bluuebunny/crossref_metadata_2025 huggingface dataset:
NIMG-49. RADIO-PATHOMIC MAPS OF DE-NOVO GLIOBLASTOMA IDENTIFY PHENOTYPES OF TUMOR INVASION ASSOCIATED WITH PROGNOSIS
Authors: Bobholz Samuel , Lowman Allison , Duenweg Savannah , Winiarz Aleksandra , Kyereme Fitzgerald , Cochran Elizabeth , Connelly Jennifer , Mueller Wade , Agarwal Mohit , Banerjee Anjishnu , LaViolette Peter
Published: November 2022

PURPOSE

Although tumor is known to exist beyond the contrast-enhancing margin, a lack of access to pathological information beyond enhancement has hindered the study of non-angiogenic tumor characteristics and their effects on patient prognosis. This study tested the hypothesis that radio-pathomic maps of tumor characteristics developed using autopsy tissue samples can identify phenotypes relevant to patient survival and treatment outcomes.

METHODS

A dataset of autopsy tissue samples aligned to the MRI as ground truth from 65 glioma patients (training set n=43, test set n=22) was used to train machine learning models that predict and map tumor cellularity (Cell), extracellular fluid (ECF), and cytoplasm (Cyt) density following our previously published methodology (Bobholz et al. 2022). Cell, ECF, and Cyt maps were then generated from the pre-surgical MRI scans from an independent dataset of 80 glioblastoma patients. Each patient was separated into groups based on the appearance of tumor characteristics beyond the contrast-enhancing margin. Group phenotypes included Well-Circumscribed (WC) tumors with no tumor activity beyond contrast enhancement, Necrotic Front (NF) tumors with areas of necrosis extending beyond the tumor margin, Hypercellular Front (HF) tumors with areas of increased cellularity surrounding the tumor, and Hybrid Front (HYF) tumors with characteristics of both HF and NF tumors. A Cox regression was used to assess survival differences between phenotypes, controlling for treatment history.

RESULTS

Across the 80 patients, 22 were classified as WC, 14 were classified as HF, 24 were classified as NF, and 20 were classified as HYF. NF, HF, and HYF tumors each showed significant/trending reductions in survival when compared to WC tumors (HR=2.02, p=0.03; HR=2.0, p=0.06; and HR=1.75, p=0.09, respectively).

CONCLUSION

Radio-pathomic phenotypes identify characteristics beyond the contrast-enhancing margin that affect overall survival outcome in glioblastoma.
NIMG-53. DELTA RELAXOMETRY WITH CONTRAST ENHANCED MAGNETIC RESONANCE FINGERPRINTING: INITIAL APPLICATION TO DIFFERENTIATE BRAIN METASTASES AND GLIOBLASTOMA
Authors: Deng Shengwen , Zhao Walter , Nirappel Abraham , Jordan David , Sloan Andrew , Ma Dan , Badve Chaitra
Published: November 2022

PURPOSE

The utility of post-contrast magnetic resonance fingerprinting (MRF) for brain tumor assessment has not been assessed. The aim of this work is to report differences in MRF-derived delta-relaxometry metrics between brain metastases and glioblastoma, offering a new strategy for tumor differentiation.

METHODS

Post- and pre-contrast MRF (T1, T2 and proton density maps) were acquired from 29 patients (14 brain metastases (Met), 15 glioblastoma (GB)) along with conventional MRI (T1w, T1w-Gd, T2w, T2w-FLAIR, and ADC). Post-contrast MRF was skull-stripped and non-linearly co-registered with pre-contrast MRF. Delta relaxometry metrics (ΔR1/ΔR2 ratio, ΔR1, ΔR2, and normalized ΔR1/ΔR2) were calculated in the native image space (1.2x1.2x3.0 mm3). Tumor regions were segmented using DeepMedic into necrotic core (NC), enhancing tumor (ET), and peritumoral edema (ED). ROI-averaged means of delta relaxometry metrics were compared using paired t-test for ET and ED regions in Met vs GB. Voxel-wise ΔR1/ΔR2 ratios (log transformed) were compared using unpaired two-tailed t-test with Bonferroni correction to quantify distribution differences in delta relaxometry between Met and GB.

RESULTS

Across all voxels of all patients in each group, ΔR1/ΔR2 ratios between Met and GB were different (0.272±0.61 vs 0.247±0.66 in ED, p < .001; 0.278±0.69 vs 0.264±0.67 in ET, p < .001). On a per-patient basis, the median, 75th percentile, and 90th percentile of ΔR1/ΔR2 ratios were different between ET and ED regions (p < .001). Within-ROI (NC, ET, and ED) averaged mean ΔR1/R2 ratios were not significantly different between Met and GB.

CONCLUSION

Voxel-wise distribution of ΔR1/ΔR2 ratios was different between tumor types (Met and GB) in both ET and ED regions. ROI-averaged ΔR1/ΔR2 ratios were different between ET and ED regions, but not specific for tumor type. Delta relaxometry provides a unique tumor-specific contrast and shows potential for solid tumor as well as peritumoral edema differentiation between Met and GB.
NIMG-55. A COMPARISON OF THREE DIFFERENT DEEP LEARNING-BASED MODELS TO PREDICT THE MGMT PROMOTER METHYLATION STATUS IN GLIOBLASTOMA USING BRAIN MRI
Authors: Faghani Shahriar , Khosravi Bardia , Moassefi Mana , Conte Gian Marco , Erickson Bradley
Published: November 2022

GBM is the most common primary malignant brain tumor in adults. O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status is an important prognostic biomarker that predicts the response to temozolomide and guides the treatment decisions. At present, the only reliable way to determine MGMT promoter methylation status is through the analysis of tumor tissues. Given the limitations and complications of histology-based methods, an imaging-based approach for non-invasively MGMT promoter methylation status prediction is beneficial. This study aimed to develop and compare three different deep-learning-based approaches for predicting MGMT promoter methylation status non-invasively. We obtained 576 T2 weighted images (T2WIs) with their corresponding tumor masks and MGMT promoter methylation status from, The Brain Tumor Segmentation (BraTS) 2021 datasets. Dataset was split into five folds at the patient's level stratified by MGMT promoter methylation status to perform a 5-fold cross-validation. We developed three different models: voxel-wise, slice-wise, and whole-brain. For voxel-wise classification, methylated and unmethylated MGMT tumor masks were made into 1 and 2 with 0 background, respectively. We converted each T2WI into 32x32x32 patches. We trained a 3D-Vnet model for tumor segmentation. After inference, we constructed the whole brain volume based on the patch's coordinates. The final prediction of MGMT methylation status was made by majority voting between the predicted voxel values of the biggest connected component. For slice-wise classification, we trained an object detection model for tumor detection and MGMT methylation status prediction; then, we used majority voting for the final prediction. For the whole-brain approach, we trained a 3D Densenet121 for prediction. Whole-brain, slice-wise, voxel-wise, accuracy was 65.42%(SD 3.97%), 61.37%(SD 1.48%), and 56.84%(SD 4.38%) respectively. We found that across the whole-brain, slice-wise, and voxel-wise deep learning approaches, the whole-brain approach is the most effective approach for MGMT methylation status prediction on the BraTS 2021 dataset.
NIMG-57. NON-INVASIVE DIAGNOSIS OF IDH-MUTANT BRAINSTEM GLIOMAS
Authors: Kushnirsky Marina , Thakur Sunitha , Karajannis Matthias , Bale Tejus , Rosenblum Marc , Malani Rachna , Gavrilovic Igor T , Schaff Lauren , Pentsova Elena , Grommes Christian , Moss Nelson , Sait Sameer Farouk , Hill Katherine , Miller Alexandra , Mellinghoff Ingo , Young Robert , Lin Andrew
Published: November 2022

INTRODUCTION

Treatment of brainstem tumors is often initiated without a tissue diagnosis due to the risk of biopsy. A subset of brainstem gliomas harbor an isocitrate dehydrogenase 1/2 (IDH) mutation, which predicts response to alkylator chemotherapy and IDH inhibitors; non-invasive diagnostic tests are needed to identify these mutations.

METHODS

We identified a cohort of patients with IDH-mutant brainstem gliomas through chart review of patients who underwent magnetic resonance spectroscopy (MRS) and/or brain biopsy. IDH mutation was established by biopsy, presence of a 2-hydroxyglutarate (2HG) peak on MRS, or identification on cerebrospinal fluid (CSF) sequencing of cell-free DNA (cfDNA).

RESULTS

We identified 15 patients with IDH-mutant brainstem gliomas, age range 5-48, 47% women. 15/15 were involving/abutting the brachium pontis, and 10/15 were non-enhancing at diagnosis. 13/15 patients were identified by biopsy, 1/15 by MRS and CSF, and 1/15 by MRS only. 10/13 patients with available data had a non-IDH1 R132H mutation in IDH1/2. 7/7 patients with MRS prior to radiation had a 2HG peak (MRS was concordant with tissue in all cases in which biopsy was obtained). 4/6 patients with MRS post-radiation retained a 2HG peak. 4 IDH-mutant tumors had sequencing of cfDNA and an IDH mutation was found in 2/4. Response data was available in 13/15 patients; all received radiation, 10 with concurrent temozolomide: best response was partial response in 8 and stable disease in 5. 4 patients received an IDH inhibitor: 2 patients after progression, and 2 as maintenance after radiation/temozolomide, achieving tumor control in all. For this cohort, median PFS was 71.4 months and median OS has not been reached.

CONCLUSION

IDH-mutant brainstem gliomas have a characteristic appearance, a high response rate to treatment, and a better overall prognosis than other brainstem tumors. MRS and CSF cfDNA sequencing allow for non-invasive diagnosis of IDH mutations in these patients.
NIMG-60. MAGNETIC RESONANCE SPECTROSCOPY IN THE DIAGNOSTIC AND MANAGEMENT OF PATIENTS WITH BRAIN TUMORS OF GLIAL ORIGIN
Authors: Acosta Pablo Moreno , Padín Trinidad González , Malaver Gina , Gamboa Oscar , Villamil Daniel Fino
Published: November 2022

PURPOSE

Magnetic resonance spectroscopy (MRS) is a quantitative technique based on the chemical shift of protons that allows the metabolic profile of tissues to be analyzed and characterized. Standard glial tumor analysis comprises Creatine (Cr), N-acetil aspartato (NAA) and Choline (Cho) metabolites, usually altered in brain pathologies (low grade tumor -LGT-, high-grade cancer -HGT-, metastasis -MTT-, gliosis -GLS-). The aim of this study is to analyze the feasibility of MRS technique in brain glial tumor diagnosis.

METHODS

The prospective study, approved by the Institutional Review Board, included 68 randomized patients (39 female and 29 male, mean age 47 y, with confirmed histopathology). Data was acquired at a Essenza Siemens 1.5T scanner, single voxel (SV) at the lesion (IT) and at healthy tissue (HT) in the contralateral hemisphere. A multivoxel (CS) sample was obtained from a ROI containing HT and IT. Postprocessing was done at Syngo workstation, statistical analyses were performed using SPSS v25.0 and p-values < 0.05 were considered statistically significant.

RESULTS

The group analysis (by pathology) for HT demonstrates homogeneity. For pathological ROIs (SV, long_TE), rNAA and rCho indexes (r stands for Cr ratio) had a p=0.003 and p=0.048 respectively; however, aCho (NAA ratio) had a p=0.11. For pathological regions, rNAA coefficient for LGT and GLS: p=0.008, LGT and MTT: p=0.02, HGT and MTT: p=0.008 and GLS with MTT: p=0.019. Meanwhile, for the rCho index, LGT and HGT: p=0.005, LGT and MTT: p=0.008, GLS and MTT: p=0.002. Short-TE SV demonstrates inhomogeneity between HT and only the aCho ratio allows to distinguish LGT and MTT (p=0.01) and GLS and MTT (p=0.008). Parametric map (from CS) of both rCho and aCho visually describes pathological regions (83% and 72%).

CONCLUSIONS

Long_TE-SV allows to characterize brain tumor lesions and CS provides a spatial metabolic description of the IT localization.
NIMG-62. RADIOMIC-BASED PROGRESSION-FREE SURVIVAL STRATIFICATION OF PEDIATRIC LOW-GRADE GLIOMA IS ASSOCIATED WITH MOLECULAR ALTERATIONS
Authors: Kazerooni Anahita Fathi , Arif Sherjeel , Haldar Debanjan , Zhao Chao , Kim Meen Chul , Madhogarhia Rachel , Familiar Ariana , Bagheri Sina , Anderson Hannah , Ware Jeffrey B , Vossough Arastoo , Storm Philip B , Resnick Adam C , Davatzikos Christos , Nabavizadeh Ali
Published: November 2022

Pediatric low-grade glioma (pLGG) encompasses a variety of tumor subtypes with heterogeneous treatment response and relatively long progression-free survival (PFS). Radiomics may serve as a non-invasive and in-vivo tool for early prediction of PFS as a surrogate marker for treatment response and to objectively gauge the efficacy of novel treatment strategies. Here, we present a multivariate model based on radiomic features and clinical variables for risk stratification of pLGGs in terms of PFS and seek associations of the predicted risk groups and mutations in key molecular markers using data from PedCBioportal. Pre-operative multi-parametric MRI scans (T1-pre, T1-post, T2, T2-FLAIR) of 129 patients with newly diagnosed pLGG (median age, 7.76, range, 0.35-19.58 years; median PFS, 28.5, range, 1.1-124.8 months) were collected and quantitative radiomic features (n = 881) were extracted. A multivariate Cox proportional hazard’s (Cox-PH) regression model was fitted based on clinical (age, sex, and extent of tumor resection) and radiomic variables using 4-fold cross-validation. A subset of radiomic features (n = 27) that were most predictive of PFS was selected by applying Elastic Net regularization penalty during Cox-PH model fitting. High-, medium- and low-risk groups were determined based on model predictions. Cox-PH modeling showed excellent performance for prediction of PFS as suggested by the concordance index of 0.78. Radiogenomic assessment (data available in 94/129 patients) showed more enrichment of mutations in NF1 and RB1 genes in the high-risk group, as compared to the low- and medium-risk groups. We showed the potential value of radiomics in providing upfront prediction of PFS, which may further be used as an added treatment arm for early assessment of treatment response of the pLGG patients enrolled in the clinical trials. In the next step of this work, we will expand the cohort and cross-validate these results in an external cohort.
NIMG-64. INTRAOPERATIVE LANGUAGE MAPPING USING GAMMA-BAND MODULATIONS OF ELECTROCORTICOGRAM (ECOG) INDUCED BY WORD/SOUND CATEGORIZATION TASK: VALIDATION WITH REPRODUCIBLE SPEECH ARRESTS DURING LINGUISTIC TASKS
Authors: Tasnim Israt , Ince Nuri , Prabhu Sujit , Noll Kyle , Swamy Chandra , Connelly Katherine , Asman Priscella , Sudhakar Tummala , Prinsloo Sarah , Ene Chibawanye , Grasu Roxana , Liu Ho-Ling , Muir Matthew , Bhavsar Shreyas , Kumar Vinodh
Published: November 2022

OBJECTIVE

Determination of the correlation between gamma-band modulations of electrocorticogram (ECoG) induced by linguistic tasks and reproducible speech arrests caused by bipolar direct cortical stimulations (DCS).

METHODS

3 subjects (age 39, 56, 64 years) with left temporal lobe glioma underwent surgery involving awake craniotomy. A 4x8 ECoG electrode grid (2.3mm contact exposure, 1cm contact spacing) was placed above the respective tumor area. A MATLAB-Simulink based real-time software system running on a portable laptop computer was used to map gamma-band modulations as a 2D heat map while the subjects engaged in different linguistic tasks: word/sound categorization by pressing a button, object naming, action naming, written descriptive naming, and auditory descriptive naming. Auditory stimulus was applied during word/sound categorization task (duration 300 – 500ms), auditory descriptive naming ( > 1s); other tasks involved visual stimulus only. The subjects repeated the four naming tasks while bipolar DCS (2/4/6 mA, 60Hz, 2s) was applied at different electrode pairs.

RESULTS

The electrodes having stronger gamma-band modulations were distinct for different tasks. Reproducible speech arrests occurred during object, action, auditory naming tasks while stimulating specific electrode pairs, even though not all these electrodes had strong activations during these tasks. Across all subjects these electrodes had strong activations consistently during word/sound categorization tasks, starting as early as 250ms and lasting even after the auditory stimuli were terminated (~ 650ms). The longer activations can be associated with word recognition process. The subjects self-reported about having difficulty in comprehension rather than speech production during speech arrests. 3D brain rendering using MRI images showed that the speech arrest electrodes were identically located on the superior temporal gyrus, inferior to central sulcus for all 3 subjects.

CONCLUSION

Intraoperative language mapping guided by gamma-band ECoG modulations induced by word/sound categorization tasks can be utilized to localize eloquent cortex associated with auditory processing.
NIMG-65. IMPROVED SPATIAL MAPPING OF TUMOR AGGRESSIVENESS WITH 1H MAGNETIC RESONANCE SPECTROSCOPY AND DEEP LEARNING IN PATIENTS WITH NEWLY-DIAGNOSED GLIOMA
Authors: Tran Nate , Li Yan , Ellison Jacob , Adegbite Oluwaseun , Phillips Joanna J , Molinaro Annette , Pedoia Valentina , Shai Anny , Nair Devika , Jakary Angela , Lafontaine Marisa , Villanueva-Meyer Javier , Berger Mitchel S , Hervey-Jumper Shawn L , Aghi Manish , Chang Susan M , Lupo Janine
Published: November 2022

INTRODUCTION

Noninvasive, radiopathomic mapping of tumor aggressiveness can benefit patients with glioma by guiding the selection of tissue samples for diagnosis, increasing extent of resection, and non-invasively characterizing residual tumor burden for subsequent treatment. Although prior studies have demonstrated the utility of metabolic metrics quantified from 1H-MR Spectroscopy (MRS) in probing tumor pathology, this study evaluated the benefit of using the entire 1D-spectrum and deep learning for radiopathomic mapping of intratumoral cellularity, proliferation (ki-67), and a new tumor aggressiveness index (TAI) defined as log((n(ki−67)+n(cellularity))*tumor-score).

METHODS

Multi-voxel 1H-MRS was acquired on 281 patients newly diagnosed with a glioma (47% IDH-wildtype) immediately before surgical resection. After reconstructing individual spectra at the locations where tissue samples were obtained during surgery and normalizing by NAA in contralateral normal-appearing-white-matter, 607 spectra with corresponding histopathology were deemed of sufficient quality for analysis. A 1D convolutional-neural-network with bidirectional long- and short-term memory deep-learning model using the entire spectrum (0.6-3.6ppm) was compared to mixed-effects regression (with choline-to-NAA index[CNI]) and Random Forest (with CNI+normalized peak heights) models for predicting ki-67, cellularity, and TAI. Results &

DISCUSSION

Using deep-learning on the entire spectrum resulted in 10.3%-22.1% lower mean absolute error (MAE) and 0.32-0.37 higher R2 values compared to using CNI alone or a random forest model with multiple metabolic metrics. MAE values for all 3 deep-learning models were 26-44% < 1 standard deviation of the ground truth, demonstrating reasonable prediction accuracy within the test data set. Although the lowest MAE (0.16) and highest R2 (0.41) was attained when predicting TAI with deep-learning, the prediction of cellularity resulted in the lowest %MAE. Colormaps of predicted pathology identified regions of heightened aggressiveness surrounding tissue samples with most abnormal pathological features that sometimes extended beyond the non-enhancing lesion. Current work is evaluating the clinical utility of our deep-learning model and predicted maps of aggressiveness.
NIMG-68. IMAGING PHOSPHOLIPID BIOSYNTHESIS ENABLES NON-INVASIVE ASSESSMENT OF BRAIN TUMOR RESPONSE TO THERAPY
Authors: Taglang Celine , Batsios Georgios , Tran Meryssa , Gillepspie Anne Marie , Viswanath Pavithra
Published: November 2022

Elevated phospholipid biosynthesis is a metabolic hallmark of cancer. Due to the high membrane turnover associated with uncontrolled proliferation, tumor cells invariably upregulate phospholipid biosynthesis. Choline is a dietary nutrient that is phosphorylated to phosphocholine (PC) and subsequently incorporated into phosphatidylcholine, which is the primary membrane phospholipid in mammalian cells. Choline kinase α (CKα) is the key enzyme in this pathway and its expression is elevated in most cancers. Identifying non-invasive methods of imaging CKα activity, can, therefore, enable assessment of tumor burden and response to therapy. Deuterium magnetic resonance spectroscopy (DMRS) following administration of 2H-labeled substrates recently emerged as a simple, robust, clinically translatable method of assessing metabolic activity in vivo. The goals of the current study were to determine whether DMRS-based assessment of PC production from [2H9]-choline tracks CKα activity and to establish the utility of [2H9]-choline for glioma imaging in vivo. First, we show that [2H9]-choline metabolism to PC can be observed in live patient-derived glioma cells (GBM6 and BT88). Silencing CKα abrogates PC production from [2H9]-choline in both GBM6 and BT88 models, thereby confirming that [2H9]-choline provides a readout of CKα activity. Next, we examined the ability of [2H9]-choline to monitor tumor burden and response to therapy in vivo. [2H9]-choline metabolism to PC can be observed in mice bearing orthotopic patient-derived GBM6 or BT257 tumors, but not in tumor-free healthy controls. Importantly, following treatment of mice bearing orthotopic BT257 tumors with temozolomide, which is standard of care for glioma patients, PC production from [2H9]-choline is reduced at early timepoints when changes in tumor volume cannot be detected by anatomical imaging. Taken together, our studies, for the first time, identify [2H9]-choline as a probe of CKα activity and highlight its ability to assess tumor burden and early response to therapy, which is a challenge in glioma imaging.
NIMG-84. PREDICTION OF RESPONSE TO LOMUSTINE-BASED CHEMOTHERAPY IN GLIOMA PATIENTS AT RECURRENCE USING MRI AND FET PET
Authors: Wollring Michael M , Werner Jan-Michael , Bauer Elena , Tscherpel Caroline , Lohmann Philipp , Stoffels Gabriele , Kabbasch Christoph , Goldbrunner Roland , Fink Gereon , Langen Karl-Josef , Galldiks Norbert
Published: November 2022

BACKGROUND

This study evaluates O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET and contrast-enhanced MRI for early response assessment in glioma patients at recurrence treated with lomustine-based chemotherapy.

METHODS

Thirty-six adult patients with WHO CNS Grade 3 or 4 gliomas (glioblastoma, 69%) at recurrence (median number of recurrences, 1; range, 1-3) were retrospectively identified. Besides MRI, serial FET PET scans were performed at baseline and early after chemotherapy initiation (median number of cycles, 2). Mean and maximum tumor-to-brain ratios (TBR), metabolic tumor volumes (MTV), the occurrence of new distant hotspots with a mean TBR > 1.6 at follow-up, and the dynamic parameter time-to-peak were derived from all FET PET scans. Threshold values of PET parameters were defined using receiver operating characteristic analyses to predict progression-free survival (PFS) of ≥ 6 months and overall survival (OS) of ≥ 12 months. MRI response assessment was based on RANO criteria. Using univariate and multivariate survival estimates, the predictive value of FET PET parameters and RANO criteria were subsequently evaluated.

RESULTS

After treatment initiation, the median follow-up time was 11 months (range, 3-71 months). Relative changes of the mean and maximum TBR, MTV, and RANO criteria predicted a significantly longer PFS (all P< 0.003) and OS (all P< 0.05). At follow-up, the occurrence of new distant hotspots (n≥ 1) predicted a worse outcome, with significantly shorter PFS (P=0.001) and OS (P< 0.001). Changes of the dynamic parameter time-to-peak did not predict a significantly longer PFS or OS (P > 0.05). Multivariate survival analyses revealed that new distant hotspots at follow-up had the highest significance level to predict non-response (P< 0.001; hazard ratio, 8.578), independent of RANO criteria, IDH mutation status, and O6-methylguanine-DNA-methyltransferase promoter methylation.

CONCLUSIONS

FET PET seems to be a powerful tool for identifying responders to lomustine-based chemotherapy early after treatment initiation.
NIMG-85. RADIOMIC FEATURES PREDICTIVE OF RESPONSE IN HGG-TARGETING CAR-T THERAPY
Authors: Filippov Aleksandr , Shaktah Lawrence , Wong Chi Wah , Bonjoc Kimberley-Jane , Shaktah Bassam , Rockne Russell C , Brown Christine , Chaudhry Ammar , Badie Behnam
Published: November 2022

SIGNIFICANCE

Radiomics may improve precision medicine in CAR-T (Chimeric Antigen Receptor T Cell) therapy patient selection.

BACKGROUND

High-Grade Glioma (HGG) is a heterogenous primary CNS neoplasm with a high recurrence rate and poor outcomes. Many studies are exploring CAR T cells to combat HGG. Radiomic models have shown value in identifying biomarkers predictive of tumor genetics, response, and patient prognosis. In this study, we explore radiomic features derived from four clinical sequences and volumes of edema and enhancing tumor to predict treatment response to the first three doses of CAR-T therapy.

METHODS

In this IRB-approved phase 1 clinical trial (IRB 13384), patients underwent surgical resection of the tumor and received CAR-T cell therapy. Of the 82 patients accrued, 59 (20 females, median age = 49) completed three cycles of therapy and had 3T field strength MRI scans with minimal imaging artifacts. T1 weighted pre-contrast, T1 weighted post-contrast, T2 weighted, and T2 FLuid Attenuated Inversion Recovery sequences were used to generate 3D and 2D radiomics features. In total 28,541 radiomic features were generated per patient using the images prior to CAR-T administration. Each patient’s response to treatment after three cycles was determined to be either stable disease (29 patients) or progression. The radiomic feature set dimensionality was reduced using Maximum Relevance Minimum Redundancy. 10-fold cross-validation XGBoost was used to determine radiomic features predictive of treatment response with a randomized grid search for hyperparameter tuning.

RESULTS

Six radiomic features (four shape-based), had high SHapley Additive exPlanations (SHAP)-based importance feature predictive of RANO response with an AUC >0.73.

CONCLUSION

Despite the limited study size, such imaging-based radiomic models can serve as a potential basis for optimizing clinical trial design through more precise patient screening and providing potential predictive imaging biomarkers of whether a patient will respond to CAR-T cell therapy in HGGs.
NIMG-86. REVEALING THE BIOLOGY BEHIND MRI SIGNATURES IN GLIOBLASTOMA
Authors: Lewis Erika , Tran Nhan , Swanson Kristin , Hu Leland , Plaisier Christopher
Published: November 2022

The brain is notoriously difficult to access because of its location and protective mechanisms, both internal and external. Imaging-based approaches, such as multiparametric magnetic resonance imaging (mpMRI), provide a method to bypass these obstacles. mpMRI can capture a wide range of data from tumors embedded in brain tissue through various imaging features. However, the biological function captured by each imaging feature remains largely unknown, particularly within the aggressive disease glioblastoma multiforme (GBM). We integrated our GBM SYstems Genetics Network AnaLysis (gbmSYGNAL) gene regulatory network (Plaisier, et al. 2016), based on the multi-omic patient data from The Cancer Genome Atlas (TCGA), with mpMRI-localized patient tumor biopsies. The gbmSYGNAL network was reconstructed within the new image-localized biopsies, and associations revealed a strong connection between the spoiled gradient recalled echo + contrast (SPGR+C) feature and the immune hallmarks of cancer. The SPGR+C method generates an image by employing a contrast agent that bypasses the blood brain barrier (BBB) through leaky blood vessels that have weakened from the force of the rapidly growing GBM tumor. Furthermore, a significant association between SPGR+C signal and the presence of both infiltrating macrophages and T cells indicated that peripheral immune cells may also cross the BBB at these leaky sites. Separately, the mean diffusivity (MD) & T2 features were linked to the sustained angiogenesis hallmark. These features displayed high association with angiogenic genes, such as FLT1, KDR, and PDGFRB, and correlated with the presence of histologically identified vessels. Detection of these disease-relevant functions via mpMRI features has powerful clinical applications, providing a non-invasive approach to GBM diagnosis, prognosis, and treatment direction.
NIMG-88. A TRANSFER LEARNING APPROACH FOR AUTOMATIC SEGMENTATION OF TUMOR SUB-COMPARTMENTS IN PEDIATRIC MEDULLOBLASTOMA USING MULTIPARAMETRIC MRI: PRELIMINARY FINDINGS
Authors: Bareja Rohan , Ismail Marwa , Martin Douglas , Nayate Ameya , Tamrazi Benita , Salloum Ralph , Margol Ashley , Judkins Alexander , Iyer Sukanya , de Blank Peter , Tiwari Pallavi
Published: November 2022

PURPOSE

Superior outcomes for medulloblastoma (MB) requires precise surgical resection which can be guided by tumor segmentation. We present the first attempt at automatic segmentation of MB tumors via a hierarchical transfer-learning model that (1) segments the entire tumor habitat (enhancing tumor (ET), necrosis/non-enhancing tumor (NET), edema), followed by (2) training separate models for each of the sub-compartments. Transfer learning from adult brain tumors is used to optimize segmentation of tumor sub-compartments for pediatric MB.

METHODS

We evaluated 300 adult glioma studies (BRATS) and 49 pediatric MB studies (2-18 years old), both consisting of Gd-T1w, T2w, FLAIR sequences. The MB cohort was collected from Children's Hospital of Los Angeles (Nf19) and Cincinnati Children’s Hospital Medical Center (Nf30). Scans were registered to age-specific pediatric atlases, followed by bias correction and skull-stripping. Ground truth for the tumor sub-compartments was generated via consensus across two experts. We employed a 3D nn-Unet segmentation model on BRATS dataset using initial learning rate of 0.01, stochastic gradient descent as optimizer, and an average of dice loss and cross-entropy loss as the loss function. A hierarchical transfer learning model with Models Genesis was then applied, which allowed for fine tuning every layer on the pediatric MB dataset, across 5-fold cross validation. Dice score was used as performance metric, such that a perfect overlap between ground truth and prediction would yield a Dice score of 1.

RESULTS

Our 3D hierarchical segmentation model yielded mean dice scores of 0.85±0.03 for the entire tumor habitat; 0.77±0.048 for ET, 0.73±0.09 for edema, and 0.56±0.09 for NET + necrosis segmentation, across cross-validation runs. Overall, tumor outline and segmentation matched well with the ground truth, especially for the entire tumor, ET and enhancing tumor sub-compartments.

CONCLUSIONS

Our segmentation approach holds promise for accurate automated delineation of the tumor sub-compartments in pediatric Medulloblastoma.
NIMG-89. DISSEMINATED SPINAL METASTASES FROM A PITUITARY CARCINOMA
Authors: Anderson Mark , Pratibhu Parakash
Published: November 2022

Pituitary carcinomas are rare malignant neoplasms and rarely result in a solitary spinal metastasis. In this report we describe a case of pituitary carcinoma that metastasized to the spinal canal and the nerve roots at numerous spinal levels, mimicking neurofibromatosis of the spine. This patient is a 72 year old right-handed female with past medical history of pituitary adenoma which was resected 5 years prior and stable on imaging. At presentation, patient was seen for right sciatica, and an MRI showed multiple enhancing intradural extramedullary lesions mainly in the lumbar spine, felt to represent nerve sheath tumors, neurofibromas. She underwent genetic testing, but NF1, NF2, SMARC1B, SPRED1, LTRZ1 were not found to have a mutation. Over a 3 year period, she had progression of her spinal tumors. The pituitary lesion remained stable in appearance. She underwent resection of multiple lumbar lesions and pathology was consistent with pituitary carcinoma.Patient tolerated up to almost 11 full cycles of temozolomide before it was put on hold due to significant deconditioning and lethargy. Imaging revealed a partial response of the spinal cord metastases. This is an unusual presentation for metastatic pituitary carcinoma and delay in diagnosis resulted in significant morbidity.
NIMG-90. DIFFERENTIATION OF INTRACRANIAL SOLITARY FIBROUS TUMOR AND MENINGIOMA ON CONVENTIONAL, DIFFUSION-WEIGHTED, AND DYNAMIC SUSCEPTIBILITY CONTRAST PERFUSION MRI
Authors: Kurokawa Ryo , Kurokawa Mariko , Baba Akira , Kim John , Capizzano Aristides , Bapuraj Jayapalli , Srinivasan Ashok , Moritani Toshio
Published: November 2022

BACKGROUND AND PURPOSE

To evaluate the differences in the imaging findings of intracranial solitary fibrous tumor (SFT) and meningioma on dynamic susceptibility contrast (DSC) perfusion MRI, apparent diffusion coefficient (ADC), and conventional sequences.

METHODS

Between January 2016 and April 2022, the study enrolled 14 (median, 46 years [range, 25–74]; six females; seven with DSC-MRI) and 27 patients (median, 53 years [21–83]; 23 females; all with DSC-MRI) with pathologically proven SFT and meningioma, respectively. The normalized relative cerebral blood volume and flow (nrCBV and nrCBF), percentage signal recovery (PSR), normalized mean ADC (nADCmean), and conventional imaging features, including T1-weighted hyperintensity, were evaluated and statistically compared using Bonferonni correction.

RESULTS

PSR was significantly lower in SFT compared with that in meningioma (median, 22.5 [range, 6.4–48.8] vs. 70.1 [range, 18.6–104.2], p< 0.001). The majority of SFT showed mainly T1-weighted hyperintensities compared to the gray matter, while only one meningioma showed the finding (8/14 [57.1%] vs. 1/27 [3.7%], p< 0.001). No significant difference was observed in nrCBV, nrCBF, or nADCmean.

CONCLUSIONS

PFS was significantly lower in intracranial SFT compared with that in meningioma, indicating the difference in capillary permeability between the tumors. Comparing the hyperintensity on T1WI of the solid components with that of the cerebral cortex was a simple and useful characteristic to differentiate SFT from meningioma.
NIMG-98. IDENTIFYING PATTERNS OF FAILURE AFTER INITIAL THERAPY IN PRIMARY CNS LYMPHOMA IN A LARGE PATIENT COHORT
Authors: Tringale Kathryn , Yahalom Joachim , Scordo Michael , Vachha Behroze , Schaff Lauren , Grommes Christian , Imber Brandon
Published: November 2022

INTRODUCTION

Treatment of primary CNS lymphoma (PCNSL) has rapidly evolved, emphasizing improved efficacy while reducing neurotoxicity. PCNSL has historically been considered a multifocal disease and many patients relapse after first-line therapy. We evaluated relapse patterns in a large cohort of contemporarily treated patients.

METHODS

Consecutive PCNSL patients treated at MSKCC between 1983-2020 were analyzed. T1 post-contrast-enhancing disease on baseline MRI was characterized. Site of initial relapse was characterized as purely local (involving/adjacent to initial site) vs distant intraparenchymal, or other (e.g., both local and distant, systemic, ocular). Progression-free survival (PFS) was evaluated using Kaplan Meier methods.

RESULTS

Of 645 patients, 564 were eligible for analysis (diffuse large B-cell histology, sufficient data, ≥ 1 MRI response assessment). Median follow-up was 2.7 years (IQR 1.2-5.6). Median age was 63 years (range 19-90). Baseline disease was often supratentorial (420, 74%), multifocal (274, 49%), and bilateral (224, 40%). Fewer had leptomeningeal disease (94/430 CSF+, 22%; 117/559 radiographically positive, 21%). Most received methotrexate (MTX)-based induction (534, 96%), most commonly rituximab, MTX, procarbazine, vincristine (R-MVP; 257, 46%) or MVP (144, 26%). Overall, 286 (51%) patients relapsed with a median PFS of 2.1 years (95% CI 1.8-2.5). Of 275 characterizable relapses, 75 (27%) were exclusively local intraparenchymal, 91 (33%) were distant intraparenchymal, and 109 (40%) were other. Baseline unifocal disease often relapsed unifocally (66/118 baseline unifocal; 56%). Of 126 unifocal relapses, 45 (36%) were local. Of 202 patients with baseline supratentorial disease, 152 (75%) relapsed supratentorially. Unilateral relapses often remain ipsilateral (49% left- and 54% right-hemispheric lesions at baseline and relapse).

CONCLUSIONS

In a large PCNSL cohort, relapses often maintained baseline characteristics. For a disease historically considered multifocal, a substantial proportion of relapses were local. Future analyses will evaluate predictors of relapse, which can further efforts in informing personalization of treatment in the era of cellular therapies.
NIMG-103. VOLUMETRIC CHANGES IN GRAY MATTER AFTER RADIOTHERAPY DETECTED WITH LONGITUDINAL MAGNETIC RESONANCE IMAGING IN GLIOMA PATIENTS
Authors: Lee Hye In , Jang Bum-Sup , Kang Min Kyoung , Hwang Kihwan , Kim Chae-Yong , Kim Yu Jung , Suh Koung Jin , Choi Byung Se , Choe Gheeyoung , Kim In Ah
Published: November 2022

PURPOSE

We evaluated volumetric changes in the gray matter (GM) after radiotherapy (RT) and identified factors that were strongly associated with GM volumetric reduction.

METHODS

A total of 461 magnetic resonance imagings (MRI) from 105 glioma patients treated with postoperative radiotherapy (RT) was retrospectively analyzed. Study patients’ MRIs were collected at five time points: before RT and 1 month, 6 months, 1 year, and 2 years after RT. Using the ‘FastSurfer’ platform, a deep learning-based neuroimaging pipeline, a total of 73 subsites was automatically segmented from longitudinal MRIs and their volumetric changes were calculated. Each subsite was grouped into 10 functional fields. A multivariable linear mixed-effects model was established to identify the potential predictors of volumetric changes.

RESULTS

The median volumetric changes in the overall, ipsilateral, and contralateral GM were -3.5%, -4.5%, and -2.4% at 2 years after RT. The functional fields of cognition and execution of movement showed the greatest volumetric reductions. In the multivariable linear mixed model, female and the interaction between age and days after RT were significantly associated with GM volume reduction. The GM volume was significantly reduced in patients older than the subsite-specific threshold age at RT (e.g., 45, 50, and 60 years for hippocampus, Broca area, and Wernicke area, respectively). However, there was no significant GM volumetric reduction in patients younger than the threshold age at RT.

CONCLUSIONS

GM volumetric changes were identified after RT that could lead to long-term treatment sequelae. Particularly for susceptible patients, individualized treatment and prevention strategies are needed.
NIMG-109. A PILOT STUDY OF LYMPHOSCINTIGRAPHY WITH TRACER INJECTION IN THE HUMAN BRAIN
Authors: Coxon Andrew , Desai Rupen , Patel Pujan , Vellimana Ananth , Willie Jon , Dowling Joshua , Leuthardt Eric , Kim Albert , Johanns Tanner , Siegel Barry , Dunn Gavin
Published: November 2022

INTRODUCTION

Many groups have reported lymphatic and glymphatic structures in animal and human brains, but tracer injection into the human brain to demonstrate real-time lymphatic drainage and mapping has not been reported. Technetium (99mTc) tilmanocept is a radiopharmaceutical agent that binds CD206 and maps draining lymph nodes. We hypothesized that peritumoral 99mTc-tilmanocept injection into the brain parenchyma would map drainage to cervical lymph nodes. Here we show a paucity of tracer movement after injection due to a presumed inefficiency of glymphatic and lymphatic drainage.

METHODS

We enrolled 14 patients undergoing resection or stereotactic biopsy of suspected benign or malignant intracranial tumors. Patients received peritumoral injections of 99mTc-tilmanocept followed by planar or tomographic imaging. One patient was excluded from analysis because of tracer leakage during injection.

RESULTS

No patients showed drainage of 99mTc-tilmanocept to regional lymph nodes. On average, after correcting for radioactive decay, 70.1% (95% CI: 60.0%, 81.6%) of the tracer in the injection site and 78.1% (95% CI: 71.1%, 85.1%) in the whole-head on the day of surgery remained the morning after, with variable radioactivity in the subarachnoid space. The remaining fraction at the injection site was much larger than the expected fraction of 1.12% (95% CI: 1.07%, 1.17%) based on previously reported clearance rates from non-brain injections. We determined that this lack of drainage was not due to sequestration by a large population of CD206+ cells via immunohistochemistry of peritumoral tissue sections. Patients with benign or malignant tumors and a patient who underwent or minimally invasive stereotactic biopsy all showed no drainage.

DISCUSSION

In this pilot study, the lymphatic tracer 99mTc-tilmanocept was injected into the brain parenchyma, and there was an absence of drainage to the cervical lymph nodes. Our work demonstrates an inefficiency of drainage from the brain parenchyma and highlights an opportunity to improve brain immunosurveillance.
NCMP-03. HEADACHE IN PATIENTS WITH NON-CNS CANCER
Authors: Cacho-Diaz Bernardo , Arrieta Oscar
Published: November 2022

BACKGROUND

Almost everybody will experience at least one headache episode and almost 40% of the world-population will be diagnosed with some sort of cancer during their life; nevertheless, their association has scantly been measured. Aim: To identify if headache characteristics and/or accompanying signs were associated with brain metastases (BM) in patients with non-CNS cancer.

METHODS

Patients with systemic cancer and headache sent for evaluation between June 2012 and June 2018 were included. Hematologic or primary CNS tumors were excluded. Magnetic resonance imaging (MRI) was performed in most; the remaining were followed for at least a year. Logistic regression analyses were used to measure associations.

RESULTS

From 572 patients with cancer and headache, 216 (38%) were diagnosed with BM. Variables significantly (P < 0.05) associated with BM after multivariable analysis were male gender (OR 1.97), headache starting after cancer diagnosis (OR 21), oppressive type (OR 1.9), presence of vomiting (OR 5.78), not increased by changes in position (OR 2.2), and generalized location (OR 0.34). Having another symptom/sign other than headache was seen in 73% of patients with BM and was significantly associated with a higher risk of BM [OR 6.08 (9%%CI 2.1-17.3)], especially if patients presented with altered mental status (OR 15), visual complaint (OR 15), focal motor weakness (OR 11), seizures (OR 15), ataxia (OR 19), and/or vertigo (OR 3.8).

CONCLUSION

Headache in patients with cancer should be considered a warning sign, it′s characteristics and accompanying signs should be considered to assess individually the risk of being diagnosed with BM.
NCMP-05. RARE CASE OF INTRAMEDULLARY SPINAL CORD METASTASIS AND CANCER-RELATED STROKE SECONDARY TO NASOPHARYNGEAL CARCINOMA
Authors: Alonto Anisah Hayaminnah , Mondia Mark Willy , Planilla Cyril Jonas , Mendoza Marvin Jonne , Urquiza Sheen , King Rich Ericson , Bagnas Marjorie Anne
Published: November 2022

INTRODUCTION

Central nervous system (CNS) metastasis from nasopharyngeal carcinoma (NPC) is rare and presents with high morbidity and mortality. As a rare entity, a few patients with CNS metastasis from NPC have been reported, and no studies were available on treatment and prognosis. Based on our clinical experience, early diagnosis with incorporation of a clear palliative plan is imperative in providing holistic care for patients with locally-invasive and metastatic nasopharyngeal carcinoma.

CASE REPORT

Our study reports a case of a 48-year-old Filipino male with known NPC Stage IVB who developed acute symptoms of constipation, urinary retention, and bilateral lower limb weakness and numbness. Magnetic resonance imaging (MRI) showed intramedullary lesions in multiple segments of the spinal cord. Steroid and radiotherapy of the spine were initiated with noted transient improvement of the motor strength. Subsequently, he developed cancer-related stroke. The patient progressively deteriorated despite best medical care. To our knowledge, this is the fourth case of intramedullary spinal cord metastasis from NPC reported worldwide but the first one in the Philippines.
NCMP-08. THE EFFECTIVENESS OF ANTISEIZURE MEDICATION TRIPLETHERAPY IN GLIOMA PATIENTS WITH REFRACTORY EPILEPSY: A MULTICENTER OBSERVATIONAL COHORT STUDY
Authors: van der Meer Pim , Dirven Linda , Fiocco Marta , Vos Maaike , Kouwenhoven Mathilde , van den Bent Martin , Taphoorn Martin , Koekkoek Johan
Published: November 2022

BACKGROUND

About 10% of glioma patients with epilepsy need antiseizure medication (ASM) tripletherapy due to refractory epilepsy. This study aimed to determine whether levetiracetam combined with valproic acid and clobazam (LEV+VPA+CLB), a commonly prescribed tripletherapy, has favorable effectiveness compared to other tripletherapy combinations in glioma patients.

METHODS

In this multicenter retrospective observational cohort study, the primary outcome was to estimate the cumulative incidence of treatment failure for any reason, from initiation of ASM tripletherapy. Secondary outcomes included cumulative incidences of: 1) treatment failure due to uncontrolled seizures; 2) treatment failure due to adverse effects; and 3) recurrent seizure. Maximum duration of follow-up was 36 months.

RESULTS

Out of n=1435 patients in the original cohort, n=90 patients received ASM tripletherapy after second-line ASM treatment failure due to uncontrolled seizures. LEV+VPA+CLB was prescribed to 48% (43/90) and other ASM tripletherapy to 52% (47/90) patients. The cumulative incidence of treatment failure for any reason of LEV+VPA+CLB did not significantly differ from other tripletherapy (12 months: 47% [95%CI, 31-62%] versus 42% [95%CI, 27-56%], p=0.892). No statistical significant differences for treatment failure due to uncontrolled seizures (12 months: 12% [95%CI, 4-25%] versus 18% [95%CI, 8-30%], p=0.445), due to adverse effects (12 months: 22% [95%CI, 11-36%] versus 15% [95%CI, 7-27%], p=0.446), or recurrent seizure (1 month: 65% [95%CI, 48-78%] versus 63% [95%CI, 47-75%], p=0.911) were found.

CONCLUSIONS

LEV+VPA+CLB showed equivalent effectiveness compared to other ASM tripletherapy combinations in glioma patients.