Background: Micro-computed tomography offers numerous advantages for small animal imaging, including the ability
to monitor the same animals throughout a longitudinal study. However, concerns are often raised regarding the effects
of x-ray dose accumulated over the course of the experiment. In this study, we scan C57BL/6 mice multiple times per
week for six weeks, to determine the effect of the cumulative dose on pulmonary tissue at the end of the study.
Methods/Results: C57BL/6 male mice were split into two groups (irradiated group=10, control group=10). The
irradiated group was scanned (80kVp/50mA) each week for 6 weeks; the weekly scan session had three scans. This
resulted in a weekly dose of 0.84 Gy, and a total study dose of 5.04 Gy. The control group was scanned on the final
week. Scans from weeks 1 and 6 were reconstructed and analyzed: overall, there was no significant difference in lung
volume or lung density between the control group and the irradiated group. Similarly, there were no significant
differences between the week 1 and week 6 scans in the irradiated group. Histological samples taken from excised lung
tissue also showed no evidence of inflammation or fibrosis in the irradiated group.
Conclusion: This study demonstrates that a 5 Gy x-ray dose accumulated over six weeks during a longitudinal micro-CT
study has no significant effects on the pulmonary tissue of C57BL/6 mice. As a result, the many advantages of micro-
CT imaging, including rapid acquisition of high-resolution, isotropic images in free-breathing mice, can be taken
advantage of in longitudinal studies without concern for negative dose-related effects.
Background: Evaluation of cardiovascular function in mice using micro-CT requires that a contrast agent (CA) be
administered to differentiate the blood from the myocardium. eXIA 160, an aqueous colloidal poly-disperse CA with a
high concentration of iodine (160mg I/mL), creates strong contrast between blood and tissue with a low injection
volume. In this study, the blood-pool enhancement time-course of eXIA 160 is monitored over a 24-hour period to
determine its optimal use during cardiac function studies.
Methods/Results: 8-second scans were performed (80kVp, 110mA) using the GE Locus Ultra micro-CT scanner. Male
mice (black, 22-24g) were injected via tail vein with 5 μL/g body weight eXIA 160 (Binitio Biomedical Inc.). A
precontrast scan was performed; following injection, mice were scanned at 15, 30, 45, and 60 minutes, 2, 4, 8, 24, and 48
hours. Overall, the highest contrast in the left ventricle occurred at 5 minutes (687 HU). Uptake of the CA by the
myocardium was also observed: myocardial tissue showed increasing enhancement over a 4-hour period, remaining even
once the contrast was eliminated from the vasculature.
Conclusion: eXIA 160 provided high contrast between blood and myocardial tissue for a period of 30 minutes following
injection. Notably, this CA was also taken up by the myocardium and provided continued enhancement when the
contrast agent was eliminated from the blood, making LV wall function studies possible. In conclusion, eXIA 160, with
its high iodine concentration and targeted tissue uptake characteristics, make it an ideal agent to use when evaluating
cardiovascular function in mice.
Advances in laboratory imaging systems for CT, SPECT, MRI, and PET facilitate routine micro-imaging during pre-clinical investigations. Challenges still arise when dealing with immune-compromised animals, biohazardous agents, and multi-modality imaging. These challenges can be overcome with an appropriate animal management system (AMS), with the capability for supporting and monitoring a rat or mouse during micro-imaging. We report the implementation and assessment of a new AMS system for mice (PRA-3000 / AHS-2750, ASI Instruments, Warren MI), designed to be compatible with a commercial micro-CT / micro-SPECT imaging system (eXplore speCZT, GE Healthcare, London ON). The AMS was assessed under the following criteria: 1) compatibility with the imaging system (i.e. artifact generation, geometric dimensions); 2) compatibility with live animals (i.e. positioning, temperature regulation, anesthetic supply); 3) monitoring capabilities (i.e. rectal temperature, respiratory and cardiac monitoring); 4) stability of co-registration; and 5) containment. Micro-CT scans performed using a standardized live-animal protocol (90 kVp, 40 mA, 900 views, 16 ms per view) exhibited low noise (±19 HU) and acceptable artifact from high-density components within the AMS (e.g. ECG pad contacts). Live mice were imaged repeatedly (with removal and replacement of the AMS) and spatial registration was found to be stable to within ±0.07 mm. All animals tolerated enclosure within the AMS for extended periods (i.e. > one hour) without distress, based on continuous recordings of rectal temperature, ECG waveform and respiratory rate. A sealed AMS system extends the capability of a conventional micro-imaging system to include immune-compromised and biosafety level 2 mouse-imaging protocols.
Technological advances in micro-CT scanners have introduced dynamic, flat-panel scanners, which allow the acquisition of volume images in a few seconds. However, motion artefacts associated with normal respiratory motion arise when imaging the thorax or abdomen. To reduce these artefacts and the accompanying loss of spatial resolution, and to enable the study of rodent respiratory function, we developed a retrospective respiratory gating technique for volume micro-CT imaging of free-breathing rodents.
Anaesthetized male C57BL6 mice were placed in the prone position on a custom-made bed containing an embedded pressure chamber that was connected to a pressure transducer. Inhalation motion caused an increase in the chamber pressure, which was monitored as a surrogate for the respiratory waveform, and measured throughout the scan.
Projection images of the mouse thorax were acquired using a GE Locus Ultra micro-CT scanner, at 80 kVp, 50 mA (entrance exposure of approximately 2.7 cGy per rotation), over ten rotations in less than 1 minute. Respiratory gating was performed retrospectively by selecting projections that were obtained during the same portion of the respiratory cycle prior to reconstruction; CT images reconstructed from three to ten rotations were evaluated. The nominal voxel spacing was 0.15 mm isotropic.
Images were assessed for image noise, artefacts and measurement accuracy of physiologically relevant structures. These measurements showed no significant differences for images reconstructed from projection images from five to ten rotations. The optimum number of rotations for imaging mouse lungs was found to be six, corresponding to a 30 second (16.2 cGy) scan.