Strategies to reduce artifacts and improve accuracy in multiplexed multi-pinhole small animal SPECT

Multi-pinhole collimation is commonly used to improve image quality in small animal SPECT. However multiplexed pinhole projections may introduce ambiguity in image reconstruction and may cause image artifacts and inaccurate quantification. We investigated strategies to optimize data sampling and minimize artifacts, including varying the pinhole configuration and providing a CT-based seed for iterative image reconstruction. Through computer simulations, we assessed the merits of these strategies in terms of quantitative accuracy, image noise, and lesion detection. Use of the CT-based seed for reconstruction significantly reduced multiplexing artifact and improved quantitative accuracy. Overall image quality was best with an imbalanced and irregular multiplexed pinhole configuration, which provided better lesion detection than the non-multiplexed configuration and with negligible artifact. Irregular pinhole patterns also appeared less sensitive to artifacts from unshielded background counts. Ultimately, the optimal pinhole configuration depends on the actual activity distribution. Having a collimator design where some pinholes may be selectively blocked may provide optimal flexibility for various mouse imaging applications.