Blood volume measurement using cardiovascular magnetic resonance and ferumoxytol: preclinical validation

The hallmark of heart failure is increased blood volume. Quantitative blood volume measures are not conveniently available and are not tested in heart failure management. We assess ferumoxytol, a marketed parenteral iron supplement having a long intravascular half-life, to measure the blood volume with cardiovascular magnetic resonance (CMR).

Swine were administered 0.7 mg/kg ferumoxytol and blood pool T₁ was measured repeatedly for an hour to characterize contrast agent extraction and subsequent effect on V_blood estimates. We compared CMR blood volume with a standard carbon monoxide rebreathing method. We then evaluated three abbreviated acquisition protocols for bias and precision.

Mean plasma volume estimated by ferumoxytol was 61.9 ± 4.3 ml/kg. After adjustment for hematocrit the resultant mean blood volume was 88.1 ± 9.4 ml/kg, which agreed with carbon monoxide measures (91.1 ± 18.9 ml/kg). Repeated measurements yielded a coefficient of variation of 6.9%, and Bland-Altman repeatability coefficient of 14%. The blood volume estimates with abbreviated protocols yielded small biases (mean differences between 0.01-0.06 L) and strong correlations (r² between 0.97-0.99) to the reference values indicating clinical feasibility.

In this swine model, ferumoxytol CMR accurately measures plasma volume, and with correction for hematocrit, blood volume. Abbreviated protocols can be added to diagnostic CMR examination for heart failure within 8 min.