CBF and Visual, Auditory, and Motoric BOLD Responses in Pediatric Patients with Sickle Cell Anemia
Poster No:
371
Submission Type:
Abstract Submission
Authors:
Ping Zou Stinnett1, Winfred Wang1, Zachary Abramson1, Jane Hankins1, Kathleen Helton1, Robert Ogg1, Ranganatha Sitaram2
Institutions:
1St. Jude Children Research Hospital, Memphis, TN, 2St. Jude Children's Research Hospital, Memphis, TN
First Author:
Co-Author(s):
Introduction:
Sickle cell anemia (SCA) is characterized by rigid sickle-shaped red blood cells with low oxygen affinity. It affects all organs, including the brain. Children with SCA often suffer neurocognitive deficits [1]. Elevated cerebral blood flow (CBF) occurs in patients with SCA [2], which may be a compensatory response to their chronic anemia through cerebrovascular dilatory reserve [3]. We have found that the BOLD response to visual stimulation decreased in children with SCA [4] and speculated that their ability to increase CBF, and in turn their BOLD signal response, at the demand of neuronal activity, may be limited due to their elevated baseline CBF. Here, we report BOLD signal changes in visual, motor, and auditory cortices relative to resting CBF in pediatric patients with SCA. We also report results from a simultaneous measure of BOLD and CBF to visual stimulus in a subgroup of patients exposed to hydroxyurea [5], a treatment known to lower CBF and improve cognitive function.
Methods:
Written informed consent for this IRB-approved study was obtained from each participant. 35 SCA patients (12.2 [7.8-17.8] years old) had fMRI with a 3T Siemens scanner. A pulsed ASL Q2TIPS sequence [6] (TR=2270ms, TE=23ms, TI1=700ms, TI1s=1200ms, and TI2=1400ms) was used to measure resting CBF and simultaneous BOLD and CBF responses to visual stimulation (blocked-design paradigm:22.7s stimulus in a 44.5s block for 8 blocks). A T2* weighted EPI sequence (TR=2.0s, TE=30ms) was used with a sensory survey task: finger tapping during visual and auditory stimulation. The fMRI paradigm included 4 blocks of brief task (2s task in a 30s block) and 3 blocks of long task (20s task in a 40s block).
The resting CBF map was calculated from the resting ASL images. The fMRI images were pre-processed and analyzed with SPM. From the EPI images with the sensory survey task, time courses from the peak activation cluster in the primary visual, auditory, and motor cortices were retrieved for each subject. The heights of BOLD signal changes were correlated with the resting gray matter CBF in the corresponding lobes.
The fMRI ASL images were analyzed for 12 patients at 2 time points: before (TP1) and after (TP2) 12 months of hydroxyurea therapy. The ASL time course of the peak-activated clusters in the primary visual cortex from BOLD activation was retrieved for each subject. The BOLD and CBF time courses were then calculated from the average of or the difference between the control and the tag signals. The BOLD and CBF changes before and after hydroxyurea were compared.
The resting CBF map was calculated from the resting ASL images. The fMRI images were pre-processed and analyzed with SPM. From the EPI images with the sensory survey task, time courses from the peak activation cluster in the primary visual, auditory, and motor cortices were retrieved for each subject. The heights of BOLD signal changes were correlated with the resting gray matter CBF in the corresponding lobes.
The fMRI ASL images were analyzed for 12 patients at 2 time points: before (TP1) and after (TP2) 12 months of hydroxyurea therapy. The ASL time course of the peak-activated clusters in the primary visual cortex from BOLD activation was retrieved for each subject. The BOLD and CBF time courses were then calculated from the average of or the difference between the control and the tag signals. The BOLD and CBF changes before and after hydroxyurea were compared.
Results:
From the sensory survey task in the 35 patients, activations were detected in primary visual, auditory, and motor cortices. The peak BOLD signal changes in these three cortices were less than 5% and were negatively associated with lobar gray matter CBF values in the visual (p=0.01) and auditory (p=0.01) cortices, but not in the motor cortex (Fig 1).
From the fMRI ASL images in the 12 treated patients, activations in the primary visual cortex were detected. The height of CBF change was similar before and after hydroxyurea, but the base was lower at TP2. The BOLD responses were significantly higher at TP2 than at TP1 (p=0.05) (Fig 2).
From the fMRI ASL images in the 12 treated patients, activations in the primary visual cortex were detected. The height of CBF change was similar before and after hydroxyurea, but the base was lower at TP2. The BOLD responses were significantly higher at TP2 than at TP1 (p=0.05) (Fig 2).
Conclusions:
The low BOLD signal in the SCA patients is consistent with our previous observation [3,7]. The parity in the height of CBF responses before and after hydroxyurea treatment suggests a ceiling effect for the CBF to increase in the patients. With a lowered baseline CBF, there is more room for CBF increase during neuronal activities, promoting a higher BOLD signal [7]. The negative association of the BOLD signal with gray matter CBF in the visual and auditory cortices also supports this assumption. Finally, the lack of association between BOLD and CBF in the motor cortex indicates variability in the neuro-vascular coupling adaptation across brain regions in patients with SCA.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Lifespan Development:
Early life, Adolescence, Aging
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI)
Physiology, Metabolism and Neurotransmission :
Cerebral Metabolism and Hemodynamics 2
Keywords:
Blood
Cerebral Blood Flow
Cerebrovascular Disease
DISORDERS
FUNCTIONAL MRI
Motor
PEDIATRIC
Pediatric Disorders
Treatment
1|2Indicates the priority used for review
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2. Strouse, J. J., Cox, C. S., Melhem, E. R., Lu, H., Kraut, M. A., Razumovsky, A., et al. (2006). Inverse correlation between cerebral blood flow measured by continuous arterial spinlabeling (CASL) MRI and neurocognitive function in children with sickle cell anemia (SCA). Blood, 108, 379–381.
3. Prohovnik, I., Hurlet-Jensen, A., Adams, R., De Vivo, D. & Pavlakis, S.G. (2009) Hemodynamic etiology of elevated flow velocity and stroke in sickle-cell disease. Journal of Cerebral Blood Flow and Metabolism, 29, 803–810
4. Ping Zou, Kathleen J. Helton, Matthew Smeltzer, Chin-Shang Li, Heather M. Conklin, Amar Gajjar, Winfred C. Wang, Russell E. Ware, Robert J. Ogg (2011). Hemodynamic responses to visual stimulation in children with sickle cell anemia. Brain Imaging and Behavior, 5:295–306
5. Wang WC, Zou P, Hwang SN, Kang G, Ding J, Heitzer AM, Schreiber JE, Helton K, Hankins JS. (2021) Effects of hydroxyurea on brain function in children with sickle cell anemia. Pediatr Blood Cancer. DOI: 10.1002/pbc.29254
6. Luh WM, Wong EC, Bandettini PA, et al. QUIPSS II with thin-slice TI1 periodic saturatin: a method for improving accuracy of quantitative perfusion imaging using pulsed arterial spin labeling. Magn Reson Med 1999; 41: 1246–1254
7. Zou P, Scoggins MA, Li Y, Jones M, Helton KJ, Ogg RJ (2021). Developmental patterns of CBF and BOLD responses to visual stimulus, J Cereb Blood Flow Metab. 2021 Mar;41(3):630-640. Doi: 10.1177/0271678X20925303.