Brain Hypoxia Influences Long Term Cardiac Function assessed by 4DUS-Derived Cardiac Strain After Mild TBI

Abstract

Background: Retrospective studies suggest that mild traumatic brain injury (mTBI) in pediatric patients may lead to an increased risk of stroke and cardiac arrhythmias. Notwithstanding, the long-term effect of mTBI on cardiovascular function is still underexplored. In this study, we combined a high-frequency four-dimensional ultrasound (4DUS) technique and photoacoustic imaging to assess long-term cardiac functionality after mTBI in juvenile mice. Methods: Juvenile mice were randomly assigned to mTBI (n = 12) and sham (n = 12) groups 17 days postnatal. The cranium was left intact for the impact of the left somatosensory cortical area. A single impact was performed under light anesthesia using an impactor with a 6 m/s impact speed. Cerebral 3D photoacoustic imaging was used to measure the oxygen saturation (SO2) in the left somatosensory cortical area 4 hours after mTBI followed by 4DUS to image the left ventricle at days 8, 14, 26, 87, and 187 post-impact. Cardiac- and respiratory-gated cine-loops were spatiotemporally compiled into 4D datasets capturing a full cardiac cycle. Using a custom MATLAB Graphical User Interface (GUI), the left ventricular endocardial and epicardial borders were segmented across the entire cardiac cycle and were used to calculate left ventricular global and regional strains. Results: Longitudinal photoacoustic imaging revealed a significant decrease in cerebrovascular SO2 in the impacted left cortex of juvenile mTBI mice 4h post-injury as compared to age-matched sham animals (59.9 ± 9.2% vs 66.4 ± 5.3%, p < 0.05). Oxygen saturation returned to levels comparable to sham animals at 8 days. More than 3 months after mTBI, cardiac 4DUS strain analysis showed a decrease in longitudinal peak strain in the anterior and posterior myocardial regions in mTBI mice compared to sham (p < 0.05), suggesting a long-term adaptation of left ventricular function. Further, decreases in regional longitudinal strains and altered strain rates during diastole were associated with regional diastolic dysfunction in the mTBI group. In addition, correlations were found between lower cerebral SO2 levels at 4h post mTBI and lower posterior (R2 = 0.61; p < 0.001) or anterior (R2 = 0.52; p < 0.001) wall peak longitudinal strain evaluated at day 187. Conclusion: 4DUS strain quantification and photoacoustic imaging are able to detect subtle cardiac and cerebral changes after mild TBI in a murine model. Experimental mTBI in juvenile mice induces long-term adaptation in cardiac function that correlates with initial cerebral SO2 levels.