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To monitor the spontaneous recovery of cervical spinal cord injury (SCI) using longitudinal multiparametric MRI methods.Quantitative MRI imaging including diffusion tensor imaging, magnetization transfer (MT), and chemical exchange saturation transfer (CEST) were conducted in anesthetized squirrel monkeys at 9.4T. The structural, cellular, and molecular features of the spinal cord were examined before and at different time points after a dorsal column lesion in each monkey.Images with MT contrast enhanced visualization of the gray and white matter boundaries and the lesion and permitted differentiation of core and rim compartments within an abnormal volume (AV). In the early weeks after SCI, both core and rim exhibited low cellular density and low protein content, with high levels of exchanging hydroxyl, amine, and amide protons, as evidenced by increased apparent diffusion coefficient, decreased fractional anisotropy, decreased MT ratio, decreased nuclear Overhauser effect, and large CEST effects. Over time, cellular density and fiber density increased, whereas amide, amine, and hydroxyl levels dropped significantly, but at differing rates. Histology confirmed the nature of the AV to be a cyst.Multiparametric MRI offers a novel method to quantify the spontaneous changes in structure and cellular and molecular compositions of SC during spontaneous recovery from injury. Magn Reson Med 74:1125–1137, 2015. © 2014 Wiley Periodicals, Inc.