Felix W Wehrli1, Yongxia Zhou1, Zachary B Rodgers1, and Michael C Langham1
1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States
Synopsis
Smoking is well known to cause vasoconstriction as a
result of the formation of reactive oxygen species, which reduce nitric oxide
availability. Vasomotor reactivity can be measured in terms of the change in
cerebral blood flow in response to a hypercapnic challenge. Here we measured
the change in superior sagittal sinus flow at 2-second temporal resolution during
breath-hold (a predominantly hypercapnic stimulus) and computed a breath-hold
index (BHI) as the slope of the flow velocity-time curve in 20 nonsmokers and
13 chronic smokers. The data suggest reduced BHI in the smoking group (0.252±0.097
vs. 0.306±0.098 cm/s2, p<0.07) indicative of dysregulation of
vascular reactivity.Background and Motivation
Endothelial cells produce a variety of vasodilators, chief
among which is nitric oxide (NO), but also vasoconstrictors such as endothelin.
Reactive oxygen species (ROS) such as the superoxide radical anion (O2
-.),
occurring in cigarette smoke, are well known to dysregulate the normal
vasodilatory response
of the endothelium to increased demand for blood flow (1).
Endothelial dysfunction is believed to
be the earliest initiator of atherogenesis followed by the well-known sequelae
leading to neurovascular and heart disease (2).
Methods
Vascular reactivity was assessed in a subset of
patients (20 nonsmokers and 13 smokers) drawn from a larger study designed to
evaluate the effect of smoking and age on a variety of vascular measures in 169
subjects without symptomatic cardiovascular disease conducted at 3T field
strength in (3).
Subjects underwent an apnea paradigm consisting of a single 30-second normal
breathing baseline period followed by three repeated blocks of a 30-second
breath-holds, each separated by a 90-second normal breathing recovery period.
Blood flow velocity in the superior sagittal sinus (SSS) during the 6-min apnea
paradigm was quantified using a non-gated phase-contrast BRISK acquisition
scheme
with BRISK k-space sampling and view sharing (4)
achieving a temporal resolution of 2s. Sequence parameters: flip angle 15°,
bandwidth 347 Hz/pixel, TE/TR 6.5/31.25 ms, VENC 50 cm/s, FOV 220×220×5 mm
3,
resolution 1.15×1.15×5 mm
3. The data were evaluated in terms of the
slope of the velocity versus time curve, expressed as cm/s
2,
referred to as BHI slope.
Results, Discussion and Conclusions
Preliminary data of SSS blood flow velocity
time-course during an apneic challenge are shown in Figs. 1 and 2. Sample SSS
velocity images are displayed in Fig. 1 while Fig. 2 shows velocity versus time
plots for three successive BH cycles. Fig. 3 shows box plots comparing smokers
to nonsmokers in terms of the BHI slope. The data suggest reduced neurovascular
reactivity in smokers (0.252±0.097 vs. 0.306±0.098 cm/s
2, p=0.07). The
effect does not appear to be driven by age since when stratified according to
age, nonsmokers were indistinguishable from their smoking peers. Due to the
large intra-group spread the method may be more appropriate to follow subjects
during treatment. Nevertheless, the results suggest that the BHI may be a
useful supplementary test to evaluate subjects
with presymptomatic vascular disease and may be equally applicable to other
subject groups at risk of developing neurovascular disease such as those with
hypertension or hypercholesterolemia. Lastly, a BHI scan can easily be appended
to a standard MRI protocol as the data take only minutes to acquire. The
current pilot study is not adequately powered and corroboration of the results
in larger subject groups is indicated.
Acknowledgements
NIH K25HL111422
NIH R01HL122754
NIH R01HL109545
References
1. Messner et al. ATBV 2014;34(3):509-515.
2. Celemajer et al. J Am Coll Cardiol 1994;24(6):1468-1474.
3. Langham
et al. J Cardiov Magn Reson 2015;17(1):19.
4. Rodgers
et al. JCBFM 2013; 33(10):1514.