The impact of water exchange on estimates of myocardial extracellular volume calculated using contrast enhanced T1 measurements: A preliminary analysis in patients with severe aortic stenosis

Abstract

Purpose: Guidelines recommend measuring myocardial extracellular volume (ECV) using T₁ -mapping before and 10-30 min after contrast agent administration. Data are then analyzed using a linear model (LM), which assumes fast water exchange (WX) between the ECV and cardiomyocytes. We investigated whether limited WX influences ECV measurements in patients with severe aortic stenosis (AS).

Methods: Twenty-five patients with severe AS and 5 healthy controls were recruited. T₁ measurements were made on a 3 T Siemens system using a multiparametric saturation-recovery single-shot acquisition (a) before contrast; (b) 4 min post 0.05 mmol/kg gadobutrol; and (c) 4 min, (d) 10 min, and (e) 30 min after an additional gadobutrol dose (0.1 mmol/kg). Three LM-based ECV estimates, made using paired T₁ measurements (a and b), (a and d), and (a and e), were compared to ECV estimates made using all 5 T₁ measurements and a two-site exchange model (2SXM) accounting for WX.

Results: Median (range) ECV estimated using the 2SXM model was 25% (21%-39%) for patients and 26% (22%-29%) for controls. ECV estimated in patients using the LM at 10 min following a cumulative contrast dose of 0.15 mmol/kg was 21% (17%-32%) and increased significantly to 22% (19%-35%) at 30 min (p = 0.0001). ECV estimated using the LM was highest following low dose gadobutrol, 25% (19%-38%).

Conclusion: Current guidelines on contrast agent dose for ECV measurements may lead to underestimated ECV in patients with severe AS because of limited WX. Use of a lower contrast agent dose may mitigate this effect.

Keywords: T1; aortic stenosis; extracellular volume; water exchange.

Figure 1:

A shows the sequence of prototype multiparametric saturation-recovery single-shot acquisition (mSASHA) T1 maps made after different times and doses of gadobutrol. Panel B shows time points (a-e) in Panel A used to measure blood R1 over time in a healthy control.

Figure 2:

An example of the non-linear association between R1 (1/T1) of the myocardium and blood in a patient with severe aortic stenosis. In this example the residence time of water in the myocytes was estimated using the 2SXM at 215 ms and the ECV at 30%. LM ECV estimates at 10 & 30 mins after 0.15 mmol/kg and at 4 mins after 0.05 mmol/kg (represented by the slopes of the straight lines in the figure) were 24%, 25% and 28%, respectively.

Figure 3:

A box-and-whisker plot showing LM ECV estimates in patients as a function of contrast agent concentration as a result of dose (and time) compared with ECV estimated by the 2SXM. ECV- extracellular volume; LM- linear model; 2SXM – two-site exchange model.

Figure 4:

The absolute difference between 2SXM and LM estimates of ECV (y-axis) increases as the residence time of water in the myocytes (x-axis) increases. Orange values represent data for patients and blue values represent data for healthy controls.