In-vivo multi-exponential T2, magnetization transfer and quantitative histology in a rat model of intramyelinic edema

•We studied a rat model of intra-myelinic edema induced by hexachlorophene ingestion.•We used multi-exponential T2 (MET2) and quantitative magnetization transfer MRI.•Histology was quantitatively evaluated to measure edema volume and myelin content.•MET2 provides a measure that correlates but overestimates with edema volume fraction.•MET2 measure of edema is affected by microscopic water dynamics.

Two MRI methods, multi-exponential analysis of transverse relaxation (MET2) and quantitative magnetization transfer (qMT), were used along with quantitative evaluation of histology in a study of intra-myelinic edema in rat spinal white matter. The results showed a strong linear correlation between a distinct long-T2 signal from MET2 analysis and the edema water volume fraction as measured by histology, although this analysis overestimated the edema water content by ≈ 100% relative to quantitative histological measurements. This overestimation was reasoned to result from the effects of inter-compartmental water exchange on observed transverse relaxation. Commonly studied MRI markers for myelin, the myelin water fraction (from MET2 analysis) and the macromolecular pool size ratio (from qMT analysis) produced results that could not be explained purely by changes in myelin content. The results demonstrate the potential for MET2 analysis as well as the limits of putative myelin markers for characterizing white matter abnormalities involving intra-myelinic edema.