Suzuki Stage VI Unilateral Moyamoya Disease Presenting With Massive Intraventricular Hemorrhage.

Moyamoya disease (MMD) is characterized by stenosis of the terminal portion of the internal carotid artery (ICA) and the development of collateral vessels. In late Suzuki stage MMD, ICA almost disappears, and the moyamoya vessels gradually regress. We report a case of late Suzuki stage unilateral MMD presenting with intraventricular hemorrhage. A 76-year-old woman who had previously been diagnosed with right ICA occlusive disease was referred to our hospital due to impaired consciousness. Radiological evaluation revealed massive intraventricular hemorrhage. After endoscopic hematoma removal, digital subtraction angiography (DSA) was performed to examine the vascular anatomy, which revealed numerous basal moyamoya vessels originating from the posterior cerebral artery. Three-dimensional rotational angiography identified a choroidal anastomosis originating from the posterior choroidal artery as the hemorrhage source. The patient had an RNF213 p.Arg4810Lys heterozygous variant in the germline. Based on the DSA findings, MMD was diagnosed, and the patient was transferred to a rehabilitation hospital with good postoperative consciousness. In conclusion, patients diagnosed with ICA occlusive disease may have late Suzuki stage MMD, potentially leading to major hemorrhage; therefore, antithrombotic medications should be administered with caution. In diagnosing ICA occlusive disease, the assessment of periventricular anastomosis should be considered, taking into account the possibility of MMD.

Region-specific DNA hydroxymethylation along the malignant progression of IDH-mutant gliomas.

The majority of low-grade isocitrate dehydrogenase-mutant (IDHmt) gliomas undergo malignant progression (MP), but their underlying mechanism remains unclear. IDHmt gliomas exhibit global DNA methylation, and our previous report suggested that MP could be partly attributed to passive demethylation caused by accelerated cell cycles. However, during MP, there is also active demethylation mediated by ten-eleven translocation, such as DNA hydroxymethylation. Hydroxymethylation is reported to potentially contribute to gene expression regulation, but its role in MP remains under investigation. Therefore, we conducted a comprehensive analysis of hydroxymethylation during MP of IDHmt astrocytoma. Five primary/malignantly progressed IDHmt astrocytoma pairs were analyzed with oxidative bisulfite and the Infinium EPIC methylation array, detecting 5-hydroxymethyl cytosine at over 850,000 locations for region-specific hydroxymethylation assessment. Notably, we observed significant sharing of hydroxymethylated genomic regions during MP across the samples. Hydroxymethylated CpGs were enriched in open sea and intergenic regions (p < 0.001), and genes undergoing hydroxymethylation were significantly associated with cancer-related signaling pathways. RNA sequencing data integration identified 91 genes with significant positive/negative hydroxymethylation-expression correlations. Functional analysis suggested that positively correlated genes are involved in cell-cycle promotion, while negatively correlated ones are associated with antineoplastic functions. Analyses of The Cancer Genome Atlas clinical data on glioma were in line with these findings. Motif-enrichment analysis suggested the potential involvement of the transcription factor KLF4 in hydroxymethylation-based gene regulation. Our findings shed light on the significance of region-specific DNA hydroxymethylation in glioma MP and suggest its potential role in cancer-related gene expression and IDHmt glioma malignancy.

Transcriptomic and epigenetic dissection of spinal ependymoma (SP-EPN) identifies clinically relevant subtypes enriched for tumors with and without NF2 mutation.

Ependymomas encompass multiple clinically relevant tumor types based on localization and molecular profiles. Tumors of the methylation class "spinal ependymoma" (SP-EPN) represent the most common intramedullary neoplasms in children and adults. However, their developmental origin is ill-defined, molecular data are scarce, and the potential heterogeneity within SP-EPN remains unexplored. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and NF2 mutations, but neither types and frequency of these alterations nor their clinical relevance have been described in a large, epigenetically defined series. Transcriptomic (n = 72), epigenetic (n = 225), genetic (n = 134), and clinical data (n = 112) were integrated for a detailed molecular overview on SP-EPN. Additionally, we mapped SP-EPN transcriptomes to developmental atlases of the developing and adult spinal cord to uncover potential developmental origins of these tumors. The integration of transcriptomic ependymoma data with single-cell atlases of the spinal cord revealed that SP-EPN display the highest similarities to mature adult ependymal cells. Unsupervised hierarchical clustering of transcriptomic data together with integrated analysis of methylation profiles identified two molecular SP-EPN subtypes. Subtype A tumors primarily carried previously known germline or sporadic NF2 mutations together with 22q loss (bi-allelic NF2 loss), resulting in decreased NF2 expression. Furthermore, they more often presented as multilocular disease and demonstrated a significantly reduced progression-free survival as compared to SP-EP subtype B. In contrast, subtype B predominantly contained samples without NF2 mutation detected in sequencing together with 22q loss (monoallelic NF2 loss). These tumors showed regular NF2 expression but more extensive global copy number alterations. Based on integrated molecular profiling of a large multi-center cohort, we identified two distinct SP-EPN subtypes with important implications for genetic counseling, patient surveillance, and drug development priorities.

Aneurysmal Inflow Rate Coefficient Predicts Ultra-early Rebleeding in Ruptured Intracranial Aneurysms: Preliminary Report of a Computational Fluid Dynamics Study.

Rebleeding from a ruptured intracranial aneurysm has poor outcomes. Although numerous factors are associated with rebleeding, studies on computational fluid dynamics (CFD) on hemodynamic parameters associated with early rebleeding are scarce. In particular, no report of rebleeding in ultra-early phase exists. We aimed to elucidate the specific hemodynamic parameters associated with ultra-early rebleeding using CFD. In this study, the rebleeding group included patients with aneurysmal subarachnoid hemorrhage (aSAH) that rebled within 6 h from the onset. The control group included patients without rebleeding, observed for >10 h following the initial rupture. Clinical images after initial rupture and before rebleeding were used to build 3D vessel models for hemodynamic analysis focusing on the following parameters: time-averaged wall shear stress (WSS), normalized WSS, low shear area, oscillatory shear index, relative residence time, pressure loss coefficient, and aneurysmal inflow rate coefficient (AIRC). Five and 15 patients in the rebleeding and control groups, respectively, met the inclusion criteria. The World Federation of Neurosurgical Surgeons grade was significantly higher in the rebleeding group (p = 0.0088). Hemodynamic analysis showed significantly higher AIRC in the rebleeding group (p = 0.042). The other parameters were not significantly different between groups. There were no significant differences or correlations between SAH severity and AIRC. AIRC was identified as a hemodynamic parameter associated with ultra-early rebleeding of ruptured intracranial aneurysms. Thus, AIRC calculation may enable the prediction of ultra-early rebleeding.

De-Identification Technique with Facial Deformation in Head CT Images.

Head CT, which includes the facial region, can visualize faces using 3D reconstruction, raising concern that individuals may be identified. We developed a new de-identification technique that distorts the faces of head CT images. Head CT images that were distorted were labeled as "original images" and the others as "reference images." Reconstructed face models of both were created, with 400 control points on the facial surfaces. All voxel positions in the original image were moved and deformed according to the deformation vectors required to move to corresponding control points on the reference image. Three face detection and identification programs were used to determine face detection rates and match confidence scores. Intracranial volume equivalence tests were performed before and after deformation, and correlation coefficients between intracranial pixel value histograms were calculated. Output accuracy of the deep learning model for intracranial segmentation was determined using Dice Similarity Coefficient before and after deformation. The face detection rate was 100%, and match confidence scores were < 90. Equivalence testing of the intracranial volume revealed statistical equivalence before and after deformation. The median correlation coefficient between intracranial pixel value histograms before and after deformation was 0.9965, indicating high similarity. Dice Similarity Coefficient values of original and deformed images were statistically equivalent. We developed a technique to de-identify head CT images while maintaining the accuracy of deep-learning models. The technique involves deforming images to prevent face identification, with minimal changes to the original information.

Invention of an Online Interactive Virtual Neurosurgery Simulator With Audiovisual Capture for Tactile Feedback.

BACKGROUND: Present neurosurgical simulators are not portable. OBJECTIVE: To maximize portability of a virtual surgical simulator by providing online learning and to validate a unique psychometric method ("audiovisual capture") to provide tactile information without force feedback probes. METHODS: An online interactive neurosurgical simulator of a posterior petrosectomy was developed. The difference in the hardness of compact vs cancellous bone was presented with audiovisual effects as inclinations of the drilling speed and sound based on engineering perspectives. Three training methods (the developed simulator, lectures and review of slides, and dissection of a 3-dimensional printed temporal bone model [D3DPM]) were evaluated by 10 neurosurgical residents. They all first attended a lecture and were randomly allocated to 2 groups by the training D3DPM (A: simulator; B: review of slides, no simulator). In D3DPM, objective measures (required time, quality of completion, injury scores of important structures, and the number of instructions provided) were compared between groups. Finally, the residents answered questionnaires. RESULTS: The objective measures were not significantly different between groups despite a younger tendency in group A (graduate year -2.4 years, 95% confidence interval -5.3 to 0.5, P = .081). The mean perceived hardness of cancellous bone on the simulator was 70% of that of compact bone, matching the intended profile. The simulator was superior to lectures and review of slides in feedback and repeated practices and to D3DPM in adaptability to multiple learning environments. CONCLUSION: A novel online interactive neurosurgical simulator was developed, and satisfactory validity was shown. Audiovisual capture successfully transmitted the tactile information.

Reproducibility of Facial Information in Three-Dimensional Reconstructed Head Images: An Exploratory Study.

BACKGROUND: Facial information acquired via three-dimensional reconstruction of head computed tomography (CT) data may be considered personal information, which can be problematic for neuroimaging studies. However, no study has verified the relationship between slice thickness and face reproducibility. This study determined the relationship and match rate between image slice thickness and face detection accuracy of face-recognition software in facial reconstructed models. METHODS: Head CT data of 60 cases comprising entire faces obtained under conditions of non-contrast and 1-mm slice thickness were resampled to obtain 2-10-mm slice-thickness data. Facial models, reconstructed by image thresholding, were acquired from the data. We performed face detection tests per slice thickness on the models and calculated the face detection rate. The reconstructed facial models created from 1-mm slice-thickness data and other slice thicknesses were used as training and test data, respectively. Match confidence scores were obtained via three programs, match rates were calculated per slice thickness, and generalized estimating equations were used to evaluate the match rate trend. RESULTS: In general, the face detection rates for the 1-10-mm slice thicknesses were 100, 100, 98.3, 98.3, 95.0, 91.7, 86.7, 78.3, 68.3, and 61.7 %, respectively. The match rates for the 2-10-mm slice thicknesses were 100, 98.3, 98.3, 95.0, 85.0, 71.7, 53.3, 28.3, and 16.7 %, respectively. CONCLUSION: The reconstructed models tended to have higher match rates as the slice thickness decreased. Thus, thin-slice head CT imaging data may increase the possibility of the information becoming personally identifiable health information.

Morphologically, genetically and spatially mixed astrocytoma and oligodendroglioma; chronological acquisition of 1p/19q codeletion and CDKN2A deletion: a case report.

"Oligoastrocytoma" disappeared as of the revised fourth edition of the World Health Organization Classification of Tumours of the Central Nervous System, except where appended with "not otherwise specified (NOS)". However, histopathological and genetic backgrounds of cases with dual features of astrocytoma/oligodendroglioma have been sparsely reported. We encountered a 54-year-old man with right frontal glioma comprising two distinct parts on imaging and histopathological examination: grade 4 astrocytoma with IDH1-R132H, ATRX loss, p53-positivity and intact 1p/19q; and oligodendroglioma with IDH1-R132H, intact ATRX, p53-negativity and partially deleted 1p/19q. At recurrence, histopathology showed low-grade mixed astrocytic and oligodendroglial features: the former with IDH1-R132H, ATRX loss, p53-positivity and intact 1p/19q and the latter showing IDH1-R132H, intact ATRX, p53-negativity and 1p/19q codeletion. At second recurrence, histopathology was astrocytoma grade 4 with IDH1-R132H, ATRX loss, p53-positivity and intact 1p/19q. Notably, 1p/19q codeletion was acquired at recurrence and CDKN2A was deleted at second recurrence. These findings suggest insights into tumorigenesis: (1) gliomas with two distinct lineages might mix to produce "oligoastrocytoma"; and (2) 1p/19q codeletion and CDKN2A deletion might be acquired during chemo-radiotherapy. Ultimately, astrocytic and oligodendroglial clones might co-exist developmentally or these two lineages might share a common cell-of-origin, with IDH1-R132H as the shared molecular feature.

Accurate Preoperative Identification of Motor Speech Area as Termination of Arcuate Fasciculus Depicted by Q-Ball Imaging Tractography.

BACKGROUND: Tractography is one way to predict the distribution of cortical functional domains preoperatively. Diffusion tensor tractography (DTT) is commonly used in clinical practice, but is known to have limitations in delineating crossed fibers, which can be overcome by Q-ball imaging tractography (QBT). We aimed to compare the reliability of these 2 methods based on the spatial correlation between the arcuate fasciculus depicted by tractography and direct cortical stimulation during awake surgery. METHODS: In this study, 15 patients with glioma underwent awake surgery with direct cortical stimulation. Tractography was depicted in a three-dimensional computer graphic model preoperatively, which was integrated with a photograph of the actual brain cortex using our novel mixed-reality technology. The termination of the arcuate fasciculus depicted by either DTT or QBT and the results of direct cortical stimulation were compared, and sensitivity and specificity were calculated in speech-associated brain gyri: pars triangularis, pars opercularis, ventral precentral gyrus, and middle frontal gyrus. RESULTS: QBT had significantly better sensitivity and lower false-positive rate than DTT in the pars opercularis. The same trend was noted for the other gyri. CONCLUSIONS: QBT is more reliable than DTT in identification of the motor speech area and may be clinically useful in brain tumor surgery.

Development of a New Image-Guided Neuronavigation System: Mixed-Reality Projection Mapping Is Accurate and Feasible.

BACKGROUND: Image-guided systems improve the safety, functional outcome, and overall survival of neurosurgery but require extensive equipment. OBJECTIVE: To develop an image-guided surgery system that combines the brain surface photographic texture (BSP-T) captured during surgery with 3-dimensional computer graphics (3DCG) using projection mapping. METHODS: Patients who underwent initial surgery with brain tumors were prospectively enrolled. The texture of the 3DCG (3DCG-T) was obtained from 3DCG under similar conditions as those when capturing the brain surface photographs. The position and orientation at the time of 3DCG-T acquisition were used as the reference. The correct position and orientation of the BSP-T were obtained by aligning the BSP-T with the 3DCG-T using normalized mutual information. The BSP-T was combined with and displayed on the 3DCG using projection mapping. This mixed-reality projection mapping (MRPM) was used prospectively in 15 patients (mean age 46.6 yr, 6 males). The difference between the centerlines of surface blood vessels on the BSP-T and 3DCG constituted the target registration error (TRE) and was measured in 16 fields of the craniotomy area. We also measured the time required for image processing. RESULTS: The TRE was measured at 158 locations in the 15 patients, with an average of 1.19 ± 0.14 mm (mean ± standard error). The average image processing time was 16.58 min. CONCLUSION: Our MRPM method does not require extensive equipment while presenting information of patients' anatomy together with medical images in the same coordinate system. It has the potential to improve patient safety.

Identification of the Facial Colliculus in Two-dimensional and Three-dimensional Images.

The facial colliculus (FC), an important landmark for planning a surgical approach to brainstem cavernous malformation (BCM), is a microstructure; therefore, it may be difficult to identify on magnetic resonance imaging (MRI). Three-dimensional (3D) images may improve the FC-identification certainty; hence, this study attempted to validate the FC-identification certainty between two-dimensional (2D) and 3D images of patients with a normal brainstem and those with BCM. In this retrospective study, we included 10 patients with a normal brainstem and 10 patients who underwent surgery for BCM. The region of the FC in 2D and 3D images was independently identified by three neurosurgeons, three times in each case, using the method for continuously distributed test results (0-100). The intra- and inter-rater reliability of the identification certainty were confirmed using the intraclass correlation coefficient (ICC). The FC-identification certainty for 2D and 3D images was compared using the Wilcoxon signed-rank test. The ICC (1,3) and ICC (3,3) in both groups ranged from 0.88 to 0.99; therefore, the intra- and inter-rater reliability were good. In both groups, the FC-identification certainty was significantly higher for 3D images than for 2D images (normal brainstem group; 82.4 vs. 61.5, P = .0020, BCM group; 40.2 vs. 24.6, P = .0059 for the unaffected side, 29.3 vs. 17.3, P = .0020 for the affected side). In the normal brainstem and BCM groups, 3D images had better FC-identification certainty. 3D images are effective for the identification of the FC.

A Novel Topical Fluorescent Probe for Detection of Glioblastoma.

PURPOSE: Five-aminolevulinic acid (5-ALA) is widely used as an intraoperative fluorescent probe for radical resection of high-grade glioma, and thus aids in extending progression-free survival of patients. However, there exist some cases where 5-ALA fails to fluoresce. In some other cases, it may undergo fluorescence quenching but cannot be orally readministered during surgery. This study aimed to develop a novel hydroxymethyl rhodamine green (HMRG)-based fluorescence labeling system that can be repeatedly administered as a topical spray during surgery for the detection of glioblastoma. EXPERIMENTAL DESIGN: We performed a three-stage probe screening using tumor lysates and fresh tumor tissues with our probe library consisting of a variety of HMRG probes with different dipeptides. We then performed proteome and transcript expression analyses to detect candidate enzymes responsible for cleaving the probe. Moreover, in vitro and ex vivo studies using U87 glioblastoma cell line were conducted to validate the findings. RESULTS: The probe screening identified proline-arginine-HMRG (PR-HMRG) as the optimal probe that distinguished tumors from peritumoral tissues. Proteome analysis identified calpain-1 (CAPN1) to be responsible for cleaving the probe. CAPN1 was highly expressed in tumor tissues which reacted to the PR-HMRG probe. Knockdown of this enzyme suppressed fluorescence intensity in U87 glioblastoma cells. In situ assay using a mouse U87 xenograft model demonstrated marked contrast of fluorescence with the probe between the tumor and peritumoral tissues. CONCLUSIONS: The novel fluorescent probe PR-HMRG is effective in detecting glioblastoma when applied topically. Further investigations are warranted to assess the efficacy and safety of its clinical use.

Development of Innovative Neurosurgical Operation Support Method Using Mixed-Reality Computer Graphics.

BACKGROUND: In neurosurgery, it is important to inspect the spatial correspondence between the preoperative medical image (virtual space), and the intraoperative findings (real space) to improve the safety of the surgery. Navigation systems and related modalities have been reported as methods for matching this correspondence. However, because of the influence of the brain shift accompanying craniotomy, registration accuracy is reduced. In the present study, to overcome these issues, we developed a spatially accurate registration method of medical fusion 3-dimensional computer graphics and the intraoperative brain surface photograph, and its registration accuracy was measured. METHODS: The subjects included 16 patients with glioma. Nonrigid registration using the landmarks and thin-plate spline methods was performed for the fusion 3-dimensional computer graphics and the intraoperative brain surface photograph, termed mixed-reality computer graphics. Regarding the registration accuracy measurement, the target registration error was measured by two neurosurgeons, with 10 points for each case at the midpoint of the landmarks. RESULTS: The number of target registration error measurement points was 160 in the 16 cases. The target registration error was 0.72 ± 0.04 mm. Aligning the intraoperative brain surface photograph and the fusion 3-dimensional computer graphics required ∼10 minutes on average. The average number of landmarks used for alignment was 24.6. CONCLUSIONS: Mixed-reality computer graphics enabled highly precise spatial alignment between the real space and virtual space. Mixed-reality computer graphics have the potential to improve the safety of the surgery by allowing complementary observation of brain surface photographs and fusion 3-dimensional computer graphics.

Correlation of Inflow Velocity Ratio Detected by Phase Contrast Magnetic Resonance Angiography with the Bleb Color of Unruptured Intracranial Aneurysms.

BACKGROUND: Intraoperative rupture is the most fatal and catastrophic complication of surgery for unruptured intracranial aneurysms (UIAs); thus, it is extremely useful to predict reddish and thin-walled regions of the UIA before surgery. Although several studies have reported a relationship between the hemodynamic characteristics and intracranial aneurysm wall thickness, a consistent opinion is lacking. We aimed to investigate the relationship between objectively and quantitatively evaluated bleb wall color and hemodynamic characteristics using phase-contrast magnetic resonance angiography (PC-MRA). METHODS: Ten patients diagnosed with UIA who underwent surgical clipping and preoperative magnetic resonance imaging along with PC-MRA were included in this study. Bleb wall color was evaluated from an intraoperative video. Based on the Red (R), Green, and Blue values, bleb wall redness (modified R value; mR) was calculated and compared with the hemodynamic characteristics obtained from PC-MRA. RESULTS: The wall redness distribution of 18 blebs in 11 UIAs in 10 patients was analyzed. Bleb/neck inflow velocity ratio (Vb/Va: r = 0.66, P = 0.003) strongly correlated with mR, whereas bleb/neck inflow rate ratio (r = 0.58, P = 0.012) correlated moderately. Multivariate regression analysis revealed that only Vb/Va (P = 0.017) significantly correlated with mR. There was no correlation between wall shear stress and mR. CONCLUSIONS: The bleb redness of UIAs and Vb/Va, calculated using PC-MRA, showed a significantly greater correlation. Thus, it is possible to predict bleb thickness noninvasively before surgery. This will facilitate more detailed pre- and intraoperative strategies for clipping and coiling for safe surgery.

Endoscopic transnasal resection of the CP angle schwannoma.

Cerebellopontine (CP) angle tumors are often resected via retrosigmoid craniotomy; however, sometimes cranial nerves (CNs) make their resection more complex. In such cases, the endoscopic transnasal approach can avoid such manipulations as delivering surgical instruments over CNs or peeling off CNs from the tumor, minimizing the risk of postoperative deficits. A 35-year-old man presented with a 37-mm cystic tumor in the right CP angle, and preoperative 3D fusion images revealed that multiple CNs (VII, VIII, and lower CNs) were running on the tumor posteriorly. The endoscopic transnasal approach enabled safe subtotal resection without causing neurological deficits, and the patient underwent stereotactic radiosurgery for the residual schwannoma. The video can be found here: https://youtu.be/xKLwdDsLpWA.

Reduced Neoantigen Expression Revealed by Longitudinal Multiomics as a Possible Immune Evasion Mechanism in Glioma.

Immune-based therapies have shown limited efficacy in glioma thus far. This might be at least in part due to insufficient numbers of neoantigens, thought to be targets of immune attack. In addition, we hypothesized that dynamic genetic and epigenetic tumor evolution in gliomas might also affect the mutation/neoantigen landscape and contribute to treatment resistance through immune evasion. Here, we investigated changes in the neoantigen landscape and immunologic features during glioma progression using exome and RNA-seq of paired primary and recurrent tumor samples obtained from 25 WHO grade II-IV glioma patients (glioblastoma, IDH-wild-type, n = 8; grade II-III astrocytoma, IDH-mutant, n = 9; and grade II-III oligodendroglioma, IDH-mutant, 1p/19q-codeleted, n = 8). The number of missense mutations, predicted neoantigens, or expressed neoantigens was not significantly different between primary and recurrent tumors. However, we found that in individual patients the ratio of expressed neoantigens to predicted neoantigens, designated the "neoantigen expression ratio," decreased significantly at recurrence (P = 0.003). This phenomenon was particularly pronounced for "high-affinity," "clonal," and "passenger gene-derived" neoantigens. Gene expression and IHC analyses suggested that the decreased neoantigen expression ratio was associated with intact antigen presentation machinery, increased tumor-infiltrating immune cells, and ongoing immune responses. Our findings imply that decreased expression of highly immunogenic neoantigens, possibly due to persistent immune selection pressure, might be one of the immune evasion mechanisms along with tumor clonal evolution in some gliomas.

Mining-Guided Machine Learning Analyses Revealed the Latest Trends in Neuro-Oncology.

In conducting medical research, a system which can objectively predict the future trends of the given research field is awaited. This study aims to establish a novel and versatile algorithm that predicts the latest trends in neuro-oncology. Seventy-nine neuro-oncological research fields were selected with computational sorting methods such as text-mining analyses. Thirty journals that represent the recent trends in neuro-oncology were also selected. As a novel concept, the annual impact (AI) of each year was calculated for each journal and field (number of articles published in the journal × impact factor of the journal). The AI index (AII) for the year was defined as the sum of the AIs of the 30 journals. The AII trends of the 79 fields from 2008 to 2017 were subjected to machine learning predicting analyses. The accuracy of the predictions was validated using actual past data. With this algorithm, the latest trends in neuro-oncology were predicted. As a result, the linear prediction model achieved relatively good accuracy. The predicted hottest fields in recent neuro-oncology included some interesting emerging fields such as microenvironment and anti-mitosis. This algorithm may be an effective and versatile tool for prediction of future trends in a particular medical field.