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Principal Investigator: EBONI I LANCE
Organization: HUGO W. MOSER RES INST KENNEDY KRIEGER
Fiscal Year: 2024
Award: $373,331
Funding agency: National Heart Lung and Blood Institute
Project Summary/Abstract
Sickle cell disease (SCD) is an inherited blood disorder with several neurological and developmental
complications. Young children with SCD between 2 and 5 years of age, in particular, have an increased risk for
ischemic stroke and silent cerebral infarctions (SCI). SCI are hyperintense T2 brain magnetic resonance
imaging (MRI) lesions with no accompanying acute neurological symptoms but with associated impaired
cognition and increased risk of future progressive or additional stroke/SCI. Neuroimaging and neurocognitive
profiles associated with SCI are well established in school-aged and adult SCD populations. This information is
largely unknown in young children under 6 years of age with SCD due to risk of sedation/anesthesia with MRI.
Our preliminary studies have shown that behavioral training can yield high quality neuroimaging data without
sedation in 3 to 4 years old children with SCD through a pilot study.
The long term goal of this application is to develop a diagnostic battery using a combination of
unsedated neuroimaging measures, neurocognitive testing, and plasma brain injury protein levels to identify
young children with SCD at risk for SCI. Through a prospective longitudinal case-control study, we will collect
medical history and clinical data and perform neurological examination and blood draws annually in 100
children with SCD from study entry to study exit. Participants will also undergo initial neuroimaging battery at 3
to 4 years of age with repeat neuroimaging at study exit as well as longitudinal neurocognitive testing at study
entry, with initial neuroimaging, and with exit neuroimaging. This multi-disciplinary and multi-modality proposal
has two Aims. Aim 1 will identify the cross-sectional neuroimaging and neurocognitive findings in 3 to 4 year-
old children with SCD and SCI on initial MRI by comparing their results to children with SCD without SCI. Aim
2 will compare longitudinal data from 6 year-old children with and without SCI on exit MRI. Exploratory aims
will explore differences in the neuroimaging measures in children on different disease-modifying treatments
(hydroxyurea) and plasma protein levels in children with and without SCI. The proposed work will determine
which neuroimaging measures and neurocognitive testing may predict SCI, leading to a multi-site study to
validate these findings in a larger regionally heterogenous SCD population. The study PI, a
neurodevelopmental physician, is an early stage investigator well suited to expand her existing study cohort
with support from a team of co-investigators, including a senior behavioral psychologist and neuroimaging
physicist, as well as existing collaborators and staff.
Terms: <0-11 years old><21+ years old><3 year old><3 years of age><4 year old><4 years of age><5 year old><5 years of age><6 year old><6 years of age><Academic accommodation><Acquired brain injury><Acute><Adult><Adult Human><Age><Anesthesia><Anesthesia procedures><Apoplexy><Axon><Behavioral><Blood><Blood Diseases><Blood Plasma><Blood Reticuloendothelial System><Brain Injuries><Brain Vascular Accident><Case-Base Studies><Case-Comparison Studies><Case-Compeer Studies><Case-Referent Studies><Case-Referrent Studies><Case/Control Studies><Cephalic><Cerebral Infarction><Cerebral Stroke><Cerebrovascular Apoplexy><Cerebrovascular Circulation><Cerebrovascular Stroke><Cerebrum><Characteristics><Child><Child Youth><Children (0-21)><Chronic Disease><Chronic Illness><Clinical><Clinical Data><Cognition><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Cohort Studies><Collection><Concurrent Studies><Cranial><Data><Data Collection><Development><Diagnosis><Diagnostic><Disease><Disorder><Disturbance in cognition><ELISA><Early identification><Early treatment><Education><Educational accommodation><Educational aspects><Enzyme-Linked Immunosorbent Assay><Evaluation><Fetal Hb><Fetal Hemoglobin><Future><Goals><Guidelines><Hb SS disease><HbF><HbSS disease><Hematologic Diseases><Hematological Disease><Hematological Disorder><Hemoglobin F><Hemoglobin S Disease><Hemoglobin concentration result><Hemoglobin sickle cell disease><Hemoglobin sickle cell disorder><Hereditary><History><Hydroxycarbamid><Hydroxycarbamide><Impaired cognition><Inflammatory><Inherited><Injury><Intelligence><Intermediary Metabolism><Investigators><Ischemic Stroke><Knowledge><Language><Lesion><Leukocyte Count><Leukocyte Number><Literature><Longitudinal Studies><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Math><Mathematics><Measures><Medical><Medical History><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Metabolic><Metabolic Processes><Metabolic stress><Metabolism><Morbidity><Morbidity - disease rate><NMR Imaging><NMR Tomography><Nerve Cells><Nerve Unit><Neural Cell><Neurocognitive><Neurocyte><Neurodevelopmental Deficit><Neurologic><Neurologic Examination><Neurologic Manifestations><Neurologic Signs and Symptoms><Neurologic Symptoms><Neurological><Neurological Examination><Neurological Manifestations><Neurological Signs and Symptoms><Neurons><Neuropsychologic Tests><Neuropsychological Tests><Nuclear Magnetic Resonance Imaging><O element><O2 element><Outcome><Oxygen><Participant><Patients><Performance><Personal Medical History><Personal Medical History Epidemiology><Physical Function><Physicians><Pilot Projects><Plasma><Plasma Proteins><Plasma Serum><Population><Predicting Risk><Proteins><Psychologist><Reading><Recommendation><Recording of previous events><Recurrence><Recurrent><Research><Research Personnel><Researchers><Reticuloendothelial System, Serum, Plasma><Risk><Risk Factors><Sample Size><Sampling><School-Age Population><Sedation procedure><Sensitivity and Specificity><Services><Sickle Cell Anemia><Site><Stroke><Test Result><Testing><Therapeutic Intervention><Time><Training><Vulnerable Populations><White Blood Cell Count><White Blood Cell Count procedure><Work><Zeugmatography><adulthood><age 3 years><age 4 years><age 5 years><age 6 years><ages><blood disorder><blood flow in brain><brain MR imaging><brain MRI><brain attack><brain blood circulation><brain blood flow><brain damage><brain magnetic resonance imaging><brain tissue><brain-injured><case-controlled studies><cerebral><cerebral MR imaging><cerebral MRI><cerebral blood flow><cerebral circulation><cerebral infarct><cerebral magnetic resonance imaging><cerebral vascular accident><cerebrocirculation><cerebrovascular accident><cerebrovascular blood flow><chronic disorder><cognitive dysfunction><cognitive loss><developmental><disability><early therapy><enzyme linked immunoassay><executive control><executive function><experience><fetal form of hemoglobin><fetal globin><five year old><five years of age><forecasting risk><four year old><four years of age><hemoglobin level><high risk><histories><hydroxy-urea><hydroxyurea><improved><injuries><intervention therapy><kids><long-term study><longitudinal outcome studies><longterm study><male><minimal risk><multi-modality><multidisciplinary><multimodality><neural imaging><neural manifestation><neuro-imaging><neurocognitive test><neuroimaging><neurological imaging><neuronal><neuroprotection><neuroprotective><pilot study><predict risk><predict risks><predicted risk><predicted risks><predicting risks><predictive biomarkers><predictive marker><predictive molecular biomarker><predictive risk><predicts risk><prevent><preventing><prospective><risk prediction><risk predictions><school age><screening><screenings><sedation><sex><sickle cell disease><sickle cell disorder><sickle disease><sicklemia><six year old><six years of age><skills><standard of care><stroked><strokes><three year old><three years of age><verbal><vulnerable group><vulnerable individual><vulnerable people><youngster>