Cardiac perfusion imaging of small rodents using cone-beam micro-CT

Mouse models of cardiac diseases have proven to be a valuable tool in preclinical research. The rapid heart and respiratory rates of free breathing mice and the consequent technical challenges up to now prohibit in vivo perfusion studies, e.g. of the myocardium, even if gating methods are applied. This makes a sacrification of the animals unavoidable and only allows for the application of static ex vivo methods. To overcome this issue we propose a low-dose scan protocol and an associated reconstruction algorithm that allows for triple phase-correlated in vivo imaging of perfusion and associated processes. The scan protocol encompasses a repetitive, retro-bulbar injection of contrast media within several consecutive scans while the ECG, respiratory motion and the timestamp of contrast media injection are recorded and synchronized to the acquired projection images. The proposed iterative reconstruction algorithm employs a six-dimensional (three spatial dimensions, three temporal dimensions: cardiac and respiratory motion, tissue perfusion) bilateral filter to provide volumes free of motion artifacts with low noise of the animal under examination. The reconstructions obtained show that the perfusion of tissue can be visualized in any desired combination of cardiac and respiratory phases with low image noise and free of motion artifacts. The proposed reconstruction method thereby keeps the administered radiation dose as low as 500 mGy and thus reduces metabolic inference to the animal allowing for longitudinal studies. Our low-dose scan protocol and our low-dose phase-correlated dynamic reconstruction algorithm allows for an easy hence effective way to visualize triple phase-correlated cardiac perfusion in free-breathing mice and can be implemented into existing systems and the laboratory routine. It thus provides the first approach to phase-correlated perfusion CT imaging in mice boosting preclinical research with a whole new range of possibilities.