Quantification of myocardial extracellular volume without blood sampling

Abstract

Aims: Cardiac magnetic resonance (CMR) T1 relaxation time mapping is an established technique primarily used to identify diffuse interstitial fibrosis and oedema. The myocardial extracellular volume (ECV) can be calculated from pre- and post-contrast T1 relaxation times and is a reproducible parametric index of the proportion of volume occupied by non-cardiomyocyte components in myocardial tissue. The conventional calculation of the ECV requires blood sampling to measure the haematocrit (HCT). Given the high variability of the HCT, the blood collection is recommended within 24 h of the CMR scan, limiting its applicability and posing a barrier to the clinical routine use of ECV measurements. In recent years, several research groups have proposed a method to determine the ECV by CMR without blood sampling. This is based on the inverse relationship between the T1 relaxation rate (R1) of blood and the HCT. Consequently, a 'synthetic' HCT could be estimated from the native blood R1, avoiding blood sampling.

Methods and results: We performed a review and meta-analysis of published studies on synthetic ECV, as well as a secondary analysis of previously published data to examine the effect of the chosen regression modell on bias. While, overall, a good correlation and little bias between synthetic and conventional ECV were found in these studies, questions regarding its accuracy remain.

Conclusion: Synthetic HCT and ECV can provide a 'non-invasive' quantitative measurement of the myocardium's extracellular space when timely HCT measurements are not available and large alterations in ECV are expected, such as in cardiac amyloidosis. Due to the dependency of T1 relaxation times on the local setup, calculation of local formulas using linear regression is recommended, which can be easily performed using available data.

Keywords: CMR; ECV classification description; T1 mapping; cardiac magnetic resonance (CMR); synthetic HCT; tissue characterization.

Graphical abstract

For the establishment of a local model, ∼500 patients with measured haematocrit (HCT) and left ventricular T1 relaxation rate (R1 = 1/T1) should be available and split evenly into derivation and validation data sets. The regression parameters from the derivation data is used for the estimation of synthetic HCT, which is then used for the calculation of the synthetic extracellular volume (ECV) instead of the measured HCT.

Figure 1

Bland–Altman analysis of measured haematocrit vs. synthetic haematocrit derived from standard linear regression (left) and Deming regression (right). The validation data set from Chen et al. was used. While the standard linear regression provides a slightly better fit, measured by R², the orthogonal regression eliminates the slope of the measurement error and is therefore more accurate at extreme values.

Figure 2

ECV vs. haematocrit (HCT) in a fictional patient. A change in HCT of 10% causes a change in ECV of ∼5%. Other parameters as follows: Post-contrast myocardial T1 430 ms, native myocardial T1 1000 ms, post-contrast blood T1 300 ms, native blood T1 1600 ms.

Figure 3

ROC curves for the diagnosis of cardiac amyloidosis using conventional ECV, synthetic ECV using standard linear regression, and synthetic ECV using a Deming regression. Data set from Chen et al.