In vivo BOLD contrast MRI mapping of subcutaneous vascular function and maturation: validation by intravital microscopy.

Bold contrast MRI was applied for mapping vascular maturation in tumor- and wound-induced skin angiogenesis using the response of mature vessels to hypercapnia (inhalation of air vs. air 5% CO(2)) and the response of all vessels to hyperoxia (air 5% CO(2) vs. oxygen 5% CO(2) (carbogen)). MRI signal enhancement with hypercapnia was reduced in centered vs. linear phase encoding, suggesting increased blood flow. However, intravital microscopy demonstrated constriction of arterioles and reduced flux and density of red blood cells in mature capillaries with hypercapnia, with no change in the diameter of wound-induced neovasculature. The discrepancy in flow between MRI and intravital microscopy is consistent with increased plasma flow and reduced hematocrit. Hyperoxia resulted in increased blood oxygenation and constriction of all vessels. These results provide a hemodynamic explanation for the selective registration of MRI response to hypercapnia with mature vessels and the response to hyperoxia with total vascular function.