Exploiting the unique quantitative capabilities offered by simultaneous PET/MRI

Both positron emission tomography (PET) and magnetic resonance imaging (MRI) are well-developed imaging methods that provide key diagnostic information in clinical studies. PET can detect very small quantities of radiolabelled tracers which illustrates ways in which the body functions and what is happening to cells and small molecules in the body. However, PET images have poor spatial resolution and can only be acquired in a relatively long time (several minutes). On the other hand, MRI provides high spatial and temporal resolution anatomical information unrivalled by any other imaging modalities, especially providing excellent soft-tissue contrast. It is widely recognized that imaging systems that incorporate two different imaging methods can add diagnostic value e.g. PET/CT. The UK's first simultaneous whole body PET/MRI system was recently installed at UCL/UCH providing a unique platform for cutting edge research. We aim to exploit the simultaneous capability of this unique instrument to improve the range of parameters available for clinical interpretation.
Our research programme will involve the following novel sub-projects.
a) We will take advantage of MRI anatomical and functional information to directly improve the accuracy and precision of PET reconstruction. This involves development of computer programs that can extract information on organ boundaries from MRI and use this information to control the PET reconstruction. In kinetic studies, where a time sequence of images is acquired, knowledge of the expected changes in time can also be used to improve image quality.
b) We will develop an efficient method for MRI motion estimation that can be applied for correction of simultaneously acquired PET data, in a practical setting. This involves the development of new methods of acquiring MRI data so that motion can be measured along with the standard methods that are required for clinical acquisition. The information on motion will be incorporated in the software used for the PET reconstruction.
c) We will develop joint solutions for simultaneously acquired PET and MRI kinetic data that has potential to benefit both modalities. A number of useful parameters can be extracted from dynamic studies performed either using PET or MRI, but there are usually quite large errors involved. No-one has previously used the information available from both techniques to improve the estimation of parameters. This is quite challenging but will permit the measurement of more specific parameters that may be more helpful in understanding disease and its treatment.
d) We will adopt an all-inclusive framework for PET reconstruction that encompasses the complementary MRI information: spatial information, motion estimation and kinetic models. This will attempt to utilize all the available information to improve the PET image quality and the reliability of quantitative parameters that can be made available to clinicians. We hope to extend this approach to a truly combined reconstruction of parameters using information from both modalities.

The proposed research necessarily involves a multidisciplinary team of researchers with complementary skills, who are well placed to direct the research to meet well defined goals. The developed techniques will be evaluated in patient studies performed on the new PET/MRI system as a basis for their future use in clinical research.

Novelty of the proposed research:
We propose an ambitious project which directly targets a new area of diagnostic imaging as the motivation for further development of novel data acquisition, image reconstruction and image processing. We extend on the experience and strengths across several UCL departments in order to address some challenging problems. The appeal in our proposed all-inclusive framework for image reconstruction is that it provides a flexible approach to capture the unique properties of the combined PET/MRI system with potential to identify novel biomarkers that have immediate application.
Health and societal impact:
This project is centred on new technology only recently made available to clinical research communities and available for the first time in the UK. An important aspect of this technology is the reduced radiation exposure compared to PET/CT, particularly important in paediatric studies and longitudinal studies that involve multiple examinations. Exploiting the unique capabilities of this technology has therefore potential for significant impact on investigative medicine and clinical practice. The research seeks to identify and validate improved, more specific, biomarkers that permit optimally directed treatment; these can potentially also inform on disease progression and treatment response across a range of diseases and conditions. There is therefore potential for significant health impact and societal benefit.
Engagement with medical specialists is intrinsic to the project, with two imaging specialists included as co-investigators. The goal is to highlight utility of the developed algorithms in demonstration clinical studies and to provide pilot data that supports more extensive clinical evaluation. We have included costing for a scientist with specific responsibility for efficient software implementation, to ensure that translation of software to the clinical research platform is efficient, bridging a common gap in technological research. The focus of the proposed research aims to exploit unique capabilities of the recently released simultaneous PET/MRI system. The development of new acquisition strategies and analysis protocols will facilitate greater insight to the underlying molecular and biochemical processes using non-invasive in vivo procedures. Development of these specific techniques therefore has potential to lead to enhanced understanding of disease and its treatment. The ability to better direct and monitor treatment has important economical and quality of life implications.
Training and education:
In addition the proposed research will be undertaken in an environment that promotes cross-modality training and skills development in an area where there will be future employment opportunities. Optimal use of the combined modalities requires advanced knowledge of both PET and MRI, expertise which is currently quite rare. Engagement of young researchers in the early development of the dual modalities will provide a nucleus of expertise to aid future development. Appointing PhD students in strategically selected projects to further extend the project team (through independent funding) provides an avenue for further shaping the UK capability to support this new technology.
Imaging by its nature is very visual and we will use outputs from our research for public engagement. We will seek opportunity to exhibit our work at open days and exhibitions and to present our work to schools and the media, activities where we have previous experience. As this is the only facility of its kind in the UK, we foresee considerable press interest.
In summary the proposed project:
- involves development of novel acquisition and processing techniques
- is timely, with potential to influence future clinical utility of PET/MRI
- has potential for significant societal benefit with direct impact on health care
- provides a nucleus for multi-disciplinary training on multi-modal imaging