bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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<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.
NIMG-34. CXCR4-TARGETED PET IMAGING OF CENTRAL NERVOUS SYSTEM LYMPHOMA AND GLIOMA USING [68GA]GA-PENTIXAFOR
Authors: Werner Jan-Michael , Tomasich Erwin , Berghoff Anna S , Wöhrer Adelheid , Albert Nathalie L , Mayerhoefer Marius E , Galldiks Norbert , Traub-Weidinger Tatjana , Hacker Marcus , Preusser Matthias
Published: November 2024

BACKGROUND

Initial results suggest that PET imaging of the chemokine receptor CXCR4 is of considerable interest for differential diagnosis and theranostic approaches. Here, we summarized findings of CXCR4 PET imaging in an institutional series of lymphoma of the central nervous system (CNSL) and glioma.

METHODS

Twenty-three patients with CNSL and 16 patients with glioma (IDH-wildtype, n=9) underwent PET imaging using the CXCR4-directed tracer [68Ga]Ga-Pentixafor. In 18 patients, serial PET imaging was performed (range, 2-14 scans), resulting in a total of 104 PET scans. For evaluation, PET scans were classified as [68Ga]Ga-Pentixafor-positive and -negative visually, and the maximum standardized uptake value (SUVmax) was obtained from [68Ga]Ga-Pentixafor-PET.

RESULTS

Twenty-four of all 39 patients (62%) had at least one [68Ga]Ga-Pentixafor-positive PET (CNSL, 57%; glioma, 69%). [68Ga]Ga-Pentixafor-positive PET scans were more common in patients with IDH-wildtype gliomas (89%) than in IDH-mutant gliomas (43%). In patients with [68Ga]Ga-Pentixafor-positive PET, the average SUVmax was 6.4±4.0 in CNSL, and 3.4±1.0 in gliomas (P=0.155). Besides visualization of tumors, [68Ga]Ga-Pentixafor uptake was observed in two patients with radionecrosis. In four CNSL patients who had undergone methotrexate/cytarabine-based first-line therapy, serial PET revealed a significant reduction of SUVmax after chemotherapy completion (average decrease of SUVmax from 4.5±3.8 to 0.6±0.7; P=0.044). In three of those four patients, tumor progression has not been reached (range of time after the follow-up PET, 4-55 months); one patient deceased 44 months after the follow-up PET. In contrast, another patient with an increase in SUVmax from 6.9 to 11.0 after first-line treatment died one month after the follow-up PET.

DISCUSSION

[68Ga]Ga-Pentixafor PET seems to be of value for non-invasively visualizing and quantifying CXCR4 receptor binding. In CNSL, changes in [68Ga]Ga-Pentixafor uptake following therapy may indicate potential for response assessment. CXCR4-targeting radioligand therapies might be more promising in CNSL than in glioma.
NIMG-39. THE “RESECTABILITY INDEX” AS A NOVEL OBJECTIVE PREDICTOR OF SURVIVAL FOR PATIENTS WITH ADULT-TYPE DIFFUSE GLIOMAS
Authors: Nichols Noah , Seenarie Nitish , Yong Raymund
Published: November 2024

Extent of resection (EOR) is a strong prognostic factor for patients with adult-type diffuse gliomas. Whole brain tractography (WBT) allows visualization of tumors in relation to functional subcortical white matter tracts connecting eloquent cortex. We developed a preoperative metric, the resectability index (RI), to estimate tumor resectability based on pre-resection volume (PRV) and unresectable tumor volume (UTV). We explore if RI predicts progression-free survival (PFS) and overall survival (OS). We retrospectively reviewed the charts of consecutive patients with adult-type diffuse gliomas resected from 2013-2020. Only patients with pre-operative DTI MRIs were included. UTV was the total overlapping volume of tumor with functionally significant tracts (corticospinal, arcuate, optic, fornix) and deep structures (basal ganglia, thalamus, brainstem). RI was (PRV-UTV)/PRV. Seventy-nine patients were included with an average age of 56 years at time of surgery. Glioblastoma was the most common histology (68%). Tumors were located in the left hemisphere (LH) (48%), right hemisphere (RH) (39%), and bilateral hemispheres or midline (BHM) (13%). EOR for LH, RH, and BHM tumors was 0.8, 0.91, and 0.29, respectively (P = 0.1^7). RI for LH, RH, and BHM tumors was 0.86, 0.912, and 0.44, respectively (P = 0.00021). Cox regression was used to model PFS and OS based on age, preoperative KPS, WHO grade, EOR, and RI. Age, recurrent status, bilaterality, residual tumor volume (RTV) and UTV predicted PFS (CI = 1.01 – 1.06, P = 0.002). For OS, UTV and RI were more strongly predictive than RTV or EOR. In a Cox regression model consisting only of preoperative variables, RI was independently predictive of OS. RI is a novel metric with potential efficacy for preoperative survival prognostication in patients with diffuse gliomas. RI may enable neurosurgeons to provide HGG patients with more accurate information about expected benefits of surgical intervention than is currently possible. RI will also enable more valid comparisons of HGG patient cohorts treated at different institutions.
NIMG-43. INFARCTION RADIOLOGICALLY MIMICKING INTRA-AXIAL BRAIN TUMORS
Authors: Kim Kyung-Min
Published: November 2024

There are several reports of brain lesions that radiologically mimicking the brain tumors. The abscess is representative lesion of resembling the intra-axial tumors in brain MRI. However, cerebral infarction is not a common lesion that resembles a brain tumor and can be easily distinguished from a brain tumor in MRI. Here, we represented the two cases of pathologically diagnosed infarction that radiologically suspected gliomas. A 67-year-old man presented with left side weakness and memory impairment. Brain MRI revealed the rim enhancing lesion radiologically suspected glioma. Navigation guided biopsy was performed and final pathological diagnosis was subacute infarction. A-41-year-old man represented the right side weakness. MRI showed the enhancing nodular lesion with perilesional edema. Surgical excision was performed and pathological diagnosis was infarction. Although advancement of brain imaging techniques, it is difficult to accurately discriminate the intracerebral lesions utilizing the MRI. Further comprehensive study should be executed for more precise differentiation of infarction and brain tumors.
NIMG-49. IMAGING PREDICTIVE FACTORS OF BRAIN ADHESION IN SUPRATENTORIAL MENINGIOMA
Authors: Tanaka Shingo , Tamai Sho , Kinoshita Masashi , Nakada Mitsutoshi
Published: November 2024

OBJECTIVES

80 % of meningioma are benign and are classified as WHO grade 1. However, meningioma frequently adheres to surrounding brain and make tumor detach difficult during surgery. This study retrospectively analyzed the adhesion of meningioma to the brain based on preoperative MR images and operative findings.

METHODS

We retrospectively reviewed 238 tumor planes of 60 supratentorial meningioma cases with WHO grade 1 (parasagittal: 15, convexity: 20, falcine: 7, sphenoidal ridge 13 and frontal base 5) underwent surgical treatment. The tumor adhesion to the surrounding brain was defined during surgery as the rupture of arachnoid membrane or leaving tumor capsule due to tight adhesion. The location of MRI image was identified during surgery and verified reference to operation video postoperatively. We assessed following items, tumor diameter, T2 hyper rim, T1 hypo rim, FLAIR hypo rim and brain edema of surrounding tumor. We performed univariate analysis for each item with and without adhesion, and extracted predictors for tumor adhesion by logistic regression analysis.

RESULTS

We confirmed 127 tumor planes without adhesion and 111 tumor planes adhered to surrounding brain. The cutoff value obtained from the ROC curve for tumor adhesion and tumor diameter was 2.3 cm. In univariate analysis, tumor diameter ≧ 2.3 cm, T2 hyper rim, T1 hypo rim, FLAIR hypo rim and brain edema of surrounding tumor were significantly associated with adhesion. In logistic regression analysis, tumor diameter ≧ 2.3 cm (odds ratio (OR) 2.7, P = 0.02), T2 hyper rim (OR 0.04, P < 0.001), and brain edema of surrounding tumor (OR 25, P < 0.001) were significantly independent predictive factors for tumor adhesion.

CONCLUSION

Meningioma adhesion to surrounding brain might be predicted by tumor diameter ≧2.3 cm, T2 hyper rim, and brain edema of surrounding tumor.
NIMG-50. MULTIPARAMETRIC MRI DISTINGUISHES NEURONAL AND IMMUNE SIGNATURES IN INVASIVE HIGH-GRADE GLIOMA RIM THROUGH GRAPH NETWORK ANALYSIS
Authors: Flick Matthew , Stevens Victoria , Plaisier Christopher , Barajas Ramon , Tran Nhan , Kannan Kasthuri , Hu Leland
Published: November 2024

BACKGROUND

Standard of care surgery for high grade glioma (HGG) employs Magnetic Resonance Imaging to identify the contrast enhancing (CE) core for resection, leaving a non-enhancing (NE) invasive rim of tumor which contributes to recurrence. Multi-parametric MRI (mpMRI) has recently been used to map regional biological heterogeneity of neuronal and immune signatures in HGG, and continues to offer a promising strategy for non-invasive surveillance of tumor progression. Here, we present a graph network analysis relating mpMRI to biological signatures in the NE tumor rim and show the utility of communities of imaging features for discriminating tumor phenotypes.

METHODS

53 mpMRI features across 101 spatially-localized RNA-sequenced biopsy samples from 64 patients with IDH-wt HGG were represented as nodes within a Neo4j graph network. Modularity optimization was used to identify communities of densely connected nodes. Communities of nodes representing high proportions of NE samples (one-tailed test) were kept for further analysis. Gene set enrichment analysis (GSEA) on samples within selected imaging communities was analyzed for biological process enrichment using clusterProfiler. Single sample GSEA (ssGSEA) using ssGSEA2 was used to annotate neuronal and immune cell states across samples within selected communities. mpMRI feature selection within each community identified the most relevant imaging features for isolating samples classified into neuronal and immune cell states.

RESULTS

11 imaging communities gathered a high proportion of NE samples. Three NE communities showed significant enrichment of neuronal signatures, while one showed significant enrichment of immune pathways. One neuronal-predominant community showed unique upregulation of 14 pathways related to neuronal migration/astrocyte projection.

CONCLUSION

Network imaging communities can identify clusters of NE glioma samples showing contrasting neuronal and immune signatures, including distinct upregulation of migration and projection pathways. Mapping these imaging feature communities to specific biological processes implicated in glioma progression may aid treatment planning and prognostication for glioma patients.
NIMG-58. MACHINE LEARNING-GENERATED WHOLE-BRAIN RADIO-PATHOMIC TUMOR PROBABILITY MAPS WITHIN CONTRAST-ENHANCEMENT STRATIFY SURVIVAL IN GLIOBLASTOMA PATIENTS UNDERGOING GROSS-TOTAL RESECTION
Authors: Aaronson Daniel , Bobholz Samuel , Duenweg Savannah , Kyereme Fitzgerald , Lowman Allison , Nath Biprojit , Winiarz Aleksandra , Connelly Jennifer , Mrachek E Kelly , Krucoff Max , Banerjee Anjishnu , LaViolette Peter
Published: November 2024

BACKGROUND

Even for those undergoing gross total resection (GTR), patients with WHO grade 4 glioblastoma (GBM) have poor overall survival (OS). Stratifying those who will have better OS vs. those that will not remains challenging, with conventional imaging and radiomic models falling short. This study utilizes machine learning (ML)-generated radio-pathomic models based on autopsy tissue as ground-truth to enhance prognostication through tumor probability maps (TPM) within preoperative contrast-enhancing (CE) regions of GBM.

METHODS

Data from the UCSF-PDGM-v2 and UPenn-GBM databases were analyzed, focusing on patients who underwent GTR with WHO 4 IDH-wildtype glioblastoma (n = 528). Preoperative tumor cellularity within CE was quantified using ML-generated TPMs, with a median threshold of 0.7242. Kaplan-Meier survival curves were employed to compare OS between patients with low (≤ 0.7242) and high (> 0.7242) TPM values in CE regions. Statistical significance was evaluated using log-rank tests.

RESULTS

Kaplan-Meier curves demonstrated significant stratification in survival outcomes based on TPM values. Patients with lower TPM values in CE regions had a median OS of 567 days, compared to 457 days for those with higher TPM values (log-rank p-value: < 0.001). These findings suggest that lower tumor cellularity in CE regions as assessed by TPMs correlates with improved survival, offering a more nuanced stratification than current MRI-based methods.

CONCLUSION

This study underscores the potential of TPM metrics as a powerful prognostic tool in GBM. The significant correlation between lower TPM values in CE regions and better median OS indicates that TPM can effectively stratify patients, aiding in clinical decision-making and personalized treatment planning. Future research is necessary to validate these findings in larger, diverse patient populations and to explore the biological mechanisms underlying these survival differences.
NIMG-63. LEVERAGING LLMS FOR ACCURATE DIFFERENTIATION OF RADIATION NECROSIS AND TUMOR PROGRESSION IN BRAIN MRI REPORTS: A STUDY ON AUTOMATED SCORING AND CLINICAL IMPLICATIONS
Authors: Liu Eulanca , Goldfinger Shir , Delery William , Jank Erika , Lamb James , Tenn Stephen , Hegde John , Kaprealian Tania , Steinberg Michael , Savjani Ricky
Published: November 2024

BACKGROUND

Accurate differentiation between radiation necrosis and tumor progression or recurrence in patients treated with stereotactic radiosurgery for brain metastases is critical for guiding clinical management. This study leverages the advanced natural language processing capabilities of Meta Llama3, an artificial intelligence (AI) large language model (LLM), combined with prompt engineering, to rapidly categorize brain magnetic resonance imaging (MRI) radiology reports. Our objective was to develop an automated scoring system to classify concern for radiation necrosis, tumor progression, equivocal findings, or stable exams.

METHODS

Using a comprehensive dataset of reports annotated by expert radiologists, we ran inference on a 70-billion parameter Llama3 model (temperature 0.2, top_p 0.9) with specific prompts designed to capture the nuanced language and diagnostic criteria related to radiation necrosis or tumor progression.

RESULTS

The first pass was performed on a training dataset of 107 reports and did not predefine the clinical conditions. This demonstrated 43.4% accuracy in scoring when compared to a human user’s classification of each report. Agreement between the human reader and Llama3 was assessed using the Gwet agreement coefficient, AC1=0.411 (99%CI 0.396-0.426). Multiple iterations of targeted prompt engineering were then employed to narrow the definition of radiation necrosis and tumor progression, with specific examples and nuanced language used to achieve a higher degree of accuracy at 72.0%, AC1=0.719 (99%CI 0.717-0.722).

DISCUSSION/FUTURE DIRECTIONS

This surpasses recent demonstration of lower human-LLM agreement in radiographic score assignment, with further room for calibration on a dataset of several thousand reports. Next, we will correlate automated interpretations with actual clinical management decisions for radiation necrosis (e.g., initiation of steroids, bevacizumab, Laser Interstitial Thermal Therapy, and/or repeat imaging). This automated scoring system holds significant potential for LLMs in clinical applications. Future work will focus on integrating this model into clinical workflows and expanding its capabilities to include longitudinal monitoring of patient outcomes.
NIMG-65. SYNTHETIC MRI GENERATION TO FACILITATE AUTOSEGMENTATION OF PEDIATRIC BRAIN TUMORS IN LIMITED DATA SCENARIOS
Authors: Chrysochoou Dimosthenis , Gandhi Deep , Familiar Ariana , Vossough Arastoo , Storm Phillip , Resnick Adam , Davatzikos Christos , Nabavizadeh Ali , Kazerooni Anahita Fathi
Published: November 2024

BACKGROUND

The availability of standard multiparametric MRI sequences, including pre-contrast T1w (T1w-pre), post-contrast T1w (T1w-post), T2w, and FLAIR images, is essential for accurate segmentation of tumor subregions and subsequent response assessment in pediatric brain tumors (PBTs). However, clinical MRI sets are often incomplete due to imaging artifacts or inconsistent acquisition protocols across different centers. This study leverages Generative Adversarial Networks (GANs) to synthesize missing FLAIR and T1w-pre images from T2w and T1w-post images, respectively, to facilitate tumor segmentation in PBTs.

METHODS

We developed two GAN models based on the pix2pix framework, trained, validated, and tested on FLAIR-T2w and T1w-post-T1w-pre pairs from a multi-histology and multi-institutional cohort of 476 subjects with PBTs from the Children’s Brain Tumor Network (CBTN). The perceptual quality of the synthesized T1w-pre and FLAIR images was evaluated using the Structural Similarity Index (SSI; ideal value = 1). The robustness of the synthesized sequences to replace missing MRI sequences was evaluated by comparing the segmentation performance (Dice score) of our pre-trained autosegmentation model using all real modalities versus replacing real sequences with their synthesized counterparts.

RESULTS

The T1w-pre and FLAIR synthesis GANs achieved mean SSI values of 0.95 and 0.93, respectively. Median Dice scores for segmentation of whole tumor (WT), enhancing tumor (ET), and tumor core (TC) were calculated for real sequences: 0.90, 0.83, 0.89, replacing real FLAIR with synthetic: 0.86, 0.81, 0.86, and replacing real T1w-pre with synthetic: 0.90, 0.75, 0.89. No statistical significance (p>0.05) was observed in segmentation performance for WT, TC, ET when replacing real T1w-pre with synthetic, and for ET when replacing real with synthetic FLAIR sequences.

CONCLUSION

This method achieves robust segmentation performance in limited data scenarios by synthesizing missing MRI sequences. Future work includes improving FLAIR synthesis and segmentation performance for WT and ET by implementing and comparing other GAN architectures.
NIMG-73. FALSE POSITIVE INTRA-OPERATIVE MAGNETIC RESONANCE IMAGING DURING HIGH GRADE GLIOMA RESECTION
Authors: Kreatsoulas Daniel , George Andrew , Kolawole Samuel , Damante Mark , Cua Santino , Finger Guilherme , Elder Brad
Published: November 2024

Intraoperative magnetic resonance imaging (iMRI) allows assessment of extent of resection during surgery for high-grade glioma (HGG). In most cases, contrast-enhancing areas noted on iMRI indicate residual tumor. However, false positives may occur, leading to inappropriate additional resection and patient morbidity. The rate and pattern of false positive findings in iMRI have not been fully described. We analyzed surgical and imaging findings in patients undergoing iMRI during resection of HGG to determine factors linked with potential false positive contrast enhancement. A single-center analysis retrospectively assessed consecutive patients undergoing resection of newly diagnosed high-grade glioma using iMRI guidance. Preoperative, intraoperative and postoperative imaging, as well as pathologic findings were assessed. One hundred seventy-four consecutive patients who underwent surgery from 2016-2023 were included. All patients had preoperative MRI showing contrast-enhancing tumor and all underwent one iMRI during surgery to assess extent of resection. 124/174 cases (71.3%) demonstrated contrast enhancement on iMRI that prompted inspection and additional resection using updated neuronavigation. Enhancement corresponding to residual tumor was identified with or without additional removal in 120/124 cases (96.8%). No residual tumor was found in 4/124 cases (3.2%, false positives). All false positive cases were the result of contrast accumulation in hematomas (2), hemostatic agents (1) or dependent portions of the resection cavity (1). Both hematomas were located in the walls of the resection cavity and confirmed as hematoma, rather than tumor, by separate pathology analysis. False positives were not associated with patient positioning, tumor sub-type, anatomic location of tumor or extent of resection. Gross total resection (GTR) was confirmed in 163/174 (93.7%) cases on postoperative imaging. False-positive iMRI during HGG surgery can mimic residual tumor. This occurs at a low rate due to contrast pooling in the cavity or accumulation within hemostatic agents or hematomas along the cavity wall. Meticulous hemostasis when preparing the patient for iMRI may help prevent false positives and prevent unnecessary additional resection.
NIMG-74. A NOVEL APPROACH FOR PERSONALIZED RADIOTHERAPY TARGET VOLUME DEFINITION USING METABOLIC MRI AND DEEP LEARNING-DRIVEN PREDICTIONS OF GLIOBLASTOMA RECURRENCE
Authors: Tran Nate , Luks Tracy , Ellison Jacob , Li Yan , Jakary Angela , Ngan Tiffany , Liu Bo , Villanueva-Meyer Javier , Molinaro Annette , Clarke Jennifer , Butowski Nicholas , Chang Susan , Braunstein Steve , Lin Hui , Lupo Janine
Published: November 2024

BACKGROUND

Machine-learning models have demonstrated great promise in predicting tumor infiltration beyond anatomical margins in glioblastoma. Yet standard-of-care (SOC) radiation therapy (RT) planning only utilizes a uniform, isotropic 2cm-expansion of the T1-post-contrast-lesion or T2-lesion to generate a clinical target volume (CTV), without considering heterogeneity in tumor infiltration. We hypothesize that using a novel deep-learning approach to predict regions of tumor progression with metabolic and diffusion-weighted MRI will result in personalized CTVs that are more sensitive to detecting normal-appearing infiltrating tumor beyond the T2-lesion, sparing more healthy brain compared to SOC-CTVs.

METHODS

Anatomical, diffusion-weighted, and metabolic MRI from 101 patients with glioblastoma, acquired post-surgery but prior to chemoradiation, were retrospectively used to predict regions of new contrast-enhancement or T2-hyperintensity at confirmed progression. A segmentation-based predictive deep-learning approach with personalized loss-functions and evaluation metrics (“Progression-Coverage-Coefficient”, PCC) that weight Dice coefficient terms by tumor size was employed with a 66/17/18 train/validation/test split of patients and the resulting DL-CTV compared to two SOC-CTVs: 1) the RTOG[T2-FLAIR+2cm]-CTV, 2) the EORTC[T1c+2cm]-CTV.

RESULTS

Our best deep-learning-CTV trained using anatomical, diffusion, and metabolic MRI achieved significantly improved median test specificity (0.87 vs. 0.77; p<0.005) and comparable sensitivity (0.92 vs. 0.95; p=0.1) and PCC (0.81 vs. 0.79; p=0.1) to the SOC RTOG[T2-FLAIR+2cm]-CTV, sparing more normal brain tissue. Compared to the more conservative EORTC[T1c+2cm]-CTV, our approach had significantly higher test sensitivity (0.92 vs. 0.85; p<0.00001) and PCC (0.81 vs. 0.77; p=0.003) in covering the progressed lesion, while maintaining similar specificity (0.87 vs. 0.89; p=0.3). Test performance dropped by 9.6% and 12.4% when removing metabolic and both metabolic and diffusion metrics, respectively (p<0.001).

CONCLUSION

This study demonstrates the benefit of using metabolic and diffusion MRI with deep learning for personalized RT planning by targeting regions of anatomically normal infiltrative disease that are highly likely to progress, while reducing treatment to normal brain.
NIMG-76. INCORPORATING IMAGING FEATURES OF NORMAL BRAIN TO ENHANCE SPATIALLY DIFFERENTIATING TREATMENT-INDUCED EFFECTS FROM RECURRENT GLIOMA WITH AI
Authors: Ellison Jacob , Ngan Tiffany , Jakary Angela , Tran Nate , Phillips Joanna , Shai Anny , Molinaro Annette , Li Yan , Luks Tracy , Nair Devika , Villanueva-Meyer Javier , Berger Mitchel , Hervey-Jumper Shawn , Aghi Manish , Chang Susan , Lupo Janine
Published: November 2024

INTRODUCTION

Although AI-based approaches have been applied to discriminate between tumor recurrence (rTumor) and treatment-induced effects (TxE) from chemoradiotherapy in patients with recurrent glioma, these models typically either do not account for within-lesion mixtures of rTumor and TxE or generalize to independent test-sets with >80% accuracy. We hypothesize that incorporating imaging features of normal-appearing brain (NAB) into existing AI-based models that leverage tissue-samples with known locations on MRI and physiological imaging will significantly improve performance for distinguishing regions of TxE from rTumor and allow for visualization of rTumor beyond the T2-lesion.

METHODS

Using 254 pathology-confirmed tissue-samples with coordinates on diffusion-weighted, perfusion-weighted, and anatomical MRI from 135 glioma suspected of progression, we modified previously-developed binary, AI-based prediction models to learn multi-class targets consisting of rTumor, TxE, and contralateral NAB-regions (3/patient) with imaging signatures of CSF, white-matter, and grey-matter (659 total 10mm-isotropic samples). The multi-class ensemble model was trained with 4 unique repeats of constrained-5-fold-cross-validation and evaluated on a held-out test set (30 patients). This process was repeated 20 times, and the performance was compared to corresponding binary AI-based models.

RESULTS

NAB was easiest to distinguish from individual and combined classes (AUC-ROCs>0.98). Multi-class model performance for predicting TxE increased by 27% to 0.93±0.03 (p<0.00001) when discriminating between NAB and rTumor as compared to just rTumor with the binary models. While TxE vs rTumor alone was most difficult to predict with the multi-class model (AUC-ROC=0.73) achieving equivalent performance to binary models, there was 67% less variance in test performance. This approach allowed for the quantification of whole-brain probability maps of rTumor, TxE, and NAB along with a combined 3-channel colormap, facilitating the visualization of rTumor predictions beyond the T2-lesion.

CONCLUSIONS

Including NAB imaging features improved performance of AI-based models of rTumor/TxE, while expanding the predicted area to produce more interpretable whole-brain probability maps. Current work is evaluating their utility in prospectively guiding sampling of rTumor tissue and predicting survival.
NIMG-77. MRI PHENOMENON OF PUNCTATE ENHANCING LESIONS IN PATIENTS TREATED WITH IDH INHIBITORS
Authors: Nisnboym Ziv Michal , Patel Mallika P , Minor Maria , Johnson Margaret O , Batich Kristen , Low Justin , Shoaf Madison L , Khasraw Mustafa , Desjardins Annick , Friedman Henry S , Ashley David M , Peters Katherine B
Published: November 2024

BACKGROUND

Magnetic Resonance Imaging (MRI) response assessment is essential in isocitrate dehydrogenase (IDH)-mutant gliomas and provides evidence of treatment efficacy. Ivosidenib, a mutant IDH1 inhibitor, and vorasidenib, a pan-mutant IDH inhibitor, may induce imaging stabilization or improvement. We describe an imaging phenomenon of punctate enhancing lesions in patients receiving ivosidenib or vorasidenib.

METHODS

From October 2020 to December 2023, we identified patients treated with IDH inhibitors who developed punctate enhancing lesions on imaging during their treatment course. We report their clinical and imaging characteristics.

RESULTS

In our cohort (n=5), patients age range was 29-47 years. Diagnoses included astrocytoma grades 2 (n=2) or 3 (n=1), and oligodendroglioma grades 2 (n=1) or 3 (n=1). Beside all having a prior resection, two had prior radiation therapy and temozolomide, one had prior temozolomide only and two were treatment-naïve. Before initiation of IDH inhibitor, all patients had some evidence of enhancement, albeit small (<1 cm) for most. Four patients received ivosidenib (500mg daily) and one received vorasidenib (40mg daily). The median time to develop punctate lesions from treatment initiation was 16 months (range 1-28 months). All but one lesion was < 1 cm and adjacent to the original tumor locations. Four had FLAIR correlation, and two had high DWI signal without associated restricted diffusion. Punctate lesions resolved on subsequent imaging, within 1-2 months, for all grade 2 tumors. Punctate lesions persisted in the grade 3 tumors, without further progression. Four patients remain on therapy. One discontinued treatment due to this enhancement, which resolved on subsequent imaging.

CONCLUSIONS

Punctate enhancing lesions may develop in patients on IDH inhibitors. We advocate for close interval imaging monitoring in these cases since they may not universally require treatment discontinuation. Future advanced imaging and tissue evaluations of punctate enhancement, to differentiate between inflammatory response and progression, would be of interest.
NIMG-80. IMPACT OF KETOGENIC DIET ON MOLECULAR METABOLIC IMAGING WITH [18F]FDG AND [18F]DASA-23 POSITRON EMISSION TOMOGRAPHY IN A PATIENT WITH GLIOBLASTOMA
Authors: Naya Lewis , Bilgin Seyma , Beinat Corinne , Khalaf Alexander , Recht Lawrence , Patel Chirag
Published: November 2024

The standard-of-care for neuroimaging in patients with glioblastoma is contrast-enhanced MRI, which does not provide tumor metabolism information. Although [18F]FDG PET is used to image tumor metabolism in many solid organ cancers, it has limited benefit in atients with brain tumors due to the high level of glucose uptake in normal brain cells. [18F]DASA-23 is a novel PET radiotracer that assesses the levels of pyruvate kinase M2 (PKM2), a protein highly expressed in cancer cells, which undergo aberrant glycolysis. Despite [18F]DASA-23 having a higher tumor-to-background ratio (TBR) of standardized uptake values (SUVs) in the brain compared to [18F]FDG, both may be susceptible to altered carbohydrate metabolism in the setting of a ketogenic diet (KD). We report the case of a patient with glioblastoma on a KD, whose [18F]FDG and [18F]DASA-23 PET brain scans were limited in identifying disease progression (PD). Background was defined as the white matter contralateral to the tumor, at the level of the centrum semiovale, for TBR of SUVmax. A 39-year-old man was diagnosed with right temporal glioblastoma after previous diagnoses of grade 2 gliofibrillary oligodendroglioma (age 20) and grade 3 anaplastic oligodendroglioma (age 22). He began a KD after the glioblastoma diagnosis. 21 months later, TBR on [18F]DASA-23 PET was 1.38. One month later, surveillance brain MRI showed PD. Ten days later, TBR on [18F]FDG PET was 1.03. The patient died 15 months later. Despite MRI-based PD, the TBR of each radiotracer was not markedly elevated, although the [18F]DASA-23 TBR 1-month pre-PD was 34% greater than the [18F]FDG PET TBR 10-days post-PD. This may suggest a limitation of metabolic imaging by PET in the setting of a KD, and provide an opportunity to develop novel PET radiotracers that are not susceptible to the patient’s diet.
NCOG-22. ELDER AGE INSTEAD OF LOW EDUCATION PREDICTS POOR LANGUAGE FUNCTION IN RECURRENT LEFT HEMISPHERIC DIFFUSE GLIOMA PATIENTS
Authors: Cheng Pi-Cheng , Wei Kuo-Chen , Chen Pin-Yuan , Chen Ko-Ting
Published: November 2024

PURPOSE

Language processing is multifactorial, requiring interactions between cognitive functions and connections of cerebral cortexes and subcortical fibers in dominant hemisphere. Previously, we identified distinct patient factors and tumor characters influencing language performance in treatment-naïve diffuse glioma. In this study, we aimed to investigate predictive factors between treatment-naïve and recurrent patients with diffuse glioma.

MATERIALS AND METHODS

Grade 2 to 4 diffuse glioma patients who underwent awake surgery with completed preoperative language assessment were included. The Chinese version of the short-form Boston Diagnostic Aphasia Examination (sfBDAE) was used for language testing. Patient age, sex, education level, tumor grade, language pathway involvement, T1 contrast enhanced (C+), and FLAIR (T2) volume were selected as variables. Univariate and multivariate logistic regression analysis were used on language function impairment. The statistical significance was defined as a p-value less than 0.05 by SPSS20.0.

RESULTS

50.7% of all awake surgeries (112 of 221) in 171 patients had repeated operations in the retrospective cohort. Comparing to treatment-naïve patients, patients with recurrent tumor had higher academic year (p=0.016), more subventricular zone invasion (p=0.03), and more subcortical language pathway involvement (p=0.035), whereas showed no difference on language performance. In language function analysis, low education was the sole predictive factor for poor language function in treatment-naïve patients. In sharp contrast with low education, elder age factor was exclusively correlated with poor language function in recurrent patients. Furthermore, times of craniotomy was also an independent predictive factor in recurrent group.

CONCLUSIONS

Neurocognitive reserve is considered a protective factor against brain damage. Both age and education level are critical factors for cognitive reserve. Whether the phenomenon of a distinct and mutually exclusive patient factor affecting language function between treatment-naïve and recurrent diffuse glioma patients could be explained by the model of cognitive reserve necessitate more study.
NCOG-46. CHROMOSOMAL LOSSES CORRELATE WITH POOR OVERALL SURVIVAL IN H3K27M-ALTERED DIFFUSE MIDLINE GLIOMAS
Authors: Steven Leal-Ekman J , Nguyen Thien , Campen Cynthia , Ryan Katherine , Wheeler Joshua , Mahdi Jasia , Monje Michelle , Partap Sonia , Prolo Laura
Published: November 2024

BACKGROUND

H3K27M-altered diffuse midline gliomas (DMG) have poor outcomes with limited biomarkers to predict overall survival. Stratification based on chromosomal and molecular rearrangements represents a strategy to improve outcomes.

METHODS

We performed a retrospective analysis of 31 pediatric patients with biopsy-proven H3K27M-mutant DMG, who have undergone molecular next generation sequencing to define cytogenetics alterations that negatively impact overall survival. Median age at diagnosis in this cohort: 9.8 years (range 2.2-24.9 years). Among the cohort, 19 had H3F3A mutations confirmed by NGS, two had confirmed HIST1H3B mutations. Patients with intracranial masses received a standard fractionated radiation course with 54Gy or 59.4Gy XRT.

RESULTS

Pairwise comparisons demonstrate chromosomal losses and deletions are associated with poor overall survival (p=0.025, difference in Overall Survival [OS]: -19.9 months, 95%CI: -37.16 to -2.730) when compared to patients in the cohort without chromosomal deletions. Further subgroup analysis demonstrate worse outcomes in patients with deletions in chromosome 12 (p=0.003, difference in OS: -21.2 months, 95%CI: -34.74 to -7.702), deletions in chromosome 14 (p=0.007, difference in OS: -19.8 months, 95%CI: -33.72 to -5.892), or amplifications in chromosome 1 (p=0.003, difference in OS: -23.1 months, 95%CI: -37.53 to -8.613) relative to those without corresponding mutations. These data suggest that chromosomal alterations may serve as a potential biomarker to risk stratify patients. Likewise, genes within these deleted or amplified chromosomal segments may represent targets for therapeutic intervention.
EXTH-11. PEDIATRIC GLIOMA IMMUNE PROFILING IDENTIFIES TIM3 AS A THERAPEUTIC TARGET IN BRAF-FUSION PILOCYTIC ASTROCYTOMA
Authors: Tripathi Shashwat , Najem Hinda , Dussold Corey , Pacheco Sebastian , Du Ruochen , Sooreshjani Moloud , Chandler James , Stupp Roger , Sonabend Adam , Horbinski Craig , Lukas Rimas , Xiu Joanne , Nicolaides Theodore , Brown Valerie , Wadhwani Nitin , Lam Sandi , James Charles , Rao Ganesh , Castro Maria , Heimberger Amy , DeCuypere Michael
Published: November 2024

Despite being the leading cause of childhood mortality, pediatric gliomas have been relatively understudied. Repurposing of adult brain tumor immunotherapies in pediatric patients has not been successful, highlighting the need for pediatric-specific immunotherapies. Pilocytic astrocytomas (PA) are the most common pediatric glioma. While surgical resection of PA is the first-line treatment, the ten-year progression-free survival rate for patients with residual tumors is <50%. Notably, some PAs undergo spontaneous regression after partial resection, suggesting potential baseline tumor immunoreactivity. Whole transcriptome sequencing performed on a commercial platform of pediatric gliomas (n=250) showed that MAPK-driven gliomas have higher interferon signatures compared to other molecular subgroups. Single-cell sequencing identified a unique activated and cytotoxic microglia population designated MG-Act in BRAF-fused MAPK-activated PA (n=13; p < 0.05), but not in pediatric high-grade gliomas (n=5) or normal brain (n=3). TIM3 was expressed on the luminal side of endothelial cells and MG-Act, but not in the surrounding normal brain based on sequential multiplex imaging. Flow cytometry showed that TIM3 intensity is upregulated on immune cells in the PA tumor microenvironment (TME) relative to matched peripheral blood immune cells (n=6; p < 0.01). Anti-TIM3 reprogrammed fresh ex vivo immune cells from the TME of human PAs (n=3) to a pro-inflammatory cytotoxic phenotype. In a genetically engineered murine model of MAPK-driven low-grade gliomas, median survival (MS) was 252 days in mice treated with anti-TIM3 (n=21; p<0.01) relative to IgG control (MS: 110 days; n=20) or anti-PD-1 (MS: 134 days; n=20). The therapeutic activity of anti-TIM3 was abrogated in the CX3CR1 microglia knockout background. ScRNA sequencing data during the therapeutic window of anti-TIM3 in wild-type mice demonstrated enrichment of the MG-Act population within low-grade gliomas at two different longitudinal time points but not in IgG-treated controls. Together, these data indicate that anti-TIM3 should be considered for clinical trials in pediatric low-grade MAPK-driven gliomas.
EXTH-21. WINNING THE TUG OF WAR BETWEEN VIRUS AND TUMOR IMMUNODOMINANCE IN GLIOMAS TREATED WITH ONCOLYTIC ADENOVIRUSES USING TOLEROGENIC STRATEGIES
Authors: Ho Shin Dong , Ozpolat Bulent , Gillard Andrew , Garcia-Moure Marc , Jiang Hong , Lopez-Rivas Andres , Parthasarathy Akhila , Fan Xuejun , Alemany Ramon , Alonso Marta , He Jiasen , Ene Chibawanye , Al-Atrash Gheath , Lang Frederick , Gomez-Manzano Candelaria , Fueyo Juan
Published: November 2024

Phase 1 and 2 clinical trials of our oncolytic adenovirus Delta-24-RGD for patients with recurrent malignant gliomas have demonstrated its safety and efficacy, and showed that 20% of the patients experienced long-term tumor remissions often associated with inflammatory responses and tumor infiltration of lymphocytes. Based on our preliminary data, we expected that the most frequent tumor-infiltrating CD8+ T cell clones will target adenoviral hexon, with a single virus-specific clone representing up to 5% of the total population. Competition between T cells for resources may limit the expansion of subdominant clones recognizing tumor antigens. We hypothesized that mitigating virus-specific immunity allows the expansion of tumor-specific T cells and results in better therapeutic efficacy. In mice, intravenously injected nanoparticles encapsulating adenoviral antigens preferentially accumulated in the liver (P<0.0001), where self-reactive immune cells are deleted through peripheral tolerance. RNA-sequencing of antigen-specific T cells isolated after nanoparticle injection revealed enriched expression of gene sets involved in immune tolerance through clonal deletion and T cell anergy, including increased expression of immune checkpoint molecules (P<0.001). In glioma-bearing mice treated with virotherapy in combination with nanoparticle administration, tumor infiltrating lymphocytes exhibited decreased IFNγ secretion against viral antigens and increased secretion against tumor antigens, suggesting a redirection of the immunity from anti-viral to anti-tumoral (P<0.05). Importantly, virotherapy with nanoparticles increased the overall survival of tumor-bearing mice compared to virus treatment alone (P<0.001). To further characterize the roles of virus- and tumor-specific immune cells during virotherapy we are analyzing the T cell receptor repertoire of surgical specimens from nine glioma patients treated with Delta-24-RGD in a phase 1 clinical trial. In summary, our data provide the basis for a future clinical trial using tolerogenic strategies to redirect immunodominance of the viral to the glioma antigens, and represent a novel strategy to enhance anti-tumor immunity during virotherapy of brain tumors.
EXTH-25. OPTIMIZATION OF NEW CHEMOTHERAPEUTIC AGENTS BY INTRA-ARTERIAL INFUSION IN GLIOBLASTOMAS
Authors: Latulippe Juliette , Roy Laurent-Olivier , Charest Gabriel , Gobeil Fernand Jr , Fortin David
Published: November 2024

Being the most aggressive malignant primary brain tumor, glioblastoma (GBM) is a difficult disease to treat. The first line treatment is well established, but most patients will relapse before or during the treatments. The overall survival is only 14,6 months while the progression-free survival is 6,9 months. In Sherbrooke, Dr Fortin prioritize the intra-arterial (IA) administration of chemotherapeutic agents (CTA) as a second line treatment. Unfortunately, certain patients will not respond or will even develop chemoresistance to the agents. Therefore, there is a strong need for bringing more CTAs onto clinical care. The maximal tolerable dosage (MTD) of every agent was first determined. Every CTAs were then administered IA by retrograde infusion in the external carotid but also intravenously (IV) by the caudal vein. We used the Fischer-F98 glioma rat model in our studies. For the efficacy study, we implanted 10 000 F98 cells into their brain. After 10 days, they received the treatment associated to their group. The animals were followed every day and were euthanized when their condition was too deteriorated. The dosages found in the MTD study for topotecan and cytarabine was 4 mg/kg and 8,75 mg/kg respectively while paclitaxel was too toxic. As for the efficacy study, the IA group of topotecan showed a promising outcome with a higher survival rate (29 days) compared to the IV one (23,5 days). As for the cytarabine, the opposite was observed (IA: 22 days, IV: 26,5 days). While topotecan and cytarabine could be given intra-arterially, only topotecan showed conclusive results. More animals will be added to this group to confirm this outcome. Cytarabine is not a good option since the IV group survived a longer time than the IA group. As for the paclitaxel, the intra-tumoral infusion will be tested to see if we can get positive results.
EXTH-27. POLYCOMB OVERACTIVITY DRIVES TUMORIGENESIS IN AGGRESSIVE CUSHING’S DISEASE
Authors: Asuzu David , Mullaney Dustin , Bhatt Shyama , Mandal Debjani , Maric Dragan , Elkahloun Abdel , Chittiboina Prashant
Published: November 2024

INTRODUCTION

Aggressive Cushing’s disease (CD) tumors (Ki67 > 3%) exhibit rapid growth, poor postsurgical outcomes, and resistance to conventional therapies. Polycomb group (PcG) proteins are canonical epigenetic silencers that can drive tumor aggressiveness. We asked if PcG underlies rare but fatal pituitary tumor progression.

METHODS

We performed paired multiome analysis (single nucleus RNAseq and ATACseq) in 5 aggressive CD adenomas, and adjacent normal gland. We verified protein expression with multiplexed immunohistochemistry (mIHC) and PcG activity by H3K27me3 ChIPseq. Aggressive murine pituitary tumor cells ATT20 were treated using PcG inhibitors (DZNep, tazemetostat), HDAC inhibitor (vorinostat), or siRNA (Ezh2, Suz12). PcG binding to the POMC promoter was assessed by reverse chromatin immunoprecipitation (rChIP). We treated one patient off-label with oral vorinostat 400mg daily for 6 days prior to radiation.

RESULTS

PcG loci (EZH2 and EED) were more accessible in aggressive CD adenoma versus normal gland corticotrophs, and EZH2, SUZ12 and EED mRNA was robustly overexpressed. mIHC confirmed SUZ12, EZH2 and H3K27me3 overexpression, and ChIPseq confirmed polycomb overactivity in aggressive CD adenomas. Polycomb inhibition by DZNep, vorinostat, or siRNAs led to proliferative arrest and Pomc suppression in ATT20 cells (P < 0.05 versus controls). Vorinostat enriched Suz12 at the Pomc promoter (P < 0.01), confirming direct silencing. In a patient with aggressive CD and hypercortisolemia despite two prior surgeries, a single course of vorinostat decreased cortisol (24mcg/dL to 7.5mcg/dL) and ACTH (63.7pg/mL to 44.9pg/mL) prior to radiation therapy initiation.

CONCLUSIONS

PcG hyperactivity is associated with a more aggressive CD phenotype. We report here the therapeutic potential of HDAC inhibition against aggressive CD adenomas in a first-in-human application.