Laser Speckle Contrast Imaging Characterizes Delayed Reperfusion After Transient Brachial Artery Occlusion in Patients with Sickle Cell Diseas

The pathophysiology of sickle cell disease (SCD) involves vascular complications such as stroke and pulmonary hypertension. Elevated pulmonary artery pressure estimated by cardiac ultrasound or measured by invasive right heart catheterization is associated with early mortality among patients with SCD. Peripheral vascular dysfunction has also been observed in SCD and may be easier to assess than pulmonary vascular resistance and therefore more suitable for epidemiologic or interventional studies of SCD. Three previous studies found no difference in the maximal blood flow (or percentage increase) stimulated by occlusion and reperfusion of the brachial artery, a conduit vessel, when measured by Doppler ultrasound at periodic intervals. However, a study using continuous laser Doppler measurements of cutaneous microvascular blood flow found that patients with SCD had prolonged time to maximal blood flow and prolonged time to return to baseline compared to healthy controls. In our study, we used two-dimensional laser speckle contrast imaging (LSCI) to assess the cutaneous microvascular blood flow response in adults with SCD after five minutes of brachial artery occlusion.

Nine subjects with sickle cell disease were enrolled and compared against nine healthy African-American control subjects matched for age, sex, ethnicity, and body mass index. Cutaneous blood flow was directly measured using LCSI at baseline, during and after a standard brachial artery occlusion-reperfusion maneuver (inflation of an occlusive pneumatic cuff for five minutes). This stimulates a transient increase in blood flow to levels above baseline during the reperfusion phase. Blood flow data were averaged over a defined region of interest on the medial aspect of the forearm. Microvascular blood flow responsiveness was calculated as the time to maximum (time elapsed from 50% of maximum to maximum blood flow) and the time to return to baseline (time elapsed from maximum to 50% of maximum blood flow). We performed measurements on each individual on two separate days, and compared the microvascular blood flow responses between the groups using two-way ANOVA with repeated measures.

We enrolled nine patients with sickle cell disease (age 35 ± 8.8, BMI 23 ± 3.9, 3 men/6 women) and nine healthy controls (age 35 ± 10.7 years, BMI 25 ± 3.2, 3 men/6 women). Baseline microvascular blood flow measured in arbitrary units (AU) was greater in patients with sickle cell disease compared to healthy controls (53.1 ± 9.2 AU vs 37.2 ± 4.4 AU, p < 0.0001) but maximal microvascular blood flow was similar (121.3 ± 29.3 AU vs 124.7 ± 26.6 AU, p = 0.58). Analysis of the time from half-maximum to maximum blood flow revealed that patients with sickle cell disease take longer to reach maximum blood flow (19.1 ± 11.6 s vs 11.8 ± 1.0 s, p = 0.03) and longer to decrease from maximum to half-maximum blood flow during the recovery period (43.5 ± 13.0 s vs 28.6 ± 10.4 s, p = 0.002).

Compared to healthy individuals, patients with SCD have greater baseline microvascular blood flow but similar maximal blood flow during reperfusion. However, patients with SCD differ significantly from healthy control subjects in the time required to reach maximal blood flow and the time required to return to baseline, both of which are prolonged in patients with SCD. This may reflect delayed or impaired endothelial responses to shear stress and/or greater viscosity of blood. Time to maximal blood flow might represent a useful physiological biomarker as a proxy for clinical severity of sickle cell anemia, and a potential surrogate marker in early phase clinical trials. This technique merits additional characterization and validation.

No relevant conflicts of interest to declare.