Neurologic decompression sickness (DCS) of the spinal cord is a diving-related injury resulting in acute and chronic sensory and motor impairments. Spinal DCS results when nitrogen bubbles form in the spinal cord vasculature and tissue in response to a rapid decrease in ambient pressure, which initiates a variety of pathological processes. Pathological correlates of spinal DCS include hemorrhage, axonal loss, myelin degeneration and inflammation [1
The preferential involvement of spinal cord white matter remains to be fully understood, but likely involves direct damage due to autochthonous, or in situ
, bubble formation. Nitrogen is highly soluble in the lipid-rich myelinated fibers of the spinal cord white matter, resulting in greater bubble formation in this region [2
]. Consequently, the myelin sheath incurs global structural damage following DCS [3
], including separation of myelin sheath layers [4
Currently, diagnosis of spinal DCS is primarily made clinically. T2-weighted magnetic resonance imaging (MRI) has been used in suspected spinal DCS patients and has identified microhemorrhage or edema in the spinal cord [5
]. However, many DCS patients suffer significant neurologic deficits despite normal T2 MRI scans, highlighting the inadequate sensitivity of currently used MRI techniques for diagnosis of spinal DCS [6
]. Improved imaging tools are needed to better detect the primary pathologies of spinal DCS and for pre-clinical development of treatment strategies.
Diffusion tensor MRI (DTI) is an advanced MR imaging technique, which may be ideally suited for investigation of spinal DCS. DTI quantifies the direction and magnitude of the diffusion of water within tissue to infer microstructural properties [7
]. The DTI metric of fractional anisotropy (FA) has been widely used in clinical and preclinical studies to report abnormalities in myelination and axonal integrity in the brain and spinal cord [9
]. In contrast, the DTI metric mean diffusivity (MD) is very sensitive to cytotoxic edema and vascular changes that can occur following stroke [11
]. Because both white matter damage and vascular compromise accompany spinal DCS, DTI is a promising tool for preclinical investigation of strategies to prevent or treat spinal DCS.
The primary objective of the present study was to identify and describe potential DTI markers of DCS-related spinal cord damage in a sheep model of hyperbaric exposure. Additionally, DTI was used to investigate the effect of variable lengths of oxygen prebreathing (O2
PB). The O2
PB intervention was designed as an alternative to lengthy staged decompression from large depths in emergency situations (e.g.
, disabled submarine) [12
] and has been shown to be effective for reducing incidence and severity of DCS [14
We hypothesized that spinal DCS would manifest as reductions in the DTI parameter fractional anisotropy (FA) corresponding to altered myelination or axonal damage. Furthermore, it was expected that O2PB would result in less spinal cord DTI abnormalities and improved clinical outcome.