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Quantitative Determination of Tumor Blood Flow and Perfusion via Deuterium Nuclear Magnetic Resonance Spectroscopy in Mice¹

Department of Chemistry, Washington University, St. Louis, Missouri 63130

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 18.5 ± 8.5 SD ml/(100 g·min) (n = 46) when analyzed by a two-compartment in-series flow model. A number of tumors (n = 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) (n = 27), than large tumors of greater than 1.0 cm³, 9.4 ± 2.9 SD ml/(100 g·min) (n = 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 H₂¹⁵O flow determinations was observed.

¹ Support for this work was provided by NIH grants GM-30331 and CA-40411, National Science Foundation instrument Grant CHE-8100211, and a gift from Mallinckrodt, Inc. This work has been presented in part at the Sixth Annual Meeting of the Society of Magnetic Resonance in Medicine, New York, NY; Book of Abstracts, Vol. 1, p. 426, August, 1987.

² To whom requests for reprints should be addressed, at Department of Chemistry, Campus Box 1134, Washington University, 1 Brookings Drive, St. Louis, MO 63130.

Received 7/27/87. Revised 12/10/87. Accepted 1/ 7/88.

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