Low-grade gliomas (LGGs) are tumors that affect mostly adults. These neoplasms are comprised mainly of oligodendrogliomas and diffuse astrocytomas. LGGs remain vexing to current management and therapeutic modalities although they exhibit more favorable survival rates compared with high-grade gliomas (HGGs). The specific genetic subtypes that these tumors exhibit result in variable clinical courses and the need to involve multidisciplinary teams of neurologists, epileptologists, neurooncologists and neurosurgeons. Currently, the diagnosis of an LGG pivots mainly around the preliminary radiological findings and the subsequent definitive surgical diagnosis (via surgical sampling). The introduction of radiomics as a high throughput quantitative imaging technique that allows for improved diagnostic, prognostic and predictive indices has created more interest for such techniques in cancer research and especially in neurooncology (MRI-based classification of LGGs, predicting Isocitrate dehydrogenase (IDH) and Telomerase reverse transcriptase (TERT) promoter mutations and predicting LGG associated seizures). Radiogenomics refers to the linkage of imaging findings with the tumor/tissue genomics. Numerous applications of radiomics and radiogenomics have been described in the clinical context and management of LGGs. In this review, we describe the recently published studies discussing the potential application of radiomics and radiogenomics in LGGs. We also highlight the potential pitfalls of the above-mentioned high throughput computerized techniques and, most excitingly, explore the use of machine learning artificial intelligence technologies as standalone and adjunct imaging tools en route to enhance a personalized MRI-based tumor diagnosis and management plan design.
Human brain organoids are models derived from human embryonic or induced pluripotent stem cells that mimic basic cerebral microanatomy and demonstrate simple functional neuronal networks. Brain organoids have been a rapidly expanding avenue for biomedical research in general and specifically: neural development, regeneration, and central nervous system pathophysiology. However, technology replicating functional aspects of the human brain, including electrically active neural networks, requires a responsible code of conduct. In this review, we focus the discussion on intrinsic and extrinsic ethical factors associated with organoids: intrinsic considerations arise with the growing complexity of human brain organoids, including human-animal chimerism, consciousness development, and questions of where these human-like beings fall in a moral hierarchy. Extrinsic considerations explore ethics on obtainment, manufacturing, and production of sophisticated human products. In summary, a thoughtful code of conduct using human brain organoids towards the advancement of science and medicine is crucial. This article shall facilitate a structured thought process approaching the moral landscape of organoid technology.
Glioblastoma (GBM) is fatal and the study of therapeutic resistance, disease progression, and drug discovery in GBM or glioma stem cells is often hindered by limited resources. This limitation slows down progress in both drug discovery and patient survival. Here we present a genetically engineered human cerebral organoid model with a cancer-like phenotype that could provide a basis for GBM-like models. Specifically, we engineered a doxycycline-inducible vector encoding shRNAs enabling depletion of the TP53, PTEN, and NF1 tumor suppressors in human cerebral organoids. Designated as inducible short hairpin-TP53-PTEN-NF1 (ish-TPN), doxycycline treatment resulted in human cancer-like cerebral organoids that effaced the entire organoid cytoarchitecture, while uninduced ish-TPN cerebral organoids recapitulated the normal cytoarchitecture of the brain. Transcriptomic analysis revealed a proneural GBM subtype. This proof-of-concept study offers a valuable resource for directly investigating the emergence and progression of gliomas within the context of specific genetic alterations in normal cerebral organoids.
The insular cortex, a critical hub in the brain’s sensory, cognitive, and emotional networks, remains an intriguing subject of study. In this article, we discuss its intricate functional neuroanatomy, emphasizing its pivotal role in processing olfactory information. Through concise exploration, we delve into the insula’s diverse connectivity and its involvement in sensory integration, particularly in olfaction. Stimulation studies in humans reveal compelling insights into the insula’s contribution to the perception of smell, hinting at its broader implications for cognitive processing. Additionally, we explore an avenue of research in which studying olfactory processing via insular stimulation could unravel higher-level cognitive processes. This innovative approach could help give a fresh perspective on the interplay between sensory and cognitive domains, offering valuable insights into the neural mechanisms underlying cognition and emotion. In conclusion, future research efforts should emphasize a multidisciplinary approach, combining advanced imaging and surgical techniques to explore the intricate functions of the human insula. Moreover, awake craniotomies could offer a unique opportunity for real-time observation, shedding light on its neural circuitry and contributions to higher-order brain functions. Furthermore, olfaction’s direct cortical projection enables precise exploration of insular function, promising insights into cognitive and emotional processes. This multifaceted approach will deepen our understanding of the insular cortex and its significance in human cognition and emotion.
12 August 2022 in Surgical Neurology International
Background: The crux in high-grade glioma surgery remains maximizing resection without affecting eloquent brain areas. Toward this, a myriad of adjunct tools and techniques has been employed to enhance surgical safety and efficacy. Despite intraoperative MRI and advanced neuronavigational techniques, as well as augmented reality, to date, the only true real-time visualization tool remains the ultrasound (US). Neuroultrasonography is a cost-efficient imaging modality that offers instant, real-time information about the changing anatomical landscape intraoperatively. Recent advances in technology now allow for the integration of intraoperative US with neuronavigation. Case Description: In this report, we present the resection technique for three cases of high-grade gliomas (two glioblastomas and one anaplastic astrocytoma). The patient presented with a variable clinical spectrum. All three cases have been performed using the Brainlab® neuronavigation system (BrainLAB, Munich, Germany) and the bk5000 US Machine® (BK Medical, Analogic Corporation, Peabody, Massachusetts, USA). Conclusion: Gross total resection was achieved in all three cases. The use of 3D navigated US was a reliable adjunct surgical tool in achieving favorable resection outcomes in these patients.
BACKGROUND: Treatment guidelines in neurosurgery are often based on evidence obtained from randomized controlled trials (RCTs). OBJECTIVE: To evaluate the robustness of RCTs supporting current central nervous tumor and cerebrovascular disease guidelines by calculating their fragility index (FI)—the minimum number of patients needed to switch from an event to nonevent outcome to change significant trial primary outcome. METHODS: We analyzed RCTs referenced in the Congress of Neurological Surgeons and American Association of Neurological Surgeons guidelines on central nervous tumor and cerebrovascular disease management. Trial characteristics, finding of a statistically significant difference in the primary endpoint favoring the experimental intervention, the FI, and FI minus number lost to follow-up were assessed. RESULTS: Of 312 RCTs identified, 158 (50.6%) were published from 2000 to 2010 and 106 (34%) after 2010. Sixty-three trials (19.2%) were categorized as surgical trials, and the rest studied medical treatment (82.0%) or percutaneous intervention (8.33%). The trials had a median power of 80.0% (IQR 80.0-90.0). Of these, 120 trials were eligible for FI calculation. The median FI was 7.0 (IQR 2.0-16.25). Forty-four (36.6%) trials had FI ≤ 3 indicating very low robustness. After adjusting for covariates, recently published trials and trials studying percutaneous interventions were associated with significantly higher FI compared with older trials and trials comparing surgical approaches, respectively. Trials limited to single centers were associated with significantly lower FI. CONCLUSION: Trials supporting current guidelines on neuro-oncological and neurovascular surgical interventions have low robustness. While the robustness of trials has improved over time, future guidelines must take into consideration this metric in their recommendations.