A patient-specific, interactive, multiuser, online mixed-reality neurosurgical training and planning system.

OBJECTIVE: Mixed-reality simulation is an emerging tool for creating anatomical models for preoperative planning. Its use in neurosurgical training (NT) has been limited because of the difficulty in real-time interactive teaching. This study describes the development of a patient-specific, interactive mixed-reality NT system. The authors took cases of intracranial tumor resection or neurovascular compression (NVC) as examples to verify the technical feasibility and efficacy of the mixed-reality NT system for residents' training and preoperative planning. METHODS: This study prospectively enrolled 40 patients who suffered from trigeminal neuralgia, hemifacial spasms, or intracranial tumors. The authors used a series of software programs to process the multimodal imaging data, followed by uploading the holographic models online. They used a HoloLens or a standard iOS device to download and display the holographic models for training. Ten neurosurgical residents with different levels of surgical experience were trained with this mixed-reality NT system. Change in surgical strategy was recorded, and a questionnaire survey was conducted to evaluate the efficacy of the mixed-reality NT system. RESULTS: The system allows the trainer and trainee to view the mixed-reality model with either a HoloLens or an iPad/iPhone simultaneously online at different locations. Interactive manipulation and instant updates were able to be achieved during training. A clinical efficacy validation test was conducted. The surgeons changed their exploration strategy in 48.3% of the NVC cases. For residents with limited experience in surgery, the exploration strategy for 75.0% of all patients with NVC was changed after the residents were trained with the mixed-reality NT system. Of the 60 responses for intracranial tumors, the trainee changed the surgical posture in 19 (31.7%) cases. The change of the location (p = 0.0338) and size (p = 0.0056) of craniotomy are significantly related to the experience of the neurosurgeons. CONCLUSIONS: The mixed-reality NT system is available for local or real-time remote neurosurgical resident training. It may effectively help neurosurgeons in patient-specific training and planning of surgery for cases of NVC and intracranial tumor. The authors expect the system to have a broader application in neurosurgery in the near future.

Mobile internet-based mixed-reality interactive telecollaboration system for neurosurgical procedures: technical feasibility and clinical implementation.

OBJECTIVE: To increase access to health interventions and healthcare services for patients in resource-constrained settings, strategies such as telemedicine must be implemented for the allocation of medical resources across geographic boundaries. Telecollaboration is the dominant form of surgical telemedicine. In this study, the authors report and evaluate a novel mobile internet-based mixed-reality interactive telecollaboration (MIMIT) system as a new paradigm for telemedicine and validate its clinical feasibility. METHODS: The application of this system was demonstrated for long-distance, real-time collaboration of neuroendoscopic procedures. The system consists of a local video processing workstation, a head-mounted mixed-reality display device, and a mobile remote device, connected over mobile internet (4G or 5G), allowing global point-to-point communication. Using this system, 20 cases of neuroendoscopic surgery were performed and evaluated. The system setup, composite video latency, technical feasibility, clinical implementation, and future potential business model were analyzed and evaluated. RESULTS: The MIMIT system allows two surgeons to perform complex visual and verbal communication during the operation. The average video delay time is 184.25 msec (range 160-230 msec) with 4G mobile internet, and 23.25 msec (range 20-26 msec) with 5G mobile internet. Excellent image resolution enabled remote neurosurgeons to visualize all critical anatomical structures intraoperatively. Remote instructors could easily make marks on the surgical view; then the composite image, as well as the audio conversation, was transferred to the local surgeon. In this way, a real-time, long-distance collaboration can occur. This system was used for 20 neuroendoscopic surgeries in various cities in China and even across countries (Boston, Massachusetts, to Jingzhou, China). Its simplicity and practicality have been recognized by both parties, and there were no technically related complications recorded. CONCLUSIONS: The MIMIT system allows for real-time, long-distance telecollaborative neuroendoscopic procedures and surgical training through a commercially available and inexpensive system. It enables remote experts to implement real-time, long-distance intraoperative interaction to guide inexperienced local surgeons, thus integrating the best medical resources and possibly promoting both diagnosis and treatment. Moreover, it can popularize and improve neurosurgical endoscopy technology in more hospitals to benefit more patients, as well as more neurosurgeons.

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.

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.

Applications of cerebrospinal fluid circulating tumor DNA in the diagnosis of gliomas.

OBJECTIVE: The 2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) was revised to include molecular biomarkers as diagnostic criteria. However, conventional biopsies of gliomas were spatially and temporally limited. This study aimed to determine whether circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) could provide more comprehensive diagnostic information to gliomas. METHODS: Combined with clinical data, we analyzed gene alterations from CSF and tumor tissues of newly diagnosed patients, and detected mutations of ctDNA in recurrent patients. We simultaneously analyzed mutations of ctDNA in different glioma subtypes, and in lower-grade gliomas (LrGG) versus glioblastoma multiforme (GBM). RESULTS: CSF ctDNA mutations had high concordance rates with tumor DNA (tDNA). CSF ctDNA mutations of PTEN and TP53 were commonly detected in recurrent gliomas patients. IDH mutation was detected in most of CSF ctDNA derived from IDH-mutant diffuse astrocytomas, while CSF ctDNA mutations of RB1 and EGFR were found in IDH-wild-type GBM. IDH mutation was detected in LrGG, whereas Rb1 mutation was more commonly detected in GBM. CONCLUSIONS: CSF ctDNA detection can be an alternative method as liquid biopsy in gliomas.

Intraoperative visualisation of functional structures facilitates safe frameless stereotactic biopsy in the motor eloquent regions of the brain.

BACKGROUND: For stereotactic brain biopsy involving motor eloquent regions, the surgical objective is to enhance diagnostic yield and preserve neurological function. To achieve this aim, we implemented functional neuro-navigation and intraoperative magnetic resonance imaging (iMRI) into the biopsy procedure. The impact of this integrated technique on the surgical outcome and postoperative neurological function was investigated and evaluated. METHOD: Thirty nine patients with lesions involving motor eloquent structures underwent frameless stereotactic biopsy assisted by functional neuro-navigation and iMRI. Intraoperative visualisation was realised by integrating anatomical and functional information into a navigation framework to improve biopsy trajectories and preserve eloquent structures. iMRI was conducted to guarantee the biopsy accuracy and detect intraoperative complications. The perioperative change of motor function and biopsy error before and after iMRI were recorded, and the role of functional information in trajectory selection and the relationship between the distance from sampling site to nearby eloquent structures and the neurological deterioration were further analyzed. RESULTS: Functional neuro-navigation helped modify the original trajectories and sampling sites in 35.90% (16/39) of cases to avoid the damage of eloquent structures. Even though all the lesions were high-risk of causing neurological deficits, no significant difference was found between preoperative and postoperative muscle strength. After data analysis, 3mm was supposed to be the safe distance for avoiding transient neurological deterioration. During surgery, the use of iMRI significantly reduced the biopsy errors (p = 0.042) and potentially increased the diagnostic yield from 84.62% (33/39) to 94.87% (37/39). Moreover, iMRI detected intraoperative haemorrhage in 5.13% (2/39) of patients, all of them benefited from the intraoperative strategies based on iMRI findings. CONCLUSIONS: Intraoperative visualisation of functional structures could be a feasible, safe and effective technique. Combined with intraoperative high-field MRI, it contributed to enhance the biopsy accuracy and lower neurological complications in stereotactic brain biopsy involving motor eloquent areas.

The diagnostic performance of magnetic resonance spectroscopy in differentiating high-from low-grade gliomas: A systematic review and meta-analysis.

OBJECTIVE: Magnetic resonance spectroscopy (MRS) is a powerful tool for preoperative grading of gliomas. We performed a meta-analysis to evaluate the diagnostic performance of MRS in differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs). METHODS: PubMed and Embase databases were systematically searched for relevant studies of glioma grading assessed by MRS through 27 March 2015. Based on the data from eligible studies, pooled sensitivity, specificity, diagnostic odds ratio and areas under summary receiver operating characteristic curve (SROC) of different metabolite ratios were obtained. RESULTS: Thirty articles comprising a total sample size of 1228 patients were included in our meta-analysis. Quantitative synthesis of studies showed that the pooled sensitivity/specificity of Cho/Cr, Cho/NAA and NAA/Cr ratios was 0.75/0.60, 0.80/0.76 and 0.71/0.70, respectively. The area under the curve (AUC) of the SROC was 0.83, 0.87 and 0.78, respectively. CONCLUSIONS: MRS demonstrated moderate diagnostic performance in distinguishing HGGs from LGGs using tumoural metabolite ratios including Cho/Cr, Cho/NAA and NAA/Cr. Although there was no significant difference in AUC between Cho/Cr and Cho/NAA groups, Cho/NAA ratio showed higher sensitivity and specificity than Cho/Cr ratio and NAA/Cr ratio. We suggest that MRS should combine other advanced imaging techniques to improve diagnostic accuracy in differentiating HGGs from LGGs. KEY POINTS: • MRS has moderate diagnostic performance in distinguishing HGGs from LGGs. • There is no significant difference in AUC between Cho/Cr and Cho/NAA ratios. • Cho/NAA ratio is superior to NAA/Cr ratio. • Cho/NAA ratio shows higher sensitivity and specificity than Cho/Cr and NAA/Cr ratios. • MRS should combine other advanced imaging techniques to improve diagnostic accuracy.

Impact of intraoperative magnetic resonance imaging and functional neuronavigation on surgical outcome in patients with gliomas involving language areas.

Balancing the benefit of extensive tumor resection with the consequence of potential postoperative language deficits remains a challenge in glioma surgery involving language areas. This study is designed to evaluate the impact of intraoperative magnetic resonance imaging (iMRI) and functional neuronavigation on surgical outcome in patients with gliomas involving language areas. Two hundred seventeen patients were prospectively enrolled, 124 in the study group underwent iMRI and functional neuronavigation-guided microsurgery and 93 in the control group underwent conventional navigation-guided microsurgery. Extent of tumor volume resection (EoR) and rate of gross total resection (rGTR) were calculated perioperatively. Aphasia quotient (AQ) was assessed to evaluate the change of language function perioperatively and at 6-month follow-up. Survival outcome for glioblastoma, including progression-free survival (PFS) and overall survival (OS), were recorded. In 198 glioma patients (112 in the study group and 86 in the control group), EoR (95.50 versus 89.85%, p < 0.001) and rGTR (69.60 versus 47.70%, p = 0.002) were significantly higher in the study group, and language functions were also better at 6-month follow-up in the study group (87.47 versus 78.73, p = 0.001). Furthermore, postoperative new aphasia occurred in 34.8% of the control group, whereas it occurred only in 2.3% of the study group (p < 0.001). In addition, PFS (12.5 versus 6.6 m, p = 0.003) and OS (19.6 versus 13.0 m, p < 0.001) for patients with glioblastomas were dramatically prolonged in the study group than in the control group. These results indicated that iMRI and functional neuronavigation may help maximize tumor resection, minimize language deficits in patients with gliomas involving language areas, and improve survival time for patients with glioblastomas.

[Magnetic resonance three dimensional sampling perfection with application optimized contrasts using different flip angle evolution sequence for obstructive hydrocephalus: impact on diagnosis and surgical strategy modification].

OBJECTIVE: To investigate the value of magnetic resonance three dimensional sampling perfection with application optimized contrasts using different flip angle evolution (3D-SPACE) sequences in diagnosis and surgical strategy modification for obstructive hydrocephalus. METHODS: From March 2013 to July 2014, there were 152 cases admitted in People's Liberation Army General Hospital suffered from hydrocephalus, including 88 male patients and 64 female patients aging from 8 months to 79 years. All patients were performed magnetic resonance T2WI and 3D-SPACE sequence scanning before operation. Surgical strategy was made after evaluation of 3D-SPACE sequence. Non-communicating hydrocephalus was treated with endoscopic third ventriculostomy (ETV) and communicating hydrocephalus was treated with ventriculo-peritoneal shunt. According to MR images of direct observation to site of obstruction to determine the detection rate. MRI 3D-SPACE and cranial CT examination were performed in regular follow-up studies. RESULTS: The relevance ratio of 3D-SPACE for the diagnosis of non-communicating hydrocephalus was 98.3% (114/116), while the relevance ratio of conventional T2-weighted MRI was 72.4% (84/116). Among the 152 patients, there were 36 cases with cerebral aqueduct film obstruction, 22 cases with space-occupying lesions in pineal region, posterior part of the third ventricle, or space-occupying lesions in quadrigeminal bodies area, 10 cases with Dandy-Walker symptom, 18 cases with cyst of the anterior pool of the bridge, 16 cases with cysticercosis, 4 cases with cyst of lateral ventricle, 2 cases with cyst of fourth ventricle, 2 cases with space-occupying lesion in foramen ofmonro, 2 cases with foramen ofmonro atresia, 4 cases with craniopharyngioma, 36 cases with communicating hydrocephalus. There were 112 hydrocephalus cases (73.7%) were treated with ETV, without shunt catheter insertion in follow-up study from 1 to 18 months (average (14±9) months). CONCLUSIONS: For obstructive hydrocephalus, MRI 3D-SPACE sequence image has high diagnostic yield rate for providing more detailed anatomical information than conventional MRI. Hence, the advanced imaging methods are helpful for surgical treatment strategy decision making.

[Analysis of the surgical strategy for the treatment of pineal region tumors].

OBJECTIVE: To evaluate and explore the optimal surgical strategy for the normalized treatment of pineal region tumors. METHODS: From September 2007 to February 2012, 43 patients were treated in Chinese People's Liberation Army General Hospital, including 30 male and 14 female patients, with pineal region tumors and non-communicating hydrocephalus were enrolled, who were 1-52 years old, mean age was (27 ± 4) years. The clinical records, treatment strategy, and prognosis were retrospectively analyzed. All the patients routinely underwent endoscopic third ventriculostomy (ETV) and tumor biopsy as the initial treatment. Twenty-seven cases (62.8%, pure endoscopic group) with histological diagnosis of germinoma (23 cases) or pineoblastoma (4 cases) were treated with chemotherapy with/without radiation therapy after ETV. The rest 16 cases (37.2%, craniotomy group) with histological diagnosis of non-germinoma and non-pineoblastoma (5 astrocytomas, 4 pineocytomas, 4 teratomas, 2 ependymomas, and 1 pineopappiloma) had craniotomy and tumor resection after ETV. All the cases had routine follow-up at 1, 3, and 6 months after the final surgery. The clinical, imaging, and tumor markers analysis were routinely examined at follow-up. RESULTS: In the pure endoscopic group, 1 case had intra-ventricular hemorrhage after ETV, followed by external ventricular drainage and recovered after 1 week. Endoscopic procedure related short-term ( < 3 months) complication rate was 2.3% (1/43), while long-term morbidity was 0. All cases in the pure endoscopic group had chemotherapy with/without radiation therapy. Long-term follow-up results showed that all cases were cured or had progression free survival (PFS). In the craniotomy group, 2 cases (2/16) developed intra-cranial hemorrhage after surgery, and had to be operated again for hematoma evacuation. In the craniotomy group, the short-term ( < 3 months) morbidity rate was 6/16. At 3 months follow-up, 1 case still had homonymous hemianopia, which made the long-term morbidity rate was 1/16. CONCLUSIONS: For pineal region tumors with non-communicating hydrocephalus, simultaneous ETV with tumor biopsy can be the most favorable initial diagnostic and therapeutic treatment. Second-stage treatment (chemotherapy, radiation therapy, or craniotomy with tumor resection) can be selected according to the histological diagnosis.

[Automated proton magnetic resonance spectroscopy imaging guided frameless stereotactic biopsy of intracranial lesions].

OBJECTIVE: To evaluate the feasibility, reliability and accuracy of the automated magnetic resonance spectroscopy ((1)H-MRS) guided frameless brain biopsy with intraoperative magnetic resonance imaging (iMRI). METHODS: Between July 2011 and July 2013, a consecutive series of 93 patients were prospectively enrolled. All the patients had intracranial lesions which need biopsy to confirm the diagnosis. Among them, 48 patients were male, 45 patients were female. Their age range from 7 years to 76 years, the median age was 47 years. All patients underwent MRS examination. With MRS automatic fusion technique, the metabolic images were integrated into a standard navigation system (Vario Guide) to guide frameless biopsy. High-field iMRI (1.5 T) was used for target inspection, brain shift correction, and intra-operative exclusion of intra-cerebral hemorrhage and other complications. RESULTS: For all the 93 patients, (1)H-MRS based metabolic images could be automatically integrated into a standard navigation system and average fusion procedure could be taken 5 minutes 6 seconds. For (1)H-MRS guided stereotactic biopsy of intracranial lesions, the diagnosis yield rate was 94.6% (88/93). Four cases did not get a clear pathological diagnosis, while 1 case did not match the pathological diagnosis result which obtained by following craniotomy. Technical related complication rate was 2.2% (2 cases, intra-cerebral hemorrhage), which were intra-operatively depicted with iMRI, and managed properly. Among them, 1 case with small volume (5 ml) intracerebral hematoma fully recovered 10 days after surgery without second surgical intervention. One case with large volume intracerebral hematoma (32 ml) was depicted with iMRI, followed by craniotomy and hematoma evacuation in the same session. This case had no new or worsened neurologic deficit post-operatively. CONCLUSIONS: (1)H-MRS based metabolic imaging can be automatically integrated into a standard navigation system and used for frameless brain biopsy. The target can be selected according to the metabolic status of the lesion. Hence, the target can be more accurate. And the pathological diagnosis yield rate is higher. With iMRI, the method is safe, and has high clinical efficacy.

Phosphocreatine promotes epigenetic reprogramming to facilitate glioblastoma growth through stabilizing BRD2.

Glioblastoma (GBM) exhibits profound metabolic plasticity for survival and therapeutic resistance, while the underlying mechanisms remain unclear. Here, we show that GBM stem cells (GSCs) reprogram the epigenetic landscape by producing substantial amounts of phosphocreatine (PCr). This production is attributed to the elevated transcription of brain-type creatine kinase (CKB), mediated by Zinc finger E-box binding homeobox 1 (ZEB1). PCr inhibits the poly-ubiquitination of the chromatin regulator bromodomain containing protein 2 (BRD2) by outcompeting the E3 ubiquitin ligase SPOP for BRD2 binding. Pharmacological disruption of PCr biosynthesis by cyclocreatine leads to BRD2 degradation and a decrease in its targets' transcription, which inhibits chromosome segregation and cell proliferation. Notably, cyclocreatine treatment significantly impedes tumor growth and sensitizes tumors to a BRD2 inhibitor in mouse GBM models without detectable side effects. These findings highlight that high production of PCr is a druggable metabolic feature of GBM and a promising therapeutic target for GBM treatment.

Resection of subependymal giant cell astrocytoma guided by intraoperative magnetic resonance imaging and neuronavigation.

PURPOSE: Subependymal giant cell astrocytoma (SEGA) is a rare, benign tumor that occurs mainly in children; complete resection can achieve cure. Guidance of surgery by combined intraoperative magnetic resonance imaging (iMRI) and functional neuronavigation is reported to achieve more radical resection and reduced complications. However, reports about the resection of SEGA with such guidance are rare. We report here our preliminary experience of the resection of SEGA guided by iMRI and neuronavigation, focusing on the feasibility, benefits, and pitfalls of this combination of techniques. METHODS: We performed resection of SEGA guided by combined iMRI and functional neuronavigation in seven children. The first iMRI was performed when the surgeon believed that the tumor had been completely resected; the last iMRI was performed immediately after closure. Additional scans were performed as needed. RESULTS: Successful resection was achieved in all seven patients using this combination of techniques. The iMRI scans detected residual tumor in three patients and a large, remote epidural hematoma in one patient. Further resection or other surgery was performed in these four patients. Complete resection was eventually achieved in all patients. There were no cases of surgery-related neurological dysfunction, except transient memory loss in one patient. No recurrence of tumor or hydrocephalus was observed in any patients during the follow-up period. CONCLUSIONS: Resection of SEGA in children guided by combined iMRI and neuronavigation is feasible and safe. This combination of techniques enables a higher complete resection rate and reduces brain injury and other unexpected events during surgery.

[Integration of metabolism images into multimodal neuronavigation for frameless stereotaxy].

OBJECTIVES: To evaluate the efficacy of integration of metabolism images into multimodal neuronavigation for frameless stereotactic biopsy. METHODS: From January to December 2012, 32 patients with brain lesions underwent frameless stereotactic biopsy guided by positron emission tomograph (PET) and proton magnetic resonance spectroscopy ((1)H-MRS)-based multimodal neuronavigation and intraoperative magnetic resonance imaging (iMRI). The cohort consisted of 16 male and 16 female patients, with a mean age of 45 years (range: 7 - 62 years). Biopsy targets were identified according to PET and (1)H-MRS. Biopsy was performed with Varioguide frameless biopsy system. Diagnostic yield and complications were assessed. RESULTS: Metabolism images-based multimodal neuronavigation and iMRI were successfully implemented in all cases. iMRI confirmed accuracy of biopsy targets. All the specimens obtained pathological diagnosis, the diagnostic yield was 100%. In 1 patient, iMRI found small hematoma (< 5 ml), surgical evacuation wasn't needed with intraoperative complication rate 3.1%. With the help of multimodal neuronavigation, no patients had new or worsened neurologic deficits. CONCLUSIONS: Integration of metabolism images into multimodal neuronavigation provide not only anatomical, but also metabolic and functional information for frameless stereotaxy, increasing diagnostic yield and avoiding postoperative neurologic deficits.

[Application of intraoperative magnetic resonance imaging and multimodal navigation in surgical resection of glioblastoma].

OBJECTIVE: To evaluate the efficacy of intraoperative magnetic resonance imaging (iMRI) and multimodal navigation in surgical resection of glioblastoma. METHODS: Between February 2009 and July 2010, 76 glioblastoma patients underwent surgical resection guided by iMRI and multimodal navigation. The cohort consisted of 43 male and 33 female patients, with a mean age of 49 years (range: 14-79 years). Rates of gross total resection (GTR) and extent of resection (EoR) were calculated at first and final iMRI scans.Pearson χ(2) test was used to compare the rates of GTR. RESULTS: iMRI and multimodal navigation were successfully implemented in all cases. Rates of GTR were misestimated by neurosurgeons in 24 cases (31.6%), which were confirmed by first iMRI. Total tumor resection were achieved in 20 cases (26.3%) as a result of iMRI scan, increasing the rates of gross total resection from 52.6% to 78.9% (χ(2) = 11.692, P = 0.001). Extent of resection in 28 patients who underwent further tumor resection were increased from 81.5% to 98.1%, leading to the overall extent of resection improved from 92.3% to 98.4%. At 3-month follow-up, 3 cases (3.9%) developed permanent neurologic deficits. The mean clinical follow-up was 15.6 months (range 3.0-45.0 months). The 2-year overall survival rate was 19.7%. The median progression-free survival of gross total resection group was 12 months (95% CI: 10.1-13.9 months), compared with 9 months (95%CI: 7.9-10.1 months) of the subtotal resection group (χ(2) = 4.756, P = 0.029). The overall survival of gross total resection group was 16 months (95% CI: 13.7-18.3 months), compared with 12 months (95% CI: 9.7-14.3 months) of the subtotal resection group (χ(2) = 7.885, P = 0.005). CONCLUSION: Combined with multimodal navigation, iMRI helps maximize surgical resection of glioblastoma, preserving neurological function while increasing progression-free survival and overall survival.

Leukocyte transcriptome of Cushing's disease are associated with nerve impairment and psychiatric disorders.

INTRODUCTION: The hypothalamus-pituitary-adrenal (HPA) axis and its end product cortisol is a major response mechanism to stress and plays a critical role in many psychiatric disorders. Cushing's disease (CD) serves as a valuable in vivo "hyperexpression" model to elucidate the effect of cortisol on brain function and mental disorders. Changes in brain macroscale properties measured by magnetic resonance imaging (MRI) have been detailed demonstrated, but the biological and molecular mechanisms underlying these changes remain poorly understood. MATERIAL AND METHODS: Here we included 25 CD patients and matched 18 healthy controls for assessment, and performed transcriptome sequencing of peripheral blood leukocytes. Weighted gene co-expression network analysis (WGCNA) was performed to construct a co-expression network of the relationships between genes and we identified a significant module and hub gene types associated with neuropsychological phenotype and psychiatric disorder identified in enrichment analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis preliminarily explored the biological functions of these modules. RESULTS: The WGCNA and enrichment analysis indicated that module 3 of blood leukocytes was enriched in broadly expressed genes and was associated with neuropsychological phenotypes and mental diseases enrichment. GO and KEGG enrichment analysis of module 3 identified enrichment in many biological pathways associated with psychiatric disorders. CONCLUSION: Leukocyte transcriptome of Cushing's disease is enriched in broadly expressed genes and is associated with nerve impairment and psychiatric disorders, which may reflect some changes in the affected brain.

[Implementation of VarioGuide in stereotactic brain biopsy: a preliminary experience].

OBJECTIVE: To evaluate the clinical value of VarioGuide in stereotactic brain biopsy. METHODS: Fifteen patients with brain lesions underwent frameless stereotactic brain biopsy guided by VarioGuide and multimodal neuronavigation. Intraoperative magnetic resonance imaging (iMRI) was used to confirm the accuracy of biopsy. And the VarioGuide-related adverse events, operative duration, surgical outcomes and postoperative complications were recorded respectively. RESULTS: In all patients, VarioGuide and multimodal neuronavigation were successfully integrated into the biopsy procedure. No VarioGuide-related adverse events were reported. The mean operative duration was (65 ± 8) min. The biopsy accuracy was confirmed by iMRI in all cases. And the postoperative histological diagnostic rate was 100%. No mortality and morbidity occurred postoperatively. CONCLUSION: The combined approach of VarioGuide and multimodal neuronavigation is accurate, safe and efficient. It may improve the histological diagnostic rate without postoperative neurological deficits in stereotactic brain biopsy.

[Influences of high-field intraoperative magnetic resonance imaging on the extent of resection in low-grade gliomas].

OBJECTIVE: To evaluate the influences of high-field intraoperative magnetic resonance imaging (iMRI) on the extent of resection (EoR) in low-grade gliomas. METHODS: Fifty-nine patients with low-grade gliomas underwent microsurgeries under the guidance of high-field iMRI and functional neuro-navigation. The rates of gross total removal and EoR were recorded after initial and final iMRI scans and neurological performances were evaluated peri-operatively and at follow-up. RESULTS: iMRI and functional neuronavigation were successfully performed in all patients. Initial iMRI found that the rates of gross total removal were misestimated in 21 cases (35.6%). In 17 cases (28.8%), initial iMRI revealed resectable residual tumors and further resection achieved gross total removal in 8 cases (13.6%). iMRI boosted the level of EoR from 90% ± 15% to 94% ± 12% (P < 0.001) in all cases and from 78% ± 17% to 91% ± 12% in 17 cases undergoing further tumor resections. At 3-month follow-up, 2 cases (3.4%) developed neurological deficits. CONCLUSION: The combination of iMRI and functional neuronavigation helped maximize safe tumor resection in low-grade gliomas.

Vestibular Schwannomas in Young Patients: A 12-Year Experience in a Single Center.

OBJECTIVE: This study evaluated the characteristics of vestibular schwannomas (VS) in young patients, including clinical features, treatment, prognosis, and histopathologic characteristics. METHODS: We retrospectively reviewed medical records and follow-up data for 36 pediatric patients <21 years of age who were surgically treated for VS in the Chinese PLA General Hospital between 2008 and 2019. RESULTS: Mean patient age was 17.4 years. Mean tumor size was 2.8 cm. Hearing loss (n = 32, 88.9%) and tinnitus (n = 20, 55.6%) were the most common symptoms. Ten patients (27.8%) had impaired facial nerve function after surgery. Gross total resection (GTR) was achieved in 26 cases (72.2%). The median tumor Ki-67 level was 5%. Tumor size was related to incomplete tumor resection (odds ratio, 0.2; 95% confidence interval, 0.1-0.9) and postoperative facial nerve dysfunction (odds ratio, 24.9; 95% confidence interval, 1.2-539.1). Tumor size was nonlinearly associated with prognosis and 2.2 cm corresponded to the inflection point at which the probability of tumor remnant and postoperative facial nerve dysfunction significantly increased. The GTR and low Ki-67 groups achieved better 3-year tumor control rate. Histopathologic findings confirmed the presence of cellular schwannoma subtype in young patients. CONCLUSIONS: Tumor size is an important factor affecting the prognosis of VS in young patients. For large VS, surgical treatment should be the first choice, rather than wait-and-scan. VS in young patients shows high tumor proliferation and a tendency to relapse. The cellular schwannoma subtype requires special attention; an accurate histopathologic diagnosis is necessary for young patients with VS, and a closer follow-up strategy should be adopted for cellular VS.

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.