0.1 mm cubic voxel reconstruction of transgenic hypertrophic mouse heart structure using diffusion tensor magnetic resonance imaging

University of Cambridge (2008) Proc Physiol Soc 11, C24

Oral Communications: 0.1 mm cubic voxel reconstruction of transgenic hypertrophic mouse heart structure using diffusion tensor magnetic resonance imaging

A. P. Benson1,4, S. H. Gilbert1,4, O. Bernus1,4, M. E. Ries2, J. F. Ainscough3,4, S. G. Ball3,4, A. V. Holden1,4

1. Institute of Membrane and Systems Biology, University of Leeds, Leeds, United Kingdom. 2. School of Physics and Astronomy, University of Leeds, Leeds, United Kingdom. 3. Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom. 4. Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, United Kingdom.

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Transgenic mouse models in which human angiotensin II type 1 (AT1) receptors are expressed specifically in the heart have been developed (1). AT1 receptor expression can be temporally controlled both prior to and after birth to allow activation over discrete periods. The resultant controlled hypertrophy is apparent in whole hearts. Diffusion tensor magnetic resonance imaging (DT-MRI) was used to reconstruct, visualise and quantify the structure of these hearts. The primary eigenvector of the diffusion tensor provides a measure of fibre orientation, while the secondary and tertiary eigenvectors provide indices of sheet structure (2). Fixed (4% formaldehyde/PBS; post mortem) and immobilised (in Fomblin) entire mouse hearts were imaged using a Bruker 9.4 T MR instrument and a standard reduced encoding diffusion-weighted gradient echo sequence at 20°C: 500 ms TR; 18.7 ms TE; diffusion gradients with 5 ms duration and 8.9 ms separation; b = 1130 s/mm2. Voxel resolution was 0.1 mm3. For each scan we acquired a single b0 image and diffusion-weighted images sensitised in each of 12 optimised directions (3). Single scan time for one heart was ∼10 hours. We performed 6 scans per heart and calculated mean measurements at each voxel. Each heart model is a dataset of ∼300 MB, and is available from us on request. We have reconstructed, visualised and quantified the geometry and the fibre and sheet structure in these mouse hearts. These fibre and sheet directions can be mapped throughout the entire heart, and allow the application of fibre tracking algorithms. Thus, the combination of transgenic and DT-MRI methods enables the morphological changes in cardiac structure to be followed and quantified at different stages during the hypertrophic process. These data add to a family of high-resolution digital models of cardiac geometry and architecture obtained from different species using DT-MRI (3,4), which can be used as platforms on which to run simulations of normal, pathological and pharmacologically-modified electrophysiology (5).



Where applicable, experiments conform with Society ethical requirements.

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