Exosomes in Vascular/Neurological Disorders and the Road Ahead.

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), stroke, and aneurysms, are characterized by the abnormal accumulation and aggregation of disease-causing proteins in the brain and spinal cord. Recent research suggests that proteins linked to these conditions can be secreted and transferred among cells using exosomes. The transmission of abnormal protein buildup and the gradual degeneration in the brains of impacted individuals might be supported by these exosomes. Furthermore, it has been reported that neuroprotective functions can also be attributed to exosomes in neurodegenerative diseases. The potential neuroprotective functions may play a role in preventing the formation of aggregates and abnormal accumulation of proteins associated with the disease. The present review summarizes the roles of exosomes in neurodegenerative diseases as well as elucidating their therapeutic potential in AD, PD, ALS, HD, stroke, and aneurysms. By elucidating these two aspects of exosomes, valuable insights into potential therapeutic targets for treating neurodegenerative diseases may be provided.

Toward an optimal cadaveric brain model for neurosurgical education: assessment of preservation, parenchyma, vascular injection, and imaging.

OBJECTIVE: We assessed types of cadaveric head and brain tissue specimen preparations that are used in a high throughput neurosurgical research laboratory to determine optimal preparation methods for neurosurgical anatomical research, education, and training. METHODS: Cadaveric specimens (N = 112) prepared using different preservation and vascular injection methods were imaged, dissected, and graded by 11 neurosurgeons using a 21-point scale. We assessed the quality of tissue and preservation in both the anterior and posterior circulations. Tissue quality was evaluated using a 9-point magnetic resonance imaging (MRI) scale. RESULTS: Formalin-fixed specimens yielded the highest scores for assessment (mean ± SD [17.0 ± 2.8]) vs. formalin-flushed (17.0 ± 3.6) and MRI (6.9 ± 2.0). Cadaver assessment and MRI scores were positively correlated (P < 0.001, R2 0.60). Analysis showed significant associations between cadaver assessment scores and specific variables: nonformalin fixation (ß = -3.3), preservation within ≤72 h of death (ß = 1.8), and MRI quality score (ß = 0.7). Formalin-fixed specimens exhibited greater hardness than formalin-flushed and nonformalin-fixed specimens (P ≤ 0.006). Neurosurgeons preferred formalin-flushed specimens injected with colored latex. CONCLUSION: For better-quality specimens for neurosurgical education and training, formalin preservation within ≤72 h of death was preferable, as was injection with colored latex. Formalin-flushed specimens more closely resembled live brain parenchyma. Assessment scores were lower for preparation techniques performed > 72 h postmortem and for nonformalin preservation solutions. The positive correlation between cadaver assessment scores and our novel MRI score indicates that donation organizations and institutional buyers should incorporate MRI as a screening tool for the selection of high-quality specimens.

Mandibular Fossa Approach to Petroclival and Anterior Pontine Lesions.

Objective To describe the anatomy related to a novel approach to the petroclival region through the mandibular fossa for the treatment of petroclival and anterior pontine lesions. Design Five dry skulls were examined for surgical approach. Three adult cadaveric heads underwent bilateral dissection. One cadaveric head was evaluated with computed tomography after dissection. Setting This study was performed in an academic medical center. Participants Neurosurgical anatomy researchers performed this study using dry skulls and cadaveric heads. Main Outcome Measurements This was a proof-of-concept anatomical study. Results The mandibular fossa approach uses a vertical preauricular incision above the facial nerve branches. Removal of the temporomandibular joint exposes the mandibular fossa. The anterior boundary is the mandibular nerve at the foramen ovale, and the posterior boundary is the jugular foramen. The chorda tympani, eustachian tube, and tensor tympani muscle are sectioned. The carotid artery is transposed out of the petrous canal, and a petrosectomy is performed from Meckel's cave to the foramen magnum and anterior occipital condyle. Dural opening exposes the anterior pons, vertebrobasilar junction, bilateral vertebral arteries, and the ipsilateral anterior and posterior inferior cerebellar arteries. At completion, the temporomandibular joint is reconstructed with a prosthetic joint utilizing a second incision along the mandible. Conclusions The mandibular fossa approach is a new trajectory to the petroclival region and the anterior pons. It combines the more anterior angle of endoscopic approaches along with the enhanced control of open approaches. Further study is necessary before this approach is used clinically.

Arteriovenous malformation with unique drainage through the emissary vein of the foramen ovale: illustrative case.

BACKGROUND: As part of the laterotrigeminal venous system (LTVS), the emissary vein of the foramen ovale (EVFO) is an underrecognized venous structure communicating between the cavernous sinus and pterygoid plexus. The sphenobasal sinus is an anatomical variation of the sphenoparietal sinus that drains directly into the EVFO. The authors present the case of a ruptured arteriovenous malformation (AVM) with a unique drainage pattern through the sphenobasal sinus and EVFO. OBSERVATIONS: A 9-year-old female initially presented with loss of consciousness and was subsequently found to have a ruptured AVM in the left basal frontal area. She underwent an immediate decompressive hemicraniectomy, with a computed tomography angiogram demonstrating a unique anatomical variation in which the sphenobasal sinus communicated with the EVFO and LTVS. The final venous drainage returned to the pterygoid plexus and external jugular vein. Postoperatively, the patient made a substantial recovery, with generalized right-sided weakness remaining as the sole deficit. LESSONS: The authors present the case of a ruptured AVM with unique venous drainage into the sphenobasal sinus and EVFO, for which the current literature remains limited. As exemplified by this illustrative case, technique modification may be warranted in the setting of this unique anatomical variation to avoid venous sinus injury.

Interactive microsurgical anatomy education using photogrammetry 3D models and an augmented reality cube.

OBJECTIVE: This study sought to assess the use of an augmented reality (AR) tool for neurosurgical anatomical education. METHODS: Three-dimensional models were created using advanced photogrammetry and registered onto a handheld AR foam cube imprinted with scannable quick response codes. A perspective analysis of the cube anatomical system was performed by loading a 3D photogrammetry model over a motorized turntable to analyze changes in the surgical window area according to the horizontal rotation. The use of the cube as an intraoperative reference guide for surgical trainees was tested during cadaveric dissection exercises. Neurosurgery trainees from international programs located in Ankara, Turkey; San Salvador, El Salvador; and Moshi, Tanzania, interacted with and assessed the 3D models and AR cube system and then completed a 17-item graded user experience survey. RESULTS: Seven photogrammetry 3D models were created and imported to the cube. Horizontal turntable rotation of the cube translated to measurable and realistic perspective changes in the surgical window area. The combined 3D models and cube system were used to engage trainees during cadaveric dissections, with satisfactory user experience. Thirty-five individuals (20 from Turkey, 10 from El Salvador, and 5 from Tanzania) agreed that the cube system could enhance the learning experience for neurosurgical anatomy. CONCLUSIONS: The AR cube combines tactile and visual sensations with high-resolution 3D models of cadaveric dissections. Inexpensive and lightweight, the cube can be effectively implemented to allow independent co-visualization of anatomical dissection and can potentially supplement neurosurgical education.

Step-by-Step Dissection of the Extreme Lateral Transodontoid Approach to the Anterior Craniovertebral Junction: Surgical Anatomy and Technical Nuances.

BACKGROUND: Multicompartmental lesions of the anterior craniovertebral junction require aggressive management. However, the lesions can be difficult to reach, and the surgical procedure is difficult to understand. The aim of this study was to create a procedural, stepwise microsurgical educational resource for junior trainees to learn the surgical anatomy of the extreme lateral transodontoid approach (ELTOA). METHODS: Ten formalin-fixed, latex-injected cadaveric heads were dissected under an operative microscope. Dissections were performed under the supervision of a skull base fellowship-trained neurosurgeon who has advanced skull base experience. Key steps of the procedure were documented with a professional camera and a high-definition video system. A relevant clinical case example was reviewed to highlight the principles of the selected approach and its application. The clinical case example also describes a rare complication: a pseudoaneurysm of the vertebral artery. RESULTS: Key steps of the ELTOA include patient positioning, skin incision, superficial and deep muscle dissection, vertebral artery dissection and transposition, craniotomy, clivus drilling, odontoidectomy, and final extradural and intradural exposure. CONCLUSIONS: The ELTOA is a challenging approach, but it allows for significant access to the anterior craniovertebral junction, which increases the likelihood of gross total lesion resection. Given the complexity of the approach, substantial training in the dissection laboratory is required to develop the necessary anatomic knowledge and to minimize approach-related morbidity.

Infragalenic triangle as a gateway to dorsal midbrain and posteromedial thalamic lesions: descriptive and quantitative analysis of microsurgical anatomy.

OBJECTIVE: Anatomical triangles provide neurosurgeons with the specificity required to access deep targets, supplementing more general instructions, such as craniotomy and approach. The infragalenic triangle (IGT), bordered by the basal vein of Rosenthal (BVR), precentral cerebellar vein (PCV), and the quadrangular lobule of the cerebellum, is one of a system of anatomical triangles recently introduced to guide dissection to brainstem cavernous malformations and has not been described in detail. This study aimed to quantitatively analyze the anatomical parameters of the IGT and present key nuances for its microsurgical use. METHODS: A midline supracerebellar infratentorial (SCIT) approach through a torcular craniotomy was performed on 5 cadaveric heads, and the IGT was identified in each specimen bilaterally. Anatomical measurements were obtained with point coordinates collected using neuronavigation. Three cadaveric brains were used to illustrate relevant brainstem anatomy, and 3D virtual modeling was used to simulate various perspectives of the IGT through different approach angles. In addition, 2 illustrative surgical cases are presented. RESULTS: The longest edge of the IGT was the lateral edge formed by the BVR (mean ± SD length 19.1 ± 2.3 mm), and the shortest edge was the medial edge formed by the PCV (13.9 ± 3.6 mm). The mean surface area of the IGT was 110 ± 34.2 mm2 in the standard exposure. Full expansion of all 3 edges (arachnoid dissection, mobilization, and retraction) resulted in a mean area of 226.0 ± 48.8 mm2 and a 2.5-times increase in surface area exposure of deep structures (e.g., brainstem and thalamus). Thus, almost the entire tectal plate and its relevant safe entry zones can be exposed through an expanded unilateral IGT except for the contralateral inferior colliculus, access to which is usually hindered by PCV tributaries. Exposure of bilateral IGTs may be required to resect larger midline lesions to increase surgical maneuverability or to access the contralateral pulvinar. CONCLUSIONS: The IGT provides a safe access route to the dorsal midbrain and reliable intraoperative guidance in the deep and complex anatomy of the posterior tentorial incisura. Its potential for expansion makes it a versatile anatomical corridor not only for intrinsic brainstem lesions but also for tumors and vascular malformations of the pineal region, dorsal midbrain, and posteromedial thalamus.

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

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

The biportal transorbital approach: quantitative comparison of the anterior subfrontal craniotomy, bilateral transorbital endoscopic, and microscopic approaches.

OBJECTIVE: The aim of this study was to assess the surgical use and applicability of a biportal bitransorbital approach. Single-portal transorbital and combined transorbital transnasal approaches have been used in clinical practice, but no study has assessed the surgical use and applicability of a biportal bitransorbital approach. METHODS: Ten cadaver specimens underwent midline anterior subfrontal (ASub), bilateral transorbital microsurgery (bTMS), and bilateral transorbital neuroendoscopic surgery (bTONES) approaches. Morphometric analyses included the length of the bilateral cranial nerves I and II, the optic tract, and A1; the area of exposure of the anterior cranial fossa floor; craniocaudal and mediolateral angles of attack (AOAs); and volume of surgical freedom (VSF; maximal available working volume for a specific surgical corridor and surgical target structure normalized to a height of 10 mm) of the bilateral paraclinoid internal carotid arteries (ICAs), bilateral terminal ICAs, and anterior communicating artery (ACoA). Analyses were conducted to determine whether the biportal approach was associated with greater instrument freedom. RESULTS: The bTMS and bTONES approaches provided limited access to the bilateral A1 segments and the ACoA, which were inaccessible in 30% (bTMS) and 60% (bTONES) of exposures. The average total frontal lobe area of exposure (AOE) was 1648.4 mm2 (range 1516.6-1958.8 mm2) for ASub, 1658.9 mm2 (1274.6-1988.2 mm2) for bTMS, and 1914.9 mm2 (1834.2-2014.2 mm2) for bTONES exposures, with no statistically significant superiority between any of the 3 approaches (p = 0.28). The bTMS and bTONES approaches were significantly associated with decreases of 8.7 mm3 normalized volume (p = 0.005) and 14.3 mm3 normalized volume (p < 0.001) for VSF of the right paraclinoid ICA compared with the ASub approach. No statistically significant difference in surgical freedom was noted between all 3 approaches when targeting the bilateral terminal ICA. The bTONES approach was significantly associated with a decrease of 105% in the (log) VSF of the ACoA compared with the ASub (p = 0.009). CONCLUSIONS: Although the biportal approach is intended to improve maneuverability within these minimally invasive approaches, these results illustrate the pertinent issue of surgical corridor crowding and the importance of surgical trajectory planning. A biportal transorbital approach provides improved visualization but does not improve surgical freedom. Furthermore, although it affords impressive anterior cranial fossa AOE, it is unsuitable for addressing midline lesions because the preserved orbital rim restricts lateral movement. Further comparative studies will elucidate whether a combined transorbital transnasal route is preferable to minimize skull base destruction and maximize instrument access.

Predictors of Outcome in Management of Paediatric Head Trauma in a Tertiary Healthcare Institution in North-Central Nigeria.

OBJECTIVE: Trauma is a leading causes of death and disability in all ages. The aim of this study was to describe the demography and characteristics of paediatric head trauma in our institution and examine the predictors of outcome and incidence of injury related mortality. METHODS: We examined our institutional Trauma Registry over a 2 year period. RESULTS: A total of 1100 trauma patients were seen over the study period. Of the 579 patients who had head injury 99 were in the paediatric age group. Of the paediatric head trauma patients 79 had documented Glasgow coma score (GCS), 38 (48.1%), 17 (21.5%) and 24 (30.4%) had mild, moderate and severe head injury respectively. The percentage mortality of head injury in the paediatric age group was 6.06% (6/99). There is an association between mortality and GCS (p=0.008), necessity for intensive care unit (ICU) admission (p=0.0001), associated burns (p=0.0001) and complications such as aspiration pneumonia (p=0.0001). The significant predictors of outcome are aspiration (p=0.004), the need for ICU admission (p=0.0001) and associated burns (p=0.005) using logistic binary regression. During the study period 46 children underwent surgical intervention with extradural haematoma 16 (34.8%), depressed skull fracture 14 (30.4%) and chronic subdural haematoma five (10.9%) being the commonest indication for surgeries. CONCLUSION: Paediatric head injury accounted for 9.0% (99/1100) of all trauma admissions. Majority of patients had mild or moderate injuries. Burns, aspiration pneumonitis and the need for ICU admission were important predictors of outcome in children with traumatic brain injury.

Large, Wide-Neck, Side-Wall Aneurysm Treatment in Canines Using NeuroCURE: A Novel Liquid Embolic.

BACKGROUND: Untreated intracranial aneurysms can rupture and result in high rates of morbidity and mortality. Although there are numerous approved endovascular aneurysm treatment devices, most require dual anti-platelet therapy, are minimally biocompatible, or are prone to recanalization. Neurovascular Controlled Uniform Rapid Embolic (NeuroCURE) is an innovative polymer gel material with long-term stability, biocompatibility, and hemocompatibility developed for the treatment of large, wide-neck aneurysms. METHODS: Sidewall aneurysms were surgically created in 10 canines and NeuroCURE was injected through a 0.025 microcatheter under a single balloon inflation period. Aneurysm treatment was angiographically assessed post-embolization and pre-term with Raymond-Roy occlusion classification and a qualitative flow grade scale. Aneurysm neck stability and biocompatibility was histologically assessed to grade platelet/fibrin thrombus, percent endothelialization, and neointimal formation. Aneurysm sac stability was assessed by NeuroCURE sac content, inflammation, and neo-angiogenesis scales. RESULTS: Explanted aneurysms exhibited a smooth surface at the aneurysm neck with nearly complete neointimal coverage at 3-months. By 6-months, neck endothelialization was 100% in all animals (average Raymond-Roy occlusion classification of 1.2), with no instances of aneurysm recanalization or parent vessel flow compromise. Biocompatibility assessments verified a lack of inflammatory response, neo-angiogenesis, and platelet/fibrin thrombus formation. CONCLUSION: The NeuroCURE material promotes progressive occlusion of wide-necked side wall aneurysms over time without the need for dual antiplatelet agents. NeuroCURE also promotes neointimal tissue infill without dependence on thrombus formation and thus resists aneurysm recanalization. NeuroCURE remains a compelling investigational device for the treatment of intracranial aneurysms.

Intraoperative confocal laser endomicroscopy for interpretation of a sellar hemangioblastoma: illustrative case.

BACKGROUND: Intraoperative frozen sections play a critical role in surgical strategy because of their ability to provide rapid histopathological information. In cases in which intraoperative biopsy carries a significant risk of bleeding, intraoperative confocal laser endomicroscopy (CLE) can assist in decision-making. OBSERVATIONS: The authors present a rare case of a large sellar hemangioblastoma. Preoperative radiographic imaging and normal pituitary function suggested a differential diagnosis that included hemangioblastoma. The patient underwent partial preoperative embolization and a right-sided pterional craniotomy for resection of the lesion. Gross intraoperative examination revealed a highly vascular sellar lesion requiring circumferential dissection to minimize blood loss. The serious vascularity precluded intraoperative frozen section analysis, and CLE imaging was performed. CLE imaging provided excellent visualization of the remarkable vascular structure and characteristic histoarchitecture with microvasculature, intracytoplasmic vacuoles, and atypical cells consistent with hemangioblastoma. Resection and decompression of the chiasm was accomplished, and the patient was discharged with improved vision. The final histopathological diagnosis was hemangioblastoma. LESSONS: When the benefits of obtaining intraoperative frozen sections greatly outweigh the associated risks, CLE imaging can aid in decision-making. CLE imaging offers real-time, on-the-fly evaluation of intraoperative tissue without the need to biopsy a vascular lesion.

Modified Puerto Rico Recurrence Scale for chronic subdural hematomas: augmenting the grading scale with postoperative pneumocephalus volume.

BACKGROUND: Chronic subdural hematomas (CSDHs) are common in the elderly, with a relatively high rate of recurrence after initial surgical intervention. Our research team previously created a predictive grading system, the Puerto Rico Recurrence Scale (PRRS), to identify patients at high risk of CSDH recurrence. In this study, we introduce a modification of the (mPRRS) that includes pneumocephalus volume, which has been independently associated with recurrence. METHODS: A single-center Puerto Rican population-based retrospective study was performed to analyze data for patients treated for CSDH at 1 institution between July 1, 2017, and December 31, 2019. Univariate and multivariate analyses were used to create a grading scale predictive of recurrence. Retrospective validation was conducted for the cohort. RESULTS: Of 108 patients included in the study, 42 had recurrence, and 66 had nonrecurrence. Postoperative subdural space, postoperative midline shift, and pneumocephalus volume were all higher with recurrence (P = 0.002, P = 0.009, and P < 0.001, respectively). Multivariate analysis was used to create a 6-point grading scale comprising 3 variables (pneumocephalus volume [< 10, 10-20, 21-30, and > 30 cm3], postoperative midline shift [< 0.4, 0.41-1.0, and > 1.0 cm], and laterality [unilateral and bilateral]). Recurrence rates progressively increased in low-risk to high-risk groups (2/18 [11%] vs 21/34 [62%]; P < 0.003). CONCLUSION: The mPRRS incorporating pneumocephalus measurement improves CSDH recurrence prediction. The mPRRS indicated that patients with higher scores have a greater risk of recurrence and emphasized the importance of measuring postoperative variables for prediction. The mPRRS grading scale for CSDHs may be applicable not only to the Puerto Rican population but also to the general population.

Combined subtarsal contralateral transmaxillary retroeustachian and endoscopic endonasal approaches to the infrapetrous region.

OBJECTIVE: The eustachian tube (ET) limits endoscopic endonasal access to the infrapetrous region. Transecting or mobilizing the ET may result in morbidities. This study presents a novel approach in which a subtarsal contralateral transmaxillary (ST-CTM) corridor is coupled with the standard endonasal approach to facilitate access behind the intact ET. METHODS: Eight cadaveric head specimens were dissected. Endoscopic endonasal approaches (EEAs) (i.e., transpterygoid and inferior transclival) were performed on one side, followed by ST-CTM and sublabial contralateral transmaxillary (SL-CTM) approaches on the opposite side, along with different ET mobilization techniques on the original side. Seven comparative groups were generated. The length of the cranial nerves, areas of exposure, and volume of surgical freedom (VSF) in the infrapetrous regions were measured and compared. RESULTS: Without ET mobilization, the combined ST-CTM/EEA approach provided greater exposure than EEA alone (mean ± SD 288.9 ± 40.66 mm2 vs 91.7 ± 49.9 mm2; p = 0.001). The VSFs at the ventral jugular foramen (JF), entrance to the petrous internal carotid artery (ICA), and lateral to the parapharyngeal ICA were also greater in ST-CTM/EEA than in EEA alone (p = 0.002, p = 0.002, and p < 0.001, respectively). EEA alone, however, provided greater VSF at the hypoglossal canal (HGC) than did ST-CTM/EEA (p = 0.01). The SL-CTM approach did not increase the EEA exposure (p = 0.48). The ST-CTM/EEA approach provided greater exposure than EEA with extended inferolateral (EIL) or anterolateral (AL) ET mobilization (p = 0.001 and p = 0.02, respectively). The ST-CTM/EEA also increased the VSF lateral to the parapharyngeal ICA in comparison with EEA/EIL ET mobilization (p < 0.001) but not with EEA/AL ET mobilization (p = 0.36). Finally, the VSFs at the HGC and JF were greater in EEA/AL ET mobilization than in ST-CTM/EEA without ET mobilization (p = 0.002 and p = 0.004, respectively). CONCLUSIONS: Combining the EEA with the more laterally and superiorly originating ST-CTM approach allows greater exposure of the infrapetrous and ventral JF regions while obviating the need for mobilizing the ET. The surgical freedom afforded by the combined approaches is greater than that obtained by EEA alone.

Quantification of motion during microvascular anastomosis simulation using machine learning hand detection.

OBJECTIVE: Microanastomosis is one of the most technically demanding and important microsurgical skills for a neurosurgeon. A hand motion detector based on machine learning tracking technology was developed and implemented for performance assessment during microvascular anastomosis simulation. METHODS: A microanastomosis motion detector was developed using a machine learning model capable of tracking 21 hand landmarks without physical sensors attached to a surgeon's hands. Anastomosis procedures were simulated using synthetic vessels, and hand motion was recorded with a microscope and external camera. Time series analysis was performed to quantify the economy, amplitude, and flow of motion using data science algorithms. Six operators with various levels of technical expertise (2 experts, 2 intermediates, and 2 novices) were compared. RESULTS: The detector recorded a mean (SD) of 27.6 (1.8) measurements per landmark per second with a 10% mean loss of tracking for both hands. During 600 seconds of simulation, the 4 nonexperts performed 26 bites in total, with a combined excess of motion of 14.3 (15.5) seconds per bite, whereas the 2 experts performed 33 bites (18 and 15 bites) with a mean (SD) combined excess of motion of 2.8 (2.3) seconds per bite for the dominant hand. In 180 seconds, the experts performed 13 bites, with mean (SD) latencies of 22.2 (4.4) and 23.4 (10.1) seconds, whereas the 2 intermediate operators performed a total of 9 bites with mean (SD) latencies of 31.5 (7.1) and 34.4 (22.1) seconds per bite. CONCLUSIONS: A hand motion detector based on machine learning technology allows the identification of gross and fine movements performed during microanastomosis. Economy, amplitude, and flow of motion were measured using time series data analysis. Technical expertise could be inferred from such quantitative performance analysis.

5-aminolevulinic acid, fluorescein sodium, and indocyanine green for glioma margin detection: analysis of operating wide-field and confocal microscopy in glioma models of various grades.

Introduction: Surgical resection remains the first-line treatment for gliomas. Several fluorescent dyes are currently in use to augment intraoperative tumor visualization, but information on their comparative effectiveness is lacking. We performed systematic assessment of fluorescein sodium (FNa), 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), and indocyanine green (ICG) fluorescence in various glioma models using advanced fluorescence imaging techniques. Methods: Four glioma models were used: GL261 (high-grade model), GB3 (low-grade model), and an in utero electroporation model with and without red fluorescence protein (IUE +RFP and IUE -RFP, respectively) (intermediate-to-low-grade model). Animals underwent 5-ALA, FNa, and ICG injections and craniectomy. Brain tissue samples underwent fluorescent imaging using a wide-field operative microscope and a benchtop confocal microscope and were submitted for histologic analysis. Results: Our systematic analysis showed that wide-field imaging of highly malignant gliomas is equally efficient with 5-ALA, FNa, and ICG, although FNa is associated with more false-positive staining of the normal brain. In low-grade gliomas, wide-field imaging cannot detect ICG staining, can detect FNa in only 50% of specimens, and is not sensitive enough for PpIX detection. With confocal imaging of low-intermediate grade glioma models, PpIX outperformed FNa. Discussion: Overall, compared to wide-field imaging, confocal microscopy significantly improved diagnostic accuracy and was better at detecting low concentrations of PpIX and FNa, resulting in improved tumor delineation. Neither PpIX, FNa, nor ICG delineated all tumor boundaries in studied tumor models, which emphasizes the need for novel visualization technologies and molecular probes to guide glioma resection. Simultaneous administration of 5-ALA and FNa with use of cellular-resolution imaging modalities may provide additional information for margin detection and may facilitate maximal glioma resection.

Liquid Embolic Agents for Endovascular Embolization: A Review.

Endovascular embolization (EE) has been used for the treatment of blood vessel abnormalities, including aneurysms, AVMs, tumors, etc. The aim of this process is to occlude the affected vessel using biocompatible embolic agents. Two types of embolic agents, solid and liquid, are used for endovascular embolization. Liquid embolic agents are usually injectable and delivered into the vascular malformation sites using a catheter guided by X-ray imaging (i.e., angiography). After injection, the liquid embolic agent transforms into a solid implant in situ based on a variety of mechanisms, including polymerization, precipitation, and cross-linking, through ionic or thermal process. Until now, several polymers have been designed successfully for the development of liquid embolic agents. Both natural and synthetic polymers have been used for this purpose. In this review, we discuss embolization procedures with liquid embolic agents in different clinical applications, as well as in pre-clinical research studies.

Virtual neurosurgery anatomy laboratory: A collaborative and remote education experience in the metaverse.

Background: Advances in computer sciences, including novel 3-dimensional rendering techniques, have enabled the creation of cloud-based virtual reality (VR) interfaces, making real-time peer-to-peer interaction possible even from remote locations. This study addresses the potential use of this technology for microsurgery anatomy education. Methods: Digital specimens were created using multiple photogrammetry techniques and imported into a virtual simulated neuroanatomy dissection laboratory. A VR educational program using a multiuser virtual anatomy laboratory experience was developed. Internal validation was performed by five multinational neurosurgery visiting scholars testing and assessing the digital VR models. For external validation, 20 neurosurgery residents tested and assessed the same models and virtual space. Results: Each participant responded to 14 statements assessing the virtual models, categorized under realism (n = 3), usefulness (n = 2), practicality (n = 3), enjoyment (n = 3), and recommendation (n = 3). Most responses expressed agreement or strong agreement with the assessment statements (internal validation, 94% [66/70] total responses; external validation, 91.4% [256/280] total responses). Notably, most participants strongly agreed that this system should be part of neurosurgery residency training and that virtual cadaver courses through this platform could be effective for education. Conclusion: Cloud-based VR interfaces are a novel resource for neurosurgery education. Interactive and remote collaboration between instructors and trainees is possible in virtual environments using volumetric models created with photogrammetry. We believe that this technology could be part of a hybrid anatomy curriculum for neurosurgery education. More studies are needed to assess the educational value of this type of innovative educational resource.