bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIMG-27. GLIOBLASTOMA IN THE MAKING? ADVANCED IMAGING TELLS "MOLECULAR GLIOBLASTOMA" APART FROM ASTROCYTOMA
Authors: Griessmair Michael , Metz Marie-Christin , Zimmer Claus , Wiestler Benedikt 
Published: November 2023

Abstract
The fifth WHO classification of tumors of the CNS allows the diagnosis of glioblastoma using specific molecular markers, even if the classical histological criteria (necrosis and neoangiogenesis) are not fulfilled. Since such cases also tend to lack blood-brain barrier disruption and necrosis on conventional imaging, these can be mistaken for low-grade astrocytomas. We investigated the potential of advanced imaging to capture tumor biology and thus reliably distinguish between those entities already preoperatively. Multimodal preoperative 3T-MRI scans were collected from 147 glioblastoma, 4 astrocytomas grade 4, 7 “Molecular glioblastoma” (molGBM) grade 4, 9 astrocytomas grade 2, and 12 astrocytomas grade 3. From AI-based multi-compartimental tumor segmentations, advanced imaging metrics from perfusion- and diffusion-imaging were automatically extracted. Two-sample t-test and one-way ANOVA analysis was performed to test for significant differences between apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV). Interestingly, rCBV (signifying neoangiogenesis) was significantly higher in molGBM as opposed to astrocytomas for the 5th percentile as well as for mean and median values (p &lt; 0.05). ADC values were consequently lower (indicating higher cellularity) in molGBM than in astrocytomas grade 2 and 3 in the 95th percentile (p &lt; 0.05). Although no molGBM showed contrast-enhancement initially, one untreated case showed a flaccid barrier disruption at 30d follow-up. Interestingly, the molecular imaging at the earlier timepoint showed significantly higher CBV values in the non-enhancing tumor than common glioblastoma and astrocytoma grade 4 (p = 0.013, ANOVA), which indicates highly active tumor portions. Perhaps it is precisely these areas that are on the verge of barrier disruption. Our results support the hypothesis that molGBM are truly early glioblastomas. Better understanding the molecular mechanisms involved in the transition to “classical” glioblastoma promises to provide important insight into tumor biology and potential therapeutic targets.
NIMG-30. DEEP LEARNING SEGMENTATION OF INFILTRATIVE AND ENHANCING CELLULAR TUMOR IN POST-TREATMENT GLIOBLASTOMA PATIENTS WITH MULTI-SHELL DIFFUSION MRI
Authors: Gagnon Louis , Gupta Diviya , Mastorakos George , White Nathan , Goodwill Vanessa , McDonald Carrie , Beaumont Thomas , Conlin Christopher , Seibert Tyler , Hattangandi-Gluth Jona , Kesari Santosh , Schulte Jessica , Piccioni David , Dale Anders , Farid Niky , Rudie Jeffrey 
Published: November 2023

Abstract
Multimodal MRI is used for the evaluation of tumor burden in glioblastoma (GBM) patients after surgical resection, radiation, and chemotherapy. However, it can be challenging to identify non-enhancing infiltrative tumor and differentiate recurrent enhancing tumor from post-treatment changes. Restriction spectrum imaging (RSI), an advanced multishell diffusion technique, has shown promise in distinguishing cellular tumor from edema and enhancing post-treatment changes including pseudoprogression and radiation necrosis. We developed a convolutional network (nnUNet) that incorporates traditional multimodal MRI with DSC perfusion and RSI to detect and quantify enhancing and nonenhancing cellular tumor in post-treatment glioblastoma patients. This cellular tumor segmentation network was evaluated in a cohort of 186 post-treatment GBM patients (55.5 +/- 13.7 years, 158 male) with 243 timepoints using 5-fold cross validation. Cellular tumor volumes were then used to predict overall survival (OS) and progression free survival (PFS) in 94 patients with imaging within 3 months of initial surgery. Accuracy for segmenting cellular tumor as measured by the Dice-similarity coefficient was 0.77 (IQR 0.55-0.87) and the AUC of the ROC curve for detecting residual/recurrent tumor compared to post-treatment changes was 0.86. The predicted cellular tumor volumes were an independent hazard over age, sex, GTR status and conventional enhancing residual tumor for both OS (p=0.0003) and PFS (p=0.0004). The tumor segmentation network was validated in an external dataset of 22 GBM patients (55 timepoints) with a median Dice of 0.73 and AUC of 0.91. Survival prediction was validated in a different external dataset of 70 post-treatment GBM patients, with cellular tumor volumes being an independent predictor of OS (p=0.03). In conclusion, deep learning models incorporating advanced imaging can accurately segment enhancing and nonenhancing cellular tumor, which can help distinguish recurrent/residual tumor from post-treatment changes and predict OS and PFS.
NIMG-32. MULTI-MODAL ANALYSIS UNCOVERS DIFFERENTIALLY REGULATED PATHWAYS ASSOCIATED WITH RADIO-PHENOTYPES IN PEDIATRIC LOW-GRADE GLIOMA
Authors: Kazerooni Anahita Fathi , Kraya Adam , Rathi Komal , Haldar Debanjan , Mahtabfar Aria , Khalili Nastaran , Familiar Ariana , Kim Meen Chul , Bagheri Sina , Anderson Hannah , Ware Jeffrey B , Storm Phillip , Davatzikos Christos , Vossough Arastoo , Resnick Adam , Nabavizadeh Ali 
Published: November 2023

Abstract

INTRODUCTION
Pediatric low-grade glioma is comprised of a broad variety of histological subtypes with heterogeneous responses to standard-of-care treatments. Understanding the biological pathways underlying clinical radiographic appearances, or radio-phenotypes, may facilitate precision diagnostics prior to the initiation of any interventions, thereby, reducing the risk of co-morbidities while improving patient outcome. Here, we aim to comprehensively harness the high-throughput multi-modal data available through Children’s Brain Tumor Network (CBTN) to elucidate the pathways that form radio-phenotypic traits of pLGG.

METHODS
On a cohort of 165 patients with pLGG, 881 radiomic features were extracted from multiparametric MRI sequences. We applied principal component analysis (PCA) followed by K-Means clustering to the radiomic features along with clinical variables of age, gender, and tumor location to group the patients into distinct imaging subtypes. We used whole transcriptomic data from OpenTargets to compare differential expression and co-expression of network- and pathway-level properties via Gene Set Enrichment Analysis (GSEA), and Gene Sets Net Correlations Analysis (GSNCA) among the discovered imaging subtypes.

RESULTS
Three imaging subtypes of pLGG were identified, among which subtype1 tumors showed increased proliferative capacity and invasive potential. This was suggested by higher expression of cell cycle regulatory, extracellular matrix (ECM) remodeling, and cell migratory pathways in subtype1 than subtypes 2 and 3. Furthermore, subtype1 exhibited differential TNF/TNFR signaling compared to subtype2, potentially related to differential regulation of pro-tumorigenic immune pathways, and differential regulation of TGF-beta and Aurora Kinase A signaling compared to subtype3, associated with differences in proliferative pathways. Subtypes 1 and 2 exhibit higher pro-tumorigenic cytokine expression while subtype3 involves higher expression of neurotransmitter release and neuronal activity, which may be targetable.

CONCLUSIONS
Our multi-modal radiogenomic analysis unraveled molecular underpinnings that give rise to the formation of distinct imaging phenotypes, with the potential to inform personalized treatments for children with brain tumors.
NIMG-35. RADIO-PATHOMIC MAPS OF TUMOR PROBABILITY IDENTIFY GLIOBLASTOMA INVASION BEYOND 5-ALA GUIDED RESECTION MARGINS THAT EVENTUALLY EXHIBIT TUMOR RECURRENCE
Authors: Winiarz Aleksandra , Bobholz Samuel , Lowman Allison , Duenweg Savannah , Stebbins Margaret , Flatley Michael , Nath Biprojit , Kyereme Fitzgerald , Connelly Jennifer , Coss Dylan , Krucoff Max , Banerjee Anjishnu , LaViolette Peter 
Published: November 2023

Abstract
Current standard of care for glioblastoma includes surgery followed by chemotherapy and radiation, with extent of resection strongly correlated with survival. There is a need to improve the detection of tumor invasion beyond traditional imaging methods, as the full extent of tumor is known to be underestimated. Fluorescence-guided surgery with 5-Aminolevulinic acid (5-ALA) allows surgeons to visualize tumor cells beyond what is seen within traditional MR imaging margins. In this study, we compared tumor probability maps (TPMs) that detect tumor outside of contrast enhancement (CE) to the 5-ALA-guided resection cavity in glioblastoma patients. 3 pathologically confirmed glioblastoma patients that followed standard of care and underwent 5-ALA surgery were included. Patient 1 was a 56-year-old male with radiographic recurrence at 26 days, patient 2 was a 61-year-old male with radiographic recurrence at 130 days, and patient 3 was a 72-year-old male with cystic recurrence at 84 days, all post 5-ALA surgery. A previously published algorithm, using T1, T1C, FLAIR, and ADC as input and autopsy tissue as ground truth, was used to generate TPMs. Pre-surgical TPMs were qualitatively compared to pre-surgical CE, post-5-ALA surgical resection cavities, and radiographic recurrence seen as CE. In patients 1 and 2, TPMs identified areas suspicious of tumor that was not resected and later exhibited radiographic recurrence. Patient 3 had cystic recurrence only identified on post-resection T1C. In all patients, the extent of 5-ALA resection was greater than CE volume, but smaller than TPM identified tumor. These findings suggest that there was residual tumor that was unidentified via 5-ALA and traditional imaging but was identified by the TPMs. Future studies could utilize these maps in conjunction with 5-ALA to maximize surgical resections and prolong overall survival.
NIMG-42. RADIOIMMUNOMIC SIGNATURES IN PEDIATRIC LOW-GRADE GLIOMA FOR NON-INVASIVE IDENTIFICATION OF IMMUNOTHERAPEUTIC TARGETS
Authors: Kazerooni Anahita Fathi , Kraya Adam , Rathi Komal , Khalili Nastaran , Haldar Debanjan , Familiar Ariana , Kim Meen Chul , Bagheri Sina , Anderson Hannah , Foster Jessica , Storm Phillip , Davatzikos Christos , Ware Jeffrey B , Vossough Arastoo , Resnick Adam , Nabavizadeh Ali 
Published: November 2023

Abstract

INTRODUCTION
Tumor immune microenvironment (TIME) plays a key role in response to anti-tumor therapies. Therefore, detailed characterization of TIME is crucial for patient stratification and enrollment onto emerging immunotherapies. As standard-of-care treatments are not feasible or confer devastating long-term morbidity for pediatric low-grade glioma (pLGG), non-invasive quantification of the TIME using radiomic analysis, may guide treatment decisions. On the largest available transcriptomic and imaging data in pLGGs, provided through Children’s Brain Tumor Network (CBTN), this data-driven study aims to discover immunological profiles of pLGG that are meaningfully related to biomarkers of tumor immune response, and radioimmunomic signatures that are predictive of immunological profiles.

METHODS
Enrichment of immune and stromal cell types and pathways in 502 subjects were inferred using xCell algorithm applied to transcriptomic data and the tumors were then clustered via consensus clustering approach. Tumor inflammation signature (TIS), as a biomarker of response to anti-PD-1 blockade, was compared across the immunological clusters. Quantitative radiomic features were extracted from the segmented tumor regions on multiparametric MRI scans of 155/502 patients. Cross-validated support vector machines with forward feature selection were trained on radiomic features using one-versus-the-rest approach to predict the immunological groups.

RESULTS
Three immunological clusters, i.e., immune-cold, -altered, and -hot were found, with different levels of enrichment in immune and microenvironment scores, CD4 T-cells, and macrophages. Significantly higher TIS values were found in immune-hot and -altered compared to immune-cold tumors (p= 1.2e-8 and p= 7e-16, respectively). Radioimmunomic models yielded average AUC of 0.75 for one-versus-the-rest differentiation of the immunological clusters.

CONCLUSIONS
The proposed analysis revealed three distinct immunological groups in pLGGs, with immune-hot tumors more likely to respond favorably to immunotherapies. Furthermore, non-invasive radioimmunomic signatures were shown to potentially stratify the patients based on their TIME, which upon further development and validation, could inform treatments for pLGGs.
NIMG-43. A 57-YEAR-OLD MALE WITH PRIMARY GLIOBLASTOMA TREATED WITH LASER INTERSTITIAL THERMAL THERAPY: IMAGING AND AUTOPSY FINDINGS
Authors: Lowman Allison , Winiarz Aleksandra , Bobholz Samuel , Duenweg Savannah , Stebbins Margaret , Flatley Michael , Nath Biprojit , Kyereme Fitzgerald , Coss Dylan , Krucoff Max , Connelly Jennifer , LaViolette Peter 
Published: November 2023

Abstract
INTRODUCTION: Glioblastoma (GBM) is an aggressive primary brain cancer with significant resistance to the current therapeutic approach of chemotherapy and radiotherapy, jointly known as chemoradiation (CRT). Magnetic hyperthermia therapy (MHT) is a promising therapy for GBM that can be used to perform multiple sessions of non-invasive, localized hyperthermia by activating locally delivered magnetic iron oxide nanoparticles (MIONPs) with an external alternating magnetic field (AMF). In this study, MHT-mediated enhancement of CRT was evaluated in murine and human glioma cell lines both in cell culture and in rodents.
NIMG-49. INTRAOPERATIVE 5-ALA INTENSITY ANALYSIS OF GLIOMA USING IMAGE J
Authors: Kon Takashi , Kobayashi Yusuke , Shimizu Katsuyoshi , Mizutani Tohru , Sato Yosuke 
Published: November 2023

Abstract
PURPOSE: The 5 aminolevulinic acid (5-ALA) is used for intraoperative tumor visualization in neurosurgery. We hypothesized that glioma may vary in malignancy according to the brightness of 5-ALA. We quantified the brightness of 5-ALA and compared it with the pathological results of glioma. MATERIALS AND METHODS: From 2019 to 2023, we investigated 35 glioma patients who underwent surgery with 5-ALA. Twenty-three cases of glioblastoma (GBM), four cases of anaplastic astrocytoma (AA), three cases of oligodendroglioma (OL), one case of anaplastic oligodendroglioma (AO), and four cases of low grade glioma (LGG) were examined. The pathological diagnosis was based on classification of WHO 2016. The 5-ALA was administered before surgery, and the 5-ALA brightness were quantified. RESULTS: In GBM, the mean brightness was 134.5 ± 65.4, except for one negative case. AA showed the mean brightness with 180.5 ± 51.6. Three cases of OL showed the mean brightness with 78.6 ± 32.7. AO showed the brightness with 153. All LGGs showed negative in the brightness. CONCLUSION: The 5-ALA showed higher brightness in GBM , AA, AO and negative in LGG. In the future, we will accumulate cases and add further studies.
NIMG-58. PET IMAGING AS A RELIABLE INDICATOR FOR EVALUATING BEVACIZUMAB TREATMENT RESPONSE IN GBM
Authors: Miyake Keisuke , Takahiro Kanda , Suzuki Kenta , Fujimori Takeshi , Toyota Yasunori , Ogawa Daisuke , Hatakeyama Tetsuhiro , Okauchi Masanobu , Kawanishi Masahiko 
Published: November 2023

Abstract

OBJECTIVE
PET scans are crucial for glioma diagnosis and treatment planning, but assessing the efficacy of Bevacizumab (Bev) treatment using MRI alone is challenging. Our study aimed to evaluate the effectiveness of Bev-based glioblastoma treatment using PET scans.

METHODS
We included ninety glioblastoma patients treated with Bev between July 2013 and May 2023. Patients were divided into three groups: the first group received Bev in addition to the Stupp regimen after biopsy or subtotal resection (first-dose group), the second group received Bev after biopsy followed by tumor resection (neoadjuvant group), and the third group received the Stupp regimen followed by TMZ + Bev at recurrence (recurrent group). PET scans (FDG, MET, FLT, and FMISO) were performed before and 4 weeks after starting Bev treatment. Tumor-to-normal ratio (TNR) was calculated for FDG, MET, and FLT, and tumor-to-blood ratio (TBR) was determined for FMISO. We used the Cox proportional hazards model to assess the percent change in TNR, TBR, and metabolic tumor volume (MTV) as prognostic factors.

RESULTS
The median PFS and OS (month) from Bev treatment were as follows: first-dose group (PFS: 8.87, OS: 12.53), neoadjuvant group (PFS: 16.53, OS: 22.13), and recurrent group (PFS: 4.0, OS: 8.0). In the first-line group, significant differences were found in the percent change in MTV for MET, FLT, and FMISO. In the recurrent group, significant differences were observed in the percent change in MTV for FDG and MET, as well as in FDG TNR and FMISO TBR. In the neoadjuvant group, significant differences were found in the percent change in MTV for MET and FLT.

CONCLUSION
Neoadjuvant Bev treatment led to prolonged PFS and OS in glioblastoma patients. Decreases in MET MTV change rate and FMISO TBR change rate were identified as potential indicators for assessing Bev treatment efficacy after recurrence.
NIMG-61. RADIOLOGICAL, CLINICAL, AND MOLECULAR ANALYSES UNRAVEL DISTINCT SUBTYPES OF ADULT GRADE 4 BUTTERFLY GLIOMAS AFFECTING THE PROGNOSIS
Authors: Shibahara Ichiyo , Tanihata Yoko , Fujitani Kazuko , Handa Hajime , Kumabe Toshihiro 
Published: November 2023

Abstract
Gliomas located at the corpus callosum (CC) and invading the bilateral hemispheres is known as butterfly gliomas (bG). Images of bG are frequently used as the hallmark of glioblastoma (GB); however, the molecular background and origins of bG remain unknown. We collected 37 bG patients, including 32 cases of GB and 5 cases of astrocytoma, WHO grade 4, IDH-mutant. Our dataset included extremely rare sequential radiological imaging before receiving a definitive diagnosis of bG. One case emerged from CC and subsequently became bG, whereas five cases emerged from the cerebral hemisphere and became bG, suggesting distinct radiological origins exist in bG. Reflecting this observation to further analysis, we subdivided the cohort into CC-type (n = 15) and hemispheric-type (n = 22) based on the ratio calculated by the tumor volume at CC and hemisphere. Survival analysis presented that CC-type was significantly poorer overall survival (OS) than hemispheric-type (P = 0.010), indicating that bG has clinically distinct two subtypes. Molecular analyses revealed that TERT promoter mutations and IDH1 mutations were observed in 73.3% and 0% in the CC-type, whereas 36.4% and 22.7% in the hemispheric-type, respectively. Other alterations such as MGMT promoter methylation, EGFR amplification/gain, CDKN2A hemi/homozygous deletion, and PTEN hemi/homozygous deletion remained the same between two groups. None of the patients had H3F3A, HIST1H3B, or BRAF mutations. In the hemispheric-type, the multisampling of hemispheric and CC specimens revealed accumulating alterations in the CC lesions, indicating an invasive trajectory from the hemisphere to the CC region. For the validation, we reviewed 993 MRI obtained from the public datasets (TCGA-GBM, CPTAC-GBM, IvyGap, and UPenn-GBM) and found the same trend: CC-type presented poor OS. bG is not a sole subtype with just extensive invasion from the hemisphere. Our results highlight the pathophysiology of bG and may influence its management.
NIMG-63. GAMMA-BAND MODULATIONS OF ELECTROCORTICOGRAM (ECOG) INDUCED BY COGNITIVE-LINGUISTIC TASKS DURING AWAKE CRANIOTOMY FOR FEASIBLE FUNCTIONAL LANGUAGE MAPPING
Authors: Tasnim Israt , Asman Priscella , Swamy Chandra Prakash , Hall Matthew , Noll Kyle , Connelly Katherine , Tummala Sudhakar , Ince Nuri Firat , Prabhu Sujit 
Published: November 2023

Abstract

INTRODUCTION
Intraoperative functional language mapping has uncertainty in predicting language function and post-surgical outcomes. We study the feasibility of functional mapping using electrocorticogram (ECoG) gamma-band modulations induced by linguistic tasks having different complexity levels.

METHODS
Five subjects with left temporal lobe glioma underwent resection involving awake language mapping using a 4x8 ECoG electrode grid. A MATLAB/Simulink based real-time software system was used to map task-induced gamma-band modulations as 2D heat maps. Tasks included verbally responding to single word/tone categorization; object, action, written descriptive and auditory naming respectively. Auditory stimuli were provided during word/tone categorization (duration 300~500ms) and auditory naming tasks ( &gt; 1s). Other tasks provided visual stimuli (line drawings or written phrases). Bipolar DCS (2~6 mA, 60Hz, 2s) was applied at different electrode pairs while repeating the naming tasks.

RESULTS
Cortical regions activated by word stimuli and the auditory naming task were similar; superior, middle temporal gyri (STG, MTG). Visual naming tasks modulated posterior MTG (pMTG) and STG (written naming). Reproducible speech arrests occurred during different naming tasks while stimulating specific electrode pairs, even though not all electrodes had strong task-specific activations. Considerable inter-personal variability of language areas identified with DCS was observed, despite the similarity of task-specific gamma-band modulated regions across subjects. Post-operative decline in language score was observed in one subject, with resection boundary covering gamma modulated regions during auditory processing tasks but no DCS identified region.

CONCLUSION
Intraoperative language mapping guided by gamma-band ECoG modulations induced by simple word/tone categorization task exhibited similar patterns to more complex naming tasks, suggesting this task may be a viable approach to localize functional cortex, especially in patients unable to reliably perform more difficult paradigms. Utilizing this method in conjunction with DCS mapping guided by visual naming tasks, eloquent cortical language areas may be better preserved reducing post-operative language deficits.
NIMG-69. LEPTOMENINGEAL METASTASES IN IDH-WILDTYPE GLIOBLASTOMAS REVISITED: COMPREHENSIVE ANALYSIS OF INCIDENCE, RISK FACTORS, AND PROGNOSIS BASED ON POSTCONTRAST FLAIR IMAGING
Authors: Park Yae Won , Ahn Sung Soo , Kang Seok-Gu , Chang Jong Hee , Kim Se Hoon 
Published: November 2023

Abstract

BACKGROUND
To comprehensively investigate the incidence, risk factors, and prognosis of leptomeningeal metastases (LM) in isocitrate dehydrogenase (IDH)-wildtype glioblastoma patients.

METHODS
Total 913 IDH-wildtype glioblastoma patients with complete molecular information on IDH mutation and MGMT promoter methylation status were enrolled between 2004 and 2022. LM diagnosis was performed with MRI including postcontrast FLAIR and CSF cytology. Logistic regression analysis for LM development at initial diagnosis and recurrence was performed with clinical, surgical, imaging, and molecular data. The overall survival (OS) was compared between patients with and without LM.

RESULTS
The incidence of LM was 21.8% (199 patients) among patients with IDH-wildtype glioblastoma, with 11.5% (105 patients) at initial diagnosis, and 10.3% (94 patients) at recurrence. Male sex (odds ratio [OR]: 1.74, P = 0.017), MGMT promoter unmethylation (OR: 1.48, P = 0.048), nonlobar location (OR: 2.27, P &lt; 0.001), and presence of necrosis (OR: 3.64, P &lt; 0.001) were independent predictors of LM at initial diagnosis, whereas ventricular opening during surgery (OR: 2.96, P &lt; 0.001) was the only independent predictor of LM at recurrence. The median OS was 16.2 months (interquartile range [IQR]: 9.6-30.4) in patients with LM and 19.3 months (IQR: 12.1-38.5) in patients without LM (log-rank test; P = 0.001).

CONCLUSION
The incidence of LM is high in patients with IDH-wildtype glioblastoma. Aggressive clinical, imaging, and molecular factors are correlated with LM at initial diagnosis, whereas ventricular entry warrant imaging surveillance for LM at recurrence. The prognosis of LM is not discouraging as expected, and promote reconsideration of focused clinical trials.