High-Definition Mapping of Multiscale Biomechanical Effects of Blast Trauma on Resilience of Fascicular Connective Tissue and Axonal Pathways in Optic Nerve Injury
Abstract
Combat Ocular Trauma (COT) is a significant cause of ocular morbidity in combat casualties. A retrospective non-comparative case series of traumatic registry data in OEF and OIF between 2002 through 2011 based on Joint Theatre Trauma Registry Data indicates that 10% of the 22,409 Service Member (SM) injuries were COT. The nature of these injuries is variable, and includes both open (intraocular foreign bodies, penetrating or perforating) and closed globe (anterior/posterior segment) trauma. Despite prophylactic measures, such as eye protection, COT can still result in ischemic, traumatic, or degenerative damage to the eye or optic nerve (ON). Vision restoration after traumatic ON (TON) injury remains a challenge with no clinical treatment. However, several teams from around the world have identified a number of molecular pathways and therapeutic approaches to enhance survival and regeneration of the ON in a broad swath of preclinical animal models. Background: This project will provide a new paradigm and research center to study blast on large mammals (sheep and man) involving controlled blast, tissue deformation high-speed, high-resolution video of tissue deformation, blood biomarker assays pre- and post blast, comprehensive magnetic resonance imaging (MRI), and histology methodology would be available for biomarker screening and research treatment interventions. It will provide new MRI-based diagnostic methods that can be used in government and civilian trauma centers. The scientific community to date has scarcely studied the effects of traumatic damage to the visual pathway in humans from the back of the eye, along the optic nerve, to the lateral geniculate nucleus (LGN) due to a lack of non-invasive diagnostic tools. This has impeded progress in accurate diagnosis, prognosis, and evaluation of potential therapeutic interventions. The development of new imaging technologies permits us to now address this gap in understanding. This project will work with sheep as well as human tissue (live and cadaver/harvested). It will also permit us to carry out mechanical stress tests of the tissue and conduct MR imaging of those tests. Specifically, the axonal tracts, bundles of axons (fascicles), myelin, vascular, and connective tissue will be examined and quantified. The sheep eyeball and visual system is similar enough to human that results will carry over to human work. Objectives: This work will address major gaps in the literature including the lack of (1) controlled blast to tissue deformation; (2) time course and sensitivity data on blood biomarkers, (3) insufficient quantification of the tissue components of the optic nerve, and, in particular, the importance of the role of connective tissue in injury and recovery; (3) MRI protocols for imaging the ON; and (4) understanding of the biomechanics of the ON in actual blast events. This project will provide MRI-based tools. These tools will be developed, validated, and calibrated in a rat TON injury. This will lay the groundwork for development of a body of data that will identify patients for whom this technology will directly apply and provide those patients with a device to treat ON degeneration along with the proper procedure to provide the treatment (as tested in an animal model). Patient Diagnostic Deliverables: This project will develop novel MR neuroimaging methods that would be usable at TRICARE hospitals to provide, for the first time, MR imaging to quantify the structural and functional integrity of the optic nerve non-invasively, localize pathology, and track treatment effectiveness in the tracts from the eyeball to the brain cortical areas (LGN and V1). We will develop a new blast screen facility and methodology to assay the sensitivity and specificity of biomarkers that could be deployed in the field. Transition Strategy: Transition to TRICARE sites for clinical research studies can be swift. The High Definition Fiber Tracking
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2211094
Entities
People
- Walter Schneider
Organizations
- United States Army
- University of Pittsburgh