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. Magn Reson Med 70:1450–1459, 2013. © 2012 Wiley Periodicals, Inc.