Contrast-enhanced ultrasound for assessing tissue perfusion and predicting functional recovery following acute traumatic spinal injury: translation from rat model to humans

Traumatic spinal cord injury (tSCI) leads to an immediate loss of neurological function, with its recovery being difficult to predict in the acute phase. Here, we developed a contrast-enhanced ultrasound (CEUS) imaging biomarker to quantify the intraspinal vascular disruption after tSCI. In rodent thoracic tSCI, CEUS revealed a perfusion area deficit (PAD) which increased with injury severity (p = 0.001). The PAD size significantly correlated with hindlimb locomotor function at 8 weeks post injury (R2 = 0.82, p < 0.001). Additionally, we calculated a spinal perfusion index (SPI) comparing the amount of perfused tissue at the injury center to that in injury periphery. Our experiments demonstrated that SPI decreased in more severe injuries and correlated significantly with hindlimb locomotor function at 8 weeks post injury (R2 = 0.83, p < 0.001). Subsequently, we demonstrated the feasibility of intraoperative CEUS imaging in 20 patients with acute tSCI. A hyper-perfusion pattern was commonly seen in cervical motor-incomplete tSCI, while necrosis penumbra pattern was associated with motor-complete cervical or thoracic tSCI. We measured both PAD and SPI and detected statistically significant differences between motor-complete and motor-incomplete patients. In our patient cohort, SPI exhibited a strong predictive capacity for functional recovery at 6 months (R2 = 0.79, p < .001) compared to PAD. In conclusion, our study suggests that an intraoperative CEUS-derived biomarker holds promise for predicting injury severity and chronic functional outcome after tSCI. Larger clinical studies are needed to better assess the reliability of the proposed CEUS-derived biomarker and its prognostic capacity. One Sentence SummaryThis paper introduces a novel biomarker utilizing contrast-enhanced ultrasound in humans and rats that accurately predicts injury severity after traumatic spinal cord injury based on tissue perfusion.