Test–retest reliability and concurrent validity of in vivo myelin content indices: Myelin water fraction and calibrated T₁w/T₂w image ratio

Abstract

In an age-heterogeneous sample of healthy adults, we examined test-retest reliability (with and without participant re-positioning) of two popular MRI methods of estimating myelin content: modeling the short spin-spin (T2) relaxation component of multi-echo imaging data and computing the ratio of T1-weighted and T2-weighted images (T1w/T2w). Taking the myelin water fraction (MWF) index of myelin content derived from the multi-component T2 relaxation data as a standard, we evaluate the concurrent and differential validity of T1w/T2w ratio images. The results revealed high reliability of MWF and T1w/T2w ratio. However, we found significant correlations of low to moderate magnitude between MWF and the T1w/T2w ratio in only two of six examined regions of the cerebral white matter. Notably, significant correlations of the same or greater magnitude were observed for T1w/T2w ratio and the intermediate T2 relaxation time constant, which is believed to reflect differences in the mobility of water between the intracellular and extracellular compartments. We conclude that although both methods are highly reliable and thus well-suited for longitudinal studies, T1w/T2w ratio has low criterion validity and may be not an optimal index of subcortical myelin content.

Intra‐cortical myelin mediates personality differences

“…At the group level (i.e., regardless of personality differences), we replicated the previous findings obtained in approximately 7% ( n = 69) of the same sample of participants, which were in turn consistent with the original postmortem map of myelination and myelin content provided by Paul Flechsig over a century ago (Arshad, Stanley, & Raz, ; Ganzetti, Wenderoth, & Mantini, ; Glasser & Van Essen, ; Leipsic, ; Shafee et al, ). Together, the data showed that the sensory‐motor cortices display the highest levels of myelin and the earliest myelination during brain maturation (Arshad et al, ; Ganzetti et al, ; Glasser & Van Essen, ; Leipsic, ; Shafee et al, ). Conversely, associative regions such as the prefrontal and temporo‐parietal cortices tend to myelinate later on during development and consequently show lighter myelin content compared to their sensory‐motor counterparts (Arshad et al, ; Ganzetti et al, ; Glasser & Van Essen, ; Leipsic, ; Shafee et al, ).…”

“…Together, the data showed that the sensory‐motor cortices display the highest levels of myelin and the earliest myelination during brain maturation (Arshad et al, ; Ganzetti et al, ; Glasser & Van Essen, ; Leipsic, ; Shafee et al, ). Conversely, associative regions such as the prefrontal and temporo‐parietal cortices tend to myelinate later on during development and consequently show lighter myelin content compared to their sensory‐motor counterparts (Arshad et al, ; Ganzetti et al, ; Glasser & Van Essen, ; Leipsic, ; Shafee et al, ). A similar relationship has been described between the intra‐cortical myelin levels and the degree of cortical expansion during evolution (Miller et al, ).…”

Magnetic resonance T1w/T2w ratio: A parsimonious marker for Parkinson disease

“…Previous studies have shown that it not only has superior sensitivity to myelin compared to diffusion MRI, but also superior test-retest reliability compared to other myelin imaging techniques. 20 …”

“…Originally proposed by Glasser et al, 19 a simple division of these images can yield a new quantitative contrast (T1w/T2w ratio) with high spatial resolution, test-retest reliability, and sensitivity to neurodegenerative changes demonstrated by recent studies. 20–22 Its simplicity and broad availability make it a promising candidate for studying PD-related changes. To our knowledge, there is neither a study that has used the T1w/T2w ratio to study structures other than cortical regions, nor has it been applied yet to a PD population.…”

Gray matter T1‐w/T2‐w ratios are higher in Alzheimer's disease

“…In disorders with a strong demyelinating component such as multiple sclerosis (MS), the T1‐w/T2‐w ratio is lowered in pathologically vulnerable regions (Beer et al, ; Nakamura, Chen, Ontaneda, Fox, & Trapp, ). However, recent studies have raised controversy on the interpretation of the T1‐w/T2‐w ratio, showing that this measure may also reflect tissue microstructure other than myelin, such as axon and dendrite density or iron content (Arshad, Stanley, & Raz, ; Righart et al, ; Uddin, Figley, Marrie, & Figley, ; van Rooden et al, ). Because disrupted brain connectivity is an important feature of AD (Dicks et al, ; Fornito et al, ; Pievani et al, ), an intracortical reduction of myelin content in AD could be hypothesized.…”