Automated apparent diffusion coefficient analysis for genotype prediction in lower grade glioma: association with the T2
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CLINICAL STUDY
Automated apparent diffusion coefficient analysis for genotype prediction in lower grade glioma: association with the T2‑FLAIR mismatch sign Eric Aliotta1 · Sunil W. Dutta1 · Xue Feng3 · Nicholas J. Tustison2 · Prem P. Batchala2 · David Schiff4 · M. Beatriz Lopes5 · Rajan Jain6 · T. Jason Druzgal2 · Sugoto Mukherjee2 · Sohil H. Patel2 Received: 22 June 2020 / Accepted: 31 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose 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. Methods 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. Results 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 V ADC>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. Conclusion 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. Keywords Lower grade glioma · Diffusion weighted imaging · Genetic classification · IDH mutation
* Sohil H. Patel [email protected] 1
Department of Radiation Oncology, University of Virginia, Charlottesville, VA 22908, USA
2
Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22908, USA
3
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA
4
Departments of Neurology, Neurological Surgery, and Medicine, University of Virginia, Charlottesville, VA 22908, USA
5
Departments of Pathology (Neuropathology) and Neurological
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