Radiologic findings and the molecular expression profile of diffuse midline glioma H3 K27M mutant

Abstract

Background Diffuse midline glioma H3 K27M-mutant (DMG) are reported to show heterogeneous radiologic imaging features in children. We hypothesized that other genetic mutations may contribute to this heterogeneity. Purpose To describe the magnetic resonance imaging (MRI) findings of DMG in adult patients and to correlate the imaging findings with the molecular expression profile. Material and Methods Eighteen patients with pathologically proven DMG were enrolled. On preoperative MRI, the following were evaluated: location; size of the lesion; ratio of non-enhancing (NE) and contrast-enhancing (CE) area; presence of cortical invasion and necrotic component; maximum relative cerebral blood volume ratio (rCBV ratio) of NE and CE portions; and minimum apparent diffusion coefficient (ADC) of NE and CE portions, among others. Molecular profiles including ATRX expression and p53 mutation were reviewed to find correlation with imaging features. Results Thalamus was the most commonly involved location, followed by pons and tectum. Five patients showed loss of normal ATRX expression. p53 mutation was positive in 12 patients. 40% of normal ATRX expression patients had cortical involvement and 20% had leptomeningeal seeding; none of the patients with ATRX loss had cortical involvement or leptomeningeal seeding. Patients with normal ATRX expression showed significantly higher rCBV ratio and lower ADC value in the NE area than patients with ATRX loss ( P=0.04, 0.016). p53 mutation status did not correlate with any imaging finding. Conclusion Cortical invasion, leptomeningeal tumor spread, lower ADC value and higher rCBV ratio in NE areas of DMG may be related to normal expression of ATRX.

Histopathology and surgical outcome of symptomatic treatment-related changes after gamma knife radiosurgery in patients with brain metastases

“…Each patient was scanned by 3-T MRI using the brain tumor MRI protocol in our institution, including pre- and post-contrast 5-mm-thick T1-weighted imaging, 5-mm-thick fat-suppressed echo T2-weighted imaging, 5-mm-thick FLAIR imaging, diffusion weighted imaging (DWI), which was performed with spin echo using a b-value of 0 and 1000 s/mm 2 and dynamic susceptibility contrast (DSC)-perfusion-weighted imaging (PWI) (Dotarem; Guerbet, Aulnay-sous-Bois, France). T2*-perfusion data were processed for the maximum regional cerebral blood volume (rCBV) ratio of non-enhanced (NE) and contrast-enhanced (CE) portions, and rCBV maps were computed using the software provided by the MR vendor (Intellispace Portal 9.0; Philips Health Tech, Best, the Netherlands) 38 , 39 .…”

Histopatholgy and Clinical Implication of Treatment-Related Changes After Gamma Knife Radiosurgery in Patients With Brain Metastases

“…The maximum regional cerebral blood volume (rCBV) ratio of non-enhanced (NE) and contrast-enhanced (CE) portions, and minimum apparent diffusion coefficient of NE and CE portions on MRI were evaluated by drawing a region of interest circle with an area of 1 cm 2 . T2*-perfusion data were processed, and rCBV maps were computed using the software provided by the MR vendor (Intellispace Portal 9.0; Philips Health Tech, Best, the Netherlands) 29,30 .…”

Prediction of H3K27M mutation status of diffuse midline gliomas using MRI features

“…Multiple monotherapies and combination chemotherapy regimens have also been tried with equivalently dismal outcomes 5 . Despite RT and chemotherapy, DMG in children had a poor prognosis as a 2‐year overall survival rate of less than 10% 11 . Since the tumor involves eloquent areas of the brain, a biopsy is usually avoided, and diagnosis of DMGs hinges on clinical and imaging features 7,10 .…”

“…5 Despite RT and chemotherapy, DMG in children had a poor prognosis as a 2year overall survival rate of less than 10%. 11 Since the tumor involves eloquent areas of the brain, a biopsy is usually avoided, and diagnosis of DMGs hinges on clinical and imaging features. 7,10 MRI feature set has been designed to facilitate reliable depictions of gliomas through organized terminology and distinct visual imaging features.…”