Noninvasive monitoring of carbogen-induced changes in tumor blood flow and oxygenation by functional magnetic resonance imaging

Purpose : The response of tumors to radiotherapy can be enhanced if carbogen (95% O 2 , 5% CO 2 ) is breathed. The timing of carbogen administration is critical, and a noninvasive method of monitoring the response of individual tumors would have obvious utility. Functional gradient recalled echo (GRE) magnetic resonance imaging (MRI) techniques are sensitive to changes in the concentrations of deoxyhemoglobin, which, thus, acts as an endogenous contrast agent for oxygenation status and blood flow. Methods and Materials : Subcutaneous GH3 prolactinomas in three rats were imaged at 4.7 Tesla with a GRE 1 H sequence [echo time (TE) = 20 ms, repetition time (TR) = 80 ms, flip angle = 45°, 1 mm slice, 256 phase encode steps, 4 cm field of view, in-plane resolution 0.08 x 0.08 mm, acquisition time = 4 min]. The rats breathed air or carbogen for four periods of 20 min ; three control rats breathed only air. Results : Carbogen breathing caused increases of up to 100% in the GRE image intensity of the tumors. Reversion to air breathing caused the image intensity to fall ; essentially the same response was observed with the second cycle of carbogen and air breathing. Control rat tumors showed no significant change. Conclusions : The response of tumors to carbogen can be monitored noninvasively by GRE MRI. In principle, this could be due to an increase in oxygen content of the blood, a decrease in tumor cell oxygen consumption, or an increase in tumor blood flow. The very large changes in signal intensity suggest that a blood flow increase is the most probable explanation. If this technique can be successfully applied in man, it should be possible to optimize carbogen treatment for individual radiotherapy patients, and perhaps also to enhance tumor uptake of chemotherapeutic agents.