Use of dynamic contrast-enhanced MRI to measure subtle blood-brain barrier abnormalities

Abstract

There is growing interest in investigating the role of subtle changes in blood-brain barrier (BBB) function in common neurological disorders and the possible use of imaging techniques to assess these abnormalities. Some studies have used dynamic contrast-enhanced MR imaging (DCE-MRI) and these have demonstrated much smaller signal changes than obtained from more traditional applications of the technique, such as in intracranial tumors and multiple sclerosis. In this work, preliminary results are presented from a DCE-MRI study of patients with mild stroke classified according to the extent of visible underlying white matter abnormalities. These data are used to estimate typical signal enhancement profiles in different tissue types and by degrees of white matter abnormality. The effect of scanner noise, drift and different intrinsic tissue properties on signal enhancement data is also investigated and the likely implications for interpreting the enhancement profiles are discussed. No significant differences in average signal enhancement or contrast agent concentration were observed between patients with different degrees of white matter abnormality, although there was a trend towards greater signal enhancement with more abnormal white matter. Furthermore, the results suggest that many of the factors considered introduce uncertainty of a similar magnitude to expected effect sizes, making it unclear whether differences in signal enhancement are truly reflective of an underlying BBB abnormality or due to an unrelated effect. As the ultimate aim is to achieve a reliable quantification of BBB function in subtle disorders, this study highlights the factors which may influence signal enhancement and suggests that further work is required to address the challenging problems of quantifying contrast agent concentration in healthy and diseased living human tissue and of establishing a suitable model to enable quantification of relevant physiological parameters. Meanwhile, it is essential that future studies use an appropriate control group to minimize these influences.

Fig. 1

Signal enhancement (A and B) and estimated contrast agent concentration (C and D) uptake profiles obtained from blood, CSF, cortical gray matter, deep gray matter and white matter ROIs in 60 stroke patients, 32 with low overall Fazekas ratings (<1.5) and 28 with high overall Fazekas ratings (≥1.5). (A) and (C) are scaled to illustrate the blood signal relative to the other tissues, while (B) and (D) illustrate the tissue signals only. It is clear that any analysis of contrast agent uptake profiles would depend significantly on whether signal enhancement or modeled contrast agent concentration data was used.

Fig. 2

Calculated percentage error in the concentration estimation, ɛ^rel (%), as a function of the concentration, C_t, plotted for different tissues (A); flip angles, α_b (B); post-contrast measurements, N (C); and number of baseline pre-contrast measurements, N_b (D).