Connie Rees

87 None of the primary MRI parameters alone were sufficient to diagnose adenomyosis conclusively, which is in line with the literature (34) . The presence of HSI foci emerged as the strongest predictor of the assessed MRI parameters (p <.001). Bazot et al. indeed described these foci as the only direct diagnostic criterion and almost pathognomonic for adenomyosis on MRI, although they are only detected in about half the cases (34). We also find, in agreement with recent insights into the (lack of) of diagnostic potential of JZ markers (197– 199), that JZ thickness alone is not specific enough to diagnose adenomyosis on MRI. Notably in our cohort for instance, the mean maximum JZ in the nonadenomyosis cohort was already over the often reported cut-off value of 12mm (see Table 2, (45)) for adenomyosis, illustrating how attaching (too) much weight to this as a diagnostic marker is not reliable. This is further reflected in the low accuracy of MRI diagnosis overall for adenomyosis of 59.4% (see Table 3) in our cohort, for which JZ thickness >12mm was a main criterion. However, our results do suggest that the likelihood of adenomyosis increases with a larger JZ, especially if it is also irregular or proportionally takes up a large part of the total myometrium (as reflected in the markers JZ Diff and JZ/MYO ratio, see Tables 2 and 4). For this reason, it still included our model as a diagnostic marker, but without attaching a cut-off value for its general (maximum) thickness. This study has several strengths and limitations that merit consideration. One strength of our study is that two researchers independently reviewed all pelvic MRIs blinded to the histopathology outcome. Furthermore, the proposed model was built on data of 296 patients and data driven variable selection was avoided, along with corrections for potential overfitting. Additionally, the combination of both clinical and MRI parameters makes this model easily implementable into daily clinical practice. The present study used broad inclusion criteria, which could be interpreted as both a strength and limitation. On the one hand, inclusion of patients with comorbidities like uterine fibroids might have prevented an overestimation of diagnostic performance of the individual potential predictors. Alternatively, severe distortion of the uterus due to fibroids or endometriosis can limit the ability for complete objective assessment of all MRI parameters. One limitation of the current study is that it was not possible to correct for the influence of the menstrual cycle on MRI parameters. Although it is known that JZ thickness changes during the menstrual cycle (46), cycle phase at time of MRI

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