A quantitative MRI method for imaging blood-brain barrier leakage in experimental traumatic brain injury.

Wei Li,Justin Alexander Long,Qiang Shen,Lora Talley Watts,Timothy Q Duong,Yunxia Li,Zhao Jiang,Richard Keep

doi:10.1371/journal.pone.0114173

Abstract

Blood-brain barrier (BBB) disruption is common following traumatic brain injury (TBI). Dynamic contrast enhanced (DCE) MRI can longitudinally measure the transport coefficient Ktrans which reflects BBB permeability. Ktrans measurements however are not widely used in TBI research because it is generally considered to be noisy and possesses low spatial resolution. We improved spatiotemporal resolution and signal sensitivity of Ktrans MRI in rats by using a high-sensitivity surface transceiver coil. To overcome the signal drop off profile of the surface coil, a pre-scan module was used to map the flip angle (B1 field) and magnetization (M0) distributions. A series of T1-weighted gradient echo images were acquired and fitted to the extended Kety model with reversible or irreversible leakage, and the best model was selected using F-statistics. We applied this method to study the rat brain one hour following controlled cortical impact (mild to moderate TBI), and observed clear depiction of the BBB damage around the impact regions, which matched that outlined by Evans Blue extravasation. Unlike the relatively uniform T2 contrast showing cerebral edema, Ktrans shows a pronounced heterogeneous spatial profile in and around the impact regions, displaying a nonlinear relationship with T2. This improved Ktrans MRI method is also compatible with the use of high-sensitivity surface coil and the high-contrast two-coil arterial spin-labeling method for cerebral blood flow measurement, enabling more comprehensive investigation of the pathophysiology in TBI.

Highlights

The blood-brain barrier (BBB) plays a vital role in regulating the entry of bloodborne factors and circulating immune cells into the brain, hereby providing a highly stable biochemical environment for the normal functioning of neuronal cells
The T1 values were in the range of 1.5 to 2.1 s, with a mean of 1.8 s
Given this narrow range of T1 variation, the ratio of M200 ms/M64 ms was dominated by the flip angle variation and was not significantly affected by the T1 distribution (Fig. 1C)

Summary

Introduction

The blood-brain barrier (BBB) plays a vital role in regulating the entry of bloodborne factors and circulating immune cells into the brain, hereby providing a highly stable biochemical environment for the normal functioning of neuronal cells. The integrity of the BBB can be disrupted by the translational and rotational forces in traumatic brain injury (TBI). The resulting BBB damage can evolve dynamically in both time and space with studies showing multi-phasic characteristics [1]. There is a growing consensus that post-traumatic BBB disruption is one of the major factors that contribute to increased severity of TBI [3]. BBB has been suggested as a target for therapeutic invention, as a normally functioning BBB is important for restoring brain hemostasis, and provides an optimal environment for neuronal repair [2, 4]

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Discussion

Conclusion