Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for prediction of radiation-induced neurocognitive dysfunction

Abstract

Purpose: To determine whether early assessment of cerebral microvessel injury can predict late neurocognitive dysfunction after brain radiation therapy (RT).

Experimental design: Ten patients who underwent partial brain RT participated in a prospective dynamic contrast-enhanced magnetic resonance imaging (MRI) study. Dynamic contrast-enhanced MRI was acquired prior to, at weeks 3 and 6 during, and 1 and 6 months after RT. Neuropsychological tests were done pre-RT and at the post-RT MRI follow-ups. The correlations between early delayed changes in neurocognitive functions and early changes in vascular variables during RT were analyzed.

Results: No patients had tumor progression up to 6 months after RT. Vascular volumes and blood-brain barrier (BBB) permeability increased significantly in the high-dose regions during RT by 11% and 52% (P<0.05), respectively, followed by a decrease after RT. Changes in both vascular volume and BBB permeability correlated with the doses accumulated at the time of scans at weeks 3 and 6 during RT and 1 month after RT (P<0.03). Changes in verbal learning scores 6 months after RT were significantly correlated with changes in vascular volumes of left temporal (P<0.02) and frontal lobes (P<0.03), and changes in BBB permeability of left frontal lobes during RT (P<0.007). A similar correlation was found between recall scores and BBB permeability.

Conclusion: Our data suggest that the early changes in cerebral vasculature may predict delayed alterations in verbal learning and total recall, which are important components of neurocognitive function. Additional studies are required for validation of these findings.

Figure 1

The differences in the vascular volumes (Vp) and blood-brain barrier permeability (K^trans) in three dose intervals at three observation times compared to the baseline values. In the high dose region (> 40 Gy), the vascular volumes increased significantly at week 6 during the course of RT and then started decreasing after the completion of RT; while in the intermediate dose interval (20−40 Gy), the vessel volume increased slowly, reached the similar maximum value 1 month after the completion of RT, and then started decreasing. The changes in the blood-brain barrier permeability were significant in the high and intermediate dose regions at week 6 during the course of RT. 10 weeks: 1 month after the completion of RT; and 32 weeks: 6 months after the completion of RT.

Figure 2

Scatter plots of the changes in the vascular volumes (Vp, top) and blood-brain permeability (K^trans, bottom) versus doses received at the time of MRI studies. Left panels: week 3 during RT; Middle panels: week 6 during RT; Right panels: 1 month after the completion of RT (10 weeks from the start of RT). Solid lines represent linear regression lines.

Figure 3

The correlations between the changes in learning scores 6 months after RT and the changes in Vp of left frontal (left top) and temporal (right top) lobes at week 3 during RT, between the changes in learning scores 6 months after RT and the changes in K^trans of left frontal lobes at week3 during RT (left bottom), and between the changes in total recall scores 6 months after RT and the changes in K^trans of left temporal lobes at week 3 during RT (right bottom).