S Shrot1,2, A Kerpel3, J Belenky3, M Lurye4, C Hoffmann3,2, M Yalon4,2. 1. From the Section of Neuroradiology, Division of Diagnostic Imaging (S.S., A.K., J.B., C.H.) shai.shrot@sheba.health.gov.il. 2. Sackler School of Medicine (S.S., C.H., M.Y.), Tel Aviv University, Tel Aviv, Israel. 3. From the Section of Neuroradiology, Division of Diagnostic Imaging (S.S., A.K., J.B., C.H.). 4. Department of Pediatric Hemato-Oncology (M.L., M.Y.), Sheba Medical Center, Ramat-Gan, Israel.
Abstract
BACKGROUND AND PURPOSE: BRAF and type 1 neurofibromatosis status are distinctive features in pediatric low-grade gliomas with prognostic and therapeutic implications. We hypothesized that DWI metrics obtained through volumetric ADC histogram analyses of pediatric low-grade gliomas at baseline would enable early detection of BRAF and type 1 neurofibromatosis status. MATERIALS AND METHODS: We retrospectively evaluated 40 pediatric patients with histologically proved pilocytic astrocytoma (n = 33), ganglioglioma (n = 4), pleomorphic xanthoastrocytoma (n = 2), and diffuse astrocytoma grade 2 (n = 1). Apart from 1 patient with type 1 neurofibromatosis who had a biopsy, 11 patients with type 1 neurofibromatosis underwent conventional MR imaging to diagnose a low-grade tumor without a biopsy. BRAF molecular analysis was performed for patients without type 1 neurofibromatosis. Eleven patients presented with BRAF V600E-mutant, 20 had BRAF-KIAA rearrangement, and 8 had BRAF wild-type tumors. Imaging studies were reviewed for location, margins, hemorrhage or calcifications, cystic components, and contrast enhancement. Histogram analysis of tumoral diffusivity was performed. RESULTS: Diffusion histogram metrics (mean, median, and 10th and 90th percentiles) but not kurtosis or skewness were different among pediatric low-grade glioma subgroups (P < .05). Diffusivity was lowest in BRAF V600E-mutant tumors (the 10th percentile reached an area under the curve of 0.9 on receiver operating characteristic analysis). There were significant differences between evaluated pediatric low-grade glioma margins and cystic components (P = .03 and P = .001, respectively). Well-defined margins were characteristic of BRAF-KIAA or wild-type BRAF rather than BRAF V600E-mutant or type 1 neurofibromatosis tumors. None of the type 1 neurofibromatosis tumors showed a cystic component. CONCLUSIONS: Imaging features of pediatric low-grade gliomas, including quantitative diffusion metrics, may assist in predicting BRAF and type 1 neurofibromatosis status, suggesting a radiologic-genetic correlation, and might enable early genetic signature characterization.
BACKGROUND AND PURPOSE: BRAF and type 1 neurofibromatosis status are distinctive features in pediatric low-grade gliomas with prognostic and therapeutic implications. We hypothesized that DWI metrics obtained through volumetric ADC histogram analyses of pediatric low-grade gliomas at baseline would enable early detection of BRAF and type 1 neurofibromatosis status. MATERIALS AND METHODS: We retrospectively evaluated 40 pediatric patients with histologically proved pilocytic astrocytoma (n = 33), ganglioglioma (n = 4), pleomorphic xanthoastrocytoma (n = 2), and diffuse astrocytoma grade 2 (n = 1). Apart from 1 patient with type 1 neurofibromatosis who had a biopsy, 11 patients with type 1 neurofibromatosis underwent conventional MR imaging to diagnose a low-grade tumor without a biopsy. BRAF molecular analysis was performed for patients without type 1 neurofibromatosis. Eleven patients presented with BRAF V600E-mutant, 20 had BRAF-KIAA rearrangement, and 8 had BRAF wild-type tumors. Imaging studies were reviewed for location, margins, hemorrhage or calcifications, cystic components, and contrast enhancement. Histogram analysis of tumoral diffusivity was performed. RESULTS: Diffusion histogram metrics (mean, median, and 10th and 90th percentiles) but not kurtosis or skewness were different among pediatric low-grade glioma subgroups (P < .05). Diffusivity was lowest in BRAF V600E-mutant tumors (the 10th percentile reached an area under the curve of 0.9 on receiver operating characteristic analysis). There were significant differences between evaluated pediatric low-grade glioma margins and cystic components (P = .03 and P = .001, respectively). Well-defined margins were characteristic of BRAF-KIAA or wild-type BRAF rather than BRAF V600E-mutant or type 1 neurofibromatosis tumors. None of the type 1 neurofibromatosis tumors showed a cystic component. CONCLUSIONS: Imaging features of pediatric low-grade gliomas, including quantitative diffusion metrics, may assist in predicting BRAF and type 1 neurofibromatosis status, suggesting a radiologic-genetic correlation, and might enable early genetic signature characterization.
Authors: Matthew Mistry; Nataliya Zhukova; Daniele Merico; Patricia Rakopoulos; Rahul Krishnatry; Mary Shago; James Stavropoulos; Noa Alon; Jason D Pole; Peter N Ray; Vilma Navickiene; Joshua Mangerel; Marc Remke; Pawel Buczkowicz; Vijay Ramaswamy; Ana Guerreiro Stucklin; Martin Li; Edwin J Young; Cindy Zhang; Pedro Castelo-Branco; Doua Bakry; Suzanne Laughlin; Adam Shlien; Jennifer Chan; Keith L Ligon; James T Rutka; Peter B Dirks; Michael D Taylor; Mark Greenberg; David Malkin; Annie Huang; Eric Bouffet; Cynthia E Hawkins; Uri Tabori Journal: J Clin Oncol Date: 2015-02-09 Impact factor: 44.544
Authors: Carrie R McDonald; Rachel L Delfanti; Anitha P Krishnan; Kelly M Leyden; Jona A Hattangadi-Gluth; Tyler M Seibert; Roshan Karunamuni; Pia Elbe; Joshua M Kuperman; Hauke Bartsch; David E Piccioni; Nathan S White; Anders M Dale; Nikdokht Farid Journal: Neuro Oncol Date: 2016-04-21 Impact factor: 12.300
Authors: C-C Wu; R Jain; A Radmanesh; L M Poisson; W-Y Guo; D Zagzag; M Snuderl; D G Placantonakis; J Golfinos; A S Chi Journal: AJNR Am J Neuroradiol Date: 2018-09-06 Impact factor: 3.825
Authors: Huy Gia Vuong; Ahmed M A Altibi; Uyen N P Duong; Hanh T T Ngo; Thong Quang Pham; Kar-Ming Fung; Lewis Hassell Journal: Mol Neurobiol Date: 2017-05-22 Impact factor: 5.590
Authors: J H Harreld; S N Hwang; I Qaddoumi; R G Tatevossian; X Li; J Dalton; K Haupfear; Y Li; D W Ellison Journal: AJNR Am J Neuroradiol Date: 2016-07-28 Impact factor: 3.825
Authors: Chintan Parmar; Emmanuel Rios Velazquez; Ralph Leijenaar; Mohammed Jermoumi; Sara Carvalho; Raymond H Mak; Sushmita Mitra; B Uma Shankar; Ron Kikinis; Benjamin Haibe-Kains; Philippe Lambin; Hugo J W L Aerts Journal: PLoS One Date: 2014-07-15 Impact factor: 3.240