Cardiac stress T1-mapping response and extracellular volume stability of MOLLI-based T1-mapping methods

Abstract

Stress and rest T1-mapping may assess for myocardial ischemia and extracellular volume (ECV). However, the stress T1 response is method-dependent, and underestimation may lead to misdiagnosis. Further, ECV quantification may be affected by time, as well as the number and dosage of gadolinium (Gd) contrast administered. We compared two commonly available T1-mapping approaches in their stress T1 response and ECV measurement stability. Healthy subjects (n = 10, 50% female, 35 ± 8 years) underwent regadenoson stress CMR (1.5 T) on two separate days. Prototype ShMOLLI 5(1)1(1)1 sequence was used to acquire consecutive mid-ventricular T1-maps at rest, stress and post-Gd contrast to track the T1 time evolution. For comparison, standard MOLLI sequences were used: MOLLI 5(3)3 Low (256 matrix) & High (192 matrix) Heart Rate (HR) to acquire rest and stress T1-maps, and MOLLI 4(1)3(1)2 Low & High HR for post-contrast T1-maps. Stress and rest myocardial blood flow (MBF) maps were acquired after IV Gd contrast (0.05 mmol/kg each). Stress T1 reactivity (delta T1) was defined as the relative percentage increase in native T1 between rest and stress. Myocardial T1 values for delta T1 (dT1) and ECV were calculated. Residuals from the identified time dependencies were used to assess intra-method variability. ShMOLLI achieved a greater stress T1 response compared to MOLLI Low and High HR (peak dT1 = 6.4 ± 1.7% vs. 4.8 ± 1.3% vs. 3.8 ± 1.0%, respectively; both p < 0.0001). ShMOLLI dT1 correlated strongly with stress MBF (r = 0.77, p < 0.001), compared to MOLLI Low HR (r = 0.65, p < 0.01) and MOLLI High HR (r = 0.43, p = 0.07). ShMOLLI ECV was more stable to gadolinium dose with less time drift (0.006-0.04% per minute) than MOLLI variants. Overall, ShMOLLI demonstrated less intra-individual variability than MOLLI variants for stress T1 and ECV quantification. Power calculations indicate up to a fourfold (stress T1) and 7.5-fold (ECV) advantage in sample-size reduction using ShMOLLI. Our results indicate that ShMOLLI correlates strongly with increased MBF during regadenoson stress and achieves a significantly higher stress T1 response, greater effect size, and greater ECV measurement stability compared with the MOLLI variants tested.

Figure 1

CMR scanning protocol for assessing T1 time dependencies. After planning, native T1-mapping is performed at rest using ShMOLLI, MOLLI Low HR, and MOLLI High HR. Stress T1-mapping is performed following administration of regadenoson (IV 400 mcg). This consists of four ShMOLLI measurements to cover the initial transition period and peak stress, followed by blocks of interleaved ShMOLLI and MOLLI variants. First-pass perfusion imaging is performed after gadolinium injection (0.05 mmol/kg). Allowing 4 min for the reconstruction of MBF data, stress is reversed with aminophylline (IV 100 mg) followed immediately by the same pattern of ShMOLLI and MOLLI acquisitions. Rest perfusion is performed after a second dose of gadolinium (0.05 mmol/kg), followed immediately by T1-mapping.

Figure 2

Modified second CMR scanning protocol for assessing stress T1 and MBF. Native T1-mapping is performed at rest using ShMOLLI, MOLLI Low HR, and MOLLI High HR in basal, mid-ventricular, and apical slice positions. Stress T1-mapping is performed following administration of regadenoson (IV 400 mcg) in the basal, apical, and mid-ventricular slices as illustrated. Stress is reversed with aminophylline (IV 100 mg) at ~ 25 min. Rest perfusion and late gadolinium enhancement images are acquired.

Figure 3

Regadenoson stress effects on heart rate (A), MBF (B) and dT1 (C) with overlaid mono-exponential decay models $y=a\ast exp(-x/b)$. In panel (B), time point 0 corresponds to the baseline conditions and is included to illustrate MBF at rest. In panel (C) the decay time b has been established for ShMOLLI only, and only amplitudes scaled to best fit other MOLLI variants; the dashed lines mark the extrapolation of the MOLLI models beyond the respective data ranges. The rising part of the T1 response to stress (dotted green line), HR and MBF responses (fitted to relative changes and transposed) are to guide the eye only.

Figure 4

Correlation between stress MBF and dT1 during regadenoson stress. Stress MBF measured at ~ 4 (early stress) and ~ 15 min (late stress) after regadenoson in the same individuals on two separate days. Comparisons between dT1 and stress MBF are made for measured dT1 at the time point closest to MBF (all stress T1 data points measured within 90 s prior to MBF acquisition). Confidence intervals for the linear regressions are included (shaded ranges).

Figure 5

Effect of time and gadolinium dose on ECV. Linear regressions are shown for half-dose and whole-dose Gd epochs. Stress was reversed at 4 min (dotted vertical line); Gd was given at 0 min and a second dose at 19 min (dashed vertical line). The early rapid variation in ECV estimates after Gd seen in the ShMOLLI panel (data points outside the ranges marked by regression models) were excluded from analysis to allow fair inter-method comparisons. ShMOLLI ECV demonstrates little change in ECV with time, whereas MOLLI ECV (particularly MOLLI Low HR) is subject to linear time drift. Confidence intervals for the linear regressions are included (shaded ranges).

Figure 6

Relationship between T1-mapping variants. Linear fit for T1-mapping variants on native rest, stress, and post-contrast T1 (A) and analysis of differences plot comparing the results from MOLLI variants against all interpolated ShMOLLI values (B). The blue solid line (B) indicates the mean difference between ShMOLLI and MOLLI. The red dotted lines (B) indicate the 95% limit of agreement for all pooled MOLLI compared to ShMOLLI. Post-contrast T1 values are measured using the MOLLI 4(1)3(1)2 sequence with Low HR and High HR sub-variants; stress T1 values are measured using the MOLLI 5(3)3 sequence and Low HR and High HR sub-variants.

Figure 7

Impacts of MOLLI choice on estimation of stress delta T1 and ECV. Only modest correlations between methods are seen for MOLLI Low HR (r = 0.5) and MOLLI High HR (r = 0.58) respectively for delta T1 (A). Relationships are stronger for ECV for MOLLI Low HR (r = 0.8) and MOLLI High HR (r = 0.81) with distributions also shown for half-dose and whole-dose gadolinium (B). MOLLI variant samples correspond to time equivalent interpolated ShMOLLI.