Details:

Alternative Title:
J Magn Reson Imaging
Personal Author:
Lin, Zixuan ; Lance, Eboni ; McIntyre, Tiffany ; Li, Yang ; Liu, Peiying ; ... More +
Lin, Zixuan ; Lance, Eboni ; McIntyre, Tiffany ; Li, Yang ; Liu, Peiying ; Lim, Chantelle ; Fan, Hongli ; Tekes, Aylin ; Cannon, Alicia ; Casella, James F. ; Lu, Hanzhang Less -
Description:
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 MRI technique. We hypothesized that SCD participants will have increased BBB permeability.

Study Type

Prospective cross-sectional.

Population

26 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

3T. Water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST) with echo-planer imaging, phase-contrast and T1-weighted magnetization-prepared-rapid-acquisition-of-gradient-echo (MPRAGE).

Assessment

Water extraction fraction (E), BBB permeability-surface area product (PS), cerebral blood flow (CBF), 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). ROIs 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±33.3mL/100g/min, SCT: 171.2±27.2mL/100g/min,). SCD participants with typically more severe phenotypes also had a significantly leakier BBB than those with typically milder phenotypes (severe: 217.3±31.7mL/100g/min, mild: 193.3±31.8mL/100g/min,). Furthermore, more severe BBB disruption was associated with worse hematological symptoms, including lower hemoglobin concentrations (β=−8.84, 95% CI [−14.69, −3.00]), lower hematocrits (β=−2.96, 95% CI [−4.84, −1.08]), and higher hemoglobin S fraction (β=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.


Subjects:
[+]
Anemia, Sickle Cell Article Blood-brain Barrier Child Cross-Sectional Studies Feasibility Studies Female Hemoglobin, Sickle Humans Magnetic Resonance Imaging Male Pediatric Permeability Prospective Studies Sickle Cell Disease Water Water Exchange WEPCAST MRI
Source:
J Magn Reson Imaging. 55(5):1551-1558
Pubmed ID:
34676938
Pubmed Central ID:
PMC9018466
Document Type:
Journal Article
Funding:
P41 EB031771/EB/NIBIB NIH HHSUnited States/ ; K23 HL133455/HL/NHLBI NIH HHSUnited States/ ; U54 HD079123/HD/NICHD NIH HHSUnited States/ ; R01 NS106702/NS/NINDS NIH HHSUnited States/ ; RF1 AG071515/AG/NIA NIH HHSUnited States/ ; ... More +
P41 EB031771/EB/NIBIB NIH HHSUnited States/ ; K23 HL133455/HL/NHLBI NIH HHSUnited States/ ; U54 HD079123/HD/NICHD NIH HHSUnited States/ ; R01 NS106702/NS/NINDS NIH HHSUnited States/ ; RF1 AG071515/AG/NIA NIH HHSUnited States/ ; P50 HD103538/HD/NICHD NIH HHSUnited States/ ; P41 EB015909/EB/NIBIB NIH HHSUnited States/ ; S10 OD021648/OD/NIH HHSUnited States/ ; S10 OD021648/CD/ODCDC CDC HHSUnited States/ ; 19PRE34380371/American Heart Association/ ; R01 NS106711/NS/NINDS NIH HHSUnited States/ ; K23 HL133455-01A1/HL/NHLBI NIH HHSUnited States/ ; R01 AG064792/AG/NIA NIH HHSUnited States/ Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:8bd04780f94cf12df2435f7769490adbf534a4b618b649ebb42c4a18159ecd50
Download URL:
https://stacks.cdc.gov/view/cdc/116633/cdc_116633_DS1.pdf
File Type:

Supporting Files

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