Contrast Agents
Noor Sharrack, MBChB, MRCP, DTM&H
Clinical Research Fellow
University of Leeds, England, United Kingdom
John D D. Biglands, PhD, MSc
Clinician scientist
Leeds Institute of Cardiovascular and Metabolic Medicine
Leeds, England, United Kingdom
David A. Broadbent, PhD
Clinician scientist
Leeds Institute of Cardiovascular and Metabolic Medicine, England, United Kingdom
Peter Kellman, PhD
Senior Scientist
National Institutes of Health, Maryland, United States
Kelvin Chow, PhD
Staff Scientist
Siemens Healthineers
Chicago, Illinois, United States
John P. Greenwood, PhD
Professor
University of Leeds
Leeds, England, United Kingdom
Eylem Levelt, PhD
Associate Professor and Honorary Consultant
University of Leeds
Leeds, England, United Kingdom
Sven Plein, MD, PhD
Professor
University of Leeds
Leeds, England, United Kingdom
David L. Buckley, PhD
Professor of Medical Physics
Leeds Institute of Cardiovascular and Metabolic Medicine, United Kingdom
Extracellular volume (ECV) is an independent predictor of mortality and outcome in patients with severe aortic stenosis (AS) . Recent SCMR guidelines recommend measurement of ECV using T1 maps taken before and 10-30 minutes after a 0.1 to 0.2 mmol/kg dose of contrast agent. However, these measurements use a conventional model (CM) which assumes rapid water exchange (WX) between the ECV and the myocytes which can result in underestimated ECV. The shutter speed model (SSM) incorporates variable WX using T1 maps at multiple time points post-contrast. The aim of this study was to investigate whether WX influences estimates of ECV in patients with severe AS.
Methods:
Patients with severe AS referred for aortic valve replacement surgery were recruited between January and August 2022. T1 measurements were made on a 3T system (MAGNETOM Prisma, Siemens Healthcare, Erlangen, Germany) using a prototype multiparametric saturation-recovery single-shot acquisition (mSASHA) , (a) before contrast, (b) 4 mins after a 0.05 mmol/kg dose of Gadovist (used for a perfusion measurement) and (c) 4, (d) 10 and (e) 30 minutes after an additional 0.1 mmol/kg which was delivered ~8 minutes after the first injection (Fig. 1). Three CM-based ECV estimates were made using recent patient hematocrit levels (Hct) and T1 measurements (a & b), (a & d) and (a & e) and these were compared to SSM ECV estimates made using Hct and all 5 T1 measurements. Late gadolinium enhancement imaging was undertaken to identify areas of scar or fibrosis which were then excluded from analysis of T1 and ECV.
Results:
25 patients were studied with a median (IQR) age of 69 (63-73) years, Hct of 0.43 (0.40-0.45) and a male: female ratio of 14:11. Median ECV estimated using the CM at 4 minutes following a 0.05 mmol/kg dose was 25 (23-27)%. ECV estimated using the CM at 10 minutes after a cumulative dose of 0.15 mmol/kg Gadovist was 21 (20-24) % and increased at 30 minutes to 22 (21-26)% (p = 0.0001; Wilcoxon signed-rank test), but was highest at 4 mins after a low dose of contrast (0.05 mmol/kg; Fig 2). ECV estimated using the SSM was 25 (24-30)%.
Alongside the results of the SSM analysis, these data suggest that it is not necessary to wait 10 to 30 mins before acquiring a post-contrast T1 map. CM ECV estimates following a cumulative dose of 0.15 mmol/kg are underestimated because of limited WX. Moreover, as the residence time of water in the myocytes increases (as the myocytes get bigger and WX slows down) the difference between CM and SSM estimates of ECV increases (Fig. 3).
Conclusion:
Measurements made following current guidelines (Gadovist dose of 0.15 mmol/kg and T1 measured between 10 and 30 mins post-contrast) may underestimate ECV (absolute difference, SSM ECV – CM ECV, of up to 12%, Fig. 3). In the absence of multiple T1 maps needed for SSM, measurement of a T1 map following a low dose of contrast agent may produce ECV estimates less affected by limited water exchange.