MAGNETIC RESONANCE IN MEDICINE 17,357-367 ( 199 1) Measurement of the Blood-Brain Barrier Permeability and Leakage Space Using Dynamic MR Imaging. 1. Fundamental Concepts

Leakage of Gd-DTPA through a defective blood-brain bamer is measured quantitatively using dynamic MRI scanning, in which repeated scans are made after a bolus injection. Image registration artifacts are minimized; a dose of 0.1 mM/kg and an IR sequence enable enhancement to be measured quantitatively. The triexponential enhancement curve is fitted to a theoretical model based on compartmental analysis. The transfer constant, or permeability surface area product per unit volume of tissue ( k) , and leakage space per unit volume of tissue ( y) are measured. Estimates for a quickly enhancing multiple sclerosis lesion are k = 0.050 min-', 11, = 21%; for a slow one k = 0.013 min-', 111 = 49%. This implies permeability in the range 4-17 X cm s-', in broad agreement with other physiological methods. The method is noninvasive and can be used to make serial mea-surements in patients and in experimental animal models. The time course of pathological aspects of diseases with blood-brain bamer breakdown, such as multiple sclerosis, tumors, and infections (e.g., HIV) can be studied, along with their response to therapy. The mea-surements are of physiological variables and are therefore independent of imaging equipment and field. Q 1991 Academic Press, Inc