Information-guided Surgery Centered on Intraoperative Magnetic Resonance Imaging Guarantees Surgical Safety with Low Mortality.

Neurosurgery is complex surgery that requires a strategy that maximizes the removal of tumors and minimizes complications; thus, a safe environment during surgery should be guaranteed. In this study, we aimed to verify the safety of brain surgery using intraoperative magnetic resonance imaging (iMRI), based on surgical experience since 2000. Thus, we retrospectively examined 2,018 surgical procedures that utilized iMRI performed in the operating room at Tokyo Women's Medical University Hospital between March 2000 and October 2019. As per our data, glioma constituted the majority of the cases (1,711 cases, 84.8%), followed by cavernous hemangioma (61 cases, 3.0%), metastatic brain tumor (37 cases, 1.8%), and meningioma (31 cases, 1.5%). In total, 1,704 patients who underwent glioma removal were analyzed for mortality within 30 days of surgery and for reoperation rates and the underlying causes within 24 hours and 30 days of surgery. As per our analysis, only one death out of all the glioma cases (0.06%) was reported within the 30-day period. Meanwhile, reoperation within 30 days was performed in 37 patients (2.2%) due to postoperative bleeding in 17 patients (1.0%), infection in 12 patients (0.7%), hydrocephalus in 6 patients (0.4%), cerebrospinal fluid (CSF) leakage in 1 patient, and brain edema in 1 patient (0.06%). Of these, 14 cases (0.8%) of reoperation were performed within 24 hours, that is, 13 cases (0.8%) due to postoperative bleeding and 1 case (0.06%) due to acute hydrocephalus. Mortality rate within 30 days was less than 0.1%. Thus, information-guided surgery with iMRI can improve the safety of surgical resections, including those of gliomas.

Localization and symptoms associated with removal of negative motor area during awake surgery.

BACKGROUND: In awake surgery, cortical mapping may identify the negative motor area (NMA). However, since speech arrest occurs regardless of whether the NMA or the frontal language area (FLA) is stimulated, the presence of speech arrest alone does not distinguish the NMA from the FLA. Furthermore, the exact location and function of the NMA is not well understood. The purpose of this study was to more accurately locate the NMA in a group of cases in which the NMA and FLA could be identified in different brain gyri, and to describe symptoms in cases in which the NMA was removed. METHODS: There were 18 cases of awake surgery at our institution between 2000 and 2013 in which cortical stimulation allowed identification of FLA and NMA in separate brain gyri. In these cases, the pre- and post-removal mapping results were projected onto a 3D model postoperatively. We investigated the symptoms and social rehabilitation in a case in which the tumour invaded the same brain gyrus as the NMA and the NMA had to be resected in combination with the tumour. RESULTS: In cases where the NMA and FLA could be identified in different brain gyri, NMA was localized inferior to the precentral gyrus in all cases. In four cases where NMA was removed with the tumour, apraxia of speech was observed during the surgery; the same symptoms persisted after it, but it improved within a few months, and the patients were able to return to work. CONCLUSION: In cases where NMA and FLA could be identified separately by awake mapping, the NMA was commonly localized inferior to the precentral gyrus. When NMAs were resected in combination with tumour invasion, they did not lead to serious, long-term complications.

Increase in serum vimentin levels in patients with glioma and its correlation with prognosis of patients with glioblastoma.

Early diagnosis of glioma is of great value to improve prognosis. We focused on serum vimentin levels as a useful biomarker for preoperative diagnosis. The aim of this study was to determine whether serum vimentin levels in patients with glioma are significantly higher than those of healthy adult volunteer and whether the serum vimentin level is associated with overall survival (OS) in patients with glioblastoma (GBM). This study included 52 consecutive patients with newly diagnosed glioma and a control group of 13 healthy adult volunteers. We measured serum vimentin levels in blood samples obtained from patients with glioma preoperatively and a control group. Furthermore, we investigated the correlation between serum vimentin levels and OS in patients with GBM. The serum vimentin levels of patients with glioma were significantly higher than those of the control group. The serum vimentin level of 2.9 ng/ml was the optimal value for differentiating patients with glioma from the control group with a sensitivity of 92.3% and specificity of 88.5%. The serum vimentin levels correlated significantly with immunoreactivity for survivin. In 27 patients with GBM, serum vimentin levels (cutoff value, median value 53.3 ng/ml) correlated with OS in univariate and multivariate analyses. Our study revealed that serum vimentin levels of patients with glioma are significantly higher than those of the control group. Therefore, we believe that serum vimentin level might be a useful and practical biomarker for preoperative diagnosis of glioma. Furthermore, high serum vimentin levels correlated significantly with shorter OS in patients with GBM.

Corrigendum: Photodynamic therapy for malignant brain tumors in children and young adolescents.

[This corrects the article DOI: 10.3389/fonc.2022.957267.].

Tumor volume and calcifications as indicators for preoperative differentiation of grade II/III diffuse gliomas.

PURPOSE: To retrospectively evaluate preoperative clinical factors for their ability to preoperatively differentiate malignancy grades in patients with incipient supratentorial grade II/III diffuse gliomas. METHODS: This retrospective study included 206 adult patients with incipient supratentorial grade II/III diffuse gliomas according to the 2016 World Health Organization classification of tumors of the central nervous system. The cohort included 136 men and 70 women, with a median age of 41 years. Preoperative factors included age, sex, presence of calcifications on computed tomography scans, and preoperative tumor volume measured using preoperative magnetic resonance imaging. RESULTS: In patients with oligodendrogliomas (IDH-mutant and 1p/19q-codeleted), calcifications were significantly more frequent (p = 0.0034) and tumor volume was significantly larger (p < 0.001) in patients with grade III tumors than in those with grade II tumors. Moreover, in patients with IDH-mutant astrocytomas, preoperative tumor volume was significantly larger (p = 0.0042) in patients with grade III tumors than in those with grade II tumors. In contrast, none of the evaluated preoperative clinical factors were significantly different between the patients with grade II and III IDH-wildtype astrocytomas. CONCLUSION: In adult patients with suspicison incipient supratentorial grade II/III diffuse gliomas, presence of calcifications and larger preoperative tumor volume might be used as preoperative indices to differentiate between malignancy grades II and III in oligodendrogliomas (IDH-mutant and 1p/19q-codeleted) and larger preoperative tumor volume might have similar utility in IDH-mutant astrocytomas.

A multicenter, randomized, placebo-controlled phase IIb trial of an autologous formalin-fixed tumor vaccine for newly diagnosed glioblastomas.

OBJECTIVE: An autologous formalin-fixed tumor vaccine (AFTV) derived from resected glioblastoma (GBM) tissue can be used against unidentified tumor antigens. Thus, the authors conducted a multicenter double-blind phase IIb trial to investigate the efficacy of an AFTV. METHODS: Eligible patients were adults with supratentorial GBMs, 16-75 years of age, with Karnofsky Performance Scale (KPS) scores ≥ 60%, and no long-term steroid administration. An AFTV comprising fixed paraffin-embedded tumor tissue with immune adjuvants or an identical placebo without fixed tumor tissue was injected intradermally over three courses before and after chemoradiotherapy. The primary and secondary end points were overall survival (OS), progression-free survival (PFS), and 3-year survival rate. RESULTS: Sixty-three patients were enrolled. The average patient age was 61 years. The median KPS score was 80%, and the median resection rate was 95%. The full analysis set of 57 patients indicated no significant difference in OS (p = 0.64) for the AFTV group (median OS 25.6 months, 3-year OS rate 38%) compared with the placebo group (31.5 months and 41%, respectively) and no difference in PFS (median PFS 13.3 months in both groups, p = 0.98). For patients with imaging-based total tumor removal, the 3-year PFS rate was 81% in the AFTV group versus 46% in the placebo group (p = 0.067), whereas the 3-year OS rate was 80% versus 54% (p = 0.16), respectively. Similar results were obtained in the p53-negative subgroups. Severe adverse effects were not observed. CONCLUSIONS: The AFTV may have potential effects in certain patient subgroups. A phase III study for patients with total tumor removal remains warranted to confirm these findings. Clinical trial registration no.: UMIN000010602 (UMIN Clinical Trials Registry).

Relationship between characteristics of glioma treatment and surgical site infections.

PURPOSE: Surgical site infections (SSIs) after neurosurgery are common in daily practice. Although numerous reports have described SSIs in neurosurgery, reports specific to gliomas are limited. This study aimed to investigate the relationship between SSIs and glioma treatment characteristics, such as reoperations, radiation therapy, and chemotherapy. METHODS: We examined 1012 consecutive patients who underwent craniotomy for glioma between November 2013 and March 2022. SSIs were defined as infections requiring reoperation during the observation period, regardless of their location. We retrospectively analyzed SSIs and patient factors. RESULTS: During the observation period, SSIs occurred in 3.1% (31/1012). In the univariate analysis, three or more surgeries (P = 0.007) and radiation therapy (P = 0.03) were associated with SSIs, whereas intraoperative magnetic resonance imaging (MRI) was not significantly associated (P = 0.35). Three or more surgeries and radiation therapy were significantly correlated with each other (P < .0001); therefore, they were analyzed separately in the multivariate analysis. Three or more surgeries were an independent factor triggering SSIs (P = 0.02); in contrast, radiation therapy was not an independent factor for SSIs (P = 0.07). Several SSIs localized in the skin occurred more than 1 year after surgery. CONCLUSIONS: Undergoing three or more surgeries for glioma is an independent risk factor for SSIs. Glioma SSIs can occur long after surgery. These results are considered characteristic of gliomas. We recommend careful long-term observation of patients at a high risk of SSIs.

Construction of brain area risk map for decision making using surgical navigation and motor evoked potential monitoring information.

PURPOSE: Surgical devices or systems typically operate in a stand-alone manner, making it difficult to perform integration analysis of both intraoperative anatomical and functional information. To address this issue, the intraoperative information integration system OPeLiNK® was developed. The objective of this study is to generate information for decision making using surgical navigation and intraoperative monitoring information accumulated in the OPeLiNK® database and to analyze its utility. METHODS: We accumulated intraoperative information from 27 brain tumor patients who underwent resection surgery. First, the risk rank for postoperative paralysis was set according to the attenuation rate and amplitude width of the motor evoked potential (MEP). Then, the MEP and navigation log data were combined and plotted on an intraoperative magnetic resonance image of the individual brain. Finally, statistical parametric mapping (SPM) transformation was performed to generate a standard brain risk map of postoperative paralysis. Additionally, we determined the anatomical high-risk areas using atlases and analyzed the relationship with each set risk rank. RESULTS: The average distance between the navigation log corresponding to each MEP risk rank and the anatomical high-risk area differed significantly between the with postoperatively paralyzed and without postoperatively paralyzed groups, except for "safe." Furthermore, no excessive deformation was observed resulting from SPM conversion to create the standard brain risk map. There were cases in which no postoperative paralysis occurred even when MEP decreased intraoperatively, and vice versa. CONCLUSION: The time synchronization reliability of the study data is very high. Therefore, our created risk map can be reported as being functional at indicating the risk areas. Our results suggest that the statistical risks of postoperative complications can be presented for each area where brain surgery is to be performed. In the future, it will be possible to provide surgical navigation with intraoperative support that reflects the risk maps created.

Photodynamic therapy for malignant brain tumors in children and young adolescents.

Photodynamic therapy (PDT) targets tumor cell remnants after resection. Here, we evaluated the feasibility of PDT for malignant brain tumors in children and young adolescents. This was a single-center, non-randomized, phase I/II clinical study. The primary endpoints were the safety of treatment with talaporfin sodium (TS) (phase I) and overall survival (OS) after PDT (phase II). The secondary endpoint was progression-free survival (PFS) after PDT. The TS dose was determined by dose escalation from 10 to 20 to 40 mg/m2 for every three cases starting from the initial enrolled case. Eight patients with a mean age of 170.2 months (129-214 months) at the time of PDT received nine procedures with a mean follow-up duration of 16.8 months (1-42 months) after PDT. Histopathological diagnoses included supratentorial anaplastic ependymoma (n = 2), anaplastic astrocytoma (n = 1), diffuse midline glioma with H3K27M mutation (n = 1), glioblastoma (n = 3), and pediatric high-grade glioma (n = 1). The outcome was survival in five patients and death in three patients. Recurrence occurred in six of the eight patients; the remaining two were recurrence-free after PDT. Therefore, OS and PFS were calculated as 21 and 6 months, respectively. Seizures and fevers, which were likely surgery-related symptoms, were commonly observed. Photosensitive skin rashes or liver dysfunction, which are common adverse effects in adults, were not observed. Our results showed that TS can be used safely in children at doses comparable to those used in adults, as there was no major complication associated with TS administration. However, we cannot make a definitive conclusion about the efficacy of PDT because of the small number of participants. Accumulating cases was difficult because of the rarity of pediatric brain tumors and the difficulty in making a preoperative differential diagnosis, considering the wide range of histopathological findings. Moreover, the psychological stress associated with light-shielding management in pediatric patients was more severe than initially expected. In conclusion, TS at doses comparable to those used in adults may be safe for use in children and young adolescents between the ages of 6 and 20 years. However, further studies are needed to clarify its efficacy.

Monitoring Cortico-cortical Evoked Potentials Using Only Two 6-strand Strip Electrodes for Gliomas Extending to the Dominant Side of Frontal Operculum During One-step Tumor Removal Surgery.

OBJECTIVE: Resection of the dominant side of gliomas extending to the frontal operculum has high risk of severe language dysfunction. Here, we report recording cortico-cortical evoked potentials (CCEP) using only two 6-strand strip electrodes to monitor language-related fibers intraoperatively. We examined whether this simple procedure is useful for removing gliomas extending to the dominant side of frontal operculum. METHODS: This study included 7 cases of glioma extending to the left frontal operculum. The frontal language area (FLA) was first identified by functional mapping during awake craniotomy. Next, a 6-strand strip electrode was placed on the FLA, while on the temporal side, an electrode was placed so as to slide parallel to the sylvian fissure toward the posterior language area. Electrical stimulation was performed using the electrode on the frontal side, and CCEPs were measured from the electrode on the temporal side. RESULTS: CCEPs were detected in all cases. Immediately after surgery, all patients demonstrated language dysfunction to varying degree. CCEP decreased to 10% in 1 patient, who recovered language function after 24 months. CCEP decreased slightly 80% in 1, and, in the 5 other cases, CCEPs did not change. These 5 patients soon recovered language function within 2 weeks to 1 month. CONCLUSIONS: This study confirmed the utility of CCEP monitoring using only two 6-strand strip electrodes during one-step surgery. We believe this simple method helped in monitoring intraoperative language function and predicting its postoperative recovery in patients with gliomas extending to the dominant side of frontal operculum.

The high incidence and risk factors of levetiracetam and lacosamide-related skin rashes in glioma patients.

OBJECTIVE: Antiseizure drug (ASD)-induced skin rash remains the main side effect of seizure management in patients with glioma. New generations of ASDs, such as levetiracetam (LEV) and lacosamide (LCM) are associated with less frequent skin rashes than conventional ASDs. However, there are few reports regarding the incidence of skin rashes by LEV and LCM in patients with glioma. Therefore, the aim of this study was to investigate the incidence and risk factors of LEV- and LCM-associated skin rashes in patients with glioma. METHODS: We compared the incidence of ASD-associated skin rash between 353 patients with glioma and 125 patients with meningioma, who received LEV or LCM and underwent surgery between 2017 and 2019 at our institution. Furthermore, to evaluate the association between potential risk factors and ASD-associated skin rashes, univariate and multivariate analyses were performed. RESULTS: The incidence of ASD-associated skin rash in patients with glioma was higher (11 %) than in those with meningiomas (1.6 %). The multivariate regression analysis showed that adjuvant treatment with radiotherapy (p = 0.023) and a history of drug allergy (p = 0.023) were significant risk factors for ASD-associated skin rash. The rate of ASD-related skin rashes in patients with glioma was also higher than the previously reported rates of 1-3 % in patients with epilepsy. CONCLUSION: Our results indicate that adjuvant treatment with radiotherapy and a history of drug allergy correlated with a high incidence of ASD-related skin rashes in patients with glioma who receive LEV and LCM. Patients with these two factors should be carefully checked for skin rashes.

Therapeutic Options for Recurrent Glioblastoma-Efficacy of Talaporfin Sodium Mediated Photodynamic Therapy.

Recurrent glioblastoma (GBM) remains one of the most challenging clinical issues, with no standard treatment and effective treatment options. To evaluate the efficacy of talaporfin sodium (TS) mediated photodynamic therapy (PDT) as a new treatment for this condition, we retrospectively analyzed 70 patients who underwent surgery with PDT (PDT group) for recurrent GBM and 38 patients who underwent surgery alone (control group). The median progression-free survival (PFS) in the PDT and control groups after second surgery was 5.7 and 2.2 months, respectively (p = 0.0043). The median overall survival (OS) after the second surgery was 16.0 and 12.8 months, respectively (p = 0.031). Both univariate and multivariate analyses indicated that surgery with PDT and a preoperative Karnofsky Performance Scale were significant independent prognostic factors for PFS and OS. In the PDT group, there was no significant difference regarding PFS and OS between patients whose previous pathology before recurrence was already GBM and those who had malignant transformation to GBM from lower grade glioma. There was also no significant difference in TS accumulation in the tumor between these two groups. According to these results, additional PDT treatment for recurrent GBM could have potential survival benefits and its efficacy is independent of the pre-recurrence pathology.

Impact of awake mapping on overall survival and extent of resection in patients with adult diffuse gliomas within or near eloquent areas: a retrospective propensity score-matched analysis of awake craniotomy vs. general anesthesia.

PURPOSE: Awake craniotomy (AC) with intraoperative mapping is the best approach to preserve neurological function for glioma surgery in eloquent or near eloquent areas, but whether AC improves the extent of resection (EOR) and overall survival (OS) is controversial. This study aimed to compare the long-term clinical outcomes of glioma resection under AC with those under general anesthesia (GA). METHODS: Data of 335 patients who underwent surgery with intraoperative magnetic resonance imaging for newly diagnosed gliomas of World Health Organization (WHO) grades II-IV between 2000 and 2013 were reviewed. EOR and OS were quantitatively compared between the AC and GA groups after 1:1 propensity score matching. The two groups were matched for age, preoperative Karnofsky performance status (KPS), tumor location, and pathology. RESULTS: After propensity score matching, 91 pairs were obtained. The median EOR was 96.1% (interquartile range [IQR] 7.3) and 97.4% (IQR 14.4) in the AC and GA groups, respectively (p = 0.31). Median KPS score 3 months after surgery was 90 (IQR 20) in both groups (p = 0.384). The median survival times were 163.3 months (95% confidence interval [CI] 77.9-248.7) and 143.5 months (95% CI 94.4-192.7) in the AC and GA groups, respectively (p = 0.585). CONCLUSION: Even if the glioma was within or close to the eloquent area, AC was comparable with GA in terms of EOR and OS. In case of difficulties in randomizing patients with eloquent or near eloquent glioma, our propensity score-matched analysis provides retrospective evidence that AC can obtain EOR and OS equivalent to removing glioma under GA.

Awake craniotomy with transcortical motor evoked potential monitoring for resection of gliomas within or close to motor-related areas: validation of utility for predicting motor function.

OBJECTIVE: The authors previously showed that combined evaluation of changes in intraoperative voluntary movement (IVM) during awake craniotomy and transcortical motor evoked potentials (MEPs) was useful for predicting postoperative motor function in 30 patients with precentral gyrus glioma. However, the validity of the previous report is limited to precentral gyrus gliomas. Therefore, the current study aimed to validate whether the combined findings of IVM during awake craniotomy and transcortical MEPs were useful for predicting postoperative motor function of patients with a glioma within or close to motor-related areas and not limited to the precentral gyrus. METHODS: The authors included 95 patients with gliomas within or close to motor-related areas who were treated between April 2000 and May 2020. All tumors were resected with IVM monitoring during awake craniotomy and transcortical MEP monitoring. Postoperative motor function was classified into four categories: "no change" or "declined," the latter of which was further categorization as "mild," "moderate," or "severe." The authors defined moderate and severe deficits as those that impact daily life. RESULTS: Motor function 6 months after surgery was classified as no change in 71 patients, mild in 18, moderate in 5, and severe in 1. Motor function at 6 months after surgery significantly correlated with IVM (p < 0.0001), transcortical MEPs (decline ≤ or > 50%) (p < 0.0001), age, preoperative motor dysfunction, extent of resection, and ischemic change on postoperative MRI. Thirty-two patients with no change in IVM showed no change in motor function at 6 months after surgery. Five of 34 patients (15%) with a decline in IVM and a decline in MEPs ≤ 50% had motor dysfunction with mild deficits 6 months after surgery. Furthermore, 19 of 23 patients (83%) with a decline in IVM and decline in MEPs > 50% had a decline in motor function, including 13 patients with mild, 5 with moderate, and 1 with severe deficits. Six patients with moderate or severe deficits had the lowest MEP values, at < 100 µV. CONCLUSIONS: This study validated the utility of combined application of IVM during awake craniotomy and transcortical MEP monitoring to predict motor function at 6 months after surgery in patients with a glioma within or close to motor-related areas, not limited to the precentral gyrus. The authors also validated the usefulness of the cutoff value, 100 µV, in MEP monitoring.

Utility of intraoperative magnetic resonance imaging for giant cell tumor of bone after denosumab treatment: a pilot study.

BACKGROUND: Giant cell tumor of bone (GCTB) is an intermediate but locally aggressive neoplasm. Current treatment of high-risk GCTB involves administration of denosumab, which inhibits bone destruction and promotes osteosclerosis. However, denosumab monotherapy is not a curative treatment for GCTB and surgical treatment remains required. Denosumab treatment complicates surgery, and the recurrence rate of GCTB is high (20%-30%). PURPOSE: To examine the utility of intraoperative magnetic resonance imaging (iMRI) for detection and reduction of residual tumor after denosumab treatment and to investigate the utility of iMRI, which is not yet widely used. MATERIAL AND METHODS: We enrolled five patients who received denosumab for a median period of eight months (range 6-12 months). Surgery was performed when the degree of osteosclerosis around the articular surface was deemed appropriate. We performed iMRI using a modified operation table to identify residual tumor after initial curettage and evaluated the rate of detection of residual tumor by iMRI, intraoperative and postoperative complications, exposure time of iMRI, and operation time. RESULTS: Suspected residual tumor tissue was identified in all five cases and was confirmed by histopathology after additional curettage. The rate of detection of residual tumor by iMRI was 100%. Residual tumor was located in sites which were difficult to remove due to osteosclerosis. The iMRI was performed safely and without trouble. During the median follow-up period of 10 months (range 6-24 months), no adverse events or recurrences occurred. CONCLUSION: Intraoperative MRI could contribute to the reduction of residual tumor tissue and it may prevent recurrence of GCTB after denosumab therapy.

Mucosal thickening of the maxillary sinus is frequently associated with diffuse glioma patients and correlates with poor survival prognosis of GBM patients: comparative analysis to meningioma patients.

Glioma patients were frequently associated with mucosal thickening of the maxillary sinus (MTMS), which reflects mucosal inflammation. We suspected that MTMS is associated with impaired mucosal immune response and correlated with dysfunction in the anti-tumor immune response in diffuse glioma patients. Therefore, the aim of this study was to determine whether the occurrence of diffuse glioma is correlated with MTMS compared to meningioma and control groups. Furthermore, we investigated whether MTMS is associated with overall survival (OS) in glioblastoma (GBM) patients. This study included 343 patients with newly diagnosed diffuse gliomas and 218 patients with meningioma treated at our institution between 2015 and 2018. As control, 201 patients with headache who did not have an intracranial organic lesion were included. Using three-axis MR images, we evaluated the incidence of MTMS in all patients. Additionally, we investigated the relationship between MTMS and OS. The incidence of MTMS in patients with diffuse glioma was significantly higher than that in the meningioma (p < .0001) and control groups (p < .0001). In 128 patients with GBM, MTMS status correlated significantly with OS (p = .0064). We revealed that the incidence of MTMS is significantly associated with patients with diffuse glioma. This suggests that MTMS is indirectly involved in the occurrence of diffuse gliomas. Furthermore, the presence of MTMS correlated significantly with shorter OS in GBM patients, indicating that MTMS is involved in suppression of anti-tumor immune response. Preoperative recognition of MTMS might be useful for improving the clinical management of GBM patients.

Combining Pre-operative Diffusion Tensor Images and Intraoperative Magnetic Resonance Images in the Navigation Is Useful for Detecting White Matter Tracts During Glioma Surgery.

PURPOSE: We developed a navigation system that superimposes the fractional anisotropy (FA) color map of pre-operative diffusion tensor imaging (DTI) and intraoperative magnetic resonance imaging (MRI). The current study aimed to investigate the usefulness of this system for neurophysiological monitoring and examination under awake craniotomy during tumor removal. METHOD: A total of 10 glioma patients (4 patients with right-side tumors; 5 men and 5 women; average age, 34 years) were evaluated. Among them, the tumor was localized to the frontal lobe, insular cortex, and parietal lobe in 8, 1, and 1 patient, respectively. There were 3 patients who underwent surgery on general anesthesia, while 7 patients underwent awake craniotomy. The index of DTI anisotropy taken pre-operatively (magnetic field: 3 tesla, 6 motion probing gradient directions) was analyzed as a color map (FA color map) and concurrently co-registered in the intraoperative MRI within the navigation. In addition to localization of the bipolar coagulator and the cortical stimulator for brain mapping on intraoperative MRI, the pre-operative FA color map was also concurrently integrated and displayed on the navigation monitor. This white matter nerve functional information was confirmed directly by using neurological examination and referring to the electrophysiological monitoring. RESULTS: Intraoperative MRI, integrated pre-operative FA color map, and microscopic surgical view were displayed on one screen in all 10 patients, and white matter fibers including the pyramidal tract were displayed as a reference in blue. Regarding motor function, motor-evoked potential was monitored as appropriate in all cases, and removal was possible while directly confirming motor symptoms under awake craniotomy. Furthermore, the white matter fibers including the superior longitudinal fasciculus were displayed in green. Importantly, it was useful not only to localize the resection site, but to identify language-related, eye movement-related, and motor fibers at the electrical stimulation site. All motor and/or language white matter tracts were identified and visualized with the co-registration and then with an acceptable post-operative neurological outcome. CONCLUSION: Co-registering an intraoperative MR images and a pre-operative FA color map is a practical and useful method to predict the localization of critical white matter nerve functions intraoperatively in glioma surgery.

Correlation between localization of supratentorial glioma to the precentral gyrus and difficulty in identification of the motor area during awake craniotomy.

OBJECTIVE: Identification of the motor area during awake craniotomy is crucial for preservation of motor function when resecting gliomas located within or close to the motor area or the pyramidal tract. Nevertheless, sometimes the surgeon cannot identify the motor area during awake craniotomy. However, the factors that influence failure to identify the motor area have not been elucidated. The aim of this study was to assess whether tumor localization was correlated with a negative cortical response in motor mapping during awake craniotomy in patients with gliomas located within or close to the motor area or pyramidal tract. METHODS: Between April 2000 and May 2019 at Tokyo Women's Medical University, awake craniotomy was performed to preserve motor function in 137 patients with supratentorial glioma. Ninety-one of these patients underwent intraoperative cortical motor mapping for a primary glioma located within or close to the motor area or pyramidal tract and were enrolled in the study. MRI was used to evaluate whether or not the tumors were localized to or involved the precentral gyrus. The authors performed motor functional mapping with electrical stimulation during awake craniotomy and evaluated the correlation between identification of the motor area and various clinical characteristics, including localization to the precentral gyrus. RESULTS: Thirty-four of the 91 patients had tumors that were localized to the precentral gyrus. The mean extent of resection was 89.4%. Univariate analyses revealed that identification of the motor area correlated significantly with age and localization to the precentral gyrus. Multivariate analyses showed that older age (≥ 45 years), larger tumor volume (> 35.5 cm3), and localization to the precentral gyrus were significantly correlated with failure to identify the motor area (p = 0.0021, 0.0484, and 0.0015, respectively). Localization to the precentral gyrus showed the highest odds ratio (14.135) of all regressors. CONCLUSIONS: Identification of the motor area can be difficult when a supratentorial glioma is localized to the precentral gyrus. The authors' findings are important when performing awake craniotomy for glioma located within or close to the motor area or the pyramidal tract. A combination of transcortical motor evoked potential monitoring and awake craniotomy including subcortical motor mapping may be needed for removal of gliomas showing negative responses in the motor area to preserve the motor-related subcortical fibers.

Impact of connectivity between the pars triangularis and orbitalis on identifying the frontal language area in patients with dominant frontal gliomas.

We have previously revealed that identification of the frontal language area (FLA) can be difficult in patients with dominant frontal glioma involving the pars triangularis (PT). The present study added new cases and performed additional analyses. We noticed a new finding that the presence of extension to the pars orbitalis (POr) was associated with negative response to the FLA. The aim of the present study was to evaluate the impact of PT involvement with extension to the POr on the failure to identify the FLA. From 2000 to 2017, awake craniotomy was performed on 470 patients. Of these patients, the present study included 148 consecutive patients with frontal glioma on the dominant side. We evaluated whether tumors involved the PT or extended to the POr. Thirty one of 148 patients showed involvement of the PT, and we examined the detailed characteristics of these 31 patients. The rate of negative response for the FLA was 61% in patients with involvement of the PT. In 31 patients with frontal glioma involving the PT, univariate analyses showed significant correlation between extension to the POr and failure to identify the FLA (P = 0.0070). Similarly, multivariate analysis showed only extension to the POr correlated significantly with failure to identify the FLA (P = 0.0129). We found new evidence that extension to the POr which impacts connectivity between the PT and POr correlated significantly with negative response to the FLA of patients with dominant frontal glioma.

Prediction of lower-grade glioma molecular subtypes using deep learning.

INTRODUCTION: It is useful to know the molecular subtype of lower-grade gliomas (LGG) when deciding on a treatment strategy. This study aims to diagnose this preoperatively. METHODS: A deep learning model was developed to predict the 3-group molecular subtype using multimodal data including magnetic resonance imaging (MRI), positron emission tomography (PET), and computed tomography (CT). The performance was evaluated using leave-one-out cross validation with a dataset containing information from 217 LGG patients. RESULTS: The model performed best when the dataset contained MRI, PET, and CT data. The model could predict the molecular subtype with an accuracy of 96.6% for the training dataset and 68.7% for the test dataset. The model achieved test accuracies of 58.5%, 60.4%, and 59.4% when the dataset contained only MRI, MRI and PET, and MRI and CT data, respectively. The conventional method used to predict mutations in the isocitrate dehydrogenase (IDH) gene and the codeletion of chromosome arms 1p and 19q (1p/19q) sequentially had an overall accuracy of 65.9%. This is 2.8 percent point lower than the proposed method, which predicts the 3-group molecular subtype directly. CONCLUSIONS: A deep learning model was developed to diagnose the molecular subtype preoperatively based on multi-modality data in order to predict the 3-group classification directly. Cross-validation showed that the proposed model had an overall accuracy of 68.7% for the test dataset. This is the first model to double the expected value for a 3-group classification problem, when predicting the LGG molecular subtype.