Smoothing effect on calculated dose We hypothesize that the radiation beams are less attenuated when a CT image has such smoothing effect. This would subsequently result in overestimation of the calculated doses. To test this hypothesis, we performed a smoothing on a real CT image via Gaussian convolution with full width at half maximum of 6 mm and recalculated the dose. Dosimetric parameters evaluated were found to be higher than the original values; for example, 1.1% of the prescription dose in D95 to the PTV, 0.6% of the original value in maximum dose to the chiasm, and 3.1%/5.6% of the original values in mean dose to the left/right cochleae. FIG S1. Age distribution of the test patient (denoted by “Test”) and the two atlas groups. The dots in this graph were “jittered” to avoid overlap. Note that the group of 6 atlases is a subset of the group of 12 atlases. The selections of the three groups were made such that age and gender distributions were not statistically different between the test patient group and either of the atlas groups (Student t-test on age, P>0.5; Fisher’s exact test on gender, P>0.1). FIG S2. Correlation between gross tumor volume and the accuracy of constructed pseudo CT evaluated by RMSD from real CT (R=0.55, P=0.040, N=14). FIG S3. Correlation between age difference (between atlas and patient) and the accuracy of constructed pseudo CT evaluated by RMSD from real CT (R=0.18, P=0.02, N=168). FIG S4. Demonstration of the case (patient #14) with problematic image deformation. The gray scale of CT images was adjusted such that ventricular structure is displayed. The images are all at the same slice location. The pseudo CTs constructed by different schemes (b-e) are compared with the real CT (a) and the corresponding MR image (f). The yellow arrows on pseudo CTs indicate a region where ventricle area in the patient image is occupied by brain tissue in the deformed single atlas image due to mis-registration. The ventricular structure in this region is not clear in MEAN6 but it is improved by PRGP6 and PRGP12. FIG S5. Variation of cranial bone density and the relation with accuracy in deformation of atlas images. (a) The distribution of bone density in test and atlas groups. The bone density was estimated by CT numbers in cranial bone structure segmented by Otsu’s method. The mean ± standard deviation values were: 1924±80 (N=14) for the test patients (denoted by “Test”) and 1927±75 (N=6) and 1899±79 and (N=12) for the two atlas groups. No difference between test patient and either of the atlas groups was found (Student t-test, P>0.44). (b) Scatter plot between ages of 26 test/atlas patients (please note that the 6 atlas group is a subset of the 12 atlas group) and CT numbers. No significant correlation was found (R=0.31, P=0.13). (c) When counting only voxels within cranial bone, the age difference between patient and atlas images was not correlated with the deformation accuracy any more (R=0.03, P=0.70, cf. Fig. S3). This must have been contributed by the individual variation of bone density which is not strongly associated with age. (a) MR images of an example patient (c) Atlases acquired by different sets of parameters before histogram matching (d) Atlases in (c) after histogram matching (denoted by “HM1” – “HM5”) HM1 (b) Atlas acquired by the same parameters as the patient images (denoted by “SAP”) HM2 HM3 Weighting (e) 0.3 HM4 0.2 0.1 0 HM5 -0.1 SAP HM1 HM2 HM3 HM4 HM5 FIG S6. Evaluation of the histogram matching algorithm. MR images of an example patient in the test group (a) were compared with images from an atlas sharing the same acquisition parameters with the patient (b, denoted by “SAP”) and the other atlases acquired by different sets of parameters (c) but processed with the histogram matching algorithm (d, denoted by “HM1”-”HM5”). The weighting values assigned to the atlases (ܓCିଵ in Eq. A3) during PRGP were evaluated. The boxplots (e) did not show any apparent bias (i.e., higher weighing values) towards SAP against HM1 - HM5. Please note that all atlas images in this figure have been deformed to the patient images.
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