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For the past three decades, neurosurgeons have utilized cranial neuro-navigation systems, bringing millimetric accuracy to operating rooms worldwide. These systems require an operating room team, anesthesia, and, most critically, cranial fixation. As a result, treatments for acute neurosurgical conditions, performed urgently in emergency rooms or intensive care units on awake and non-immobilized patients, have not benefited from traditional neuro-navigation. These emergent procedures are performed freehand, guided only by anatomical landmarks with no navigation, resulting in inaccurate catheter placement and neurological deficits. A rapidly deployable image-guidance technology that offers highly accurate, real-time registration and is capable of tracking awake, moving patients is needed to improve patient safety. The Zeta Cranial Navigation System is currently the only non-fiducial-based, FDA-approved neuro-navigation device that performs real-time registration and continuous patient tracking. To assess this system's performance, we performed registration and tracking of phantoms and human cadaver heads during controlled motions and various adverse surgical test conditions. As a result, we obtained millimetric or sub-millimetric target and surface registration accuracy. This rapid and accurate frameless neuro-navigation system for mobile subjects can enhance bedside procedure safety and expand the range of interventions performed with high levels of accuracy outside of an operating room.
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BACKGROUND: Robotic neurosurgery may improve the accuracy, speed, and availability of stereotactic procedures. We recently developed a computer vision and artificial intelligence-driven frameless stereotaxy for nonimmobilized patients, creating an opportunity to develop accurate and rapidly deployable robots for bedside cranial intervention. OBJECTIVE: To validate a portable stereotactic surgical robot capable of frameless registration, real-time tracking, and accurate bedside catheter placement. METHODS: Four human cadavers were used to evaluate the robot's ability to maintain low surface registration and targeting error for 72 intracranial targets during head motion, ie, without rigid cranial fixation. Twenty-four intracranial catheters were placed robotically at predetermined targets. Placement accuracy was verified by computed tomography imaging. RESULTS: Robotic tracking of the moving cadaver heads occurred with a program runtime of 0.111 ± 0.013 seconds, and the movement command latency was only 0.002 ± 0.003 seconds. For surface error tracking, the robot sustained a 0.588 ± 0.105 mm registration accuracy during dynamic head motions (velocity of 6.647 ± 2.360 cm/s). For the 24 robotic-assisted intracranial catheter placements, the target registration error was 0.848 ± 0.590 mm, providing a user error of 0.339 ± 0.179 mm. CONCLUSION: Robotic-assisted stereotactic procedures on mobile subjects were feasible with this robot and computer vision image guidance technology. Frameless robotic neurosurgery potentiates surgery on nonimmobilized and awake patients both in the operating room and at the bedside. It can affect the field through improving the safety and ability to perform procedures such as ventriculostomy, stereo electroencephalography, biopsy, and potentially other novel procedures. If we envision catheter misplacement as a "never event," robotics can facilitate that reality.
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Robótica , Inteligencia Artificial , Cadáver , Humanos , Sistemas de Identificación de Pacientes , Técnicas EstereotáxicasRESUMEN
OBJECTIVE: A major obstacle to improving bedside neurosurgical procedure safety and accuracy with image guidance technologies is the lack of a rapidly deployable, real-time registration and tracking system for a moving patient. This deficiency explains the persistence of freehand placement of external ventricular drains, which has an inherent risk of inaccurate positioning, multiple passes, tract hemorrhage, and injury to adjacent brain parenchyma. Here, the authors introduce and validate a novel image registration and real-time tracking system for frameless stereotactic neuronavigation and catheter placement in the nonimmobilized patient. METHODS: Computer vision technology was used to develop an algorithm that performed near-continuous, automatic, and marker-less image registration. The program fuses a subject's preprocedure CT scans to live 3D camera images (Snap-Surface), and patient movement is incorporated by artificial intelligence-driven recalibration (Real-Track). The surface registration error (SRE) and target registration error (TRE) were calculated for 5 cadaveric heads that underwent serial movements (fast and slow velocity roll, pitch, and yaw motions) and several test conditions, such as surgical draping with limited anatomical exposure and differential subject lighting. Six catheters were placed in each cadaveric head (30 total placements) with a simulated sterile technique. Postprocedure CT scans allowed comparison of planned and actual catheter positions for user error calculation. RESULTS: Registration was successful for all 5 cadaveric specimens, with an overall mean (± standard deviation) SRE of 0.429 ± 0.108 mm for the catheter placements. Accuracy of TRE was maintained under 1.2 mm throughout specimen movements of low and high velocities of roll, pitch, and yaw, with the slowest recalibration time of 0.23 seconds. There were no statistically significant differences in SRE when the specimens were draped or fully undraped (p = 0.336). Performing registration in a bright versus a dimly lit environment had no statistically significant effect on SRE (p = 0.742 and 0.859, respectively). For the catheter placements, mean TRE was 0.862 ± 0.322 mm and mean user error (difference between target and actual catheter tip) was 1.674 ± 1.195 mm. CONCLUSIONS: This computer vision-based registration system provided real-time tracking of cadaveric heads with a recalibration time of less than one-quarter of a second with submillimetric accuracy and enabled catheter placements with millimetric accuracy. Using this approach to guide bedside ventriculostomy could reduce complications, improve safety, and be extrapolated to other frameless stereotactic applications in awake, nonimmobilized patients.
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PURPOSE: To perform a paired-eye comparison of secondary iris-claw intraocular lens (IOL) implantation for aphakia. METHODS: Retrospective, comparative, nonrandomized interventional case series of aphakic eyes, which underwent secondary iris-claw Artisan IOL (Ophtec BV) implantation for aphakia in one eye and no surgery (group 1) or cataract surgery (group 2) in the fellow eye. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical equivalent, central endothelial cell count (cECC), and complications were evaluated before surgery, and at yearly intervals up to 5 years. RESULTS: Thirty aphakic eyes implanted with the Artisan were included, and the fellow eyes served as controls. In group 1, postoperative logMAR UDVA and CDVA was significantly higher in the Artisan-implanted eyes (P < 0.01). In group 2, no differences were found in postoperative UDVA and postoperative CDVA between the Artisan-implanted eyes and the eyes that underwent cataract surgery throughout the follow-up (P ≥ 0.05). No statistically significant differences were found in postoperative spherical equivalent between the Artisan-implanted eyes and unoperated eyes or eyes that underwent cataract surgery (P ≥ 0.05). In group 1, cECC was significantly lower in the Artisan-implanted eyes [1973 ± 822 vs. 2616 ± 481 cells per square millimeter at 2 years (P < 0.01)] throughout the follow-up (P < 0.01). In group 2, cECC was not significantly lower in the Artisan-implanted eyes (P ≥ 0.05) [1934 ± 689 vs. 2058 ± 818 cells per square millimeter at 2 years (P = 0.67)]. CONCLUSIONS: Visual rehabilitation with secondary iris-claw IOL implantation in aphakic eyes without capsular support seems to be an effective and safe procedure. As expected, uncomplicated cataract surgery with posterior chamber IOL implantation showed lower endothelial cell count loss. Close monitoring of the corneal endothelium is mandatory.
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Afaquia Poscatarata/cirugía , Iris/cirugía , Implantación de Lentes Intraoculares/métodos , Lentes Intraoculares , Adulto , Anciano , Afaquia Poscatarata/fisiopatología , Recuento de Células , Pérdida de Celulas Endoteliales de la Córnea/diagnóstico , Endotelio Corneal/patología , Femenino , Estudios de Seguimiento , Humanos , Queratoplastia Penetrante , Masculino , Persona de Mediana Edad , Facoemulsificación , Complicaciones Posoperatorias , Seudofaquia/fisiopatología , Refracción Ocular , Estudios Retrospectivos , Agudeza Visual/fisiologíaRESUMEN
The bone morphogenetic protein (BMP) signaling pathway is essential for normal development and tissue homeostasis. BMP signal transduction occurs when ligands interact with a complex of type 1 and type 2 receptors to activate downstream transcription factors. It is well established that a single BMP receptor may bind multiple BMP ligands with varying affinity, and this has been largely attributed to conformation at the amino acid level. However, all three type 2 BMP receptors (BMPR2, ACVR2A/B) contain consensus N-glycosylation sites in their extracellular domains (ECDs), which could play a role in modulating interaction with ligand. Here, we show a differential pattern of N-glycosylation between BMPR2 and ACVR2A/B. Site-directed mutagenesis reveals that BMPR2 is uniquely glycosylated near its ligand binding domain and at a position that is mutated in patients with heritable pulmonary arterial hypertension. We further demonstrate using a cell-free pulldown assay that N-glycosylation of the BMPR2-ECD enhances its ability to bind BMP2 ligand but has no impact on binding by the closely-related ACVR2B. Our results illuminate a novel aspect of BMP signaling pathway mechanics and demonstrate a functional difference resulting from post-translational modification of type 2 BMP receptors. Additionally, since BMPR2 is required for several aspects of normal development and defects in its function are strongly implicated in human disease, our findings are likely to be relevant in several biological contexts in normal and abnormal human physiology.