Kolind, S. | bioRxiv Science

bioRxiv2020

Non-negative least squares computation for in vivo myelin mapping using simulated multi-echo spin-echo T2 decay data

Multi-compartment T2-mapping has gained particular relevance for the study of myelin water in brain. As a facilitator of rapid saltatory axonal signal transmission, myelin is a cornerstone indicator of white matter development and function. Regularized non-negative least squares fitting of multi-echo T2 data has been widely employed for the computation of the myelin water fraction (MWF) and the obtained MWF maps have been histopathologically validated. MWF measurements depend upon the quality of the data acquisition, B1+-homogeneity and a range of fitting parameters. In this special issue article, we discuss the relevance of these factors for the accurate computation of multi-compartment T2 and MWF maps. We generated multi-echo spin-echo T2 decay curves following the approach of CarrPurcell-Meiboom-Gill for various myelin concentrations and myelin T2 scenarios by simulating the evolution of the magnetization vector between echoes based on the Bloch equations. We demonstrated that noise and imperfect refocusing flip angles yield systematic underestimations in MWF and intra-/extracellular water geometric mean (gm) T2. MWF estimates were more stable than myelin water gmT2 time across different settings of the T2 analysis. We observed that the lower limit of the T2 distribution grid should be slightly shorter than TE1. Both TE1 and the acquisition echo spacing also have to be sufficiently short to capture the rapidly decaying myelin water T2 signal. Among all parameters of interest, the estimated MWF and intra-/extracellular water gmT2 differed by approximately 0.13-4 percentage points and 3-4 ms, respectively, from the true values, with larger deviations observed in the presence of greater B1+-inhomogeneities and at lower signal-to-noise ratio. Tailoring acquisition strategies may allow to better characterize the T2 distribution, including the myelin water, in vivo.

biophysics↗

bioRxiv2019

Brain morphology predicts long-term placebo response in multiple sclerosis patients

Although significant insights have been gained into the neural mechanisms of acute placebo responses, less is known about the mechanisms of longer-term placebo responses, such as those seen in clinical trials, or the interactions between these mechanisms and brain disease. We examined neuropathological and morphological brain correlates of placebo responses in a randomized clinical trial of a controversial endovascular treatment ("liberation therapy") for multiple sclerosis. Patients were randomized to receive either balloon or sham extracranial venoplasty and followed for 48 weeks. The trial did not support therapeutic efficacy of venoplasty, but a subset of both venoplasty- and sham-treated patients reported an improvement in health-related quality of life that peaked at 12 weeks following treatment, suggesting a placebo response. Placebo responders had higher lesion activity than placebo non-responders. Although placebo responders did not differ from non-responders in terms of total normalized brain volume, regional grey or white matter volume or cortical thickness, graph theoretical analysis of cortical thickness covariance showed that placebo non-responders had a more homogenous cortical thickness topology with a more small-world-like architecture. In placebo non-responders, lesion load inversely predicted cortical thickness in primary somatosensory and motor areas, association areas, precuneus and insula, primarily in the right hemisphere. In placebo responders, lesion load was unrelated to cortical thickness. The neuropathological process in MS may result in a cortical configuration that is less suited to functional integration and less capable of generating a sustained placebo response.

neuroscience↗