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 car bogen (95% O-2, 5% CO2) is breathed. The timing of carbogen administra tion is critical, and a noninvasive method of monitoring the response of individual tumors would have obvious utility. Functional gradient r ecalled echo (GRE) magnetic resonance imaging (MRI) techniques are sen sitive to changes in the concentrations of deoxyhemoglobin, which, thu s, acts as an endogenous contrast agent for oxygenation status and blo od flow. Methods and Materials: Subcutaneous GH3 prolactinomas in thre e rats were imaged at 4.7 Tesla with a GRE H-1 sequence [echo time (TE ) = 20 ms, repetition time (TR) = 80 ms, hip angle = 45 degrees, 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 c arbogen for four periods of 20 min; three control rats breathed only a ir. Results: Carbogen breathing caused increases of up to 100% in the GRE image intensity of the tumors. Reversion to air breathing caused t he image intensity to fall; essentially the same response was observed with the second cycle of carbogen and air breathing. Control rat tumo rs showed no significant change. Conclusions: The response of tumors t o carbogen can be monitored noninvasively by GRE MRI. In principle, th is could be due to an increase in oxygen content of the blood, a decre ase in tumor cell oxygen consumption, or an increase in tumor blood fl ow. The very large changes in signal intensity suggest that a blood fl ow increase is the most probable explanation. If this technique can be successfully applied in man, it should be possible to optimize carbog en treatment for individual radiotherapy patients, and perhaps also to enhance tumor uptake of chemotherapeutic agents.