title: Assessment of tumor necrotic fraction by dynamic contrast-enhanced MRI: a preclinical study of human tumor xenografts with histopathologic correlation.
abstract: Contrary to the common notion that tumor necrotic regions are non-enhancing after contrast administration, recent evidence has shown that necrotic regions exhibit delayed and slow uptake of gadolinium tracer on dynamic contrast-enhanced MRI (DCE MRI). The purpose of this study is to explore whether the mapping of tumor voxels with delayed and slow enhancement on DCE MRI can be used to derive estimates of tumor necrotic fraction. Patient-derived tumor xenograft lines of seven human cancers were implanted in 26 mice which were subjected to DCE MRI performed using a spoiled gradient recalled sequence. Gadolinium tracer concentration was estimated using the variable flip angle technique. To identify tumor voxels exhibiting delayed and slow uptake of contrast medium, clustering analysis was performed using a k-means clustering algorithm that classified tumor voxels according to their contrast enhancement patterns. Comparison of the percentage of tumor voxels exhibiting delayed and slow enhancement with the tumor necrotic fraction estimated on histology showed a strong correlation (r = 0.962, p < 0.001). The mapping of tumor regions with delayed and slow contrast uptake on DCE MRI correlated strongly with tumor necrotic fraction, and can potentially serve as a non-invasive imaging surrogate for the in vivo assessment of necrotic fraction.
authors.affiliation: Department of Oncologic Imaging, National Cancer Center, Singapore; Center for Quantitative Biology, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Tong San
authors.initials: TS
authors.lastname: Koh
authors.forename: Choon Hua
authors.initials: CH
authors.lastname: Thng
authors.forename: Septian
authors.initials: S
authors.lastname: Hartono
authors.forename: Lourdes T M
authors.initials: LT
authors.lastname: Dominguez
authors.forename: Tony K H
authors.initials: TK
authors.lastname: Lim
authors.forename: Hung
authors.initials: H
authors.lastname: Huynh
authors.forename: Laurent
authors.initials: L
authors.lastname: Martarello
authors.forename: Quan Sing
authors.initials: QS
authors.lastname: Ng
mesh_terms: D000818:Animals; D003287:Contrast Media; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009336:Necrosis; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology; D013194:Staining and Labeling; D023041:Xenograft Model Antitumor Assays
chemical_list: D003287:Contrast Media
keywords: dynamic contrast-enhanced MRI; tracer diffusivity; tumor necrosis