Characterizing inter‐compartmental water exchange in myelinated tissue using relaxation exchange spectroscopy

PURPOSE: To investigate inter-compartmental water exchange in two model myelinated tissues ex vivo using relaxation exchange spectroscopy. METHODS: Building upon a previously developed theoretical framework, a three-compartment (myelin, intra-axonal, and extra-axonal water) model of the inversion-recovery prepared relaxation exchange spectroscopy signal was applied in excised rat optic nerve and frog sciatic nerve samples to estimate the water residence time constants in myelin (τmyelin ). RESULTS: In the rat optic nerve samples, τmyelin = 138 ± 15 ms (mean ± standard deviation) was estimated. In sciatic nerve, which possesses thicker myelin sheaths than optic nerve, a much longer τmyelin = 2046 ± 140 ms was observed. CONCLUSION: Consistent with previous studies in rat spinal cord, the extrapolation of exchange rates in optic nerve to in vivo conditions indicates that τmyelin < 100 ms. This suggests that there is a significant effect of inter-compartmental water exchange on the transverse relaxation of water protons in white matter. The much longer τmyelin values in sciatic nerve supports the postulate that the inter-compartmental water exchange rate is mediated by myelin thickness. Together, these findings point to the potential for MRI methods to probe variations in myelin thickness in white matter.