Probing the myelin water compartment with a saturation‐recovery, multi‐echo gradient‐recalled echo sequence

PurposeTo investigate the effect of varying levels of urn:x-wiley:07403194:media:mrm28695:mrm28695-math-0001‐weighting on the evolution of the complex signal from white matter in a multi‐echo gradient‐recalled echo (mGRE) saturation‐recovery sequence.Theory and MethodsAnalysis of the complex signal evolution in an mGRE sequence allows the contributions from short‐ and long‐urn:x-wiley:07403194:media:mrm28695:mrm28695-math-0002 components to be separated, thus providing a measure of the relative strength of signals from the myelin water, and the external and intra‐axonal compartments. Here we evaluated the effect of different levels of urn:x-wiley:07403194:media:mrm28695:mrm28695-math-0003‐weighting on these signals, expecting that the previously reported, short urn:x-wiley:07403194:media:mrm28695:mrm28695-math-0004 of the myelin water would lead to a relative enhancement of the myelin water signal in the presence of signal saturation. Complex, saturation‐recovery mGRE data from the splenium of the corpus callosum from 5 healthy volunteers were preprocessed using a frequency difference mapping (FDM) approach and analyzed using the 3‐pool model of complex signal evolution in white matter.ResultsAn increase in the apparent urn:x-wiley:07403194:media:mrm28695:mrm28695-math-0005 as a function of echo time was demonstrated, but this increase was an order of magnitude smaller than that expected from previously reported myelin water urn:x-wiley:07403194:media:mrm28695:mrm28695-math-0006‐values. This suggests the presence of magnetization transfer and exchange effects which counteract the urn:x-wiley:07403194:media:mrm28695:mrm28695-math-0007‐weighting.ConclusionVariation of the urn:x-wiley:07403194:media:mrm28695:mrm28695-math-0008 amplitude in a saturation‐recovery mGRE sequence can be used to modulate the relative strength of signals from the different compartments in white matter, but the modulation is less than predicted from previously reported urn:x-wiley:07403194:media:mrm28695:mrm28695-math-0009‐values

Multi-compartment analysis of the complex gradient-echo signal quantifies myelin breakdown in premanifest Huntington's disease

White matter (WM) alterations have been identified as a relevant pathological feature of Huntington’s disease (HD). Increasing evidence suggests that WM changes in this disorder are due to alterations in myelin‐associated biological processes. Multi-compartmental analysis of the complex gradient-echo MRI signal evolution in WM has been shown to quantify myelin in vivo, therefore pointing to the potential of this technique for the study of WM myelin changes in health and disease. This study first characterized the reproducibility of metrics derived from the complex multi-echo gradient-recalled echo (mGRE) signal across the corpus callosum in healthy participants, finding highest reproducibility in the posterior callosal segment. Subsequently, the same analysis pipeline was applied in this callosal region in a sample of premanifest HD patients (n = 19) and age, sex and education matched healthy controls (n = 21). In particular, we focused on two myelin-associated derivatives: i. the myelin water signal fraction (fm), a parameter dependent on myelin content; and ii. the difference in frequency between myelin and intra-axonal water pools (Δω), a parameter dependent on the ratio between the inner and the outer axonal radii. fm was found to be lower in HD patients (β = -0.13, p = 0.03), while Δω did not show a group effect. Performance in tests of working memory, executive function, social cognition and movement was also assessed, and a greater age-related decline in executive function was detected in HD patients (β = -0.06, p = 0.006), replicating previous evidence of executive dysfunction in HD. Finally, the correlation between fm, executive function, and proximity to disease onset was explored in patients, and a positive correlation between executive function and fm was detected (r = 0.542; p = 0.02). This study emphasises the potential of complex mGRE signal analysis for aiding understanding of HD pathogenesis and progression. Moreover, expanding on evidence from pathology and animal studies, it provides novel in vivo evidence supporting myelin breakdown as an early feature of HD