Venous cerebral blood flow quantification and cognition in patients with sickle cell anemia

Stotesbury, Hanne; Hales, Patrick W.; Kölbel, Melanie; Hood, Anna; Kawadler, Jamie M.; Saunders, Dawn; Sahota, Sati; Rees, David C.; Wilkey, Olu; Layton, Mark; Pelidis, Maria; Inusa, Baba Pd; Howard, Jo; Chakravorty, Subarna; Clark, Chris A.; Kirkham, Fenella J.

doi:10.1177/0271678x211072391

Cited by 10 publications

(22 citation statements)

References 71 publications

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“…For the SAC study, patients were enrolled without regard to past sickle- or sleep-related morbidity or transfusion status. We have previously described average ASL parameters across grey matter, white matter, and high signal regions of the sagittal sinus in this sample of participants ( Stotesbury et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

“…As described in prior ASL studies in this cohort ( Stotesbury et al, 2022 ), raw single-TI and multi-TI ASL images were inspected, and excluded if there were major motion-related artifacts. As ASL model fitting requires a value representing the T1 relaxation rate of blood (T1 bl ), and T1 bl is dependent on hematocrit and oxygen saturation, estimated values were calculated based on measured (patients) or estimated (controls) hematocrit and measured oxygen saturation ( Hales et al, 2016 ).…”

Section: Methodsmentioning

confidence: 99%

“…It is relatively well established that global gray matter CBF is on average elevated in “steady-state” patients with SCA. Elevated CBF occurs in the context of reduced arterial oxygen content ( Bush et al, 2016 ; Stotesbury et al, 2022 ), indicative of a compensatory mechanism, which appears to maintain oxygen delivery when averaged globally ( Chai et al, 2019 ), but is associated with reduced cerebrovascular reserve ( Nur et al, 2009 ; Prohovnik et al, 2009 ; Kim et al, 2016 ; Kosinski et al, 2017 ; Václavů et al, 2019 ) and abnormal oxygen extraction fraction (OEF) ( Jordan et al, 2016 ; Bush A. M. et al, 2018 ; Fields et al, 2018 ; Vaclavu et al, 2018 ; Watchmaker et al, 2018 ). Although several studies also indicate that global white matter CBF is on average elevated ( Helton et al, 2009 ; Fields et al, 2015 , 2018 ; Stotesbury et al, 2022 ), the elevation appears to be lower than that observed for gray matter, and may therefore be insufficient to maintain oxygen delivery during acute illness (e.g., acute anemic events, acute chest syndrome), particularly in the deep watershed white matter, where vascular supply and CBF are already inherently low ( Stotesbury et al, 2018a , 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…In the multi-TI studies that have been conducted to date, patients with SCA have been shown to exhibit increased CBF and reduced bolus (i.e. blood) arrival times (BAT) across gray ( Juttukonda et al, 2017 ; Kawadler et al, 2018 ; Stotesbury et al, 2022 ) and white matter ( Stotesbury et al, 2022 ). Interestingly, across high-signal regions of the sagittal sinus, both CBF and BAT have been found to be increased ( Stotesbury et al, 2022 ), potentially reflecting increased resistance in the microcirculation secondary to abnormal erythrocyte rheology ( Stotesbury et al, 2022 ) and functional shunting ( Østergaard et al, 2016 ; Juttukonda et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…blood) arrival times (BAT) across gray ( Juttukonda et al, 2017 ; Kawadler et al, 2018 ; Stotesbury et al, 2022 ) and white matter ( Stotesbury et al, 2022 ). Interestingly, across high-signal regions of the sagittal sinus, both CBF and BAT have been found to be increased ( Stotesbury et al, 2022 ), potentially reflecting increased resistance in the microcirculation secondary to abnormal erythrocyte rheology ( Stotesbury et al, 2022 ) and functional shunting ( Østergaard et al, 2016 ; Juttukonda et al, 2019 ). Using multi-TI ASL, increased CBF has also been associated with worse cognitive performance across white matter and high-signal sagittal sinus regions, but not across gray matter ( Stotesbury et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Individual Watershed Areas in Sickle Cell Anemia: An Arterial Spin Labeling Study

et al. 2022

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Previous studies have pointed to a role for regional cerebral hemodynamic stress in neurological complications in patients with sickle cell anemia (SCA), with watershed regions identified as particularly at risk of ischemic tissue injury. Using single- and multi-inflow time (TI) arterial spin labeling sequences (ASL) in 94 patients with SCA and 42 controls, the present study sought to investigate cerebral blood flow (CBF) and bolus arrival times (BAT) across gray matter, white matter with early arrival times, and in individual watershed areas (iWSAs). In iWSAs, associations between hemodynamic parameters, lesion burden, white matter integrity, and general cognitive performance were also explored. In patients, increases in CBF and reductions in BAT were observed in association with reduced arterial oxygen content across gray matter and white matter with early arrival times using both sequences (all p < 0.001, d = −1.55–−2.21). Across iWSAs, there was a discrepancy between sequences, with estimates based on the single-TI sequence indicating higher CBF in association with reduced arterial oxygen content in SCA patients, and estimates based on the multi-TI sequence indicating no significant between-group differences or associations with arterial oxygen content. Lesion burden was similar between white matter with early arrival times and iWSAs in both patients and controls, and using both sequences, only trend-level associations between iWSA CBF and iWSA lesion burden were observed in patients. Further, using the multi-TI sequence in patients, increased iWSA CBF was associated with reduced iWSA microstructural tissue integrity and slower processing speed. Taken together, the results highlight the need for researchers to consider BAT when estimating CBF using single-TI sequences. Moreover, the findings demonstrate the feasibility of multi-TI ASL for objective delineation of iWSAs and for detection of regional hemodynamic stress that is associated with reduced microstructural tissue integrity and slower processing speed. This technique may hold promise for future studies and treatment trials.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Individual Watershed Areas in Sickle Cell Anemia: An Arterial Spin Labeling Study

et al. 2022

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Neurocognitive functioning in children with sickle cell anemia and history of abnormal transcranial doppler ultrasonography

Longoria

Wang

Kang

et al. 2022

Pediatric Blood & Cancer

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Background Transcranial doppler (TCD) ultrasonography can be used to identify stroke risk in children with sickle cell anemia. Previous studies have reported mixed findings on neurocognitive outcomes in children with elevated TCD. This study examined associations between TCD velocity and neurocognitive outcomes in children and adolescents without prior history of stroke. Procedure Participants were selected from the Sickle Cell Clinical Research Intervention Program cohort. The highest recorded mean maximum TCD velocity was selected for analysis, along with participant's most recent data from serial neurocognitive surveillance. Results A total of 200 children with sickle cell anemia completed neurocognitive testing (109 males, 91 females; mean age 12.7 years [SD = 3.56]). Most participants were prescribed hydroxyurea (72%) at the time of neurocognitive testing and nearly 16% had a history of chronic transfusions prior to neurocognitive evaluation. Mean age at time of highest TCD value was 6.6 years (SD = 2.5) and 13.5% of screenings were abnormal (≥200 cm/s). Mean interval between TCD and most recent neurocognitive evaluation was 6.1 years (±3.5). There were no significant differences in the interval between TCD and neurocognitive testing across normal, conditional, and abnormal groups. Maximum TCD velocity was not significantly associated with neurocognitive outcomes in multivariate models. Conclusions History of elevated TCD in the absence of overt stroke should not be considered a risk factor for poor neurocognitive outcomes in children and adolescents with sickle cell anemia on modern disease‐modifying therapy.

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Perfusion MRI in the brain: Insights from sickle cell disease and the healthy brain

Afzali-Hashemi,

Baas,

Wood

et al. 2023

Advances in Magnetic Resonance Technology and Applications

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Venous cerebral blood flow quantification and cognition in patients with sickle cell anemia

Cited by 10 publications

References 71 publications

Individual Watershed Areas in Sickle Cell Anemia: An Arterial Spin Labeling Study

Individual Watershed Areas in Sickle Cell Anemia: An Arterial Spin Labeling Study

Neurocognitive functioning in children with sickle cell anemia and history of abnormal transcranial doppler ultrasonography

Perfusion MRI in the brain: Insights from sickle cell disease and the healthy brain

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