To gate or not to gate: An evaluation of respiratory gating techniques to improve volume measurement of murine lung tumors in micro-CT imaging
Small animal imaging has become essential in evaluating new cancer therapies as they are translated from the preclinical to clinical domain. However, preclinical imaging is faced with unique challenges that emphasize the gap between mouse and man. One example is the difference in breathing patterns and breath-holding ability, which can dramatically affect tumor burden assessment in lung tissue. Our group is developing quantitative imaging methods for the preclinical arm of a co-clinical trial studying synergy between immunotherapy (anti-PD-1) and radiotherapy in a soft tissue sarcoma model. To mimic imaging performed in patients, primary sarcomas lesions are imaged with micro-MRI, while detection of lung metastases is performed with micro-CT. This study addresses whether respiratory gating during micro-CT acquisition improves lung tumor volume quantitation. Accuracy and precision of lung tumor measurements was determined by performing experiments involving simulations, a pocket phantom and in vivo scans with and without prospective respiratory gating. Sensitivity and precision of segmentation with and without gating was studied using simulated lung tumors. A clinically-inspired "pocket phantom" was used during in vivo mouse scanning to aid in refining and assessing the gating protocols. Finally, we performed a series of in vivo scans on tumor-bearing mice while varying the animal's position (test-retest), and performing the analyses in triplicate to assess the effects of gating. Application of respiratory gating techniques reduced variance of repeated volume measurements and significantly improved the accuracy of tumor volume quantitation in vivo.