Flow and oxygenation dependent (flood) contrast MR imaging to monitor the response of rat tumors to carbogen breathing

Gradient recalled echo (GRE) images are sensitive to both paramagnetic deox yhaemoglobin concentration (via T-2*) and flow (via T-1*). Large GRE signal intensity increases have been observed in subcutaneous tumors during carbo gen (5% carbon dioxide, 95% oxygen) breathing. We term this combined effect how and oxygenation-dependent (FLOOD) contrast. We have now used both spin echo (SE) and GRE images to evaluate how changes in relaxation times and h ow contribute to image intensity contrast changes. T-1-weighted images, wit h and without outer slice suppression, and calculated T-2, T-2* and "flow" maps, were obtained for subcutaneous GH3 prolactinomas in rats during air a nd carbogen breathing. T-1-weighted images showed bright features that incr eased in size, intensity and number with carbogen breathing. H&E stained hi stological sections confirmed them to be large blood vessels. Apparent T-1 and T-2 images were fairly homogeneous with average relaxation times of 850 ms and 37 ms, respectively, during air breathing, with increases of 2% for T-1 and 11% for T-2 during carbogen breathing. The apparent T-2* over all tumors was very heterogeneous, with values between 9 and 23 ms and localize d increases of up to 75% during carbogen breathing. Synthesised "flow" maps also showed heterogeneity, and regions of maximum increase in how did not always coincide with maximum increases in T-2*. Carbogen breathing caused a threefold increase in arterial rat blood p(a)O(2), and typically a 50% inc rease in tumor blood volume as measured by Cr-51-labelled RBC uptake. The T -2* increase is therefore due to a decrease in blood deoxyhaemoglobin conce ntration with the magnitude of the FLOOD response being determined by the v ascular density and responsiveness to blood flow modifiers. FLOOD contrast may therefore be of value in assessing the magnitude and heterogeneity of r esponse of individual tumors to blood flow modifiers for both chemotherapy, antiangiogenesis therapy in particular, and radiotherapy. (C) 1999 Elsevie r Science Inc.