Microvascular disruption after traumatic spinal cord injury (SCI) causes bleeding within the spinal cord, known as intraparenchymal hemorrhage (IPH). IPH observed on early imaging is associated with poor neurological outcomes, and blood and its degradation products can further damage neural tissue, highlighting the importance of understanding factors influencing IPH progression. During the first week after injury, acute SCI patients are prone to 1) hypotension, which reduces spinal cord blood flow and may worsen secondary ischemic injury, and 2) thromboembolic disease, as their immobility makes them vulnerable to developing blood clots. The therapeutic approaches include augmenting mean arterial pressure (MAP) with vasopressors to restore perfusion and providing venous thromboembolism (VTE) prophylaxis with anticoagulants to prevent blood clot formation. While beneficial, each intervention may also inadvertently worsen IPH. This thesis examines IPH progression using a multimodal imaging approach, including intraoperative high-frequency ultrasound (US) imaging, ex vivo 7 Tesla (7T) magnetic resonance imaging (MRI), and histology. In Chapter 1, I provided an overview of traumatic SCI, IPH, and standard clinical management. In Chapter 2, I reviewed methods for detecting and quantifying IPH using US, MRI, and histology. In Chapter 3, I developed and evaluated a semi-automated pipeline to segment and quantify IPH progression using intraoperative high-frequency US in a porcine model. In Chapter 4, I developed and evaluated a semi-automated pipeline to segment and quantify IPH progression using ex vivo 7T MRI in a porcine model. In Chapter 5, I investigated the effects of MAP augmentation and VTE prophylaxis on IPH progression in a porcine model. In Chapter 6, I compared IPH progression between pigs and humans, identifying similarities and differences in the temporal dynamics of blood products after traumatic SCI. In Chapter 7, I summarized the main findings. In summary, these studies provide new insights into IPH progression in pigs and humans and how commonly used treatments (vasopressors for MAP augmentation and anticoagulants for VTE prophylaxis) might influence this important pathophysiologic process. In doing so, I have established semi-automated pipelines for IPH segmentation and quantification across US, MRI, and histology, providing validated tools for standardized IPH assessment in pre-clinical SCI research.
Aysha Allard Brown (Thu,) studied this question.