White matter has impaired resting oxygen delivery in sickle cell patients

Chai, Yaqiong; Bush, Adam; Coloigner, Julie; Nederveen, Aart J.; Tamrazi, Benita; Vu, Chau; Choi, Soyoung; Coates, Thomas D.; Leporé, Natasha; Wood, John C.

doi:10.1002/ajh.25423

Cited by 33 publications

(64 citation statements)

References 51 publications

(64 reference statements)

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“…48 Shorter MTT in anemic subjects was apparent in the gray matter as well as regions of normally perfused white matter; however, these subjects also displayed abnormally slower contrast dynamics in the deep white matter at the end of the perfusion branches. These borderzone regions coincided with typical watershed areas of flow limitation and peak oxygen extraction 13,49 and were consistent with previous studies that showed reduced flow reserve in areas vulnerable to silent strokes, 50 suggesting a connection between hemodynamic impairment and the development of strokes in anemic patients.…”

Section: Controlsupporting

confidence: 90%

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Quantitative perfusion mapping with induced transient hypoxia using BOLD MRI

Chai

Coloigner

et al. 2020

Magnetic Resonance in Med

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Purpose: Gadolinium-based dynamic susceptibility contrast (DSC) is commonly used to characterize blood flow in patients with stroke and brain tumors. Unfortunately, gadolinium contrast administration has been associated with adverse reactions and long-term accumulation in tissues. In this work, we propose an alternative deoxygenation-based DSC (dDSC) method that uses a transient hypoxia gas paradigm to deliver a bolus of paramagnetic deoxygenated hemoglobin to the cerebral vasculature for perfusion imaging. Methods: Through traditional DSC tracer kinetic modeling, the MR signal change induced by this hypoxic bolus can be used to generate regional perfusion maps of cerebral blood flow, cerebral blood volume, and mean transit time. This gas paradigm and blood-oxygen-level-dependent (BOLD)-MRI were performed concurrently on a cohort of 66 healthy and chronically anemic subjects (age 23.5 ± 9.7, female 64%). Results: Our results showed reasonable global and regional agreement between dDSC and other flow techniques, such as phase contrast and arterial spin labeling. Conclusion: In this proof-of-concept study, we demonstrated the feasibility of using transient hypoxia to generate a contrast bolus that mimics the effect of gadolinium and yields reasonable perfusion estimates. Looking forward, optimization of the hypoxia boluses and measurement of the arterial-input function is necessary to improve the accuracy of dDSC. Additionally, a cross-validation study of dDSC and DSC in brain tumor and ischemic stroke subjects is warranted to evaluate the clinical diagnostic utility of this approach.

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Section: Controlsupporting

confidence: 90%

“…A comprehensive discussion of these parameters has been detailed in our previous publications. 13,29 The BOLD images were preprocessed with FSL using a standard spatial functional pipeline. Images were first slicetime corrected, realigned to remove physiological motion and then co-registered to the MNI template space.…”

Section: Image Pre-processingmentioning

confidence: 99%

Quantitative perfusion mapping with induced transient hypoxia using BOLD MRI

Chai

Coloigner

et al. 2020

Magnetic Resonance in Med

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“…The brain compensates by elevating baseline cerebral blood flow, in attempt to maintain normal global oxygen delivery at rest . However, while oxygen delivery to gray matter appears to be preserved, deep white matter structures are relatively hypoperfused and ischemic . In addition, elevated baseline cerebral blood flow consequently lowers cerebral vascular reserve, and leaves patients more susceptible to ischemic brain injury under metabolic stress .…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, in a longitudinal study of SCD patients, low baseline hemoglobin level was the only independent risk factor for silent cerebral infarcts . Despite compensatory increases in cerebral blood flow, deep white matter structures remain hypoxic in SCD patients, proportionally to the severity of anemia . Taken together this suggests that the severity of chronic anemia could be the strongest predictor of hypoxic‐ischemia white matter injury in SCD patients.…”

Section: Introductionmentioning

confidence: 99%

Anemia predicts lower white matter volume and cognitive performance in sickle and non‐sickle cell anemia syndrome

et al. 2019

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Severe chronic anemia is an independent predictor of overt stroke, white matter damage, and cognitive dysfunction in the elderly. Severe anemia also predisposes to white matter strokes in young children, independent of the anemia subtype. We previously demonstrated symmetrically decreased white matter (WM) volumes in patients with sickle cell disease (SCD). In the current study, we investigated whether patients with non-sickle anemia also have lower WM volumes and cognitive dysfunction. Magnetic Resonance Imaging was performed on 52 clinically asymptomatic SCD patients (age = 21.4 ± 7.7; F = 27, M = 25; hemoglobin = 9.6 ± 1.6 g/dL), 26 non-sickle anemic patients (age = 23.9 ± 7.9; F = 14, M = 12; hemoglobin = 10.8 ± 2.5 g/dL) and 40 control subjects (age = 27.7 ± 11.3; F = 28, M = 12; hemoglobin = 13.4 ± 1.3 g/dL). Voxel-wise changes in WM brain volumes were compared to hemoglobin levels to identify brain regions that are vulnerable to anemia. White matter volume was diffusely lower in deep, watershed areas proportionally to anemia severity. After controlling for age, sex, and hemoglobin level, brain volumes were independent of disease. WM volume loss was associated with lower Full Scale Intelligence Quotient (FSIQ; P = .0048; r 2 = .18) and an abnormal burden of silent cerebral infarctions (P = .029) in males, but not in females.Hemoglobin count and cognitive measures were similar between subjects with and without white-matter hyperintensities. The spatial distribution of volume loss suggests chronic hypoxic cerebrovascular injury, despite compensatory hyperemia. Neurocognitive consequences of WM volume changes and silent cerebral infarctionwere strongly sexually dimorphic. Understanding the possible neurological consequences of chronic anemia may help inform our current clinical practices.

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“…This lack of a significant OEF increase in response to anemia in normocapnia contrasts to that observed in sickle cell children Guilliams et al 2018) and infants (Morris et al 2018) where OEF increases in concert with CBF in response to anemia, and may be the result of an increased CMRO 2 (Bush et al 2014), which is predicted by the model but not shown. Further, in regions of the brain such as the white matter where perfusion is poor (Mandell et al 2008), D O 2 is decreased Chai et al 2019).…”

Section: Cbf In Anaemia and Hypocapniamentioning

confidence: 99%

A mathematical model of cerebral blood flow control in anaemia and hypoxia

Duffin

Hare

Fisher

2020

The Journal of Physiology

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Key points The control of cerebral blood flow in hypoxia, anaemia and hypocapnia is reviewed with an emphasis on the links between cerebral blood flow and possible stimuli. A mathematical model is developed to examine the changes in the partial pressure of oxygen in brain tissue associated with changes in cerebral blood flow regulation produced by carbon dioxide, anaemia and hypoxia. The model demonstrates that hypoxia, anaemia and hypocapnia, alone or in combination, produce varying degrees of cerebral hypoxia, an effect exacerbated when blood flow regulation is impaired. The suitability of brain hypoxia as a common regulator of cerebral blood flow in hypoxia and anaemia was explored, although we failed to find support for this hypothesis. Rather, cerebral blood flow appears to be related to arterial oxygen concentration in both anaemia and hypoxia. Abstract A mathematical model is developed to examine the changes in the partial pressure of oxygen in brain tissue associated with changes in cerebral blood flow regulation produced by carbon dioxide, anaemia and hypoxia. The model simulation assesses the physiological plausibility of some currently hypothesized cerebral blood flow control mechanisms in hypoxia and anaemia, and also examines the impact of anaemia and hypoxia on brain hypoxia. In addition, carbon dioxide is examined for its impact on brain hypoxia in the context of concomitant changes associated with anaemia and hypoxia. The model calculations are based on a single compartment of brain tissue with constant metabolism and perfusion pressure, as well as previously developed equations describing oxygen and carbon dioxide carriage in blood. Experimental data are used to develop the control equations for cerebral blood flow regulation. The interactive model illustrates that there are clear interactions of anaemia, hypoxia and carbon dioxide in the determination of cerebral blood flow and brain tissue oxygen tension. In both anaemia and hypoxia, cerebral blood flow increases to maintain oxygen delivery, with brain hypoxia increasing when cerebral blood flow control mechanisms are impaired. Hypocapnia superimposes its effects, increasing brain hypoxia. Hypoxia, anaemia and hypocapnia, alone or in combination, produce varying degrees of cerebral hypoxia, and this effect is exacerbated when blood flow regulation is degraded by conditions that negatively impact cerebrovascular control. Differences in brain hypoxia in anaemia and hypoxia suggest that brain oxygen tension is not a plausible sensor for cerebral blood flow control.

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White matter has impaired resting oxygen delivery in sickle cell patients

Cited by 33 publications

References 51 publications

Quantitative perfusion mapping with induced transient hypoxia using BOLD MRI

Quantitative perfusion mapping with induced transient hypoxia using BOLD MRI

Anemia predicts lower white matter volume and cognitive performance in sickle and non‐sickle cell anemia syndrome

A mathematical model of cerebral blood flow control in anaemia and hypoxia

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