Purpose: Xerostomia (dry mouth), secondary to irradiation of the parotid glands, is one of the most common side effects of head-and-neck cancer radiotherapy. Diagnostic tools able to accurately and efficiently measure parotid gland injury have yet to be introduced into the clinic. This studys purpose is to investigate sonographic textural features as potential imaging signatures for quantitative assessment of parotid-gland injury after head-and-neck radiotherapy. Methods: The authors have investigated a series of sonographic features obtained from the gray level co-occurrence matrix (GLCM) - a second order statistical method of texture analysis. These GLCM textural features were selected based on empirical observations that the normal parotid gland exhibits homogeneous echotexture, whereas the postradiotherapy parotid gland often exhibits heterogeneous echotexture. We employed eight sonographic features: (1) angular second moment (ASM), (2) inverse differential moment (IDM), (3) contrast, (4) variance, (5) correlation, (6) entropy, (7) cluster shade, and (8) cluster prominence. Altogether, sonographic properties of the parotid glands were quantified by their degrees of homogeneity (ASM and IDM), heterogeneity (contrast and variance), smoothness (correlation), randomness (entropy), and symmetry (cluster shade and prominence). The sonographic features were tested in a pilot study of 12 postradiotherapy patients and 7 healthy volunteers. The mean follow-up time for the postradiotherapy patients was 17.2 months (range: 12.1-23.9 months) and the mean radiation dose to the parotid glands was 32.3 Gy (range: 11.0-63.4 Gy). Each participant underwent one ultrasound study in which longitudinal (vertical) ultrasound scans were performed on the bilateral parotids - a total of 24 postirradiation and 14 normal parotid glands were examined. The 14 normal parotid glands served as the control group. A radiologist contoured the parotid glands on the B-mode images and the sonographic features were computed from the contoured region-of-interest. Results: The authors observed significant differences (p 0.05) in all sonographic features between the normal and postradiotherapy parotid glands. The sonographic findings were consistent with the clinical observations of the ultrasound images: normal parotid glands exhibited homogeneous texture, while the postradiotherapy parotid glands exhibited heterogeneous echotexture (e.g., hyperechoic lines and spots), which likely represents fibrosis. Conclusions: The authors have demonstrated the feasibility of ultrasonic texture evaluation of parotid glands; and the sonographic features may serve as imaging signatures to assess radiation-induced parotid injury. © 2012 American Association of Physicists in Medicine.