T2/FLAIR-mismatch sign for noninvasive detection of IDH-mutant 1p/19q non-codeleted gliomas: validity and pathophysiology

Abstract

Background This study aimed to assess the validity and pathophysiology of the T2/FLAIR-mismatch sign for noninvasive identification of isocitrate dehydrogenase (IDH)-mutant 1p/19q non-codeleted glioma. Methods Magnetic resonance imaging scans from 408 consecutive patients with newly diagnosed glioma (113 lower-grade gliomas and 295 glioblastomas) were evaluated for the presence of T2/FLAIR-mismatch sign by 2 independent reviewers. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the performance of the T2/FLAIR-mismatch sign for identifying IDH-mutant 1p/19q non-codeleted tumors. An exploratory analysis of differences in contrast-enhancing tumor volumes, apparent diffusion coefficient (ADC) values, and relative cerebral blood volume (rCBV) values in IDH-mutant gliomas with versus without the presence of a T2/FLAIR-mismatch sign (as well as analysis of spatial differences within tumors with the presence of a T2/FLAIR-mismatch sign) was performed. Results The T2/FLAIR-mismatch sign was present in 12 cases with lower-grade glioma (10.6%), all of them being IDH-mutant 1p/19q non-codeleted tumors (sensitivity = 10.9%, specificity = 100%, PPV = 100%, NPV = 3.0%, accuracy = 13.3%). There was a substantial interrater agreement to identify the T2/FLAIR-mismatch sign (Cohen’s kappa = 0.75 [95% CI, 0.57–0.93]). The T2/FLAIR-mismatch sign was not identified in any other molecular subgroup, including IDH-mutant glioblastoma cases (n = 5). IDH-mutant gliomas with a T2/FLAIR-mismatch sign showed significantly higher ADC (P < .0001) and lower rCBV values (P = .0123) as compared to IDH-mutant gliomas without a T2/FLAIR-mismatch sign. Moreover, in IDH-mutant gliomas with T2/FLAIR-mismatch sign the ADC values were significantly lower in the FLAIR-hyperintense rim as compared to the FLAIR-hypointense core of the tumor (P = .0005). Conclusions This study confirms the high specificity of the T2/FLAIR-mismatch sign for noninvasive identification of IDH-mutant 1p/19q non-codeleted gliomas; however, sensitivity is low and applicability is limited to lower-grade gliomas. Whether the higher ADC and lower rCBV values in IDH-mutant gliomas with a T2/FLAIR-mismatch sign (as compared to those without) translate into a measurable prognostic effect requires investigation in future studies. Moreover, spatial differences in ADC values between the core and rim of tumors with a T2/FLAIR-mismatch sign potentially reflect specific distinctions in tumor cellularity and microenvironment.

Multi-institutional noninvasive in vivo characterization of IDH, 1p/19q, and EGFRvIII in glioma using neuro-Cancer Imaging Phenomics Toolkit (neuro-CaPTk)

“…The authors suggested that translation of this biomarker into a clinically applicable quantifiable prognostic measure would require extensive validation on larger datasets. 39 In contrast, our study introduces simple and automated image-based assessment of molecular markers which appears to be highly accurate ( IDH: specificity = 87.68%, sensitivity = 82.80%; 1p/19q-codeletion: specificity = 73.96%, sensitivity = 81.49%) of underlying molecular status.…”

“…Multiple recent studies have attempted to correlate T2–FLAIR mismatch with IDH and 1p/19q codeletion status in lower-grade gliomas. 38 , 39 For example, MRIs of 125 lower-grade gliomas from the TCIA dataset were evaluated by 2 independent neuroradiologists to assess for the presence/absence of T2–FLAIR mismatch sign. 38 All 15 cases declared positive by the readers for the T2–FLAIR mismatch sign were IDH -mutant 1p/19q-noncodeleted tumors.…”

“… 38 All 15 cases declared positive by the readers for the T2–FLAIR mismatch sign were IDH -mutant 1p/19q-noncodeleted tumors. Extending upon this initial work, Foltyn et al 39 evaluated MRI scans of 408 glioma patients (113 low-grade and 295 glioblastomas) for the presence of T2–FLAIR mismatch sign by 2 independent reviewers. The T2–FLAIR mismatch sign was present in 12 low-grade gliomas, all of them being IDH -mutant 1p/19q-noncodeleted tumors, and was not found in any of the glioblastoma patients.…”

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

“…Therefore, the T2–FLAIR mismatch sign could also have an important role in predicting the IDH status of gliomas, which may alter the extent of surgical removal of a glioma [ 16 , 19 ]. The purpose of our current study was to evaluate the presence of the T2–FLAIR mismatch sign in patients with LGG tumors, but also to evaluate the presence of this sign in high-grade tumors as well in a Greek cohort.…”

Editorial for “Predicting Isocitrate Dehydrogenase (IDH) Mutation Status in Gliomas Using Multiparameter MRI Radiomics Features”

“…There are specific imaging features that correlate with altered metabolic processes of the tumor and thus contain the desired information. Examples are relative cerebral blood volume (rCBV) imaging 6 and mismatch of signal intensity distribution of T 2 w and FLAIR images (T 2 ‐FLAIR mismatch) 7 . Also, subtle imaging features of common diagnostic protocols may indicate the IDH mutation status.…”