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. 2015 Nov;35(11):1746-56.
doi: 10.1038/jcbfm.2015.114. Epub 2015 Jul 1.

Measuring Cerebrovascular Reactivity: The Dynamic Response to a Step Hypercapnic Stimulus

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Free PMC article

Measuring Cerebrovascular Reactivity: The Dynamic Response to a Step Hypercapnic Stimulus

Julien Poublanc et al. J Cereb Blood Flow Metab. .
Free PMC article

Abstract

We define cerebral vascular reactivity (CVR) as the ratio of the change in blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) signal (S) to an increase in blood partial pressure of CO2 (PCO2): % Δ S/Δ PCO2 mm Hg. Our aim was to further characterize CVR into dynamic and static components and then study 46 healthy subjects collated into a reference atlas and 20 patients with unilateral carotid artery stenosis. We applied an abrupt boxcar change in PCO2 and monitored S. We convolved the PCO2 with a set of first-order exponential functions whose time constant τ was increased in 2-second intervals between 2 and 100 seconds. The τ corresponding to the best fit between S and the convolved PCO2 was used to score the speed of response. Additionally, the slope of the regression between S and the convolved PCO2 represents the steady-state CVR (ssCVR). We found that both prolongations of τ and reductions in ssCVR (compared with the reference atlas) were associated with the reductions in CVR on the side of the lesion. τ and ssCVR are respectively the dynamic and static components of measured CVR.

Conflict of interest statement

RespirAct is currently a noncommercial research tool assembled, and made available by Thornhill Research Inc. (TRI), a spin-off company from the University Health Network, to research institutions to enable CVR studies. JAF is the Chief Scientist and JD is the Senior Scientist at (TRI), and JP, OS, APC, DJM, and DMM have contributed to the development of RespirAct and have received payments from, or shares in, TRI.

Figures

Figure 1
Figure 1
Generation of steady-state cerebrovascular reactivity (ssCVR) and time constant (τ) maps from a standardized abrupt two-step stimulus. (A) (i) Target (dotted line) and actual (solid line) end-tidal partial pressure of CO2 (PETCO2). (ii) The set of first-order exponentials with τ ranging from 2 to 100 seconds used to convolve the actual PETCO2 to generate a set of convolved curves seen in (iii). (B and C) (i) Actual PETCO2 (solid black line) and blood oxygen level-dependent (BOLD) signal (green and red lines) from voxels X and Y, respectively, shown in (D). (ii) Set of curves resulting from the convolution of PETCO2. The highlighted line is that which has the best fit to the voxel BOLD signal shown in (i). (iii) The regression with the best fit between the convolved PETCO2 and the BOLD signal is shown. The difference in the pattern of the data results from the extent of distortion the convolution imposes on the PETCO2 input function. (D) The ssCVR map is generated from the slope of the line with the highest correlation coefficient as illustrated in the graphs in row (iii). The τ map is generated from the τ of the exponential used to generate the line with the highest correlation coefficient. The ssCVR and the τ values are color coded according to the color scales shown and mapped onto the corresponding voxels in the anatomic scan.
Figure 2
Figure 2
The relationship between cerebrovascular reactivity (CVR) and steady-state CVR (ssCVR). Data from the same patient as presented in Figures 1 and 5. CVR and ssCVR values are expressed in %S/mm Hg. (A) Plot of blood oxygen level-dependent (BOLD) signal versus convolved end-tidal partial pressure of CO2 (PETCO2) and line of best fit (green dots and line, same data as Figure 1); and the signal versus actual PETCO2 with its line of best fit (black dots and line), both from the same voxel with slow response. (B) Similar graph of signal versus convolved PETCO2 (red dots and line, same data as Figure 1) and signal versus actual PETCO2 (black dots and line). Note that when the time course of response is rapid, little convolution of PETCO2 is required and the CVR is close to ssCVR.
Figure 3
Figure 3
Atlas for cerebrovascular reactivity (CVR), steady-state CVR (ssCVR), and τ from 46 healthy subjects. In each view, the mean value for all corresponding voxels of the atlas was calculated and mapped onto the anatomic image of the standard space using the color scales shown (see Supplementary Table 1 for more detail characterization of the color scales). Areas containing major veins and venous sinuses register greater CVR values due to a reduction in deoxyhemoglobin, and possibly also in diameter, resulting from the reduced extraction fraction, and increased arterial blood volume, respectively, accompanying the hypercapnia-induced increased cerebral blood flow.
Figure 4
Figure 4
One slice of CVR, z-CVR and z-τ maps for patients number 01 to 10. Patients' characteristics are presented in Table 1.
Figure 5
Figure 5
One slice of CVR, z-CVR and z-τ maps for patients number 11 to 20. Patients' characteristics are presented in Table 1.
Figure 6
Figure 6
Cerebrovascular reactivity (CVR), steady-state CVR (ssCVR), τ, and respective z maps from a healthy patient. Top row: The CVR map reflects the net response of both the amplitude signal and its time course seen in isolated form in the ssCVR map and τ map, respectively. Bottom row: The z maps illustrate the extent and distribution of z values in a healthy subject. The yellow tinge to the z-τ map indicates briskly responding vasculature within the normal range.
Figure 7
Figure 7
Cerebrovascular reactivity (CVR), steady-state CVR (ssCVR), τ, and respective z maps from a patient (patient 20, Figure 5) showing moderate changes. Scans from a 46-year-old male with a history of hypertension, type II diabetes mellitus, and hypercholesterolemia who presented to hospital with transient symptoms of slurred speech, dizziness and memory loss, left facial droop, and left side weakness. Magnetic resonace angiography showed right carotid artery occlusion, and anatomic magnetic resonance imaging scans were normal. Top row: The CVR map shows steal in the cortical area. ssCVR maps show a smaller extent of changes, suggesting that the CVR changes strongly affected by changes in time of response. Bottom row: The z-CVR maps show that the reductions in amplitude of response are primarily in the right cortical territory. In the cortical gray matter, the z-τ map shows that the spatial extent of reduced rate of vascular response is much more extensive than the extend of the reduced reactivity in the z-CVR.
Figure 8
Figure 8
Cerebrovascular reactivity (CVR), steady-state CVR (ssCVR), τ, and respective z maps from a patient (patient 10, Figure 4) showing severe changes. Scans from a 58-year-old male with a history of treated hypertension and lymphoma who presented for investigation of a new onset of recurrent transient left sided weakness. There were no neurologic deficits on clinical examination. Imaging showed that the right internal carotid artery was occluded above the origin by a calcified plaque. The left system was free of disease. The anterior and posterior communicating arteries were patent. Top row: CVR and ssCVR maps are nearly identical indicating the predominance of reductions in CVR over reductions in τ. The τ map requires different interpretations regarding the severity of underlying pathology in the areas with positive response (red-green color scale) and those with negative response (blue color scale). This is discussed in greater detail in Results section. Bottom row: The z maps show that reduced CVR is mostly due to reduced amplitude of response. Note that the z-τ map shows only voxels with positive τ.

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