Fusion of information from PET and MR imaging can increase the diagnostic value of both modalities. This work sought to improve 18 F FDG PET image quality by using MR Dixon fat-constrained images to constrain PET image reconstruction to low-fat regions, with the working hypothesis that fatty tissue metabolism is low in glucose consumption. Methods: A novel constrained PET reconstruction algorithm was implemented via a modification of the system matrix in list-mode timeof-flight ordered-subsets expectation maximization reconstruction, similar to the way time-of-flight weighting is incorporated. To demonstrate its use in PET/MR imaging, we modeled a constraint based on fat/water-separating Dixon MR images that shift activity away from regions of fat tissue during PET image reconstruction. PET and MR imaging scans of a modified National Electrical Manufacturers Association/ International Electrotechnical Commission body phantom simulating body fat/water composition and in vivo experiments on 2 oncology patients were performed on a commercial time-of-flight PET/MR imaging system. Results: Fat-constrained PET reconstruction visibly and quantitatively increased resolution and contrast between high-uptake and fatty-tissue regions without significantly affecting the images in nonfat regions. Conclusion: The incorporation of MR tissue information, such as fat, in image reconstruction can improve the quality of PET images. The combination of a variety of potential other MR tissue characteristics with PET represents a further justification for merging MR data with PET data in hybrid systems. PET/ MR is rapidly emerging as a promising new hybrid imaging modality. Among several differentiating features when compared with PET/CT, the combination of PET with MR imaging can potentially benefit from reduced radiation for the patient and predominantly from the wider range of tissue characteristics generated by appropriate MR imaging sequences and their multiparametric combinations (1). MR provides anatomic imaging with better soft-tissue depiction and more dedicated tissue contrast than CTand furthermore offers insight into a variety of aspects of human physiology with the potential to image metabolic processes and physiologic function (2-4), complementing metabolic and molecular information afforded by PET for better assessment of the underlying physiopathology (5). Beyond these diagnostic aspects, in the hybrid setting with PET, MR data are also used to estimate tissuedependent photon attenuation and scatter to improve the quantitative accuracy of PET images (6-8). The MR-based motion correction of PET reconstruction to improve PET image quality is also supported (9,10).Spatial resolution and quantification accuracy in PET imaging are limited by the low detector spatial resolution and poor photon counting statistics. Early developments in PET reconstruction techniques have addressed this limitation by modeling the underlying photon generation statistics and taking advantage of the physics of coincidence detection to find an app...