Mapping Hypoxia in Renal Carcinoma with Oxygen-enhanced MRI: Comparison with Intrinsic Susceptibility MRI and Pathology.
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Date
2018-09-01Author
Little, RA
Jamin, Y
Boult, JKR
Naish, JH
Watson, Y
Cheung, S
Holliday, KF
Lu, H
McHugh, DJ
Irlam, J
West, CML
Betts, GN
Ashton, G
Reynolds, AR
Maddineni, S
Clarke, NW
Parker, GJM
Waterton, JC
Robinson, SP
O'Connor, JPB
Type
Journal Article
Metadata
Show full item recordAbstract
Purpose To cross-validate T1-weighted oxygen-enhanced (OE) MRI measurements of tumor hypoxia with intrinsic susceptibility MRI measurements and to demonstrate the feasibility of translation of the technique for patients. Materials and Methods Preclinical studies in nine 786-0-R renal cell carcinoma (RCC) xenografts and prospective clinical studies in eight patients with RCC were performed. Longitudinal relaxation rate changes (∆R1) after 100% oxygen inhalation were quantified, reflecting the paramagnetic effect on tissue protons because of the presence of molecular oxygen. Native transverse relaxation rate (R2*) and oxygen-induced R2* change (∆R2*) were measured, reflecting presence of deoxygenated hemoglobin molecules. Median and voxel-wise values of ∆R1 were compared with values of R2* and ∆R2*. Tumor regions with dynamic contrast agent-enhanced MRI perfusion, refractory to signal change at OE MRI (referred to as perfused Oxy-R), were distinguished from perfused oxygen-enhancing (perfused Oxy-E) and nonperfused regions. R2* and ∆R2* values in each tumor subregion were compared by using one-way analysis of variance. Results Tumor-wise and voxel-wise ∆R1 and ∆R2* comparisons did not show correlative relationships. In xenografts, parcellation analysis revealed that perfused Oxy-R regions had faster native R2* (102.4 sec-1 vs 81.7 sec-1) and greater negative ∆R2* (-22.9 sec-1 vs -5.4 sec-1), compared with perfused Oxy-E and nonperfused subregions (all P < .001), respectively. Similar findings were present in human tumors (P < .001). Further, perfused Oxy-R helped identify tumor hypoxia, measured at pathologic analysis, in both xenografts (P = .002) and human tumors (P = .003). Conclusion Intrinsic susceptibility biomarkers provide cross validation of the OE MRI biomarker perfused Oxy-R. Consistent relationship to pathologic analyses was found in xenografts and human tumors, demonstrating biomarker translation. Published under a CC BY 4.0 license. Online supplemental material is available for this article.
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https://pubs.rsna.org/doi/pdf/10.1148/radiol.2018171531Collections
Subject
Kidney
Animals
Humans
Mice
Carcinoma, Renal Cell
Kidney Neoplasms
Disease Models, Animal
Oxygen
Magnetic Resonance Imaging
Image Enhancement
Prospective Studies
Feasibility Studies
Reproducibility of Results
Adult
Aged
Middle Aged
Female
Male
Biomarkers
Hypoxia
Research team
Pre-Clinical MRI
Quantitative Biomedical Imaging
Language
eng
Date accepted
2017-12-21
License start date
2018-09
Citation
Radiology, 2018, 288 (3), pp. 739 - 747
Publisher
RADIOLOGICAL SOC NORTH AMERICA