Cerebral hemodynamics and oxygenation in adult patients with sickle cell disease after stem cell transplantation.

Sickle cell disease (SCD) is characterized by chronic hemolytic anemia associated with impaired cerebral hemodynamics and oxygen metabolism. Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for patients with SCD. Whereas normalization of hemoglobin levels and hemolysis markers has been reported after HSCT, its effects on cerebral perfusion and oxygenation in adult SCD patients remain largely unexplored. This study investigated the effects of HSCT on cerebral blood flow (CBF), oxygen delivery, cerebrovascular reserve (CVR), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2 ) in 17 adult SCD patients (mean age: 25.0 ± 8.0, 6 females) before and after HSCT and 10 healthy ethnicity-matched controls (mean age: 28.0 ± 8.8, 6 females) using MRI. For the CVR assessment, perfusion scans were performed before and after acetazolamide as a vasodilatory stimulus. Following HSCT, gray and white matter (GM and WM) CBF decreased (p < .01), while GM and WM CVR increased (p < .01) compared with the baseline measures. OEF and CMRO2 also increased towards levels in healthy controls (p < .01). The normalization of cerebral perfusion and oxygen metabolism corresponded with a significant increase in hemoglobin levels and decreases in reticulocytes, total bilirubin, and LDH as markers of hemolysis (p < .01). This study shows that HSCT results in the normalization of cerebral perfusion and oxygen metabolism, even in adult patients with SCD. Future follow-up MRI scans will determine whether the observed normalization of cerebral hemodynamics and oxygen metabolism prevents new silent cerebral infarcts.

Assessment of functional shunting in patients with sickle cell disease.

Silent cerebral infarcts (SCI) are common in patients with sickle cell disease (SCD) and are thought to be caused by a mismatch between oxygen delivery and consumption. Functional cerebrovascular shunting is defined as reduced oxygen offloading due to the rapid transit of blood through the capillaries caused by increased flow and has been suggested as a potential mechanism underlying reduced oxygenation and SCI. We investigated the venous arterial spin labeling signal (VS) in the sagittal sinus as a proxy biomarker of cerebral functional shunting, and its association with hemodynamic imaging and hematological laboratory parameters. We included 28 children and 38 adults with SCD, and ten healthy racematched adult controls. VS, cerebral blood flow (CBF), velocity in the brain feeding arteries, oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) were measured before and after acetazolamide administration. VS was higher in patients with SCD compared to controls (P<0.01) and was increased after acetazolamide administration in all groups (P<0.01). VS was primarily predicted by CBF (P<0.01), but CBF-corrected VS was also associated with decreased CMRO2 (P<0.01). Additionally, higher disease severity defined by low hemoglobin and increased hemolysis was associated with higher CBF-corrected VS. Finally, CMRO2 was negatively correlated with fetal hemoglobin, and positively correlated with lactate dehydrogenase, which could be explained by changes in oxygen affinity. These findings provide evidence for cerebral functional shunting and encourage future studies investigating the potential link to aberrant capillary exchange in SCD.

Impairment of Cerebrovascular Hemodynamics in Patients With Severe and Milder Forms of Sickle Cell Disease.

In patients with sickle cell disease (SCD), cerebral blood flow (CBF) is elevated to counteract anemia and maintain oxygen supply to the brain. This may exhaust the vasodilating capacity of the vessels, possibly increasing the risk of silent cerebral infarctions (SCI). To further investigate cerebrovascular hemodynamics in SCD patients, we assessed CBF, arterial transit time (ATT), cerebrovascular reactivity of CBF and ATT (CVR CBF and CVR ATT ) and oxygen delivery in patients with different forms of SCD and matched healthy controls. We analyzed data of 52 patients with severe SCD (HbSS and HbSß0-thal), 20 patients with mild SCD (HbSC and HbSß+-thal) and 10 healthy matched controls (HbAA and HbAS). Time-encoded arterial spin labeling (ASL) scans were performed before and after a vasodilatory challenge using acetazolamide (ACZ). To identify predictors of CBF and ATT after vasodilation, regression analyses were performed. Oxygen delivery was calculated and associated with hemoglobin and fetal hemoglobin (HbF) levels. At baseline, severe SCD patients showed significantly higher CBF and lower ATT compared to both the mild SCD patients and healthy controls. As CBF postACZ was linearly related to CBF preACZ , CVR CBF decreased with disease severity. CVR ATT was also significantly affected in severe SCD patients compared to mild SCD patients and healthy controls. Considering all groups, women showed higher CBF postACZ than men (p < 0.01) independent of baseline CBF. Subsequently, post ACZ oxygen delivery was also higher in women (p < 0.05). Baseline, but not post ACZ, GM oxygen delivery increased with HbF levels. Our data showed that baseline CBF and ATT and CVR CBF and CVR ATT are most affected in severe SCD patients and to a lesser extent in patients with milder forms of SCD compared to healthy controls. Cerebrovascular vasoreactivity was mainly determined by baseline CBF, sex and HbF levels. The higher vascular reactivity observed in women could be related to their lower SCI prevalence, which remains an area of future work. Beneficial effects of HbF on oxygen delivery reflect changes in oxygen dissociation affinity from hemoglobin and were limited to baseline conditions suggesting that high HbF levels do not protect the brain upon a hemodynamic challenge, despite its positive effect on hemolysis.

Detection of small traumatic hemorrhages using a computer-generated average human brain CT.

Computed tomography is a standard diagnostic imaging technique for patients with traumatic brain injury (TBI). A limitation is the poor-to-moderate sensitivity for small traumatic hemorrhages. A pilot study using an automatic method to detect hemorrhages [Formula: see text] in diameter in patients with TBI is presented. We have created an average image from 30 normal noncontrast CT scans that were automatically aligned using deformable image registration as implemented in Elastix software. Subsequently, the average image was aligned to the scans of TBI patients, and the hemorrhages were detected by a voxelwise subtraction of the average image from the CT scans of nine TBI patients. An experienced neuroradiologist and a radiologist in training assessed the presence of hemorrhages in the final images and determined the false positives and false negatives. The 9 CT scans contained 67 small haemorrhages, of which 97% was correctly detected by our system. The neuroradiologist detected three false positives, and the radiologist in training found two false positives. For one patient, our method showed a hemorrhagic contusion that was originally missed. Comparing individual CT scans with a computed average may assist the physicians in detecting small traumatic hemorrhages in patients with TBI.