bluuebunny/crossref_metadata_2025_split huggingface dataset:
PATH-59. HISTOLOGIC CORRELATES FOR MOLECULAR FEATURES IN MENINGIOMAS
Authors: Congivaram Harrshavasan , Thirunavu Vineeth , Santana-Santos Lucas , Jamshidi Pouya , Chen William , Nandoliya Khizar , Sukhanova Madina , Smith Heather , McCord Matthew , Steffens Alicia , Walshon Jordain , McCortney Kathleen , Flowers Mariah , Wang Wenxia , Lu Xinyan , Lesniak Maciej , Sonabend Adam , Tate Matthew , Khan Osaama , Heimberger Amy , Brat Daniel , Chandler James , Raleigh David , Magill Stephen , Youngblood Mark , Horbinski Craig 
Published: November 2024

Abstract
Histologic findings are the primary determinant of meningioma prognosis and post-operative management. However, the association of specific pathologic features with molecular alterations has not yet been comprehensively investigated. Here we utilized a large dataset of well-characterized meningiomas to identify correlates between clinically relevant histological and molecular features. Detailed histologic information was collected for 809 resected meningiomas, including cases with DNA methylation (n=380), copy number array (n=252), next-generation sequencing (n=52), RNA risk score (n=394), and/or TERT promoter profiling (n=238). Analyses were conducted on prognostic pathologic features, including WHO Grade, Ki-67, mitotic index (MI), brain invasion, and atypical histologic findings (necrosis, hypercellularity, prominent nucleoli, sheeting, and small cells). Correlation with molecular variables was performed using Fisher’s Exact Tests, including DNA methylation subgroup, RNA risk score, CNV profiles, and TERT promoter mutations. All statistics were corrected for multiple hypothesis testing. Nearly 65% of meningiomas exhibited at least one atypical histologic feature. Among said features, Ki-67/MI, WHO Grade, sheeting, and necrosis were associated with recurrent lesions and known clinical features of aggressive meningiomas. Several histologic features, including hypercellularity, elevated Ki-67/mitotic index, and WHO grade, also correlated with DNA methylation and RNA risk groups. Several chromosomal arm events were related to specific pathologic features (prominent nucleoli, Ki-67, MI, and grade), including chromosomes 1, 4, 10, 14, and 18. Our analysis highlights the continued value in screening for histologic markers of aggressive behavior in meningiomas, as they correlate with the presence of high-risk molecular features and may serve as proxy markers when advanced molecular testing is not available.
PATH-61. GENOMIC SIGNATURE IN NON-SMALL CELL LUNG CANCER PATIENTS METASTATIC TO BRAIN-A SINGLE INSTITUTION EXPERIENCE
Authors: Zafar Maha , Nwankwo Nkolika , Reddy Aswanth 
Published: November 2024

Abstract

BACKGROUND
Lung cancer is leading cause of cancer-related death in US, with 10-30 % of NSCLC patients developing brain metastasis, which challenges curative treatment and life expectancy. Somatic mutations in KRAS and EGFR genes have been commonly implicated with brain metastasis. Other studies have shown higher amplification frequencies in MYC, YAP1, and MMP13 and deletions in CDKN2A/B.

METHODS
We conducted a retrospective study on observational cohort of NSCLC patients from January 2022 to July 2023, using IRB-approved data in patients with confirmed brain metastasis (CBS). Beyond demographic information, data on genomic signatures was obtained from maximum parallel/next-generation sequencing on tumor biopsy samples. Comparative analysis was conducted to predict commonalities in brain metastasis gene signatures.

RESULTS
The study involved 143 newly diagnosed lung cancer patients, with 29 having CBS. Genomic data was available in 24 patients. Most common abnormality was noted in TP53 gene in about 47% of patients, followed by LRP1B (12%). Mutations in KRAS, EGFR, NF1, MET, SMARCA4, KEAP1, and STK11 genes were seen in two patients each. Interestingly, 3 of 4 patients with LRP1B had brain metastasis. Actionable mutations/rearrangements were significantly lower compared to general prevalence of these mutations (KRAS gene 8% and EGFR gene 5%).

CONCLUSIONS
Lung cancer with brain metastasis has an abysmal prognosis due to poor CNS penetration of chemotherapeutic agents. Surgical resection and RT remain cornerstones of treatment, but certain TKI has shown some potential. Our study uncovered a notably higher prevalence of TP53 mutation among patients with brain metastasis. While patient cohort was small, those harboring an LRP1B mutation exhibited significantly higher incidence of brain metastasis. Contrary to prevalent epidemiological data, our patient population demonstrated a lower frequency of targetable mutations (specifically in EGFR and KRAS genes). We hypothesize that this observation is due to a markedly higher smoking prevalence in our region.
NIMG-11. DISCOVERING POSTOPERATIVE APHASIA RECOVERY IN GLIOMA PATIENTS: THE ROLE OF THE RIGHT BROCA’S HOMOLOG AND VERIFICATION
Authors: Weng Shimeng , Wang Peng , Fang Shengyu , Jiang Tao 
Published: November 2024

Abstract

OBJECTIVE
This study aimed to elucidate the neurological mechanisms that support the recovery of postoperative aphasia by examining alterations in language and extended networks in patients with glioma. Additionally, we sought to determine the causal relationship between the right Broca’s homolog and language recovery using neuro-navigated repetitive transcranial magnetic stimulation (nrTMS).

METHODS
Sixty-two patients with left hemisphere gliomas were retrospectively analyzed and categorized into aphasia and non-aphasia groups based on Aphasia Quotient (AQ) scores. Resting-state functional MRI (rs-fMRI) data were collected and analyzed to investigate differences in functional connectivity (FC) and topological properties of language-related networks. Additionally, eight patients with surgery-induced aphasia were prospectively treated with nrTMS, targeting the node identified from the retrospective analysis.

RESULTS
Significant increases in FC between the left auditory cortex and the right inferior frontal gyrus in the Executive Control Network were observed in the non-aphasia group. Nodal properties, such as the nodal efficiency of the right Broca’s homolog, were independently associated with postoperative language function. The nrTMS treatment group demonstrated significant improvements in AQ scores, with correlations between increased nodal efficiency and positive language outcomes.

CONCLUSION
The right hemisphere, specifically the right inferior frontal gyrus, plays a compensatory role in maintaining language function after glioma resection. These findings suggest the therapeutic potential of nrTMS for enhancing postoperative language recovery, offering insights into individualized patient care and rehabilitation strategies for patients with glioma.
NIMG-21. EARLY-STAGE GLIOBLASTOMA AND MOLECULAR ANALYSIS REVEAL THE RADIOLOGICAL INITIATION OF IDH WILDTYPE GLIOBLASTOMA
Authors: Shibahara Ichiyo , Shigeeda Ryota , Orihashi Yasushi , Tanihata Yoko , Fujitani Kazuko , Hyakutake Yuri , Toyoda Mariko , Sato Sumito , Hide Takuichiro , Kumabe Toshihiro 
Published: November 2024

Abstract
Glioblastoma (GB), IDH wildtype, is an aggressive and malignant tumor that necessitate early surgical intervention upon radiological suspicion. Consequently, the natural growth dynamics of GB remain not fully understood. Previous studies have examined GB growth using multiple MRIs between initial radiological diagnosis of GB and preoperative MRI, but these studies have short-term intervals between MRIs (defined as shortGB-cohort). Unless GB growth is a constant phenomenon, shortGB cannot estimate radiological initiation. In this study, we focused on early-stage GB (eGB), characterized by small, nonspecific lesions on MRI that eventually progress to classic GB findings. We compared three cohorts: 49 cases of eGB. 68 cases of shortGBt, and 23 cases of eGB from previous publications (other-eGB). Molecular analyses revealed that TERT promoter mutations, EGFR amplification/gain, CDKN2A hemi/homozygous deletion, and PTEN hemi/homozygous deletion were consistent between eGB and shortGB. Our analysis indicated that the radiological initiation of GB in eGB was -0.84 years (95% confidence interval (CI): -1.09 to -0.68), compared to -0.35 years (95%CI: -0.46 to -0.28) in shortGB. In eGB, factors such as age &lt; 65, MIB1 &gt; 30%, TERTp mutation, and the presence of copy-number alterations (CNA) in EGFR/PTEN/CDKN2A, with or without TERTp mutation, correlated with faster tumor progression. In cases without these alterations, the estimated radiological initiation was -2.31 years (95%CI: -100 to -0.80), indicating slower progression. The ShortGB-cohort did not show any significant changes based on these factors, suggesting it does not actually reflect tumor origin. The other-eGB cohort presented radiological initiation between -0.92 and -0.15 year, consistent with our eGB-cohort. This study investigates the radiological origin of GB using extremely rare cases of eGB, providing insights into the radiological pathophysiology and its association with molecular alterations in IDH-wildtype GB.
NIMG-23. A NOVEL APPROACH TO PERFUSION MRI STUDIES IN BRAIN TUMOR PATIENTS USING ENDOGENOUS DEOXYHEMOGLOBIN AS A CONTRAST AGENT: A PROOF-OF-CONCEPT STUDY
Authors: Stumpo Vittorio , Sayin Ece Su , Bellomo Jacopo , Sobczyk Oliva , van Niftrik Christiaan Hendrik Bas , Sebök Martina , Weller Michael , Regli Luca , Kulcsar Zsolt , Pangalu Athina , Bink Andrea , Duffin James , Mikulis David D , Fisher Joseph A , Fierstra Jorn 
Published: November 2024

Abstract

BACKGROUND
Assessment of resting perfusion in brain tumors is clinically relevant and relies on dynamic susceptibility contrast magnetic resonance imaging using gadolinium contrast. Preliminary studies have introduced the use of controlled hemoglobin desaturation by means of a transient hypoxic stimulus during echo-planar imaging(EPI) as a surrogate for gadolinium for resting perfusion assessment in healthy subjects. In this proof of concept study, we investigated whether this approach is feasible in brain tumors and warrant further validation.

METHODS
A computer controlled gas blender was used to induce transient and standardized hypoxic stimulus in isocapnic conditions during EPI acquisition in a heterogenous cohort of tumor patients. The induced blood-oxygen-level-dependent(BOLD) signal changes determined by transit of a bolus of deoxygenated blood in the brain vasculature were used as a surrogate of gadolinium to calculate cerebral blood volume(CBV), cerebral blood flow(CBF) and mean transit time(MTT) using a global arterial input functions obtained through the BOLD signal measured over the middle cerebral artery as previously described by Poublanc et al. Perfusion parameters were calculated in the whole-brain voxel-by-voxel and in automatically segmented region of interest(ROI) using SPM, AFNI, Verbena softwares and MATLAB in-house written scripts.

RESULTS
Nine patients were included. MTT, rCBV, rCBF were calculated voxel-per-voxel. Obtained maps were overlayed on the co-registered T1 MRI scans and compared to T1CE and FLAIR to identify perfusion patterns in tumor ROIs (contrast enhancement, edema, necrosis). The deoxy-hemoglobin BOLD MRI perfusion were compared to clinical DSC-MRI when available and showed high qualitative agreement.

CONCLUSION
Transient and precise hemoglobin desaturation by controlled hypoxic gas modulation is safe and repeatable in brain tumor patients. The induced BOLD signal change allows measurement of resting perfusion, which qualitatively closely mimic gadolinium perfusion in different brain tumors. Deoxyhemoglobin-based perfusion warrant further quantitative validation against gadolinium in a larger cohort of heterogenous tumor patients.
NIMG-24. PRECISION GLIOBLASTOMA MANAGEMENT USING MET AND FMISO PET SCANS
Authors: Miyake Keisuke , Tatano Masaki , Kanda Takahiro , Suzuki Kenta , Ogawa Daisuke , Hatakeyama Tetsuhiro 
Published: November 2024

Abstract

OBJECTIVE
Positron Emission Tomography (PET) may be useful in diagnosing glioblastoma, determining resection areas, and evaluating therapeutic efficacy. This study evaluated the usefulness of PET scans using 11C-Methionine (MET) to assess amino acid metabolism and 18F-Fluoromisonidazole (FMISO) to assess hypoxic regions in glioblastoma treatment.

METHODS
Thirty glioblastoma patients who underwent MET and FMISO PET studies from July 2013 to March 2024 were included. Patients underwent the Stupp regimen post-tumor resection and were treated with temozolomide (TMZ) and bevacizumab (Bev) upon recurrence. PET scans were performed before and after two courses of Bev treatment. Changes in tumor to normal ratio (TNR) for MET, tumor to blood ratio (TBR) for FMISO, and metabolic tumor volume (MTV) for both MET and FMISO were evaluated. Progression-free survival (PFS) and overall survival (OS) were compared based on the rate of change in MTV for MET and FMISO.

RESULTS
The residual volumes (contrast-enhanced MRI, MET, and FMISO) with a MET removal rate of &gt;90% were 0.08 ml, 0.1 ml, and 0.08 ml, respectively. For FMISO removal rates of &gt;90%, residual volumes were 0.36 ml, 1.54 ml, and 0.05 ml, respectively. Groups with a decreased rate of change in MET MTV had significantly better outcomes: PFS (months) 10.7 vs. 2.8 (p=0.19) and OS (months) 18.6 vs. 4.9 (p=0.09). In the FMISO groups, decreased TBR change rates correlated with better outcomes: PFS (months) 16.6 vs. 2.5 (p&lt;0.01) and OS (months) 22.8 vs. 4.9 (p&lt;0.01). MTV change rates also showed significant differences in outcomes: PFS (months) 10.5 vs. 3.7 (p=0.76) and OS (months) 14.9 vs. 7.0 (p=0.87).

CONCLUSION
Higher MET removal rates correlate with fewer contrast-enhanced MRI and FMISO accumulation areas, suggesting MET as a reliable tumor removal indicator. Both MET and FMISO PET scans are valuable in determining glioblastoma treatment response.
NIMG-27. RADIOMETHYLOMICS FOR NON-INVASIVE PREDICTION OF TUMOR PHENOTYPES AND SURVIVAL IN GLIOBLASTOMA
Authors: Matsumoto Yuji , Singh Omkar , Garcia Jose , Kwak Sunwoo , Abdullaev Zied , Freeburg Nelson , Silverbush Dana , Aldape Kenneth , Davatzikos Christos , Nasrallah MacLean 
Published: November 2024

Abstract

BACKGROUND
DNA methylation profiling has become a pivotal tool in neuro-oncology. However, little is known about the impact of methylation profiling on radiological imaging in IDH-wildtype glioblastoma (GBM). This study explored the potential of radiomics to non-invasively predict molecular characteristics based on the methylation profiling of GBM.

METHODS
This study included a multi-sampling cohort of 32 patients with 113 samples and a single-sampling cohort of 87 patients with 87 samples, which underwent genome-wide methylation analysis and were classified as GBM by the DKFZ/Heidelberg CNS tumor classifier. We performed two different methylation-based deconvolution analyses. Deconvolution 1 estimated the fractions of tumor subtypes (RTK_I, RTK_II, MES_TYP, and MES_ATYP) and cell types in the microenvironment. Deconvolution 2 inferred the abundance of malignant cell states (stem-like and differentiated cell components) and cell types in the microenvironment. We derived 6084 radiomic features from preoperative multi-parametric MRI in each patient.

RESULTS
In the multi-sampling cohort, Deconvolution 1 and Deconvolution 2 demonstrated that tumor subclass components and immune components exhibited heterogeneous distribution across samples within patients; however, the stem-like to differentiated cell ratio was preserved across samples within patients. In the entire cohort, patients with tumors exhibiting a high proportion of the stem-like component, defined as stem-like tumors, had significantly shorter overall survival. Stem-like tumors exhibited significantly higher levels of the RTK_I component and lower proportions of the RTK_II component compared to non-stem-like tumors. A machine learning model that utilizes support vector machines to classify stem-like tumors using radiomic features achieved a mean AUC of 0.71 (95% confidence interval: 0.56–0.85) in nested cross-validation.

CONCLUSIONS
We showed that radiomethylomics can be used to predict tumor composition and patient survival from preoperative MRI in GBM. Based on these promising results we will increase our power with additional samples to facilitate a personalized approach to GBM management.
NIMG-28. HYPERPOLARIZED13C IMAGING OF D-2-HYDROXYGLUTARATE-INDUCED DOWNREGULATION OF PYRUVATE DEHYDROGENASE ACTIVITY PROVIDES AN EARLY READOUT OF RESPONSE TO VORASIDENIB IN MUTANT IDH GLIOMAS
Authors: Batsios Georgios , Gillespie Anne Marie , Viswanath Pavithra 
Published: November 2024

Abstract
Mutations in isocitrate dehydrogenase (IDHm) define a distinct class of gliomas. IDHm converts a-ketoglutarate (a-KG) to D-2-hydroxyglutarate (D-2HG), which inhibits a-KG-dependent histone/DNA demethylases and induces epigenetic alterations that drive tumorigenesis. The IDHm inhibitor vorasidenib extends progression-free survival in IDHm glioma patients and is expected to be widely used for this patient population. However, not all patients respond to vorasidenib, and magnetic resonance imaging (MRI) does not assess whether a patient is responding to vorasidenib. Therefore, the goal of this study was to identify metabolic alterations induced by D-2HG that can be leveraged for non-invasive imaging of IDHm gliomas. Using clinically relevant patient-derived models (BT257, BT142, BT54, SF10417, SF10602), we show that D-2HG downregulates the activity of pyruvate dehydrogenase (PDH), the rate-limiting enzyme for oxidation of glucose-derived pyruvate via the tricarboxylic acid cycle, by multiple mechanisms. Drug affinity target stability assays show that D-2HG directly binds to and inhibits PDH activity. D-2HG also inhibits a-KG-dependent prolyl hydroxylases that target hypoxia-inducible factor 1-a (HIF-1a) for degradation. As a result, D-2HG stabilizes HIF-1a and drives expression of pyruvate dehydrogenase kinase 3, which phosphorylates and inhibits PDH activity. Suppressing D-2HG using vorasidenib upregulates PDH activity in IDHm glioma cells and intracranial tumors. Next, we examined whether hyperpolarized 13C-MRS, which is an advanced MRI-based method of imaging metabolic activity, monitors PDH activity in IDHm gliomas. Following administration of hyperpolarized [2-13C]-pyruvate, metabolic conversion to [5-13C]-glutamate provides a readout of PDH activity. Our studies indicate that [5-13C]-glutamate production from hyperpolarized [2-13C]-pyruvate is upregulated in IDHm glioma cells treated with vorasidenib. Importantly, [5-13C]-glutamate production is elevated within 5 days of treatment with vorasidenib in rats bearing intracranial BT257 or BT142 xenografts, when changes cannot be observed by MRI. Collectively, our studies identify hyperpolarized [2-13C]-pyruvate as a unique probe of D-2HG-induced metabolic rewiring and highlight its ability to assess IDHm glioma response to therapy, which is a challenge in the clinic.
NIMG-31. CASE REPORT: DIAGNOSIS OF AN INFILTRATIVE GLIOMA IN A LI-FRAUMENI SYNDROME PATIENT OBSCURED BY LESION RESPONSIVENESS TO NSCLC TREATMENT
Authors: Janatpour Zachary , Gregory Timothy 
Published: November 2024

Abstract
Li-Fraumeni syndrome is a rare, autosomal dominant disorder linked to germline mutations of the TP53 suppressor gene. Patients with this syndrome are predisposed to various malignancies and a variety of brain tumors to include choroid plexus carcinoma, medulloblastoma, and glioma. We present a 46-year-old woman with a history of Li-Fraumeni syndrome which manifested with multiple systemic malignancies including breast cancer, ovarian teratoma, and leiomyosarcoma. The patient had been undergoing MRI brain surveillance since 2018, which was initially notable for a right cerebellar midline focus of enhancement associated with slowly evolving right middle cerebellar peduncle FLAIR signal, with no detectable neurologic symptoms. She underwent systemic therapy for non-small cell lung cancer (NSCLC) with pemetrexed/cisplatin. Her next MRI brain in August 2023 showed resolution of the cerebellar enhancement with small residual FLAIR signal. In April 2024, the patient presented with new neurologic symptoms to include ataxia, dizziness, difficulty swallowing, and memory loss. Repeat MRI brain revealed new infiltrative FLAIR signal throughout the right temporal lobe extending from the posterior fossa, contiguous with the previously seen cerebellar findings and consistent with infiltrative glioma. Due to fragmented records and care in multiple systems, her updated MRI initially created a diagnostic challenge with a radiographic interpretation of likely encephalitis. This is a unique case documenting a middle-aged female with Li-Fraumeni syndrome, followed for multiple cancers, presenting with new neurologic symptoms and progressive infiltrative FLAIR changes spanning from the cerebellum into the right temporal lobe. These findings highlight the natural history of a TP53 deficient tumor that ostensibly responded to a cisplatin-based regimen given for a different indication, thereby delaying time to symptom onset and need for biopsy. Surveillance of low grade lesions in patients with underlying tumor predisposition syndromes must be interpreted in context of systemic disease burden and concurrent treatments for other neoplasms.
NIMG-33. HIGH-RESOLUTION SODIUM MRI OF HUMAN GLIOMAS AT 3T USING PHYSICS-BASED GENERATIVE AI
Authors: Raymond Catalina , Yao Jingwen , Feiweier Thorsten , Clifford Bryan , Meyer Heiko , Zhong Xiaodong , Kolkovsky Alfredo L Lopez , Sanvito1 Francesco , Oshima Sonoko , Cho Nicholas S , Salamon Noriko , Everson Richard , Cloughesy Timothy F , Ellingson Benjamin M 
Published: November 2024

Abstract

BACKGROUND
Sodium neuroimaging is a promising technique for diagnosing and monitoring brain tumors, providing insights into microenvironment and metabolism. However, at 3T, it is limited by low signal-to-noise ratio and resolution, resulting in long acquisition times and low-quality images. To address these limitations, we developed a physics-informed generative adversarial network (GAN) approach for high-resolution sodium neuroimaging of brain tumors at 3T.

METHODS
5,078 anatomical sequences from 1,330 brain tumor patients undergoing routine proton MRI were used to create a synthetic dataset with physics-based simulated artifacts, including B0 magnetic susceptibility artifacts, chemical shift artifacts, Nyquist aliasing artifacts, Gibbs artifacts, and low-resolution images, with Rician noise added during training to augment the dataset. By using multiple proton MRI contrasts, we hypothesized that the GAN model would learn to correct artifacts while preserving the inherent contrast information. We employed a transfer learning approach with a modified Pix2PixGAN architecture and an Attention-R2UNet generator. Twenty glioma patients consented to participate in this IRB-approved prospective study. Sodium and proton MRIs were acquired in the same sessions using a 3T Siemens scanner using a dual-tuned head coil, with a 3D spoiled gradient-echo sequence optimized for short TE. Sodium-proton exchanger (NHE1) expression was tested with immunohistochemistry from image-guided surgical biopsies.

RESULTS
High-resolution synthetic-sodium MR images were generated using the GAN model. The proposed method successfully reconstructed high-resolution synthetic-sodium MR images with improved SNR compared to traditional sodium images. Synthetic and native measurements were strongly correlated (R2=0.8539, P&lt;0.0001). A significant correlation was seen between synthetic-sodium MR measurements and relative NHE1 tissue expression (ρ=0.5817, P=0.0036).

CONCLUSION
Results suggest that high-resolution synthetic-sodium MRI retains much of the inherent information from native sodium MR while accurately representing NHE1 expression. This approach could make high-resolution sodium neuroimaging at 3T feasible in the clinical environment, potentially improving diagnosis, monitoring, and treatment of brain tumors.