissection" across various laboratories and hospitals. Intra-rater agreement (Dice score) was approximately 0.77, while inter-rater was approximately 0.65. The protocol provided to participants was not necessarily optimal, but its design mimics, in essence, what will be required in future protocols. Reporting tractometry results such as average fractional anisotropy, volume or streamline count of a particular bundle without a sufficient reproducibility score could make the analysis and interpretations more difficult. Coordinated efforts by the diffusion MRI tractography community are needed to quantify and account for reproducibility of WM bundle extraction protocols in this era of open and collaborative science.

Patient-specific 3-dimensionally printed models for neurosurgical planning and education.

OBJECTIVE: Advances in 3-dimensional (3D) printing technology permit the rapid creation of detailed anatomical models. Integration of this technology into neurosurgical practice is still in its nascence, however. One potential application is to create models depicting neurosurgical pathology. The goal of this study was to assess the clinical value of patient-specific 3D printed models for neurosurgical planning and education. METHODS: The authors created life-sized, patient-specific models for 4 preoperative cases. Three of the cases involved adults (2 patients with petroclival meningioma and 1 with trigeminal neuralgia) and the remaining case involved a pediatric patient with craniopharyngioma. Models were derived from routine clinical imaging sequences and manufactured using commercially available software and hardware. RESULTS: Life-sized, 3D printed models depicting bony, vascular, and neural pathology relevant to each case were successfully manufactured. A variety of commercially available software and hardware were used to create and print each model from radiological sequences. The models for the adult cases were printed in separate pieces, which had to be painted by hand, and could be disassembled for detailed study, while the model for the pediatric case was printed as a single piece in separate-colored resins and could not be disassembled for study. Two of the models were used for patient education, and all were used for presurgical planning by the surgeon. CONCLUSIONS: Patient-specific 3D printed models are useful to neurosurgical practice. They may be used as a visualization aid for surgeons and patients, or for education of trainees.

Generalized q-sampling imaging fiber tractography reveals displacement and infiltration of fiber tracts in low-grade gliomas.

PURPOSE: Low-grade gliomas (LGGs) are slow growing brain tumors that often cause displacement and/or infiltration of the surrounding white matter pathways. Differentiation between infiltration and displacement of fiber tracts remains a challenge. Currently, there is no reliable noninvasive imaging method capable of revealing such white matter alteration patterns. We employed quantitative anisotropy (QA) derived from generalized q-sampling imaging (GQI) to identify patterns of fiber tract alterations by LGGs. METHODS: Sixteen patients with a neuropathological diagnosis of LGG (WHO grade II) were enrolled. Peritumoral fiber tracts underwent qualitative and quantitative evaluation. Contralateral hemisphere counterparts were used for comparison. Tracts were qualitatively classified as unaffected, displaced, infiltrated or displaced, and infiltrated at once. The average QA of whole tract (W), peritumoral tract segment (S), and their ratio (S/W) were obtained and compared to the healthy side for quantitative evaluation. RESULTS: Qualitative analysis revealed 9 (13.8%) unaffected, 24 (36.9%) displaced, 13 (20%) infiltrated, and 19 (29.2%) tracts with a combination of displacement and infiltration. There were no disrupted tracts. There was a significant increase in S/W ratio among displaced tracts in the pre-operative scans in comparison with the contralateral side. QA values of peritumoral tract segments (S) were significantly lower in infiltrated tracts. CONCLUSION: WHO grade II LGGs might displace, infiltrate, or cause a combination of displacement and infiltration of WM tracts. QA derived from GQI provides valuable information that helps to differentiate infiltration from displacement. Anisotropy changes correlate with qualitative alterations, which may serve as a potential biomarker of fiber tract integrity.

A diffusion spectrum imaging-based tractographic study into the anatomical subdivision and cortical connectivity of the ventral external capsule: uncinate and inferior fronto-occipital fascicles.

PURPOSE: The inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus (UF) are major fronto-capsular white matter pathways. IFOF connects frontal areas of the brain to parieto-occipital areas. UF connects ventral frontal areas to anterior temporal areas. Both fascicles are thought to subserve higher language and emotion roles. Controversy pertaining to their connectivity and subdivision persists in the literature, however. METHODS: High-definition fiber tractography (HDFT) is a non-tensor tractographic method using diffusion spectrum imaging data. Its major advantage over tensor-based tractography is its ability to trace crossing fiber pathways. We used HDFT to investigate subdivisions and cortical connectivity of IFOF and UF in 30 single subjects and in an atlas comprising averaged data from 842 individuals. A per-subject aligned, atlas-based approach was employed to seed fiber tracts and to study cortical terminations. RESULTS: For IFOF, we observed a tripartite arrangement corresponding to ventrolateral, ventromedial, and dorsomedial frontal origins. IFOF volume was not significantly lateralized to either hemisphere. UF fibers arose from ventromedial and ventrolateral frontal areas on the left and from ventromedial frontal areas on the right. UF volume was significantly lateralized to the left hemisphere. The data from the averaged atlas was largely in concordance with subject-specific findings. IFOF connected to parietal, occipital, but not temporal, areas. UF connected predominantly to temporal poles. CONCLUSION: Both IFOF and UF possess subdivided arrangements according to their frontal origin. Our connectivity results indicate the multifunctional involvement of IFOF and UF in language tasks. We discuss our findings in context of the tractographic literature.

Biofilms-Impacts on Human Health and Its Relevance to Space Travel.

As the world looks towards the stars, the impacts of endogenous and exogenous microorganisms on human health during long-duration space flight are subjects of increased interest within the space community. The presence and continued growth of bacterial biofilms about spacecraft has been documented for decades; however, the impact on crew health is in its infancy. The impacts of biofilms are well known in the medical, agricultural, commercial, and industrial spaces. It less known that biofilms are undermining many facets of space travel and that their effects need to be understood and addressed for future space missions. Biofilms can damage space crew health and spoil limited food supply. Yet, at the same time, they can benefit plant systems for food growth, nutrient development, and other biological systems that are being explored for use in space travel. Various biofilm removal techniques have been studied to mitigate the hazards posed by biofilm persistence during space travel. Because the presence of biofilms can advance or hinder humanity's space exploration efforts, an understanding of their impacts over the duration of space flights is of paramount importance.

Neurosurgery and Manned Spaceflight.

There has been a renewed interest in manned spaceflight due to endeavors by private and government agencies. Publicized goals include manned trips to or colonization of Mars. These missions will likely be of long duration, exceeding existing records for human exposure to extra-terrestrial conditions. Participants will be exposed to microgravity, temperature extremes, and radiation, all of which may adversely affect their physiology. Moreover, pathological mechanisms may differ from those of a terrestrial nature. Known central nervous system (CNS) changes occurring in space include rises in intracranial pressure and spinal unloading. Intracranial pressure increases are thought to occur due to cephalad re-distribution of body fluids secondary to microgravity exposure. Spinal unloading in microgravity results in potential degenerative changes to the bony vertebrae, intervertebral discs, and supportive musculature. These phenomena are poorly understood. Trauma is of highest concern due to its potential to seriously incapacitate crewmembers and compromise missions. Traumatic pathology may also be exacerbated in the setting of altered CNS physiology. Though there are no documented instances of CNS pathologies arising in space, existing diagnostic and treatment capabilities will be limited relative to those on Earth. In instances where neurosurgical intervention is required in space, it is not known whether open or endoscopic approaches are feasible. It is obvious that prevention of trauma and CNS pathology should be emphasized. Further research into neurosurgical pathology, its diagnosis, and treatment in space are required should exploratory or colonization missions be attempted.

Promises and Perils of Artificial Intelligence in Neurosurgery.

Artificial intelligence (AI)-facilitated clinical automation is expected to become increasingly prevalent in the near future. AI techniques may permit rapid and detailed analysis of the large quantities of clinical data generated in modern healthcare settings, at a level that is otherwise impossible by humans. Subsequently, AI may enhance clinical practice by pushing the limits of diagnostics, clinical decision making, and prognostication. Moreover, if combined with surgical robotics and other surgical adjuncts such as image guidance, AI may find its way into the operating room and permit more accurate interventions, with fewer errors. Despite the considerable hype surrounding the impending medical AI revolution, little has been written about potential downsides to increasing clinical automation. These may include both direct and indirect consequences. Directly, faulty, inadequately trained, or poorly understood algorithms may produce erroneous results, which may have wide-scale impact. Indirectly, increasing use of automation may exacerbate de-skilling of human physicians due to over-reliance, poor understanding, overconfidence, and lack of necessary vigilance of an automated clinical workflow. Many of these negative phenomena have already been witnessed in other industries that have already undergone, or are undergoing "automation revolutions," namely commercial aviation and the automotive industry. This narrative review explores the potential benefits and consequences of the anticipated medical AI revolution from a neurosurgical perspective.

Neuroendovascular-specific engineering modifications to the CorPath GRX Robotic System.

OBJECTIVE: The aim of this study was to evaluate new, neuroendovascular-specific engineering and software modifications to the CorPath GRX Robotic System for their ability to support safer and more effective cranial neurovascular interventions in a preclinical model. METHODS: Active device fixation (ADF) control software, permitting automated manipulation of the guidewire relative to the microcatheter, and a modified drive cassette suitable for neuroendovascular instruments were the respective software and hardware modifications to the current CorPath GRX robot, which was cleared by the FDA for percutaneous coronary and peripheral vascular intervention. The authors then trialed the modified system in a live porcine model with simulated neuroendovascular pathology. Femoral access through the aortic arch to the common carotid artery was accomplished manually (without robotic assistance), and the remaining endovascular procedures were performed with robotic assistance. The system was tested for the enhanced ability to navigate and manipulate neurovascular-specific guidewires and microcatheters. The authors specifically evaluated the movement of the wire forward and backward during the advancement of the microcatheter. RESULTS: Navigation of the rete mirabile and an induced aneurysm within the common carotid artery were successful. The active device fixation feature enabled independent advancement and retraction of the guidewire and working device relative to the microcatheter. When ADF was inactive, the mean forward motion of the guidewire was 5 mm and backward motion was 0 mm. When ADF was active, the mean forward motion of the guidewire was 0 mm and backward motion was 1.5 mm. The modifications made to the robotic cassette enabled the system to successfully manipulate the microcatheter and guidewire safely and in a manner more suited to neuroendovascular procedures than before. There were no occurrences of dissection, extravasation, or thrombosis. CONCLUSIONS: The robotic system was originally designed to navigate and manipulate devices for cardiac and peripheral vascular intervention. The current modifications described here improved its utility for the more delicate and tortuous neurovascular environment. This will set the stage for the development of a neurovascular-specific robot.

Structure, asymmetry, and connectivity of the human temporo-parietal aslant and vertical occipital fasciculi.

We previously proposed a bipartite 'dorsal-ventral' model of human arcuate fasciculus (AF) morphology. This model does not, however, account for the 'vertical,' temporo-parietal subdivision of the AF described in earlier dissection and tractographic studies. In an effort to address the absence of the vertical AF (VAF) within 'dorsal-ventral' nomenclature, we conducted a dedicated tractographic and white-matter dissection study of this tract and another short, vertical, posterior-hemispheric fascicle: the vertical occipital fasciculus (VOF). We conducted atlas-based, non-tensor, deterministic tractography in 30 single subjects from the Human Connectome Project database and verified our results using an average diffusion atlas compiled from 842 separate normal subjects. We also performed white-matter dissection in four post-mortem specimens. Our  tractography results demonstrate that the VAF is, in fact, a bipartite system connecting the ventral parietal and temporal regions, with variable connective, and no volumetric lateralization. The VOF is a non-lateralized, non-segmented system connecting lateral occipital areas with basal-temporal regions. Importantly, the VOF was spatially dissociated from the VAF. As the VAF demonstrates no overall connective or volumetric lateralization, we postulate its distinction from the AF system and propose its re-naming to the 'temporo-parietal aslant tract,' (TPAT), with unique dorsal and ventral subdivisions. Our tractography results were supported by diffusion atlas and white-matter dissection findings.

Machine Learning Versus Logistic Regression Methods for 2-Year Mortality Prognostication in a Small, Heterogeneous Glioma Database.

BACKGROUND: Machine learning (ML) is the application of specialized algorithms to datasets for trend delineation, categorization, or prediction. ML techniques have been traditionally applied to large, highly dimensional databases. Gliomas are a heterogeneous group of primary brain tumors, traditionally graded using histopathologic features. Recently, the World Health Organization proposed a novel grading system for gliomas incorporating molecular characteristics. We aimed to study whether ML could achieve accurate prognostication of 2-year mortality in a small, highly dimensional database of patients with glioma. METHODS: We applied 3 ML techniques (artificial neural networks [ANNs], decision trees [DTs], and support vector machines [SVMs]) and classical logistic regression (LR) to a dataset consisting of 76 patients with glioma of all grades. We compared the effect of applying the algorithms to the raw database versus a database where only statistically significant features were included into the algorithmic inputs (feature selection). RESULTS: Raw input consisted of 21 variables and achieved performance of accuracy/area (C.I.) under the curve of 70.7%/0.70 (49.9-88.5) for ANN, 68%/0.72 (53.4-90.4) for SVM, 66.7%/0.64 (43.6-85.0) for LR, and 65%/0.70 (51.6-89.5) for DT. Feature selected input consisted of 14 variables and achieved performance of 73.4%/0.75 (62.9-87.9) for ANN, 73.3%/0.74 (62.1-87.4) for SVM, 69.3%/0.73 (60.0-85.8) for LR, and 65.2%/0.63 (49.1-76.9) for DT. CONCLUSIONS: We demonstrate that these techniques can also be applied to small, highly dimensional datasets. Our ML techniques achieved reasonable performance compared with similar studies in the literature. Although local databases may be small versus larger cancer repositories, we demonstrate that ML techniques can still be applied to their analysis; however, traditional statistical methods are of similar benefit.

Tractography for Surgical Neuro-Oncology Planning: Towards a Gold Standard.

Magnetic resonance imaging tractography permits in vivo visualization of white matter structures. Aside from its academic value, tractography has been proven particularly useful to neurosurgeons for preoperative planning. Preoperative tractography permits both qualitative and quantitative analyses of tumor effects upon surrounding white matter, allowing the surgeon to specifically tailor their operative approach. Despite its benefits, there is controversy pertaining to methodology, implementation, and interpretation of results in this context. High-definition fiber tractography (HDFT) is one of several non-tensor tractography approaches permitting visualization of crossing white matter trajectories at high resolutions, dispensing with the well-known shortcomings of diffusion tensor imaging (DTI) tractography. In this article, we provide an overview of the advantages of HDFT in a neurosurgical context, derived from our considerable experience implementing the technique for academic and clinical purposes. We highlight nuances of qualitative and quantitative approaches to using HDFT for brain tumor surgery planning, and integration of tractography with complementary operative adjuncts, and consider areas requiring further research.

Feasibility of Clinician-Facilitated Three-Dimensional Printing of Synthetic Cranioplasty Flaps.

BACKGROUND: Integration of three-dimensional (3D) printing and stereolithography into clinical practice is in its nascence, and concepts may be esoteric to the practicing neurosurgeon. Currently, creation of 3D printed implants involves recruitment of offsite third parties. We explored a range of 3D scanning and stereolithographic techniques to create patient-specific synthetic implants using an onsite, clinician-facilitated approach. METHODS: We simulated bilateral craniectomies in a single cadaveric specimen. We devised 3 methods of creating stereolithographically viable virtual models from removed bone. First, we used preoperative and postoperative computed tomography scanner-derived bony window models from which the flap was extracted. Second, we used an entry-level 3D light scanner to scan and render models of the individual bone pieces. Third, we used an arm-mounted, 3D laser scanner to create virtual models using a real-time approach. RESULTS: Flaps were printed from the computed tomography scanner and laser scanner models only in a ultraviolet-cured polymer. The light scanner did not produce suitable virtual models for printing. The computed tomography scanner-derived models required extensive postfabrication modification to fit the existing defects. The laser scanner models assumed good fit within the defects without any modification. CONCLUSIONS: The methods presented varying levels of complexity in acquisition and model rendering. Each technique required hardware at varying in price points from $0 to approximately $100,000. The laser scanner models produced the best quality parts, which had near-perfect fit with the original defects. Potential neurosurgical applications of this technology are discussed.

A Quantitative Tractography Study Into the Connectivity, Segmentation and Laterality of the Human Inferior Longitudinal Fasciculus.

The human inferior longitudinal fasciculus (ILF) is a ventral, temporo-occipital association tract. Though described in early neuroanatomical works, its existence was later questioned. Application of in vivo tractography to the neuroanatomical study of the ILF has generally confirmed its existence, however, consensus is lacking regarding its subdivision, laterality and connectivity. Further, there is a paucity of detailed neuroanatomic data pertaining to the exact anatomy of the ILF. Generalized Q-Sampling imaging (GQI) is a non-tensor tractographic modality permitting high resolution imaging of white-matter structures. As it is a non-tensor modality, it permits visualization of crossing fibers and accurate delineation of close-proximity fiber-systems. We applied deterministic GQI tractography to data from 30 healthy subjects and a large-volume, averaged diffusion atlas, to delineate ILF anatomy. Post-mortem white matter dissection was also carried out in three cadaveric specimens for further validation. The ILF was found in all 60 hemispheres. At its occipital extremity, ILF fascicles demonstrated a bifurcated, ventral-dorsal morphological termination pattern, which we used to further subdivide the bundle for detailed analysis. These divisions were consistent across the subject set and within the atlas. We applied quantitative techniques to study connectivity strength of the ILF at its anterior and posterior extremities. Overall, both morphological divisions, and the un-separated ILF, demonstrated strong leftward-lateralized connectivity patterns. Leftward-lateralization was also found for ILF volumes across the subject set. Due to connective and volumetric leftward-dominance and ventral location, we postulate the ILFs role in the semantic system. Further, our results are in agreement with functional and lesion-based postulations pertaining to the ILFs role in facial recognition.

Surgical Management of Vertex Epidural Hematoma: Technical Case Report and Literature Review.

BACKGROUND: Vertex epidural hematoma (VEH) is an uncommon presentation of extra-axial hematomas. It can represent a surgical dilemma regarding when and how to operate, particularly considering the potential implication of the superior sagittal sinus (SSS). OBJECTIVE: Here, we illustrate the surgical technique for VEH as well as a review of the existing literature. METHODS: A 60-year-old man sustained a ground-level fall resulting in complete diastasis of the sagittal suture with underlying large VEH causing significant mass effect on the SSS and bihemispheric convexities. Twenty-four hours later, the patient deteriorated, with decreased level of alertness and worsening asymmetric paresis on his lower extremities. He subsequently underwent surgical evacuation of the hematoma, decompression of the SSS, and fracture repair. A modified bicoronal approach, with bilateral parasagittal craniotomies, was performed. A central island of bone was left intact to spare the diastatic fracture from the craniotomies. This was done to ensure a stable anchor point for tacking-up the underlying displaced dura and SSS. The central bone prevents extensive bleeding from the diastatic fracture and eliminates the risk of further blood reaccumulation and tearing of a possible injured sinus during bone flap elevation. RESULTS: The technique performed allowed us to evacuate completely the hematoma while preserving the SSS and repairing the sagittal suture to avoid further bleeding. Complete neurologic recovery of the patient occurred after VEH evacuation. CONCLUSIONS: Because of its rare nature, VEH represents a surgical challenge. Because neurosurgeons encounter this condition relatively infrequently, literature regarding the medical and surgical management of this entity is warranted.

High-Definition Fiber Tractography in the Evaluation and Surgical Planning of Lhermitte-Duclos Disease: A Case Report.

BACKGROUND: Preoperative delineation of normal tissue displacement patterns in Lhermitte-Duclos disease has not been feasible with conventional imaging means. Surgical resection of this type of lesion remains challenging, because the boundaries of the lesion are indistinguishable during surgery. CASE DESCRIPTION: The clinical presentation, preoperative and postoperative magnetic resonance imaging (MRI) findings, high-definition fiber tractography (HDFT) and histopathological studies, are presented in a 46-year-old male subject with symptomatic Lhermitte-Duclos disease. HDFT was performed using a quantitative anisotropy-based generalized deterministic tracking algorithm to define fiber tracts. Displacement of the cerebellar and brainstem tracts on the affected side was performed using the unaffected contralateral side as a comparison. The displacement of the normal tissues was not apparent on preoperative MRI but was immediately evident on the preoperative HDFT. Of note, there was a relative paucity of fiber tracts within the lesion. By tailoring our operative boundaries based on the HDFT findings, we were able to spare the displaced fiber tracts when debulking the tumor. Restoration of normal fiber tract anatomy on postoperative HDFT imaging was correlated with clinical resolution of preoperative symptoms. CONCLUSIONS: This case report suggests that HDFT may be a powerful surgical planning tool in cases of Lhermitte-Duclos disease, in which the pattern of normal tissue displacement is not evident with conventional imaging, allowing maximal lesion resection without damage to the unaffected tracts. Therefore, this report contributes to solving the greatest challenge when operating on this type of lesion, which has not been resolved in any previous report in our review of the English literature.