Measurement of the blood‐brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts

Abstract

Leakage of Gd-DTPA through a defective blood-brain barrier 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 (v1) are measured. Estimates for a quickly enhancing multiple sclerosis lesion are k = 0.050 min-1, v1 = 21%; for a slow one k = 0.013 min-1, v1 = 49%. This implies permeability in the range 4-17 x 10(-6) cm s-1, in broad agreement with other physiological methods. The method is noninvasive and can be used to make serial measurements in patients and in experimental animal models. The time course of pathological aspects of diseases with blood-brain barrier breakdown, such as multiple sclerosis, tumors, and infections (e.g., HIV) can be studied, along with their response to therapy. The measurements are of physiological variables and are therefore independent of imaging equipment and field.

Vessel imaging with viable tumor analysis for quantification of tumor angiogenesis

“…Low-molecularweight gadolinium-based contrast agents have been used for mapping blood volume in tissue (9) and for MR angiography (10). T 1 -weighted dynamic contrast-enhanced MRI has been used extensively as a measure of various parameters associated with angiogenesis that can be calculated using compartmental modeling (11,12), including vascular permeability, vascular and extravascular volumes, and blood flow (13). Ultrasmall paramagnetic iron oxide (USPIO) contrast agents, which remain intravascular with a half-life of several hours, have also proven useful for MR angiography (14) and blood volume measurements (15).…”

DCE‐MRI pixel‐by‐pixel quantitative curve pattern analysis and its application to osteosarcoma

“…An AIF, C b , was generated according to the experimentally derived functional form (25), which was consistent with our averaged AIF from five selected pediatric patients with osteosarcoma. The original tracer concentration curve in tissue, C t , was generated based on Tofts' model (17).…”

“…The methods for DCE-MRI data processing can be divided into three types: Heuristic models (9 -14), pharmacokinetic models (15)(16)(17)(18)(19), and pattern analysis (20,21). Within each type there is a variety of derived models.…”

“…Pharmacokinetic models are widely used in DCE-MRI (15)(16)(17)(18)(19). After converting the dynamic signal to the contrast agent concentration, several pharmacokinetic parameters can be assessed on the basis of pharmacokinetic modeling.…”

Comparative study into the robustness of compartmental modeling and model‐free analysis in DCE‐MRI studies

“…In this study we implemented two commonly-applied kinetic models (5,12) to attempt to extract specific information regarding the characteristics of the tumor microvasculature. The model we applied is that introduced by Tofts and Kermode (5) and further developed by Tofts (12), which provides estimates of the volume transfer coefficient, K trans (min Ϫ1 ), between the blood pool and the extracellular extravascular space (EES). It also provides estimates of the volume occupied by the EES, v e (no units), as a fraction of total tissue volume.…”