Imaging Blood-Brain Barrier Permeability Through MRI in Pediatric Sickle Cell Disease: A Feasibility Study.

BACKGROUND: Blood-brain barrier (BBB) disruption may lead to endothelium dysfunction and inflammation in sickle cell disease (SCD). However, abnormalities of BBB in SCD, especially in pediatric patients for whom contrast agent administration less than optimal, have not been fully characterized. PURPOSE: To examine BBB permeability to water in a group of pediatric SCD participants using a non-invasive magnetic resonance imaging technique. We hypothesized that SCD participants will have increased BBB permeability. STUDY TYPE: Prospective cross-sectional. POPULATION: Twenty-six pediatric participants (10 ± 1 years, 15F/11M) were enrolled, including 21 SCD participants and 5 sickle cell trait (SCT) participants, who were siblings of SCD patients. FIELD STRENGTH/SEQUENCE: 3 T. Water extraction with phase-contrast arterial spin tagging with echo-planer imaging, phase-contrast and T1 -weighted magnetization-prepared rapid acquisition of gradient echo. ASSESSMENT: Water extraction fraction (E), BBB permeability-surface area product (PS), cerebral blood flow, hematological measures (hemoglobin, hematocrit, hemoglobin S), neuropsychological scores (including domains of intellectual ability, attention and executive function, academic achievement and adaptive function, and a composite score). Regions of interest were drawn by Z.L. (6 years of experience). STATISTICAL TESTS: Wilcoxon rank sum test and chi-square test for group comparison of demographics. Multiple linear regression analysis of PS with diagnostic category (SCD or SCT), hematological measures, and neuropsychological scores. A two-tailed P value of 0.05 or less was considered statistically significant. RESULTS: Compared with SCT participants, SCD participants had a significantly higher BBB permeability to water (SCD: 207.0 ± 33.3 mL/100 g/minute, SCT: 171.2 ± 27.2 mL/100 g/minute). SCD participants with typically more severe phenotypes also had a significantly leakier BBB than those with typically milder phenotypes (severe: 217.3 ± 31.7 mL/100 g/minute, mild: 193.3 ± 31.8 mL/100 g/minute). Furthermore, more severe BBB disruption was associated with worse hematological symptoms, including lower hemoglobin concentrations (ß = -8.84, 95% confidence interval [CI] [-14.69, -3.00]), lower hematocrits (ß = -2.96, 95% CI [-4.84, -1.08]), and higher hemoglobin S fraction (ß = 0.77, 95% CI [0.014, 1.53]). DATA CONCLUSION: These findings support a potential role for BBB dysfunction in SCD pathogenesis of ischemic injury. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Brain Oxygen Extraction and Metabolism in Pediatric Patients With Sickle Cell Disease: Comparison of Four Calibration Models.

Sickle cell disease (SCD) is an inherited hemoglobinopathy with an increased risk of neurological complications. Due to anemia and other factors related to the underlying hemoglobinopathy, cerebral blood flow (CBF) increases as compensation; however, the nature of alterations in oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) in SCD remains controversial, largely attributed to the different calibration models. In addition, limited studies have been done to investigate oxygen metabolism in pediatric patients. Thus, this study used a non-invasive T2-based MR oximetry, T2-Relaxation-Under-Spin-Tagging (TRUST) MRI, to measure oxygen homeostasis in pediatric patients with SCD using four different calibration models and examined its relationship to hematological measures. It was found that, compared with controls, SCD patients showed an increased CBF, unchanged total oxygen delivery and increased venous blood T2. The results of OEF and CMRO2 were dependent on the calibration models used. When using sickle-specific, hemoglobin S (HbS) level-dependent calibration, there was a decreased OEF and CMRO2, while the bovine model showed an opposite result. OEF and CMRO2 were also associated with hemoglobin and HbS level; the direction of the relationship was again dependent on the model. Future studies with in vivo calibration are needed to provide more accurate information on the T2-Y v relationship.

Pandemic intake questionnaire to improve quality, effectiveness, and efficiency of outpatient neurologic and developmental care at the Kennedy Krieger institute during the COVID-19 pandemic.

Background: The COVID-19 pandemic uniquely affects patients with neurologic and developmental disabilities at the Kennedy Krieger Institute. These patients are at increased risk of co-morbidities, increasing their risk of contracting COVID-19. Disruptions in their home and school routines, and restrictions accessing crucial healthcare services has had a significant impact. Methods: A Pandemic Intake questionnaire regarding COVID-19 related medical concerns of guardians of patients was distributed using Qualtrics. Data from May-December 2020 were merged with demographic information of patients from 10 clinics (Center for Autism and Related Disorders (CARD), Neurology, Epigenetics, Neurogenetics, Center for Development and Learning (CDL) Sickle Cell, Spinal Cord, Sturge-Weber syndrome (SWS), Tourette's, and Metabolism). A provider feedback survey was distributed to program directors to assess the effectiveness of this intervention. Results: Analysis included responses from 1643 guardians of pediatric patients (mean age 9.5 years, range 0-21.6 years). Guardians of patients in more medically complicated clinics reported perceived increased risk of COVID-19 (p < 0.001) and inability to obtain therapies (p < 0.001) and surgeries (p < 0.001). Guardian responses from CARD had increased reports of worsening behavior (p = 0.01). Providers increased availability of in-person and virtual therapies and visits and made referrals for additional care to address this. In a survey of medical providers, five out of six program directors who received the responses to this survey found this questionnaire helpful in caring for their patients. Conclusion: This quality improvement project successfully implemented a pre-visit questionnaire to quickly assess areas of impact of COVID-19 on patients with neurodevelopmental disorders. During the pandemic, results identified several major areas of impact, including patient populations at increased risk for behavioral changes, sleep and/or disruptions of medical care. Most program directors reported improved patient care as a result.