Abstract

One of the most devastating complications of SCD is cerebral infarction. Cerebral infarcts are present on MRI scans in one third of SCD patients at the age of 18 years, although most of them are not accompanied by overt, focal neurological deficits. These so-called silent infarcts appear to be associated with diminished neurocognitive functioning and an increased risk of new infarcts. The risk of infarction is commonly attributed to the hyperemia that is associated with anemia and reduces the cerebral vascular reserve. In patients with anemia, adequate oxygenation of the brain tissue is presumably preserved by vasodilatation of the cerebral vasculature. In this hyperemic state there is limited reserve for further vasodilatation to assure adequate oxygen supply to the brain if the arterial pressure falls or metabolic demands increase. The lack of reserve capacity and ensuing ischemia is thought to predispose to cerebral infarction. The regional cerebral blood flow (rCBF) can be measured non-invasively by continuous arterial spin labeling (CASL) MRI. Proximal to entry in the brain, protons in the arterial blood are labeled using a radiofrequency pulse and quantified in terms of tissue perfusion on distal images in the brain. We performed a study to evaluate whether CASL MRI could detect differences in rCBF when these regions appear unaffected on conventional 3T MRI. The purpose of this study was to examine rCBF in children with SCD and compare it to rCBF in healthy children. Neurologically normal patients with sickle cell disease (HbSS or HbS-β0-thalassemia) and normal flow on Transcranial Doppler Ultrasonography (TCD) and healthy children (HbAA, matched for ethnicity and age) underwent 3T MRI examination in a stable clinical situation between August 2006 and June 2007. Conventional MRI and MRA images were assessed by a standardized evaluation protocol by two independent observers (MW and CM), blinded to the clinical data. Cerebral infarcts, leukoareosis and vasculopathy were scored. From CASL MRI the rCBF was calculated for 6 vascular territories (left and right anterior, middle and posterior cerebral artery, respectively ACA, MCA and PCA). Left-right asymmetry in rCBF for the vascular territories within each patient was evaluated by calculating differences in flow between both hemispheres. Asymmetry was defined as > 11.7 ml/100g/min between the two hemispheres. Mean differences between patients and controls and 95% confidence intervals were calculated. The Chi-square test was performed to test the hypothesis that left-right asymmetry was equally distributed among the patients and controls. We enrolled 24 SCD patients (mean age 13.4 yr, SD 3.0) and 12 controls (mean age 13.4 yr, SD 3.5). The rCBF was of similar magnitude in SCD patients and controls in the frontal, middle and posterior territories (Table 1). A left-right asymmetry of rCBF in one or more vascular territories was present in the majority of SCD patients (58%), whereas this was absent in all controls. The difference in proportions of patients and controls with left-right asymmetry was statistically significant for the MCA and PCA territory (Chi-square test respectively p=0.005 and p=0.037). In contrast to previous studies we found no difference in CBF between patients and controls. We did observe an asymmetry in rCBF in the majority of patients with SCD that was not present in healthy controls.

Table 1. rCBF (ml/100g/min) values of patients and healthy controls.

Patients n=24Healthy controls n=12Mean difference95% CI
TerritoriesMeanSDMeanSD
ACA 73.2 17.4 71.5 14.4 −1.7 (−13.6–10.1) 
MCA 77.1 19.9 76.1 16.4 −1.0 (−14.5–12.5) 
PCA 89.6 16.4 84.5 16.6 −5.1 (−17.0–6.7) 
Right hemisphere 77.6 19.2 76.3 15.3 −1.3 (−14.3–11.5) 
Left hemisphere 77.5 17.7 76.6 16.1 −0.9 (−13.3–11.4) 
Total 77.6 17.4 76.4 15.6 −1.2 (−13.4–11.0) 
Patients n=24Healthy controls n=12Mean difference95% CI
TerritoriesMeanSDMeanSD
ACA 73.2 17.4 71.5 14.4 −1.7 (−13.6–10.1) 
MCA 77.1 19.9 76.1 16.4 −1.0 (−14.5–12.5) 
PCA 89.6 16.4 84.5 16.6 −5.1 (−17.0–6.7) 
Right hemisphere 77.6 19.2 76.3 15.3 −1.3 (−14.3–11.5) 
Left hemisphere 77.5 17.7 76.6 16.1 −0.9 (−13.3–11.4) 
Total 77.6 17.4 76.4 15.6 −1.2 (−13.4–11.0) 

Disclosures: No relevant conflicts of interest to declare.

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