Author + information
- Received September 28, 2015
- Revision received November 30, 2015
- Accepted November 30, 2015
- Published online January 1, 2016.
- Thomas A. Treibel, MBBS∗,†,
- Marianna Fontana, MD∗,†,
- Viviana Maestrini, MD∗,‡,
- Silvia Castelletti, MD∗,†,
- Stefania Rosmini, MD∗,†,
- Joanne Simpson, MBBS∗,
- Arthur Nasis, MD∗,
- Anish N. Bhuva, MBBS∗,†,
- Heerajnarain Bulluck, MBBS∗,†,
- Amna Abdel-Gadir, MBBS∗,†,
- Steven K. White, MB, ChB∗,†,
- Charlotte Manisty, PhD∗,†,
- Bruce S. Spottiswoode, PhD§,
- Timothy C. Wong, MD‖,
- Stefan K. Piechnik, PhD, MScEE¶,
- Peter Kellman, PhD#,
- Matthew D. Robson, PhD¶,
- Erik B. Schelbert, MD, MS‖ and
- James C. Moon, MD∗,†∗ ()
- ∗Barts Heart Centre, St Bartholomew’s Hospital, London, United Kingdom
- †Institute of Cardiovascular Science, University College London, London, United Kingdom
- ‡Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology & Geriatric Sciences, Sapienza University, Rome, Italy
- §Siemens Healthcare, Chicago, Illinois
- ‖UPMC Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
- ¶Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
- #National Heart, Lung, and Blood Institute, National Institute for Health, Bethesda, Maryland
- ↵∗Reprint requests and correspondence:
Prof James C. Moon, The Heart Hospital Imaging Centre and Barts Heart Centre, St Bartholomew’s Hospital, 2nd Floor, King George V Block, London EC1A 7BE, United Kingdom.
Objectives The authors sought to generate a synthetic extracellular volume fraction (ECV) from the relationship between hematocrit and longitudinal relaxation rate of blood.
Background ECV quantification by cardiac magnetic resonance (CMR) measures diagnostically and prognostically relevant changes in the extracellular space. Current methodologies require blood hematocrit (Hct) measurement—a complication to easy clinical application. We hypothesized that the relationship between Hct and longitudinal relaxation rate of blood (R1 = 1/T1blood) could be calibrated and used to generate a synthetic ECV without Hct that was valid, user-friendly, and prognostic.
Methods Proof-of-concept: 427 subjects with a wide range of health and disease were divided into derivation (n = 214) and validation (n = 213) cohorts. Histology cohort: 18 patients with severe aortic stenosis with histology obtained during valve replacement. Outcome cohort: For comparison with external outcome data, we applied synthetic ECV to 1,172 consecutive patients (median follow-up 1.7 years; 74 deaths). All underwent CMR scanning at 1.5-T with ECV calculation from pre- and post-contrast T1 (blood and myocardium) and venous Hct.
Results Proof-of-concept: In the derivation cohort, native R1blood and Hct showed a linear relationship (R2 = 0.51; p < 0.001), which was used to create synthetic Hct and ECV. Synthetic ECV correlated well with conventional ECV (R2 = 0.97; p < 0.001) without bias. These results were maintained in the validation cohort. Histology cohort: Synthetic and conventional ECV both correlated well with collagen volume fraction measured from histology (R2 = 0.61 and 0.69, both p < 0.001) with no statistical difference (p = 0.70). Outcome cohort: Synthetic ECV related to all-cause mortality (hazard ratio 1.90; 95% confidence interval 1.55 to 2.31; for every 5% increase in ECV). Finally, we engineered a synthetic ECV tool, generating automatic ECV maps during image acquisition.
Conclusions Synthetic ECV provides validated noninvasive quantification of the myocardial extracellular space without blood sampling and is associated with cardiovascular outcomes.
Drs. Treibel and Fontana are supported by doctoral research fellowships by the U.K. National Institute of Health Research and British Heart Foundation, respectively. Dr. Spottiswoode is an employee of Siemens Medical Solutions USA, Inc. Dr. Wong was supported by a grant from the Agency for Healthcare Research and Quality. Drs. Piechnik and Robson are supported by the NIHR Oxford Biomedical Research Centre, Oxford University Hospitals Trust, University of Oxford. Dr. Schelbert was supported by grants from The Pittsburgh Foundation, and the American Heart Association Scientist Development fund; he has accepted contrast material from Bracco Diagnostics for research purposes beyond the scope of this work. Prof. Moon is directly and indirectly supported by the University College London Hospitals NIHR Biomedical Research Centre and Biomedical Research Unit at Barts Hospital, respectively. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received September 28, 2015.
- Revision received November 30, 2015.
- Accepted November 30, 2015.
- American College of Cardiology Foundation