Arterial Spin Labeling to Predict Brain Tumor Grading in Children: Correlations between Histopathologic Vascular Density and Perfusion MR Imaging

Abstract

Purpose To compare arterial spin labeling (ASL) data between low- and high-grade brain tumors in children to establish a cutoff to distinguish low- from high-grade neoplasms and to assess potential correlations between cerebral blood flow (CBF) and quantitative histologic microvascular data. Materials and Methods Approval was obtained from the regional review board. ASL data obtained in 129 children between 2011 and 2015 were retrospectively analyzed. CBF and relative CBF in the most perfused area of each neoplasm and contrast enhancement were quantified with a semiquantitative ratio. The correlation between CBF and microvascular density was analyzed in specimens stained with anti-CD34. Results were controlled in two validation cohorts with 1.5- and 3.0-T magnetic resonance (MR) imaging. Results Mean CBF was significantly higher for high-grade than for low-grade hemispheric (116 mL/min/100 g [interquartile range {IQR}, 73-131 mL/min/100 g] vs 29 mL/min/100 g [IQR, 23-35 29 mL/min/100 g], P < .001), thalamic (87 mL/min/100 g [IQR, 73-100 mL/min/100 g] vs 36 mL/min/100 g [IQR, 30-40 mL/min/100 g], P = .016), and posterior fossa (59 mL/min/100 g [IQR, 45-91 mL/min/100 g] vs 33 mL/min/100 g [IQR, 25-40 mL/min/100 g], P < .001) tumors. With a cutoff of 50 mL/min/100 g, sensitivity and specificity were 90% (95% confidence interval [CI]: 68, 100) and 93% (95% CI: 66, 100), respectively, for hemispheric tumors; 100% (95% CI: 48, 100) and 80% (95% CI: 28, 100), respectively, for thalamic tumors; and 65% (95% CI: 51, 78) and 94% (95% CI: 80, 99), respectively, for posterior fossa tumors. In posterior fossa tumors, additional use of the CBF-to-contrast enhancement ratio yielded sensitivity and specificity of 96% (95% CI: 87, 100) and 97% (95% CI: 84, 100), respectively. Use of a simple algorithm based on these values yielded an accuracy of 93% (95% CI: 87, 97). Validation sets yielded similar results, with grading accuracy of 88% (95% CI: 62, 98) with 1.5-T MR imaging and 77% (95% CI: 46, 95) with 3.0-T MR imaging. CBF was strongly correlated with microvascular density (R = 0.66, P < .001). Conclusion High-grade pediatric brain tumors display higher CBF than do low-grade tumors, and they may be accurately graded by using these values. CBF is correlated with tumor microvascular density. RSNA, 2016 Online supplemental material is available for this article.

Role of Dynamic Contrast-Enhanced Perfusion Magnetic Resonance Imaging in Grading of Pediatric Brain Tumors on 3T

“…Angiogenesis in this group of neoplasms has been investigated and it has been shown that tumors with a higher neovascularity do poorly and have worse outcomes [22] . In our study, we noted wide variations in both hemodynamic and blood brain barrier permeability parameters of high-grade tumors and medulloblastomas, which are consistent with the results of previous imaging studies [5,23] . A wide variety of proangiogenic factors that individually or together play a direct role in medulloblastoma tumor growth, including vascular endothelial growth factor (VEGF), are expressed in embryonal tumors [24] .…”

“…Few studies have evaluated contrast-enhanced DSC perfusion MRI for grading of pediatric brain tumors, and all of them have found rCBV to be a useful parameter for discriminating high-grade neoplasms from low grade ones [7,17,18] . Arterial spin labeling perfusion techniques have also been used to grade pediatric brain tumors [5] . Vajapeyam et al [8] recently showed the value of DCE perfusion MRI-derived pharmacokinetic parameters for grading of pediatric brain tumors.…”

“…Advanced imaging techniques such as perfusion MRI, diffusion imaging, MR spectroscopy, and positron emission tomography are useful for the assessment of tumor vascularity, cellularity, and metabolism. They are useful for predicting the biological behavior of childhood brain tumors [1,5,6] .…”

“…MR perfusion imaging quantifies tumor neoangiogenesis and it has been sparingly used for brain tumor assessment in children [2,5,7,8] . Dynamic susceptibility contrast (DSC) imaging is the most commonly used MR perfusion technique that requires administration of a high dose of contrast with a rapid injection rate.…”

“…Other drawbacks of the DSC perfusion method are calcification and hemorrhage-induced susceptibility within the tumor, as well as blood brain barrier breakdown-related contrast leakage [9] . Arterial spin labeling is an alternative MRI perfusion technique which uses magnetically labelled water as endogenous contrast and has been used to study pediatric brain tumors [5] . However, it is limited by a low signal-to-noise ratio, the need for greater magnetic strength, and the presence of susceptibility and commonly provides only an estimate of the CBF.…”