Brain Maturation Patterns on Normalized FLAIR MR Imaging in Children and Adolescents.

BACKGROUND AND PURPOSE: Signal analysis of FLAIR sequences is gaining momentum for studying neurodevelopment and brain maturation, but FLAIR intensity varies across scanners and needs to be normalized. This study aimed to establish normative values for standardized FLAIR intensity in the pediatric brain. MATERIALS AND METHODS: A new automated algorithm for signal normalization was used to standardize FLAIR intensity across scanners and subjects. Mean intensity was extracted from GM, WM, deep GM, and cortical GM regions. Regression curves were fitted across the pediatric age range, and ANOVA was used to investigate intensity differences across age groups. Correlations between intensity and regional volume were also examined. RESULTS: We analyzed 429 pediatric FLAIR sequences in children 2-19 years of age with a median age of 11.2 years, including 199 males and 230 females. WM intensity had a parabolic relationship with age, with significant differences between various age groups (P < .05). GM and cortical GM intensity increased over the pediatric age range, with significant differences between early childhood and adolescence (P < .05). There were no significant relationships between volume and intensity in early childhood, while there were significant positive and negative correlations (P < .05) in WM and GM, respectively, for increasing age groups. Only the oldest age group showed significant differences between males and females (P < .05). CONCLUSIONS: This work presents a FLAIR intensity standardization algorithm to normalize intensity across large data sets, which allows FLAIR intensity to be used to compare regions and individuals as a surrogate measure of the developing pediatric brain.

FLAIR MRI biomarkers of the normal appearing brain matter are related to cognition.

A novel biomarker panel was proposed to quantify macro and microstructural biomarkers from the normal-appearing brain matter (NABM) in multicentre fluid-attenuation inversion recovery (FLAIR) MRI. The NABM is composed of the white and gray matter regions of the brain, with the lesions and cerebrospinal fluid removed. The primary hypothesis was that NABM biomarkers from FLAIR MRI are related to cognitive outcome as determined by MoCA score. There were three groups of features designed for this task based on 1) texture: microstructural integrity (MII), macrostructural damage (MAD), microstructural damage (MID), 2) intensity: median, skewness, kurtosis and 3) volume: NABM to ICV volume ratio. Biomarkers were extracted from over 1400 imaging volumes from more than 87 centres and unadjusted ANOVA analysis revealed significant differences in means of the MII, MAD, and NABM volume biomarkers across all cognitive groups. In an adjusted ANCOVA model, a significant relationship between MoCA categories was found that was dependent on subject age for MII, MAD, intensity, kurtosis and NABM volume biomarkers. These results demonstrate that structural brain changes in the NABM are related to cognitive outcome (with different relationships depending on the age of the subjects). Therefore these biomarkers have high potential for clinical translation. As a secondary hypothesis, we investigated whether texture features from FLAIR MRI can quantify microstructural changes related to how "structured" or "damaged" the tissue is. Based on correlation analysis with diffusion weighted MRI (dMRI), it was shown that FLAIR MRI texture biomarkers (MII and MAD) had strong correlations to mean diffusivity (MD) which is related to tissue degeneration in the GM and WM regions. As FLAIR MRI is routinely collected for clinical neurological examinations, novel biomarkers from FLAIR MRI could be used to supplement current clinical biomarkers and for monitoring disease progression. Biomarkers could also be used to stratify patients into homogeneous disease subgroups for clinical trials, or to learn more about mechanistic development of dementia disease.