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CADASIL is a monogenic small vessel disease characterized by the accumulation of brain tissue lesions of microvascular origin leading to strokes and cognitive deficits. Both cortical and parenchymal alterations have been described using various MRI markers. However, relationships between cortical and subcortical alterations remain largely unexplored. While brain atrophy is a preponderant feature in cerebral small vessel disease, recent results in CADASIL suggest slightly larger brain volumes and increased white matter water content at early stages of the disease by comparison to controls. We hypothesized in this study that increased water content in gyral white matter balances expected brain atrophy. Direct white matter volume computation is challenging in these patients given widespread subcortical alterations. Instead, our approach was that a gyral white matter swelling would translate into a modification of the shape of cortical gyri. Our goal was then to assess the relationship between subcortical lesions and possible alteration of the cortex shape. More specifically, aims of this work were to assess 1) morphometric differences of the cortex shape between CADASIL patients and controls 2) the relationship between the cortex shape and the volume of white matter hyperintensities (WMH), a reflect of white matter alterations. Twenty-one patients at the early stage of the disease and 28 age- and sex-matched controls were included. Cortical surfaces were reconstructed from 3D-T1-weighted images. Folding power assessed from spectral analysis of gyrification and cortical morphometry using curvedness and shape index were computed as proxies of the cortex shape. Influence of segmentation errors were evaluated through the simulation of WMH in controls. As a result, patients had larger folding power and curvedness compared to controls. They also presented lower shape indices both related to sulci and gyri. In patients, the volume of WMH was associated with decreased gyral shape index. These results suggest that the cortex shape of CADASIL patients is different compared to controls and that the enlargement of gyri is related to the extent of white matter alterations. The study of the cortex shape might be another way to evaluate subcortical swelling or atrophy in various neurological disorders.

Alteration of the Cortex Shape as a Proxy of White Matter Swelling in Severe Cerebral Small Vessel Disease