Diffusivity mapping of the ovaries: Variability of apparent diffusion and kurtosis variables over the menstrual cycle and influence of oral contraceptives

Purpose: We aimed to investigate whether quantitative diffusivity variables of healthy ovaries vary during the menstrual cycle and to evaluate alterations in women using oral contraceptives (OC). Methods: This prospective study (S-339/2016) included 30 healthy female volunteers, with (n = 15) and without (n = 15) intake of OC between 07/2017 and 09/2019. Participants underwent 3T diffusion-weighted MRI (bvalues 0-2000 s/mm2) three times during a menstrual cycle (T1 = day 1-5; T2 = day 7-12; T3 = day 19-24). Both ovaries were manually three-dimensionally segmented on b = 1500 s/mm2; apparent diffusion coefficient (ADC) calculation and kurtosis fitting (Dapp, Kapp) were performed. Differences in ADC, Dapp and Kapp between time points and groups were compared using repeated measures ANOVA and t-test after Shapiro-Wilk and Brown-Forsythe test for normality and equal variance. Results: In women with a natural menstrual cycle, ADC and kurtosis variables showed significant changes in ovaries with the dominant follicle between T1 vs T2 and T1 vs T3, whilst no differences were observed between T2 vs T3: ADC +/- SD for T1 1.524 +/- 0.160, T2 1.737 +/- 0.160, and T3 1.747 +/- 0.241 mu m2/ms (p = 0.01 T2 vs T1; p = 1.0 T2 vs T3, p = 0.003 T3 vs T1); Dapp +/- SD for T1 2.018 +/- 0.140, T2 2.272 +/- 0.189, and T3 2.230 +/- 0.256 mu m2/ms (p = 0.003 T2 vs T1, p = 1.0 T2 vs T3, p = 0.02 T3 vs T1); Kapp +/- SD for T1 0.614 +/- 0.0339, T2 0.546 +/- 0.0637, and T3 0.529 +/- 0.0567 (p < 0.001 T2 vs T1, p = 0.86 T2 vs T3, p < 0.001 T3 vs T1). No significant differences were found in the contralateral ovaries or in females taking OC. Conclusion: Physiological cycle-dependent changes in quantitative diffusivity variables of ovaries should be considered especially when interpreting radiomics analyses in reproductive women.

Automated summary

This study found significant changes in ADC and kurtosis variables in healthy ovaries during the menstrual cycle, but no significant differences were observed in women using oral contraceptives.