research, cardiac micro-CT

back to research page

We designed a non-invasive micro-CT based imaging technique appropriate for in vivo characterization of cardiac structure and function in mouse models of cardiovascular disease.

This prototype micro-CT system addressed two significant barriers to micro-CT in small animals—reduced signal-to-noise imposed by the smaller voxels and motion (C Badea, L. Hedlund, GA Johnson, Micro-CT with respiratory and cardiac gating, Medical Physics 31[12] 3324-3329, 2004; pdf of article). We used high instantaneous X -ray photon fluence with fully integrated monitoring and control of physiologic motion.

Figure 1 shows the micro-CT system with a fixed tube/detector and a rotating specimen. We used a large focal spot (0.3/1 mm) x-ray tube to produce high fluence rates with short exposure times. We optimized the geometry to match focal spot blur with detector pitch and the resolution limits imposed by the reproducibility of gating. Thus, it is possible to achieve isotropic spatial resolution of 100 microns with a fluence rate at the detector 250-times that of a conventional cone beam micro-CT system with rotating detector and microfocal x-ray tube. Motion is minimized for any single projection with 10 ms exposures that are synchronized to cardiac and breathing motion.

Fig 1: (a) X-ray tube (a) and (b) detector are stationary. The mouse is supported in an acrylic tube (c) placed on a support that is rotated by a computer-controlled stepping motor (d). The tube and detector are supported on a gantry (e). The relative position of the elements of the scanner is easily adjusted. The valve for scan-synchronous ventilation (f) and ECG leads are supported from the top of the gantry.

Figure 2 graphically shows the gating sequence corresponding to R peak in the ECG cycle. An acquisition window of 100 ms was defined at end expiration. Typically the end-expiration phase of our ventilation method is longer than the period of held breath to ensure more complete exhalation. Any QRS occurring within the window triggers an x-ray pulse. This ensured that the images were always acquired at the same phase of the cardiac cycle, and within the same ventilation window. Acquisition in other points of the ECG cycle is achieved by detecting the R peak and adding a constant delay.

Fig 2: The gating sequence used to sample at end expiration and fixed points during the cardiac cycle. Data sets corresponding to other points on the ECG cycle were acquired by sampling with a constant delay after detecting the R peak. A relatively constant heart rate (±8%) is maintained throughout each study.

We used two ways to increase contrast between myocardium and blood: a) a conventional iodinated contrast agent (Isovue 370 mg/ml Iodine) given as a constant infusion; and b) a new generation of a blood pool contrast agent containing iodine in a concentration of 50 mg/ml (Fenestra^TM VC, Alerionbio, San Diego, CA). The blood pool contrast agent yielded excellent demonstration of the cardiac structure, while the conventional iodinated contrast agents were less successful because of rapid renal clearance.

Results: 11 points were acquired during the cardiac cycle (R-R interval =110 ms i.e. 10 ms temporal resolution. The two movies below show heart motion in short and long axis. From the measurements of ventricular 3D volumes at different points of the cardiac cycle, one can assess the cardiac function. Since voxels are isotropic, ventricular volumes can be measured at different phases of the cardiac cycle to support assessment of ejection fraction/cardiac output and wall dynamics (C Badea, B Fubara, L. Hedlund, GA Johnson; 4D cardiac micro-CT of the mouse heart, Molecular Imaging, 4(2): 110-116, 2005). pdf of article

Conclusions: Image quality is sufficient for morphological and functional studies of detection of chamber volume and wall motion that will be required for a standardized method for cardiac phenotyping in the mouse. Current studies are dedicated to validating the techniques and imaging mice with cardiac dysfunction.

Movie of beating heart in short axis axial section

Movie of beating heart in coronal section

CIVM research

4D micro-CT of the mouse heart