Volume 13 Supplement 1

Abstracts of the 2011 SCMR/Euro CMR Joint Scientific Sessions

Open Access

Equilibrium contrast CMR for the detection of amyloidosis in mice

  • Adrienne E Campbell1,
  • Anthony N Price2,
  • Stephan Ellmerich3,
  • Paul Simons3,
  • Raya Al-Shawi3,
  • Philip N Hawkins3,
  • Roger J Ordidge4,
  • Mark B Pepys3,
  • James C Moon5 and
  • Mark F Lythgoe1
Journal of Cardiovascular Magnetic Resonance201113(Suppl 1):O60

DOI: 10.1186/1532-429X-13-S1-O60

Published: 2 February 2011

Objective

In this study, we optimise equilibrium contrast CMR (EQ-CMR) protocols in mice and apply EQ-CMR to detect AA amyloidosis in the heart and liver of mice with inducible transgenic overexpression of serum amyloid A protein.

Background

Systematic amyloidosis is a severe, diagnostically challenging, disorder characterised by the extracellular deposition of insoluble abnormal protein fibrils [1]. Recently, Flett et al [2] showed that the volume of distribution of gadolinium (Gd) contrast agents, calculated by EQ-CMR, can be used to measure fibrosis. This technique uses the extracellular nature of Gd to relate the volume of distribution of the agent (Vd) to extracellular pathology.

Methods

A bolus followed by steady infusion of Magnevist was used to generate a blood - tissue equilibrium of [Gd]. The optimal dose and timing protocol, determined empirically, is displayed in Figure 1. An ECG-gated Look-Locker technique [3] was used to measure the T1 and the Vd can be calculated: Vd=ΔR1,tissue/ ΔR1,blood
https://static-content.springer.com/image/art%3A10.1186%2F1532-429X-13-S1-O60/MediaObjects/12968_2011_Article_1529_Fig1_HTML.jpg
Figure 1

T1,eff plotted to demonstrate the optimized equilibrium protocol in mice. Dotted lines represent values within 5% of final T1 measurement (defined as equilibrium).

Nine control and 11 amyloidotic mice [4] (confirmed by histology to have major amyloid deposits in the liver and minor deposits in the heart) were imaged using a standard cine stack and EQ-CMR. A mid-ventricle short-axis slice through the heart, which included a section of liver was used. The hematocrit (Hct) was measured using a blood sample from the tail vein.

Results

Analysis of cardiac functional parameters calculated from cine images showed no significant difference between the groups. Figure 2 presents box-and-whisker plots comparing Vd between groups for the (a) myocardium and (b) liver. The amyloidotic group shows a significantly increased Vd of Gd compared to the control group in both organs. The Vd of the control group was 15.4% ± 0.2% (myocardium) and 15.4±0.3% (liver) and of the amyloidotic group 19.8±0.4% (myocardium) and 23.6± 0.4% (liver) (mean±s.e.m).
https://static-content.springer.com/image/art%3A10.1186%2F1532-429X-13-S1-O60/MediaObjects/12968_2011_Article_1529_Fig2_HTML.jpg
Figure 2

Comparison of Vd between groups

Conclusion

An EQ-CMR procedure has been optimised in the mouse. The results of this study show that EQ-CMR techniques can detect minor amyloid deposits with good sensitivity. This approach has the potential to become a sensitive diagnostic tool with considerable utility in serial quantitative monitoring of response to novel therapy aimed at elimination of amyloid deposits [5, 6].

Authors’ Affiliations

(1)
Centre for Advanced Biomedical Imaging, University College London
(2)
Robert Steiner MRI Unit, Imperial College London
(3)
Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College London
(4)
Department of Medical Physics and Biomedical Engineering, University College London
(5)
Heart Hospital and Division of Medicine, University College London

References

  1. Pepys MB: Annu Rev Med. 2006, 57: 223-224. 10.1146/annurev.med.57.121304.131243.View ArticlePubMedGoogle Scholar
  2. Flett AS, et al: Circulation. 2010, 122: 138-144. 10.1161/CIRCULATIONAHA.109.930636.View ArticlePubMedGoogle Scholar
  3. Kober F, et al: MRM. 2004, 51: 62-67.View ArticlePubMedGoogle Scholar
  4. Simons P, et al: Amyloid. 2010, 17 (sl): 45-46.Google Scholar
  5. Pepys MB: Clin. Med. 2007, 7: 562-578.View ArticlePubMedGoogle Scholar
  6. Bodin K, et al: Nature. 2010,Google Scholar

Copyright

© Campbell et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Advertisement