Dataset Information

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

ABSTRACT:

Background and purpose

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.

Materials and methods

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.

Results

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.

Conclusions

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.

SUBMITTER: Mohammed S

PROVIDER: S-EPMC8757555 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Mohammed S S Ravikumar V V Warner E E Patel S H SH Bakas S S Rao A A Jain R R

AJNR. American journal of neuroradiology 20211111 1

<h4>Background and purpose</h4>The T2-FLAIR mismatch sign is a validated imaging sign of <i>isocitrate dehydrogenase</i>-mutant 1p/19q noncodeleted gliomas. It is identified by radiologists through visual inspection of preoperative MR imaging scans and has been shown to identify <i>isocitrate dehydrogenase</i>-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 stat ...[more]

PMID: 34764084

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Project description:Background and purposeThe 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.Materials and methodsTwo 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.ResultsThresholds 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.ConclusionsT2-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.

Project description: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.

Project description:Survival outcomes for patients with lower grade gliomas (LrGG) continue to improve. However, damage caused both by tumor growth and by the consequences of treatment often leads to significantly impaired cognitive function and quality of life (QoL). While neuropsychological testing is not routine, serial clinical MRIs are standard of care for patients with LrGG. Thus, having a greater understanding of MRI indicators of cognitive and QoL impairment risk could be beneficial to patients and clinicians. In this work we sought to test the hypothesis that in clinically stable LrGG patients, T2 FLAIR hyperintensity volumes at the time of cognitive assessment are associated with impairments of cognitive function and QoL and could be used to help identify patients for cognitive and QoL assessments and interventions. We performed anatomical MR imaging, cognitive testing and QoL assessments cross-sectionally in 30 clinically stable grade 2 and 3 glioma patients with subjective cognitive concerns who were 6 or more months post-treatment. Larger post-surgical T2 FLAIR volume at testing was significantly associated with lower cognitive performance, while pre-surgical tumor volume was not. Older patients had lower cognitive performance than younger patients, even after accounting for normal age-related declines in performance. Patients with Astrocytoma, IDH mutant LrGGs were more likely to show lower cognitive performance than patients with Oligodendroglioma, IDH mutant 1p19q co-deleted LrGGs. Previous treatment with combined radiation and chemotherapy was associated with poorer self-reported QoL, including self-reported cognitive function. This study demonstrates the importance of appreciating that LrGG patients may experience impairments in cognitive function and QoL over their disease course, including during periods of otherwise sustained clinical stability. Imaging factors can be helpful in identifying vulnerable patients who would benefit from cognitive assessment and rehabilitation.

Project description:PurposeThis study compared the classification performance of normalized apparent diffusion coefficient (nADC) with percentage T2-FLAIR mismatch-volume (%T2FM-volume) for differentiating between IDH-mutant astrocytoma (IDHm-A) and other glioma molecular subtypes.MethodsA total of 105 non-enhancing gliomas were studied. T2-FLAIR digital subtraction maps were used to identify T2FM and T2-FLAIR non-mismatch (T2FNM) subregions within tumor volumes of interest (VOIs). Median nADC from the whole tumor, T2FM, and T2NFM subregions and %T2FM-volume were obtained. IDHm-A classification analyses using receiver-operating characteristic curves and multiple logistic regression were performed in addition to exploratory survival analyses.ResultsT2FM subregions had significantly higher nADC than T2FNM subregions within IDHm-A with ≥ 25% T2FM-volume (P < 0.0001). IDHm-A with ≥ 25% T2FM-volume demonstrated significantly higher whole tumor nADC compared to IDHm-A with < 25% T2FM-volume (P < 0.0001), and both IDHm-A subgroups demonstrated significantly higher nADC compared to IDH-mutant oligodendroglioma and IDH-wild-type gliomas (P < 0.05). For classification of IDHm-A vs. other gliomas, the area under curve (AUC) of nADC was significantly greater compared to the AUC of %T2FM-volume (P = 0.01, nADC AUC = 0.848, %T2FM-volume AUC = 0.714) along with greater sensitivity. In exploratory survival analyses within IDHm-A, %T2FM-volume was not associated with overall survival (P = 0.2), but there were non-significant trends for nADC (P = 0.07) and tumor volume (P = 0.051).ConclusionT2-FLAIR subtraction maps are useful for characterizing IDHm-A imaging characteristics. nADC outperforms %T2FM-volume for classifying IDHm-A amongst non-enhancing gliomas with preserved high specificity and increased sensitivity, which may be related to inherent diffusivity differences regardless of T2FM. In line with previous findings on visual T2FM-sign, quantitative %T2FM-volume may not be prognostic.

Project description:BackgroundThis 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.MethodsMagnetic 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.ResultsThe 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).ConclusionsThis 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.

Dataset Information

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

Background and purpose

Materials and methods

Results

Conclusions

Publications

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

Similar Datasets

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