bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIMG-41. ASSOCIATION BETWEEN PERFUSION IMAGING METRICS AND RADIO-PATHOMIC MAPS OF TUMOR PROBABILITY WITHIN AND BEYOND THE CONTRAST-ENHANCING VOLUME IN GLIOMA PATIENTS
Authors: Bobholz Samuel , Lowman Allison , Duenweg Savannah , Winiarz Aleksandra , Stebbins Margaret , Flatley Michael , Nath Biprojit , Kyereme Fitzgerald , Connelly Jennifer , Coss Dylan , Krucoff Max , Banerjee Anjishnu , LaViolette Peter 
Published: November 2023

Abstract
Perfusion MRI, using both contrast-based techniques such as dynamic susceptibility imaging (DSC) and non-contrast-based techniques like arterial spin labeling (ASL) have been used to monitor blood flow as a marker of angiogenic glioma presence, and showed substantial potential in the differentiation of true progression from pseudoprogression post-treatment. This study uses radio-pathomic maps of cellularity sensitive to areas of non-enhancing tumor to test the hypothesis that perfusion-derived markers of tumor probability will associate with tumor presence within contrast-enhancement but not beyond the enhancing margin. This study included pre-surgical relative cerebral blood volume (rCBV) estimates derived from DSC perfusion data from the PENN-GBM dataset (n=456) and presurgical ASL images from the UCSF-PDGM dataset (n=426) for analyses. The T1, T1C, FLAIR, and ADC images from each patient were used to generate radio-pathomic cell density maps using a previously validated model that excels at accurate detection of non-enhancing tumor presence. Mean cell density, rCBV, and ASL were computed for each corresponding patient within included segmentations for contrast-enhancement (excluding necrotic core) and FLAIR hyperintensity (excluding both necrotic core and enhancement). Pearson’s correlations were then used to quantify the association between perfusion-derived estimates and mean cell density within each region of interest. Both rCBV and ASL showed positive associations with cell density within contrast enhancement (rCBV: R=0.280, p&lt; 0.001; ASL: R=0.117, p=0.016). However, both perfusion metrics also showed no association with cell density within the non-enhancing, FLAIR hyperintense region (rCBV: R=0.0162, p=0.731; ASL: R=-0.213, p=0.634). These results suggest that perfusion imaging successfully identifies angiogenic tumor but may be less efficacious in detecting non-enhancing tumor presence. Future studies should examine how perfusion’s relationship with hypercellular tumor presence evolves in the presence of treatment, as well as in relation to other advanced imaging metrics such as MR spectroscopy and CEST imaging.
NIMG-45. EXTERNAL EVALUATION OF A MACHINE LEARNING MODEL EMPLOYING RADIOMICS TO IDENTIFY REGIONS OF LOCAL RECURRENCE IN GLIOBLASTOMA FROM POSTOPERATIVE MRI
Authors: Cepeda Santiago , Luppino Luigi , Wodsinski Marek , Solheim Ole , Perez-Nuñez Angel , Garcia-Garcia Sergio , Karlberg Anna , Eikenes Live , Zamora Tomas , Sarabia Rosario , Arrese Ignacio , Kuttner Samuel 
Published: November 2023

Abstract
The standard surgical goal for operable glioblastomas worldwide is the complete excision of the enhancing tumor. Nevertheless, the peritumoral region harbors infiltrating cells leading to recurrence. Our study aims to evaluate a predictive model designed to predict potential regions of recurrence using voxel-based radiomics analysis on postoperative magnetic resonance imaging (MRI). This retrospective, multi-institutional study involved glioblastoma patients who had undergone complete resection. The training cohort comprised 49 patients from two Spanish institutions, with model evaluation using an external dataset of 27 patients from a Norwegian institution and the public Ivy-Gap dataset. We used follow-up MRI scans for ground truth definition of recurrence, while postoperative multiparametric MRI scans provided the data for extracting voxel-based radiomic features. Our method employed an unsupervised, hybrid approach, which combined a deep neural network and instance optimization, to align the MRI sequences for each patient, registering the follow-up with the postoperative scans. To generate ground truth labels, we segmented the peritumoral region in the postoperative scans, identified as the area showing T2/FLAIR signal alterations, in addition to the enhancing tumor visible in the registered follow-up scan. Overlapping voxels between the peritumoral and enhancing tumor regions were classified as recurrence, while non-overlapping voxels were labeled as nonrecurrence. Radiomic features were subsequently extracted from the postoperative peritumoral region. We trained four machine learning classifiers to predict recurrence. Among these, the Categorical Boosting (CatBoost) classifier demonstrated excellent performance on the test dataset, achieving an average area under the curve (AUC) of 0.83 ± 0.07, and an accuracy of 0.80 ± 0.12, based on voxel-wise comparison with the ground truth. Our study resulted in a method that accurately predicts the area of future tumor recurrence in glioblastoma patients' MRI scans. This innovation could potentially tailor surgical and radiotherapy treatment strategies to these specific areas, possibly extending patient survival.
NIMG-48. ASSOCIATIONS BETWEEN HETEROGENEITY OBSERVED IN O-6-METHYLGUANINE-DNA METHYLTRANSFERASE (MGMT) ASSAY MEASUREMENTS AND MGMT-BASED IMAGING SIGNATURE BASED ON MRI AND DEEP LEARNING
Authors: Saxena Sanjay , Kazerooni Anahita Fathi , Toorens Erik , Bakas Spyridon , Akbari Hamed , Mamourian Elizabeth , Ganguly Tapan , Nasrallah MacLean P , Davatzikos Christos 
Published: November 2023

Abstract

BACKGROUND
O-6-methylguanine-DNA methyltransferase(MGMT), a gene promoter, corresponds with the efficacy of standard therapy for Glioblastoma (GBM) patients. If a single sample is sequenced, an appropriate diagnosis of MGMT methylation may be hampered by intratumoral heterogeneity. This work proposes a non-invasive in-vivo estimation of MGMT methylation using deep learning and multi-parametric MRI (mpMRI). Further, it quantifies spatial heterogeneity and establishes the associations between MGMT assay measurement and MGMT imaging signature heterogeneity.

METHODS
For this study, mpMRI structural scans (T1, T2, FLAIR and T1-Gd) of 498 newly diagnosed GBM patients were considered. These patients underwent surgical tumor resection, and MGMT methylation testing was retrospectively collected. By overlaying local and regional 2D patches of size 32 X 32 over the whole tumor on mpMRI scans, a 10-fold cross-validated deep convolutional neural network model was trained considering five layers on the discovery cohort (n=458). The trained model was applied to an independent multi-sample cohort (n=40) to compute the MGMT methylation at the pixel level for imaging-derived maps generation and heterogeneity quantification. The independent cohort included the patients for whom multiple tissue specimens were sequenced for MGMT methylation.

RESULTS
The patch-based deep model produced an area under the ROC curve of 0.76 (95% CI: 0.71–0.82) for MGMT status prediction. This model showed a strong association between homogeneously MGMT methylated and heterogeneous cases with MGMT Assay measurement of multiple samples with Pearson’s correlation coefficients of 0.64 (p &lt; 0.05) and 0.78 (p &lt; 0.01), respectively. Further, heterogeneity with a significantly higher variance was also observed in heterogeneous cases in developed MGMT imaging signature.

CONCLUSION
The proposed model efficiently determines MGMT promoter methylation and quantifies GBM spatial heterogeneity non-invasively. Also, it showed a significant association between the heterogeneity observed in MGMT-based imaging signature and MGMT assay measurements.
NIMG-53. IMAGING FEATURES AND CONSIDERATION OF PROGRESSION PATTERN OF DIFFUSE HEMISPHERIC GLIOMAS, H3 G34-MUTANT
Authors: Kibe Yuji , Ohka Fumiharu , Motomura Kazuya , Aoki Kosuke , Maeda Sachi , Yamaguchi Junya , Shimizu Hiroki , Saito Ryuta 
Published: November 2023

Abstract

BACKGROUND
Diffuse hemispheric gliomas, H3 G34-mutant (DHGs-G34m) are newly recognized pediatric-type diffuse high-grade gliomas. We describe detail imaging features of seven cases of DHGs-G34m and consider about progression pattern of DHGs-G34m.

RESULTS
H3 G34R or H3 G34V was detected by sanger sequencing in all tumors. Mean age of onset was 16.5 years (range: 10-26). Tumors were located on frontal (2), parietal (2), temporal lobe (1) and insular cortex (1), respectively. In one case, gliomatosis cerebri-like multiple lesions involving the cortex and basal ganglia occurred. Magnetic resonance imaging showed T2/FLAIR high lesions with poor contrast enhancement in all cases. All tumors harbored restriction of diffusion. Cystic component and hemorrhage were observed in five and three cases, respectively. Six patients underwent preoperative positron emission tomography. Strong accumulation of methionine and partial accumulation of FDG in all cases. All tumors harbored T2/FLAIR high lesions in the deep white matter, most of which showed methionine accumulation. All patients underwent surgery (total resection in one case, partial resection in five cases, and biopsy in one case) followed by radiation chemotherapy. The mean progression free survival was 9.9 months (range: 1.6-33.1 months). All tumors harbored diffuse infiltration along the white matter, which was temporarily reduced by bevacizumab, but eventually invaded into cerebral peduncle via pyramidal tract and into contralateral brain via corpus callosum or anterior commissure in six cases. Extensive infiltration of tumor cells into the contralateral brain and brain stem was confirmed histopathologically in the autopsy brain of one case. The mean overall survival was 21.6 months (range: 8.9-48.3 months).

CONCLUSION
DHGs-G34m showed deep white matter infiltration from the time of initial onset, which made gross total resection difficult. Residual lesions extensively infiltrated along the white matter and eventually invaded the brainstem and contralateral brain, leading to death.
NIMG-54. CONFOCAL FLUORESCENCE ENDOMICROSCOPY: A PROSPECTIVE MULTI-CENTERED, ASSESSOR BLINDED PILOT STUDY FOR THE DIAGNOSIS OF BRAIN TUMORS
Authors: Byun Yoon Hwan , Won Jae-Kyung , Hong Duk Hyun , Kang Ho , Kim Jang Hun , Yu Mi Ok , Kim Min-Sung , Kim Yong-Hwy , Park Kyung-Jae , Jeong Min-Jae , Hwang Kyungmin , Kong Doo-Sik , Park Chul-Kee , Kang Shin-Hyuk 
Published: November 2023

Abstract
Frozen section analysis remains the gold standard for intraoperative diagnosis during brain tumor surgeries; however, it is associated with extensive time consumption and the potential for freezing artifacts. In recent years, confocal laser endomicroscopy (CLE) has been actively studied as a promising alternative to address these limitations of frozen section analysis. In this prospective, multi-centered, assessor-blinded pilot study, our aim was to evaluate the diagnostic effectiveness of cCeLL - Ex vivo, a second-generation CLE model, compared to frozen section analysis for brain tumor diagnosis. We enrolled a total of 55 patients with newly diagnosed brain tumors between October 2022 and December 2022. Biopsy samples were obtained during surgical resection, and each tissue sample was divided into three smaller samples for permanent section analysis, frozen section analysis, and imaging acquisition using cCeLL - Ex vivo. The efficacy of both frozen section analysis and cCeLL - Ex vivo was assessed by comparing their diagnoses to the results from permanent section analysis. The diagnostic accuracy of cCeLL - Ex vivo was slightly higher than that of frozen section analysis, with accuracies of 89.2% and 86.5%, respectively. Both methods demonstrated a sensitivity of 92.2%. Notably, cCeLL - Ex vivo exhibited a higher specificity of 70% compared to frozen section analysis, which had a specificity of 50%. Additionally, the mean time from sample preparation to diagnosis was significantly shorter in cCeLL - Ex vivo (13 min 17 sec) compared to frozen section analysis (28 min 28 sec). These results indicate the promising potential of cCeLL - Ex vivo as a complementary tool for intraoperative diagnosis of brain tumors. Future studies are expected to provide more evidence regarding the potential clinical utility of CLEs in clinical settings.
NIMG-55. PREDICTING SITES OF TUMOR PROGRESSION IN THE INVASIVE MARGIN OF GLIOBLASTOMAS (PRAM-GBM STUDY): AN INTERIM ANALYSIS OF A MULTI-CENTER IMAGING BIOMARKER STUDY
Authors: Price Stephen , Mayrand Roxanne , Wan Yizhou , Cream Lynn , Cook Julia , Dayimu Alimu , Jenkinson Michael , Varma Anil , Ashkan Keyoumars , Thomson Simon , Smith Stuart , Demiris Nikolaos , Matys Tomasz , Li Chao 
Published: November 2023

Abstract

INTRODUCTION
Although glioblastoma cells extend throughout the brain, virtually all patients die from local progressive disease. This progressive tumor occurs at the resection margins and usually within the high-dose radiotherapy field. If we could identify where the tumor would progress, we could consider personalizing radiotherapy and surgical targets. Previous work has shown diffusion tensor MR as a potential biomarker of occult invasion. Biopsy studies reveal that the q-anisotropic component correlates with high-density tumor, and the extent of resection correlates with improved survival. We hypothesize that this is a biomarker that can predict where glioblastomas may progress. STUDY DESIGN: A multicentre, pragmatic, longitudinal observational cohort study from 6 centers. This is a planned interim analysis of the first cohort.

METHODS
Patients with glioblastomas suitable for maximal resection were imaged pre-operatively with a diffusion tensor MRI protocol. This was processed using a tensor decomposition method to generate the q-anisotropic component. Masks of the abnormal q-component were overlaid on the masks of new areas of contrast enhancement at progression (ground truth). Intersecting voxels were classified as true positive, true negative, false positive, and false negative, and the sensitivity and specificity were calculated.

RESULTS
139 patients were recruited, but 50 were withdrawn. The interim analysis was planned for the first 2/3rds of the cohort (55 patients). Combining q and contrast enhancement provided the best predictor of site of tumor progression with a mean sensitivity of 79% [95%CI: 71-88%] compared to contrast enhancement of only 50% [95%CI: 39-61%]. Specificity remained high in both groups (CE+q mean 94% [95%CI: 93-95%] vs. CE alone 98% [95%CI: 97-98%]).

CONCLUSION
The anisotropic diffusion component, q, provides the best biomarker for identifying ‘residual tumor.’ This biomarker will form the basis of an early phase surgical trial IDEAL Stage 1 and 2a study to change surgical resection target.
NIMG-60. PATTERNS OF PROGRESSION IN GLIOBLASTOMA PATIENTS UNDERGOING IMMUNE CHECKPOINT INHIBITOR THERAPY
Authors: Rochand Adrien , Baldini Capucine , Touat Mehdi 
Published: November 2023

Abstract
Glioblastoma (GBM) is the most common primary brain neoplasm with a median survival of 15 months. This retrospective study investigated the patterns of radiologic progression in GBM patients treated with immune checkpoint inhibitors (ICI). Among 16 patients, PseudoProgression (PsPD) was observed in 43% and Hyperprogression (HPD) in 19% of cases. Patients with PsPD had an overall survival of 17.6 months versus 2.9 months for HPD. Identifying these atypical responses early is crucial for optimizing treatment strategies and patient selection. Further research is needed to identify prognostic indicators and biomarkers for immunotherapy efficacy in GBM.
NIMG-62. QUANTITATIVE ASSESSMENT OF T2-FLAIR MISMATCH IN HUMAN NON-ENHANCING GLIOMAS USING SUBTRACTION MAPS OF T2-W AND FLAIR MRI
Authors: Cho Nicholas , Sanvito Francesco , Le Vien , Oshima Sonoko , Teraishi Ashley , Yao Jingwen , Raymond Catalina , Pope Whitney , Nghiemphu Phioanh , Lai Albert , Cloughesy Timothy , Salamon Noriko , Ellingson Benjamin 
Published: November 2023

Abstract

INTRODUCTION
The T2-FLAIR mismatch (T2FM) sign on anatomical MRI is highly specific for isocitrate dehydrogenase (IDH)-mutant 1p/19q-intact gliomas (astrocytomas) and is characterized by relative hypointense FLAIR signal within the T2 hyperintense lesion. However, studies on T2FM sign have mostly utilized qualitative visual assessment. This study explored quantitative subtraction maps of T2-w and FLAIR MRI in human non-enhancing gliomas to quantify the extent of T2FM and assess T2FM subregion volumetric and diffusion MRI differences.

METHODS
Seventy-two newly-diagnosed, non-enhancing gliomas with known IDH- and 1p/19q-status from The Cancer Imaging Archive (TCIA) were studied. An institutional cohort (n= 36) was analyzed for validation. T2-FLAIR subtraction maps were generated from voxel-wise subtraction of co-registered, normalized T2-w and FLAIR MRI scans. Tumor volumes of interest (VOIs) were segmented on the T2 hyperintensity excluding macroscopic cysts. Tumor VOIs were split into mismatched and non-mismatched subregions using consistent T2-FLAIR subtraction map thresholds. Tumor subregion volumes and normalized apparent diffusion coefficient (nADC) values were obtained, and tumor T2FM percentage was calculated.

RESULTS
In the TCIA cohort, a threshold of &gt; 16% T2FM had 92.3% specificity and 34.8% sensitivity and a threshold of &gt; 42% T2FM had 100% specificity and 21.7% sensitivity for classifying IDH-mutant astrocytomas (AUC= 0.704, P= 0.004). IDH-mutant astrocytomas with &gt; 16% T2FM had higher nADC in mismatched compared to non-mismatched subregions (mean difference= 0.51; P&lt; 0.0001). Using the same T2FM thresholds, these findings were validated in the institutional cohort for glioma classification (AUC= 0.918, P&lt; 0.0001; &gt; 16% T2FM: 100% specificity, 66.7% sensitivity, PPV= 100%, NPV= 65.2%; &gt; 42% T2FM: 100% specificity, 23.8% sensitivity, PPV= 100%, NPV= 48.3%) and subregion nADC differences (mean difference= 0.56, P&lt; 0.0001).

CONCLUSIONS
T2-FLAIR subtraction maps may be a useful, automated tool for classifying non-enhancing gliomas and exploring T2FM subregion differences. Elevated nADC in mismatched subregions may reflect microcystic changes.
NIMG-64. IN VIVO METABOLIC PROFILING FOR RECURRENT GLIOMA
Authors: Li Yan , Lafontaine Marisa , Autry Adam , Jiang Fei , Shai Anny , Phillips Joanna , Chang Susan 
Published: November 2023

Abstract

INTRODUCTION
The 2021 WHO classification has identified the importance of molecular features in diagnosing adult glioma. The goal of this study was to use short echo MR spectroscopic imaging (MRSI) to evaluate the metabolite profiles at recurrence and characterize in vivo metabolism in relation to pathology by combining it with image-guided tissue samples.

METHODS
Fifty-one patients with an initial diagnosis of glioma (18 astrocytoma, 14 oligodendroglioma, and 19 glioblastoma) received MR examinations before surgical resection of progressive disease confirmed histologically. The 3D MRSI data were combined, processed, and quantified by LCModel with a simulated basis set. Metabolite levels were compared between contrast-enhancing lesions (CEL), non-enhancing lesions (NEL), and patient groups. Spectra data centered at the tissue target location were correlated to pathological parameters from the samples (0-4 samples/subject).

RESULTS
74.5% (38/51) patients had enhancing tumors, with median CEL volume of 4.2 cm3 (min-max: 0.2-28.5 cm3) and median NEL volumes of 50.6 cm3 (4.8-167.2 cm3). The patients with GBM had significantly larger CEL volumes than the others (p=0.009).18/29 (62%) patients with lower-grade glioma had malignant progression to higher grades. Those who progressed from grade 2 to 3 or 4 had higher myo-inositol/choline (mean±SD, 2.62±0.64, N=18) compared to those who recurred as grade 2 (1.88±0.52, N=5, p = 0.015). Of the 51 patients, 40/65 in vivo spectra voxels centered where the tissues were sampled displayed good quality, with 27 having active tumors, 7 having treatment effects, and 6 having mixed tumors/treatment effects. The levels of choline/creatine and myo-inositol+glycline/creatine were significantly correlated with MIB-1 (p&lt; 0.0001, =0.034; r=0.563, 0.349), but no difference was found between the locations with active tumors and treatment effects. DISCUSSION: This study demonstrated metabolite variations at the recurrence. Ongoing studies will further characterize the metabolite profiles for malignant progression and differences between active tumors and treatment effects.
NIMG-65. METHYLTHIOADENOSINE PHOSPHORYLASE STATUS CORRELATES WITH CLINICAL OUTCOME AND11C-METHIONINE UPTAKE IN ASTROCYTOMA, IDH-MUTANT
Authors: Yamamura Toshihiro , Tamura Kaoru , Kobayashi Daisuke , Inaji Motoki , Toyama Yuka , Hara Shoko , Tanaka Yoji , Nariai Tadashi , Kiyokawa Juri , Ishii Kenji , Maehara Taketoshi 
Published: November 2023

Abstract

PURPOSE
Methylthioadenosine phosphorylase (MTAP) immuno histochemistry staining has been proposed as a surrogate of Cyclin-dependent kinase inhibitor 2A homozygous deletion (CDKN2A HD) in various types of tumors. This study was designed to determine whether MTAP status correlates with clinical outcome and uptake of 11C-methionine in astrocytoma, IDH-mutant.

METHODS
We conducted a MTAP immunohistochemistry staining of 30 astrocytoma, IDH-mutant patients who underwent 11C-methionine positron emission tomography scans prior to surgical resection from 2000 to 2020. The tumor-to-normal (T/N) ratio of 11C-methionine uptake was calculated by dividing the mean standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain.

RESULTS
Eight (26.7%) of the thirty astrocytoma, IDH-mutant patients exhibited loss of cytoplasmic MTAP expression, which is accompanied with a poor prognosis. The median progression free survival (PFS) in astrocytoma, IDH-mutant patients with loss of MTAP was 1.88 years and significantly shorter than that of those with MTAP retention (6.80 years, p = 0.003). The median Overall survival in astrocytoma, IDH-mutant patients with loss of MTAP was 5.23 years, again significantly shorter than that of those with MTAP retention (10.69 years, p = 0.0191). Multivariate analysis revealed that MTAP status was an independent prognostic marker for PFS in astrocytoma, IDH-mutant patients. The median T/N ratio in tumors with loss of cytoplasmic MTAP expression was 2.12 (IQR 1.92-2.50), i.e., significantly higher than that of tumors with MTAP retention (1.65, IQR 1.23-1.94, p = 0.0116, U test). Thirteen (59.1%) of twenty-two patients with MTAP retention recurred and nine patients underwent a second surgery after radiation treatment with or without chemotherapy. Three (33.3%) of the nine recurrent patients showed loss of MTAP immunoreactivity, suggesting a role for this loss in tumor progression.

CONCLUSION
Our study showed MTAP status to correlate with clinical outcome and T/N ratio of 11C-methionine in astrocytoma, IDH-mutant patients.