Quantitative Determination of Tumor Blood Flow and Perfusion via Deuterium Nuclear Magnetic Resonance Spectroscopy in Mice

Murine RIF-1 tumor blood flow and perfusion were quantified by deuterium NMR using D2O as a freely diffusible tracer. After direct intratumor injection of D2O saline solution, the tracer (HOD) residue from the tumor was detected by deuterium NMR and the deuterium residue washout time course was then analyzed employing multicompartment- flow models(S-G. Kim and J. J. H. Ackerman, manuscript submitted for publication). The mean tumor blood flow and perfusion rate was 18i ± 8.5 SD ml/(100 g-min) (a = 46) when analyzed by a two-compartment in-series flow model. A number of tumors (a = 15 out of 61 total) showed a biexponential deuterium tracer washout curve. Application of a three-compartment flow model (S-G. Kim and J. J. H. Ackerman, manuscript submitted for publication) fitted the biexponential residue decay data well and yielded a mean tumor blood flow of 15.7 ± 9.7 SD, fast- and slow-flow components of 36.8 ± 19.8 SD and 9.7 ± 5.8 SD ml/(100 g-min), and a fast-flow component fraction of 21 ± 10 SD%. Small tumors of less than 0.5 cm3 had faster blood flow, 21.1 ± 8.4 SD ml/(100 g-min) (R = 27), than large tumors of greater than 1.0 cm3,9.4 ± 2.9 SD ml/(100 g-min) (a = 13). The NMR measurement of tumor blood flow and perfusion was not dependent on the number of direct intratumor injection sites and was found reproducible upon repeated measurements of individual tumors. Good agreement with previous in situ photon activation H2lsO flow determinations was observed.