Abstract:Sickle cell anaemia is a monogenetic disorder with a high incidence of stroke. While stroke screening procedures exist for children with sickle cell anaemia, no accepted screening procedures exist for assessing stroke risk in adults. The purpose of this study is to use novel magnetic resonance imaging methods to evaluate physiological relationships between oxygen extraction fraction, cerebral blood flow, and clinical markers of cerebrovascular impairment in adults with sickle cell anaemia. The specific goal is… Show more
“…We demonstrate that more than 96% of the variability in blood R 2 can be described by a bilinear model using hematocrit and the squared oxygen extraction, even with hematocrit values into the teens. We further demonstrate that existing T 2b calibrations are highly inaccurate for hematocrits below 30% and should not be used in anemic patient populations . In fact, the commonly used bovine calibration has sizable bias even for patients with normal hematocrit values.…”
Purpose
We sought a human blood T2-oximetery calibration curve over the wide range of hematocrits commonly found in anemic patients applicable with T2 Relaxation Under Spin Tagging (TRUST).
Methods
Blood was drawn from 5 healthy control subjects. Ninety-three in vitro blood transverse relaxation (T2b) measurements were performed at 37° C over a broad range of hematocrits (10–55%) and oxygen saturations (14–100%) at 3T. In vivo TRUST was performed on 35 healthy African American control subjects and 11 patients with chronic anemia syndromes.
Results
1/T2 rose linearly with hematocrit (r2 = 0.96), for fully saturated blood. Upon desaturation, 1/T2 rose linearly with the square of the oxygen extraction, (1−Y)2, and the slope was linearly proportional to hematocrit (r2= 0.88). The resulting bilinear model between 1/T2, (1−Y)2 and hematocrit had a combined r2 of 0.96 and a coefficient of variation of 6.1%. Using the in-vivo data, the bilinear model had significantly lower bias and variability than existing calibrations, particularly for low hematocrits. In-vivo Bland Altman analysis demonstrated clinically relevant bias that was −6% (absolute saturation) for hematocrits near 30% and rose to +6% for hematocrits near 45%.
Conclusion
This work introduces a robust bilinear calibration model that should be used for MRI oximetry.
“…We demonstrate that more than 96% of the variability in blood R 2 can be described by a bilinear model using hematocrit and the squared oxygen extraction, even with hematocrit values into the teens. We further demonstrate that existing T 2b calibrations are highly inaccurate for hematocrits below 30% and should not be used in anemic patient populations . In fact, the commonly used bovine calibration has sizable bias even for patients with normal hematocrit values.…”
Purpose
We sought a human blood T2-oximetery calibration curve over the wide range of hematocrits commonly found in anemic patients applicable with T2 Relaxation Under Spin Tagging (TRUST).
Methods
Blood was drawn from 5 healthy control subjects. Ninety-three in vitro blood transverse relaxation (T2b) measurements were performed at 37° C over a broad range of hematocrits (10–55%) and oxygen saturations (14–100%) at 3T. In vivo TRUST was performed on 35 healthy African American control subjects and 11 patients with chronic anemia syndromes.
Results
1/T2 rose linearly with hematocrit (r2 = 0.96), for fully saturated blood. Upon desaturation, 1/T2 rose linearly with the square of the oxygen extraction, (1−Y)2, and the slope was linearly proportional to hematocrit (r2= 0.88). The resulting bilinear model between 1/T2, (1−Y)2 and hematocrit had a combined r2 of 0.96 and a coefficient of variation of 6.1%. Using the in-vivo data, the bilinear model had significantly lower bias and variability than existing calibrations, particularly for low hematocrits. In-vivo Bland Altman analysis demonstrated clinically relevant bias that was −6% (absolute saturation) for hematocrits near 30% and rose to +6% for hematocrits near 45%.
Conclusion
This work introduces a robust bilinear calibration model that should be used for MRI oximetry.
“…Recent demonstration that OEF is globally increased in SCD, likely reflects ongoing compensation for oxygen metabolic stress. 31 Furthermore, acute ischemic lesions have been identified on brain MRIs in children with SCD experiencing an acute decrease in oxygen delivery, such as in splenic sequestration or aplastic crisis. 32 …”
Background
Large-vessel vasculopathy (LVV) increases stroke risk in pediatric sickle cell disease (SCD) beyond the baseline elevated stroke risk in this vulnerable population. The mechanisms underlying this added risk and its unique impact on the developing brain are not established.
Methods
We analyzed magnetic resonance imaging (MRI) and angiography (MRA) scans of 66 children with SCD and infarcts by infarct density heatmaps and Jacobian determinants, a metric utilized to delineate focal volume change, to investigate if infarct location, volume, frequency, and cerebral atrophy differed among hemispheres with and without LVV.
Results
Infarct density heatmaps demonstrated infarct “hot spots” within the deep white matter internal borderzone region in both LVV and non-LVV hemispheres, but with greater infarct density and larger infarct volumes in LVV hemispheres (2.2 mL vs 0.25 mL, p <0.001). Additional scattered cortical infarcts in the internal carotid artery territory occurred in LVV hemispheres, but were rare in non-LVV hemispheres. Jacobian determinants revealed greater atrophy in gray and white matter of the parietal lobes of LVV compared to non-LVV hemispheres.
Conclusion
LVV in SCD appears to increase ischemic vulnerability in the borderzone region, as demonstrated by the increased frequency and extent of infarction within deep white matter, and increase risk of focal atrophy. Scattered infarctions across the LVV-affected hemispheres suggest additional stroke etiologies of vasculopathy (i.e. thrombo-embolism) in addition to chronic hypoxia-ischemia.
“…It should also be noted that many patients were in no to little pain during our experiments, meaning they were in a relatively stable condition. Recent studies have also shown that during resting state, SCD patients have increased cerebral blood flow compared to healthy controls to compensate for decreased oxygen levels so that oxygen delivery at rest is normal (Bush et al, 2016, Jordan et al, 2016). This suggests fMRI measurements should be normal during rest in SCD patients.Fig.…”
Sickle cell disease (SCD) is a red blood cell disorder that causes many complications including life-long pain. Treatment of pain remains challenging due to a poor understanding of the mechanisms and limitations to characterize and quantify pain. In the present study, we examined simultaneously recording functional MRI (fMRI) and electroencephalogram (EEG) to better understand neural connectivity as a consequence of chronic pain in SCD patients. We performed independent component analysis and seed-based connectivity on fMRI data. Spontaneous power and microstate analysis was performed on EEG-fMRI data. ICA analysis showed that patients lacked activity in the default mode network (DMN) and executive control network compared to controls. EEG-fMRI data revealed that the insula cortex's role in salience increases with age in patients. EEG microstate analysis showed patients had increased activity in pain processing regions. The cerebellum in patients showed a stronger connection to the periaqueductal gray matter (involved in pain inhibition), and negative connections to pain processing areas. These results suggest that patients have reduced activity of DMN and increased activity in pain processing regions during rest. The present findings suggest resting state connectivity differences between patients and controls can be used as novel biomarkers of SCD pain.
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