Ultrasound-Based Biomarker to Identify Tissue at Risk for Secondary Injury After Traumatic Spinal Cord Injury
Abstract
Rationale. Modern medicine typically utilizes biomarkers to enable the physician to prognosticate the extent of damage, guide and monitor therapeutic interventions. Patients, for example, who have sustained severe head trauma, receive an intracranial pressure monitor that provides real-time information regarding the condition of the contused brain and informs the physician regarding the success of intensive care interventions. This has led to a significantly improved functional outcome for patients with head trauma during the last decades. We hypothesize that a lack of comparable therapeutic progress for traumatic spinal cord injury is partially due to the lack of a biomarker that provides an objective and real-time "damage report" acutely after spinal cord injury. Ideally, a biomarker for traumatic spine injury should provide quantitative information regarding the areas within the spinal cord that are damaged, but also be able to identify potentially "rescue-able" tissue. We propose here to identify and quantify such a biomarker, collectable non-invasively during surgical decompression and stabilization that is routinely carried out within 24 hours of traumatic spinal cord injury. Our laboratory has demonstrated that swelling of the injured spinal cord increases intraspinal pressure and inhibits adequate blood perfusion acutely after injury. Importantly we have identified the tissue compartments that restrict the contused spinal cord and have developed a surgical technique to alleviate intraspinal pressure and partially restore the blood supply. This intervention has led to improved healing of the damaged spinal cord and promoted functional recovery in rats. In a quest to identify patients who might benefit from such an intervention, we have developed non-invasive, ultrafast contrast-enhanced ultrasound Doppler to detect damaged but potentially "rescue-able" spinal cord tissue based upon the perfusion of that tissue (our proposed biomarker), tested in rat spinal cord injury. Objectives. The current proposal aims to develop an early contrast-enhanced ultrasound biomarker that can predict injury severity and spontaneous functional recovery. This would greatly benefit the care of spinal cord injured patients, as it would help with prognostication, treatment decisions, and monitoring of neurological progress. We also plan to identify biomarker characteristics that determine injured spinal cord tissue in the periphery of the lesion that is initially viable but undergoes secondary injury mainly due to an inadequate blood supply. This tissue is the target for neuroprotective treatment strategies. While neuroprotective therapies have been promising in animal spinal cord research, to date, they have failed to improve functional outcome in clinical trials. We believe that a lack of early clinical biomarkers for identifying the tissue at risk for secondary injury has been a major obstacle for development and evaluation of neuroprotective treatment strategies. Once validated, we plan to translate this novel contrast-enhanced ultrasound-based biomarker via a large animal model into the clinic. A pig spinal cord injury model will be used to generate a clinical workflow for clinical translation of our biomarker. A limited pilot clinical observational trial will explore the feasibility of ultrafast contrast-enhanced ultrasound during routine surgery after spinal cord injury. Collecting this biomarker in a limited cohort of patients will provide us with valuable information regarding blood perfusion in the injury center and the penumbra with exceptional spatial resolution. This knowledge will feed back into revising and optimizing our current animal models of traumatic spinal cord injury. Ultimate applicability of our research – applications, benefits, and risks. We anticipate that the proposed research will yield an intraoperative biomarker collectable during routine decompression and stabilization surgery, which is typically pe
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810753
Entities
People
- Christoph Hofstetter
Organizations
- United States Army
- University of Washington