A multi-centre evaluation of eleven clinically feasible brain PET/MRI attenuation correction techniques using a large cohort of patients

AIM: To accurately quantify the radioactivity concentration measured by PET, emission data need to be corrected for photon attenuation; however, the MRI signal cannot easily be converted into attenuation values, making attenuation correction (AC) in PET/MRI challenging. In order to further improve the current vendor-implemented MR-AC methods for absolute quantification, a number of prototype methods have been proposed in the literature. These can be categorized into three types: template/atlas-based, segmentation-based, and reconstruction-based. These proposed methods in general demonstrated improvements compared to vendor-implemented AC, and many studies report deviations in PET uptake after AC of only a few percent from a gold standard CT-AC. Using a unified quantitative evaluation with identical metrics, subject cohort, and common CT-based reference, the aims of this study were to evaluate a selection of novel methods proposed in the literature, and identify the ones suitable for clinical use. METHODS: In total, 11 AC methods were evaluated: two vendor-implemented (MR-AC(DIXON) and MR-AC(UTE)), five based on template/atlas information (MR-AC(SEGBONE) (Koesters et al., 2016), MR-AC(ONTARIO) (Anazodo et al., 2014), MR-AC(BOSTON) (Izquierdo-Garcia et al., 2014), MR-AC(UCL) (Burgos et al., 2014), and MR-AC(MAXPROB) (Merida et al., 2015)), one based on simultaneous reconstruction of attenuation and emission (MR-AC(MLAA) (Benoit et al., 2015)), and three based on image-segmentation (MR-AC(MUNICH) (Cabello et al., 2015), MR-AC(CAR-RiDR) (Juttukonda et al., 2015), and MR-AC(RESOLUTE) (Ladefoged et al., 2015)). We selected 359 subjects who were scanned using one of the following radiotracers: [(18)F]FDG (210), [(11)C]PiB (51), and [(18)F] florbetapir (98). The comparison to AC with a gold standard CT was performed both globally and regionally, with a special focus on robustness and outlier analysis. RESULTS: The average performance in PET tracer uptake was within ± 5% of CT for all of the proposed methods, with the average ± SD global percentage bias in PET FDG uptake for each method being: MR-AC(DIXON) (−11.3 ± 3.5)%, MR-AC(UTE) (−5.7 ± 2.0)%, MR-AC(ONTARIO) (−4.3 ± 3.6)%, MR-AC(MUNICH) (3.7 ± 2.1)%, MR-AC(MLAA) (−1.9 ± 2.6)%, MR-AC(SEGBONE) (−1.7 ± 3.6)%, MR-AC(UCL) (0.8 ± 1.2)%, MR-AC(CAR-RiDR) (−0.4 ± 1.9)%, MR-AC(MAXPROB) (−0.4 ± 1.6)%, MR-AC(BOSTON) (−0.3 ± 1.8)%, and MR-AC(RESOLUTE) (0.3 ± 1.7)%, ordered by average bias. The overall best performing methods (MR-AC(BOSTON), MR-AC(MAXPROB), MR-AC(RESOLUTE) and MR-AC(UCL), ordered alphabetically) showed regional average errors within ± 3% of PET with CT-AC in all regions of the brain with FDG, and the same four methods, as well as MR-AC(CAR-RiDR), showed that for 95% of the patients, 95% of brain voxels had an uptake that deviated by less than 15% from the reference. Comparable performance was obtained with PiB and florbetapir. CONCLUSIONS: All of the proposed novel methods have an average global performance within likely acceptable limits ( ± 5% of CT-based reference), and the main difference among the methods was found in the robustness, outlier analysis, and clinical feasibility. Overall, the best performing methods were MR-ACBOSTON, MR-ACMAXPROB, MR-ACRESOLUTE and MR-ACUCL, ordered alphabetically. These methods all minimized the number of outliers, standard deviation, and average global and local error. The methods MR-ACMUNICH and MR-ACCAR-RiDR were both within acceptable quantitative limits, so these methods should be considered if processing time is a factor. The method MR-ACSEGBONE also demonstrates promising results, and performs well within the likely acceptable quantitative limits. For clinical routine scans where processing time can be a key factor, this vendor-provided solution currently outperforms most methods. With the performance of the methods presented here, it may be concluded that the challenge of improving the accuracy of MR-AC in adult brains with normal anatomy has been solved to a quantitatively acceptable degree, which is smaller than the quantification reproducibility in PET imaging.