Transcranial contrast-enhanced ultrasound in the rat brain reveals substantial hyperperfusion acutely post-stroke

Abstract

Direct and real-time assessment of cerebral hemodynamics is key to improving our understanding of cerebral blood flow regulation in health and disease states such as stroke. While a number of sophisticated imaging platforms enable assessment of cerebral perfusion, most are limited either spatially or temporally. Here, we applied transcranial contrast-enhanced ultrasound (CEU) to measure cerebral perfusion in real-time through the intact rat skull before, during and after ischemic stroke, induced by intraluminal filament middle cerebral artery occlusion (MCAO). We demonstrate expected decreases in cortical and striatal blood volume, flow velocity and perfusion during MCAO. After filament retraction, blood volume and perfusion increased two-fold above baseline, indicative of acute hyperperfusion. Adjacent brain regions to the ischemic area and the contralateral hemisphere had increased blood volume during MCAO. We assessed our data using wavelet analysis to demonstrate striking vasomotion changes in the ischemic and contralateral cortices during MCAO and reperfusion. In conclusion, we demonstrate the application of CEU for real-time assessment of cerebral hemodynamics and show that the ischemic regions exhibit striking hyperemia post-MCAO. Whether this post-stoke hyperperfusion is sustained long-term and contributes to stroke severity is not known.

The Role of Ultrasound as a Diagnostic and Therapeutic Tool in Experimental Animal Models of Stroke: A Review

“…In a 1999 study conducted on focal cerebral ischemia in rabbits, Els T et al demonstrated the usefulness of ultrasound for the continuous monitoring of CBF velocity to follow rapid changes in the dynamics of the ischemic process [ 11 ], thereby offering a tool for stroke control from early monitoring to therapy. These changes in CBF were studied using contrast-enhanced ultrasound (CEUS) [ 12 ], Doppler velocimetry [ 13 ], and functional ultrasound [ 14 ]. Ultrasound contrast agents are encapsulated microbubbles in suspension with great echogenicity that can enhance the echo signals [ 15 , 16 ]).…”

“…Premilovac D et al applied transcranial CEUS to rats with middle cerebral artery occlusion (MCAO) to measure cerebral perfusion after stroke in real-time. In this noninvasive manner, the authors observed a reduction in cerebral perfusion during ischemia and hyperperfusion during recanalization [ 12 ].…”

Improved reperfusion following alternative surgical approach for experimental stroke in mice

“…There are many studies showing that CBF in the contralateral hemisphere can be altered during MCAO 271678X20905493 3 and others). Given that the quantification of the ipsilateral CBF is a % of the contralateral, any changes in CBF in the contralateral hemisphere in response to MCAO or reperfusion could alter the reference point for this analysis.…”

“…Current approved treatment options are limited for acute ischemic stroke patients, involving either thrombolytic clot breakdown or physical clot removal. Recombinant tissue plasminogen activator (rtPA) is the only pharmacological treatment available with proven efficacy 3,4 , eligibility for this treatment is low and, due to a narrow therapeutic time window (<4.5 h), only ~1 5% of stroke patients are able to receive iv-rtPA treatment, with recanalisation success at less than 50% 5,6 . In addition to this, endovascular thrombectomy is increasingly being used in the treatment of large vessel occlusions, where the clot is removed from within the vessel allowing recanalisation, especially in patients who respond poorly to rtPA treatment 5 .…”

Improved reperfusion following alternative surgical approach for experimental stroke in mice

“…First developed by Koizumi et al 11 and later modified by Longa et al 12 , with numerous minor variations to the model since then. These two models are widely used in preclinical experimental stroke research largely due to their minimally invasive technique and ability to induce post-occlusion reperfusion 13 . However, although surgical procedures follow a defined protocol, lesion volumes have large standard deviations [14][15][16] .…”