Functional MR imaging and the IQ-EMBRACE study

Functional MR imaging in cervical cancer

Functional imaging that reflects hypoxia, metabolism, heamodynamics and tissue structure have been applied to locally advanced cervical cancer with the goal to identify imaging markers that may predict outcome early on and improve tissue classification. DCE-MRI may be the most investigated so far for locally advanced cervical cancer. A comprehensive literature review including papers investigating the prognostic value of DCE-MRI in patients with locally advanced cervical cancer identified 20 papers from 10 research groups, with a median number of 30 patients (range 7-102 patients). A total number of 17 papers publish a positive association between pre-treatment DCE-MRI and outcome in terms of local control or disease free survival (1–17). However, not all studies present independent cohorts of patients. Three papers show no effect (18–20). The studies on cervical cancer points in the direction that DCE-MRI has the capability to identify aggressive forms of cervical cancer, and that the pre-treatment measurements may serve as, predictive markers for outcome after chemo-radiotherapy. The largest studies indicate that in particular the tumour fraction with the lowest signal enhancement is an important parameter, though the diversity in methodology is significant.

Diffusion weighted MRI (DWI-MRI) has to a lesser extent than DCE-MRI been investigated in locally advanced cervical cancer. Most studies using DWI-MRI in cervical cancer have investigated its diagnostic capabilities (21–28) all concluding high sensitivity and specificity (review by Kundu et al. (29)). The Toronto group; McVeight et al. (26) and later Gladwish et al. (30) found prior to the onset of treatment that the highest 90th % ADC value correlated with response, similar finding was found by the group in Tianjin; Liu et al. (22). Both groups found that higher ADC value insides the tumour was predictive of poor response to treatment and suggest the higher ADC to be connected to tumour necrosis. When tumour necrosis, occur there is loss of cell membrane integrity and therefore an increase in the extracellular volume and a decrease in intracellular volume effectively increasing the ADC. Conversely, the group from London UK; Harry et al. (31) and Somoye et al. (32) showed no correlation to treatment response at the time prior to treatment. Instead the ADC at 2 weeks (and the change in ADC) into treatment was predictive of treatment response and prognostic of patient outcome. Finally, Marconi et al. (33) found a relation between minimum ADC in the tumor and both DSS and DFS.


To determine the prognostic value of multi-parametric quantitative imaging, consisting of DCE-MRI, DWI-MRI and quantitative T2 mapping, the IQ-EMBRACE study has started. This study will acquire standardized quantitative MRI techniques for patients enrolled in the EMBRACE II study, prior to the onset of treatment. The primary objective is to evaluate the sensitivity and specificity of dynamic contrast enhanced (DCE-MRI) to identify patients who have increased risk of disease recurrence (local, nodal, systemic) after radio-chemotherapy of cervix cancer. It is hypothesised that low perfusion in the primary tumour - as determined from DCE-MRI - is a risk factor for persistent and recurrent disease (local, nodal and systemic). The complete study protocol can be found here.

Quantitative MRI

Within the group of participating centers a wide variety in scanners exists, from different manufactures, field strengths, and ages. As a result, novel sequences may be available in one institute but not in another. One approach to achieve consistency between centers would be to specify the trial sequences in great detail. The drawback however is that this inevitably would force all participants to design sequences for the oldest platforms, resulting in relatively old, slow and possibly imprecise sequences. Therefore, a strategy has been adopted where each participating center can optimize quantitative sequences, making optimal use of the possibilities of their scanner.

A quality assurance procedure has been designed that consists of a series of measurements on phantoms, aimed to validate the accuracy and precision of the quantitative sequences proposed by each center for use in the clinical trial. The measurements are compared to ground-truth values available for the applicable phantoms. A description of the QA procedure can be found here.


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