Accurate and precise estimation of organ activities is essential for treatment planning in targeted radionuclide therapy. We have previously evaluated the impact of processing methodology, statistical noise and variability in activity distribution and anatomy on the accuracy and precision of organ activity estimates obtained with quantitative SPECT (QSPECT) and planar (QPlanar) processing. Another important factor impacting the accuracy and precision of organ activity estimates is accuracy of and variability in the definition of organ regions of interest (ROI) or volumes of interest (VOI). The goal of this work was thus to systematically study the effects of VOI definition on the reliability of activity estimates. To this end, we performed Monte Carlo simulation studies using randomly perturbed and shifted VOIs to assess the impact on organ activity estimates. The 3D NCAT phantom was used with activities that modeled clinically observed (111)In ibritumomab tiuxetan distributions. In order to study the errors resulting from misdefinitions due to manual segmentation errors, VOIs of the liver and left kidney were first manually defined. Each control point was then randomly perturbed to one of the nearest or next-nearest voxels in three ways: with no, inward or outward directional bias, resulting in random perturbation, erosion or dilation, respectively, of the VOIs. In order to study the errors resulting from the misregistration of VOIs, as would happen, e.g. in the case where the VOIs were defined using a misregistered anatomical image, the reconstructed SPECT images or projections were shifted by amounts ranging from -1 to 1 voxels in increments of with 0.1 voxels in both the transaxial and axial directions. The activity estimates from the shifted reconstructions or projections were compared to those from the originals, and average errors were computed for the QSPECT and QPlanar methods, respectively. For misregistration, errors in organ activity estimations were linear in the shift for both the QSPECT and QPlanar methods. QPlanar was less sensitive to object definition perturbations than QSPECT, especially for dilation and erosion cases. Up to 1 voxel misregistration or misdefinition resulted in up to 8% error in organ activity estimates, with the largest errors for small or low uptake organs. Both types of VOI definition errors produced larger errors in activity estimates for a small and low uptake organs (i.e. -7.5% to 5.3% for the left kidney) than for a large and high uptake organ (i.e. -2.9% to 2.1% for the liver). We observed that misregistration generally had larger effects than misdefinition, with errors ranging from -7.2% to 8.4%. The different imaging methods evaluated responded differently to the errors from misregistration and misdefinition. We found that QSPECT was more sensitive to misdefinition errors, but less sensitive to misregistration errors, as compared to the QPlanar method. Thus, sensitivity to VOI definition errors should be an important criterion in evaluating quantitative imaging methods.
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