Accelerated Microstructure Imaging via Convex Optimization (AMICO) in crossing fibers

Mapping the microstructure properties of the local tissues in the brain is crucial to understand any pathological condition from a biological perspective. Most of the existing techniques to estimate the microstructure of the white matter assume a single axon orientation whereas numerous regions of the brain actually present a fiber-crossing configuration. The purpose of the present study is to extend a recent convex optimization framework to recover microstructure parameters in regions with multiple fibers.

Accelerated Microstructure Imaging via Convex Optimisation for regions with multiple fibres (AMICOx)

This paper reviews and extends our previous work to enable fast axonal diameter mapping from diffusion MRI data in the presence of multiple fibre populations within a voxel. Most of the existing mi-crostructure imaging techniques use non-linear algorithms to fit their data models and consequently, they are computationally expensive and usually slow. Moreover, most of them assume a single axon orientation while numerous regions of the brain actually present more complex configurations, e.g. fiber crossing. We present a flexible framework, based on convex optimisation, that enables fast and accurate reconstructions of the microstructure organisation, not limited to areas where the white matter is coherently oriented. We show through numerical simulations the ability of our method to correctly estimate the microstructure features (mean axon diameter and intra-cellular volume fraction) in crossing regions.

The VZV/IE63-specific T cell response prevents herpes zoster in fingolimod-treated patients.

OBJECTIVE: To assess longitudinally the antiviral immune response of T cells from patients with multiple sclerosis (MS) treated with fingolimod (FTY) vs other disease-modifying treatments (DMTs). METHODS: We assessed cellular immune responses specific to influenza virus (FLU), JC virus (JCV), and varicella-zoster virus (VZV) using quantification of interferon-γ secretion by enzyme-linked immunospot in patients with MS on FTY (n = 31), including 2 with herpes zoster (HZ), natalizumab (n = 11), and other DMTs (n = 11). We used viral lysates for FLU and VZV and a pool of peptides for FLU, JCV (VP-1), and VZV (IE63). RESULTS: Besides an expected drop of T cells, we found that, proportionally to the number of CD3(+) T cells, only FTY-treated patients with MS exhibited an increased VZV/IE63-specific T cell response peaking 6 months into treatment, a response that returned to baseline after 12 and 24 months. Two FTY-treated patients developed an HZ 6 months into treatment, coinciding with an absent VZV/IE63-specific T cell response. However, cellular immune responses specific to VZV lysate, JCV, and FLU (lysate and pool of peptide epitopes) were similar between all 3 categories (FTY, natalizumab, and other DMTs) of study patients. CONCLUSIONS: FTY-treated patients with MS exhibit an increased VZV/IE63-specific cellular immune response after 6 months of treatment. FTY-treated patients who develop an HZ are not able to mount such a response, suggesting that a T cell response directed against this viral protein may be key in preventing the occurrence of HZ.