Normal variation of magnetic resonance T1 relaxation times in the human population at 1.5 T using ShMOLLI

Abstract

Background: Quantitative T1-mapping is rapidly becoming a clinical tool in cardiovascular magnetic resonance (CMR) to objectively distinguish normal from diseased myocardium. The usefulness of any quantitative technique to identify disease lies in its ability to detect significant differences from an established range of normal values. We aimed to assess the variability of myocardial T1 relaxation times in the normal human population estimated with recently proposed Shortened Modified Look-Locker Inversion recovery (ShMOLLI) T1 mapping technique.

Methods: A large cohort of healthy volunteers (n = 342, 50% females, age 11-69 years) from 3 clinical centres across two countries underwent CMR at 1.5T. Each examination provided a single average myocardial ShMOLLI T1 estimate using manually drawn myocardial contours on typically 3 short axis slices (average 3.4 ± 1.4), taking care not to include any blood pool in the myocardial contours. We established the normal reference range of myocardial and blood T1 values, and assessed the effect of potential confounding factors, including artefacts, partial volume, repeated measurements, age, gender, body size, hematocrit and heart rate.

Results: Native myocardial ShMOLLI T1 was 962 ± 25 ms. We identify the partial volume as primary source of potential error in the analysis of respective T1 maps and use 1 pixel erosion to represent "midwall myocardial" T1, resulting in a 0.9% decrease to 953 ± 23 ms. Midwall myocardial ShMOLLI T1 was reproducible with an intra-individual, intra- and inter-scanner variability of ≤2%. The principle biological parameter influencing myocardial ShMOLLI T1 was the female gender, with female T1 longer by 24 ms up to the age of 45 years, after which there was no significant difference from males. After correction for age and gender dependencies, heart rate was the only other physiologic factor with a small effect on myocardial ShMOLLI T1 (6ms/10bpm). Left and right ventricular blood ShMOLLI T1 correlated strongly with each other and also with myocardial T1 with the slope of 0.1 that is justifiable by the resting partition of blood volume in myocardial tissue. Overall, the effect of all variables on myocardial ShMOLLI T1 was within 2% of relative changes from the average.

Conclusion: Native T1-mapping using ShMOLLI generates reproducible and consistent results in normal individuals within 2% of relative changes from the average, well below the effects of most acute forms of myocardial disease. The main potential confounder is the partial volume effect arising from over-inclusion of neighbouring tissue at the manual stages of image analysis. In the study of cardiac conditions such as diffuse fibrosis or small focal changes, the use of "myocardial midwall" T1, age and gender matching, and compensation for heart rate differences may all help to improve the method sensitivity in detecting subtle changes. As the accuracy of current T1 measurement methods remains to be established, this study does not claim to report an accurate measure of T1, but that ShMOLLI is a stable and reproducible method for T1-mapping.

Figure 1

Typical T1 maps from a single healthy subject. Basal (A), mid-ventricular (B) and apical (C) short-axis slices. Thin dashed lines denote manually contoured endo- and epi-cardial outlines. Thick coloured outlines mark the left (dark green) and right (yellow) ventricular blood pool, placed within the left- and right-ventricular cavity, respectively, avoiding papillary muscle.

Figure 2

The effect of partial volume on A) average myocardial T1 and B) average segmental pixel variability. Notes: Myocardial ROI thickness is calculated as distance between endo- and epi-cardial contours. Filled large symbols represent the T1 derived from myocardial contours drawn manually by the operator (original) compared to systematic erosion or dilatation in 1-pixel increments. P values refer to comparisons between subsequent inflation/erosion steps.

Figure 3

Intra- and inter-centre reproducibility of myocardial T1 measurements. Repetition accuracy within the Oxford centre and amongst the three test centres.

Figure 4

Age- and gender-dependence of myocardial and blood T1. A) Measured myocardial T1 within manually drawn myocardial contours demonstrated a small elevation of T1 in young females. B) Myocardial midwall T1 (see partial volume section), indicated a similar persistent gender difference, albeit at a slightly lower T1 likely due to reduction of blood partial volume. C) Left Ventricle blood T1. D) Right Ventricle blood T1. Note: Unpaired student T-test p-values are marked above each bar for age-groups when Bonferroni-corrected significance threshold is achieved for gender difference.

Figure 5

The effects of common physiological parameters on the myocardial midwall T1 and blood T1 after correcting for age and gender differences. (A) Blood hematocrit is the principle driving force of blood T1s, but not myocardial T1, variation. (B) Increase in heart rate is associated with an increase in myocardial T1 and a decrease in blood T1s. (C) There is no relation between myocardial thickness and myocardial T1, but blood T1s change in opposite direction. (D) Increased body size does not influence myocardial T1, but decreases blood T1s. Note: statistical significance of marked correlations reaches Bonferroni-corrected significance of p < 0.002 (p < 0.05/18 comparisons including height and weight not shown here) for r² > 0.15 (n = 62, A) and r² > 0.026 (n = 374, B-D).