Silent Infarcts, White Matter Integrity, and Oxygen Metabolic Stress in Young Adults With and Without Sickle Cell Trait

Abstract

Background: Individuals with sickle cell anemia have heightened risk of stroke and cognitive dysfunction. Given its high prevalence globally, whether sickle cell trait (SCT) is a risk factor for neurological injury has been of interest; however, data have been limited. We hypothesized that young, healthy adults with SCT would show normal cerebrovascular structure and hemodynamic function. Methods: As a case-control study, young adults with (N=25, cases) and without SCT (N=24, controls) underwent brain magnetic resonance imaging to quantify brain volume, microstructural integrity (fractional anisotropy), silent cerebral infarcts (SCI), intracranial stenosis, and aneurysms. Pseudocontinuous arterial spin labeling and asymmetric spin echo sequences measured cerebral blood flow and oxygen extraction fraction, respectively, from which cerebral metabolic oxygen demand was calculated. Imaging metrics were compared between SCT cases and controls. SCI volume was correlated with baseline characteristics. Results: Compared with controls, adults with SCT demonstrated similar normalized brain volumes (SCT 0.80 versus control 0.81, P =0.41), white matter fractional anisotropy (SCT 0.41 versus control 0.43, P =0.37), cerebral blood flow (SCT 62.04 versus control, 61.16 mL/min/100 g, P =0.67), oxygen extraction fraction (SCT 0.27 versus control 0.27, P =0.31), and cerebral metabolic oxygen demand (SCT 2.71 versus control 2.70 mL/min/100 g, P =0.96). One per cohort had an intracranial aneurysm. None had intracranial stenosis. The SCT cases and controls showed similar prevalence and volume of SCIs; however, in the subset of participants with SCIs, the SCT cases had greater SCI volume versus controls (0.29 versus 0.07 mL, P =0.008). Of baseline characteristics, creatinine was mildly elevated in the SCT cohort (0.9 versus 0.8 mg/dL, P =0.053) and correlated with SCI volume (ρ=0.49, P =0.032). In the SCT cohort, SCI distribution was similar to that of young adults with sickle cell anemia. Conclusions: Adults with SCT showed normal cerebrovascular structure and hemodynamic function. These findings suggest that healthy individuals with SCT are unlikely to be at increased risk for early or accelerated ischemic brain injury.

Management of the Sickle Cell Trait: An Opinion by Expert Panel Members

“…The risk of stroke in individuals with SCT does not seem to be higher than in subjects with homozygous adult Hb. Individuals with SCT and stroke, however, have worse 30-day mortality and outcomes than patients with normal adult Hb [65][66][67].…”

Cerebral hemodynamic changes after haploidentical hematopoietic stem cell transplant in adults with sickle cell disease

“…Prior work by another group has shown that individuals with sickle cell trait (HbAS) have similar CBF and OEF to individuals without sickle cell trait (HbAA); thus, our results are consistent. 46 …”

Vascular space occupancy asymmetric spin echo (VASO‐ASE) for non‐invasive quantification of cerebral oxygen extraction fraction

“…These images with different $$$ \tau $$$ were randomized in acquisition order to reduce systematic artifacts from scanner drift. Each scan was repeated once for a total of two acquisitions per participant for each of three ASE variants, ASE RF− : This method was designed to reproduce the sequence most frequently performed in neuroimaging applications of ASE 22–24 . A dual‐echo (TE 2 = 107 ms) multi‐slice ASE sequence without a 180‐degree refocusing pulse between the first and second readouts to increase overall susceptibility weighting (Figure 1A), ASE RF+ : A similar dual‐echo (TE 2 = 107 ms) multi‐slice ASE sequence with a 180‐degree refocusing pulse between the first and second readouts (Figure 1B), and VASO‐ASE: A single‐slice, single‐echo ASE sequence with TI = 1039 ms (Figure 1C).…”

“…Each scan was repeated once for a total of two acquisitions per participant for each of three ASE variants, i ASE RF− : This method was designed to reproduce the sequence most frequently performed in neuroimaging applications of ASE. [22][23][24] A dual-echo (TE 2 = 107 ms) multi-slice ASE sequence without a 180-degree refocusing pulse between the first and second readouts to increase overall susceptibility weighting (Figure 1A), ii ASE RF+ : A similar dual-echo (TE 2 = 107 ms) multi-slice ASE sequence with a 180-degree refocusing pulse between the first and second readouts (Figure 1B), and iii VASO-ASE: A single-slice, single-echo ASE sequence with TI = 1039 ms (Figure 1C). 18 Geometry and readout parameters were matched between variants, however, the VASO-ASE method included only a single echo owing to lower signal-to-noise ratio (SNR), given residual gray and white matter longitudinal magnetization of only 10%-20% of equilibrium magnetization at the blood water TI prescribed.…”