Temperature dependence and histological correlation of inhomogeneous magnetization transfer and myelin water imaging in ex vivo brain

The promise of inhomogeneous magnetization transfer (ihMT) as a new myelin imaging method was studied in ex vivo human brain tissue and in relation to myelin water fraction (MWF). The temperature dependence of both methods was characterized, as well as their correspondence with a histological measure of myelin content. Unfiltered and filtered ihMT protocols were studied by adjusting the saturation scheme to preserve or attenuate signal from tissue with short dipolar relaxation time T1D. ihMT ratio (ihMTR) and MWF maps were acquired at 7 T from formalin-fixed human brain samples at 22.5 °C, 30 °C and 37 °C. The impact of temperature on unfiltered ihMTR, filtered ihMTR and MWF was investigated and compared to myelin basic protein staining. Unfiltered ihMTR exhibited no temperature dependence, whereas filtered ihMTR increased with increasing temperature. MWF decreased at higher temperature, with an increasing prevalence of areas where the myelin water signal was unreliably determined, likely related to a reduction in T2 peak separability at higher temperatures ex vivo. MWF and ihMTR showed similar per-sample correlation with myelin staining at room temperature. At 37 °C, filtered ihMTR was more strongly correlated with myelin staining and had increased dynamic range compared to unfiltered ihMTR. Given the temperature dependence of filtered ihMT, increased dynamic range, and strong myelin specificity that persists at higher temperatures, we recommend carefully controlled temperatures close to 37 °C for filtered ihMT acquisitions. Unfiltered ihMT may also be useful, due to its independence from temperature, higher amplitude values, and sensitivity to short T1D components. Ex vivo myelin water imaging should be performed at room temperature, to avoid fitting issues found at higher temperatures.