Multicontrast connectometry: A new tool to assess cerebellum alterations in early relapsing‐remitting multiple sclerosis

Abstract

Background: Cerebellar pathology occurs in late multiple sclerosis (MS) but little is known about cerebellar changes during early disease stages. In this study, we propose a new multicontrast "connectometry" approach to assess the structural and functional integrity of cerebellar networks and connectivity in early MS. Methods: We used diffusion spectrum and resting-state functional MRI (rs-fMRI) to establish the structural and functional cerebellar connectomes in 28 early relapsing-remitting MS patients and 16 healthy controls (HC). We performed multicontrast "connectometry" by quantifying multiple MRI parameters along the structural tracts (generalized fractional anisotropy-GFA, T1/T2 relaxation times and magnetization transfer ratio) and functional connectivity measures. Subsequently, we assessed multivariate differences in local connections and network properties between MS and HC subjects; finally, we correlated detected alterations with lesion load, disease duration, and clinical scores. Results: In MS patients, a subset of structural connections showed quantitative MRI changes suggesting loss of axonal microstructure and integrity (increased T1 and decreased GFA, P < 0.05). These alterations highly correlated with motor, memory and attention in patients, but were independent of cerebellar lesion load and disease duration. Neither network organization nor rs-fMRI abnormalities were observed at this early stage. Conclusion: Multicontrast cerebellar connectometry revealed subtle cerebellar alterations in MS patients, which were independent of conventional disease markers and highly correlated with patient function. Future work should assess the prognostic value of the observed damage. Hum Brain Mapp 36:1609-1619, 2015. V C 2014 Wiley Periodicals, Inc.

Connectometry evaluation in patients undergoing carotid endarterectomy: an exploratory study

“…As indicated above, previously published studies has investigated connectometry differences in other neurological diseases [24][25][26][27][28][29][30][31][32][33][34], adopting SDF as biomarker of investigation. SDF is a densitybased measurement of diffusion at different orientations and it measures the density of diffusing water, differently from other diffusivity measurements such as Fractional Anisotropy (FA), Apparent Diffusion Coefficient (ADC) and Radial Diffusivity.…”

“…The spin distribution function (SDF) is the parameter used for the analysis [23]. This method has been already used for example for the study of Parkinson disease [24][25][26][27][28][29][30], mood disorders [31,32], multiple sclerosis [33] and amyotrophic lateral sclerosis [34].…”

Synaptic pathology in the cerebellar dentate nucleus in chronic multiple sclerosis

“…The presence of cerebellar symptoms is associated with a progressive disease course , and cerebellar cortical atrophy and diffuse pathology are independent contributors to cognitive and motor impairment . These structural changes are further accompanied by functional alterations in cerebellar connectivity, implicating early synaptic dysfunction .…”

Graph Theory-Based Brain Connectivity for Automatic Classification of Multiple Sclerosis Clinical Courses

“…This graph theory approach has become a sensitive tool to detect alterations in brain pathologies by providing both local and global characterization of WM connections (Achard et al, 2012). Recently applied to MS patients, these methods demonstrated several alterations in brain connectivity (He et al, 2009; Richiardi et al, 2012; Li et al, 2013; Nigro et al, 2015; Romascano et al, 2015). Indeed, a negative correlation was reported between network efficiency and WM lesion load (He et al, 2009).…”