T2-FLAIR Mismatch Sign Research Articles

Impact of Inversion Time for FLAIR Acquisition on the T2-FLAIR Mismatch Detectability for IDH-Mutant, Non-CODEL Astrocytomas.

The current research tested the hypothesis that inversion time (TI) shorter than 2,400 ms under 3T for FLAIR can improve the diagnostic accuracy of the T2-FLAIR mismatch sign for identifying IDHmt, non-CODEL astrocytomas. We prepared three different cohorts; 94 MRI from 76 IDHmt, non-CODEL Lower-grade gliomas (LrGGs), 33 MRI from 31 LrGG under the restriction of FLAIR being acquired with TI < 2,400 ms for 3T or 2,016 ms for 1.5T, and 112 MRI from 112 patients from the TCIA/TCGA dataset for LrGG. The presence or absence of the “T2-FLAIR mismatch sign” was evaluated, and we compared diagnostic accuracies according to TI used for FLAIR acquisition. The T2-FLAIR mismatch sign was more frequently positive when TI was shorter than 2,400 ms under 3T for FLAIR acquisition (p = 0.0009, Fisher’s exact test). The T2-FLAIR mismatch sign was positive only for IDHmt, non-CODEL astrocytomas even if we confined the cohort with FLAIR acquired with shorter TI (p = 0.0001, Fisher’s exact test). TCIA/TCGA dataset validated that the sensitivity, specificity, PPV, and NPV of the T2-FLAIR mismatch sign to identify IDHmt, non-CODEL astrocytomas improved from 31, 90, 79, and 51% to 67, 94, 92, and 74%, respectively and the area under the curve of ROC improved from 0.63 to 0.87 when FLAIR was acquired with shorter TI. We revealed that TI for FLAIR impacts the T2-FLAIR mismatch sign’s diagnostic accuracy and that FLAIR scanned with TI < 2,400 ms in 3T is necessary for LrGG imaging.

The T2-FLAIR mismatch sign as a predictor of IDH-mutant, 1p/19q-noncodeleted lower-grade gliomas: a systematic review and diagnostic meta-analysis.

To evaluate the diagnostic performance of the T2-FLAIR mismatch sign for prediction of isocitrate dehydrogenase (IDH)-mutant, 1p/19q-noncodeleted lower-grade gliomas (LGGs) and review studies with false positive results. The MEDLINE and EMBASE databases were searched up to March 13, 2020, to identify articles reporting the diagnostic performance of the T2-FLAIR mismatch sign for prediction of IDH-mutant, 1p/19q-noncodeleted LGGs (IDHmut-Noncodel) using the search terms (T2 FLAIR mismatch). Pooled sensitivity, specificity, and correlation coefficient for interobserver agreement were calculated. Twelve studies including a total of 1053 patients were included. The median age was 43 (median; range, 14-56). The pooled sensitivity and specificity were 42% (95% CI, 28-58%) and 100% (95% CI, 88-100%), respectively. According to the HSROC curve, the area under the curve was 0.77 (95% CI, 0.73-0.80). Considerable heterogeneity was possible among the studies in terms of both sensitivity and specificity. A threshold effect was suggested and was considered to explain most of the heterogeneity. Four studies reported false positive results for the T2-FLAIR mismatch sign, including dysembryoplastic neuroepithelial tumor, pediatric-type gliomas, and non-neoplastic lesions. The 2 original articles with false positive results showed the highest sensitivities among the 10 studies included in the quantitative analysis, supporting the probability of the threshold effect. The pooled correlation coefficient was 0.87 (95% CI, 0.73-0.94). The T2-FLAIR mismatch sign had a high specificity and interobserver agreement for the prediction of IDHmut-Noncodel. However, the sign demonstrated low sensitivity, and a few studies with false positive cases were also reported. • The pooled sensitivity and specificity of the T2-FLAIR mismatch sign for prediction of IDH-mutant, 1p/19q-noncodeleted lower-grade gliomas were 42% and 100%, respectively. • Four studies reported false positive results. • The pooled correlation coefficient was 0.87, suggesting almost perfect interobserver agreement.

Improvement of T2-FLAIR Mismatch Sign Detectability for IDHmt/nonCODEL Astrocytomas by Shortening the Inversion Time in FLAIR Acquisition

Kinoshita, Manabu MD, PhD; Takahashi, Masamichi; Arita, Hideyuki MD, PhD; Takehiro, Uda; Fukai, Junya; Ishibashi, Kenichi MD; Narita, Yoshitaka MD, PhD; Ichimura, Koichi; Kanemura, Yonehiro; Kishima, Haruhiko Author Information

The Role of the T2-FLAIR Mismatch Sign as an Imaging Marker of IDH Status in a Mixed Population of Low- and High-Grade Gliomas.

Our study evaluated the role of the T2–fluid-attenuated inversion recovery (FLAIR) mismatch sign in detecting isocitrate dehydrogenase (IDH) mutations based on a mixed sample of 24 patients with low- and high- grade gliomas. The association between the two was realized using univariate and multivariate logistic regression analysis. There was a substantial agreement between the two raters for the detection of the T2–FLAIR mismatch sign (Cohen’s kappa coefficient was 0.647). The T2–FLAIR mismatch sign when co-registered with the degree of tumor homogeneity were significant predictors of the IDH status (OR 29.642; 95% CI 1.73–509.15, p = 0.019). The probability of being IDH mutant in the presence of T2–FLAIR mismatch sign was as high as 92.9% (95% CI 63–99%). The sensitivity and specificity of T2–FLAIR mismatch sign in the detection of the IDH mutation was 88.9% and 86.7%, respectively. The T2–FLAIR mismatch sign may be an easy to use and helpful tool in recognizing IDH mutant patients, particularly if formal IDH testing is not available. We suggest that the adoption of a protocol based on imaging and histological data for optimal glioma characterization could be very helpful.

NIMG-11. IMPACT OF INVERSION TIME FOR FLAIR ACQUISITION ON THE T2-FLAIR MISMATCH DETECTABILITY FOR IDH-MUTANT, NON-CODEL ASTROCYTOMAS

Abstract PURPOSE The current research tested the hypothesis that TI shorter than 2400 ms under 3T for FLAIR can improve the diagnostic accuracy of the T2-FLAIR mismatch sign for identifying IDHmt, non-CODEL astrocytomas. EXPERIMENTAL DESIGN We prepared three different cohorts; 94 MRI from 76 IDHmt, non-CODEL LrGGs, 33 MRI from 31 LrGG under the restriction of FLAIR being acquired with TI &amp;lt; 2400 ms for 3T or 2016 ms for 1.5T, and 103 MRI from 103 patients from the TCIA/TCGA dataset for LrGG. The presence or absence of the “T2-FLAIR mismatch sign” was evaluated, and we compared diagnostic accuracies according to TI used for FLAIR acquisition. RESULTS The T2-FLAIR mismatch sign was more frequently positive when TI was shorter than 2400 ms under 3T for FLAIR acquisition (p = 0.0009, Fisher’s exact test). The T2-FLAIR mismatch sign was positive only for IDHmt, non-CODEL astrocytomas even if we confined the cohort with FLAIR acquired with shorter TI (p = 0.0001, Fisher’s exact test). TCIA/TCGA dataset validated that the sensitivity, specificity, PPV, and NPV of the T2-FLAIR mismatch sign to identify IDHmt, non-CODEL astrocytomas improved from 31%, 90%, 79%, and 51% to 67%, 94%, 92%, and 74%, respectively if we acquired FLAIR with TI shorter than 2400 ms. CONCLUSIONS We revealed that TI for FLAIR impacts diagnostic accuracy of the T2-FLAIR mismatch sign and that FLAIR scanned with TI &amp;lt; 2400 ms in 3T is necessary for LrGG imaging.

Automated apparent diffusion coefficient analysis for genotype prediction in lower grade glioma: association with the T2-FLAIR mismatch sign.

The prognosis of lower grade glioma (LGG) patients depends (in large part) on both isocitrate dehydrogenase (IDH) gene mutation and chromosome 1p/19q codeletion status. IDH-mutant LGG without 1p/19q codeletion (IDHmut-Noncodel) often exhibit a unique imaging appearance that includes high apparent diffusion coefficient (ADC) values not observed in other subtypes. The purpose of this study was to develop an ADC analysis-based approach that can automatically identify IDHmut-Noncodel LGG. Whole-tumor ADC metrics, including fractional tumor volume with ADC > 1.5 × 10-3mm2/s (VADC>1.5), were used to identify IDHmut-Noncodel LGG in a cohort of N = 134 patients. Optimal threshold values determined in this dataset were then validated using an external dataset containing N = 93 cases collected from The Cancer Imaging Archive. Classifications were also compared with radiologist-identified T2-FLAIR mismatch sign and evaluated concurrently to identify added value from a combined approach. VADC>1.5 classified IDHmut-Noncodel LGG in the internal cohort with an area under the curve (AUC) of 0.80. An optimal threshold value of 0.35 led to sensitivity/specificity = 0.57/0.93. Classification performance was similar in the validation cohort, with VADC>1.5 ≥ 0.35 achieving sensitivity/specificity = 0.57/0.91 (AUC = 0.81). Across both groups, 37 cases exhibited positive T2-FLAIR mismatch sign-all of which were IDHmut-Noncodel. Of these, 32/37 (86%) also exhibited VADC>1.5 ≥ 0.35, as did 23 additional IDHmut-Noncodel cases which were negative for T2-FLAIR mismatch sign. Tumor subregions with high ADC were a robust indicator of IDHmut-Noncodel LGG, with VADC>1.5 achieving > 90% classification specificity in both internal and validation cohorts. VADC>1.5 exhibited strong concordance with the T2-FLAIR mismatch sign and the combination of both parameters improved sensitivity in detecting IDHmut-Noncodel LGG.

Conventional MRI features of adult diffuse glioma molecular subtypes: a systematic review.

Molecular parameters have become integral to glioma diagnosis. Much of radiogenomics research has focused on the use of advanced MRI techniques, but conventional MRI sequences remain the mainstay of clinical assessments. The aim of this research was to synthesize the current published data on the accuracy of standard clinical MRI for diffuse glioma genotyping, specifically targeting IDH and 1p19q status. A systematic search was performed in September 2019 using PubMed and the Cochrane Library, identifying studies on the diagnostic value of T1 pre-/post-contrast, T2, FLAIR, T2*/SWI and/or 3-directional diffusion-weighted imaging sequences for the prediction of IDH and/or 1p19q status in WHO grade II-IV diffuse astrocytic and oligodendroglial tumours as defined in the WHO 2016 Classification of CNS Tumours. Forty-four studies including a total of 5286 patients fulfilled the inclusion criteria. Correlations between key glioma molecular markers, namely IDH and 1p19q, and distinctive MRI findings have been established, including tumour location, signal composition (including the T2-FLAIR mismatch sign) and apparent diffusion coefficient values. Consistent trends have emerged indicating that conventional MRI is valuable for glioma genotyping, particularly in presumed lower grade glioma. However, due to limited interobserver testing, the reproducibility of qualitatively assessed visual features remains an area of uncertainty.

Clinicopathological analysis of T2-FLAIR mismatch sign in lower-grade gliomas

T2-FLAIR mismatch sign is known as a highly specific imaging marker of IDH-mutant astrocytomas. This study was intended to clarify what the T2-FLAIR mismatch sign represents by pathological analysis of lower-grade gliomas rediagnosed in accordance with the WHO 2016 classification. We retrospectively analyzed the records of 64 patients diagnosed with WHO grade II and III diffuse gliomas between June 2009 and November 2018. T2-FLAIR mismatch sign was found in 10 (45%) out of 22 patients with IDH-mutant astrocytoma, 1 (5%) out of 20 with oligodendroglioma, and 1 (5%) out of 22 with IDH-wild-type astrocytoma. T2-FLAIR mismatch sign as a marker of IDH-mutant astrocytomas showed positive predictive value of 83%. Among 22 patients with IDH-mutant astrocytomas, microcystic change was found in eight, of which seven showed T2-FLAIR mismatch sign. Microcystic change was significantly associated with T2-FLAIR mismatch sign (P < 0.01). From multi-sampling in a patient, abundant microcysts were observed upon HE staining of specimens from the T2-FLAIR mismatched region, while microcysts were hardly observed from the T2-FLAIR matched one. All three protoplasmic astrocytomas among our IDH-mutant astrocytomas presented T2-FLAIR mismatch sign. In conclusion, T2-FLAIR mismatch sign may reflect microcyst formation in IDH-mutant astrocytomas and be common in IDH-mutant protoplasmic astrocytoma.

The clinical significance of the T2-FLAIR mismatch sign in grade II and III gliomas: a population-based study

BackgroundThe T2-FLAIR mismatch sign is an imaging finding highly suggestive of isocitrate dehydrogenase mutated (IDH-mut) 1p19q non-codeleted (non-codel) gliomas (astrocytomas). In previous studies, it has shown excellent specificity but limited sensitivity for IDH-mut astrocytomas. Whether the mismatch sign is a marker of a clinically relevant subtype of IDH-mut astrocytomas is unknown.MethodsWe included histopathologically verified supratentorial lower-grade gliomas (LGG) WHO grade II-III retrospectively during the period 2010–2016. In the period 2017–2018, patients with suspected LGG radiologically were prospectively included, and in this cohort other diagnoses than glioma could occur. Clinical, radiological and molecular data were collected. For clinical evaluation we included all patients with IDH-mut astrocytomas. In the 2010–2016 cohort DNA methylation analysis with Infinium MethylationEPIC BeadChip (Illumina) was performed for patients with an IDH-mut astrocytoma with available tissue. We aimed to examine the association of the T2-FLAIR mismatch sign with clinical factors and outcomes. Additionally, we evaluated the diagnostic reliability of the mismatch sign and its relation to methylation profiles.ResultsOut of 215 patients with LGG, 135 had known IDH-mutation and 1p19q codeletion status. Fifty patients had an IDH-mut astrocytoma and 12 of these (24.0%) showed a mismatch sign. The sensitivity and specificity of the mismatch sign for IDH-mut detection were 26.4 and 97.6%, respectively. There were no differences between patients with an IDH-mut astrocytoma with or without mismatch sign when grouped according to T2-FLAIR mismatch sign with respect to baseline characteristics, clinical outcomes and methylation profiles. The overall interrater agreement between neuroradiologist and clinical neurosurgeons for the T2-FLAIR mismatch sign was significant when all 215 MRI examination assessed (κ = 0.77, p < 0.001, N = 215).ConclusionThe T2-FLAIR mismatch sign in patients with an IDH-mut astrocytoma is not associated with clinical presentation or outcome. It seems unlikely that the IDH-mut astrocytomas with mismatch sign represent a specific subentity. Finally, we have validated that the T2-FLAIR mismatch sign is a reliable and specific marker of IDH-mut astrocytomas.

Erratum. The T2-FLAIR-mismatch sign as an imaging biomarker for IDH and 1p/19q status in diffuse low-grade gliomas: a systematic review with a Bayesian approach to evaluation of diagnostic test performance.

"Erratum. The T2-FLAIR–mismatch sign as an imaging biomarker for IDH and 1p/19q status in diffuse low-grade gliomas: a systematic review with a Bayesian approach to evaluation of diagnostic test performance" published on May 2020 by American Association of Neurological Surgeons.

Unifying Variability in T2-FLAIR Mismatch Sign for Diagnosing IDH-mutant Astrocytomas and Characterizing Evolution After Treatment (1095)

Unifying Variability in T2-FLAIR Mismatch Sign for Diagnosing IDH-mutant Astrocytomas and Characterizing Evolution After Treatment (1095)

T2-FLAIR mismatch sign in dysembryoplasticneuroepithelial tumor

PurposeT2-FLAIR mismatch sign was reported as specific imaging marker in non-enhancing diffuse astrocytoma, IDH-mutant & 1p/19q non-codeleted. However, most of the previous studies for T2-FLAIR mismatch sign were confirmed only among lower grade glioma. The aim of this study is to assess the T2-FLAIR mismatch sign in dysembryoplastic neuroepithelial tumor (DNET) and unveil the exception rules of the sign. MethodEleven patients with histopathologically confirmed DNET were included in this study. The MR images were evaluated by 2 independent reviewers to assess (i) the presence or absence of T2-FLAIR mismatch sign and (ii) the presence or absence of gadolinium enhancement. CT was also performed to evaluate calcification and localized thinning of the skull bone. Inter-reviewer agreement with Cohen’s kappa (κ) was calculated. ResultsThe T2-FLAIR mismatch sign was present in 8 cases (72.7 %) and absent in 3 cases (27.3 %). None of them showed contrast enhancement on initial MR images. The inter-reviewer agreement for T2-FLAIR mismatch and CT characteristics was excellent (κ = 1.00). All of the DNET without T2-FLAIR mismatch presented with calcification on CT. All of the DNET adjacent to skull vault (5 cases) presented with localized bone thinning overlying the tumor. ConclusionsThe T2-FLAIR mismatch sign was observed in more than half of the DNET and the sign is not specific for diffuse astrocytoma, IDH-mutant & 1p19q non-codeleted. The localized skull bone thinning overlying the tumor might help for diagnosis of DNET in some cases.

T2-FLAIR Mismatch Sign Is Caused by Long T1 and T2 of IDH-mutant, 1p19q Non-codeleted Astrocytoma.

T2-fluid-attenuated inversion recovery images (FLAIR) mismatch sign is now known to be a specific yet insensitive image feature for IDH-mutant, 1p19q non-codeleted astrocytoma. The current study revealed that lesion presenting T2-FLAIR mismatch exhibited extremely long T1- and T2-relaxation time while T2-FLAIR matched lesions showed low to moderate values. On the other hand, IDH-wildtype tumors presented noticeably short T1- and T2-relaxation time. These different relaxation time characteristics seemed to render T2-FLAIR mismatch sign of becoming such a unique and specific image feature for IDH-mutant, 1p19q non-codeleted astrocytoma.

"Real world" use of a highly reliable imaging sign: "T2-FLAIR mismatch" for identification of IDH mutant astrocytomas.

AbstractThe T2-FLAIR (fluid attenuated inversion recovery) mismatch sign is an easily detectable imaging sign on routine clinical MRI studies that suggests diagnosis of isocitrate dehydrogenase (IDH)-mutant 1p/19q non-codeleted gliomas. Multiple independent studies show that the T2-FLAIR mismatch sign has near-perfect specificity, but low sensitivity for diagnosing IDH-mutant astrocytomas. Thus, the T2-FLAIR mismatch sign represents a non-invasive radiogenomic diagnostic finding with potential clinical impact. Recently, false positive cases have been reported, many related to variable application of the sign's imaging criteria and differences in image acquisition, as well as to differences in the included patient populations. Here we summarize the imaging criteria for the T2-FLAIR mismatch sign, review similarities and differences between the multiple validation studies, outline strategies to optimize its clinical use, and discuss potential opportunities to refine imaging criteria in order to maximize its impact in glioma diagnostics.

NI-17 T2-FLAIR MISMATCH SIGN IN DIFFUSE GLIOMA AND DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOR

BACKGROUNDT2-FLAIR mismatch sign was reported as a specific imaging marker for diffuse astrocytoma with IDH-mutant and 1p/19q non-codeletion. However, most of the previous studies for T2-FLAIR mismatch were confirmed only among low grade glioma. The purpose of this study is to assess the T2-FLAIR mismatch sign in supratentorial diffuse glioma, diffuse midline glioma and dysembryoplastic neuroepithelial tumor (DNT) to unveil the exception rules of the sign.METHODSIn total, 51 patients were included in this study; 33 supratentorial diffuse glioma (18 diffuse astrocytoma with IDH mutant (IDHmut-Noncodel), 12 oligodendroglioma with IDH-mutant and 1p19q codeletion (IDHmut-Codel), 3 diffuse astrocytoma with IDH wildtype (IDHwt)), 18 diffuse midline glioma and 11 DNT. The tumors were evaluated by 2 independent reviewers to assess presence or absence of T2-FLAIR mismatch sign.RESULTTen out of 18 cases of IDHmut-Noncodel presented T2-FLAIR mismatch sign. None of the other supratentorial diffuse glioma (IDHmut-Codel and IDHwt) presented T2-FLAIR mismatch. The T2-FLAIR mismatch sign for IDHmut-Noncodel presented 100% positive predictive values among supratentorial diffuse glioma. However, 8 out of 18 cases of diffuse midline glioma and 8 out of 11 cases of DNT also presented the T2-FLAIR mismatch.CONCLUSIONThe T2-FLAIR mismatch sign was specific marker for IDHmut-NonCodel among supratentorial diffuse glioma. Physicians need to be aware that diffuse midline glioma and DNT could present the T2-FLAIR mismatch sign.

NI-09 CLINICAL SIGNIFICANCE OF T2-FLAIR MISMATCH SIGN IN LOWER GRADE GLIOMAS

Lower grade glioma is classified based on genetic information of mutation of IDH1/2 gene and co-deletion of chromosome 1p19q. Knowledge of these genetic information preoperatively is useful for making surgical planning, treatment strategy and prognostication. Recently, T2-FLAIR mismatch sign has been reported to be specific for astrocytoma with IDH mutation (mut) / non-1p19q co-deletion (co-del). This study aims to verify it in our patients. We retrospectively analyzed 152 patients aged over 15 years who were pathologically diagnosed with WHO grade 2 or 3 gliomas from April 2003 to December 2018. We excluded 88 patients without genetic information or without T2-weighted and FLAIR images. T2-FLAIR mismatch sign was defined as in the original description, namely, with homogeneously hyperintense signal on T2-weighted image and a peripheral hyperintense signal with central hypointensity signal on FLAIR image. Among 22 patients with IDH mut / non-1p19q codel, 10 were positive for T2-FLAIR mismatch sign. On the other hand, only one patient was positive for T2-FLAIR mismatch sign respectively in 19 with IDH mut / 1p19q codel and 23 patients with IDH wild-type. Sensitivity, specificity, positive predictive value, and negative predictive value of T2-FLAIR mismatch for the patients with IDH mut / non-1p19q codel are 0.46 (95% confidence interval: 0.24–0.68), 0.95 (0.84–0.99), 0.83 (0.52–0.98). and 0.77 (0.63–0.88), respectively. In 22 patients with IDH mut / non-1p19q codel, we compared 10 patients with and 12 without T2-FLAIR mismatch sign. Median age was 35 and 39 years old. WHO grade 3 was 3 patients each. Tumor location was frontal lobe in 9 (90%) and 10 patients (83%). A statistically significant difference was not found in these factors. PFS and OS were not reached in both groups. The specificity of the T2-FLAIR mismatch sign for astrocytoma with IDH mut / non-1p19q codel was very high, which may be helpful as preoperative imaging marker.

The T2-FLAIR-mismatch sign as an imaging biomarker for IDH and 1p/19q status in diffuse low-grade gliomas: a systematic review with a Bayesian approach to evaluation of diagnostic test performance.

With the revised WHO 2016 classification of brain tumors, there has been increasing interest in imaging biomarkers to predict molecular status and improve the yield of genetic testing for diffuse low-grade gliomas (LGGs). The T2-FLAIR-mismatch sign has been suggested to be a highly specific radiographic marker of isocitrate dehydrogenase (IDH) gene mutation and 1p/19q codeletion status in diffuse LGGs. The presence of T2-FLAIR mismatch indicates a T2-hyperintense lesion that is hypointense on FLAIR with the exception of a hyperintense rim. In accordance with PRISMA guidelines, we performed a systematic review of the Ovid Medline, Embase, Scopus, and Cochrane databases for reports of studies evaluating the diagnostic performance of T2-FLAIR mismatch in predicting the IDH and 1p/19q codeletion status in diffuse LGGs. Results were combined into a 2 × 2 format, and the following diagnostic performance parameters were calculated: sensitivity, specificity, positive predictive value, negative predictive value, and positive (LR+) and negative (LR-) likelihood ratios. In addition, we utilized Bayes theorem to calculate posttest probabilities as a function of known pretest probabilities from previous genome-wide association studies and the calculated LRs. Calculations were performed for 1) IDH mutation with 1p/19q codeletion (IDHmut-Codel), 2) IDH mutation without 1p/19q codeletion (IDHmut-Noncodel), 3) IDH mutation overall, and 4) 1p/19q codeletion overall. The QUADAS-2 (revised Quality Assessment of Diagnostic Accuracy Studies) tool was utilized for critical appraisal of included studies. A total of 4 studies were included, with inclusion of 2 separate cohorts from a study reporting testing and validation (n = 746). From pooled analysis of all cohorts, the following values were obtained for each molecular profile-IDHmut-Codel: sensitivity 30%, specificity 73%, LR+ 1.1, LR- 1.0; IDHmut-Noncodel: sensitivity 33.7%, specificity 98.5%, LR+ 22.5, LR- 0.7; IDH: sensitivity 32%, specificity 100%, LR+ 32.1, LR- 0.7; 1p/19q codeletion: sensitivity 0%, specificity 54%, LR+ 0.01, LR- 1.9. Bayes theorem was used to calculate the following posttest probabilities after a positive and negative result, respectively-IDHmut-Codel: 32.2% and 29.4%; IDHmut-Noncodel: 95% and 40%; IDH: 99.2% and 73.5%; 1p/19q codeletion: 0.4% and 35.1%. The T2-FLAIR-mismatch sign is an insensitive but highly specific marker of IDH mutation but not 1p/19q codeletion in diffuse LGGs, although there may be significant exceptions. These findings support the utility of T2-FLAIR mismatch as an imaging-based biomarker for positive selection of patients with IDH-mutant gliomas.

NIMG-05. THE T2-FLAIR MISMATCH SIGN IN IDH-MUTANT ASTROCYTOMAS - IS THERE AN ASSOCIATION WITH FET PET UPTAKE?

Abstract BACKGROUND The purpose of this study was (i) to assess the reproducibility of the previously described T2-FLAIR mismatch sign as a highly specific MR imaging marker in non-enhancing IDH-mutant, 1p/19q non-codeleted lower-grade gliomas (LGG) of the WHO grades II or III, and (ii) its association with the uptake of the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) in PET to further metabolically characterize that sign, which is currently poorly understood. METHODS Consecutive MRI and dynamic FET PET scans (n=134) from newly diagnosed and neuropathologically confirmed IDH-mutant LGG (n=65) and IDH-wildtype gliomas as control group (n=69) were evaluated by two independent raters to assess presence/absence of the T2-FLAIR mismatch sign as well as FET uptake. Interrater agreement was assessed using Cohen’s kappa (κ), as well as diagnostic performance (i.e., positive/negative predictive value; PPV, NPV) of the T2-FLAIR mismatch sign to identify IDH-mutant astrocytomas. RESULTS In the LGG group, 13 patients (20%) had a T2-FLAIR mismatch sign, which could be identified with a substantial interrater agreement (κ=0.75). In contrast, that sign was absent in IDH-wildtype gliomas. All 13 cases that were positive for the T2/FLAIR mismatch sign were IDH-mutant, 1p/19q non-codeleted tumors (PPV=100%, NPV=57%). Interestingly, compared to IDH-mutant gliomas without the T2-FLAIR mismatch sign, the sign was significantly (P=0.027; 10 of 13 patients) associated with a negative FET PET scan (i.e., 5 tumors with indifferent FET uptake comparable to the background activity, or FET uptake below background activity (photopenic defect) in 5 tumors). CONCLUSIONS With a robust interrater agreement, our findings are in line with previously reported findings regarding the T2-FLAIR mismatch sign. Additionally, the T2-FLAIR mismatch sign seems to be significantly related with a lack of increased FET uptake in PET, which may help to further characterize patients with that sign. Notwithstanding, the clinical relevance of this imaging constellation warrants further investigation.

NIMG-01. T2WI-FLAIR MISMATCH SIGN IN LOWER GRADE GLIOMA AND DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOR

Abstract BACKGROUND T2-FLAIR mismatch sign was reported as a specific imaging marker for diffuse astrocytoma with IDH-mutant and 1p/19q non-codeletion. However, most of the previous studies for T2-FLAIR mismatch were confirmed only among lower grade glioma (LGG). The purpose of this study is to explore the T2-FLAIR mismatch sing in supratentorial non-enhancing tumor including LGG and dysembryoplastic neuroepithelial tumor (DNET) and to unveil the exception rules of the sign. METHODS Forty-four patients of non-enhancing LGG and DNET were included in this study. LGG（diffuse astrocytoma with IDH mutant (IDHmut-Noncodel), oligodendroglioma with IDH-mutant and 1p19q codeletion (IDHmut-Codel), diffuse astrocytoma with IDH wildtype (IDHwt)）and DNET were diagnosed based on WHO 2016 classification. The tumors were evaluated MRI by 2 independent reviewers to assess presence or absence of T2-FLAIR mismatch sign. CT was also performed to evaluate the localized thinning of the skull bone. Inter-reviewer agreement with Cohen’s kappa (κ) was calculated. RESULT: Ten out of 18 cases (55.6%) of IDHmut-Noncodel presented T2-FLAIR mismatch sign. None of the other LGG (IDHmut-Codel and IDHwt) presented T2-FLAIR mismatch. Eight out of 11 cases (72.7%) of DNET also present the T2-FLAIR mismatch. The overlying part of the skull bone thinning was observed in 5 cases of DNET, but none of LGG presented the localized skull bone thinning. The inter-rater agreement for the T2-FLAIR mismatch and the localized thinning of the skull bone were excellent (κ= 1.00). CONCLUSION The T2-FLAIR mismatch sign was specific marker for IDHmut-Noncodel among LGG. However, DNET also presented the T2-FLAIR mismatch sign. The localized skull bone thinning could be useful for differentiating between IDHmut-Noncodel and DNET

NIMG-14. THE RELATION BETWEEN T2-FLAIR MISMATCH SIGN AND ADC VALUES REFLECTING PATHOLOGICAL MICROSTRUCTURE IN LOWER-GRADE GLIOMAS

Abstract BACKGROUND Although the recent studies have identified “T2-FLAIR mismatch sign” specific to IDH-mutant and 1p/19q-intact gliomas, it is unclear what the mismatch sign represents. We aimed to investigate the mechanisms and validate the clinical utility. METHODS We identified 79 lower-grade gliomas treated at Kobe University Hospital, and classified into three groups: (i) LGGIDH(m),1p19q(-) (n = 18): IDH-mutant and 1p/19q-intact, (ii) LGGIDH(m),1p19q(+) (n=26): IDH-mutant and 1p/19q co-deleted, (iii) LGGIDH(w) (n=35): IDH wild-type. We retrospectively analyzed the relation with apparent diffusion coefficient (ADC) values, metabolites in magnetic resonance spectroscopy and pathological features, and examined the influence of the presence of the mismatch sign on progression-free survival (PFS) and overall survival in LGGIDH(m),1p19q(-). RESULTS Compared to the rim presenting hyperintense on T2WI and FLAIR, the core presenting hyperintense on T2WI and reversely hypointense on FLAIR had significantly higher ADC values (p = 0.002). The core/rim ratios of ADC values were significantly higher in the cases with the mismatch sign (p = 0.001), not depending on IDH status, 1p/19q status and WHO grade. There was no significant difference in metabolites changing between the presence and absence of the mismatch sign. The cases with the mismatch sign in LGGIDH(m),1p19q(-) had abundant microcysts as a pathological feature, and longer PFS than those without the mismatch sign (5-yr PFS: 100% vs 37.5%). Multivariate analysis found the mismatch sign to be the only significant predictor for preferable PFS in LGGIDH(m),1p19q(-) (p = 0.044). CONCLUSION Our study provided the new evidence that the T2-FLAIR mismatch sign had the significantly different ADC values between the core and the rim, suggesting that the mismatch sign reflected the difference of the tumor cellularity and the microenvironment.