3795

In vivo micro-CT of mouse lungs without respiratory gating

Tuesday, Apr 19, 2005, 8:00 AM -12:00 PM

Board #10

Erin Trachet, Jonathan B. Moody, Patrick McConville, William L. Elliott, Wilbur R. Leopold. MIR Preclinical Services, Ann Arbor, MI

Introduction: In vivo applications of high resolution x-ray micro-computed tomography (μCT) are now becoming feasible, particularly for in vivo detection of lung nodules in mouse tumor models [1]. In order to quantify the incidence and size of lung nodules in individual animals over time, image artifacts due to respiratory motion must be minimized. Using a novel μCT scanner (GE Healthcare) that allows unusually short exposure times, we examined the influence of breathing motion in a model of B-16 melanoma metastatic to the lung in mice.
Methods: Twenty-four C57 mice were implanted with B-16 tumor cells by IV injection. Serial scanning of mice by μCT began after 14 days. The μCT scanner is specially designed to allow a 30 msec per frame exposure time. The influence of respiratory motion was assessed by scanning animals freely breathing and immediately after euthanasia. Lungs were harvested and fixed in formalin for ex vivo imaging by μCT, visual inspection and histological analysis of tumor incidence and size. A cohort of animals was selected and euthanized at regular intervals to monitor tumor growth.
Results and Discussion: Lung tumors developed in 96% of implanted animals. Early stage tumors (2 weeks post-implant) were 0.5-1 mm in size and 3-6 were found per animal. At four weeks post-implant, the number of visible tumors increased (>50 per lung), and tumor size increased to 1-3 mm. μCT images of lung tumors correlated well with the results of visual inspection. The accuracy of tumor size measurements was somewhat enhanced in the absence of breathing motion due to sharper tumor boundaries. However, tumors less than 1 mm in diameter could be detected and followed in vivo without respiratory gating (Fig. 1) .
Conclusion: Using a novel μCT scanner designed for rapid in vivo imaging, the evaluation of lung nodule incidence and size correlated well with autopsy results. Future work will focus on developing a more clinically relevant subcutaneous model of B-16 metastasis, as well as serial imaging of individual animals over time to monitor tumor response to chemotherapeutics.
[1] Cavanaugh, D, et al. (2004), Molecular Imaging, 3 pp. 55-62.
Figure 1: μCT of mouse lung nodules with (A) and without (B) respiratory motion.