Cerebrovascular resistance responses to CO2 improve after revascularization surgery
Larissa McKetton1, Olivia Sobczyk2, Julien Poublanc1, Kevin Sam3, Adrian P. Crawley1, Lakshmikumar Venkat Raghavan4, James Duffin4,5, Joseph A. Fisher2,4,5, and David J. Mikulis1,4,5

1Division of Neuroradiology, Joint Department of Medical Imaging, University Health Network, Toronto, ON, Canada, 2Institute of Medical Science, University of Toronto, Toronto, ON, Canada, 3The Russell H. Morgan Department of Radiology & Radiological Science, The John Hopkins University School of Medicine, Baltimore, MD, United States, 4Department of Anaesthesia and Pain Management, University Health Network, Toronto, ON, Canada, 5Department of Physiology, University of Toronto, Toronto, ON, Canada


The cerebral hemodynamics of patients undergoing revascularization surgery for intracranial steno-occlusive disease (IC-SOD) were assessed by deriving an estimate of their cerebrovascular resistance response to CO2 from their BOLD response to CO2. Significant improvements were found in the sigmoid parameters describing their resistance responses.


To assess changes in cerebrovascular resistance responses to CO2 in patients before and after revascularization surgery. Anatomical maps of resistance response sigmoid parameters were calculated from BOLD responses to a CO2 ramp stimulus (hypocapnia to hypercapnia) using a model of vascular interactions. This novel measurement of cerebrovascular hemodynamics based on resistance may provide an improved objective metric to assess the efficacy of revascularization surgery.


Cerebrovascular reactivity (CVR) is the change in cerebral blood flow (CBF) in response to increases in the arterial partial pressure of CO2 (PaCO2), and is used to assess cerebral hemodynamic impairment. In a healthy brain, the association between CBF and PaCO2 is sigmoidal in shape, whereas patients with intracranial steno-occlusive disease (IC-SOD) typically show regions where CBF decreases in response to CO2. This paradoxical response is known as the vascular steal phenomenon, where blood flow is redistributed from regions of exhausted vasodilatory reserve to those with intact vasodilatory reserve able to decrease their resistance1.

Previous studies show that surgical revascularization can reverse cortical thinning in areas of steal 2, improve CVR in ipsilateral and contralateral hemispheres 3-4, and improve cognitive function.5-7 However, CVR measures only the linear response slope, and so we sought details of how the vascular resistance response is affected after revascularization surgery. To answer this question, we used a model of the interactions between two parallel vascular beds whose resistances changed sigmoidally with CO2. Unlike flow responses, resistance responses are unconfounded by the cerebrovascular network flow interactions that influence the shape of the BOLD-CO2 response and CVR.


We used a ramp CO2 stimulus to survey the full extent of blood flow responses including nonlinearities. 11 patients were recruited (2 were removed due to unusable data). Of this total, 6 had a unilateral extracranial-intracranial (EC-IC) bypass, 1 a bilateral EC-IC bypass, and 1 patient an encephaloduroarteriosynangiosis (EDAS) revascularization surgery). All were scanned on a 3-Tesla GE system MRI scanner using an eight-channel phased array head coil at Toronto Western Hospital. The ramp CO2 stimulus sequence was programmed into a computer controlled gas blender (RespirActTM) that ran a prospective gas-targeting algorithm 8, which controlled the CO2 stimulus such that PETCO2 was equivalent to PaCO2.9-10

Statistical z-map analysis on voxels 2 standard deviations (SD) below the reference atlases for resistance sigmoid parameters and ramp CVR in both gray matter (GM) and white matter (WM) were assessed for pre- and post-conditions.


A paired-t-test revealed no significant changes in resting PETCO2 values after surgery, p = 0.44, although a trend towards 39 mmHg was observed (Figure 1). Ramp CVR improved in GM after surgery (p < 0.001) (Figure 2.1a), but not in WM (Figure 2.1b). Resting resistance reserve, the decrease in resistance from resting PETCO2 to full vasodilation improved in GM (p<0.001) (Figure 2.2a) and in WM (p<0.05) (Figure 2.2b). Resting resistance sensitivity, the slope of the resistance sigmoid CO2 response at resting PETCO2, improved in GM (p<0.05) (Figure 2.3a), but not in WM (Figure 2.3b). There was no change in resistance sigmoid range in both GM and WM (Figure 2.4a/b) after surgery. Resistance sigmoid midpoints, the PETCO2 at the sigmoid inflexion point where slope (sensitivity) is maximum, showed improvement, changing towards the reference resistance midpoint (39 mm Hg) in both GM and WM after surgery (p<0.05) (Figure 2.5a/b).

Discussion and Conclusion:

This study is the first to compare the application of a novel measure of cerebral hemodynamics based on sigmoidal vascular resistance profiles. The advantage of the resistance model is that it is not influenced by non-linear responses commonly caused by the interaction of vascular beds during a global CO2 stimulus. This is evident in the improvement in white matter resistance post surgery compared to the conventional flow based CVR analysis as seen in Figure 1b. and 2b. We found significant improvements in resting resistance reserve for GM and WM, a metric that may be the best identifier of pathophysiology since it shows regions that have exhausted their vasodilatory reserve and are unable to respond to vasodilatory demands.

Resting resistance sensitivity significantly improved in GM after surgery, indicating an increase in the vasculature’s ability to regulate CBF in response to vasodilatory demands. Resistance sigmoid midpoints significantly improved after surgery in both GM and WM; changing towards the midpoint PetCO2 of the healthy reference sigmoid midpoint. Differences in midpoint from the control atlas for the pre-op maps may indicate an adaptation of resistance regulation to accommodate chronic underperfusion and acidosis (higher midpoint) or chronic over-perfusion and alkalosis (lower midpoint). In summary, our findings show that revascularization surgery in IC-SOD patients results in significant improvements in cerebral resistance hemodynamics on the first post-op assessment.


We acknowledge Abby Skanda with her assistance in patient recruitment and Eugen Hlasny with his assistance in MRI scanning.


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Resting pCO2 values pre- and post revascularization surgery (Ntotal = 11). There were no significant differences between resting PETCO2 values after surgery, p = 0.44, although a trend was observed towards ~39 mmHg

Volumes of regions 2 standard deviations (SD) below the control atlas after revascularization surgery in 1a) ramp CVR gray matter (GM) 1b) white matter (WM); 2a) resting resistance reserve GM, 2b) WM; 3a) resting resistance sensitivity GM, 3b) WM; 4a) Resistance sigmoid range GM, 4b) WM, and 5a) midpoint GM, and 5b) WM. Significant differences are reported as *p<0.05, **p<0.01.

Ramp CVR and resistance sigmoid parameter z-maps in a representative patient (F, 36) pre and post right EC-IC bypass revascularization surgery. 3(A) ramp CVR z-maps, 3(B) resting resistance reserve z-maps, 3(C) resting resistance sensitivity z-maps, 3(D) resistance sigmoid midpoint z-maps, (E) resistance sigmoid range z-maps in pre and post conditions. The z-map colour scale denotes areas of interest that are 2 SD above or below the control CVR and resistance atlases.

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)