FLGS-02. What is the role of intraoperative MRI when performing a high-grade glioma resection using 5-ALA? A single center series reporting extent of resection of contrast-enhancing tumor and FLAIR signal abnormality with clinical outcomes

OBJECTIVE Use of intraoperative MRI (iMRI) and 5-ALA together is poorly investigated although both appear individually superior to standard resection alone in meta-analyses. METHODS We identified 54 patients who underwent 5-ALA guided resection of an intracranial high-grade glioma. Intraoperative ultrasound and frameless stereotactic neuronavigation with tractography were used in all cases. iMRI was selectively used in 33 cases. MRI scans were used to measure extent of resection (EOR) of T1-weighted contrast enhancing (T1WCE) tumor and FLAIR signal abnormality. Clinical data were collected prospectively and survival data retrospectively. RESULTS The mean EOR of T1WCE tumor was 93.7% (range 38 – 100%) with mean residual volume of 2.2 cc. The mean EOR of FLAIR signal abnormality was 59% (range 15–100%) with mean residual volume of 35.7 cc. Compared to using 5-ALA alone, using iMRI+5-ALA did not reduce the volume of residual T1WCE tumor (Mann-Whitney U, p = 0.557) and no more patients achieved complete resection (14/21 vs. 24/33, Chi-Square, p = 0.634). The volume of residual FLAIR signal abnormality was no different (Mann-Whitney U, p= 0.081) but more patients in the 5-ALA+iMRI group achieved resection of >53.21% of the FLAIR signal abnormality, which is known to be a predictor of improved prognosis (20/31 vs 5/21, Chi-Square, p = 0.004*). There was no difference in new neurological deficits at 30 days (Fisher’s exact test, p=0.549). Median OS was 14.3 months and median PFS was 5.2 months. There were no significant differences in OS or PFS between patients operated with iMRI in addition to 5-ALA. CONCLUSIONS 5-ALA and iMRI both assist in safely maximizing EOR when combined with adjuncts such as awake craniotomy and cortical/subcortical mapping. The role and interaction of these two technologies needs further study to understand whether they are additive and what their influence on clinical outcomes is.

ITVT-08. Combined use of awake surgery and intraoperative MRI augments extent of resection in eloquent gliomas without neurological impairment

Maximizing the extent of resection (EOR) while preserving functional integrity is a mainstay of glioma surgery. Intraoperative MRI (iMRI) helps to augment the EOR. However, in eloquently located gliomas the significance of iMRI is controversial since the EOR is limited by functional rather than image-based boundaries. Thus, we sought to determine the impact of iMRI in our institutional series of awake glioma resections within or adjacent to eloquent (language, motor, sensory) areas since the implementation of a 1.5 Tesla iMRI in 2009. Tumor- and procedure-related data and functional outcome were assessed through medical charts review. The EOR was determined volumetrically on pre-, intra- and postoperative T1 contrast-enhanced (CE) and FLAIR MR images. 131 of 166 awake surgeries (79%) were performed under iMRI-guidance with concurrent language (n=72) and/or motor (n=50) mapping. iMRI was done when functional boundaries were reached (62%), for resection control (28%) or for other reasons (10%). Additional resection after iMRI (AR) was performed in 63 cases (73%); otherwise resection was terminated because the targeted EOR or functional boundaries were reached. New or deteriorated neurological deficits occurred in 20 patients prior and 15 patients post iMRI; however, all but 3 resolved within 6 months. Median EOR significantly increased after AR from 92.6% to 98.4% (∆5.8%; p<0.0001) in CE tumors and from 64.5% to 85.8% (∆21.3%; p<0.0001) in non-enhancing tumors. Remarkably, the reason to perform iMRI (resection control or functional limitations), did not affect the frequency of AR, deficits acquired post iMRI or the increase in EOR after AR. In conclusion, iMRI is a valuable adjunct to maximize the EOR in awake glioma resections without increasing the risk for functional impairment, particularly in non-enhancing tumors. Importantly, iMRI contributes to a maximized EOR even in cases where the resection had to be stopped because functional boundaries were reached.

ITVT-04. Management of intraoperative technological advances [intraoperative MRI, neuronavigation system using PET, and 5-aminolevulinic acid (5-ALA)–induced fluorescence image-guided surgery] for glioblastoma

OBJECTIVE The maximum resection of Glioblastoma (GBM) is the standard therapy and is expected to improve prognosis. Image-guided surgery using a neuronavigation system is the standard technique for glioma. However, due to the brain shift during surgery, intraoperative technologies, such as 5-ALA fluorescence and intraoperative MRI (IoMRI), are employed. Radiotracers are used during positron emission tomography (PET) for metabolic imaging and assist the evaluation of glioma metabolism. We compared the effectiveness of these intraoperative technologies. METHODS Between January 2016 and May 2021, 52 patients with gliomas underwent IoMRI. 21 patients were selected for 5-ALA fluorescence-guided resection of GBM and underwent multiple PET studies (MET, FLT, and FMISO). We graded fluorescence level as strong, vague, or none. Following tumor resection, we identified the fluorescence level and evaluated the residual volume of gadolinium-enhanced T1WI (T1-Gd) on IoMRI and at each PET study. After calculating the extent of resection (EOR) for T1-Gd, we compared the residual volume on T1-Gd for IoMRI and each PET study, between EOR ≥ 93% and EOR < 93%. RESULTS We detected strong 5-ALA fluorescence during induction and before tumor resection in all 21 (100%) patients with a newly-diagnosed and histopathologically-confirmed GBM. Following tumor resection, we noted an EOR ≥ 93% for T1-Gd in 12 cases (vague, 4; none, 8) and an EOR < 93% for T1-Gd in 9 cases (vague, 5; none, 4). The compared median residual volume (mL) with no fluorescence between EOR ≥ 93% and EOR < 93% for T1-Gd were T1-Gd (0.22, 0.74), MET (0.29, 3.31), FLT (0.24, 1.77), and FMISO (0.22, 1.02). CONCLUSIONS GBM cells are difficult to distinguish in cases without 5-ALA fluorescence. For cases without 5-ALA fluorescence, we were able to maximize the resection of GBM by extracting the area of MET accumulation.

Challenges and Opportunities of Intraoperative 3D Ultrasound With Neuronavigation in Relation to Intraoperative MRI

IntroductionNeuronavigation greatly improves the surgeon’s ability to approach, assess and operate on brain tumors, but tends to lose its accuracy as the surgery progresses and substantial brain shift and deformation occurs. Intraoperative MRI (iMRI) can partially address this problem but is resource intensive and workflow disruptive. Intraoperative ultrasound (iUS) provides real-time information that can be used to update neuronavigation and provide real-time information regarding the resection progress. We describe the intraoperative use of 3D iUS in relation to iMRI, and discuss the challenges and opportunities in its use in neurosurgical practice.MethodsWe performed a retrospective evaluation of patients who underwent image-guided brain tumor resection in which both 3D iUS and iMRI were used. The study was conducted between June 2020 and December 2020 when an extension of a commercially available navigation software was introduced in our practice enabling 3D iUS volumes to be reconstructed from tracked 2D iUS images. For each patient, three or more 3D iUS images were acquired during the procedure, and one iMRI was acquired towards the end. The iUS images included an extradural ultrasound sweep acquired before dural incision (iUS-1), a post-dural opening iUS (iUS-2), and a third iUS acquired immediately before the iMRI acquisition (iUS-3). iUS-1 and preoperative MRI were compared to evaluate the ability of iUS to visualize tumor boundaries and critical anatomic landmarks; iUS-3 and iMRI were compared to evaluate the ability of iUS for predicting residual tumor.ResultsTwenty-three patients were included in this study. Fifteen patients had tumors located in eloquent or near eloquent brain regions, the majority of patients had low grade gliomas (11), gross total resection was achieved in 12 patients, postoperative temporary deficits were observed in five patients. In twenty-two iUS was able to define tumor location, tumor margins, and was able to indicate relevant landmarks for orientation and guidance. In sixteen cases, white matter fiber tracts computed from preoperative dMRI were overlaid on the iUS images. In nineteen patients, the EOR (GTR or STR) was predicted by iUS and confirmed by iMRI. The remaining four patients where iUS was not able to evaluate the presence or absence of residual tumor were recurrent cases with a previous surgical cavity that hindered good contact between the US probe and the brain surface.ConclusionThis recent experience at our institution illustrates the practical benefits, challenges, and opportunities of 3D iUS in relation to iMRI.

Maximum Resection and Immunotherapy Improve Glioblastoma Patient Survival: A Single-institution Prognostic Analysis

Purpose. Glioblastoma (GBM) is a refractory disease with a poor prognosis and various methods, including maximum resection and immunotherapy, have been tested to improve outcomes. This retrospective study analyzed the prognostic factors of initially diagnosed glioblastoma patients at our institution to analyze the effect of these methods on prognosis. Methods. Two hundred seventy-seven patients with initially diagnosed glioblastoma who were treated in our institution from 2009 to 2020. Various data, including extent of removal (EOR) and type of adjuvant therapy, were examined and prognostic relationships were analyzed. Results. The median OS of the entire 277-case cohort, 200 non-biopsy cases, and 77 biopsy cases were 16.6 months, 19.7 months, and 9.7 months, respectively. Gross total removal (GTR; 100% of EOR) was achieved in 32.9% of the cases. Univariate analysis revealed younger age, right side, higher Karnofsky performance status, GTR, intraoperative MRI use for removal, proton therapy, combination immunotherapy, and discharge to home as good prognostic factors. Intraoperative MRI use and EOR were closely related. In the multivariate analysis, GTR, proton therapy, and combination of immunotherapies including autologous formalin-fixed tumor vaccine were the significant prognostic factors. A multivariate analysis of 91 GTR cases showed that immunotherapy contributed to prognostic improvements. The median OS and 5-year OS% values were 36.9 months and 43.3% in GTR cases receiving immunotherapy. Conclusion. GTR, proton therapy, and immunotherapy were good prognostic factors in single-center GBM cases. Tumor vaccine therapy for GTR cases achieved a notably high median survival time and long-term survival ratio, indicating its usefulness in GTR cases.

Intraoperative MRI in Brain Tumor Surgeries

Intraoperative MRI (ioMRI) has evolved since it used in 1991. ioMRI has been effective tool not only in glioma surgeries but also in other neurosurgical procedures. It provides real time information with high quality resolution and it is not affected by brain shift. ioMRI images can be uploaded in the navigation which helps in further resection of residual tumors. ioMRI can be used for confirmation of complete excision of tumor or location of microelectrode catheter tip DBS/sterotatic biopsy. It provides valuable information like location and amount of residue which guides surgeon for further resection safely as possible. ioMRI requires specialized operation theater with MRI compatible instruments which makes this setup expensive and it is available in only few centers across the globe.

Impact of combined use of intraoperative MRI and awake microsurgical resection on patients with gliomas: a systematic review and meta-analysis

Microsurgical resection of primary brain tumors located within or near eloquent areas is challenging. Primary aim is to preserve neurological function, while maximizing the extent of resection (EOR), to optimize long-term neurooncological outcomes and quality of life. Here, we review the combined integration of awake craniotomy and intraoperative MRI (IoMRI) for primary brain tumors, due to their multiple challenges. A systematic review of the literature was performed, in accordance with the Prisma guidelines. Were included 13 series and a total number of 527 patients, who underwent 541 surgeries. We paid particular attention to operative time, rate of intraoperative seizures, rate of initial complete resection at the time of first IoMRI, the final complete gross total resection (GTR, complete radiological resection rates), and the immediate and definitive postoperative neurological complications. The mean duration of surgery was 6.3 h (median 7.05, range 3.8–7.9). The intraoperative seizure rate was 3.7% (range 1.4–6; I^2 = 0%, P heterogeneity = 0.569, standard error = 0.012, p = 0.002). The intraoperative complete resection rate at the time of first IoMRI was 35.2% (range 25.7–44.7; I^2 = 66.73%, P heterogeneity = 0.004, standard error = 0.048, p < 0.001). The rate of patients who underwent supplementary resection after one or several IoMRI was 46% (range 39.8–52.2; I^2 = 8.49%, P heterogeneity = 0.364, standard error = 0.032, p < 0.001). The GTR rate at discharge was 56.3% (range 47.5–65.1; I^2 = 60.19%, P heterogeneity = 0.01, standard error = 0.045, p < 0.001). The rate of immediate postoperative complications was 27.4% (range 15.2–39.6; I^2 = 92.62%, P heterogeneity < 0.001, standard error = 0.062, p < 0.001). The rate of permanent postoperative complications was 4.1% (range 1.3–6.9; I^2 = 38.52%, P heterogeneity = 0.123, standard error = 0.014, p = 0.004). Combined use of awake craniotomy and IoMRI can help in maximizing brain tumor resection in selected patients. The technical obstacles to doing so are not severe and can be managed by experienced neurosurgery and anesthesiology teams. The benefits of bringing these technologies to bear on patients with brain tumors in or near language areas are obvious. The lack of equipoise on this topic by experienced practitioners will make it difficult to do a prospective, randomized, clinical trial. In the opinion of the authors, such a trial would be unnecessary and would deprive some patients of the benefits of the best available methods for their tumor resections.