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Purpose To compare the value of diffusion-weighted MRI (DWI), dynamic contrast-enhanced (DCE) MRI, and microbubble contrast-enhanced ultrasound (CEUS) for assessment of the thermal lesion created by interstitial microwave heating of the normal canine prostate. Materials and Methods A microwave antenna was inserted into each lobe of the prostate in seven dogs to induce coagulation necrosis. Immediately after therapy the lesion was assessed using CEUS, DCE-MRI, and DWI. The prostates were excised, photographed, and prepared for hematoxylin and eosin staining. Results from posttreatment MRI and ultrasound were compared to histology. Results The apparent diffusion coefficient (ADC) was slightly lowered within the thermal lesion but was drastically reduced in a ring-like region that corresponds to a grossly appearing red thermal damage zone immediately peripheral to the central coagulum. Both DCE-MRI and CEUS delineated a smaller area of vascular damage, for which the borders lie within the red zone. Conclusion The red zone encompasses a range of vascular responses, including hyperemia and hemostasis, and is known to progress to necrosis and tissue nonviability. DWI clearly depicts this zone as a region of sharply reduced ADC, and may be better than contrast-enhanced imaging for accurate assessment of the eventual full extent of thermal damage. J. Magn. Reson. Imaging 2008;28:136–143. © 2008 Wiley-Liss, Inc.