MRI Imaging of the Hemodynamic Vasculature of Neuroblastoma Predicts Response to Antiangiogenic Treatment
Zormpas-Petridis, Konstantinos; Jerome, Neil Peter; Blackledge, Matthew D.; Carceller, Fernando; Poon, Evon; Clarke, Matthew; McErlean, Ciara; Barone, Guiseppe; Koers, Alexander; Vaidya, Sucheta; Marshall, Lynley; Pearson, Andrew D. J.; Moreno, Lucas; Anderson, John; Sebire, Neil; McHugh, Kieran; Koh, Dow-Mu; Yuan, Yinyin; Chesler, Louis; Robinson, Simon; Jamin, Yann
Journal article, Peer reviewed
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Childhood neuroblastoma is a hypervascular tumor of neural origin, for which antiangiogenic drugs are currently being evaluated; however, predictive biomarkers of treatment response, crucial for successful delivery of precision therapeutics, are lacking. We describe an MRI-pathologic cross-correlative approach using intrinsic susceptibility (IS) and susceptibility contrast (SC) MRI to noninvasively map the vascular phenotype in neuroblastoma Th-MYCN transgenic mice treated with the vascular endothelial growth factor receptor inhibitor cediranib. We showed that the transverse MRI relaxation rate R2* (second−1) and fractional blood volume (fBV, %) were sensitive imaging biomarkers of hemorrhage and vascular density, respectively, and were also predictive biomarkers of response to cediranib. Comparison with MRI and pathology from patients with MYCN-amplified neuroblastoma confirmed the high degree to which the Th-MYCN model vascular phenotype recapitulated that of the clinical phenotype, thereby supporting further evaluation of IS- and SC-MRI in the clinic. This study reinforces the potential role of functional MRI in delivering precision medicine to children with neuroblastoma.