UCL Institute of Cardiovascular Science
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- Structural heart disease
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The UCL Centre for Advanced Biomedical Imaging (CABI) is a new multidisciplinary research centre for focused on experimental imaging. The Centre houses a state-of-the-art BHF 9.4T MRI system, a new photoacoustic imaging facility, in-vivo confocal endoscopy, ultrasound, bioluminescence and fluorescence imaging, as well as SPECT/CT.
Our goals are to establish an integrated strategy for the development and application of novel in- vivo cardiac imaging technologies aimed at further understanding the mechanisms of disease in order to develop new therapeutic strategies. Furthermore, we aim to deliver a multimodal imaging programme to investigate the molecular, functional, and structural consequences of the disease process on a range of different scales.
Key research activities
Preclinical cardiac imaging is technically challenging as the heart is literally a moving target. Beating 10 times faster than the human heart, we can now capture a mouse heart beat in a fraction of a second using our state-of-the-art MRI system funded by the British Heart Foundation. These ultrafast techniques are used to generate information about cardiac structure, function, tissue health and cellular viability. In collaboration with Mark Pepys, Paul Riley, Derek Hausenloy, we are using our high-speed imaging techniques and novel forms of image contrast to study life-threatening diseases such as amyloidosis and heart attacks. Our aim is to use a cross-disciplinary approach to tackle heart disease, which remains the leading cause of death in the developed world.
For a selection of preclinical imaging methods see: Price AN et al. Cardiovascular magnetic resonance imaging in experimental models. Open Cardiovasc Med J. 2010 Nov 26;4:278-92.
scientists finished sequencing the mouse genome. In a massive worldwide
initiative, 25,000 genetically altered mice are currently being produced to
investigate the impact of faulty genes on our well-being. We are
developing 3D micro magnetic resonance imaging techniques to visualise tiny
changes in brain and heart structure. In a project with Peter Scambler, we are
looking at the effects of genes responsible for hole in the heart in babies - a
hole about the size of a human hair in the embryo heart.
Magnetic nanoparticles can be used to image and steer cells to sites of injury. We are using superparamagnetic iron oxide nanoparticles, which become magnetic in the presence of a magnetic field, to guide tagged cells. Magnetic nanoparticles can be made small enough to be incorporate into cells or on to antibodies, affording a safe and reliable means of magnetically tagging. In CABI we have developed ways of imaging cells or antibodies using nanoparticles and once magnetically tagged, steering them to sites of tissue damage using the MRI scanner - a new technique known as Magnetic Resonance Targeting has been developed with Quentin Pankhurst.
One approach available in CABI for assessing myocardial viability is delayed enhancement MRI or late gadolinium enhancement (LGE) which involves administrating a contrast agent to directly image non-viable myocardium. In this method, an extracellular contrast agent (usually Gd-DTPA) is injected into the subject. On first-pass images, normal myocardium with normal perfusion would be enhanced by the contrast agent, whereas infarcted regions would appear hypoenhanced due to reduced/ absent perfusion from microvascular obstruction. However, the hypoenhanced region would gradually become hyperenhanced as a consequence of increased retention of contrast agent, which is thought to be caused by increased extracellular matrix within collagenous scar, and delayed washout due to reduced capillary density. This method is well-validated clinically for predicting the distribution of infarcted myocytes and for excluding irreversible damage where no delayed enhancement is observed. It is also well validated in a mouse occlusion/ reperfusion model with TTC staining.
The discovery of stem cells and their potential for tissue regeneration led to the hypothesis that regeneration of the adult damaged heart might be possible via stem cell transplantation. It is hoped that stem cells will differentiate into cardiomyocytes or fuse with resident myocytes and functionally integrate if they receive the right clues from their microenvironment. MRI together with stem cells labelled with super paramagnetic iron oxide (SPIO) can be used to image cells. SPIOs generate local field inhomogeneities when placed into a magnetic field. This causes local hypointensity (darkness) on in T2 or T2* weighted MR images. The sensitivity of T2* images to SPIOs allows the detection of a few thousand cells weakly labelled with small SPIOs (<200nm particle diameter, ~10pg iron oxide per cell) or the detection of single cells labelled with micrometer sized particles. The non-invasive nature of MRI allows monitoring of the distribution of transplanted cells over time. It is also possible to estimate the amount of cells present which should improve data analysis.
MRI is important for the assessment of cardiac structure and function in pre-clinical studies of cardiac disease. We have developed an Arterial Spin Labeling (ASL) technique that can be used to measure perfusion non-invasively in the mouse heart. ASL perfusion measurements are generated by the comparison of two T1 maps: one obtained using a global inversion recovery and the other with a slice-selective inversion recovery for a slab slightly larger than the imaging slice. In the slice-selective case, spins that enter the imaging slice due to perfusion are not inverted, causing an apparent acceleration in T1 recovery. An assessment of the difference between the global and slice-selective T1 maps provides a quantification of the blood perfusion in the imaging slice. In this work, an ECG-gated Look-Locker sequence with segmented k-space acquisition has been implemented, which can acquire ASL data sets in 15 minutes in the mouse heart. Thus we have methods to assess cardiac blood flow for longitudinal imaging in a non-invasive fashion.