A new method for imaging perfusion and contrast extraction fraction: Input functions derived from reference tissues

This study describes a new method for analysis of dynamic MR contrast data that greatly increases the time available for data acquisition. The capillary input function, CB(t), is estimated from the rate of contrast agent uptake in a reference tissue such as muscle, based on literature values for perfusion rate, extraction fraction, and extracellular volume. The rate constant for contrast uptake (the product of perfusion rate, F, and extraction fraction, E; F‐E) is then determined in each image pixel using CB(t), extracellular volume (relative to the reference tissue) measured from MR and the tissue concentration of contrast media as a function of time calculated from the MR data. The “reference tissue method” was tested using rats with mammary (n = 10) or prostate (n = 15) tumors implanted in the hindlimb. Dynamic MR images at 4.7 T were acquired before and after Gd‐DTPA intravenous bolus injections to determine F·EGd‐DTPA. Acquisition parameters were optimized for detection of the first pass of the contrast agent bolus, so that “first‐pass analysis” could be used as the “gold standard” for determination of F·E. The accuracy of values of F·E determined using the reference tissue method was determined based on comparison with first‐pass analysis. In some cases, deuterated water (D2O) was injected IV immediately after Gd‐DTPA measurements, and the reference tissue method was used to calculate F, based on the rate of uptake of D2O. Comparison of rate constants for Gd‐DTPA uptake and D2O uptake allowed calculation of EGd‐DTPA. Values for F·EGd‐DTPA, F, and EGd.DTPA were determined for selected regions and on a pixel‐by‐pixel basis. Values for F·E and EGd.DTPA measured using the reference tissue method correlated well (P = .90 with a standard error of ±.016, n = 15) with values determined based on first‐pass contrast media uptake. The reference tissue method has important advantages: (a) A large volume of reference tissue can be used to determine the contrast agent input function with high precision. (b) Data obtained for 20 minutes after injection are used to calculate F or F·E. The greatly increased acquisition time can be used to increase the spatial resolution, field of view or SNR of measurements. The reference tissue method is most useful when the volume of tissue that must be imaged and/or the spatial resolution required precludes use of traditional first‐pass methods.