T2-FLAIR Mismatch Research Articles

NI-8 Molecular diagnostic prediction combining T2-FLAIR mismatch sign, calcification, and methionine PET in grade II and III gliomas

Background: The 2016 WHO Classification classified grade II and III gliomas into three molecular subtypes depending on the presence of IDH mutation and 1p/19q codeletion. We combined T2-FLAIR mismatch sign, tumor calcification, and methionine PET uptake to examine whether molecular diagnosis could be predicted. Methods: 53 grade II and III glioma patients with preoperative MRI, CT, and MET-PET who underwent surgical resection or biopsy during 2000–2019 were included in this study. Out of the 53 cases, astrocytic tumors (A group: IDH-mutant, 1p19q non-codeleted) were 17, oligodendroglial tumors (O group: IDH-mutant, 1p19q codeleted) were 15, and IDH wild tumors (W group) were 21. MR and CT scans were evaluated by 3 independent reviewers to assess presence/absence of T2-FLAIR mismatch sign and calcification in the tumor, respectively. The tumor-to-normal (T/N) ratio of methionine uptake was calculated by dividing the maximum standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain. Results: Out of the 53 cases, T2-FLAIR mismatch sign was present in 6 cases in group A and 9 cases in group W (p=0.008). Calcification in tumor was present in 2 cases in group A, 7 cases in group O, and 3 cases in group W (p=0.046). In the T2-FLAIR mismatch-positive cases, assuming MET-PET T/N>1.401 was group W and <1.401 was group A, sensitivity was 100% and specificity was 67%. In the T2-FLAIR mismatch-negative and calcification-positive cases, assuming those group O, the diagnostic predictive value was 70%. In the T2-FLAIR mismatch-negative and calcification-negative cases, assuming MET-PET T/N>2.349 was group W and <2.349 was group A or O, sensitivity was 60% and specificity was 94%. Conclusions: Combined diagnostic prediction of T2-FLAIR mismatch, calcification, and MET-PET T/N may be useful for preoperative molecular diagnosis of grade II and III gliomas.

NIMG-76. DISCRETE LOWER-GRADE GLIOMA (DLGG) VERSUS INFILTRATIVE LOWER-GRADE GLIOMA (ILGG): CORRELATION OF RADIOLOGICAL CHARACTERISTICS WITH CLINICAL OUTCOMES

Abstract INTRODUCTION Lower grade gliomas encompass grade 2 and 3 tumors. However, this term is more generalized and does not include the spectrum of radiological and tumor morphological patterns seen. Here we have established two distinct patterns of radiographic appearance seen within lower grade gliomas: ILGG and DLGG. Imaging plays a vital role in diagnosis, surveillance, characterization, and monitoring of intracranial tumors. Of particular importance is the differentiation of tumor features to reliably predict malignancy, tumor grade, possible molecular or genetic features, disease progression and recurrence, potential for malignant transformation, and postoperative outcomes. Our study will look at these radiographic characteristics of diffuse and infiltrating lower grade gliomas and discuss their predictive value. Understanding the distinct nature of these varieties of LGG will help us in surgical decision-making, prognostication, biopsy target and precision medicine. METHODS Pre-operative and post-operative MRI images of Grade 2 and 3 tumors were identified and analyzed in order to extract radiographic data, and correlated with patient demographics, clinical outcomes, extent of surgical resection, and molecular genetic analysis. RESULTS Out of 35 patients evaluated, 22 (62.9%) were labeled ILGGs and 13 (37.1%) were deemed DLGGs according to the pre-defined criteria. T2 habitat was higher in ILGG (mean = 2162) than DLGG (mean = 1482) as well as size, in cm (6.02 vs. 4.92). ADC habitat, lesion ADC, and percentage of the lesion that showed contrast-enhancement were similar. T2-FLAIR mismatch was significantly higher in ILGG (p = 0.02). Post-operative KPS scores were significantly higher in the DLGG group (p = 0.03). CONCLUSION T2-FLAIR mismatch can be a significant classifier for lower-grade gliomas. Our study shows there are differences in tumor morphology of diffuse and infiltrative lower-grade gliomas which can be correlated to outcomes after surgery. *Indicates corresponding author.

Quantifying T2-FLAIR Mismatch Using Geographically Weighted Regression and Predicting Molecular Status in Lower-Grade Gliomas.

The T2-FLAIR mismatch sign is a validated imaging sign of isocitrate dehydrogenase-mutant 1p/19q noncodeleted gliomas. It is identified by radiologists through visual inspection of preoperative MR imaging scans and has been shown to identify isocitrate dehydrogenase-mutant 1p/19q noncodeleted gliomas with a high positive predictive value. We have developed an approach to quantify the T2-FLAIR mismatch signature and use it to predict the molecular status of lower-grade gliomas. We used multiparametric MR imaging scans and segmentation labels of 108 preoperative lower-grade glioma tumors from The Cancer Imaging Archive. Clinical information and T2-FLAIR mismatch sign labels were obtained from supplementary material of relevant publications. We adopted an objective analytic approach to estimate this sign through a geographically weighted regression and used the residuals for each case to construct a probability density function (serving as a residual signature). These functions were then analyzed using an appropriate statistical framework. We observed statistically significant (P value = .05) differences between the averages of residual signatures for an isocitrate dehydrogenase-mutant 1p/19q noncodeleted class of tumors versus other categories. Our classifier predicts these cases with area under the curve of 0.98 and high specificity and sensitivity. It also predicts the T2-FLAIR mismatch sign within these cases with an under the curve of 0.93. On the basis of this retrospective study, we show that geographically weighted regression-based residual signatures are highly informative of the T2-FLAIR mismatch sign and can identify isocitrate dehydrogenase-mutation and 1p/19q codeletion status with high predictive power. The utility of the proposed quantification of the T2-FLAIR mismatch sign can be potentially validated through a prospective multi-institutional study.

T2-FLAIR mismatch sign for diagnosis of 1p19q non-codeleted or ATRX mutant astrocytoma

Abstract Aims The World Health Organisation (WHO) classification of adult gliomas has undergone significant revision in recent years, with current emphasis on the role of the molecular biomarkers IDH, 1p19q, ATRX, and p53 for classification of glioblastoma, astrocytoma, and oligodendroglioma. When correctly applied the T2-FLAIR mismatch sign is reported to have 100% specificity for WHO grade II or III IDH mutant 1p19q non-codeleted astrocytoma. We sought to verify this classic imaging-molecular correlate in our cohort at a single tertiary level neurosurgical referral centre in the United Kingdom. Method Data were gathered by searching the histopathology database for cases between 2014 and 2019 containing the keywords ‘IDH Mutant’ AND ‘Astrocytoma’ or ‘Glioblastoma’ or ‘Oligodendroglioma’ in the report. Inclusion criteria: Biopsy/resection proven IDH mutant tumours in adults (age &amp;gt;17). A strict application of the T2-FLAIR mismatch sign was used when evaluating MRI. Native T2 signal was required to be homogenous or near homogenous, with hypointense signal on T2 weighted FLAIR except for a hyperintense peripheral rim. In addition, the T2-FLAIR mismatch sign was not applied to tumours showing any unequivocal contrast enhancement or macrocystic change. Results 66/185 cases were excluded for reasons of insufficient imaging, duplication, 1p19q partial deletion/unknown + ATRX wild type/unknown, IDH wild type/negative, Grade IV histology. 119 cases fit the inclusion criteria, all IDH positive. Group 1 comprised 49 (39%) 1p19q codeleted tumours, or oligodendrogliomas. ATRX was wild type (78%), unknown (18%), or mutated (&amp;lt;1%). Group 2 comprised 37 (29%) 1p19q non-codeleted tumours, or astrocytomas. ATRX was mutated (70%), unknown (22%), wild type (5%), or equivocal (3%). Group 3 comprised 41 (32%) 1p19q unknown tumours, all ATRX mutated, p53 expressed (83%). When p53 status was unaltered/equivocal, microscopy was convincingly astrocytic. Groups 2 and 3 comprised the astrocytomas (61%). T2-FLAIR mismatch was positive in 5 1p19q non-codeleted astrocytomas, 5 1p19q unknown ATRX mutant astrocytomas, and no 1p19q co-deleted oligodendrogliomas. Test sensitivity and specificity was 14% and 100% for 1p19q non-codeletion, 13% and 100% for ATRX mutation. Conclusion Although relatively uncommon, when present and correctly applied we confirm 100% specificity of the T2-FLAIR mismatch sign for IDH mutant 1p19q non-codeleted astrocytoma. However, if 1p19q status is unknown, clear astrocytic histology and ATRX mutation and/or p53 overexpression is also considered sufficient to diagnose astrocytoma. When 1p19q status is unavailable we also report 100% specificity of T2-FLAIR mismatch for ATRX mutated astrocytomas. T2-FLAIR mismatch was not observed in any 1p19q codeleted oligodendrogliomas or ATRX wild type tumours. More accurate methods of non-invasive glioma diagnosis will help improve neurohistopathological correlation, prognostication, and guide the tempo of the pre-operative planning phase.

T2-FLAIR mismatch sign: a roadmap of pearls and pitfalls.

T2-FLAIR mismatch sign has been advocated to be 100% specific for IDH-mutant 1p/19q non-codeleted gliomas (diffuse astrocytomas). However, false positives have been reported in recent works. Loose application of the criteria may lead to erroneous classification, especially by non-trained neuroradiologists. In this pictorial essay, we aim to bring attention to the need for strict criteria for the application of T2-FLAIR mismatch sign and to discuss the potential pitfalls in the application of these criteria. For that, a series of adult brain tumour cases are presented to demonstrate how to apply this radiological sign in the clinical practice.

The T2-FLAIR Mismatch Sign as an Imaging Indicator of IDH-Mutant, 1p/19q Non-Codeleted Lower Grade Gliomas: A Systematic Review and Diagnostic Accuracy Meta-Analysis.

The study’s objective was the evaluation of the diagnostic accuracy of the T2-FLAIR mismatch sign in terms of diagnosing IDH-mutant non-codeleted (IDHmut-Noncodel) lower grade gliomas (LGG) of the brain. We searched the MEDLINE, Scopus and Cochrane Central databases. The last database search was performed on 12 April 2021. Studies that met the following were included: MRI scan assessing the presence of T2-FLAIR mismatch sign, and available IDH mutation and 1p/19q codeletion status. The quality of studies was assessed using the QUADAS-2 tool. Twelve studies involving 14 cohorts were included in the quantitative analysis. The diagnostic odds ratio [DOR (95% confidence interval; CI)] was estimated at 34.42 (20.95, 56.56), Pz < 0.01. Pooled sensitivity and specificity (95% CI) were estimated at 40% (31–50%; Pz = 0.05) and 97% (93–99%; Pz < 0.01), respectively. The likelihood ratio (LR; 95% CI) for a positive test was 11.39 (6.10, 21.29; Pz < 0.01) and the LR (95% CI) for a negative test was 0.40 (0.24, 0.65; Pz < 0.01).The T2-FLAIR mismatch sign is a highly specific biomarker for the diagnosis of IDHmut-Noncodel LGGs. However, the test was found positive in some other tumors and had a high number of false negative results. The diagnostic accuracy of the mismatch sign might be improved when combined with further imaging parameters.

Magnetic resonance imaging criteria for prediction of isocitrate dehydrogenase (IDH) mutation status in patients with grade II-III astrocytoma and oligodendroglioma

BackgroundIDH mutation status is an important prognostic marker for glial tumors, which is detected immunohistochemically after surgery. Since this method is invasive, easy and noninvasive magnetic resonance imaging (MRI) methods have recently been used in predicting the IDH mutation status. However, there is currently no standard MRI technique to predict IDH mutation. We analyzed the value of conventional MRI to predict IDH mutation and its effect on survival among grade II-III astrocytoma and oligodendroglioma patients. Material and methodsWe included WHO grade II-III astrocytoma and oligodendroglioma patients who underwent surgery at Bahcesehir University Goztepe Medical Park Hospital. All patients were analyzed according to their immunohistochemical IDH mutation status. Preoperative conventional MRI studies with respect to their location, diffusion restriction, contrast enhancement, calcification and hemorrhage on susceptibility-weighted image (SWI) or T2*- weighted imaging (T2*WI), and T2 -FLAIR mismatch properties were retrospectively assessed by a neuroradiologist. The relation between MRI characteristics and IDH mutation was analyzed using a chi-square test. The sensitivity and specificity of radiological IDH mutation were determined by ROC analysis. The impact of IDH mutation on survival was also analyzed by Kaplan-Meier tests. ResultsIDH mutation was found to be positive in 82.5% of tumors histopathologically and 54.4% radiologically. The sensitivity and specificity were 63.8% and 90%, respectively (Area under the curve/AUC = 0.369, p = 0.08). IDH wild gliomas were predominantly diffusion-restricted tumors. IDH mutant tumors were less likely to have contrast enhancement and had lower grades compared to the IDH wild tumors. The median survival time could not be reached and the overall survival was not related to any tumor characteristics or IDH mutation. ConclusionsConventional MRI predicts IDH-mutation status in Grade II-III astrocytoma and oligodendroglioma. Contrast-enhancement and restricted diffusion were strongly associated with grade III astrocytoma and oligodendroglioma, IDH-wild type. Location, T2-FLAIR mismatch, and SWI did not contribute to making a decision on the IDH mutation status. There was no significant difference between the survival times of patients and their IDH status.

The Histopathologic and Radiologic Features of T2-FLAIR Mismatch Sign in IDH-Mutant 1p/19q Non-codeleted Astrocytomas

The T2-FLAIR mismatch sign is a useful imaging sign in clinical magnetic resonance imaging studies for detecting isocitrate dehydrogenase (IDH)-mutant 1p/19q non-codeleted astrocytomas. However, the association between the mismatch sign and pathologic findings is poorly understood. Therefore, the aim of this study was to elucidate the relationship of histopathologic and radiologic features with the mismatch sign in IDH-mutant 1p/19q non-codeleted astrocytomas. We divided 17 IDH-mutant 1p/19q non-codeleted patients into 2 groups according to mismatch sign presence (WITH, n= 9; WITHOUT, n= 8) and retrospectively analyzed their pathologic findings and apparent diffusion coefficient (ADC) values. We also compared these findings between the tumor Core (central area) and Rim (marginal area). In the pathologic analysis, Core of the WITH group contained numerous microcysts whereas Rim had abundant neuroglial fibrils and cellularity. In contrast, Core of the WITHOUT group had highly concentrated neuroglial fibrils. In ADC analysis, Core of the WITH group had significantly higher ADC values compared with Rim (P < 0.001). However, there was no significant difference between Core and Rim in the WITHOUT group (P= 0.12). The WITH group had a significantly higher Core/Rim ratio of ADC values compared with the WITHOUT group (P < 0.001). This study provides evidence that a region-dependent microstructural difference could reflect the mismatch sign in IDH-mutant 1p/19q non-codeleted astrocytomas. Core of the mismatch sign characteristically had microcystic changes accompanied by higher ADC values, whereas Rim had abundant neuroglial fibrils and cellularity accompanied by lower ADC values.

T2-FLAIR Mismatch Sign and Response to Radiotherapy in Diffuse Intrinsic Pontine Glioma

Purpose: The T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign was previously reported as a diagnostic indicator of diffuse astrocytoma, isocitrate dehydrogenase-mutant, and 1p/19q noncodeletion. Subsequently, it was reported that the same findings were observed in diffuse intrinsic pontine glioma (DIPG). We investigated the clinical significance of T2-FLAIR mismatch sign in DIPG. Methods: Twenty-one patients with DIPG (Male: Female = 12:9) were treated at our institute between 2004 and 2019. All patients were treated with local radiotherapy of 54 Gy/30 fractions. The positive T2-FLAIR mismatch sign was defined if it fulfilled the following criteria: (1) T2-FLAIR mismatch volume was >50% of T2 high volume at nonenhanced area, (2) the FLAIR low lesion is not associated with gadolinium enhancement (inside of enhancement or just outside of enhancement defined as edema), and (3) signal-intensity of FLAIR lowest lesion at tumor is lower than the normal cerebellar cortex. Results: In our patient series, T2-FLAIR mismatch sign was found in 5 out of 21 patients. Objective response rate of radiotherapy was 100% in patients positive for T2-FLAIR mismatch, while it was 25.0% in patients negative for T2-FLAIR mismatch, and this difference was statistically significant (p < 0.01, Fisher’s exact test). In patients under the age of 18-years, T2-FLAIR mismatch positive had a slightly better prognosis (p < 0.05, Wilcoxon test). Conclusion: T2-FLAIR mismatch sign in DIPG may be an indicator for better response to radiotherapy and a better prognostic factor.

IDH-Mutant Low-grade Glioma: Advances in Molecular Diagnosis, Management, and Future Directions.

IDH-mutant low-grade gliomas (LGG) have emerged as a distinct clinical and molecular entity with unique treatment considerations. Here, we review updates in IDH-mutant LGG diagnosis and classification, imaging biomarkers, therapies, and neurocognitive and patient-reported outcomes. CDKN2A/B homozygous deletion in IDH-mutant astrocytoma is associated with shorter survival, similar to WHO grade 4. The T2-FLAIR mismatch, a highly specific but insensitive sign, is diagnostic of IDH-mutant astrocytoma. Maximal safe resection is currently indicated in all LGG cases. Radiotherapy with subsequent PCV (procarbazine, lomustine, vincristine) provides longer overall survival compared to radiotherapy alone. Temozolomide in place of PCV is reasonable, but high-level evidence is still lacking. LGG adjuvant treatment has important quality of life and neurocognitive side effects that should be considered. Although incurable, IDH-mutant LGG have a favorable survival compared to IDH-WT glioma. Recent advances in molecular-based classification, imaging, and targeted therapies will hopefully improve survival and quality of life.

Comparative evaluation of intracranial oligodendroglioma and astrocytoma of similar grades using conventional and T1-weighted DCE-MRI.

This retrospective study was performed on a 3T MRI to determine the unique conventional MR imaging and T1-weighted DCE-MRI features of oligodendroglioma and astrocytoma and investigate the utility of machine learning algorithms in their differentiation. Histologically confirmed, 81 treatment-naïve patients were classified into two groups as per WHO 2016 classification: oligodendroglioma (n = 16; grade II, n = 25; grade III) and astrocytoma (n = 10; grade II, n = 30; grade III). The differences in tumor morphology characteristics were evaluated using Z-test. T1-weighted DCE-MRI data were analyzed using an in-house built MATLAB program. The mean 90th percentile of relative cerebral blood flow, relative cerebral blood volume corrected, volume transfer rate from plasma to extracellular extravascular space, and extravascular extracellular space volume values were evaluated using independent Student's t test. Support vector machine (SVM) classifier was constructed to differentiate two groups across grade II, grade III, and grade II+III based on statistically significant features. Z-test signified only calcification among conventional MR features to categorize oligodendroglioma and astrocytoma across grade III and grade II+III tumors. No statistical significance was found in the perfusion parameters between two groups and its subtypes. SVM trained on calcification also provided moderate accuracy to differentiate oligodendroglioma from astrocytoma. We conclude that conventional MR features except calcification and the quantitative T1-weighted DCE-MRI parameters fail to discriminate between oligodendroglioma and astrocytoma. The SVM could not further aid in their differentiation. The study also suggests that the presence of more than 50% T2-FLAIR mismatch may be considered as a more conclusive sign for differentiation of IDH mutant astrocytoma.

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.