Multimodality Imaging of Tumor Xenografts in Mice with dedicated Small-Animal PET, Small-Animal CT, and Small-Animal MRI: Hardware and Software Solutions

Dedicated small-animal tomographs are nowadays available for the three major modalities PET, MRI, and CT. Utilization of all three techniques for true multimodality imaging requires the solution of several technical problems including reproducible animal positioning, overcoming file format incompatibilities and coregistration of the different image volumes, preferably without application of markers.
Methods: We developed an isolation chamber and adapter for imaging devices, enabling physiologic animal control, reproducible positioning, pathogen barrier, anesthesia, probe application and the use of catheter systems. Furthermore, we developed the necessary software for file format conversions and coregistration of the image volumes.
The basis is the animal holder system, consisting of the fixing adapters and the animal chamber that could be positioned in our three tomographs (microPET P4, SkyScan 1178, and BioScan 70/30 USR).
The animal holder system is temperature-controled. It allows gas anesthesia of the animals and could be used as a closed system. The bed is air heated.
In the different modalities the data are stored in different formats using different image matrix and pixel sizes. In order to analyze the data they are converted to a common data format (Siemens ECAT7) and the pixel sizes are adjusted. Residual differences in the relative positioning of the animals are corrected via coregistration. We implemented a mutual information algorithm using the conjugate gradient maximization method.
Validation studies showed a good coregistration of the images from PET, CT, and MRI. In longitudinal [18F]FDG studies the coregistration allowed to compare the tumor SUVmax data between different studies.
Conclusion: Multimodality imaging of small animal PET, -CT, and MRI allows the direct comparison and quantification of regional PET, CT, and MRI/MRS parameters enabling the characterization of functional and anatomical changes during tumor development and therapy.
The project was partly supported by the EU project BioCare No. 505785.