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 multi-centre fluid-attenuation inversion recovery (FLAIR) MRI. The hypothesis was that NABM biomarkers from FLAIR MRI are related to cognition as determined by the Montreal Cognitive Assessment (MoCA). ANOVA analysis of seven biomarkers revealed significant differences between the means for three of the biomarkers in the cross-sectional and four biomarkers for all-data approaches, across all cognitive groups (p<0.01). An adjusted ANCOVA model found significant relationships between MoCA categories dependent on age and sex for four biomarkers exclusively in the all-data approach. Furthermore, quantification of microstructural changes was performed based on correlation analysis through diffusion MRI (dMRI), with up to r=0.87 (p<0.01) correlation to mean diffusivity (MD). These biomarkers demonstrate that structural differences in the NABM in FLAIR MRI are associated with cognition and that they have high potential for clinical translation.</p

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.</p

Delusional Severity Is Associated with Abnormal Texture in FLAIR MRI

Background: This study examines the relationship between delusional severity in cognitively impaired adults with automatically computed volume and texture biomarkers from the Normal Appearing Brain Matter (NABM) in FLAIR MRI. Methods: Patients with mild cognitive impairment (MCI, n = 24) and Alzheimer&rsquo;s Disease (AD, n = 18) with delusions of varying severities based on Neuropsychiatric Inventory-Questionnaire (NPI-Q) (1&mdash;mild, 2&mdash;moderate, 3&mdash;severe) from the Alzheimer&rsquo;s Disease Neuroimaging Initiative (ADNI) were analyzed for this task. The NABM region, which is gray matter (GM) and white matter (WM) combined, was automatically segmented in FLAIR MRI volumes with intensity standardization and thresholding. Three imaging biomarkers were computed from this region, including NABM volume and two texture markers called &ldquo;Integrity&rdquo; and &ldquo;Damage&rdquo;. Together, these imaging biomarkers quantify structural changes in brain volume, microstructural integrity and tissue damage. Multivariable regression was used to investigate relationships between imaging biomarkers and delusional severities (1, 2 and 3). Sex, age, education, APOE4 and baseline cerebrospinal fluid (CSF) tau were included as co-variates. Results: Biomarkers were extracted from a total of 42 participants with longitudinal time points representing 164 imaging volumes. Significant associations were found for all three NABM biomarkers between delusion level 3 and level 1. Integrity was also sensitive enough to show differences between delusion level 1 and delusion level 2. A significant specified interaction was noted with severe delusions (level 3) and CSF tau for all imaging biomarkers (p &lt; 0.01). APOE4 homozygotes were also significantly related to the biomarkers. Conclusion: Cognitively impaired older adults with more severe delusions have greater global brain disease burden in the WM and GM combined (NABM) as measured using FLAIR MRI. Relative to patients with mild delusions, tissue degeneration in the NABM was more pronounced in subjects with higher delusional symptoms, with a significant association with CSF tau. Future studies are required to establish potential tau-associated mechanisms of increased delusional severity

Delusional Severity Is Associated with Abnormal Texture in FLAIR MRI

Background: This study examines the relationship between delusional severity in cognitively impaired adults with automatically computed volume and texture biomarkers from the Normal Appearing Brain Matter (NABM) in FLAIR MRI. Methods: Patients with mild cognitive impairment (MCI, n = 24) and Alzheimer's Disease (AD, n = 18) with delusions of varying severities based on Neuropsychiatric Inventory-Questionnaire (NPI-Q) (1-mild, 2-moderate, 3-severe) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed for this task. The NABM region, which is gray matter (GM) and white matter (WM) combined, was automatically segmented in FLAIR MRI volumes with intensity standardization and thresholding. Three imaging biomarkers were computed from this region, including NABM volume and two texture markers called "Integrity" and "Damage". Together, these imaging biomarkers quantify structural changes in brain volume, microstructural integrity and tissue damage. Multivariable regression was used to investigate relationships between imaging biomarkers and delusional severities (1, 2 and 3). Sex, age, education, APOE4 and baseline cerebrospinal fluid (CSF) tau were included as co-variates. Results: Biomarkers were extracted from a total of 42 participants with longitudinal time points representing 164 imaging volumes. Significant associations were found for all three NABM biomarkers between delusion level 3 and level 1. Integrity was also sensitive enough to show differences between delusion level 1 and delusion level 2. A significant specified interaction was noted with severe delusions (level 3) and CSF tau for all imaging biomarkers (p < 0.01). APOE4 homozygotes were also significantly related to the biomarkers. Conclusion: Cognitively impaired older adults with more severe delusions have greater global brain disease burden in the WM and GM combined (NABM) as measured using FLAIR MRI. Relative to patients with mild delusions, tissue degeneration in the NABM was more pronounced in subjects with higher delusional symptoms, with a significant association with CSF tau. Future studies are required to establish potential tau-associated mechanisms of increased delusional severity. </p