Workpackages
At HYPERImage, the combination of leadership in technology and biomedicine is our bet for succeeds in this project. The project work packages are divided into three major research areas:
A - hardware development
B - systems analysis development
C - systems pre-clinical and clinical validation
- Organisation of the workpackages with main information paths and partner contributions
WP1 focuses on the development of MR-compatible PET detector modules, which are the building blocks of all PET/MR systems planned in this project. These modules will be upgraded with last submissions of SiPMs and TAC/ADC ASICs during the entire project span. The results already achieved in 2007 will ensure stable electrical and mechanical interfaces between the modules and the PET backbone, to facilitate simultaneous work on WP1 and WP2. Thus, the project can focus in WP1 on the improvement of the SiPMs, the ASIC, and the PCB-design to limit the interference between PET and MR. The partners FBK and UH are mainly responsible for this WP, having expertise in silicon design and test close to the processing and measurement limits.
WP2 focuses on building ToF-PET/MR test systems, which can be used from the clinical and preclinical partners in the project. Important system aspects are addressed here: adaptation of the Tx/Rx animal and WB coil, shielding and electromagnetic decoupling, as well as the design of an MR compatible high throughput PET pre-processing electronics. Emphasis will be put on investigating and reducing the crosstalk between the systems to allow simultaneous image acquisition.
Philips will be mainly responsible for this task, having years of experience and leading products in high-end PET and MR imaging domain. A sketch of the proposed system is given Figure 1.3.4: The PET-detector ring will be located centrally inside the magnet, surrounded by a split gradient coil. The high PET sensitivity due to a pixelated ToF readout reduces the necessary PET detector volume dramatically and a high performance PET system could fit within a small 12-15cm gap. A re-design of the current (gap-free) gradient coil can reliably be planned as Philips has long term experience with a validated software design tool.
The RF body coil will be located centrally and will be transparent for the gamma-photons. The performance of the RF-body-coil (field homogeneity, power sensitivity and dissipatigon) will be on the same order as an standard 3T integrated body coil. A special RF-shield will suppress the leakage of the transmit RF-pulse into the PET-detector volume. The shieldin of the PET-detector modules will be adapted to handle the higher RF field-strength present in the whole-body system. Shielding of the PET-detector modules, the PCBs and the wiring will be adapted to reduce the mechanical vibrations due to the eddy currents. In order to guaranty concurrent image acquisition, the signal paths will be further redesigned to reduce the interference between the MR gradient and the low-power signal acquisition.
For the assembly, the SiPM with the highest PDE and timing performance will be selected, to realize the targeted 200ps coincidence resolving time for a high sensitivity PET/MR system. After testing and calibration of the system based on phantom tests, it will be available for the first clinical studies.
- Fully integrated whole body PET/MR system using a split gradient coil. Source: Philips
WP3 will address the algorithms required to advance multi-modality imaging. Here, the emphasis is on the use of special MR sequences that will allow the acquisition of functional data and 4D anatomical information to generate 4D attenuation maps.
In order to start the development of algorithms and software parallel to the system development, we decided to extract the motion transformation fields for different organs from volunteers and from patient data of MR investigations. This data will allow the early development of special MR sequences and motion models for different organs (e.g., heart and lung), enabling the acquisition of motion and functional data. Also, directly from the start of the project, we will investigate algorithms and special sequences for MR-based attenuation correction of PET images.
Thus, after the feasibility proof based on the animal system in WP2, this insert can be used directly to test the developed dedicated MR sequences for concurrent PET/MR imaging of the heart. This activity is followed by the first preclinical investigation of the static attenuation correction on the animal system.
Once the whole-body system is characterized, the PET reconstruction with motion compensation will be tested using phantom studies and clinical experiments. Main responsibility will be taken over by KCL.
WP4 - Cardiovascular diseases and cancer are the two leading causes of death in the world. Therefore, investigation in the development of technological platforms focused on early detection of disease are today one of the main tasks of Biomedical research.
Pre-clinical studies in cardiovascular disease will be developed in the Department of Atherotrombosis and Cardiovascular Imaging at CNIC. WP4 will focus on multiple approaches by PET/MR to investigate two main cardiovascular pathologies in a rabbit model of disease: atherosclerosis and myocardial infarction.
Regarding to atherosclerosis, one of the key challenges in cardiovascular research is related to early identifying high risk atherosclerotic plaques, since patients are often asymptomatic and heart attack and stroke are usually the first manifestations of this condition. In this context, we will not only assess atheroma plaque detection, but we will also evaluate imaging capabilities of the system by analyzing plaque size, plaque composition (determination of fat content, thrombus formation, and calcium deposition) and plaque metabolism (inflammatory cell content) in the main arterial districts. Very advantageous is the high soft-tissue contrast of MR with automatic registration and visualization tools developed by WP3. Therefore, the PET/MR system will allow the simultaneous characterization of focal inflammation (PET) plus anatomical localization (MRI) of the plaque in the vessel wall, all in one single assay. The PET/MRI system will decrease the radiation dose regarding the current PET/CT system as CT radiates and MRI is radiation free.
The animal PET/MR system provided by WP2 will also be evaluated in a rabbit model of myocardial infarction analyzing the accuracy for the simultaneous assessment of myocardial metabolism, perfusion, scar development and wall motion of the heart. In addition, this model will be critical for technical validation of MR-based attenuation correction of PET images also developed by WP3, which will also evaluate myocardial perfusion in rabbit hearts.
The accuracy of the PET/MR system will also be evaluated by performing appropriated time-course of disease, in order to improve as much as possible early detection of plaque formation and infarction of the heart: the sooner the better.
WP5 - To validate the use of a concurrent PET/MR system in diagnostic oncology, we will start with preclinical validation studies, using animal mouse models of human cancers. The NKI-AVL has developed a well-characterized series of “spontaneous” mouse models for a variety of solid tumours, e.g., (non-) small cell lung cancer, invasive ductal breast carcinoma, BRCA1- and BRCA2-associated hereditary breast cancer, metastatic lobular breast cancer, pituitary cancer, and mesothelioma.
This combined panel of animal models enables both longitudinal studies and the validation of a range of diagnostic approaches on cohorts of genetically identical tumour types in-vivo. Initially, separate 3T MR (with mouse coil) and (micro-) PET/CT will be used to investigate these features and to validate their diagnostic significance. Such studies will lead to a set of PET and MR features that are predictive in early detection, staging, or response to therapy. A combination of gene–profiling and conventional pathology will be performed to validate the in-vivo findings.
As soon as the preclinical PET/MR system from WP2 becomes available, the advantages of dual modality PET/MR scanning will be explored in mouse models using predefined imaging features, and will be compared directly to PET/CT data. In addition to the mouse studies for breast cancer, initial studies on human patients with breast cancer will be performed towards the end of the project, using a WB ToF-PET/MR system from WP2.
Currently the supplemental value of separate PET/CT and (contrast enhanced) MR is evaluated at both the NKI-AVL and the UKE for breast tumour detection, staging, and response monitoring. Optimal motion correction and image registration combined with the knowledge obtained in the preclinical setting is expected to significantly advance diagnostic oncology for breast tumours.
WP6, WP7
In addition to the technical work packages there will be work packages devoted to the knowledge management (WP6) and the project management (WP7).
