Abstract

<h3>Background</h3> Extracellular volume (ECV) quantification by cardiovascular magnetic resonance (CMR) measures the extracellular space. Current methodologies require blood haematocrit (Hct) correction, a barrier to easy clinical use. We hypothesised that the relationship between Hct and longitudinal relaxation time of blood (T1<sub>blood</sub>) could be calibrated and used to generate a <i>synthetic</i> ECV without Hct. <h3>Methods</h3> 427 subjects with a wide range of health and disease were divided into derivation (n = 214) and validation (n = 213) cohorts (Table 1 for patient characteristics). All subjects underwent T1 mapping with ShMOLLI at 1.5 Tesla for ECV quantification. Venous blood for Hct was obtained prior to scanning with 44 patients having a repeat Hct within 6 h. ECV was calculated as: ECV = (Δ[1/T1<sub>myo</sub>] / Δ[1/T1<sub>blood</sub>]) * [1-haematocrit]). <i>Synthetic</i> Hct was approximated from the linear relationship between Hct and native T1<sub>blood</sub>, and used to calculate <i>synthetic</i> ECV. Histological validation was performed on 18 patients with severe aortic stenosis (age 71 ± 10 years, 78% male). ECV was compared with collagen volume fraction from intra-operative biopsies taken during surgical valve replacement. <h3>Results</h3> In the derivation cohort, native T1<sub>blood</sub> and Hct showed a linear relationship (R<sup>2</sup>=0.45; <i>p &lt; 0.001</i>, Figure 1). This was used to derive <i>synthetic </i>Hct<i> = </i>0.88 – (T1<sub>blood</sub>/ 3240). <i>Synthetic </i>ECVcorrelated well with ECV (R<sup>2</sup> = 0.99; <i>p &lt; 0.001</i>). These results were maintained in the validation cohort. Test:retest variability of haematocrit was higher than expected (n = 44, variability 10% with Hct:Hct R<sup>2</sup> = 0.86). On histological validation, <i>synthetic </i>and conventional ECV both correlated well with collagen volume fraction (R<sup>2</sup> = 0.61 and 0.69, <i>p &lt; 0.001</i>). <h3>Conclusion</h3> <i>Synthetic </i>ECV allows instantaneous non-invasive quantification of the myocardial extracellular space without blood sampling. Inline application of <i>synthetic</i> ECV may be an attractive alternative in clinical practice.

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