Dr. Veerle Kersemans is the Lead Biological Scientist at the Imaging Core of the Department of Oncology at the University of Oxford. The Imaging Core is equipped with a range of preclinical imaging equipment and radiotherapy instruments and is staffed with biological and physical scientists. The synergistic capabilities of the imaging systems, including the VECTor PET/SPECT/CT as the molecular imaging platform, are exploited both to improve the clinical relevance and translational capabilities of research at the CRUK/MRC Oxford Institute for Radiation Oncology, and to enable multimodal imaging characterisation and image-guided radiotherapy of preclinical models of cancer.
Can you give us an overview of what the Imaging Core provides?
Our imaging research services and capabilities are very broad. Our program aims to optimize imaging methods and to enhance the technological synergy of the systems so these can be applied in preclinical animal models of cancer and radiobiology.
As an Imaging Core, we always try to optimize the imaging process without compromising either performance of the imaging systems or animal welfare, and many of our customizations are aimed at ensuring compatibility between systems. As such we have developed a cradle system that can transfer small animals between any of our imaging and radiotherapy platforms, transforming these stand-alone units into multimodal imaging and treatment systems. As a matter of routine, we can perform PET/SPECT/CT imaging, using the VECTor/CT, in combination with our MRI systems. An example can be seen below where the skeleton (white) was imaged by CT, whilst MAG3 (red), FDG (purple) and Gadodiamide (green) were used for SPECT, PET and DCE-MRI of the kidneys, respectively.
What was one of your most memorable imaging challenges using the VECTor/CT?
The latest challenge was to image a genetically engineered rat model of Parkinson’s disease which translated in imaging very large, aged rats. We were able to use the VECTor/CT system to image these 900-gram rats using the set of collimators that we already had in place. However, it meant designing a new cradle system, including physiological monitoring and a headframe, and working closely with the MILabs team to integrate it so that we could optimize the FOV available and to not compromise on the available resolution and sensitivity. We successfully imaged those ‘fat rats’ with PET-CT and this within a month of being informed of the project.
What other unique imaging challenges are you currently working on?
At the moment we are running dual-isotope imaging combining Indium-111 with Zirconium-89. We successfully ran phantom studies to better understand the eventual interaction between both images, and now we are doing in vivo experiments as well. For this, we inject the control compound together with the compound that we are interested in. By exploiting the simultaneous imaging capabilities of ‘PET’ and ‘SPECT’ isotopes of the VECTor/CT, we can have the control and the targeted imaging done in the same animal, with the images of both tracers co-registered in space and time. The advantage for the users is that they can see how their control probe behaves in relation to a specific probe in the same tumor at the same time; the resulting statistics will be much better, and they can run studies using significantly fewer animals than before.
What are other exciting research projects with interesting customizations currently in development?
We are implementing our own gating system to make the VECTor/CT even more compatible and standardized to all our other imaging systems. We are converting the signals from a respiration balloon and subcutaneous placed ECG needles into 5V TTL signals which are then send to the VECTor/CT system. This means that the VECTor/CT system had to be modified slightly to allow 2, instead of 1, TTL input signals. However, this was a trivial task for the MILabs team and following a short onsite visit, this function was enabled. Our gating control signals are recognized by the existing acquisition software allowing a real time display of the cardiac and respiration rate on the acquisition interface and which allows retrospective gated PET/SPECT/CT imaging.
Over time, we would like to implement our gating control systems that allow prospective gating acquisitions similar to our MRI imaging techniques.
What are the research plans for the future?
Previously, we have developed CT methods to look at the tumor vessels in vivo in high detail and we have applied this method to link MR imaging biomarkers of vascular function to structural changes in tumor vessels following anti-angiogenic therapy in preclinical xenograft models. However, this work was all performed on our previous CT system.
We will implement and further optimise the same methods on our VECTor/CT taking advantage of its dynamic imaging capabilities. In addition, we can take advantage of the system’s high-resolution capabilities in combination with the relatively low image radiation doses delivered to the tumor to allow us to study those tumors longitudinally. This was, previously, impossible because of the high radiation dose using our previous CT scanner attenuated tumor growth. The VECTor/CT will help us achieve this goal, generate better quality data and also reduce the number of animals needed.
We believe we are a rather unique group in that we not only fully exploit the characteristics of the VECTor/CT for routine, standard applications but also customize the VECTor/CT to allow optimized imaging of specialized target applications for which we integrate our hardware to ensure compatibility between PET, SPECT, CT and MRI. Working together with the MILabs’ team has been a very successful approach – allowing to take our capabilities beyond straightforward imaging applications. The fact that one can have such a close collaboration with the manufacturer means that when users want to do something that is not yet customarily done yet, it can be realized, and quickly.
What are other system integration tools that you are working on?
With the VECTor/CT system, we are finishing the deployment of a new electrical heating system that is compatible with all our imaging systems. We have projects coming up where users want to combine PET imaging with the radiation therapy platform and with MRI in the same session on the same mouse. We developed the heating system that can be used in either one of the systems without compromising image quality.
Furthermore, we would like to incorporate optical thermometry to monitor the animal’s rectal temperature using cabling that is housed within the gantry. Currently we use thermistor temperature probes when using in-gantry cabling but these contain metal which reduces CT image quality. When using our fibre optic thermometer system we currently run the cables outside the cradle support arm.