PF742 CEREBRAL OXYGEN METABOLISM MEASUREMENTS WITH MRI IN ADULTS WITH SICKLE CELL DISEASE
Authors: Vaclavu L. , Petersen E. , Mutsaerts H. , Petr J. , Majoie C. , Wood J. , VanBavel E. , Nederveen A. , Biemond B. 
Published: June 2019

Background:

MRI studies have demonstrated a high prevalence of silent cerebral infarcts (SCI) in both children and adults with sickle cell disease (SCD). SCI are associated with cognitive impairment and lesion progression in adults with SCD. Disrupted oxygen transport can contribute to cerebral ischemic lesions, despite the compensatory elevation in cerebral blood flow (CBF) in SCD. Investigating the cerebral metabolic rate of oxygen (CMRO2) may therefore give insight into the hemodynamic etiology of SCI in SCD patients. We hypothesized that CMRO2 is reduced in adult patients with SCD as a result of chronic anemia and that vasodilation can improve CMRO2 by generating an increase in blood and oxygen flow.

Aims:

The purpose of this study was to measure CBF and OEF to compute CMRO2 and to measure the response to vasodilation with acetazolamide.

Methods:

We included adults with SCD (HbSS or HbSb0‐thalassaemia), and age‐, sex‐, and race‐matched controls. Exclusion criteria were contraindications to MRI and acetazolamide, and a clinical history of a cerebrovascular event or neurologic disease affecting cerebral autoregulation.

The MRI protocol comprised fluid‐attenuated inversion recovery (FLAIR) for anatomy and lesions, T2‐prepared tissue relaxation with inversion recovery (T2‐TRIR) for oxygenation and T1 of blood, and pseudo continuous arterial spin labelling (pCASL) for cerebral blood flow. Paired tests were used to assess statistical significance of changes from baseline to post‐acetazolamide conditions. P < .05 was considered significant. Variables were summarized by means and standard deviations.

Results:

Hb was lower in patients compared to controls (8.8 ± 1.4 vs 13.7 ± 1.3 g/dL, P < .001). Oxygen delivery was similar in patients compared to controls (371 ± 70 vs 368 ± 39 μmol O2/100 g/min, P = .832), due to compensatory elevated CBF in patients versus controls (73 ± 16 vs 46 ± 4 mL/100 g/min, P < .001). OEF was lower in patients compared to controls (27.1 ± 4.4 vs 35.3 ± 3.6 %, P = .001). SCD patients had lower CMRO2 compared to controls (99.7 ± 24.2 vs 126.6 ± 18.9 μmol O2/100 g/min, P = .003) (Figure 2). Cerebrovascular reserve was lower in patients versus controls (43.1 ± 12.5 vs 67.0 ± 20.0%, P = .003). After acetazolamide, CMRO2 did not change significantly in the healthy controls (P = .844), but declined in SCD patients (P = .036), showing that the ACZ challenge was indeed isometabolic in controls but not in patients. Finally, we found that increased CBF after ACZ was accompanied by a drop in OEF in patients with SCD (P < .001) as well as in controls (P = .003).

Summary/Conclusion:

Our findings support our hypothesis that SCD patients have reduced CMRO2. This indicates that in this chronic condition, CMRO2, and therefore likely also neuronal function, have adapted to chronic low oxygen availability. Heterogeneous flow distribution could be the reason for the reduced CMRO2 we observed in patients with SCD, whereby oxygen shunted to the venous side without delivering oxygen to the brain tissue, and this was exacerbated by acetazolamide. We conclude that CMRO2 does not adjust quickly to transient changes in oxygen availability at the microvascular level despite the increase in CBF

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