The role of vessel maturation and vessel functionality in spontaneous fluctuations of T2-weighted GRE signal within tumors

• Published in: NMR in biomedicine 2006-02, Vol.19 (1), p.69-76
• Main Authors: Baudelet, Christine, Cron, Greg O., Ansiaux, Réginald, Crokart, Nathalie, DeWever, Julie, Feron, Olivier, Gallez, Bernard
• Format: Article
• Language: English
• Subjects: acute hypoxia; Animals; blood flow; blood oxygen level-dependent MRI; BOLD; carbogen; Cell Hypoxia; Cell Line, Tumor; Fibrosarcoma - blood supply; Fibrosarcoma - complications; Fibrosarcoma - metabolism; Fibrosarcoma - pathology; fluctuations; Image Interpretation, Computer-Assisted - methods; Magnetic Resonance Imaging - methods; Male; Mice; Mice, Inbred C3H; Neovascularization, Pathologic - complications; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Oxygen - metabolism; Reproducibility of Results; Sensitivity and Specificity; tumor; vessel maturation
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/nbm.1002

Acute hypoxia (transient cycles of hypoxia‐reoxygenation) is known to occur in solid tumors and is generally believed to be caused by tumor blood flow instabilities. It was recently demonstrated that T2*‐weighted (T2*w) gradient echo (GRE) MRI is a powerful non‐invasive method for investigating periodic changes in tumor pO2 and blood flow associated with acute hypoxia. Here, the possible correlation between tumor vessel immaturity, vessel functionality and T2*w GRE signal fluctuations was investigated. Intramuscularly implanted FSa II fibrosarcoma‐bearing mice were imaged at 4.7 T. Maps of spontaneous fluctuations of MR signal intensity in tumor tissue during air breathing were obtained using a T2*w GRE sequence. This same sequence was also employed during air–5% CO2 breathing (hypercapnia) and carbogen breathing (hypercapnic hyperoxia) to obtain parametric maps representing vessel maturation and vessel function, respectively. Vascular density, vessel maturation and vessel perfusion were also assessed histologically by using CD31 labeling, α‐smooth muscle actin immunoreactivity and Hoechst 33242 labeling, respectively. About 50% of the tumor fluctuations occurred in functional tumor regions (responsive to carbogen) and 80% occurred in tumor regions with immature vessels (lack of response to hypercapnia). The proportion of hypercapnia‐responsive voxels were found to be twice as great in fluctuating than in non‐fluctuating tumor areas (P: 0.22 vs 0.13). Similarly, the proportion of functional voxels was somewhat greater in fluctuating tumor areas (P: 0.54 vs 0.43). The mean values of MR signal changes during hypercapnia (VD) and during carbogen breathing (VF) (significant voxels only) were also larger in fluctuating than in non‐fluctuating tumor areas (P