Improved R2* measurements in myocardial iron overload

Abstract

Purpose: To optimize R2*(1/T2*) measurements for cardiac iron detection in sickle cell and thalassemia patients.

Materials and methods: We studied 31 patients with transfusion-dependent sickle cell disease and 48 patients with thalassemia major; myocardial R2* was assessed in a single midpapillary slice using a gated gradient-echo pulse sequence. Pixel-wise maps were coregistered among the patients to determine systematic spatial fluctuations in R2*. The contributions of minimum TE, echo spacing, signal-decay model, and region-of-interest (ROI) choice were compared in synthetic and acquired images.

Results: Cardiac relaxivity demonstrated characteristic circumferential variations regardless of the degree of iron overload. Within the interventricular septum, a gradient in R2* from right to left ventricle was noted at high values. Pixel-wise and ROI techniques yielded nearly identical values. Signal decay was exponential but a constant offset or second exponential term was necessary to avoid underestimation at high iron concentration. Systematic underestimation of R2* was observed for higher minimum TE, limiting the range of iron concentrations that can be profiled. Fat-water oscillations, although detectable, represented only 1% of the total signal.

Conclusion: Clinical cardiac R2* measurements should be restricted to the interventricular septum and should have a minimum TE < or = 2 msec. ROI analysis techniques are accurate; however, offset-correction is essential.

Figure 1

a–h: The short-axis mid papillary heart slice from a representative patient at specified TE. i: A magnified view of the myocardium (TE = 3 msec) with manually traced endocardial and epicardial boundaries dividing the LV and RV. R2* measurements were made in four segments of the myocardium as indicated (–4); segment 1 was the reference segment comprising most of the interventricular septum.

Figure 2

a: Pixel-wise computed R2* map of the myocardium (Fig. 1) within manually traced ROI in the septum; TE-dependent signal decay measured within indicated ROI is shown along with two fitting models: exponential (b) and exponential with constant (c).

Figure 3

Mean R2*, measured after processing of TE-dependent synthetic images, compared to true value. The mean represents a simple average of uniform, dualtone, and ramp R2* distributions. Pixel-wise and ROI-based methods are more accurate when an offset in used with the exponential model.

Figure 4

a: Mean R2* (uniform, dualtone, and ramp) comparison between two fitting models: exponential (Exp) and exponential with constant (Exp+C). Pixel-wise based processing was used in both cases. Patient data have been overlaid on synthetic data, indicating comparable behavior. b: Mean R2* comparison between pixel-wise and ROI based methods; Exp+C model used in both cases.

Figure 5

Mean R2* compared to true value in the case of synthetic images for different minimum TEs but same echo duration (18 msec).

Figure 6

a: Normalized signal decay curves for interventricular septum of all patients, superimposed over unit-amplitude exponential curve having time constant of 1. Signals have been divided into five groups based on relaxation times. Note that all data points follow the exponential curve; however, for T2* > 20 msec, they do not span over the complete curve leading to some inaccuracy in measurement. b: The plot demonstrates normalized mean residual signal as a function of TE. For TE < 10 msec, the residual signal oscillates or “beats” about the phase markers. For TE > 10 msec, aliasing effects may be occurring due to insufficient data points and rapid signal decay under high iron-based susceptibility conditions.

Figure 7

a: Mean-normalized circumferential variation in R2* across four indicated segments of the myocardium (–4); the inferior and anterior regions demonstrate elevated values. Mean values for the groups are: SCD and TM (T2* > 20 msec) = 38.03 Hz, TM (T2* < 20 msec) = 157.26 Hz. b: Mean-normalized radial variation in R2* from endocardium to epicardium within the septum; a large gradient can be noted for high iron-based susceptibility group. Mean values for the groups are: SCD = 24.49 Hz, TM (T2* > 20 msec) = 25.93 Hz, and TM (T2* < 20 msec) = 145.39 Hz.