Estimating blood-brain barrier opening in a rat model of hemorrhagic transformation with Patlak plots of Gd-DTPA contrast-enhanced MRI

Abstract

Patlak plot processing [2, 3] of Gd-shifted T₁ relaxation-time images from a rat model of hemorrhagic transformation yielded estimates and maps of the blood-to-brain influx rate constant of Gd-DTPA (K₁). The Patlak plots also produced a heretofore unrecognized parameter, the distribution space of the intravascularGd-shifted protons (V_p), an index of blood-to-tissue transfer of water. The K₁ values for Gd-DTPA were very high for the regions of blood-brain barrier (BBB) opening and were similar to those of ¹⁴C-sucrose concurrently obtained by quantitative autoradiographic (QAR) analysis. In these same ROI’s, V_p was five-fold greater than normal, which suggests that the permeability of the BBB to water was also increased. The ¹⁴C-sucrose space of distribution in the ischemic ROI’s was around 8%, thus indicating a sizable interstitial space. The spatial resolving power of Gd-DTPA-ΔT₁ imaging was rather good, although no match for ¹⁴C-sucrose-QAR. This study shows that quantitative ΔT₁-MRI estimates of regional blood-brain transfer constants of Gd-DTPA and water distribution are possible when Patlak plots are employed to process the data. This approach may be useful for tracking the time-course of BBB barrier function in both animals and humans.