Abstract
Progress in experimental stroke and translational medicine could be accelerated by high-resolution in vivo imaging of disease progression in the mouse cortex. Here, we introduce optical microscopic methods that monitor brain injury progression using intrinsic optical scattering properties of cortical tissue. A multi-parametric Optical Coherence Tomography (OCT) platform for longitudinal imaging of ischemic stroke in mice, through thinned-skull, reinforced cranial window surgical preparations, is described. In the acute stages, the spatiotemporal interplay between hemodynamics and cell viability, a key determinant of pathogenesis, was imaged. In acute stroke, microscopic biomarkers for eventual infarction, including capillary non-perfusion, cerebral blood flow deficiency, altered cellular scattering, and impaired autoregulation of cerebral blood flow, were quantified and correlated with histology. Additionally, longitudinal microscopy revealed remodeling and flow recovery after one week of chronic stroke. Intrinsic scattering properties serve as reporters of acute cellular and vascular injury and recovery in experimental stroke. Multi-parametric OCT represents a robust in vivo imaging platform to comprehensively investigate these properties.
Highlights
Experimental stroke research could benefit from new microscopic techniques to image disease during both its acute and chronic stages
Transient filament middle cerebral artery occlusion (fMCAO) Model A transient fMCAO model was used to study the relationship between hemodynamics and tissue scattering changes in acute stroke
Capillary perfusion was investigated with Optical Coherence Tomography (OCT) angiography at baseline, during fMCAO, and after filament withdrawal
Summary
Experimental stroke research could benefit from new microscopic techniques to image disease during both its acute and chronic stages. The penumbra is an area of brain tissue which is compromised but may possibly be salvaged. Unless perfusion is improved through thrombolysis, or cells are made more resistant to injury within hours, the penumbra dies as the infarct core expands over time. Diffusion and perfusion magnetic resonance imaging (MRI) [1] can assess tissue viability and flow concurrently, and help identify salvageable tissue at risk of infarction. Over days to weeks, neurovascular responses underlie a transition from acute injury to delayed repair as the brain initiates plasticity and remodeling.
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