Correlating Quantitative MRI-based Apparent Diffusion Coefficient Metrics with 24-month Neurodevelopmental Outcomes in Neonates from the HEAL Trial

Abstract

Background Multiple qualitative scoring systems have been created to capture the imaging severity of hypoxic ischemic brain injury. Purpose To evaluate quantitative volumes of acute brain injury at MRI in neonates with hypoxic ischemic brain injury and correlate these findings with 24-month neurodevelopmental outcomes and qualitative brain injury scoring by radiologists. Materials and Methods In this secondary analysis, brain diffusion-weighted MRI data from neonates in the High-dose Erythropoietin for Asphyxia and Encephalopathy trial, which recruited participants between January 2017 and October 2019, were analyzed. Volume of acute brain injury, defined as brain with apparent diffusion coefficient (ADC) less than 800 × 10^-6 mm²/sec, was automatically computed across the whole brain and within the thalami and white matter. Outcomes of death and neurodevelopmental impairment (NDI) were recorded at 24-month follow-up. Associations between the presence and volume (in milliliters) of acute brain injury with 24-month outcomes were evaluated using multiple logistic regression. The correlation between quantitative acute brain injury volume and qualitative MRI scores was assessed using the Kendall tau-b test. Results A total of 416 neonates had available MRI data (mean gestational age, 39.1 weeks ± 1.4 [SD]; 235 male) and 113 (27%) showed evidence of acute brain injury at MRI. Of the 387 participants with 24-month follow-up data, 185 (48%) died or had any NDI. Volume of acute injury greater than 1 mL (odds ratio [OR], 13.9 [95% CI: 5.93, 32.45]; P < .001) and presence of any acute injury in the brain (OR, 4.5 [95% CI: 2.6, 7.8]; P < .001) were associated with increased odds of death or any NDI. Quantitative whole-brain acute injury volume was strongly associated with radiologists' qualitative scoring of diffusion-weighted images (Kendall tau-b = 0.56; P < .001). Conclusion Automated quantitative volume of brain injury is associated with death, moderate to severe NDI, and cerebral palsy in neonates with hypoxic ischemic encephalopathy and correlated well with qualitative MRI scoring of acute brain injury. Clinical trial registration no. NCT02811263 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Huisman in this issue.

Graphical abstract

Figure 1:

Flowchart of participant exclusion criteria from enrollment to 24-month follow-up. DTI = diffusion tensor imaging, HEAL = High-dose Erythropoietin for Asphyxia and Encephalopathy.

Figure 2:

Representative examples of MRI-based diffusion-weighted images (left) and corresponding apparent diffusion coefficient (ADC) maps (right) without (top row) and with (bottom row) automated acute injury segmentation color overlays. (A) Axial diffusion-weighted and ADC images at the level of the thalamus demonstrate a basal ganglia–thalamic pattern of injury in a participant with basal ganglia–thalamic predominant pattern of acute injury (arrowheads). This male participant was born via emergent Cesarian section at 40+6 weeks after uterine rupture with Apgar scores of 1, 3, and 4 at 1, 5, and 10 minutes of life, respectively. The participant was initially treated for pulmonary hypertension, systemic hypotension, and disseminated intravascular coagulation. Subsequent electroencephalography consistently showed low voltage burst suppression, and the participant died on day of life 5 after transition to comfort care. (B) Axial diffusion-weighted and ADC images at the level of the centrum semiovale show a watershed pattern of injury in a participant with cortical and subcortical predominate watershed pattern of acute injury (arrowheads). This male participant was born at 40+0 weeks gestation via unassisted vaginal delivery and was noted to have a tight nuchal umbilical cord. Apgar scores were 2, 3, and 3 at 1, 5, and 10 minutes of life, respectively. The participant was treated for systemic hypotension and subclinical seizures with good response and was subsequently discharged home off all antiseizure medication.

Figure 3:

Acute injury frequency map for the two primary outcome groups displayed as colorized heat maps. Frequency maps for participants who did not die or have neurodevelopmental impairment (NDI) at follow-up are shown in the top two rows. The top row shows superior, lateral, and anterior projection views of volume rendered injury maps, with cool colors indicating relatively low injury frequency. The second row shows coronal, axial, and sagittal sections of the population-averaged neonatal brain atlas with colorized heat map overlays using the same color scale. The location of the displayed sections is indicated on the volume rendered projections with a dotted line. Brain regions where there was no acute injury in this outcome group are displayed as clear to show the underlying brain atlas anatomy (gray scale). Rows 3 and 4 are identical to rows 1 and 2 except that they represent frequency of acute injury in participants who died or had NDI at follow-up. Warm colors indicate a relatively higher frequency of acute injury and correspond to typical locations of acute brain injury described in the setting of hypoxic ischemic encephalopathy.