Imaging of Perfusion, Angiogenesis, and Tissue Elasticity after Stroke

Abstract

Blood flow interruption in a cerebral artery causes brain ischemia and induces dramatic changes of perfusion and metabolism in the corresponding territory. We performed in parallel positron emission tomography (PET) with [(15)O]H(2)O, single photon emission computed tomography (SPECT) with [(99m)Tc]hexamethylpropylene-amino-oxime ([(99m)Tc]HMPAO) and ultrasonic ultrafast shear wave imaging (SWI) during, immediately after, and 1, 2, 4, and 7 days after middle cerebral artery occlusion (MCAO) in rats. Positron emission tomography and SPECT showed initial hypoperfusion followed by recovery at immediate reperfusion, hypoperfusion at day 1, and hyperperfusion at days 4 to 7. Hyperperfusion interested the whole brain, including nonischemic areas. Immunohistochemical analysis indicated active angiogenesis at days 2 to 7, strongly suggestive that hyperperfusion was supported by an increase in microvessel density in both brain hemispheres after ischemia. The SWI detected elastic changes of cerebral tissue in the ischemic area as early as day 1 after MCAO appearing as a softening of cerebral tissue whose local internal elasticity decreased continuously from day 1 to 7. Taken together, these results suggest that hyperperfusion after cerebral ischemia is due to formation of neovessels, and indicate that brain softening is an early and continuous process. The SWI is a promising novel imaging method for monitoring the evolution of cerebral ischemia over time in animals.

Evidence of Changes in Brain Tissue Stiffness After Ischemic Stroke Derived From Ultrasound‐Based Elastography

“…The decrease in ipsilateral elasticity reported here is also consistent with the work of Rousseaux and Steinling, 16 who found mean cerebral blood flow values in stroke patients to be generally lower than those of control participants in the ipsilateral hemisphere. Finally, this observation is also consistent with very recently published work on the elasticity of rat brains after stroke 17 …”

Modulation of the peri‐infarct neurogliovascular function by delayed COX‐1 inhibition

“…In a rat transient occlusion model of stroke, perilesional hyperperfusion is observed 2–4 days following ischemia . In a 2‐hour intraluminal middle cerebral artery occlusion (MCAO) model of focal ischemia, the 7‐day perilesional perfusion is double that of sham‐operated rats, in excellent agreement with the present finding. Further, in a rat 60‐minute transient MCAO model, Wegener et al identified three outcome patterns.…”

A blinded randomized assessment of laser Doppler flowmetry efficacy in standardizing outcome from intraluminal filament MCAO in the rat

“…Variability in infarct volume or functional outcome attributable to these concerns could decrease reliability of this model. There are methods for confirmation of ischemia during intraluminal MCAO including positron emission tomography (Martin et al, 2012), magnetic resonance imaging (Bihel et al, 2010), laser speckle imaging (Akamatsu et al, 2012), hydrogen clearance (Laing et al, 1993), and fluorometric measurement of mitochondrial NADH (Livnat et al, 2010). While these monitors have important roles in certain experimental paradigms, LDF has been advocated because the LDF system is compact, easy to use, and does not require complex surgery or radionuclide use.…”