MRI Imaging of the Hemodynamic Vasculature of Neuroblastoma Predicts Response to Anti-angiogenic Treatment.
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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 a MRI-pathological cross-correlative approach using intrinsic susceptibility (IS-) and susceptibility contrast (SC-) MRI to non-invasively 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* (s-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.
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Computational Pathology & Integrated Genomics
Paediatric Solid Tumour Biology and Therapeutics
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Cancer Res, 2019