Rationale and Objectives: Treatment of brain neoplasms can greatly benefit from better delineation of bulk neoplasm boundary and the extent and degree of more subtle neoplastic infiltration. MRI is the primary imaging modality for evaluation before and after therapy, typically combining conventional sequences with more advanced techniques like perfusion-weighted imaging and diffusion tensor imaging (DTI). The purpose of this study is to quantify the multi-parametric imaging profile of neoplasms by integrating structural MRI and DTI via statistical image analysis methods, in order to potentially capture complex and subtle tissue characteristics that are not obvious from any individual image or parameter. Materials and Methods: Five structural MR sequences, namely, B0, Diffusion Weighted Images, FLAIR, T1-weighted, and gadolinium-enhanced T1-weighted, and two scalar maps computed from DTI, i.e., fractional anisotropy and apparent diffusion coefficient, are used to create an intensity-based tissue profile. This is incorporated into a non-linear pattern classification technique to create a multi-parametric probabilistic tissue characterization, which is applied to data from 14 patients with newly diagnosed primary high grade neoplasms who have not received any therapy prior to imaging. Results: Preliminary results demonstrate that this multi-parametric tissue characterization helps to better differentiate between neoplasm, edema and healthy tissue, and to identify tissue that is likely progress to neoplasm in the future. This has been validated on expert assessed tissue. Conclusion: This approach has potential applications in treatment, aiding computer-assisted surgery by determining the spatial distributions of healthy and neoplastic tissue, as well as in identifying tissue that is relatively more prone to tumor recurrence.