Quantitative measurement of blood-brain barrier permeability in human using dynamic contrast-enhanced MRI with fast T₁ mapping

Breakdown of the blood-brain barrier (BBB), occurring in many neurological diseases, has been difficult to measure noninvasively in humans. Dynamic contrast-enhanced magnetic resonance imaging measures BBB permeability. However, important technical challenges remain and normative data from healthy humans is lacking. We report the implementation of a method for measuring BBB permeability, originally developed in animals, to estimate BBB permeability in both healthy subjects and patients with white matter pathology. Fast T₁ mapping was used to measure the leakage of contrast agent Gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) from plasma into brain. A quarter of the standard Gd-DTPA dose for dynamic contrast-enhanced magnetic resonance imaging was found to give both sufficient contrast-to-noise
and high T₁ sensitivity. The Patlak graphical approach was used to calculate the permeability from changes in 1/T₁. Permeability constants were compared with cerebrospinal fluid albumin index. The upper limit of the 95% confidence interval for white matter BBB permeability for normal subjects was 3 x 10^-4 L/g min. MRI measurements correlated strongly with levels of cerebrospinal fluid albumin in those subjects undergoing lumbar puncture. Dynamic contrast-enhanced magnetic resonance imaging with low dose Gd-DTPA and fast T₁ imaging is a sensitive method to measure subtle differences in BBB permeability in humans and may have advantages over techniques based purely on the
measurement of pixel contrast changes. Magn Reson Med 65:1036–1042, 2011.VC 2010Wiley-Liss, Inc.