A tridimensional atlas of the developing human head.

The evolution and development of the head have long captivated researchers due to the crucial role of the head as the gateway for sensory stimuli and the intricate structural complexity of the head. Although significant progress has been made in understanding head development in various vertebrate species, our knowledge of early human head ontogeny remains limited. Here, we used advanced whole-mount immunostaining and 3D imaging techniques to generate a comprehensive 3D cellular atlas of human head embryogenesis. We present detailed developmental series of diverse head tissues and cell types, including muscles, vasculature, cartilage, peripheral nerves, and exocrine glands. These datasets, accessible through a dedicated web interface, provide insights into human embryogenesis. We offer perspectives on the branching morphogenesis of human exocrine glands and unknown features of the development of neurovascular and skeletomuscular structures. These insights into human embryology have important implications for understanding craniofacial defects and neurological disorders and advancing diagnostic and therapeutic strategies.

Distinct molecular profiles of skull bone marrow in health and neurological disorders.

The bone marrow in the skull is important for shaping immune responses in the brain and meninges, but its molecular makeup among bones and relevance in human diseases remain unclear. Here, we show that the mouse skull has the most distinct transcriptomic profile compared with other bones in states of health and injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals that the skull marrow is the most distinct, with differentially expressed neutrophil-related pathways and a unique synaptic protein signature. 3D imaging demonstrates the structural and cellular details of human skull-meninges connections (SMCs) compared with veins. Last, using translocator protein positron emission tomography (TSPO-PET) imaging, we show that the skull bone marrow reflects inflammatory brain responses with a disease-specific spatial distribution in patients with various neurological disorders. The unique molecular profile and anatomical and functional connections of the skull show its potential as a site for diagnosing, monitoring, and treating brain diseases.

Insights into morphology and disease from the dog genome project.

Although most modern dog breeds are less than 200 years old, the symbiosis between man and dog is ancient. Since prehistoric times, repeated selection events have transformed the wolf into man's guardians, laborers, athletes, and companions. The rapid transformation from pack predator to loyal companion is a feat that is arguably unique among domesticated animals. How this transformation came to pass remained a biological mystery until recently: Within the past decade, the deployment of genomic approaches to study population structure, detect signatures of selection, and identify genetic variants that underlie canine phenotypes is ushering into focus novel biological mechanisms that make dogs remarkable. Ironically, the very practices responsible for breed formation also spurned morbidity; today, many diseases are correlated with breed identity. In this review, we discuss man's best friend in the context of a genetic model to understand paradigms of heritable phenotypes, both desirable and disadvantageous.

Effect of skull morphology on fox snow diving.

Certain fox species plunge-dive into snow to catch prey (e.g., rodents), a hunting mechanism called mousing. Red and arctic foxes can dive into snow at speeds ranging between 2 and 4 m/s. Such mousing behavior is facilitated by a slim, narrow facial structure. Here, we investigate how foxes dive into snow efficiently by studying the role of skull morphology on impact forces it experiences. In this study, we reproduce the mousing behavior in the lab using three-dimensional (3D) printed fox skulls dropped into fresh snow to quantify the dynamic force of impact. Impact force into snow is modeled using hydrodynamic added mass during the initial impact phase. This approach is based on two key facts: the added mass effect in granular media at high Reynolds numbers and the characteristics of snow as a granular medium. Our results show that the curvature of the snout plays a critical role in determining the impact force, with an inverse relationship. A sharper skull leads to a lower average impact force, which allows foxes to dive head-first into the snow with minimal tissue damage.

The emergence of the calvarial hematopoietic niche in health and disease.

The diploë region of skull has recently been discovered to act as a myeloid cell reservoir to the underlying meninges. The presence of ossified vascular channels traversing the inner skull of cortex provides a passageway for the cells to traffic from the niche, and CNS-derived antigens traveling through cerebrospinal fluid in a perivascular manner reaches the niche to signal myeloid cell egress. This review will highlight the recent findings establishing this burgeoning field along with the known role this niche plays in CNS aging and disease. It will further highlight the anatomical routes and physiological properties of the vascular structures these cells use for trafficking, spanning from skull to brain parenchyma.

Ap-2ß regulates cranial osteogenic potential via the activation of Wnt/ß-catenin signaling pathway.

The skull is a fundamental bone that protects the development of brain and consists of several bony elements, such as the frontal and parietal bones. Frontal bone exhibited superior in osteogenic potential and regeneration of cranial defects compared to parietal bone. However, how this regional difference is regulated remains largely unknown. In this study, we identified an Ap-2ß transcriptional factor with a higher expression in frontal bone, but its molecular function in osteoblasts needs to be elucidated. We found that Ap-2ß knockdown in preosteoblasts leads to reduced proliferation, increased cell death and impaired differentiation. Through RNA-seq analysis, we found that Ap-2ß influences multiple signaling pathways including the Wnt pathway, and overexpression of Ap-2ß showed increased nuclear ß-catenin and its target genes expressions in osteoblasts. Pharmacological activation of Wnt/ß-catenin signaling using LiCl treatment cannot rescue the reduced luciferase activities of the ß-catenin/TCF/LEF reporter in Ap-2ß knockdown preosteoblasts. Besides, transient expression of Ap-2ß via the lentivirus system could sufficiently rescue the inferior osteogenic potential in parietal osteoblasts, while Ap-2ß knockdown in frontal osteoblasts resulted in reduced osteoblast activity, reduced active ß-catenin and target genes expressions. Taken together, our data demonstrated that Ap-2ß modulates osteoblast proliferation and differentiation through the regulation of Wnt/ß-catenin signaling pathway and plays an important role in regulating regional osteogenic potential in frontal and parietal bone.

Ciliary and non-ciliary functions of Rab34 during craniofacial bone development.

The primary cilium is a hair-like projection that controls cell development and tissue homeostasis. Although accumulated studies identify the molecular link between cilia and cilia-related diseases, the underlying etiology of ciliopathies has not been fully understood. In this paper, we determine the function of Rab34, a small GTPase, as a key regulator for controlling ciliogenesis and type I collagen trafficking in craniofacial development. Mechanistically, Rab34 is required to form cilia that control osteogenic proliferation, survival, and differentiation via cilia-mediated Hedgehog signaling. In addition, Rab34 is indispensable for regulating type I collagen trafficking from the ER to the Golgi. These results demonstrate that Rab34 has both ciliary and non-ciliary functions to regulate osteogenesis. Our study highlights the critical function of Rab34, which may contribute to understanding the novel etiology of ciliopathies that are associated with the dysfunction of RAB34 in humans.

The molecular complex of ciliary and golgin protein is crucial for skull development.

Intramembranous ossification, which consists of direct conversion of mesenchymal cells to osteoblasts, is a characteristic process in skull development. One crucial role of these osteoblasts is to secrete collagen-containing bone matrix. However, it remains unclear how the dynamics of collagen trafficking is regulated during skull development. Here, we reveal the regulatory mechanisms of ciliary and golgin proteins required for intramembranous ossification. During normal skull formation, osteoblasts residing on the osteogenic front actively secreted collagen. Mass spectrometry and proteomic analysis determined endogenous binding between ciliary protein IFT20 and golgin protein GMAP210 in these osteoblasts. As seen in Ift20 mutant mice, disruption of neural crest-specific GMAP210 in mice caused osteopenia-like phenotypes due to dysfunctional collagen trafficking. Mice lacking both IFT20 and GMAP210 displayed more severe skull defects compared with either IFT20 or GMAP210 mutants. These results demonstrate that the molecular complex of IFT20 and GMAP210 is essential for the intramembranous ossification during skull development.

Cyclic loading failed to promote growth in a pig model of midfacial hypoplasia.

Yucatan miniature pigs, often used as large animal models in clinical research, are distinguished by a breed-specific midfacial hypoplasia with anterior crossbite. Although this deformity can be corrected by distraction osteogenesis, a less invasive method is desirable. We chose a mechanical cyclic stimulation protocol that has been successful in enhancing sutural growth in small animals and in a pilot study on standard pigs. Yucatan minipigs (n = 14) were obtained in pairs, with one of each pair randomly assigned to sham or loaded groups. All animals had loading implants installed on the right nasal and frontal bones and received labels for cell proliferation and mineral apposition. After a week of healing and under anesthesia, experimental animals received cyclic tensile loads (2.5 Hz, 30 min) delivered to the right nasofrontal suture daily for 5 days. Sutural strains were recorded at the final session for experimental animals. Sham animals received the same treatment except without loading or strain gauge placement. In contrast to pilot results on standard pigs, the treatment did not produce the expected sutural widening and increased growth. Although sutures were not fused and strains were in the normal range, the targeted right nasofrontal suture was narrowed rather than widened, with no statistically significant changes in sutural cell proliferation, mineral apposition, or vascularity. In general, Yucatan minipig sutures were more vascular than those of standard pigs and also tended to have more proliferating cells. In conclusion, either because the sutures themselves are abnormal or because of growth restrictions elsewhere in the skull, this cyclic loading protocol was unable to produce the desired response of sutural widening and growth. This treatment, effective in normal animals, did not improve naturally occurring midfacial hypoplasia in Yucatan minipigs.

Geometric growth of the normal human craniocervical junction from 0 to 18 years old.

The craniocervical junction (CCJ) forms the bridge between the skull and the spine, a highly mobile group of joints that allows the mobility of the head in every direction. The CCJ plays a major role in protecting the inferior brainstem (bulb) and spinal cord, therefore also requiring some stability. Children are subjected to multiple constitutive or acquired diseases involving the CCJ: primary bone diseases such as in FGFR-related craniosynostoses or acquired conditions such as congenital torticollis, cervical spine luxation, and neurological disorders. To design efficient treatment plans, it is crucial to understand the relationship between abnormalities of the craniofacial region and abnormalities of the CCJ. This can be approached by the study of control and abnormal growth patterns. Here we report a model of normal skull base growth by compiling a collection of geometric models in control children. Focused analyses highlighted specific developmental patterns for each CCJ bone, emphasizing rapid growth during infancy, followed by varying rates of growth and maturation during childhood and adolescence until reaching stability by 18 years of age. The focus was on the closure patterns of synchondroses and sutures in the occipital bone, revealing distinct closure trajectories for the anterior intra-occipital synchondroses and the occipitomastoid suture. The findings, although based on a limited dataset, showcased specific age-related changes in width and closure percentages, providing valuable insights into growth dynamics within the first 2 years of life. Integration analyses revealed intricate relationships between skull and neck structures, emphasizing coordinated growth at different stages. Specific bone covariation patterns, as found between the first and second cervical vertebrae (C1 and C2), indicated synchronized morphological changes. Our results provide initial data for designing inclusive CCJ geometric models to predict normal and abnormal growth dynamics.

BounTI (boundary-preserving threshold iteration): A user-friendly tool for automatic hard tissue segmentation.

X-ray Computed Tomography (CT) images are widely used in various fields of natural, physical, and biological sciences. 3D reconstruction of the images involves segmentation of the structures of interest. Manual segmentation has been widely used in the field of biological sciences for complex structures composed of several sub-parts and can be a time-consuming process. Many tools have been developed to automate the segmentation process, all with various limitations and advantages, however, multipart segmentation remains a largely manual process. The aim of this study was to develop an open-access and user-friendly tool for the automatic segmentation of calcified tissues, specifically focusing on craniofacial bones. Here we describe BounTI, a novel segmentation algorithm which preserves boundaries between separate segments through iterative thresholding. This study outlines the working principles behind this algorithm, investigates the effect of several input parameters on its outcome, and then tests its versatility on CT images of the craniofacial system from different species (e.g. a snake, a lizard, an amphibian, a mouse and a human skull) with various scan qualities. The case studies demonstrate that this algorithm can be effectively used to segment the craniofacial system of a range of species automatically. High-resolution microCT images resulted in more accurate boundary-preserved segmentation, nonetheless significantly lower-quality clinical images could still be segmented using the proposed algorithm. Methods for manual intervention are included in this tool when the scan quality is insufficient to achieve the desired segmentation results. While the focus here was on the craniofacial system, BounTI can be used to automatically segment any hard tissue. The tool presented here is available as an Avizo/Amira add-on, a stand-alone Windows executable, and a Python library. We believe this accessible and user-friendly segmentation tool can benefit the wider anatomical community.

Functionally mediated cranial allometry evidenced in a genus of rock-wallabies.

In assessments of skeletal variation, allometry (disproportionate change of shape with size) is often corrected to examine size-independent variation for hypotheses relating to function. However, size-related trade-offs in functional demands may themselves be an underestimated driver of mammalian cranial diversity. Here, we use geometric morphometrics alongside dental measurements to assess craniodental allometry in the rock-wallaby genus Petrogale (all 17 species, 370 individuals). We identified functional aspects of evolutionary allometry that can be both extensions of, and correlated negatively with, static or ontogenetic allometric patterns. Regarding constraints, larger species tended to have relatively smaller braincases and more posterior orbits, the former of which might represent a constraint on jaw muscle anatomy. However, they also tended to have more anterior dentition and smaller posterior zygomatic arches, both of which support the hypothesis of relaxed bite force demands and accommodation of different selective pressures that favour facial elongation. By contrast, two dwarf species had stouter crania with divergent dental adaptations that together suggest increased relative bite force capacity. This likely allows them to feed on forage that is mechanically similar to that consumed by larger relatives. Our results highlight a need for nuanced considerations of allometric patterns in future research of mammalian cranial diversity.

Global facial soft tissue thicknesses for craniofacial identification (2023): a review of 140 years of data since Welcker's first study.

This year (2023) marks 140 years since the first publication of a facial soft tissue thickness (FSTT) study. Since 1883, a total of 139 studies have been published, collectively tallying > 220,000 tissue thickness measurements of > 19,500 adults. In just the last 5-years, 33 FSTT studies have been conducted. Herein, we add these data (plus an additional 20 studies) to the 2018 T-Table to provide an update of > 81,000 new datapoints to the global tallied facial soft tissue depths table. In contrast to the original 2008 T-Table, some notable changes are as follows: increased FSTTs by 3 mm at infra second molar (ecm2-iM2'), 2.5 mm at gonion (go-go'), 2 mm at mid-ramus (mr-mr'), and 1.5 mm at zygion (zy-zy'). Rolling grand means indicate that stable values have been attained for all nine median FSTT landmarks, while six out of nine bilateral landmarks continue to show ongoing fluctuations, indicating further data collection at these landmarks holds value. When used as point estimators for individuals with known values across 24 landmarks (i.e., C-Table data), the updated grand means produce slightly less estimation error than the 2018 T-Table means (3.5 mm versus 3.6 mm, respectively). Future efforts to produce less noisy datasets (i.e., reduce measurement and sampling errors as much as possible between studies) would be useful.

Estimation of ancestry from cranial measurements based on MDCT data acquired in a Japanese and Western Australian population.

The estimation of ancestry is important not only towards establishing identity but also as a required precursor to facilitating the accurate estimation of other attributes such as sex, age at death, and stature. The present study aims to analyze morphological variation in the crania of Japanese and Western Australian individuals and test predictive models based on machine learning for their potential forensic application. The Japanese and Western Australian samples comprise computed tomography (CT) scans of 230 (111 female; 119 male) and 225 adult individuals (112 female; 113 male), respectively. A total of 18 measurements were calculated, and machine learning methods (random forest modeling, RFM; support vector machine, SVM) were used to classify ancestry. The two-way unisex model achieved an overall accuracy of 93.2% for RFM and 97.1% for SVM, respectively. The four-way sex and ancestry model demonstrated an overall classification accuracy of 84.0% for RFM and 93.0% for SVM. The sex-specific models were most accurate in the female samples (♀ 95.1% for RFM and 100% for SVM; ♂91.4% for RFM and 97.4% for SVM). Our findings suggest that cranial measurements acquired in CT images can be used to accurately classify Japanese and Western Australian individuals into their respective population. This is the first study to assess the feasibility of ancestry estimation using three-dimensional CT images of the skull.

Skull fractures by glass bottles tested on cadaveric heads.

Head trauma is frequently related to the misuse of drinking vessels as weapons. Forensic reports usually evaluate these blunt injuries as having occurred in scenarios where the alcohol intake is high. Fatal consequences are seen in blows with glass bottles aiming at the head. To prove the outcome that a glass bottle thrown to the head could cause, three intact human cadaver heads were impacted with 1-liter glass bottles at 9.5 m/s using a drop-tower. The impact location covered the left temporal bone, sphenoid bone, and zygomatic arch. The contact between the head and the bottle was produced at an angle of 90° with (1) the valve of the bottle, (2) the bottom of the bottle, and (3) with the head rotated 20° in the frontal plane touching again with the bottom of the bottle. The three bottles remained intact after the impact, and the injury outcomes were determined by computed tomography (CT). The alterations were highly dependent on the impact orientation. The outcome varied from no injury to severe bone fractures. In the most injurious case (#3), fractures were identified in the cranial base, sphenoid bone, and zygomatic bone. These testing conditions were selected to replicate one specific legal case, as required by the plaintiff. Physical disputes with bar glassware can lead to complex combinations of blunt and sharp-force injuries. Controlled biomechanical studies can benefit forensic analyses of violence involving glassware by providing a better understanding of the underlying injury mechanisms.

Subject-specific finite element head models for skull fracture evaluation-a new tool in forensic pathology.

Post-mortem computed tomography (PMCT) enables the creation of subject-specific 3D head models suitable for quantitative analysis such as finite element analysis (FEA). FEA of proposed traumatic events is an objective and repeatable numerical method for assessing whether an event could cause a skull fracture such as seen at autopsy. FEA of blunt force skull fracture in adults with subject-specific 3D models in forensic pathology remains uninvestigated. This study aimed to assess the feasibility of FEA for skull fracture analysis in routine forensic pathology. Five cases with blunt force skull fracture and sufficient information on the kinematics of the traumatic event to enable numerical reconstruction were chosen. Subject-specific finite element (FE) head models were constructed by mesh morphing based on PMCT 3D models and A Detailed and Personalizable Head Model with Axons for Injury Prediction (ADAPT) FE model. Morphing was successful in maintaining subject-specific 3D geometry and quality of the FE mesh in all cases. In three cases, the simulated fracture patterns were comparable in location and pattern to the fractures seen at autopsy/PMCT. In one case, the simulated fracture was in the parietal bone whereas the fracture seen at autopsy/PMCT was in the occipital bone. In another case, the simulated fracture was a spider-web fracture in the frontal bone, whereas a much smaller fracture was seen at autopsy/PMCT; however, the fracture in the early time steps of the simulation was comparable to autopsy/PMCT. FEA might be feasible in forensic pathology in cases with a single blunt force impact and well-described event circumstances.

Integrated Molecular and Histological Insights for Targeted Therapies in Mesenchymal Sinonasal Tract Tumors.

PURPOSE OF REVIEW: This review aims to provide a comprehensive overview of mesenchymal sinonasal tract tumors (STTs), a distinct subset of STTs. Despite their rarity, mesenchymal STTs represent a unique clinical challenge, characterized by their rarity, often slow progression, and frequently subtle or overlooked symptoms. The complex anatomy of the sinonasal area, which includes critical structures such as the orbit, brain, and cranial nerves, further complicates surgical treatment options. This underscores an urgent need for more advanced and specialized therapeutic approaches. RECENT FINDINGS: Advancements in molecular diagnostics, particularly in next-generation sequencing, have significantly enhanced our understanding of STTs. Consequently, the World Health Organization has updated its tumor classification to better reflect the distinct histological and molecular profiles of these tumors, as well as to categorize mesenchymal STTs with greater accuracy. The growing understanding of the molecular characteristics of mesenchymal STTs opens new possibilities for targeted therapeutic interventions, marking a significant shift in treatment paradigms. This review article concentrates on mesenchymal STTs, specifically addressing sinonasal tract angiofibroma, sinonasal glomangiopericytoma, biphenotypic sinonasal sarcoma, and skull base chordoma. These entities are marked by unique histopathological and molecular features, which challenge conventional treatment approaches and simultaneously open avenues for novel targeted therapies. Our discussion is geared towards delineating the molecular underpinnings of mesenchymal STTs, with the objective of enhancing therapeutic strategies and addressing the existing shortcomings in the management of these intricate tumors.

Post-traumatic seizures and factors associated among adult patients with depressed skull fractures at Mulago National Referral hospital; cross-sectional study.

INTRODUCTION: Post-traumatic seizures (PTS) are common among patients with depressed skull fractures (DSF). Understanding the burden of post traumatic seizures and the factors associated among adult patients with DSF is important to improve clinical care. OBJECTIVE: To determine the prevalence and factors associated with post-traumatic seizures among adult patients with DSF at Mulago National Referral hospital (MNRH). METHODS: A cross-sectional study was conducted among 333 study participants between March 2021 and February 2022. Socio-demographic, clinical laboratory factors and anti-seizure medications were collected using a study questionnaire. Data was analysed to determine the prevalence of PTS and factors associated with occurrence of PTS among patients with DSF. RESULTS: The mean age (±SD) of study participants was 31.2, (±10.5) years, with a male to female ratio of 10.4:1. Nearly half of the study participants had attained secondary level of education, while 31.6 % (105) were peasants (subsistence farmers). The overall prevalence of PTS among DSF study participants was 16.2 % (54participants). Late presentation of PTS was the highest at 9.0 % (30) followed by early PTS at 3.9 % [13] and immediate PTS at 3.3 % [11]. Moderate Glasgow coma score (GCS: 9-13), p < 0.015, severe traumatic brain injury (GCS: 3-8), p < 0.026 at the time of admission and midline brain shift (≥5mm), p < 0.009 were associated with PTS. Phenytoin (94.3 %) was the most commonly used ASM followed by phenobarbitone (1.4 %) and Valproate (1.1 %) among study participants. CONCLUSION: Patients with moderate and severe traumatic brain injury and midline brain shift were associated with post traumatic seizures. Early identification and intervention may reduce the burden of posttraumatic seizures in this category of patients.

Safety and histopathologic yield of percutaneous CT-guided biopsies of the skull base, orbit, and calvarium.

PURPOSE: Although CT-guided biopsies of the calvarium, skull base, and orbit are commonly performed, the best approaches, efficacy, and safety of such procedures remain scantly described in the literature. This retrospective review of percutaneous biopsies illustrates several approaches to challenging biopsy targets and provides a review of procedural planning considerations and histopathologic yield. METHODS: A retrospective review of CT-guided biopsies of the skull base, calvarium, and orbit between 1/1/2010 and 10/30/2020 was conducted. Patient demographics and procedural factors were recorded, including lesion size and location, biopsy approach, and needle gauge. Outcomes were also noted, including CT dose length product, complications, and histopathologic yield. RESULTS: Sixty-one CT-guided biopsies were included in the final analysis: 34 skull base, 23 calvarial, and 4 orbital lesions. The initial diagnostic yield was 32/34 (94%) for skull base lesions, with one false-negative and one non-diagnostic sample. Twenty-one of twenty-three (91%) biopsies in the calvarium were initially diagnostic, with one false-negative and one non-diagnostic sample. In the orbit, 4/4 biopsies were diagnostic. The total complication rate for the cohort was 4/61 (6.6%). Three complications were reported in skull base procedures (2 immediate and 1 delayed). A single complication was reported in a calvarial biopsy, and no complications were reported in orbital biopsies. CONCLUSION: Percutaneous CT-guided core needle biopsies can be performed safely and with a high diagnostic yield for lesions in the skull base, calvarium, and orbit.

Current status of artificial intelligence technologies in pituitary adenoma surgery: a scoping review.

PURPOSE: Pituitary adenoma surgery is a complex procedure due to critical adjacent neurovascular structures, variations in size and extensions of the lesions, and potential hormonal imbalances. The integration of artificial intelligence (AI) and machine learning (ML) has demonstrated considerable potential in assisting neurosurgeons in decision-making, optimizing surgical outcomes, and providing real-time feedback. This scoping review comprehensively summarizes the current status of AI/ML technologies in pituitary adenoma surgery, highlighting their strengths and limitations. METHODS: PubMed, Embase, Web of Science, and Scopus were searched following the PRISMA-ScR guidelines. Studies discussing the use of AI/ML in pituitary adenoma surgery were included. Eligible studies were grouped to analyze the different outcomes of interest of current AI/ML technologies. RESULTS: Among the 2438 identified articles, 44 studies met the inclusion criteria, with a total of seventeen different algorithms utilized across all studies. Studies were divided into two groups based on their input type: clinicopathological and imaging input. The four main outcome variables evaluated in the studies included: outcome (remission, recurrence or progression, gross-total resection, vision improvement, and hormonal recovery), complications (CSF leak, readmission, hyponatremia, and hypopituitarism), cost, and adenoma-related factors (aggressiveness, consistency, and Ki-67 labeling) prediction. Three studies focusing on workflow analysis and real-time navigation were discussed separately. CONCLUSION: AI/ML modeling holds promise for improving pituitary adenoma surgery by enhancing preoperative planning and optimizing surgical strategies. However, addressing challenges such as algorithm selection, performance evaluation, data heterogeneity, and ethics is essential to establish robust and reliable ML models that can revolutionize neurosurgical practice and benefit patients.