Deuterium nuclear magnetic resonance imaging of tracer distribution in D2O clearance measurements of tumor blood flow in mice.

Proper implementation of direct injection clearance techniques to measure tumor blood flow (TBF) requires knowledge of the tracer distribution because TBF distribution is often inhomogeneous. Therefore, deuterium nuclear magnetic resonance imaging was used to follow tracer (HOD) distribution after direct injection of 10-40 microliters isotonic saline/D2O into RIF-1 tumors. Within 2 to 4 min after intratumor injection, tracer clearance was imaged by obtaining deuterium images every 1.4 min. The mean volume occupied by HOD in tumors in the first image acquired after injection with 10, 20, or 40 microliters D2O was 56 +/- 37 (SD) mm3, 44 +/- 2.9 mm3, and 174 +/- 83 mm3, respectively (n = 3 for each). In these control tumors, HOD was cleared from that volume without an appreciable increase in tracer distribution. In tumors heated for 45 min at 45 degrees C to greatly reduce TBF, the mean tracer volume in the first image after 10-microliters D2O injection was 41 +/- 10 mm3 and increased to 111 +/- 24 mm3 at 30 min (n = 3). For 10 microliters D2O injected at two distinct sites, the intensity decreased at each site while the sites remained separate (n = 6). The TBF at the two sites, measured independently by fitting the integrated HOD intensity from each site to a monoexponential decay function, was significantly different in only one of the six tumors examined. The use of deuterium nuclear magnetic resonance imaging to measure TBF from two (or more in larger tumors) independent sites provides a practical approach to assess TBF heterogeneity. The direct measurement of the tissue volume labeled with tracer and its dependence on injection volume should aid in determining how best to implement direct injection tracer clearance methods.