bluuebunny/crossref_metadata_2025_split huggingface dataset:
PATH-65. MONITORING MENINGIOMA CELL CYCLE ACTIVITY THROUGH DREAM-MMB ACTIVITY SWITCHING
Authors: Kona Abhinav , Rai Ansh , Rojas Diego , Klisch Tiemo , Patel Akash 
Published: November 2024

Abstract
Meningiomas account for over 40% of all primary intracranial brain tumors, with approximately one-fifth of these tumors recurring. Our lab has previously used molecular techniques to identify three subgroups: MenG A, B, and C, which have been independently validated. Interestingly, only MenG C tumors harbor recurring patients, making it an aggressive subtype of meningioma. One hallmark of MenG C tumors is the overexpression of a distinct set of genes that harbor in their promoter the CDE-CHR DNA-binding element, used by a transcriptional complex that in dormant cells functions as a repressor (DREAM). Before phosphorylation, this complex functions as an activator (MBB) in cycling cells. Upon a phosphorylation-dependent switch, the dual-specificity tyrosine kinase DYRK1A phosphorylates S28 on LIN52, which itself is dimerized with LIN9 of the core complex. Phosphorylation shifts the complex to DREAM, while lack thereof allows the core complex to interact with MYBL2 (now MBB) and activate the same genes repressed in quiescent cells. We seek to quantify this switch activity using an in vivo luciferase sensor using NanoBiT technology. Our biosensor is based on a split nanoluciferase, where one half is fused to the LIN52/LIN9 dimer and the other is fused to MYBL2. When MYBL2 binds to the LIN52/LIN9 dimer, a functional nanoluciferase is formed, and its activity can be measured using a luciferase-specific substrate. As proof of principle, we have increased cell proliferation by increasing FBS concentration in cultured cells as well as by blocking S28 phosphorylation using the DYRK1A-specific inhibitor Harmine. We screened all possible combinations (alternating NanoBiT fragments) for the highest luciferase activity after stimulation. In the future, this biosensor can be used to monitor cell cycle activity in vitro as well as in vivo using low-cost Luciferase reporter assays to better understand the regulation of specific genes in MenG C tumors.
PATH-68. THE CLINICAL AND PROTEOMIC CLASSIFICATION FOR THE PRECISION TREATMENT STRATEGY OF CHORDOMA
Authors: Meng Tong 
Published: November 2024

Abstract
Chordoma is a rare and heterogeneous mesenchymal malignancy, with distinct clinical and biological behaviors. Till now, its comprehensive clinical-molecular characteristics and accurate molecular classification remain obscure, leading to numerous diagnostic and therapeutic challenges. In this research, we enroll a large cohort of chordoma (102 patients) and describe their clinical, imageological and histopathological features. Through tandem mass tag-based proteomic analysis and nonnegative matrix factorization clustering, we classify chordoma into the following three molecular subtypes: bone microenvironment dominant, mesenchymal derived, and mesenchymal to epithelial transition mediated pattern. The three subtypes exhibit discrete clinical prognosis and distinct biological attributes of osteoclastogenesis and immunogenicity, oxidative phosphorylation, and receptor tyrosine kinase activation, suggesting targeted therapeutic strategies of Denosumab, S-Gboxin and Anlotinib, respectively. Notably, these approaches demonstrate positive treatment outcomes for each subtype in vivo and in vitro, as well as in patient-derived xenograft models. Altogether, this work sheds light on the clinical-proteomic characteristics of chordoma that deepens our understanding of this rare disease and provides candidate precision treatment strategy for chordoma according to molecular classification, underscoring their potential for clinical application.
NIMG-05. ARTIFICIAL INTELLIGENCE-BASED RESPONSE ASSESSMENT FOR PATIENTS RECEIVING LASER INTERSTITIAL THERMAL THERAPY
Authors: Haskell-Mendoza Aden , Reason Ellery , Gonzalez Ariel , Jackson Joshua , Sankey Eric , Srinivasan Ethan , Herndon II James , Fecci Peter , Calabrese Evan 
Published: November 2024

Abstract

BACKGROUND
Laser interstitial thermal therapy (LITT) is a minimally invasive option for tissue diagnosis, cytoreduction, and rapid post-operative return to systemic therapies for patients with brain tumors or radiation necrosis. As ablated tissue remains in situ, post-LITT edema may be associated with apparent increased lesion size and transient clinical worsening, complicating assessment of progression.

METHODS
All patients receiving LITT at a single center for tumors or radiation necrosis from 2015 – 2023 with ≥ 9 months of MRI follow-up were retrospectively reviewed. A 3D U-net segmentation model implemented in nnU-Net was developed for automated segmentation of Contrast-enhancing Lesion Volume (CeLV) of LITT-treated lesions on T1-weighted post-contrast MR images. CeLVs were analyzed to establish volumetric post-LITT response assessments.

RESULTS
Across 384 unique MRI exams, 61LITT-treated lesions and 6 control cases of medically-managed radiation necrosis were analyzed. Automated segmentation was qualitatively accurate in 367/384 (95.6%) images. CeLV increased to a median of 68.3% (IQR 35.1 – 109.2%) from baseline at 1 – 3 months from LITT (P = 0.0012) and returned to baseline thereafter. Based on established criteria, volumetric disease progression was defined as lesion expansion 40% from volumetric nadir or baseline. Twenty-one of 56 (37.5%) patients experienced volumetric progression with a progression-free survival of 21.4 (6.0 – 93.4) months. Patients experiencing volumetric progression had lower mOS (17.3 vs 62.1 months, P = 0.0015).

CONCLUSIONS
We observed a stereotyped increase in CeLV at 1 – 3 months post-LITT, which resolved within 6 months of the procedure. Post-LITT disease response can be reliably and feasibly assessed with criteria that account for this transient CeLV expansion. Automated lesion segmentation may speed adoption of volumetric response assessment criteria to clinical practice.
NIMG-07. GLIOBLASTOMA AS A MIMIC OF ACUTE ISCHEMIC STROKE: AN UNDERRECOGNIZED PHENOMENON AND THE IMPACT ON PATIENT OUTCOMES
Authors: Vazquez Sima , Spirollari Eris , Soldozy Sauson , Dominguez Jose , Al-Mufti Fawaz , Aiken Robert , Hanft Simon 
Published: November 2024

Abstract

BACKGROUND
Glioblastoma may present similarly to acute ischemic stroke. This study aims to determine characteristics and outcomes of patients with glioblastoma presenting with stroke-like symptoms. Our objective is to characterize patients with glioblastoma who present as mimics of acute ischemic stroke and identify differences in outcomes when compared to those diagnosed with glioblastoma only.

METHODS
The 2016-2019 National Inpatient Sample (NIS) database was queried for all patients who had a new diagnosis of glioblastoma. Patients with new glioblastoma who carried an admission diagnosis of acute ischemic stroke, but did not undergo thrombectomy, chemical thrombolysis, or hemicraniectomy were categorized as “GBM-Stroke Mimic”. The characteristics and comorbidities between GBM-Stroke Mimic and new glioblastoma patients were compared. Primary outcomes analyzed were discharge disposition and mortality.

RESULTS
Of 61,755 patients newly diagnosed with glioblastoma, 1,000 (1.6%) were GBM-Stroke Mimics. GBM-Stroke Mimic patients more commonly presented with aphasia (P &lt; 0.001) and hemiplegia (P &lt; 0.001). Age greater than 65, atrial fibrillation, diabetes mellitus, hypertension, hyperlipidemia, and long-term anticoagulation/antiplatelet therapy were more commonly associated with GBM-Stroke Mimic patients (all P &lt; 0.001). GBM-Stroke Mimic patients were more likely to be discharged to skilled nursing facility, (p &lt; 0.001), and a diagnosis of GBM-Stroke Mimic was an independent risk factor for inpatient death (P &lt; 0.001).

CONCLUSION
To our knowledge, this is the first study formally investigating the clinical outcomes of glioblastoma when initially diagnosed as stroke. When this misdiagnosis is made, we found an association with increased inpatient mortality, delays of care, and inappropriate resource allocation.
NIMG-13. CHANGES IN CORTICAL ARCHITECTURE ASSOCIATED WITH GLIOBLASTOMA ASSOCIATED EPILEPSY
Authors: Anzak Anam , Pimentel Bernardo Crespo , Caciagli Lorenzo , Marino Silvia , Wandschneider Britta 
Published: November 2024

Abstract

BACKGROUND
Emerging evidence suggests both local hyper-excitability promoting epilepsy, and synaptic and paracrine mediated integration of Glioblastoma into brain-wide neural networks. In this study we sought clinical evidence of disease progression, and concurrent radiological evidence of differences in remote cortical architecture, in Glioblastoma patients with and without epilepsy.

METHODS
55 patients with biopsy-confirmed Glioblastoma, mean-age 59.4yrs±10.9yrs, were studied. 23 patients had a diagnosis of Glioblastoma-related epilepsy on presentation. We compared clinical markers of disease progression in individuals with and without epilepsy. Further, we explored differences in cortical architecture between both groups. Utilising pre-operative T1-weighted, contrast-enhanced MRI scans (n=45), we performed vertex-wise measurements of cortical thickness (CT) and cortical surface area (CSA) using the Virtual Brain Grafting Toolbox and FreeSurfer v.7.0. Radiologically-identifiable tumour and oedema was masked and excluded from analysis. Scans with right-hemispheric tumours were flipped to the left. Linear mixed-effects models were applied to pre-processed imaging-data.

RESULTS
Individuals with epilepsy had shorter progression-free survival (median 4.2 months) than those without seizures (9.3 months, p&lt;0.05) with gold-standard treatment. No significant difference between lesion volumes (tumour and oedema) existed between the two groups (unpaired t-test, p&gt;0.05). Controlling for age and tumour location, significant increases (p&lt;0.01) in CT and CSA were observed in patients with Glioblastoma-related epilepsy in lesion-ipsilateral supramarginal gyrus, superior parietal lobule, precuneus/cuneus and temporal lobe compared to those without epilepsy. Interestingly, significant (p&lt;0.05) increases in CT in lesion-contralateral supramarginal gyrus were additionally observed in those with epilepsy compared to those without.

CONCLUSIONS
Glioblastoma-related epilepsy was associated with poorer survival outcomes and changes in remote cortical architecture. Implicated regions form part of the default mode network, which has previously been identified as a crucial hub for epilepsy. Biological underpinnings of cortical network alterations, and their possible role in promoting not only hyper-excitability but also Glioblastoma progression, require correlation with histopathological characteristics and validation in larger study cohorts.
NIMG-14. HEAD-TO-HEAD COMPARISON OF18F-FET PET AND68GA-PSMA-11 PET IN DISTINGUISHING SMALL VOLUME TUMOR PROGRESSION VS TREATMENT-RELATED CHANGE IN POST-STANDARD OF CARE TREATMENT OF HIGH-GRADE GLIOMA USING DYNAMIC ACQUISITION AND KINETIC MODELING
Authors: Ocana Jesus , Green Mark , Territo Wendy , Hutchins Gary , Veronesi Michael , Nevel Kathryn , Umber Shafique 
Published: November 2024

Abstract

BACKGROUND
The inability to accurately distinguish between tumor progression and treatment-related changes in patients with high-grade glioma on routine imaging can negatively impact patient management and in some cases, outcome. Various imaging methods have been used to address this issue, including 18F-fluoro-ethyl-tyrosine (FET) PET and MR perfusion. However, these methods may not provide reliable results in cases of small lesion size or hemorrhage within the treatment site. The prostate-specific membrane antigen (PSMA) has been observed to be expressed by neovasculature in brain tumors. Since PSMA cannot cross the blood brain barrier, uptake of PSMA in the brain carries high-level of suspicion for residual tumor. Still, further work is needed to better understand PSMA uptake in the tumor bed following standard of care (SOC) treatment and to compare to currently available neuro-oncologic radiotracers, such as FET. We hypothesize that PSMA imaging of glioma neovasculature will provide unique diagnostic information that will aid in the differentiation of small volume tumor progression from treatment-related changes in the post-SOC treatment setting.

METHODS
Patients who underwent clinical Expanded Access PET/MR imaging with 18F-FET were re-imaged in a research protocol that collected a brain 68Ga-PSMA-11 PET/CT scan, as well as a repeat 18F-FET PET/CT. Kinetic modeling of dynamic radiotracer uptake was performed. Scans were assessed for correlation with subsequent imaging and changes in clinical management.

RESULTS
All PSMA scans that were performed were concordant with the initial clinical FET scan, subsequent imaging follow up and appropriate changes in clinical management. The PSMA-detected site was confirmed to be tumor in a single case with subsequent tissue sampling. One patient who was started on bevacizumab after their clinical FET demonstrated a significant decrease in uptake on the research FET scan, but persistent uptake on PSMA.

CONCLUSION
PSMA may effectively show tumor recurrence in post-SOC treatment high-grade glioma patients.
NIMG-22. QUANTITATIVE BRIGHTNESS ANALYSIS OF 5-ALA FLUORESCENCE IN GLIOMA SURGERY
Authors: Kon Takashi , Kobayashi Yusuke , Shimizu Katsuyoshi , Mizutani Tohru , Sato Yosuke 
Published: November 2024

Abstract

OBJECTIVE
The 5 aminolevulinic acid (5-ALA) is used for intraoperative tumor visualization in neurosurgery. We hypothesized that glioma may vary in pathology according to the brightness of 5-ALA fluorescence, which we quantified and compared with the pathological results of glioma.

METHODS
From 2019 to 2023, we investigated 28 glioma patients who underwent surgery with 5-ALA. The pathological diagnosis was based on classification of WHO 2016. The 5-ALA was administered before surgery, and the brightness of 5-ALA fluorescence was quantified.

RESULTS
Seventeen cases of glioblastoma (GBM), four cases of anaplastic astrocytoma (AA), three cases of oligodendroglioma (OL), and four cases of low grade glioma (LGG) were examined. The mean (SD) brightness of 5-ALA fluorescence was 155.9 (56.0) in GBM, 180.5 (64.7) in AA, and 66.3 (18.8) in OL. The brightness in OL was significantly lower than that in GBM and AA (Scheffe’s test, p&lt;0.05). All LGGs showed negative in the brightness.

CONCLUSIONS
The brightness of 5-ALA fluorescence was shown to vary by pathology, which may contribute to intraoperative diagnostic support.
NIMG-30. DEUTERIUM METABOLIC IMAGING (DMI) SHOWS A STRONG RELATION BETWEEN TUMOR GRADE AND GLUCOSE METABOLISM IN PRIMARY BRAIN TUMORS
Authors: Thaw-Poon Serena , Blondin Nicholas A , Liu Yanning , Corbin Zachary A , Baehring Joachim , Omuro Antonio , Moliterno Jennifer , Omay Sacit Bulent , Fulbright Robert K , de Graaf Robin A , De Feyter Henk M 
Published: November 2024

Abstract

BACKGROUND
Metabolic imaging using FDG-PET is a key component of disease management in many cancers outside of the brain, but in brain tumors, it often shows low tumor-to-brain contrast because of high background signal from normal brain. Deuterium metabolic imaging (DMI) is a new 2H magnetic resonance spectroscopic imaging-based technique that when combined with administration of 2H-labeled glucose can provide high tumor-to-brain image contrast because it can detect downstream metabolism instead of only glucose uptake. In this observational study, DMI of glucose metabolism was performed in 22 patients with primary brain tumors of different grades, and at different disease stages.

METHODS
DMI data were acquired using a 4 tesla MRI scanner after oral administration of 0.75g/kg of [6,6’-2H2]-glucose in water. Metabolic maps were generated of 2H-labeled glucose, glutamate+glutamine (Glx), lactate (Lac), and Lac/(Lac+Glx), a proxy for the metabolic shift observed in many cancers known as the Warburg effect. Volumes of interest (VOI) based on contrast-enhancing and non-enhancing tumor regions were created using clinical MRIs and combined with DMI maps to generate tumor-specific values for Lac/(Lac+Glx). Eta-squared was calculated using tumor grade and Lac/(Lac+Glx) as independent and dependent variables; data are reported as mean±SD. Results – Tumor-to-brain image contrast for Lac/(Lac+Glx) was 2.57±0.93 for grade 4 (n=14), 1.74±0.75 for grade 3 (n=6) and 0.94±0.28 for grade 2 lesions (n=3). Lac/(Lac+Glx) was 0.36±0.13 for grade 4; 0.19±0.049 for grade 3; 0.09±0.042 for grade 2 lesions; and 0.14±0.043 for normal brain. Eta-squared between tumor grade and Lac/(Lac+Glx) was 0.52.

CONCLUSIONS
VOI-based analysis showed a high dependence of metabolism-specific image contrast to tumor grade. The apparent relation between lesion grade and Lac/(Lac+Glx) indicates the potential of DMI to complement anatomical MRI and possibly provide a valuable biomarker indicating active tumor tissue and could improve evaluating disease progression.
NIMG-32. ORAL ADMINISTRATION OF DEUTERATED CHOLINE AS A NEW APPROACH TO PROVIDE HIGH TUMOR-TO-BRAIN IMAGE CONTRAST IN DEUTERIUM METABOLIC IMAGING (DMI)
Authors: Osoliniec Victor , Thomas Monique , de Graaf Robin , De Feyter Henk 
Published: November 2024

Abstract

BACKGROUND
Metabolic imaging using FDG-PET is a key component of disease management in many cancers outside of the brain, but in brain tumors it often shows low tumor-to-brain contrast because of high background signal from normal brain. We explore generating cancer-specific metabolic image contrast using Deuterium Metabolic Imaging (DMI), which is a novel 2H magnetic resonance spectroscopic imaging-based technique. DMI was applied after oral administration of deuterated choline, an essential nutrient needed for membrane synthesis whose uptake is often increased in tumors.

METHODS
Total choline (tCho) DMI was performed in an orthotopic model of glioblastoma, F344 rats (n=11) implanted with RG2 cells, on an 11.7 tesla MRI scanner, with isotropic spatial resolution of 2.5 mm. tCho-DMI data were collected for 36 min during intravenous infusion (IV, n=6) or after 3 days of oral administration (PO, n=5) of [2H9]-choline chloride dissolved in sterile water. At a dose of 285 mg/kg body weight, bolus-continuous IV infusion via the tail vein required 1.57 ml for a 250-gram rat. PO administration via gavage on 3 consecutive days used the max daily dose recommended for human adults, 50 mg/kg. Results - In the PO group, average tumor tCho concentration was 0.78±0.14 mM and 0.20±0.05 mM in contralateral normal brain. In the IV group, the tCho concentration was 0.88±0.18 mM in the tumor, and 0.18±0.03 mM in normal brain (PO vs. IV: p=0.52). Tumor-to-brain contrast was 5.9±1.2 in PO-administered animals, and 7.1±3.3 for animals receiving IV 2H-choline, (p=0.54).

CONCLUSIONS
- In a preclinical GBM model oral administration of [2H9]-choline resulted in comparably high tumor-to-brain image contrast on tCho-DMI-based maps as during IV infusion. Work is ongoing to identify the different choline metabolites that contribute to the tCho signal. Because oral administration of choline is very safe, this approach could facilitate the translation of tCho-DMI to human subjects.
NIMG-35. IMPACT OF RESECTION AT TIME OF FIRST RECURRENCE IN WHO GRADE 2 IDH-MUTANT GLIOMAS
Authors: Ospina Juan Pablo , Viera Maya , Wetzel Ethan , Cahill Daniel , Gerstner Elizabeth R , Miller Julie J 
Published: November 2024

Abstract

INTRODUCTION
Maximal safe resection standard of care treatment of IDH-mutant gliomas and is associated with improved overall survival (OS). However, the impact of extent of resection (EOR) at first recurrence is not well established and there are no data on its impact on prognosis.

METHODS
We retrospectively collected clinical data on patients with IDH-mutant WHO grade 2 astrocytoma and oligodendroglioma treated at our institution from 1997 to 2023. To assess the impact of EOR at first recurrence, we excluded patients who exclusively underwent diagnostic biopsy. Dates of progression were determined by the treating neuro-oncologist or tumor board consensus. Volumetric measurements of contrast-enhancing (CE) tumor and total T2/FLAIR pre- and post second surgery were obtained with BrainLab SmartBrush tool.

RESULTS
One-hundred patients with recurrent astrocytoma and 35 patients with recurrent oligodendroglioma were identified, of whom 57 and 25, respectively, underwent a second resection and had imaging available for volumetric analysis. In patients with astrocytoma, 13/57 had CE at diagnosis, and 28/57 at first recurrence. EOR of T2/FLAIR and CE volume correlated with improved OS. In multivariate regression analyses, T2/FLAIR EOR at first recurrence correlated with improved OS adjusted for gender, preoperative T2/FLAIR volume, prior radiotherapy or chemotherapy, and initial CE (HR 0.977, p&lt; 0.001). In patients with CE, contrast-EOR correlated with OS adjusted for gender, initial CE, preoperative contrast volume, and prior radiotherapy or chemotherapy (HR 0.929, p&lt; 0.001). Conversely, in patients with WHO grade 2 oligodendroglioma, T2/FLAIR EOR did not significantly impact OS (EOR&gt; 90% p= 0.92, EOR&gt; 20% p= 0.13). Only 5/25 patients had CE at first recurrence precluding further analysis.

CONCLUSIONS
The EOR of CE and total FLAIR hyperintensity at first recurrence appears to positively impact prognosis in patients with WHO grade 2 astrocytoma but not in oligodendroglioma. These findings should be evaluated in prospective trials.