Continuous Instrument Tracking in a Cerebral Corticectomy Ex Vivo Calf Brain Simulation Model: Face and Content Validation.

BACKGROUND AND OBJECTIVES: Subpial corticectomy involving complete lesion resection while preserving pial membranes and avoiding injury to adjacent normal tissues is an essential bimanual task necessary for neurosurgical trainees to master. We sought to develop an ex vivo calf brain corticectomy simulation model with continuous assessment of surgical instrument movement during the simulation. A case series study of skilled participants was performed to assess face and content validity to gain insights into the utility of this training platform, along with determining if skilled and less skilled participants had statistical differences in validity assessment. METHODS: An ex vivo calf brain simulation model was developed in which trainees performed a subpial corticectomy of three defined areas. A case series study assessed face and content validity of the model using 7-point Likert scale questionnaires. RESULTS: Twelve skilled and 11 less skilled participants were included in this investigation. Overall median scores of 6.0 (range 4.0-6.0) for face validity and 6.0 (range 3.5-7.0) for content validity were determined on the 7-point Likert scale, with no statistical differences between skilled and less skilled groups identified. CONCLUSION: A novel ex vivo calf brain simulator was developed to replicate the subpial resection procedure and demonstrated face and content validity.

Toward Estimating MRI-Ultrasound Registration Error in Image-Guided Neurosurgery.

Image-guided neurosurgery allows surgeons to view their tools in relation to preoperatively acquired patient images and models. To continue using neuronavigation systems throughout operations, image registration between preoperative images [typically magnetic resonance imaging (MRI)] and intraoperative images (e.g., ultrasound) is common to account for brain shift (deformations of the brain during surgery). We implemented a method to estimate MRI-ultrasound registration errors, with the goal of enabling surgeons to quantitatively assess the performance of linear or nonlinear registrations. To the best of our knowledge, this is the first dense error estimating algorithm applied to multimodal image registrations. The algorithm is based on a previously proposed sliding-window convolutional neural network that operates on a voxelwise basis. To create training data where the true registration error is known, simulated ultrasound images were created from preoperative MRI images and artificially deformed. The model was evaluated on artificially deformed simulated ultrasound data and real ultrasound data with manually annotated landmark points. The model achieved a mean absolute error (MAE) of 0.977 ± 0.988 mm and a correlation of 0.8 ± 0.062 on the simulated ultrasound data, and an MAE of 2.24 ± 1.89 mm and a correlation of 0.246 on the real ultrasound data. We discuss concrete areas to improve the results on real ultrasound data. Our progress lays the foundation for future developments and ultimately implementation of clinical neuronavigation systems.

DNA hypomethylation of MB-COMT promoter in the DNA derived from saliva in schizophrenia and bipolar disorder.

The failure in the discovery of etiology of psychiatric diseases, despite extensive genetic studies, has directed the attention of neuroscientists to the contribution of epigenetic modulations, which play important roles in fine-tuning of gene expression in response to environmental factors. Previously, we analyzed 115 human post-mortem brain samples from the frontal lobe and reported DNA hypo methylation of the membrane-bound catechol-O-methyltransferase (MB-COMT) gene promoter, associated with an increased gene expression, as a risk factor for schizophrenia (SCZ) and bipolar disorder (BD). Since most epigenetic modifications are tissue specific and the availability of brain tissue to identify epigenetic aberrations in living subjects is limited, detection of epigenetic abnormalities in other tissues that represent the brain epigenetic marks is one of the critical steps to develop diagnostic and therapeutic biomarkers for mental diseases. Here, hypothesizing that; those factors that lead to the brain MB-COMT promoter DNA hypo-methylation may also cause concurrent epigenetic aberrations in peripheral tissues, we analyzed MB-COMT promoter methylation in DNA derived from the saliva in SCZ, BD and their first-degree relatives (20 cases each) as well as 25 control subjects. Using bisulfite DNA sequencing and quantitative methylation specific PCR (qMSP), we found that similar to the brain, MB-COMT promoter was hypo-methylated (∼50%) in DNA derived from the saliva in SCZ and BD compared to the control subjects (p = 0.02 and 0.037, respectively). These studies suggest that DNA methylation analysis of MB-COMT promoter in saliva can potentially be used as an available epigenetic biomarker for disease state in SCZ and BD.

Hypomethylation of the serotonin receptor type-2A Gene (HTR2A) at T102C polymorphic site in DNA derived from the saliva of patients with schizophrenia and bipolar disorder.

Several lines of evidence indicate that dysfunction of serotonin signaling and HTR2A receptor are involved in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BD). DNA methylation of HTR2A at T102C polymorphic site influences HTR2A expression and aberrant DNA methylation of HTR2A promoter was reported in postmortem brain of patients with SCZ and BD. Hypothesizing that the brain's epigenetic alteration of HTR2A may also exist in peripheral tissues that can be used as a diagnostic/therapeutic biomarker, we analyzed HTR2A promoter DNA methylation in DNA extracted from the saliva of patients with SCZ and BD, and their first degree relatives versus normal controls. Bisulfite sequencing was used to screen DNA methylation status of the HTR2A promoter CpGs and qMSP was used to quantify the degree of cytosine methylation at differentially methylated sites. Most of the cytosines of the HTR2A promoter were unmethylated. However, CpGs of the -1438A/G polymorphism site, -1420 and -1223 were >95% methylated. The CpG at T102C polymorphic site and neighboring CpGs were ∼70% methylated both in the patients and controls. qMSP analysis revealed that the cytosine of the T102C polymorphic site was significantly hypo-methylated in SCZ, BD, and their first degree relatives compared to the controls. Cytosine methylation of HTR2A at T102C polymorphic site in DNA derived from the saliva can potentially be used as a diagnostic, prognostic, and/or therapeutic biomarker in SCZ and BD. However, these preliminary observations need to be replicated in other populations with a larger sample size to be considered for clinical applications.