Clinical Physics
Dr John Dickson leads our ongoing collaborations in Neuroimaging. These include projects using Dopamine Transporter imaging with Datscan to explore different elements of Parkinsonian syndromes.
With Movement Disorder colleagues in Queen Square, there are several projects using Dopamine Transporter imaging with Datscan to explore different elements of Parkinsonian syndromes, and a pilot project examining the therapeutic effects of Exendin on Parkinson's disease. The EANM Normal Database (ENCDAT) project is also continuing to produce both clinical and scientific research.
Using FDG-PET there are several ongoing projects. With Epilepsy neurologists, work is taking place to determine the role and efficacy of FDG-PET in the management of Epilepsy patients. Led by INM, a collaboration of UK PET sites is also starting up to examine the portability of FDG normal databases between different scanner types and ages. Finally using PET/MR there is a project to assess the differences in PET signal when attenuation corrected using CT, DIXON (T1) MR, and a new UTE MR sequence.
A growing area of interest is in the kinetic modelling of PET studies. Developing from our experience and continuing research with quantitative blood flow measurements using Rubidium Cardiac PET, there are also developments in assessing flow independent uptake (Volume of Distribution) in Fluorocholine neuro-oncological PET and kinetic analysis of Fluorocholine uptake in the Prostate.
Movement Disorder Imaging
Imaging of movement disorders, primarily with 123I-FP-CIT (DaTSCANTM) SPECT is a key research area.
The noise handling effects of iterative reconstruction with resolution-modelling has been successfully used as a strategy to reduce scan duration in Bone and Myocardial Perfusion SPECT. Work is underway to assess different studies that can utilise these reconstruction techniques to reduce scan time. 123I-FP-CIT (DaTScan) is a cocaine analogue that binds to dopamine transporters and reduced uptake in the putamen indicates early IPD (Idiopathic Parkinson's Disease).
Current scan times for this study are 45 minutes long, using the resolution-modelling reconstruction technique has the potential to reduce these scan times, improving image quality and patient experience. 123I-FP-CIT (DaTSCAN) SPECT images were reconstructed with different reconstruction methods and reduced counts to assess how resolution-modelling affects the interpretation of the images.
We work with Movement Disorder specialists within UCL supporting projects including the monitoring of possible disease modifying drugs for Parkinson's disease and testing the efficacy of new techniques to identify people with a high risk for Parkinson's disease. Our collaborations with EARLs ENCDAT initiatives also continue, both in the support of research into factors that may affect 123I-FP-CIT binding, and in the acquisition and reconstruction methodologies that can be used effectively with the normal healthy database that ENCDAT holds.
Molecular Radiotherapy
Molecular radiotherapy (MRT) may be defined as the delivery of radiation to malignant tissue via the interaction of a radiopharmaceutical with molecular sites and receptors. This is a rapidly evolving discipline, particularly regarding quantification of uptake in normal and malignant tissue. Internal dosimetry is essential to the future development of MRT.
Of interest are the radiopharmaceuticals 131I-mIBG and 177Lu-DOTATATE.
Metaiodobenzylguanidine (mIBG) is highly sensitive and specific for neuroblastoma (a form of childhood cancer), concentrating in >90% of tumours. It may be labelled to 123I as a routine tool for neuroblastoma gamma camera and SPECT-CT imaging. Patients eligible for treatment may be treated with 131I-mIBG, often in combination with a radiosensitiser such as Topotecan. Therapies are performed on an in-patient basis in one of the radionuclide therapy rooms within UCLH. Response rates are monitored using imaging techniques within INM.
Further work with mIBG involves using 124I-mIBG as a novel PET radiotracer, with the ability to offer improved spatial resolution and quantification. We aim to compare 124I-mIBG PET/CT to 123I-mIBG scintigraphy in their ability to detect lesions in metastatic neuroblastoma.
Another well-established technique is 68Ga-DOTATATE PETCT imaging. This is a useful diagnostic tool to determine disease extent and evaluate patients for targeted 177Lu-DOTATATE therapy. A phase 2 trial is currently underway to evaluate 177Lu-DOTATATE therapy in the treatment of refractory or relapsed neuroblastoma. Key components of the trial are evaluating 68Ga-DOTATATE uptake correlation with response and a dosimetry study to investigate tumour and normal organ dose.
Clinical multi-parametric imaging
Using PET/CT and PET/MR we are working towards a better understanding of neurological conditions such as neurodegenerative disorders, neuro-oncology, and epilepsy. The various metrics that we can derive from CT, and MR, are being used together with dynamic PET data to produce multiple quantitative functional maps of dementia. Multi-modal techniques are also being used to characterize tumour metabolism and flow in the brain, and to devise novel methods of assessing epileptic foci.
Figure 1: PET/MR study using 1 injection of F18 Amyvid to display multiple parameters (a) R1 images defined from dynamic PET show areas of hypo-perfusion, some of which is caused by cortical atrophy (b) Amyloid Imaging shows no build-up of amyloid plaques in hypo-perfusion.
In cardiac PET, we continue to refine methodologies and better understand metrics such as coronary flow reserve and myocardial blood flow. Working on how these metrics fit clinically with other anatomical techniques such as CT coronary angiography and CT calcium score is a further area we are exploring. Beyond coronary artery disease, we are also looking at providing techniques and multi-parametric measures to better understand systemic diseases with cardiac findings such as sarcoidosis and amyloidosis.
Figure 2: An example of quantitative myocardial blood flow.
Our experience in kinetic modelling and dynamic PET is now being extended into oncological applications with the aim of maximizing the potential of readily available tracers such as FDG, fluorocholine and Rubidium-82. Using these tracers together with functional CT and MR imaging, we are working towards a better understanding of tumour physiology by relating our findings to histology.
Figure 3: Non-small cell lung cancer shown on (a) a standard CT (b) a PET/CT image with colour overlay signifying blood flow as measured by Rb82 PET, (c) a high-resolution CT pre contrast and (d) post contrast.
Brain PET and SPECT imaging for pre-surgical epilepsy evaluation
At INM a variety of imaging techniques are being used for the pre-surgical evaluation of drug-resistant epilepsy aiming to identify the seizure onset zone, in collaboration with The National Hospital for Neurology and Neurosurgery (NHNN).
We use FDG PET scans to map brain metabolism and identify hypometabolic areas which can point to the location of seizure onset. Voxel-based analysis comparing to an age-matched database of normal scans is in use to help pinpoint the areas of significant hypometabolism.
Ictal/Interictal HMPAO SPECT scans are also performed to visualize brain perfusion patterns. My research focuses on SPECT/CT imaging using Ictal/Interictal subtraction analysis by Statistical Parametric Mapping. This analysis serves to highlight areas of significant hyperperfusion which are being used by researchers at NHNN to help plan intra-cranial EEG implantation.
Although PET/CT is the current clinical standard, the use of PET/MRI in epilepsy is also being explored at INM. Combining the excellent soft tissue contrast of anatomical brain MRI with metabolic information derived from PET can facilitate the seizure onset zone localization.
Colleagues from INM (John Dickson) and UCL (Ninon Burgos) are working on the difficult task of MR-based attenuation correction for PET, which is a pre-requisite for quantitative PET analysis. Finally, new MR imaging techniques such as Arterial Spin Labelling and MR Spectroscopy are put to the test (Anna Barnes and Francesco Fraioli) aiming to obtain complementary information about brain perfusion and tissue metabolites to improve seizure onset localisation.
