Evaluation of imaging for cancer detection and localization can be achieved by correlation of gold-standard histopathology with imaging data. Usage of a 3D biomechanical-based deformable registration for correlation of the histopathology of whole-tissue specimens with ex vivo imaging necessitates measurement of the distribution of biomechanical properties in the ex vivo tissue specimen and changes that occur during pathology fixation. To measure high-resolution 3D distributions of Young's modulus (E) prefixation and postfixation, a quasi-static magnetic resonance elastography method was developed at 7 T. Use of echo-planar imaging allowed for shorter imaging times, in line with limited time frames allowable for pathology specimens. The finite element modeling algorithm produced voxel-wise E measures, and mechanical indentation was used for comparison. An initial preclinical evaluation with canine prostate specimens (n 5 5) demonstrated a consistent increase in E with fixation (P < 0.002) by a factor of 4 (61). Increases were a function of distance from the tissue edge and correlated with fixation time (r 5 1, P < 0.02). The technique will be used to generate population-averaged data of E from clinical ex vivo specimens prefixation and postfixation to inform registration of whole-mount histopathology with in vivo imaging. Magn Reson Med 68:152-165, 2012. V C 2011 Wiley Periodicals, Inc.Key words: quasi-static magnetic resonance elastography; biomechanical registration; histopathology correlation; pathology fixation MR imaging parameters have been used to detect and localize prostate cancer for targeted therapy, e.g., T 2 -weighted signal, dynamic contrast-enhanced MRI, and diffusion-weighted MRI (1,2). To determine sensitivity and specificity, parameters must be evaluated against the gold standard of histology (3). Whole-mount histopathology of radical prostatectomy specimens maps the spatial distribution of disease across the tissue cross section (3) and can be reconstructed into a 3D digital histopathology volume with the tumor as a subvolume (4). As prostate tissue undergoes deformation and shrinkage between the in vivo and histopathology states, a deformable registration approach is required for accurate correlation (5). The multiple sources of deformation necessitate a step-wise approach through the varying tissue states: in vivo (where the prostate is compressed through the use of an endorectal radiofrequency receiver coil); ex vivo postsurgery; ex vivo after wholespecimen submersion in pathology fixative solution; and histology (where pathology processing and sectioning cause shrinkage and deformation). MRI volumes of the whole ex vivo specimen can be acquired before and after fixation to determine deformation under gravity during fixation. A biomechanical-based deformable registration approach has demonstrated high accuracy in mapping tumor volumes from radiation therapy planning images into the images acquired at treatment, to assess targeting accuracy after morphological changes (6). This involves split...