Magnetization transfer MRI metrics predict the accumulation of disability 8 years later in patients with multiple sclerosis

Abstract

In multiple sclerosis, the relationship between conventional MRI findings and the clinical evolution of the disease is weak. Magnetization transfer (MT) MRI can provide markers reflecting the more disabling features of multiple sclerosis pathology. The aim of the present study was to assess the value of MT MRI quantities and their short-term changes in predicting the long-term accumulation of disability in multiple sclerosis patients. Conventional and MT MRI scans of the brain were obtained at baseline and after 12 months in 73 patients, who were followed prospectively with clinical visits for a median period of 8 years. At baseline and at 12 months, T2-hyperintense and T1-hypointense lesion volume, normalized brain volume [with grey (GM) and white matter (WM) fractions] and average lesion MT ratio (MTR) were measured. At the two time points, metrics derived from the MTR histograms of the whole-brain parenchyma, GM and normal-appearing WM were also computed. A multivariate analysis, adjusted for follow-up duration, was performed to establish which variables were significant predictors of long-term neurological deterioration. At the end of follow-up, 44 patients (60%) showed a significant disability worsening. A multivariable model included baseline GM MTR histogram peak height [P = 0.029, odds ratio (OR) = 0.97], and average lesion MTR percentage change after 12 months (P = 0.016, OR = 0.88) as independent predictors of disability worsening at 8 years (r2 = 0.28). The discriminating ability of such a model in predicting the individual patients' outcome was 66%. MT MRI provides useful prognostic markers for the prediction of the long-term evolution of multiple sclerosis. This study also suggests that GM damage is one of the key factors associated with disability accumulation in this 'white matter' condition.

Dendritic cells are abundant in non-lesional gray matter in multiple sclerosis

“…Our data showing the presence of DCs and the inflammatory infiltrates in NLGM is not surprising in view of the recent brain MRI data using non-conventional MRI techniques such as the magnetization transfer ratio (MTR) (Agosta et al, 2006). In addition, post-mortem data have shown perivascular infiltration, myelin thinning and axonal loss in the NLWM (Allen and McKeown, 1979;Trapp et al, 1998), diffuse demyelination (Kutzelnigg et al, 2005), axonal transaction (Rus et al, 2005) and apoptotic loss of neurons (Peterson et al, 2001) in cortical MS lesions.…”

“…In addition, post-mortem data have shown perivascular infiltration, myelin thinning and axonal loss in the NLWM (Allen and McKeown, 1979;Trapp et al, 1998), diffuse demyelination (Kutzelnigg et al, 2005), axonal transaction (Rus et al, 2005) and apoptotic loss of neurons (Peterson et al, 2001) in cortical MS lesions. These features, especially irreversible demyelination and neuroaxonal damage, are likely to be major contributors to the MTR decrease seen in NLGM of MS brains (Agosta et al, 2006). Moreover it is important to mention that NLGM damage was found to be one of the key factors associated with disability accumulation (Agosta et al, 2006).…”

“…These features, especially irreversible demyelination and neuroaxonal damage, are likely to be major contributors to the MTR decrease seen in NLGM of MS brains (Agosta et al, 2006). Moreover it is important to mention that NLGM damage was found to be one of the key factors associated with disability accumulation (Agosta et al, 2006).…”

MRI in Multiple Sclerosis: What’s Inside the Toolbox?

“…[105][106][107][108] Data from various longitudinal studies suggest that MTR may be a sensitive marker for predicting subsequent disability and disease progression. 103,104,109 MTI is beginning to be applied to the study of the spinal cord in patients with MS (e.g., see section on "Spinal cord imaging" as follows).…”

Time-Series Modeling of Multiple Sclerosis Disease Activity: A Promising Window on Disease Progression and Repair Potential?

“…21 Although subject to short-term fluctuations similar to lesion contrast, MT has been strongly associated with demyelination and axonal loss in histology. 22,23 MT is therefore expected to be more sensitive to the destructive aspects of disease activity, supporting the concept of subacute disease that reaches neither a clinical threshold nor becomes visible as focal MRI changes.…”