Department of Radiology

Research in Radiology

Imaging Research

 

Imaging has become an essential part of the biomedical sciences, not only for diagnosis within clinical medicine and the delivery and objective monitoring of subsequent therapy, but also for providing unique insights into causation of disease, pathophysiology and the translation of novel treatments from the laboratory into patients.

Through diverse initiatives and risk sharing between funding agencies including the NHS (local, regional, and national - NIHR), University, Charities (local and national: Wellcome Trust, CRUK, etc), Research Councils (MRC, EPSRC) and Industry, the Cambridge Biomedical campus has established excellent imaging facilities (CT, MR, ultrasound, Nuclear Medicine, PET, and radiochemistry, MEG); PET/CT has been in place since the end of 2008 courtesy of the recent successful NIHR Biomedical Centre bid, again helped by Industry and the Cambridge University Teaching Hospitals NHS Trust.

An experienced, innovative and expanding group of imaging scientists develop their own ideas and collaborations whilst providing support for clinical researchers and their carefully characterised patient populations. The Clinical School has formed an Imaging Strategy Group whose aim is to:

• create a world class imaging group to facilitate experimental and translational medicine
• improve cohesion and interaction between imaging groups and stakeholders
• expand and maintain state-of-the-art research capacity with cost-effective purchasing
• underpin intramural and extramural collaborations to maximise productivity
• increase industrial, university and research charity partnerships
• create a School of Imaging Science to train the next generation of imaging scientists
• establish better ring-fenced time and infrastructure for staff to fulfil their R&D potential

Existing Imaging Capacity

Scientists, clinicians and management on the Addenbrooke’s campus have together developed and maintained a modern portfolio of imaging equipment to provide both research capacity and capability. The Cambridge University Teaching Hospitals NHS Foundation Trust Radiology department houses:

• Numerous modern full capability Ultrasound systems. The Ultrasound Department has just been refurbished so that it has 8 dedicated Ultrasound rooms each equipped with a high specification machine complete with colour flow and power Doppler.

• The new CT suite comprises of 3 multi detector machines, one 4, one 16 and one 64 slice respectively and within this suite there is a new 1.5 Tesla MR Unit. The intention is to upgrade the 4-slice machine to a 128-slice machine during 2009, and a 4th CT machine (16 slice) is being installed currently.

• The main MR Unit has recently been refurbished and it houses 2 x 1.5 Tesla and one 3.0 Tesla MR Units, with research collaborations with both industry (GSK) and charity (CRUK). Two of the systems have full multi-nuclear spectroscopy capability. These NHS based machines are all used extensively for research as well as for routine NHS work.

• Both the Neuro-angiography and the Angiography suites on level 4 have been completely replaced during the last few years. There are 2 further screening rooms for Gastrointestinal and Musculoskeletal Fluoroscopic studies.

• The Nuclear Medicine Department is situated on levels 2 and 3 of the out-patient department and its facilities include 4 Gamma cameras. There is a plan to build a new Nuclear Medicine department over the next 2 years. The new PET/CT unit, funded with a grant from the recent successful NIHR Biomedical Research Centre bid and Industrial support, will be predominantly used for research.

Comprehensive research agreements with the vendors underpin the ability to develop and evaluate new technology and applications on these systems and Cambridge is a research reference site for GE, Siemens and Toshiba. All machines are linked by a sophisticated network to a central Picture Archiving Computed Storage (PACS) system.

Further state-of-the-art 3.0 T MRI/S and PET research capabilities are situated in the Wolfson Brain Imaging Centre (WBIC) which is imaginatively placed within the envelope of the Neurosciences Critical Care Unit so that critically ill patients may be studied. The WBIC facilities include a PACS system, two cyclotrons and a GMP-compliant PET Radiochemistry laboratory with some 15 radioligands currently available. The University is also currently refurbishing a laboratory on the West Forvie site that will provide for small animal imaging systems to support phenotyping and molecular imaging studies for metabolic, endocrine, neuroscience and cardiovascular medical research. In addition to 4.7T preclinical MR and microPET, it also houses an experimental PET/MR system and chemistry research laboratories for developing imaging probes. MR and mobile microPET facilities are also available at the Veterinary School.

The CRUK funded Cambridge Research Institute (CRI) has recently developed an Imaging Section and there is close liaison between its imaging scientists and those elsewhere on the campus. Imaging goals at the CRI include using MR and MRS for the evaluation and design of novel tumour therapies, including immunotherapy and anti-vascular and gene therapies. Such research will also increase understanding of the biology of cancer and the determination of tumour-associated MR parameters for diagnosis, prognosis and monitoring of therapy. Current work includes the use of hyerpolarised gases and paramagnetic particles for imaging cell death and measuring pH.

There are further Imaging facilities (3T fMRI and MEG) at the MRC funded Brain Behaviour and Cognition Unit at Chaucer Road.  

Cambridge is fortunate to have not only excellent cross-sectional imaging facilities but closely integrated NHS and Academic Imaging departments with experienced faculty who have both technique and body system expertise, many nationally and internationally recognised. They all are involved in teaching and research and collaborate closely with their specialty based clinicians, many of whom are also research active. These clinical imagers enjoy close interaction with the more basic scientist imagers on site at the WBIC, the CRUK CRI, the MRC/Wellcome funded Behavioural and Clinical Neurosciences Institute and the MRC funded Brain Behaviour and Cognition Unit

Track Record on Development and Expansion of Existing Technologies

Cambridge imagers have extensively exploited Computed Tomography (CT), Magnetic Resonance (MR), Nuclear Medicine (NM) including Positron Emission Tomography (PET), and Ultrasound (US) for the detection, diagnosis and monitoring of human disease in novel ways, many of which have translated into clinical practice. For example, pioneering studies using CT for diagnosing and characterising abdominal conditions have removed the need for ‘diagnostic’ laparotomy. Multiple studies on the accuracy and efficacy of MR examinations of the knee have contributed to the redundancy of surgical diagnostic knee arthroscopy. Numerous non-invasive image-guided biopsy strategies have been developed which have replaced formal open surgical diagnostic biopsy for many diseases – most recently using ultrasound guidance for core biopsies of head and neck tumours and lymph nodes. 

The replacement of therapeutic surgery has been achieved in several conditions through development of novel image guided techniques that allow drainage of acute abdominal and pelvic abscesses and collections in almost any location. In breast malignancy sophisticated percutaneous image guided methods have been extended to incorporate therapeutic excision using wide core needle biopsy, likely to replace much formal breast surgery. 

Improved therapeutic surgery has been made possible through triage studies on acute surgical admissions using rapid multi-detector CT providing surgeons with a pre-operative specific diagnosis and location of disease - informing their decision to operate, better informing the patient and guiding surgical planning.

On site research has underpinned replacing other invasive diagnostics by original work using CT to replace X-ray lymphography through to replacement of diagnostic ERCP by the early development and demonstration of a non-invasive MR cholangio-pancreatography technique.  The development of novel US imaging techniques for the perineum and urethra have allowed replacement of other established invasive and X-ray based procedures. 

Improvement of invasive diagnostic procedures has been possible through research demonstrating the value of chest CT before bronchoscopy (for suspected cancer) for increasing the diagnostic yield.

As modern imaging techniques have evolved, we have continually studied the replacement and improvement of existing non-invasive diagnostic imaging techniques such as proving the advantages of US over venography for DVT. More recent work has demonstrated the value of CT over NM in the diagnosis of pulmonary embolism and contrast enhanced MRI over X-ray mammography for certain breast malignancies (MRC funded). Cambridge has been a pioneering centre for white cell scintigraphy techniques, showing improved diagnostic capabilities in numerous areas such as inflammatory bowel disease activity compared with conventional barium examination. MR enteroclysis has been developed and investigated as a replacement for X-ray based small bowel studies in inflammatory bowel disease. Recent work has proven the initial diagnostic performance of a technical refinement of MRCP (adaptive averaging) that allows for improved demonstration of small bile ducts likely to be of value in the detection and monitoring of diffuse cholangiopathies.

We have also performed numerous efficacy studies evaluating the benefit of widely employed diagnostic MRI examinations and their impact on clinical diagnostic confidence, management and patient outcomes. These have proven the effectiveness of MRI in the triage of patients with diverse but common clinical problems such as intracranial/spinal symptoms, knee/shoulder/wrist disorders and sensorineural deafness. Such work has been critical in the development of nationally established ‘Guidelines for Imaging’ and ‘Health Technology Assessments’, helping NHS decisions about additional MR purchasing. Our cumulative applied clinical research work outlined above has had considerable beneficial impact on routine NHS clinical practice and the delivery of patient care.

At a more fundamental level several imaging groups in Cambridge are developing novel imaging technologies for future clinical application.  These include the development of real-time interactive magnetic resonance based fluoroscopy, high resolution carotid artery wall and plaque imaging and a novel PET/MR system (EPSRC funded) which is being developed in collaboration with the Cavendish Physics laboratory. A collaboration with Engineering (also EPSRC funded) has developed novel 3D ultrasound imaging technology which is currently being tested for eventually supporting real time 3D ultrasound monitoring of percutaneous interventions and elastographic measurements of tissue stiffness. All these developments have attracted industry interest and support (GE, GSK, Siemens, and Toshiba). Other imaging related research in collaboration with the Cavendish Physics Department includes work on Terahertz imaging applications and network grid computing (e-Science funded) for image processing and transfer.

Current imaging research activity includes several ongoing pilot studies that may eventually contribute to improved patient care. We are evaluating newer functional methods such as MR perfusion for assessing early solid tumour response to therapy (e.g. cervix tumour response to radiotherapy with biopsy validation, NCI, RCR funded). These are based on the pioneering CT perfusion techniques originally developed in Cambridge in the early 90s. MR based direct arthrography that avoids the need for X-ray fluoroscopy is undergoing evaluation and MR venography is being investigated in the characterisation of benign intracranial hypertension. A range of quantitative techniques for measuring body and hepatic fat distribution are also being evaluated along with spectroscopic (¹H and ³¹P) techniques for diffuse liver disease. Studies in collaboration with GSK assessing carotid artery plaque macrophage response using iron agents (USPIOs) are aimed at identifying surrogate markers of “vulnerable” plaque that might be used for patient treatment selection. Diffusion Tensor Imaging (DTI, a technique pioneered by the WBIC) with MR is being evaluated to delineate important nerve tracts in relation to brain tumours and has the potential to both improve outcomes from tumour resection and radiotherapy, thereby predicting likely impairments following surgery.

Imaging Infrastructure Support: alongside this primary imaging research, the radiological services have also supported numerous local, national and international trials that often require additional imaging beyond routine NHS patient care. In this infrastructure role there is now an urgent requirement for increased access to PET and in particular modern PET/CT; we possess the expertise to evaluate its role in a variety of conditions of interest to the NHS as well as being able to continue support the increasing research activities which now require established FDG based PET/CT imaging.

Future Research Aims & Development of Novel Technologies

(a) Support Molecular Imaging: Current cross-sectional MR and CT anatomically based imaging is becoming more sensitive but less specific as their ability to detect small lesions (e.g. in liver and lung) increases. More specific disease markers are required to enable further progression in the development of imaging technology and this is particularly relevant for cancer. Recent major investment in both Clinical and Academic Oncology Departments and by CRUK in the Cambridge Research Institute (CRI) is bringing fresh opportunities for new imaging technique development in support of translational oncology research. There is considerable clinical MR collaboration with the newly formed CRI Imaging Group which is developing an animal imaging department. Clinical collaboration aims to develop novel molecular imaging agents for tissue function and metabolism using conventional ¹H based MR, ¹³C hyperpolarised methodologies as well as optical and novel PET radionuclide methods. There will be a focus on apoptosis and epithelial dysplasia with initial evaluation in mouse models and ex-vivo human tissues and translation of successful agents to human evaluation studies using clinical imaging systems. The initial funding for clinical MRI has been provided by CRUK and a local charity but additional NHS funding will allow expansion and enhancement of this collaboration. Through links with the Stanford University Molecular Imaging Program a joint educational program has been established to support training fellowships that could be linked to the CRUK CRI and the proposed CCI molecular imaging groups. A specific target of this work is in-vivo reporter gene imaging that can provide information not only on cell trafficking, but also on cellular function and survival. This should lead on to the use of molecular imaging in reparative medicine applications, e.g. neurogenesis (in the context of neural injury e.g. stroke, trauma, neurodegeneration, and neuroinflammation), as well as other applications to understand cancer biology and therapy.

(b) Extend MRI Applications: As life expectancy increases so is concern at the rapidly increasing population exposure to ionising radiation. We will extend the diagnostic role of conventional whole body MRI systems and perform studies to demonstrate where MR could eventually replace many more X-ray procedures. This will involve the development of user interfaces, in room control and display capabilities, and innovative sequence and application design. This will be a progression of our existing work on MR fluoroscopy techniques, gastro-intestinal (MR enteroclysis) and musculoskeletal systems (MR arthrography). Alongside this work we will continue to extend existing MR research techniques using ¹H and ³¹P MRS for metabolic tumour profiling and investigate the potential benefit of new MR staging methods in guiding robotic prostate surgery and other forms of tumour therapy. We have patented a methodology that combines PET with MR data: this venture between the WBIC and the Cavendish laboratory is resolving the distribution of novel chemicals within the living brain.

(c) Develop Robust Quantitative Imaging: We will develop and validate quantitative imaging methods for monitoring disease progress and the effects of therapeutic interventions in a wide range of specialties, particularly oncology, cardiology, gastroenterology, metabolic science and neuroscience. The aim will be to provide several generic robust quantitative measurements including: tissue perfusion parameters (e.g., brain perfusion in acute stroke), spatial enhancement patterns, T2 mapping, vascular bulk flow, fat distribution and tissue fat content.

(d) Novel Imaging of the Neurologically Impaired: The refinement and development of imaging techniques for characterising carotid disease and stroke will continue with the aim of developing robust non-invasive imaging techniques to identify both patients at risk of stroke and those who respond to treatment. New imaging methods are helping to distinguish ‘safe’ from ‘unsafe’ atheroma and hence predicting the risk of a stroke, the need for preventive surgery and the determination of which treatments are safe and effective. The unique facilities of 3T MR and PET adjacent to the acutely ill patients in the Neurosciences Critical Care Unit provide exceptional research opportunities for Neurosurgery, Neurology, Psychiatry, Anaesthesiology and Radiology. We are developing new state-of-the-art real time fMRI including online methods of analysing the resulting data, particularly for studying those emerging from coma and with minimal consciousness. These will show what happens to the brain as patients emerge from coma; this should help predict outcome and the most appropriate form of rehabilitation. fMRI techniques will be used to further our understanding of attention, memory, speech, language, eating disorders and emotion. We will attempt to distinguish between the different types of dementia using morphometric imaging, functional imaging and neuropsychology. Novel analysis algorithms are being developed in order to better assess anatomical connections between brain structures and their impairment in disease or following trauma. We will assess brain viability in acute ischaemic stroke and determine the secondary changes, and their impact on functional recovery. We will assess how drugs interact with parts of the brain concerned with learning and higher mental function in order to increase understanding of mental illness and addiction. We will use fMRI to follow changes in brain organisation after focal injury and to see how neurorehabilitation modulates brain plasticity. We will continue to exploit these studies in association with the MRC funded Cambridge Cognition and Brain Sciences Unit and the MRC/Wellcome Trust funded Behavioural and Clinical Neurosciences Institute based in Experimental Psychology and the Brain Mapping Unit in Psychiatry. These facilities have been well used despite relatively little NHS R&D support to date and require considerable physics, data handling and computing support, as well as clinical infrastructure. The much needed improvement in the radiopharmaceuticals laboratory will underpin future research using novel PET ligands.

(e) Define New Roles for CT: Cambridge is well placed in collaboration with Papworth (recent installation of a 64 slice double tube CT system) to continue investigating the role of CT for cardiac and coronary imaging, extending the preliminary work based on existing 16 and 64 slice systems. This research will ultimately determine which patients can be safely managed with CT, thereby avoiding invasive coronary angiography. We will continue to evaluate the role of immediate CT in the triage of acute medical and surgical conditions (including trauma), especially assessing volume CT data manipulation. In addition we will exploit this volume imaging capability to develop new CT and PET/CT techniques for the detection and monitoring of early lung cancer in collaboration with Clinical Oncology.

Conclusion

Cambridge imagers have demonstrated considerable innovation and research excellence over several years generating 70-100 peer reviewed imaging related papers per annum - See publications, staff lists and related web-sites.

Linked Websites

http://www.wbic.cam.ac.uk/

http://www.neuroscience.cam.ac.uk/

http://www.cambridgecancer.org.uk/