Impact of therapeutic hypothermia on MRI diffusion changes in neonatal encephalopathy

Abstract

Objective: The objective of this work was to determine the impact of therapeutic hypothermia (TH) on the magnitude and time course of mean diffusivity (MD) changes following hypoxic-ischemic encephalopathy (HIE) in newborns.

Methods: Cerebral MRI scans of infants undergoing whole body TH for HIE from 2007 to 2010 were retrospectively reviewed. The data were analyzed identically to a control group of newborns with HIE previously published, prior to the development of TH. Anatomic injury was defined on T1- and T2-weighted ("late") MRI obtained after the fifth day of life. Since MD values vary regionally, the ratios of MD values for injured and normal tissue were calculated for areas of injury. Normal values were obtained from corresponding brain regions of 12 infants undergoing TH who had no injury on MRI studies.

Results: Twenty-three of 59 infants who underwent TH and MRI displayed cerebral injury on late MRI and were included in the study. MD ratios were decreased in all injured infants within the first 7 days of life. The return of MD to normal (pseudonormalization) occurred after the tenth day as compared to 6-8 days in the control group. Infants with severest injury demonstrated greater reduction in MD, but no difference in time to pseudonormalization.

Conclusion: TH slows the evolution of diffusion abnormalities on MRI following HIE in term infants.

Figures

Figure 1. Images from 4 patients scanned at 2 timepoints

The first presented with global injury (A, E, I, and M); the second presented with basal ganglia and posterior limb internal capsule (PLIC) injuries (B, F, J, and N); the third presented with cortical injury (C, G, K, and O); the fourth presented with border zone injury (D, H, L, and P). Diffusion imaging during the first 4 days after birth (A–D) shows respectively global (cortex and deep nuclear gray matter), bilateral PLIC, right temporal cortex, and right occipital border zone reductions in mean diffusivity (MD) with resolving reductions in MD seen in the delayed images obtained at 5–10 days after birth (I–L). The most persistent reduction in MD is seen in the global injury case (I). Corresponding T2-weighted images during the first 4 days after birth (E–H) showed mild lesions, more conspicuous in T2 images obtained after day 4 (M–P), demonstrating respectively a complete loss of cortical ribbon and an absence of differentiation between white and gray matter, absence of normal ventral thalami nuclei and PLIC signal (M), an absence of normal signal in the PLIC (N), a hypointensity surrounded by hyperintensity in right temporal lobe suggestive of hemorrhagic infarct (O), and subtle signal abnormality in the right occipital region (P). DWI = diffusion-weighted imaging.

Figure 2. Time course of the changes in the MD ratio over the 2 weeks following injury

In (A) the red circles are reproduced from figure 1 in reference 17 and represent the mean diffusivity (MD) ratio in normothermic patients. The black circles represent the MD ratio in patients treated by hypothermia. Superposed on the figure are γ-variate functions that approximate the time course of the data. The red line represents the time course for the normothermic cohort, and the black line approximates the time course for the hypothermic group. Notice the delay in time to pseudonormalization in the hypothermia cohort as compared to the normothermia group. In (B) only the hypothermic cohort is presented and is divided into 2 groups. The red circles represent the mild/moderate injured group, and the black circles represent the severely injured group. The red line is the γ-variate approximation for the mild/moderate injured group, and the black line represents the time course for the severely injured cohort. Notice that the MD ratio is lower on average in the severely injured group but there is no difference in the time of pseudonormalization in the 2 groups.

Figure 3. Correlation between global score (horizontal axis) and MD ratio (vertical axis)

A highly significant negative linear correlation is seen between the global score and the mean diffusivity (MD) ratio (Pearson correlation coefficient, r = −0.59).