Misclassification of females and males in cardiovascular magnetic resonance parametric mapping: the importance of sex-specific normal ranges for diagnosis of health vs. disease.

Aims: Cardiovascular magnetic resonance parametric mapping enables non-invasive quantitative myocardial tissue characterization. Human myocardium has normal ranges of T1 and T2 values, deviation from which may indicate disease or change in physiology. Normal myocardial T1 and T2 values are affected by biological sex. Consequently, normal ranges created with insufficient numbers of each sex may result in sampling biases, misclassification of healthy values vs. disease, and even misdiagnoses. In this study, we investigated the impact of using male normal ranges for classifying female cases as normal or abnormal (and vice versa).

Methods And Results: One hundred and forty-two healthy volunteers (male and female) were scanned on two Siemens 3T MR systems, providing averaged global myocardial T1 and T2 values on a per-subject basis. The Monte Carlo method was used to generate simulated normal ranges from these values to estimate the statistical accuracy of classifying healthy female or male cases correctly as 'normal' when using sex-specific vs. mixed-sex normal ranges. The normal male and female T1- and T2-mapping values were significantly different by sex, after adjusting for age and heart rate.

Conclusion: Using 15 healthy volunteers who are not sex specific to establish a normal range resulted in a typical misclassification of up to 36% of healthy females and 37% of healthy males as having abnormal T1 values and up to 16% of healthy females and 12% of healthy males as having abnormal T2 values. This paper highlights the potential adverse impact on diagnostic accuracy that can occur when local normal ranges contain insufficient numbers of both sexes. Sex-specific reference ranges should thus be routinely adopted in clinical practice.