BACKGROUND: A number of clinical tools exist for measuring the severity of cervical spondylotic myelopathy (CSM). Several studies have recently described the use of non-invasive imaging biomarkers to assess severity of disease. These imaging markers may provide an additional tool to measure disease progression and represent a surrogate marker of response to therapy. Correlating these imaging biomarkers with clinical quantitative measures is critical for accurate therapeutic stratification and quantification of axonal injury. METHODS: Fourteen patients and seven healthy control subjects were enrolled. Patients were classified as mildly (7) or moderately (7) impaired based on Modified Japanese Orthopedic Association Scale. All patients underwent diffusion tensor imaging (DTI) and diffusion basis spectrum imaging (DBSI) analyses. In addition to standard neurological examination, all participants underwent 30-m Walking Test, 9-hole Peg Test (9HPT), grip strength, key pinch, and vibration sensation thresholds in the index finger and great toe. Differences in assessment scores between controls, mild and moderate CSM patients were correlated with DTI and DBSI derived fractional anisotropy (FA). RESULTS: Clinically, 30-meter walking times were significantly longer in the moderately impaired group than in the control group. Maximum 9HPT times were significantly longer in both the mildly and moderately impaired groups as compared to normal controls. Scores on great toe vibration sensation thresholds were lower in the mildly impaired and moderately impaired groups as compared to controls. We found no clear evidence for any differences in minimum grip strength, minimum key pinch, or index finger vibration sensation thresholds. There were moderately strong associations between DTI and DBSI FA values and 30-meter walking times and 9HPT. CONCLUSIONS: The 30-m Walking Test and 9HPT were both moderately to strongly associated with DTI/DBSI FA values. FA may represent an additional measure to help differentiate and stratify patients with mild or moderate CSM. © 2016 EDIZIONI MINERVA MEDICA.