Micro-Single-Photon Emission Computed Tomography Image Acquisition and Quantification of Sodium-Iodide Symporter-Mediated Radionuclide Accumulation in Mouse Thyroid and Salivary Glands

Background: Micro-single-photon emission computed tomography (SPECT) provides a noninvasive way to evaluate the effects of genetic and/or pharmacological modulation on sodium-iodide symporter (NIS)-mediated radionuclide accumulation in mouse thyroid and salivary glands. However, parameters affecting image acquisition and analysis of mouse thyroids and salivary glands have not been thoroughly investigated. In this study, we investigated the effects of region-of-interest (ROI) selection, collimation, scan time, and imaging orbit on image acquisition and quantification of thyroidal and salivary radionuclide accumulation in mice. Methods: The effects of data window minima and maxima on thyroidal and salivary ROI selection using a visual boundary method were examined in SPECT images acquired from mice injected with I-123 NaI. The effects of collimation, scan time, and imaging orbit on counting linearity and signal intensity were investigated using phantoms filled with various activities of I-123 NaI or Tc-99m pertechnetate. Spatial resolution of target organs in whole-animal images was compared between circular orbit with parallel-hole collimation and spiral orbit with five-pinhole collimation. Lastly, the inter-experimental variability of the same mouse scanned multiple times was compared with the intra-experimental variability among different mice scanned at the same time. Results: Thyroid ROI was separated from salivary glands by empirically increasing the data window maxima. Counting linearity within the range of 0.5-14.2 mu Ci was validated by phantom imaging using single- or multiple-pinhole collimators with circular or spiral imaging orbit. Scanning time could be shortened to 15 minutes per mouse without compromising counting linearity despite proportionally decreased signal intensity. Whole-animal imaging using a spiral orbit with five-pinhole collimators achieved a high spatial resolution and counting linearity. Finally, the extent of inter-experimental variability of NIS-mediated radionuclide accumulation in the thyroid and salivary glands by SPECT imaging in the same mouse was less than the magnitude of variability among the littermates. Conclusions: The impacts of multiple variables and experimental designs on micro-SPECT imaging and quantification of radionuclide accumulation in mouse thyroid and salivary glands can be minimized. This platform will serve as an invaluable tool to screen for pharmacologic reagents that differentially modulate thyroidal and salivary radioiodine accumulation in preclinical mouse models.