Discriminating between neurofibromatosis‐1 and typically developing children by means of multimodal MRI and multivariate analyses

Abstract

Neurofibromatosis Type 1 leads to brain anomalies involving both gray and white matter. The extent and granularity of these anomalies, together with their possible impact on brain activity, is still unknown. In this multicentric cross‐sectional study we submitted a sample of 42 typically developing and 38 neurofibromatosis‐1 children to a multimodal MRI assessment including T1, diffusion weighted and resting state functional sequences. We used a pipeline involving several features selection steps coupled with multivariate statistical analysis (supporting vector machine) to discriminate between the two groups while having interpretable models. We used MRI indexes measuring macro (gray matter volume) and microstructural (fractional anisotropy, mean diffusivity) characteristics of the brain, as well as indexes of brain activity (fractional amplitude of low frequency fluctuations) and connectivity (local and global correlation) at rest. We found that structural indexes could discriminate between the two groups, with the mean diffusivity leading to performance as high as the combination of all structural indexes combined (accuracy = 0.86), while functional indexes had worse performances. The MRI signature of NF1 brain pathology is a combination of gray and white matter abnormalities, as measured with gray matter volume, fractional anisotropy, and mean diffusivity.

Can the Cognitive Phenotype in Neurofibromatosis Type 1 (NF1) Be Explained by Neuroimaging? A Review

“…Recently, a study by our group using a multimodal approach involving measures of gray matter volume, fractional anisotropy, and mean diffusivity highlighted a NF1 brain signature (11).…”

“…However, the presence of UBOs does not explain the cognitive and behavioral phenotype in NF1 disease (9,10). A recent study using multimodal neuroimaging including structural, diffusion and resting state functional magnetic resonance imaging (fMRI) (11) showed that NF1 patients and healthy controls can be differentiated using neuroimaging that combines the measurement of gray matter volume, fractional anisotropy and mean diffusivity. This suggests a complex physiopathology involving gray and white matter abnormalities.…”

Non-Oncological Neuroradiological Manifestations in NF1 and Their Clinical Implications

“…Conversely, grey matter density is lower in the frontal parietal and temporal lobes (and, to a lesser extent, in cingulate and insular regions) with simplified cortical gyration and abnormal cortical thickness that decreases with age [ 18 , 23 , 45 , 46 ]. From a micro-structural point of view, these volumetric changes correspond to an extensive global and local white matter disruption, as documented with diffusion tensor imaging (DTI) and a diffusion parameters analysis; indeed, several studies have documented an increased radial diffusivity with reduced fractional anisotropy in lobar white matter, suggesting a link between an impaired microstructure and abnormal fluid accumulation, potentially due to subtle myelin vacuolization [ 47 , 48 , 49 ]. Focal alterations are more evident in the frontal lobe white matter, [ 48 ] and in the anterior thalamic radiation, a white matter bundle connecting the thalamus with frontal lobes that are associated with higher executive functioning [ 33 ].…”

Brain-wide structural and functional disruption in mice with oligodendrocyte specificNf1deletion is rescued by inhibition of NOS

“…Diffusion tensor imaging (DTI) has been used to examine white matter microstructure in NF1. Fractional anisotropy (FA) is higher in heavily myelinated fiber tracts than in other brain regions (Feldman et al, 2010), and is reduced in NF1 children compared to typically developing children; 60-70% of NF1 children exhibit abnormalities in white matter, including reduced FA (Aydin et al, 2016;Brown et al, 2010;Karlsgodt et al, 2012;Koini et al, 2017;Nemmi et al, 2019;van der Vaart et al, 2016). All these changes lack treatment.…”