The primary findings of the current study are that tissue inversion of water and fat has a not negligible prevalence in Dixon MRI of the brain and head/neck (23 of 283 patients). When Dixon MRI is subsequently used for attenuation correction, tissue inversion has a large quantitative effect on the resulting PET images (up to 35% error and non-uniformly distributed). Quantitative errors of this large magnitude are important for both clinical and research use of PET/MR.
For both brain and H/N patients, there was no overlap in the fraction of water voxels between inverted and non-inverted AC maps (Figure 3). This suggests that the identification of inverted MR-ACDixon can easily be automated based on the fat fraction in the image. Visual inspection is needed in the case of partial inversions, which were observed only infrequently (2 of 283 patients). We did not analyze the data with respect to anatomical anomalies occurring post surgery or from metallic implants, except for dental implants where no correlation with tissue inversion was found.
To analyze the extent of the error introduced by the fat/water inversion, we chose to use patients without inversion in order to have a gold standard PET image as a fair comparator. The images following the simulated inversion had tissue-fraction distributions similar to the brain patients with actual fat/water inversion, although with a slightly higher fraction of fat. We trust the results to be representative despite this overestimation introduced by the simulation.
The error for a given line-of-response (LOR) depends on the attenuation coefficient error and length of the path through the inverted tissue. The LORs passing the center must on average intersect more misclassified tissue than tangential LORs near the edges. This explains the radial bias observed (Figure 4G). The bias was consistent in all ten patients.
Problems using Dixon MR-based attenuation correction in PET/MR have previously been reported , including a case of false tissue assignment to lower thorax where lung tissue is assigned the attenuation coefficient of air. The phenomenon of inversion of water and fat is also well known  and occurs due to off-resonance effects caused by inhomogeneity of the B0 magnetic field. Off-resonance effects render the identification of water and fat from in- and opposed-phase images ambiguous, thus, leading to potential inversion artifacts. This ambiguity can be resolved using a number of methods; however, without knowing the exact implementation details, the reason for the fat/water inversion can only be speculated on. The most common method is the region-growing approach where the off-resonance region is determined one voxel at a time starting from one or more seed points. Choosing incorrect seed points might lead to incorrect tissue identification. This might be the explanation in the case imaging the legs (Figure 2 A,B,C,D,E). Multiple seed points are needed since the legs are not connected and choosing incorrect seed point in one leg could explain the inversion. This is further supported by the fact that the in-phase and opposed-phase images (Figure 2A,B) have identical left and right legs, indicating that the error occurs when identifying water and fat images.
The manufacturer's user manual advises that the attenuation maps should be visually inspected prior to continuation of the scan. In the case of an error, such as with tissue inversions, the manual advises a repetition of the scan. However, in our experience (supported by the few repeat examinations reported here), the error can be reproducible, so a rescan does not necessarily provide non-inverted images. For two patients, the inversion was only present in one of the repeat scans. With an underestimation of PET uptake of 10% to 35% in the case of inversion, such cases of inconsistent inversions are of course a significant problem for follow-up examinations and response evaluation which Wahl et al.  discussed in the case of solid tumors. Hence, the problem can only be corrected for by an off-line user-implemented inversion of fat and water, as was performed here. It is expected that tissue inversion is more frequent in the case of small body parts. A systematic comparison of the frequency of the effect for different body parts is out of the scope of the present work.
The findings in this paper add further concerns to those previously voiced ,,-. Tissue inversion needs to be considered if the construction of normal PET databases is performed based on Dixon-AC or if quantitative measures for simple semiquantitative analysis such as the standardized uptake value (SUV) are being used to set cut-off thresholds or follow treatment effects. We do not recommend the use of Dixon-AC for pharmacokinetic modeling of physiological parameters in the brain . In longitudinal follow-up in, e.g., dementia using FDG, regional activity may increase or decrease and using FET for tumor imaging the metabolically active area may change configuration. The study was limited to screening a large database of head and neck patients. However, the observed tissue swap effect can occur also in areas outside the head and neck as illustrated by the anecdotal example of the tissue inversion in the upper thighs. Therefore, utmost care is needed if Dixon-AC is to be used in clinical routine.