T2-FLAIR Mismatch Sign Research Articles

NIMG-12. EVALUATING THE SUPER T2-FLAIR MISMATCH SIGN IN OLIGODENDROGLIOMA, IDH-MUTANT AND 1P/19Q CODELETED

Abstract BACKGROUND We reported the super T2-FLAIR mismatch sign as a prognostic imaging biomarker for non-enhanced astrocytoma, IDH-mutant, CNS WHO grade 2 or 3. However, it remains unclear whether this novel imaging biomarker is applicable for oligodendroglioma, IDH-mutant and 1p/19q codeleted. METHODS We conducted a retrospective evaluation of non-enhanced oligodendroglioma, IDH-mutant and 1p/19q codeleted, including 14 cases from at our institute and 15 cases from TCGA/TCIA database. We defined “super T2-FLAIR mismatch sign” positivity as having a significantly strong low signal comparable to cerebrospinal fluid, rather than just a pale FLAIR low-signal tumor region as in regular T2-FLAIR mismatch. We evaluated the presence or absence of T2-FLAIR mismatch sign and super T2-FLAIR mismatch sign using preoperative MRI and statistically analyzed the progression-free survival (PFS) and overall survival (OS) using log-rank test. RESULTS The median age of this patient group was 47 (ranging 20-77) years and consisted with 16 males and 13 females. There were 27 cases of grade 2 and two cases of grade 3. The regular T2-FLAIR mismatch sign was observed in three cases (10%) (grade 2: 2 cases, grade 3: 1 case). While the super T2-FLAIR mismatch sign was observed in three cases (10%) (grade 2: 2 cases, grade 3: 1 case). One case had both regular and super T2-FLAIR mismatch signs. The mean follow-up period was 33.4 months, during which there were 3 cases of progression and 1 death. Both regular and super T2-FLAIR mismatch sign were not associated with PFS, OS. CONCLUSIONS The presence of the super T2-FLAIR mismatch sign was not associated with prognosis in oligodendroglioma, IDH-mutant and 1p/19q codeleted. Because the sample size was insufficient, further larger investigation through is needed to assess the utility of this sign.

Comment on, "T2-FLAIR mismatch sign, an imaging biomarker for CDKN2A-intact in non-enhancing astrocytoma, IDH-mutant".

The study by Onishi et al. (2024) investigates the correlation between the T2-FLAIR mismatch sign and CDKN2A status in non-enhancing astrocytoma, IDH-mutant. Through the use of radiological and molecular pathological analyses, the research explores the potential of T2-FLAIR mismatch as an imaging biomarker for predicting CDKN2A-intact astrocytomas. Immunohistochemical staining and next-generation sequencing were employed to confirm molecular diagnosis, enhancing the study's robustness. While the findings contribute significantly to preoperative diagnostics and treatment planning, limitations exist. The relatively small sample size (31 patients) and exclusion of gadolinium-enhancing astrocytomas may restrict the generalizability of the results. Additionally, variation in imaging protocols and the retrospective nature of the study limit the overall impact. Future research with a larger cohort, standardized imaging protocols, and a prospective design is recommended to validate the clinical utility of T2-FLAIR mismatch in differentiating CDKN2A status in astrocytomas.

Enhancing glioma care with advanced imaging: T2-FLAIR mismatch as a predictive biomarker in IDH-mutant astrocytoma.

The study highlights that diffuse glioma, a prevalent type of brain tumor, affect approximately 100,000 individuals worldwide each year. IDH-mutant astrocytoma and oligodendrogliomas typically have a more favorable prognosis compared to IDH-wildtype glioblastomas. However, many IDH-mutant astrocytoma has the potential to progress to grade 4 glioblastomas, leading to a less favorable prognosis. In a recent investigation, Shumpei Onishi et al. examined the T2-FLAIR mismatch sign as a possible imaging biomarker for assessing CDKN2A status in non-enhancing IDH-mutant astrocytoma. The findings indicate that the T2-FLAIR mismatch sign is linked to CDKN2A-intact astrocytoma, providing a valuable tool for diagnostic and prognostic purposes. Additionally, the use of Indocyanine Green (ICG) for real-time visualization during neurosurgical procedures demonstrates potential, though it may have limitations in specificity. While these advancements offer promise in glioma management, there remains a critical need for larger, standardized studies to validate these findings and further improve treatment outcomes.

Usefulness of synthetic MRI for differentiation of IDH-mutant diffuse gliomas and its comparison with the T2-FLAIR mismatch sign.

The T2-FLAIR mismatch sign is a characteristic imaging biomarker for astrocytoma, isocitrate dehydrogenase (IDH)-mutant. However, investigators have provided varying interpretations of the positivity/negativity of this sign given for individual cases the nature of qualitative visual assessment. Moreover, MR sequence parameters also influence the appearance of the T2-FLAIR mismatch sign. To resolve these issues, we used synthetic MR technique to quantitatively evaluate and differentiate astrocytoma from oligodendroglioma. This study included 20 patients with newly diagnosed non-enhanced IDH-mutant diffuse glioma who underwent preoperative synthetic MRI using the Quantification of Relaxation Times and Proton Density by Multiecho acquisition of a saturation-recovery using Turbo spin-Echo Readout (QRAPMASTER) sequence at our institution. Two independent reviewers evaluated preoperative conventional MR images to determine the presence or absence of the T2-FLAIR mismatch sign. Synthetic MRI was used to measure T1, T2 and proton density (PD) values in the tumor lesion. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance. The pathological diagnoses included astrocytoma, IDH-mutant (n = 12) and oligodendroglioma, IDH-mutant and 1p/19q-codeleted (n = 8). The sensitivity and specificity of T2-FLAIR mismatch sign for astrocytoma were 66.7% and 100% [area under the ROC curve (AUC) = 0.833], respectively. Astrocytoma had significantly higher T1, T2, and PD values than did oligodendroglioma (p < 0.0001, < 0.0001, and 0.0154, respectively). A cutoff lesion T1 value of 1580 ms completely differentiated astrocytoma from oligodendroglioma (AUC = 1.00). Quantitative evaluation of non-enhanced IDH-mutant diffuse glioma using synthetic MRI allowed for better differentiation between astrocytoma and oligodendroglioma than did conventional T2-FLAIR mismatch sign. Measurement of T1 and T2 value by synthetic MRI could improve the differentiation of IDH-mutant diffuse gliomas.

T2-FLAIR mismatch sign, an imaging biomarker for CDKN2A-intact in non-enhancing astrocytoma, IDH-mutant

IntroductionThe WHO classification of central nervous system tumors (5th edition) classified astrocytoma, IDH-mutant accompanied with CDKN2A/B homozygous deletion as WHO grade 4. Loss of immunohistochemical (IHC) staining for methylthioadenosine phosphorylase (MTAP) was developed as a surrogate marker for CDKN2A-HD. Identification of imaging biomarkers for CDKN2A status is of immense clinical relevance. In this study, we explored the association between radiological characteristics of non-enhancing astrocytoma, IDH-mutant to the CDKN2A/B status.MethodsThirty-one cases of astrocytoma, IDH-mutant with MTAP results by IHC were included in this study. The status of CDKN2A was diagnosed by IHC staining for MTAP in all cases, which was further confirmed by comprehensive genomic analysis in 12 cases. The T2-FLAIR mismatch sign, cystic component, calcification, and intratumoral microbleeding were evaluated. The relationship between the radiological features and molecular pathological diagnosis was analyzed.ResultsTwenty-six cases were identified as CDKN2A-intact while 5 cases were CDKN2A-HD. The presence of > 33% and > 50% T2-FLAIR mismatch was observed in 23 cases (74.2%) and 14 cases (45.2%), respectively, and was associated with CDKN2A-intact astrocytoma (p = 0.0001, 0.0482). None of the astrocytoma, IDH-mutant with CDKN2A-HD showed T2-FLAIR mismatch sign. Cystic component, calcification, and intratumoral microbleeding were not associated with CDKN2A status.ConclusionIn patients with non-enhancing astrocytoma, IDH-mutant, the T2-FLAIR mismatch sign is a potential imaging biomarker for the CDKN2A-intact subtype. This imaging biomarker may enable preoperative prediction of CDKN2A status among astrocytoma, IDH-mutant.

Super T2-FLAIR mismatch sign: a prognostic imaging biomarker for non-enhancing astrocytoma, IDH-mutant

PurposeThe T2-FLAIR mismatch sign is a highly specific diagnostic imaging biomarker for astrocytoma, IDH-mutant. However, a definitive prognostic imaging biomarker has yet to be identified. This study investigated imaging prognostic markers, specifically analyzing T2-weighted and FLAIR images of this tumor.MethodsWe retrospectively analyzed 31 cases of non-enhancing astrocytoma, IDH-mutant treated at our institution, and 30 cases from The Cancer Genome Atlas (TCGA)/The Cancer Imaging Archive (TCIA). We defined “super T2-FLAIR mismatch sign” as having a significantly strong low signal comparable to cerebrospinal fluid at non-cystic lesions rather than just a pale FLAIR low-signal tumor lesion as in conventional T2-FLAIR mismatch sign. Cysts were defined as having a round or oval shape and were excluded from the criteria for the super T2-FLAIR mismatch sign. We evaluated the presence or absence of the T2-FLAIR mismatch sign and super T2-FLAIR mismatch sign using preoperative MRI and analyzed the progression-free survival (PFS) and overall survival (OS) by log-rank test.ResultsThe T2-FLAIR mismatch sign was present in 17 cases (55%) in our institution and 9 cases (30%) within the TCGA-LGG dataset without any correlation with PFS or OS. However, the super T2-FLAIR mismatch sign was detected in 8 cases (26%) at our institution and 13 cases (43%) in the TCGA-LGG dataset. At our institution, patients displaying the super T2-FLAIR mismatch sign showed significantly extended PFS (122.7 vs. 35.9 months, p = 0.0491) and OS (not reached vs. 116.7 months, p = 0.0232). Similarly, in the TCGA-LGG dataset, those with the super T2-FLAIR mismatch sign exhibited notably longer OS (not reached vs. 44.0 months, p = 0.0177).ConclusionThe super T2-FLAIR mismatch is a promising prognostic imaging biomarker for non-enhancing astrocytoma, IDH-mutant.

IMG-14. DIAGNOSTIC UTILITY OF THE T2-FLAIR MISMATCH SIGN FOR DNETS AND ITS ASSOCIATION WITH FGFR1 ALTERATIONS

Abstract BACKGROUND The T2-FLAIR mismatch sign, hyperintense T2-weighted signals with corresponding hypointensity on FLAIR sequence, has emerged as a potential diagnostic tool for identifying specific brain tumor subtypes. We tested the diagnostic utility of the sign in dysembryoplastic neuroepithelial tumors (DNETs) with and without FGFR1 alterations. METHODS We evaluated the T2-FLAIR mismatch sign in a cohort of 43 patients with definitive or probable DNET. Low-grade glioma patients with definite non-DNET diagnoses were chosen as control (n=43). Receiver operative curve analysis was performed, and the corresponding odds ratios were calculated. RESULTS Of the 43 DNET cases, 35 were definite, and 8 were probable DNETs. FGFR1 alterations were confirmed in 9 definitive DNETs. The area under the curve (AUC) for diagnosing DNET with the T2-FLAIR mismatch sign was 0.884 (DeLong CI: 0.2, 0.95) (Accuracy: 0.88, 95% CI: 0.80, 0.94; Sensitivity: 0.84; Specificity: 0.95); for definite DNET it was 0.891 (DeLong CI: 0.82, 0.96) (Accuracy: 0.90, 95% CI: 0.81, 0.95; Sensitivity: 0.87; Specificity: 0.94); for probable DNET it was 0.852 (DeLong CI: 0.69, 1;) (Accuracy 0.92, 95% CI: 0.81, 0.98; Sensitivity: 0.84; Specificity: 0.75), and for DNET with FGFR1 alterations was 0.977 (DeLong CI: 0.95, 1) (Accuracy 0.96, 95% CI: 0.87, 1; Sensitivity: 1; Specificity: 0.81). The odds of having DNET (definite +probable) if the T2-FLAIR mismatch sign was positive was 81.96 (CI: 16.25, 852.48, P&amp;lt;0.001), and DNET with FGFR1 is 315.4 (CI: 312.3, 318.5, P&amp;lt;0.001). CONCLUSION The T2-FLAIR mismatch sign is a reliable radiological biomarker for DNET and strongly predicts FGFR1 alterations in these tumors.

MRI Scoring Systems for Predicting Isocitrate Dehydrogenase Mutation and Chromosome 1p/19q Codeletion in Adult-type Diffuse Glioma Lacking Contrast Enhancement.

Background According to 2021 World Health Organization criteria, adult-type diffuse gliomas include glioblastoma, isocitrate dehydrogenase (IDH)-wildtype; oligodendroglioma, IDH-mutant and 1p/19q-codeleted; and astrocytoma, IDH-mutant, even when contrast enhancement is lacking. Purpose To develop and validate simple scoring systems for predicting IDH and subsequent 1p/19q codeletion status in gliomas without contrast enhancement using standard clinical MRI sequences. Materials and Methods This retrospective study included adult-type diffuse gliomas lacking contrast at contrast-enhanced MRI from two tertiary referral hospitals between January 2012 and April 2022 with diagnoses confirmed at pathology. IDH status was predicted primarily by using T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign, followed by 1p/19q codeletion prediction. A visual rating of MRI features, apparent diffusion coefficient (ADC) ratio, and relative cerebral blood volume was measured. Scoring systems were developed through univariable and multivariable logistic regressions and underwent calibration and discrimination, including internal and external validation. Results For the internal validation cohort, 237 patients were included (mean age, 44.4 years ± 14.4 [SD]; 136 male patients; 193 patients in IDH prediction and 163 patients in 1p/19q prediction). For the external validation cohort, 35 patients were included (46.1 years ± 15.3; 20 male patients; 28 patients in IDH prediction and 24 patients in 1p/19q prediction). The T2-FLAIR mismatch sign demonstrated 100% specificity and 100% positive predictive value for IDH mutation. IDH status prediction scoring system for tumors without mismatch sign included age, ADC ratio, and morphologic characteristics, whereas 1p/19q codeletion prediction for IDH-mutant gliomas included ADC ratio, cortical involvement, and mismatch sign. For IDH status and 1p/19q codeletion prediction, bootstrap-corrected areas under the receiver operating characteristic curve were 0.86 (95% CI: 0.81, 0.90) and 0.73 (95% CI: 0.65, 0.81), respectively, whereas at external validation they were 0.99 (95% CI: 0.98, 1.0) and 0.88 (95% CI: 0.63, 1.0). Conclusion The T2-FLAIR mismatch sign and scoring systems using standard clinical MRI predicted IDH and 1p/19q codeletion status in gliomas lacking contrast enhancement. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Badve and Hodges in this issue.

Patterns of T2-FLAIR discordance across a cohort of adult-type diffuse gliomas and deviations from the classic T2-FLAIR mismatch sign.

T2-FLAIR mismatch serves as a highly specific but insensitive marker for IDH-mutant (IDHm) astrocytoma with potential limitations in real-world application. We aimed to assess the utility of a broader definition of T2-FLAIR discordance across a cohort of adult-type diffuse lower-grade gliomas (LrGG) to see if specific patterns emerge and additionally examine factors determining deviation from the classic T2-FLAIR mismatch sign. Preoperative MRIs of non-enhancing adult-type diffuse LrGGs were reviewed. Relevant demographic, molecular, and MRI data were compared across tumor subgroups. Eighty cases satisfied the inclusion criteria. Highest discordance prevalence and > 50% T2-FLAIR discordance volume were noted with IDHm astrocytomas (P < 0.001), while < 25% discordance volume was associated with oligodendrogliomas (P = 0.03) and IDH-wildtype (IDHw) LrGG (P = 0.004). "T2-FLAIRmatched pattern" was associated with IDHw LrGG (P < 0.001) and small or minimal areas of discordance with oligodendrogliomas (P = 0.03). Sensitivity and specificity of classic mismatch sign for IDHm astrocytoma were 25.7% and 100%, respectively (P = 0.06). Retained ATRX expression and/or non-canonical IDH mutation (n = 10) emerged as a significant factor associated with absence of classic T2-FLAIR mismatch sign in IDHm astrocytomas (100%, P = 0.02) and instead had minimal discordance or matched pattern (40%, P = 0.04). T2-FLAIR discordance patterns in adult-type diffuse LrGGs exist on a diverging but distinct spectrum of classic mismatch to T2-FLAIRmatched patterns. Specific molecular markers may play a role in deviations from classic mismatch sign.

T2-FLAIR mismatch sign and machine learning-based multiparametric MRI radiomics in predicting IDH mutant 1p/19q non-co-deleted diffuse lower-grade gliomas

To investigate the application of the T2-weighted (T2)-fluid-attenuated inversion recovery (FLAIR) mismatch sign and machine learning-based multiparametric magnetic resonance imaging (MRI) radiomics in predicting 1p/19q non-co-deletion of lower-grade gliomas (LGGs). One hundred and forty-six patients, who had pathologically confirmed isocitrate dehydrogenase (IDH) mutant LGGs were assigned randomly to the training cohort (n=102) and the testing cohort (n=44) at a ratio of 7:3. The T2-FLAIR mismatch sign and conventional MRI features were evaluated. Radiomics features extracted from T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), FLAIR, apparent diffusion coefficient (ADC), and contrast-enhanced T1WI images (CE-T1WI). The models that displayed the best performance of each sequence were selected, and their predicted values as well as the T2-FLAIR mismatch sign data were collected to establish a final stacking model. Receiver operating characteristic curve (ROC) analyses and area under the curve (AUC) values were applied to evaluate and compare the performance of the models. The T2-FLAIR mismatch sign was more common in the IDH mutant 1p/19q non-co-deleted group (p<0.05) and the area under the curve (AUC) value was 0.692 with sensitivity 0.397, specificity 0.987, and accuracy 0.712, respectively. The stacking model showed a favourable performance with an AUC of 0.925 and accuracy of 0.882 in the training cohort and an AUC of 0.886 and accuracy of 0.864 in the testing cohort. The stacking model based on multiparametric MRI can serve as a supplementary tool for pathological diagnosis, offering valuable guidance for clinical practice.

Quantification of T2-FLAIR Mismatch in Nonenhancing Diffuse Gliomas Using Digital Subtraction.

The T2-FLAIR mismatch sign on MR imaging is a highly specific imaging biomarker of isocitrate dehydrogenase (IDH)-mutant astrocytomas, which lack 1p/19q codeletion. However, most studies using the T2-FLAIR mismatch sign have used visual assessment. This study quantified the degree of T2-FLAIR mismatch using digital subtraction of fluid-nulled T2-weighted FLAIR images from non-fluid-nulled T2-weighted images in human nonenhancing diffuse gliomas and then used this information to assess improvements in diagnostic performance and investigate subregion characteristics within these lesions. Two cohorts of treatment-naïve, nonenhancing gliomas with known IDH and 1p/19q status were studied (n = 71 from The Cancer Imaging Archive (TCIA) and n = 34 in the institutional cohort). 3D volumes of interest corresponding to the tumor were segmented, and digital subtraction maps of T2-weighted MR imaging minus T2-weighted FLAIR MR imaging were used to partition each volume of interest into a T2-FLAIR mismatched subregion (T2-FLAIR mismatch, corresponding to voxels with positive values on the subtraction maps) and nonmismatched subregion (T2-FLAIR nonmismatch corresponding to voxels with negative values on the subtraction maps). Tumor subregion volumes, percentage of T2-FLAIR mismatch volume, and T2-FLAIR nonmismatch subregion thickness were calculated, and 2 radiologists assessed the T2-FLAIR mismatch sign with and without the aid of T2-FLAIR subtraction maps. Thresholds of ≥42% T2-FLAIR mismatch volume classified IDH-mutant astrocytoma with a specificity/sensitivity of 100%/19.6% (TCIA) and 100%/31.6% (institutional); ≥25% T2-FLAIR mismatch volume showed 92.0%/32.6% and 100%/63.2% specificity/sensitivity, and ≥15% T2-FLAIR mismatch volume showed 88.0%/39.1% and 93.3%/79.0% specificity/sensitivity. In IDH-mutant astrocytomas with ≥15% T2-FLAIR mismatch volume, T2-FLAIR nonmismatch subregion thickness was negatively correlated with the percentage T2-FLAIR mismatch volume (P < .0001) across both cohorts. The percentage T2-FLAIR mismatch volume was higher in grades 3-4 compared with grade 2 IDH-mutant astrocytomas (P < .05), and ≥15% T2-FLAIR mismatch volume IDH-mutant astrocytomas were significantly larger than <15% T2-FLAIR mismatch volume IDH-mutant astrocytoma (P < .05) across both cohorts. When evaluated by 2 radiologists, the additional use of T2-FLAIR subtraction maps did not show a significant difference in interreader agreement, sensitivity, or specificity compared with a separate evaluation of T2-FLAIR and T2-weighted MR imaging alone. T2-FLAIR digital subtraction maps may be a useful, automated tool to obtain objective segmentations of tumor subregions based on quantitative thresholds for classifying IDH-mutant astrocytomas using the percentage T2 FLAIR mismatch volume with 100% specificity and exploring T2-FLAIR mismatch/T2-FLAIR nonmismatch subregion characteristics. Conversely, the addition of T2-FLAIR subtraction maps did not enhance the sensitivity or specificity of the visual T2-FLAIR mismatch sign assessment by experienced radiologists.

Comparison of diagnostic performance of radiologist- and AI-based assessments of T2-FLAIR mismatch sign and quantitative assessment using synthetic MRI in the differential diagnosis between astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant and 1p/19q-codeleted

PurposeThis study aimed to compare assessments by radiologists, artificial intelligence (AI), and quantitative measurement using synthetic MRI (SyMRI) for differential diagnosis between astrocytoma, IDH-mutant and oligodendroglioma, and IDH-mutant and 1p/19q-codeleted and to identify the superior method.MethodsThirty-three cases (men, 14; women, 19) comprising 19 astrocytomas and 14 oligodendrogliomas were evaluated. Four radiologists independently evaluated the presence of the T2-FLAIR mismatch sign. A 3D convolutional neural network (CNN) model was trained using 50 patients outside the test group (28 astrocytomas and 22 oligodendrogliomas) and transferred to evaluate the T2-FLAIR mismatch lesions in the test group. If the CNN labeled more than 50% of the T2-prolonged lesion area, the result was considered positive. The T1/T2-relaxation times and proton density (PD) derived from SyMRI were measured in both gliomas. Each quantitative parameter (T1, T2, and PD) was compared between gliomas using the Mann–Whitney U-test. Receiver-operating characteristic analysis was used to evaluate the diagnostic performance.ResultsThe mean sensitivity, specificity, and area under the curve (AUC) of radiologists vs. AI were 76.3% vs. 94.7%; 100% vs. 92.9%; and 0.880 vs. 0.938, respectively. The two types of diffuse gliomas could be differentiated using a cutoff value of 2290/128 ms for a combined 90th percentile of T1 and 10th percentile of T2 relaxation times with 94.4/100% sensitivity/specificity with an AUC of 0.981.ConclusionCompared to the radiologists’ assessment using the T2-FLAIR mismatch sign, the AI and the SyMRI assessments increased both sensitivity and objectivity, resulting in improved diagnostic performance in differentiating gliomas.

Beyond T2-FLAIR mismatch sign in isocitrate dehydrogenase mutant 1p19q non-codeleted astrocytoma: Analysis of tumor core and evolution with multiparametric magnetic resonance imaging.

The T2-FLAIR mismatch sign is an imaging correlate for isocitrate dehydrogenase (IDH)-mutant 1p19q non-codeleted astrocytomas. However, it is only seen in a part of the cases at certain stages. Many of the tumors likely lose T2 homogeneity as they grow in size, and become heterogenous. The aim of this study was to investigate the timecourse of T2-FLAIR mismatch sign, and assess intratumoral heterogeneity using multiparametric magnetic resonance imaging techniques. A total of 128 IDH-mutant gliomas were retrospectively analyzed. Observers blinded to molecular status used strict criteria to select T2-FLAIR mismatch astrocytomas. Pre-biopsy and follow-up standard structural sequences of T2, FLAIR and apparent diffusion coefficient, MR spectroscopy (both single- and multi-voxel techniques), and DSC perfusion were observed. Nine T2-FLAIR mismatch astrocytomas were identified. 7 had MR spectroscopy and perfusion data. The smallest astrocytomas began as rounded T2 homogeneous lesions without FLAIR suppression, and developed T2-FLAIR mismatch during follow-up with falls in NAA and raised Cho/Cr ratio. Larger tumors at baseline with T2-FLAIR mismatch signs developed intratumoral heterogeneity, and showed elevated Cho/Cr ratio and raised relative cerebral blood volume (rCBV). The highest levels of intratumoral Cho/Cr and rCBV changes were located within the tumor core, and this area signifies the progression of the tumors toward high grade. T2-FLAIR mismatch sign is seen at a specific stage in the development of astrocytoma. By assessing the subsequent heterogeneity, MR spectroscopy and perfusion imaging are able to predict the progression of the tumor towards high grade, thereby can assist targeting for biopsy and selective debulking.

Multi-level Feature Exploration and Fusion Network for Prediction of IDH Status in Gliomas from MRI.

Isocitrate dehydrogenase (IDH) is one of the most important genotypes in patients with glioma because it can affect treatment planning. Machine learning-based methods have been widely used for prediction of IDH status (denoted as IDH prediction). However, learning discriminative features for IDH prediction remains challenging because gliomas are highly heterogeneous in MRI. In this paper, we propose a multi-level feature exploration and fusion network (MFEFnet) to comprehensively explore discriminative IDH-related features and fuse different features at multiple levels for accurate IDH prediction in MRI. First, a segmentation-guided module is established by incorporating a segmentation task and is used to guide the network in exploiting features that are highly related to tumors. Second, an asymmetry magnification module is used to detect T2-FLAIR mismatch sign from image and feature levels. The T2-FLAIR mismatch-related features can be magnified from different levels to increase the power of feature representations. Finally, a dual-attention feature fusion module is introduced to fuse and exploit the relationships of different features from intra- and inter-slice feature fusion levels. The proposed MFEFnet is evaluated on a multi-center dataset and shows promising performance in an independent clinical dataset. The interpretability of the different modules is also evaluated to illustrate the effectiveness and credibility of the method. Overall, MFEFnet shows great potential for IDH prediction.

Identifying IDH-mutant and 1p/19q noncodeleted astrocytomas from nonenhancing gliomas: Manual recognition followed by artificial intelligence recognition.

The T2-FLAIR mismatch sign (T2FM) has nearly 100% specificity for predicting IDH-mutant and 1p/19q noncodeleted astrocytomas (astrocytomas). However, only 18.2%-56.0% of astrocytomas demonstrate a positive T2FM. Methods must be considered for distinguishing astrocytomas from negative T2FM gliomas. In this study, positive T2FM gliomas were manually distinguished from nonenhancing gliomas, and then a support vector machine (SVM) classification model was used to distinguish astrocytomas from negative T2FM gliomas. Nonenhancing gliomas (regardless of pathological type or grade) diagnosed between January 2022 and October 2022 (N = 300) and November 2022 and March 2023 (N = 196) will comprise the training and validation sets, respectively. Our method for distinguishing astrocytomas from nonenhancing gliomas was examined and validated using the training set and validation set. The specificity of T2FM for predicting astrocytomas was 100% in both the training and validation sets, while the sensitivity was 42.75% and 67.22%, respectively. Using a classification model of SVM based on radiomics features, among negative T2FM gliomas, the accuracy was above 85% when the prediction score was greater than 0.70 in identifying astrocytomas and above 95% when the prediction score was less than 0.30 in identifying nonastrocytomas. Manual screening of positive T2FM gliomas, followed by the SVM classification model to differentiate astrocytomas from negative T2FM gliomas, may be a more effective method for identifying astrocytomas in nonenhancing gliomas.

10268-NI-13 T2-FLAIR MISMATCH SIGN CORRELATES WITH11C-METHIONINE UPTAKE IN LOWER-GRADE DIFFUSE GLIOMAS

Abstract PURPOSE The T2-FLAIR mismatch sign is recognized as an imaging finding highly suggestive of IDH-mutant astrocytomas. This study was designed to determine whether the T2-FLAIR mismatch sign correlates with uptake of 11C-methionine in lower-grade gliomas. METHODS We included 78 histopathologically verified lower-grade gliomas (grade 2: 31 cases, grade 3: 47 cases) in this study. 78 patients underwent 11C-methionine positron emission tomography (MET-PET) scans and magnetic resonance (MR) imaging scans prior to histological diagnosis. The tumor-to-normal ratio (T/N) of 11C-methionine uptake was calculated by dividing the maximum standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain. MR imaging scans were evaluated for the presence of the T2-FLAIR mismatch sign by three independent reviewers. We compared molecular status, the T2-FLAIR mismatch sign and 11C-methionine uptake among patients with different lower-grade glioma molecular types. RESULTS The 78 lower-grade gliomas were assigned to one of three molecular groups: Group A (IDH-mutant and 1p/19q non-codeleted, n=22), Group O (IDH-mutant and 1p/19q codeleted, n=20), and Group W (IDH wildtype, n=36). T2-FLAIR mismatch was found in 16 cases (20.5%) that were comprised of 8 (36.4%), 0 (0%), 8 (22.2%) cases in the molecular group A, O and W, respectively. The median T/N ratio of MET-PET in tumors with T2-FLAIR mismatch was 1.50, which was significantly lower than that of tumors without T2-FLAIR mismatch (1.83, p&amp;lt;0.001, Mann-Whitney U test). In the Groups A and W (excluding Group O), the median T/N ratio on MET-PET in groups A and W (but not group O) with T2-FLAIR mismatch was 1.50, which was significantly lower than that of tumors without T2-FLAIR mismatch (1.81, p=0.002, Mann-Whitney U test). CONCLUSION The T2-FLAIR mismatch sign correlated with lower 11C-methionine uptake in lower grade gliomas.

NIMG-40. SUPER T2-FLAIR MISMATCH SIGN AS PROGNOSTIC IMAGING BIOMARKER FOR NON-ENHANCED ASTROCYTOMA, IDH-MUTANT

Abstract BACKGROUND The T2-FLAIR mismatch sign has been established as a highly specific diagnostic imaging biomarker for astrocytoma, IDH-mutant. However, prognostic imaging biomarker for this tumor has not been well established. METHODS We retrospectively reviewed 31 cases of non-enhanced astrocytoma, IDH-mutant, WHO grade 2 and 3 treated at our hospital. We defined “super T2-FLAIR mismatch sign” positivity as having a significantly strong low signal comparable to cerebrospinal fluid, rather than just a pale FLAIR low-signal tumor region as in regular T2-FLAIR mismatch. We evaluated the presence or absence of T2-FLAIR mismatch sign and super T2-FLAIR mismatch sign using preoperative MRI and statistically analyzed the progression-free survival (PFS) and overall survival (OS) using log-rank test. RESULTS The median age of this patient group was 40 (ranging 19-75) years, and consisted with 21 males and 10 females., with 21 males and 10 females. There were 25 cases of grade 2 and six cases of grade 3. T2-FLAIR mismatch sign was observed in 17 cases (54.8%) (grade 2: 16 cases, grade 3: 1 case), and super T2-FLAIR mismatch sign was observed in eight cases (25.8%) (grade 2: 8 cases). The presence or absence of T2-FLAIR mismatch sign was not associated with both PFS (46.8 months vs. 33.6 months, p=0.2526) and OS (not reached vs. 152 months, p=0.2087). Positive super T2-FLAIR mismatch sign cases have propensity to show longer PFS (112.7 months vs. 36.0 months, p=0.0710), and significantly longer OS (not reached vs. 152 months, p=0.0392). When super T2-FLAIR mismatch sign-positive cases were compared to negative cases in patients who did not accomplish entire removal, the PFS was significantly longer (p=0.0045) and there was a propensity for a longer OS (p=0.0543). CONCLUSIONS Super T2-FLAIR mismatch sign can be considered as a prognostic imaging biomarker for non-enhanced astrocytoma, IDH-mutant.

NIMG-62. QUANTITATIVE ASSESSMENT OF T2-FLAIR MISMATCH IN HUMAN NON-ENHANCING GLIOMAS USING SUBTRACTION MAPS OF T2-W AND FLAIR MRI

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

Radiogenomics Provides Insights into Gliomas Demonstrating Single-Arm 1p or 19q Deletion.

IDH-mutant gliomas are further divided on the basis of 1p/19q status: oligodendroglioma, IDH-mutant and 1p/19q-codeleted, and astrocytoma, IDH-mutant (without codeletion). Occasionally, testing may reveal single-arm 1p or 19q deletion (unideletion), which remains within the diagnosis of astrocytoma. Molecular assessment has some limitations, however, raising the possibility that some unideleted tumors could actually be codeleted. This study assessed whether unideleted tumors had MR imaging features and survival more consistent with astrocytomas or oligodendrogliomas. One hundred twenty-one IDH-mutant grade 2-3 gliomas with 1p/19q results were identified. Two neuroradiologists assessed the T2-FLAIR mismatch sign and calcifications, as differentiators of astrocytomas and oligodendrogliomas. MR imaging features and survival were compared among the unideleted tumors, codeleted tumors, and those without 1p or 19q deletion. The cohort comprised 65 tumors without 1p or 19q deletion, 12 unideleted tumors, and 44 codeleted. The proportion of unideleted tumors demonstrating the T2-FLAIR mismatch sign (33%) was similar to that in tumors without deletion (49%; P = .39), but significantly higher than codeleted tumors (0%; P = .001). Calcifications were less frequent in unideleted tumors (0%) than in codeleted tumors (25%), but this difference did not reach statistical significance (P = .097). The median survival of patients with unideleted tumors was 7.8 years, which was similar to that in tumors without deletion (8.5 years; P = .72) but significantly shorter than that in codeleted tumors (not reaching median survival after 12 years; P = .013). IDH-mutant gliomas with single-arm 1p or 19q deletion have MR imaging appearance and survival that are similar to those of astrocytomas without 1p or 19q deletion and significantly different from those of 1p/19q-codeleted oligodendrogliomas.

P03.03.A T2-FLUID-ATTENUATED INVERSION RECOVERY MISMATCH SIGN IN LOWER-GRADE GLIOMAS: CORRELATION WITH PATHOLOGICAL AND MOLECULAR FINDINGS

Abstract BACKGROUND After the new molecular-based classification was reported to be useful for predicting prognosis, the T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign has gained interest as one of the promising methods for detecting lower-grade gliomas (LGGs) with isocitrate dehydrogenase (IDH) mutations and chromosome 1p/19q non-codeletion (IDH mut-Noncodel) with high specificity. Although all institutions could use T2-FLAIR mismatch sign without any obstacles, this sign was not completely helpful because of its low sensitivity. In this study, we attempted to uncover the mechanism of T2-FLAIR mismatch sign for clarifying the cause of this sign’s low sensitivity. MATERIAL AND METHODS In this study, data on 101 consecutive and unselected patients with LGGs (WHO grades 2 and 3) admitted to Miyazaki University Hospital between November 2005 and January 2021 were collected. The inclusion criteria were as follows: (1) obtained molecular information on IDH mutation and chromosome 1p/19q codeletion status and (2) obtained preoperative MRI data, including T2-weighted imaging and FLAIR sequences. In this study, 99 patients were enrolled and then classified into three groups based on IDH mutation and chromosome 1p/19q codeletion status: (1) IDH-mutant, 1p/19q-codeleted LGGs (IDH mut-codel); (2) IDH-mutant, 1p/19q-noncodeleted LGGs (IDH mut-Noncodel); and (3) IDH wild-type LGGs (IDH wt). RESULTS Among 99 patients with LGGs, 22 were T2-FLAIR mismatch sign-positive (22%), and this sign as a marker of IDH mut-Noncodel showed a sensitivity of 55.6% and specificity of 96.8%. Via pathological analyses, we could provide evidence that not only microcystic changes but the enlarged intercellular space was associated with T2-FLAIR mismatch sign (p =0.017). As per the molecular analyses, overexpression of mTOR-related genes (m-TOR, RICTOR) were detected as the molecular events correlated with T2-FLAIR mismatch sign (p = 0.020, 0.030. respectively). CONCLUSION We suggested that T2-FLAIR mismatch sign could pick up the IDH mut-Noncodel LGGs with enlarged intercellular space or that with overexpression of mTOR-related genes.