Misclassification of Females and Males in Cardiovascular Magnetic Resonance Parametric Mapping - The Importance of Sex-Specific Normal Ranges for Diagnosis of Health versus Disease.

AIMS: Cardiovascular magnetic resonance parametric mapping enables non-invasive quantitative myocardial tissue characterisation. 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 versus disease, and even misdiagnoses. We investigated the impact of using male normal ranges for classifying female cases as normal or abnormal (and vice versa). METHODS AND RESULTS: 142 healthy volunteers (male and female) were scanned on two Siemens 3 T 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 versus mixed-sex normal ranges. 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 which are not sex-specific to establish a normal range typically misclassified 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 into clinical practice.