Reference range determination for imaging biomarkers: Myocardial T₁

Background: Imaging biomarkers, such as the T₁ relaxation time of the myocardium using MRI, can be valuable in cardiac medicine if they are properly validated. Consensus statements recommend that for myocardial T₁ , each investigator should establish a reference range.

Purpose: To describe a statistically valid method for determining and reporting the reference range in each center, which simultaneously minimizes the twin risks of undersampling, leading to a uselessly uncertain range, and oversampling, which exposes volunteers to unnecessary scanning and wastes resources.

Study type: Cohort.

Population: In all, 278 normal human subjects without cardiac disease from two cardiac MR centers.

Field strength/sequence: 1.5 T and 3 T; Modified Look-Locker Inversion recovery sequence.

Assessment: The T₁ relaxation time was estimated from multiple samples of tissue magnetization after inversion. A valid method for calculating a reference range was used.

Statistical tests: Shapiro-Wilk test for normality; Tukey robust approach for identification of outliers; reference range calculation with confidence intervals.

Results: Reference ranges for measurement of myocardial T₁ were calculated, with confidence intervals, enabling comparison with clinically important differences. At 3 T: 1129 to 1301 msec at site 1 (n = 21) and 1160 to 1309 msec at site 2 (n = 59), and at 1.5 T at site 2: 933 to 1020 msec (male, n = 130) and 965 to 1054 msec (female, n = 68). The 3 T reference range from site 1 was successfully benchmarked against the 3 T reference range at site 2.

Data conclusion: Myocardial T₁ reference ranges can be properly characterized, enabling clinical comparison to a valid reference range with known confidence intervals, using methodology similar to that described in this report.

Level of evidence: 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2019;50:771-778.