CMR-based blood oximetry via multi-parametric estimation using multiple T2 measurements

Abstract

Background: Measurement of blood oxygen saturation (O2 saturation) is of great importance for evaluation of patients with many cardiovascular diseases, but currently there are no established non-invasive methods to measure blood O2 saturation in the heart. While T2-based CMR oximetry methods have been previously described, these approaches rely on technique-specific calibration factors that may not generalize across patient populations and are impractical to obtain in individual patients. We present a solution that utilizes multiple T2 measurements made using different inter-echo pulse spacings. These data are jointly processed to estimate all unknown parameters, including O2 saturation, in the Luz-Meiboom (L-M) model. We evaluated the accuracy of the proposed method against invasive catheterization in a porcine hypoxemia model.

Methods: Sufficient data diversity to estimate the various unknown parameters of the L-M model, including O2 saturation, was achieved by acquiring four T2 maps, each at a different τ ₁₈₀ (12, 15, 20, and 25 ms). Venous and arterial blood T2 values from these maps, together with hematocrit and arterial O2 saturation, were jointly processed to derive estimates for venous O2 saturation and other nuisance parameters in the L-M model. The technique was validated by a progressive graded hypoxemia experiment in seven pigs. CMR estimates of O2 saturation in the right ventricle were compared against a reference O2 saturation obtained by invasive catheterization from the right atrium in each pig, at each hypoxemia stage. O2 saturation derived from the proposed technique was also compared against the previously described method of applying a global calibration factor (K) to the simplified L-M model.

Results: Venous O2 saturation results obtained using the proposed CMR oximetry method exhibited better agreement (y = 0.84× + 12.29, R² = 0.89) with invasive blood gas analysis when compared to O2 saturation estimated by a global calibration method (y = 0.69× + 27.52, R² = 0.73).

Conclusions: We have demonstrated a novel, non-invasive method to estimate O2 saturation using quantitative T2 mapping. This technique may provide a valuable addition to the diagnostic utility of CMR in patients with congenital heart disease, heart failure, and pulmonary hypertension.

Keywords: Cardiovascular magnetic resonance; Oxygen saturation; T2 mapping.

Fig. 1

Overall framework of proposed CMR oximetry technique. The graph depicts the simulation of the L-M model (described in gray box at top of the figure, adapted from [14]). The transverse relaxation time of blood is plotted as a function of O2 saturation ( %SbO ₂) and inter-echo spacing (τ ₁₈₀). Other parameters used in the simulation were: Hct = 0.41, T _2O = 300 ms, α = 0.545 ppm, and τ _ex = 3 ms. Four different T2 maps, each with a fixed τ ₁₈₀ at 12, 15, 20, and 25 ms, were acquired to generate a set of equations for the L-M model relating T2 and O2 saturation. The data, along with known Hct and arterial O2 saturation, are jointly processed by NLLS curve fitting to estimate the unknown parameters - venous O2 saturation, α, τ _ex, and T _2O

Fig. 2

Pulse sequence scheme for acquisition of quantitative blood T2 map. The figure depicts the scheme for the T2 preparation module to acquire a single quantitative T2 map of the blood for a given τ ₁₈₀. Four such T2 maps were acquired at different τ ₁₈₀ for the estimation of blood O2 saturation

Fig. 3

Setup for animal hypoxemia experiment. Each animal was allowed to inspire different concentrations of oxygen (FiO ₂). At each level of FiO ₂, arterial and venous blood O2 saturation were measured by invasive catheter sampling and blood gas analysis before and after the acquisition of CMR data. Blood T2 was measured in the ventricles by means of T2 maps. Blood T2 measured in the right and left ventricles, along with hematocrit and arterial O2 saturation, were then analyzed for each data set to determine venous O2 sat in the right ventricle

Fig. 4

Example of blood T2 maps acquired in one animal at different stages of hypoxemia. The four T2 maps (at τ ₁₈₀ = 12, 15, 20, and 25 ms) acquired in an animal at four different levels of inspired oxygen (FiO ₂) are shown. The corresponding venous (RV) and arterial (LV) O2 saturation levels measured in the right and left ventricles by invasive catheterization and blood gas analysis are shown at the top of each row. Note the decrease in T2 in both arterial and venous blood pools with increasing τ ₁₈₀ (left to right) as well as with decreasing oxygen (top to bottom)

Fig. 5

Regression plots comparing CMR measurements of O2 saturation against reference O2 saturation by catheterization. The regression plots indicate the linear relationship between CMR measures of O2 saturation (%, measured in the right ventricle) estimated from a global calibration, b unconstrained optimization, c fixed nuisance parameter, and d constrained nuisance parameter solutions to the L-M model, with the reference O2 saturation by catheter sampling (measured in the right atrium). The regression line is depicted by the solid black line. Also shown are the 95% confidence band (within the red lines) and 95% prediction band (within the orange lines). Note that the y-axis in plot (b) is on a different scale

Fig. 6

Bland Altman plots comparing CMR measurements of O2 saturation against reference O2 saturation by catheterization. The plots show the agreement between the CMR estimates of O2 saturation from the different solutions to the L-M model - a global calibration, b unconstrained optimization, c fixed nuisance parameter, and d constrained nuisance parameter - with the reference O2 saturation by catheter sampling. Note that the y-axis in plot (b) is on a different scale