Extended Reality-Based Head-Mounted Displays for Surgical Education: A Ten-Year Systematic Review.

Surgical education demands extensive knowledge and skill acquisition within limited time frames, often limited by reduced training opportunities and high-pressure environments. This review evaluates the effectiveness of extended reality-based head-mounted display (ExR-HMD) technology in surgical education, examining its impact on educational outcomes and exploring its strengths and limitations. Data from PubMed, Cochrane Library, Web of Science, ScienceDirect, Scopus, ACM Digital Library, IEEE Xplore, WorldCat, and Google Scholar (Year: 2014-2024) were synthesized. After screening, 32 studies comparing ExR-HMD and traditional surgical training methods for medical students or residents were identified. Quality and bias were assessed using the Medical Education Research Study Quality Instrument, Newcastle-Ottawa Scale-Education, and Cochrane Risk of Bias Tools. Results indicate that ExR-HMD offers benefits such as increased immersion, spatial awareness, and interaction and supports motor skill acquisition theory and constructivist educational theories. However, challenges such as system fidelity, operational inconvenience, and physical discomfort were noted. Nearly half the studies reported outcomes comparable or superior to traditional methods, emphasizing the importance of social interaction. Limitations include study heterogeneity and English-only publications. ExR-HMD shows promise but needs educational theory integration and social interaction. Future research should address technical and economic barriers to global accessibility.

Head model dataset for mixed reality navigation in neurosurgical interventions for intracranial lesions.

Mixed reality navigation (MRN) technology is emerging as an increasingly significant and interesting topic in neurosurgery. MRN enables neurosurgeons to "see through" the head with an interactive, hybrid visualization environment that merges virtual- and physical-world elements. Offering immersive, intuitive, and reliable guidance for preoperative and intraoperative intervention of intracranial lesions, MRN showcases its potential as an economically efficient and user-friendly alternative to standard neuronavigation systems. However, the clinical research and development of MRN systems present challenges: recruiting a sufficient number of patients within a limited timeframe is difficult, and acquiring low-cost, commercially available, medically significant head phantoms is equally challenging. To accelerate the development of novel MRN systems and surmount these obstacles, the study presents a dataset designed for MRN system development and testing in neurosurgery. It includes CT and MRI data from 19 patients with intracranial lesions and derived 3D models of anatomical structures and validation references. The models are available in Wavefront object (OBJ) and Stereolithography (STL) formats, supporting the creation and assessment of neurosurgical MRN applications.

The Feasibility and Accuracy of Holographic Navigation with Laser Crosshair Simulator Registration on a Mixed-Reality Display.

Addressing conventional neurosurgical navigation systems' high costs and complexity, this study explores the feasibility and accuracy of a simplified, cost-effective mixed reality navigation (MRN) system based on a laser crosshair simulator (LCS). A new automatic registration method was developed, featuring coplanar laser emitters and a recognizable target pattern. The workflow was integrated into Microsoft's HoloLens-2 for practical application. The study assessed the system's precision by utilizing life-sized 3D-printed head phantoms based on computed tomography (CT) or magnetic resonance imaging (MRI) data from 19 patients (female/male: 7/12, average age: 54.4 ± 18.5 years) with intracranial lesions. Six to seven CT/MRI-visible scalp markers were used as reference points per case. The LCS-MRN's accuracy was evaluated through landmark-based and lesion-based analyses, using metrics such as target registration error (TRE) and Dice similarity coefficient (DSC). The system demonstrated immersive capabilities for observing intracranial structures across all cases. Analysis of 124 landmarks showed a TRE of 3.0 ± 0.5 mm, consistent across various surgical positions. The DSC of 0.83 ± 0.12 correlated significantly with lesion volume (Spearman rho = 0.813, p < 0.001). Therefore, the LCS-MRN system is a viable tool for neurosurgical planning, highlighting its low user dependency, cost-efficiency, and accuracy, with prospects for future clinical application enhancements.

A Novel Registration Method for a Mixed Reality Navigation System Based on a Laser Crosshair Simulator: A Technical Note.

Mixed Reality Navigation (MRN) is pivotal in augmented reality-assisted intelligent neurosurgical interventions. However, existing MRN registration methods face challenges in concurrently achieving low user dependency, high accuracy, and clinical applicability. This study proposes and evaluates a novel registration method based on a laser crosshair simulator, evaluating its feasibility and accuracy. A novel registration method employing a laser crosshair simulator was introduced, designed to replicate the scanner frame's position on the patient. The system autonomously calculates the transformation, mapping coordinates from the tracking space to the reference image space. A mathematical model and workflow for registration were designed, and a Universal Windows Platform (UWP) application was developed on HoloLens-2. Finally, a head phantom was used to measure the system's target registration error (TRE). The proposed method was successfully implemented, obviating the need for user interactions with virtual objects during the registration process. Regarding accuracy, the average deviation was 3.7 ± 1.7 mm. This method shows encouraging results in efficiency and intuitiveness and marks a valuable advancement in low-cost, easy-to-use MRN systems. The potential for enhancing accuracy and adaptability in intervention procedures positions this approach as promising for improving surgical outcomes.

The Angiotensin Antagonist Losartan Modulates Social Reward Motivation and Punishment Sensitivity via Modulating Midbrain-Striato-Frontal Circuits.

Social deficits and dysregulations in dopaminergic midbrain-striato-frontal circuits represent transdiagnostic symptoms across psychiatric disorders. Animal models suggest that interactions between the dopamine (DA) and renin-angiotensin system (RAS) may modulate learning and reward-related processes. The present study therefore examined the behavioral and neural effects of the Angiotensin II type 1 receptor (AT1R) antagonist losartan on social reward and punishment processing in humans. A preregistered randomized double-blind placebo-controlled between-subject pharmacological design was combined with a social incentive delay (SID) functional MRI (fMRI) paradigm during which subjects could avoid social punishment or gain social reward. Healthy volunteers received a single-dose of losartan (50 mg, n = 43, female = 17) or placebo (n = 44, female = 20). We evaluated reaction times (RTs) and emotional ratings as behavioral and activation and functional connectivity as neural outcomes. Relative to placebo, losartan modulated the reaction time and arousal differences between social punishment and social reward. On the neural level the losartan-enhanced motivational salience of social rewards was accompanied by stronger ventral striatum-prefrontal connectivity during reward anticipation. Losartan increased the reward-neutral difference in the ventral tegmental area (VTA) and attenuated VTA associated connectivity with the bilateral insula in response to punishment during the outcome phase. Thus, losartan modulated approach-avoidance motivation and emotional salience during social punishment versus social reward via modulating distinct core nodes of the midbrain-striato-frontal circuits. The findings document a modulatory role of the renin-angiotensin system in these circuits and associated social processes, suggesting a promising treatment target to alleviate social dysregulations.SIGNIFICANCE STATEMENT Social deficits and anhedonia characterize several mental disorders and have been linked to the midbrain-striato-frontal circuits of the brain. Based on initial findings from animal models we here combine the pharmacological blockade of the Angiotensin II type 1 receptor (AT1R) via losartan with functional MRI (fMRI) to demonstrate that AT1R blockade enhances the motivational salience of social rewards and attenuates the negative impact of social punishment via modulating the communication in the midbrain-striato-frontal circuits in humans. The findings demonstrate for the first time an important role of the AT1R in social reward processing in humans and render the AT1R as promising novel treatment target for social and motivational deficits in mental disorders.

Angiotensin II Regulates the Neural Expression of Subjective Fear in Humans: A Precision Pharmaco-Neuroimaging Approach.

BACKGROUND: Rodent models and pharmacological neuroimaging studies in humans have been used to test novel pharmacological agents to reduce fear. However, these strategies are limited with respect to determining process-specific effects on the actual subjective experience of fear, which represents the key symptom that motivates patients to seek treatment. In this study, we used a novel precision pharmacological functional magnetic resonance imaging approach based on process-specific neuroaffective signatures to determine effects of the selective angiotensin II type 1 receptor (AT1R) antagonist losartan on the subjective experience of fear. METHODS: In a double-blind, placebo-controlled, randomized pharmacological functional magnetic resonance imaging design, healthy participants (N = 87) were administered 50 mg losartan or placebo before they underwent an oddball paradigm that included neutral, novel, and fear oddballs. Effects of losartan on brain activity and connectivity as well as on process-specific multivariate neural signatures were examined. RESULTS: AT1R blockade selectively reduced neurofunctional reactivity to fear-inducing visual oddballs in terms of attenuating dorsolateral prefrontal activity and amygdala-ventral anterior cingulate communication. Neurofunctional decoding further demonstrated fear-specific effects in that AT1R blockade reduced the neural expression of subjective fear but not of threat or nonspecific negative affect and did not influence reactivity to novel oddballs. CONCLUSIONS: These results show a specific role of the AT1R in regulating the subjective fear experience and demonstrate the feasibility of a precision pharmacological functional magnetic resonance imaging approach to the affective characterization of novel receptor targets for fear in humans.

Choice of Voxel-based Morphometry processing pipeline drives variability in the location of neuroanatomical brain markers.

Fundamental and clinical neuroscience has benefited tremendously from the development of automated computational analyses. In excess of 600 human neuroimaging papers using Voxel-based Morphometry (VBM) are now published every year and a number of different automated processing pipelines are used, although it remains to be systematically assessed whether they come up with the same answers. Here we examined variability between four commonly used VBM pipelines in two large brain structural datasets. Spatial similarity and between-pipeline reproducibility of the processed gray matter brain maps were generally low between pipelines. Examination of sex-differences and age-related changes revealed considerable differences between the pipelines in terms of the specific regions identified. Machine learning-based multivariate analyses allowed accurate predictions of sex and age, however accuracy differed between pipelines. Our findings suggest that the choice of pipeline alone leads to considerable variability in brain structural markers which poses a serious challenge for reproducibility and interpretation.

Smartphone navigated endoscopic port surgery of hypertensive basal ganglia hemorrhage.

OBJECTIVE: Endoscopic port surgery is a promising alternative for the surgical treatment of intracerebral hypertensive basal ganglia hemorrhage (HBGH). The precise location of hematoma is a crucial step for surgery. The authors developed a simple, low-cost navigation method using an Android smartphone for the localization of HBGH. METHODS: All patients' CT DICOM data were processed with an open-source software (3D Slicer). The volume of hematoma, angle, and length of trajectory were calculated automatically. A smartphone running the Android system and the Compass APP was used to help insert the inner introducer. An endoscopic port system was applied to create a working channel for neuro-endoscopic hematoma evacuation. RESULTS: There were 27 patients enrolled in this study (mean age 56). All patients underwent successful surgical evacuation of HBGH with neuroendoscopic evacuation. The mean time taken for the surgical plan was 4 min. The total operation time from skin incision to final suture was 82.6 min. Compared with standard neuronavigation, mean error of trajectory was 5.1 mm. The mean preoperative hematoma volume was 44.8 ml. The optimal trajectory angle averaged 39.5°and the length was 71 mm. Intraoperative blood loss was about 45 ml. Post-operative hematoma volume was 2.9 ml, and the average evacuation rate was 93.6%. One week after surgery, the mean GCS score was improved from 8.2 to 13.8 (p < 0.01). CONCLUSIONS: This simple, low-cost navigation method using 3D Slicer, an Android smartphone with the Compass APP, helps precisely insert the endoscopic working channel to the desired point, which is crucial for satisfactory evacuation of HBGH.

A novel 3D-vision-based collaborative robot as a scope holding system for port surgery: a technical feasibility study.

OBJECTIVE: A clear, stable, suitably located vision field is essential for port surgery. A scope is usually held by hand or a fixing device. The former yields fatigue and requires lengthy training, while the latter increases inconvenience because of needing to adjust the scope. Thus, the authors innovated a novel robotic system that can recognize the port and automatically place the scope in an optimized position. In this study, the authors executed a preliminary experiment to test this system's technical feasibility and accuracy in vitro. METHODS: A collaborative robotic (CoBot) system consisting of a mechatronic arm and a 3D camera was developed. With the 3D camera and programmed machine vision, CoBot can search a marker attached to the opening of the surgical port, followed by automatic alignment of the scope's axis with the port's longitudinal axis so that optimal illumination and visual observation can be achieved. Three tests were conducted. In test 1, the robot positioned a laser range finder attached to the robot's arm to align the sheath's center axis. The laser successfully passing through two holes in the port sheath's central axis defined successful positioning. Researchers recorded the finder's readings, demonstrating the actual distance between the finder and the sheath. In test 2, the robot held a high-definition exoscope and relocated it to the setting position. Test 3 was similar to test 2, but a metal holder substituted the robot. Trained neurosurgeons manually adjusted the holder. The manipulation time was recorded. Additionally, a grading system was designed to score each image captured by the exoscope at the setting position, and the scores in the two tests were compared using the rank-sum test. RESULTS: The CoBot system positioned the finder successfully in all rounds in test 1; the mean height errors ± SD were 1.14 mm ± 0.38 mm (downward) and 1.60 mm ± 0.89 mm (upward). The grading scores of images in tests 2 and 3 were significantly different. Regarding the total score and four subgroups, test 2 showed a more precise, better-positioned, and more stable vision field. The total manipulation time in test 2 was 20 minutes, and for test 3 it was 52 minutes. CONCLUSIONS: The CoBot system successfully acted as a robust scope holding system to provide a stable and optimized surgical view during simulated port surgery, providing further evidence for the substitution of human hands, and leading to a more efficient, user-friendly, and precise operation.

A distributed fMRI-based signature for the subjective experience of fear.

The specific neural systems underlying the subjective feeling of fear are debated in affective neuroscience. Here, we combine functional MRI with machine learning to identify and evaluate a sensitive and generalizable neural signature predictive of the momentary self-reported subjective fear experience across discovery (n = 67), validation (n = 20) and generalization (n = 31) cohorts. We systematically demonstrate that accurate fear prediction crucially requires distributed brain systems, with important contributions from cortical (e.g., prefrontal, midcingulate and insular cortices) and subcortical (e.g., thalamus, periaqueductal gray, basal forebrain and amygdala) regions. We further demonstrate that the neural representation of subjective fear is distinguishable from the representation of conditioned threat and general negative affect. Overall, our findings suggest that subjective fear, which exhibits distinct neural representation with some other aversive states, is encoded in distributed systems rather than isolated 'fear centers'.

Holographic mixed-reality neuronavigation with a head-mounted device: technical feasibility and clinical application.

OBJECTIVE: The authors aimed to evaluate the technical feasibility of a mixed-reality neuronavigation (MRN) system with a wearable head-mounted device (HMD) and to determine its clinical application and accuracy. METHODS: A semiautomatic registration MRN system on HoloLens smart glasses was developed and tested for accuracy and feasibility. Thirty-seven patients with intracranial lesions were prospectively identified. For each patient, multimodal imaging-based holograms of lesions, markers, and surrounding eloquent structures were created and then imported to the MRN HMD. After a point-based registration, the holograms were projected onto the patient's head and observed through the HMD. The contour of the holograms was compared with standard neuronavigation (SN). The projection of the lesion boundaries perceived by the neurosurgeon on the patient's scalp was then marked with MRN and SN. The distance between the two contours generated by MRN and SN was measured so that the accuracy of MRN could be assessed. RESULTS: MRN localization was achieved in all patients. The mean additional time required for MRN was 36.3 ± 6.3 minutes, in which the mean registration time was 2.6 ± 0.9 minutes. A trend toward a shorter time required for preparation was observed with the increase of neurosurgeon experience with the MRN system. The overall median deviation was 4.1 mm (IQR 3.0 mm-4.7 mm), and 81.1% of the lesions localized by MRN were found to be highly consistent with SN (deviation < 5.0 mm). There was a significant difference between the supine position and the prone position (3.7 ± 1.1 mm vs 5.4 ± 0.9 mm, p = 0.001). The magnitudes of deviation vectors did not correlate with lesion volume (p = 0.126) or depth (p = 0.128). There was no significant difference in additional operating time between different operators (37.4 ± 4.8 minutes vs 34.6 ± 4.8 minutes, p = 0.237) or in localization deviation (3.7 ± 1.0 mm vs 4.6 ± 1.5 mm, p = 0.070). CONCLUSIONS: This study provided a complete set of a clinically applicable workflow on an easy-to-use MRN system using a wearable HMD, and has shown its technical feasibility and accuracy. Further development is required to improve the accuracy and clinical efficacy of this system.

Disorder- and emotional context-specific neurofunctional alterations during inhibitory control in generalized anxiety and major depressive disorder.

Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) are highly debilitating and often co-morbid disorders. The disorders exhibit partly overlapping dysregulations on the behavioral and neurofunctional level. The determination of disorder-specific behavioral and neurofunctional dysregulations may therefore promote neuro-mechanistic and diagnostic specificity. In order to determine disorder-specific alterations in the domain of emotion-cognition interactions the present study examined emotional context-specific inhibitory control in treatment-naïve MDD (n = 37) and GAD (n = 35) patients and healthy controls (n = 35). On the behavioral level MDD but not GAD exhibited impaired inhibitory control irrespective of emotional context. On the neural level, MDD-specific attenuated recruitment of inferior/medial parietal, posterior frontal, and mid-cingulate regions during inhibitory control were found during the negative context. GAD exhibited a stronger engagement of the left dorsolateral prefrontal cortex relative to MDD. Overall the findings from the present study suggest disorder- and emotional context-specific behavioral and neurofunctional inhibitory control dysregulations in major depression and may point to a depression-specific neuropathological and diagnostic marker.

Dual-energy computed tomography could reliably differentiate metastatic from non-metastatic lymph nodes of less than 0.5 cm in patients with papillary thyroid carcinoma.

BACKGROUND: Dual-energy computed tomography (DECT) has been widely applied to detect lymph node (LN) and lymph node metastasis (LNM) in various cancers, including papillary thyroid carcinoma (PTC). This study aimed to quantitatively evaluate metastatic cervical lymph nodes (LNs) <0.5 cm in patients with PTC using DECT, which has not been done in previous studies. METHODS: Preoperative DECT data of patients with pathologically confirmed PTC were retrospectively collected and analyzed between May 2016 and June 2018. A total of 359 LNs from 52 patients were included. Diameter, iodine concentration (IC), normalized iodine concentration (NIC), and the slope of the energy spectrum curve (λHU) of LNs in the arterial and the venous phases were compared between metastatic and non-metastatic LNs. The optimal parameters were obtained from the receiver operating characteristic (ROC) curves. The generalized estimation equation (GEE) model was used to evaluate independent diagnostic factors for LNM. RESULTS: A total of 139 metastatic and 220 non-metastatic LNs were analyzed. There were statistical differences of quantitative parameters between the two groups (P value 0.000-0.007). The optimal parameter for diagnosing LNM was IC in the arterial phase, and its area under the curve (AUC), sensitivity, and specificity were 0.775, 71.9%, and 73.6%, respectively. When the three parameters of diameter, IC in the arterial phase, and NIC in the venous phase were combined, the prediction efficiency was better, and the AUC was 0.819. The GEE results showed that LNs located in level VIa [odds ratio (OR) 2.030, 95% confidence interval (CI): 1.134-3.634, P=0.017], VIb (OR 2.836, 95% CI: 1.597-5.038, P=0.000), diameter (OR 2.023, 95% CI: 1.158-3.532, P=0.013), IC in the arterial phase (OR 4.444, 95% CI: 2.808-7.035, P=0.000), and IC in the venous phase (OR 5.387, 95% CI: 3.449-8.413, P=0.000) were independent risk factors for LNM in patients with PTC. CONCLUSIONS: DECT had good diagnostic performance in the differentiation of cervical metastatic LNs <0.5 cm in patients with PTC.

2',5'-Oligoadenylate synthetase 1(OAS1) inhibits PRRSV replication in Marc-145 cells.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically destructive disease for global pig industry. Although its invasion mechanism is clear, the knowledge of pathogen and host interaction is less known. Here, we found that PPRSV infection led to induction of 2', 5'-oligoadenylate synthetase gene 1(OAS1), an important interferon-stimulated gene. More importantly, ectopic overexpression of OAS1 significantly restricted the replication of PRRSV in 24 and 36 h post-infection in Marc-145 cells, and indirect immunofluorescence assay with antibody against PRRSV N protein displayed significantly lower frequency of fluorescence stained cells and reduced cytopathogenic effects of PRRSV on OAS1-transfected Marc-145 cells. Meanwhile, knockdown of endogenous OAS1 increased the PRRSV ORF7 mRNA level to 1.6 and 1.7 times of that in control in 24 and 36 h post-infection of PRRSV, and led to approximate 5.5 times increase of the frequency of fluorescence positive cells compared to negative control (p < 0.01). The obtained results strongly support a direct restriction function of OAS1 to PRRSV replication, which may contribute to the antiviral effect of the interferon system on PRRSV replication.

LSM14A inhibits porcine reproductive and respiratory syndrome virus (PRRSV) replication by activating IFN-ß signaling pathway in Marc-145.

Porcine reproductive and respiratory syndrome virus (PRRSV) is considered as a significant contributor to porcine reproductive and respiratory syndrome, one of the most economically important diseases for the pig industry worldwide. Emerging evidence indicates that pattern recognition receptors play key roles in recognizing pathogen-associated molecular patterns. In the present study, we investigated the effects of a novel pattern recognition receptor LSM14A in regulating PRRSV replication. Results in Marc-145 cells and porcine alveolar macrophages (PAMs) indicated that overexpression of porcine LSM14A effectively inhibited the replication of PRRSV, and knockdown of LSM14A by siRNA enhanced the replication of PRRSV. Mechanistically, LSM14A up-regulated the activities of IFN-ß and ISRE promoters, enhanced the production of IFN-ß, RIG-I, and ISGs, and inhibited the production of the inflammatory cytokines of TNF-α and IL-6 mRNA. Additionally, the expression pattern of LSM14A during the infection of PRRSV in Tongcheng and Large White pigs was suppressed by the PRRSV challenge. Taken together, our results suggest that LSM14A is an important PRR that inhibits PPRSV replication by inducing IFN-ß signaling and restraining inflammatory responses. Furthermore, the down-regulation of LSM14A by PRRSV might represent an important mechanism by which PRRSV invades the host. Our study sheds light on the possibility of developing a new strategy to control this disease.