Predicting outcome of children with diffuse intrinsic pontine gliomas using multiparametric imaging

Abstract

Noninvasive evaluation using MRI is the primary means to routinely assess children with diffuse intrinsic pontine gliomas (DIPGs). However, no standard MR sequence has correlated with outcome in these patients. In this study, patients with DIPGs were assessed to determine the combined prognostic value via dynamic susceptibility contrast (DSC) MRI, single-voxel spectroscopy (SVS), multivoxel MR spectroscopy (MRS), and T1-weighted post-gadolinium imaging. Eligible patients had clinical and radiographic findings consistent with a DIPG. Imaging studies were acquired on a 1.5T MRI at various time points during each patient's course. Data were evaluated using a Cox proportional hazard model, a time-dependent covariant Cox model, a Wald test, and a Kaplan-Meier analysis. Ninety-eight studies were performed on 34 patients of median age 5.5 years. Median survival from diagnosis was 468 days. At baseline imaging only, increased ratio of choline to n-acetylaspartate (Cho:NAA) on SVS and increased perfusion on DSC-MRI each predicted shorter survival (relative risk [RR] = 1.48, P = .015 and RR = 4.91, P = .0012, respectively). When analyzing all subsequent time points, increased maximum Cho:NAA on MRS (RR = 1.45, P = .042), increased Cho:NAA on SVS (RR = 1.69, P = .003), increased perfusion (RR = 4.68, P = .0016), and the presence of enhancement (RR = 5.69, P = .022) each predicted shorter survival. Kaplan-Meier analysis showed shorter survival associated with increased perfusion at baseline (P = .0004). Increased perfusion at any time point predicts a significantly shorter survival in children with DIPG. In addition, enhancement, increased Cho:NAA on SVS, and increased maximum Cho:NAA on chemical shift imaging are predictive of shorter survival over time. Routine baseline and subsequent imaging for children with DIPG should, at minimum, incorporate DSC-MRI and SVS.

Correlation of Tumor Immunohistochemistry with Dynamic Contrast-Enhanced and DSC-MRI Parameters in Patients with Gliomas

“…[1][2][3][4][5] Maps of blood volume or vascular permeability can also be generated across the whole tumor, allowing the neurosurgeon to determine preoperatively the most appropriate target for biopsy and/or resection. Validation of MR imaging-derived blood volume with microvessel area and density from immunohistochemistry is important because absolute CBV measurement is more difficult with MR imaging compared with CT.…”

“…[1][2][3][4][5] Measurements of blood volume can be obtained by using dynamic contrast-enhanced (DCE) MR imaging or dynamic susceptibility contrast MR imaging. Both techniques have their own advantages and disadvantages.…”

Preoperative Prognostic Value of Dynamic Contrast-Enhanced MRI-Derived Contrast Transfer Coefficient and Plasma Volume in Patients with Cerebral Gliomas

“…[5][6][7] However, use of DSC-derived rCBV as a potential biomarker in a multiinstitutional trial is currently limited because it is a semiquantitative measurement, which can be influenced by many postprocessing steps, including the technique of correction for contrast agent extravasation and the choice of the normal contralateral white matter. 8,9 For patients with gliomas, CBV obtained from the normal contralateral white matter has been shown to have significant interscanner variability.…”

“…1 Recently, by using dynamic susceptibility contrast MR imaging, the relative CBV was identified as an important prognostic marker for survival independent of tumor grade. [5][6][7] For example, Law et al 5 have shown that gliomas with high relative cerebral blood volume (rCBV) (Ͼ1.75) have a shorter time to progression compared with tumors with similar grades but lower rCBV, regardless of tumor grade. While dynamic susceptibility contrast-derived rCBV has been shown to predict survival in patients with gliomas in single-center studies, the need for normalization of semiquantitative values with a manually defined reference region can introduce interpatient and interscanner variability and thus limits its use in a multiinstitutional clinical trial.…”

MRI and PET: Noninvasive Tools to Probe the Biology of Diffuse Intrinsic Pontine Glioma

“…Contrast enhancement can be variable, however, and therefore does not always predict behavior. MR spectroscopy to measure ratios of choline to N-acetylaspartate has been proposed as a useful tool, with higher ratios being associated with worse survival (4,5). Elevated cerebral blood volume has also been associated with worse outcome (4).…”