Multi-site laser Doppler flowmetry for assessing collateral flow in experimental ischemic stroke: Validation of outcome prediction with acute MRI

Abstract

High variability in infarct size is common in experimental stroke models and affects statistical power and validity of neuroprotection trials. The aim of this study was to explore cerebral collateral flow as a stratification factor for the prediction of ischemic outcome. Transient intraluminal occlusion of the middle cerebral artery was induced for 90 min in 18 Wistar rats. Cerebral collateral flow was assessed intra-procedurally using multi-site laser Doppler flowmetry monitoring in both the lateral middle cerebral artery territory and the borderzone territory between middle cerebral artery and anterior cerebral artery. Multi-modal magnetic resonance imaging was used to assess acute ischemic lesion (diffusion-weighted imaging, DWI), acute perfusion deficit (time-to-peak, TTP), and final ischemic lesion at 24 h. Infarct volumes and typology at 24 h (large hemispheric versus basal ganglia infarcts) were predicted by both intra-ischemic collateral perfusion and acute DWI lesion volume. Collateral flow assessed by multi-site laser Doppler flowmetry correlated with the corresponding acute perfusion deficit using TTP maps. Multi-site laser Doppler flowmetry monitoring was able to predict ischemic outcome and perfusion deficit in good agreement with acute MRI. Our results support the additional value of cerebral collateral flow monitoring for outcome prediction in experimental ischemic stroke, especially when acute MRI facilities are not available.

Neuroprotection by remote ischemic conditioning in the setting of acute ischemic stroke: a preclinical two-centre study

“…a total of 210 operated rats to include 126 animals in the analysis. Of note, this is assuming that all the included animals have had an ischemia, which may be more difficult to ascertain without per-occlusion MRI (the conventional use of Laser Doppler Flowmetry having its own limitations) 51 . The additional advantage of using an MRI measurement of IS is that the brain may then potentially be used for evaluating mechanistic hypothesis rather than lesion size only, thus further refining the experiments.…”

Pharmacologically increasing collateral perfusion during acute stroke using a carboxyhemoglobin gas transfer agent (Sanguinate™) in spontaneously hypertensive rats

“…25,26 This method of measuring changes in collateral flow was validated using MRI and perfusion-diffusion mismatch to visualize the penumbra. 26 We confirmed that distinct hemodynamic territories were being measured by the 2 probes during filament occlusion (Figure 1), making us confident that the change in flow measured by probe 2 was indeed collateral flow between the ACA and MCA territories. Using this approach, we found that collateral flow in vehicle-treated SHR was minimal.…”

“…We used a validated method to measure changes in collateral flow by placing dual laser Doppler probes at two different sites over the core and peri-infarct vascular territories. 25,26 This method of measuring changes in collateral flow was validated using MRI and perfusion-diffusion mismatch to visualize the penumbra. 26 We confirmed that distinct hemodynamic territories were being measured by the 2 probes during filament occlusion (Figure 1), making us confident that the change in flow measured by probe 2 was indeed collateral flow between the ACA and MCA territories.…”

“…Laser Doppler flowmetry (Perimed Inc., Ardmore, PA, USA) was used to measure changes in CBF in both the MCA and collateral arterial territories using dual probes, as previously described. 25,26 This method of continuously and simultaneously measuring changes in MCA core and collateral flow during MCAO using multi-site dual laser Doppler probes has been used previously and validated using magnetic resonance imaging (MRI). 26 Briefly, needle probes were secured to the skull in holders above small burr holes at specified coordinates determined from a rat brain atlas: 27 Probe 1 was placed at +4 mm lateral of midline and −2 mm posterior of Bregma to measure changes in core MCA flow; Probe 2 was placed +3 mm lateral of midline suture and +2 mm anterior of Bregma to measure changes in flow just lateral to the border zone between the anterior cerebral artery (ACA) and MCA perfusion territories.…”

β-Caryophyllene/Hydroxypropyl-β-Cyclodextrin Inclusion Complex Improves Cognitive Deficits in Rats with Vascular Dementia through the Cannabinoid Receptor Type 2 -Mediated Pathway

“…A paramedian skin incision was performed, and the subcutaneous tissue and cranial fascia were dissected to reach the skull bone. The probe of the monitor was placed at the settled skull bone area to detect the CBF (Cuccione et al, 2016). CBF changes in the rats were monitored before 2VO operation at the following successive periods: 1, 6, 24 h, 3, 7, 14, and 28 days after operation, as well as 1, 7, 14, and 28 days after drug treatment.…”