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Diffusion-weighted imaging in gynaecological malignancy
Clinical Radiology xxx (2017) 1e10
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Review
Diffusion-weighted imaging in gynaecological malignancy H. Addley, P. Moyle, S. Freeman* Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK
art icl e i nformat ion Article history: Received 5 December 2016 Received in revised form 10 July 2017 Accepted 17 July 2017
Diffusion weighted imaging (DWI) has become an essential part of the gynaecological magnetic resonance imaging (MRI) protocol. DWI is used as an adjunct to conventional MRI sequences and has been shown to improve reporting accuracy in the imaging of gynaecological malignancy. In this review, we discuss the role of DWI in the diagnosis, staging, and assessment of treatment response of endometrial, cervical, and ovarian cancer. We also review the role of DWI in the assessment of the sonographically indeterminate ovarian lesion. Further, we highlight potential pitfalls that can beset the accurate interpretation of DWI in patients with gynaecological malignancy. Crown Copyright Ó 2017 Published by Elsevier Ltd on behalf of The Royal College of Radiologists. All rights reserved.
Introduction Diffusion weighted imaging (DWI) has become an essential part of the gynaecological magnetic resonance imaging (MRI) protocol. Amongst several advantages, DWI has been shown to improve reporting accuracy in the staging of uterine and ovarian cancers; however, there are pitfalls associated with DWI, which must be understood to avoid image misinterpretation. This review article aims to outline the role of DWI in the investigation and staging of gynaecological malignancy and aims to highlight the potential pitfalls. DWI is a method to visualise the three-dimensional microscopic movement of water molecules within the intra- and extracellular compartments. DWI visualises the variability in water mobility due to changes in tissue cellularity, cell membrane integrity, and fluid viscosity.1,2 * Guarantor and correspondent: S. Freeman, Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK. Tel.: þ1223 216203; fax: þ1223 217847. E-mail address: [email protected] (S. Freeman).
The more restricted the movement of water, the higher the signal intensity generated on DWI. The apparent diffusion coefficient (ADC) can provide quantitative assessment by using different b-values to calculate the degree of diffusion; restricted diffusion is displayed as low signal intensity on an ADC map. The movement of water molecules is typically restricted within the tumour microenvironment due to the increased cellularity.3 Due to this restriction in movement of water molecules, the majority of tumours demonstrate higher DWI signal intensity and lower ADC values when compared with adjacent normal tissue. As a consequence of increased conspicuity, DWI can be utilised to improve tumour detection, staging, and response assessment.
Image acquisition technique Diffusion-weighted (DW) images are acquired at a low bvalue (typically b¼0 or b¼50 s/mm2) and at high b-values (typical high b-values include 500, 800, or 1000 s/mm2). The acquisition of a minimum of two b-values allows assessment of restricted diffusion as the b-value increases
http://dx.doi.org/10.1016/j.crad.2017.07.014 0009-9260/Crown Copyright Ó 2017 Published by Elsevier Ltd on behalf of The Royal College of Radiologists. All rights reserved.
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and improves the accuracy of the ADC value. There is variability between different institutions regarding optimal bvalues, but it is well recognised that b-values >1000 s/mm2 reduce the signal-to-noise ratio (SNR) giving no further benefit in the assessment of ADC value. Methods to reduce artefacts seen at the higher b-value acquisition include parallel imaging or multiple averaging. The plane of DWI acquisition depends upon the disease entity being investigated. Typically, in the assessment of endometrial cancer, DWI is acquired in the sagittal and axial oblique plane (perpendicular to the endometrial cavity), to help assess myometrial invasion. In cervical cancer, sagittal, and axial oblique DWI perpendicular to the endocervical canal is obtained to help assess the parametrium. Obtaining the DWI sequences in the same plane as the T2-weighted (T2W) images allows for direct correlation, which is vital for correct assessment of restricted diffusion. The field of view used for the axial oblique in DWI should remain the same as for the T2W sequence (typically 20e24 cm). The quality of the high b-value DWI should be assessed to ensure that the high signal intensity of fluid within the bladder has been successfully suppressed: urine in the bladder should be seen as low signal intensity. Once this has been ascertained, the lesion should be interrogated for the presence of increased signal intensity, and subsequently, comparison made with the ADC map. Only once the lesion has been shown to be of high signal intensity on DWI and low signal intensity on ADC maps can the lesion be interpreted as having restricted diffusion.
Artefacts There are unique challenges to the acquisition and interpretation of DWI in gynaecological imaging. These include the movement of the pelvic organs within the pelvis secondary to bladder filling and bowel peristalsis. This causes misregistration between T2W and DWI as the uterine body and cervix can become displaced between the acquisitions of the different sequences. Acquiring T2W and DWI contemporaneously in the same plane can reduce this difficulty. In addition, the use of intramuscular or intravenous hyoscine butylbromide is strongly recommended to reduce bowel peristalsis. DWI is highly susceptible to metal artefact. The presence of orthopaedic implants such as a hip replacement can distort DWI images rendering them non-diagnostic. In this scenario, dynamic contrast-enhanced imaging postgadolinium administration may be warranted as an alternative to DWI to improve tumour delineation. In addition, pelvic DWI is also susceptible to distortion arising from rectal gas within the spatial field. This susceptibility artefact can be reduced by parallel imaging techniques, utilising multiphase array coils, which allows the echo time and echo train length to be shortened.4
Pitfalls T2 shine-through is a potential pitfall, where the presence of high signal intensity on T2W imaging remains
visible on high b-value DWI.5 This pitfall can be avoided by scrupulously correlating the DWI findings with the ADC map (Fig 1). In T2 shine-through, the lesion will be of high signal intensity on T2W imaging and high signal intensity on DWI, but importantly will also retain high signal intensity on ADC maps. Not all areas of restricted diffusion on DWI are malignant tumours, and there are several normal tissues and benign processes that can cause restricted diffusion. Notably, all lymph nodes demonstrate restricted diffusion on DWI and research remains inconclusive whether ADC values can be used to differentiate normal from infiltrated nodes.6e8 The diagnosis of lymph node tumour invasion remains dependent upon the node size and signal intensity on T2W imaging (replacement of the fatty hilum and similar signal intensity to the primary tumour); however, the degree of restriction on DWI improves the conspicuity of lymph nodes, which in turn improves staging accuracy.9 Similarly, the ovaries commonly demonstrate restricted diffusion on DWI and ADC maps. Therefore, correlation with the appearance on T2W imaging is essential to identify whether pathology is present. The presence of high signal intensity on DWI can enable the identification of the ovaries, which can be difficult with multiple abutting bowel loops. In particular, DWI can be useful in the evaluation of € llerian duct anomalies when the ovaries may have an Mu ectopic position. Benign pelvic disease, including endometriomas, dermoid cysts, fibroids, fibromas, and tubo-ovarian abscesses, can also result in restricted diffusion on DWI. Nearly 50% of endometriomas demonstrate restricted diffusion on DWI, usually within intra-cystic blood clots and should not be over-interpreted as the presence of tumour10,11(Fig 2). Endometriomas can be fully characterised with conventional sequences including T1W and T1W imaging with fat saturation; however, given the risk of malignancy within endometriomas, the T2W imaging should be carefully assessed for the presence of corresponding internal solid mural nodules. If soft-tissue mural nodules are identified, further evaluation following administration of intravenous gadolinium is recommended.11 Mature teratomas commonly demonstrate restricted diffusion on DWI. The restricted diffusion is seen within keratinoid substances and Rokitansky nodules; however, mature teratomas can be fully characterised on T1W and T1W fat-saturated imaging, by the presence of fat within an ovarian mass. This scenario exemplifies the importance of the use of DWI as an adjunct rather than a replacement for conventional imaging sequences in lesion characterisation.10 The presence of restricted diffusion within cellular leiomyomas and ovarian fibromas occurs due to their inherent dense cellularity.12,13 Image interpretation should always be made in context with the appearances on T1W and T2W imaging. DWI cannot reliably distinguish between cellular leiomyomas and leiomyosarcomas, as both may show restricted diffusion. ADC is also unable to differentiate between these two entities as both demonstrate low signal intensity on ADC maps, with overlap of ADC values of leiomyosarcoma with typical fibroids.13
Please cite this article in press as: Addley H, et al., Diffusion-weighted imaging in gynaecological malignancy, Clinical Radiology (2017), http:// dx.doi.org/10.1016/j.crad.2017.07.014
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Figure 1 A 72-year-old woman had an incidental left ovarian mass identified at CT. MRI was performed for further characterisation and identified a cystic mass with fibrous low signal intensity elements, consistent with a cystadenofibroma. The fluid within the lesion demonstrates high signal intensity on T2W imaging (a) which remained high signal intensity on DWI (b) and ADC map (c) (arrows) representing T2 shinethrough.
Figure 2 A 33-year-old woman presented with pelvic pain. An ultrasound revealed a complex right ovarian cyst. On MRI, the lesion was characterised as an endometrioma on T1WI with fat saturation (a). The high signal intensity on DWI (b) and low signal intensity on ADC map (c) represents restricted diffusion within blood products and should not be misinterpreted as malignancy.
Tubo-ovarian abscesses also represent a pitfall on DWI as the abscess contents demonstrate restricted diffusion due to highly concentrated molecular components14 (Fig 3). Confusion can be avoided by interpreting the conventional MRI images in the appropriate clinical context.
Endometrial cancer Diagnosis In Europe, endometrial cancer represents the commonest gynaecological cancer, with an increase in incidence of 25% seen in the UK over the last decade.15,16 Endometrial cancer commonly presents with postmenopausal bleeding where ultrasound remains the primary investigation of choice. An endometrial thickness of >4e5 mm should be further investigated with endometrial biopsy.17,18 When endometrial sampling is not possible (usually due to cervical stenosis) or if histopathology results are inconclusive or inconsistent with the clinical suspicion,
DWI can be helpful to differentiate the presence of endometrial cancer over benign disease. The presence of restricted diffusion within an endometrial mass will raise suspicion for the presence of tumour regardless of biopsy findings, which can be subject to sampling error. Studies have shown that the ADC values of endometrial cancer are significantly lower than in benign endometrial polyps and normal endometrium, with a sensitivity of approximately 96%.19e21 Endometrial cancer is usually well delineated on T2W imaging as an intermediate signal intensity soft-tissue mass within the endometrial cavity; however, in cases where the endometrium is distorted by the presence of leiomyomas or adenomyosis, the restricted diffusion in endometrial cancer aids tumour detection on DWI. Inada et al., found that 96% of tumours could be identified on fused DWI or T2W imaging.22 The ADC values of endometrial cancer have been evaluated and no correlation was found with tumour grade, depth of myometrial invasion, or the presence of nodal metastases.23 More recent studies, however, have shown
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Figure 3 An 81-year-old woman presented with weight loss, lower abdominal pain and raised inflammatory markers. CT identified a right adnexal mass. MRI identified a thick-walled cystic collection in the right ovary on T2W imaging (a) with high signal intensity on DWI (b) and low signal intensity on ADC (c) (arrows). The restricted diffusion is due to the thick pus impeding the diffusion of water.
that there is a significant difference in ADC histograms between high- and low-grade tumours.24
Staging The staging of endometrial cancers is based upon both surgical and histological findings, using the FIGO (Federation Internationale Gynecologie Obstetrique) staging classification.25 The European Society of Urogenital Radiology (ESUR) recommends the use of MRI to stage patients preoperatively.26 The MRI stage, in conjunction with histological type and grade of tumour, enables risk stratification and treatment planning for the individual patient.27 Stage I disease represents endometrial cancer confined to the myometrium and is subdivided into Stage IA (<50% myometrial invasion) or stage IB (50% myometrial invasion). DWI is acquired in the sagittal and axial oblique plane (perpendicular to the endometrial cavity) to enable accurate assessment of the depth of myometrial invasion, as this correlates with the risk of lymph node metastases.28 Multiple studies have reviewed DWI and dynamic contrastenhanced (DCE) imaging for their role of improving assessment of the depth of myometrial invasion. Studies have shown that the addition of DWI to T2W imaging improves staging accuracy of myometrial invasion, with a sensitivity of up to 92%29,30 (Fig 4). DWI has many
advantages over DCE imaging as it does not require estimated glomerular filtration rate (eGFR) measurement and can be utilised when gadolinium is contraindicated (allergy, poor renal function). In addition, peri-tumoural inflammation may overestimate the extent of tumour invasion on DCE. This pitfall is avoided in DWI as inflammation does not cause restricted diffusion.31 DWI can also aid the detection of unexpected extrauterine tumour deposits. For example, drop metastases within the endocervical canal and vagina (Fig 5) as well as spread to the adnexa and peritoneum can be more clearly identified using DWI.29 Fuji et al. have also shown that DWI enables the detection of peritoneal spread of disease, with a sensitivity and specificity of 90% and 95.5%, respectively.32
Treatment planning Despite the current FIGO staging guidelines, full pelvic and abdominal lymph node dissection is controversial due to the associated morbidity, with limited improvement in prognosis.33 It is therefore essential to identify potentially infiltrated lymph nodes prior to surgery to aid surgical planning. Although DWI cannot be utilised to distinguish benign from malignant nodes, its usage improves nodal detection due to the improved conspicuity of high signal intensity on DWI.6e8
Figure 4 A 73-year-old woman with post-menopausal bleeding was shown to have endometrial thickening on ultrasound. Subsequent histology from Pipelle sampling revealed an endometrial carcinoma. (a) MRI staging showed a markedly thickened endometrium on sagittal T2W imaging (arrow); however, the assessment of the depth of myometrial invasion was difficult in the presence of multiple fibroids. The DWI (b) and ADC map (c) reveal >50% myometrial invasion posteriorly (arrow). Please cite this article in press as: Addley H, et al., Diffusion-weighted imaging in gynaecological malignancy, Clinical Radiology (2017), http:// dx.doi.org/10.1016/j.crad.2017.07.014
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Figure 5 A 67-year-old woman presented with post-menopausal bleeding. A polyp containing grade 2 endometrioid carcinoma was removed at hysteroscopy; however, at staging MRI, the sagittal T2W imaging (a) revealed subtle intermediate signal intensity in the lower third of the vagina. (b) On sagittal DWI, the drop metastasis is clearly visible as a high signal intensity lesion (white arrows). The soft-tissue lesion invading the distal sigmoid serosa seen on T2W imaging does not demonstrate restricted diffusion on DWI and represents an endometriotic deposit (arrowhead).
Recurrence Surgery is curative in the majority of patients with endometrial cancer; however, patients with high-grade histology, type II endometrial cancers (clear cell and serous papillary tumours) or an advanced stage at diagnosis are at a higher risk of recurrence. The minimum ADC value of endometrial cancer correlates with the risk of recurrence; a low minimum ADC value within the primary endometrial cancer correlates with lower disease-free survival.34 Tumour recurrence typically occurs in the first 3 years after surgery (87%) with the commonest sites of recurrence being the vaginal vault (42%) and regional lymph nodes (46%).35 Computed tomography (CT) is routinely used in the follow-up of high-risk patients to identify recurrent disease within the lungs or lymph nodes; however, the vaginal vault can be difficult to assess with CT and MRI provides improved soft-tissue resolution, if recurrence is suspected. DWI is particularly useful to distinguish between postradiotherapy soft-tissue thickening or inflammation and recurrent disease.
Cervical cancer Diagnosis Cervical cancer is the third most common gynaecological cancer, but the commonest cancer in females under 35years old.15 Cervical cancer is diagnosed clinically in the majority of cases, with a limited role for imaging in the initial diagnosis.
DWI is as accurate as DCE in the detection of cervical tumours, but can have a role in the diagnosis of tumours situated high within the endocervical canal, not immediately amenable to biopsy.36 In small tumours, DWI improves tumour detection following biopsy or excision (LLETZ or cone biopsy) as post-procedure inflammatory changes can distort the normal anatomy on T2W imaging. The presence of restricted diffusion can differentiate inflammation from malignancy. Some authors propose the use of an endovaginal coil to improve signal return.37 The ADC value has been shown to be significantly lower in malignant tumours when compared with the normal background parenchyma.38 In addition, Xue et al. have shown that there is correlation between histological grade of tumours and the ADC value, with higher-grade tumours having lower-grade ADC values.39
Staging Cervical cancer staging is performed clinically using the revised 2009 FIGO staging classification40; however, MRI now has an established role in cervical cancer staging and has been adopted in the main radiological and oncological guidelines.41 High resolution T2W imaging is required to accurately depict tumour size. DWI, in combination with T2W imaging, has been shown to be equivalent to DCE-MRI in distinguishing between Ib1 and Ib2 tumours (lesions confined to the cervix 4 cm and >4 cm, respectively); however, DWI has the advantage of alleviating the cost and additional factors associated with the administration of intravenous contrast medium.42 Axial oblique imaging (perpendicular to the endocervical canal), with T2W imaging and DWI, allows assessment of
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parametrial invasion (stage IIB), which determines whether surgery or chemoradiotherapy is the appropriate treatment strategy.27 On T2W imaging, the presence of an intact low signal intensity cervical stromal ring excludes parametrial invasion.43 One study demonstrated that the use of wholebody DWI fused with T2W imaging improved detection of parametrial invasion with a significantly higher specificity (up to 99%), when compared with T2W imaging alone (up to 88.7%).44 Utilising multivariate analysis to define independent imaging predictors for pathologically-proven parametrial invasion, Park et al. identified low tumour ADC value and the presence of parametrial extension on T2W imaging.45 DWI is also very helpful in patients with infiltrative tumours, when the tumour boundaries are difficult to depict on T2W imaging.31 By comparing the area of restricted diffusion on DWI with the T2W imaging findings, the delineation of tumour infiltration is improved. Sagittal DWI aids the detection of direct tumour spread to the vagina and the presence of drop metastases.
Treatment planning Accurate local staging of the tumour enables optimal treatment planning for patients, either for chemoradiation or surgery. In clinical practice, restricted diffusion within the cervical tumour can provide more accurate delineation of small tumours, particularly if fertility-sparing surgery is being planned37,46(Fig 6). In the group of patients requiring chemoradiation, further MRI examinations are crucial both to aid treatment planning and to assess treatment response. The role of DWI in treatment response during radiation treatment is vital. Following chemoradiation, the margin between tumour and normal tissues becomes less well-defined on T2W imaging. DWI has a major role in differentiating between post-treatment changes, such as oedema, inflammation, and fibrosis, from residual tumour in these patients. DWI findings have been evaluated as a biomarker of cervical tumour treatment response47e49 (Fig 3). The ADC values have been demonstrated to increase as early as 2 weeks post-treatment before detectable involution of tumour. The tumour ADC value and the change in ADC value predicts
successful clinical response.47 Identification of residual disease following chemoradiation is essential to patient management, as there is a window of opportunity for these patients to undergo exenterative surgery following their chemoradiation.
Recurrence In cervical cancer, 60e70% of cases of post-treatment recurrence occur within 2 years of treatment.50 MRI is the best technique for assessment of local recurrence in the pelvis and is combined with 2-[18F]-fluoro-2-deoxy-Dglucose positron-emission tomography (PET)/CT for the assessment of distant metastases.51 Recurrent disease on T2W imaging is demonstrated as an area of intermediate signal intensity which, given the changes within the pelvis following either surgery or chemoradiation, can be challenging to diagnose in small volume disease.52 Abnormal signal intensity within the cervix on T2W imaging is further assessed with DWI. Both tumour recurrence and posttreatment inflammation may reveal high signal intensity on DWI, but only recurrent tumour will demonstrate restriction on ADC maps (Fig 7). Although post-radiation fibrosis can give low ADC values, the appearance on T2W imaging is frequently also low signal intensity and will not demonstrate high signal intensity compared to tumour on the high b-value images.46
Ovarian cancer Diagnosis Ovarian cancer is the sixth most common cancer in women in the UK. The clinical presentation is relatively non-specific, resulting in almost 60% of patients being diagnosed at a late stage (stage III of IV). Survival is strongly linked to the stage at diagnosis with 1-year survival of 99% for stage I disease declining to 51% for stage IV disease.15 Therefore, It is imperative that patients undergo accurate ultrasound assessment once a pelvic mass is suspected. Ultrasound remains the predominant imaging method in the initial detection and diagnosis of an adnexal mass.
Figure 6 A 36-year-old woman with post-coital bleeding underwent staging MRI following histological confirmation of cervical malignancy. (a) Axial T2W imaging demonstrates intermediate signal intensity area within the cervix. On axial oblique imaging, the tumour demonstrates high signal intensity on DWI (b) and low signal intensity on the ADC map (c) in keeping with restricted diffusion. The boundaries of the tumour are clearly defined on the DWI with no evidence of parametrial invasion. Please cite this article in press as: Addley H, et al., Diffusion-weighted imaging in gynaecological malignancy, Clinical Radiology (2017), http:// dx.doi.org/10.1016/j.crad.2017.07.014
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Figure 7 A 46-year-old woman with a FIGO stage IIIb carcinoma of the cervix was treated with chemoradiation. The end of treatment MRI identified residual intermediate signal intensity in the lower uterine segment/cervix (a) with high signal intensity on DWI (b) and low signal intensity on ADC map (c) (arrows). This was confirmed as residual tumour on histology.
Nevertheless, even using the International Ovarian Tumour Analysis group (IOTA) simple rules, 22% of ovarian lesions remained indeterminate on ultrasound.53 MRI now plays a pivotal role in the investigation of sonographicallyindeterminate adnexal masses. Ovarian cancer often presents at a late stage with peritoneal disease and ascites already present; however, in patients presenting with early-stage disease, without clear extra-ovarian spread of disease, MRI is invaluable in differentiating the adnexal masses with high risk of malignancy from those of potentially benign origin. Using standard MRI sequences including T2W imaging, T1W imaging with and without fat saturation, the majority of adnexal lesions can be accurately diagnosed. The ESUR has recently updated the recommendations for MRI of the sonographically-indeterminate adnexal mass, by defining the role and diagnostic value of DWI.11 Diagnostic confidence is increased by approximately 15% when DWI is added to conventional MRI and is particularly helpful in characterising benign lesions with no restricted diffusion.54 The Adnex MRI scoring system is a standardised method of MRI and reporting to categorise complex adnexal masses, which includes DWI as one of its criteria.55 The Adnex MRI score system divides masses into five categories from score 1 corresponding to no mass through to score 5 that describes a probably malignant mass and has shown excellent validation in feasibility studies.56 Specifically these studies show the value of DWI in assessing non-fatty, non-haemorrhagic pelvic masses that are entirely solid, or complex masses that are either septate cysts or complex solid and cystic masses.57 The adnexal masses seen in ovarian cancer of both highgrade and low-grade tumours both demonstrate restricted diffusion on DWI and ADC.55 Takeuchi et al. demonstrated there was a difference in the mean ADC values between benign and malignant ovarian tumors.12 With a cut-off ADC value of 1.15103 mm2/s, there was a sensitivity of 74% and a specificity of 80% for differentiating benign from malignant or borderline ovarian lesions. By reducing the ADC cutoff further to 1103 mm2/s, the sensitivity drops to 46% but specificity increases to 100%.
Care must be taken in interpreting tumours with low cellular density and high fluid content such as mucinous tumours, serous papillary tumours or tumours with necrosis or cystic areas. These can have high signal intensity on DWI due to T2 shine-through of the fluid component and therefore careful reference to the ADC map and T2W imaging is mandatory. If an indeterminate adnexal mass is of low signal intensity on T2W imaging, and the entire mass displays low signal on DWI obtained with a b-value of 800e1000 s/mm2, there is a very high likelihood of benign disease, for example, cystadenofibromas, ovarian fibromas, and pedunculated leiomyomas.58 In this scenario, DWI can replace DCE T1W imaging, which can be particularly useful in women when gadolinium should be avoided. It should be remembered that some fibromas are densely cellular and therefore demonstrate restricted diffusion on DWI; however, these lesions are often fully characterised on conventional MRI sequences. When there is an indeterminate adnexal mass, which has a solid component revealing high signal on the high-bvalue DWI, it may be benign or malignant. In these cases DCE MRI is recommended as per the ESUR 2016 update.11
Staging Ovarian cancer is usually staged according to the FIGO surgicalepathological staging system.59 CT is the standard technique to stage ovarian cancer given its fast image acquisition and wide availability; however, there are limitations of soft-tissue contrast resolution between normal and malignant tissue on CT; in particular, there remains difficulty in distinguishing between bowel wall and serosal deposits, as well as between unopacified small bowel loops and peritoneal deposits, even with the use of oral and intravenous contrast medium. Advanced MRI techniques, such as DWI, can overcome many of these staging issues.60 The combined interpretation of DWI with conventional MRI sequences has been shown to increase reporting accuracy in lesion detection beyond the adnexa and therefore confirm the presence of disseminated malignant disease32 (Fig 8).
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Figure 8 A 58-year-old woman with stage IIIC high-grade serous carcinoma of the ovary. (a) T2W axial imaging demonstrates bilateral solid adnexal masses (arrows). (b) The ovarian tumours reveal high signal intensity on DWI and (c) low signal intensity on ADC map. Although peritoneal disease can be seen on the T2W imaging, the restricted diffusion on DWI significantly improves disease identification (b). The arrowheads identify the peritoneal disease outlining the pouch of Douglas and peritoneal reflection.
Patients with isolated retroperitoneal lymph node metastases (FIGO stage IIIA1) have been shown to have a better prognosis than those patients with peritoneal metastases >2 cm (stage IIIC) with a 5-year survival of 57.5% versus 35.8%.61 As previously discussed, DWI cannot accurately differentiate normal from infiltrated lymph nodes; however, their increased conspicuity on DWI aids detection, which in turn can be cross-correlated with size and morphology on conventional MRI sequences.62 The same principle exists with extra-abdominal nodes and therefore potentially highlights changes in staging, for example, inguinal lymph nodes represent stage IVB disease. Ovarian carcinoma commonly metastases to the peritoneum through transcoelomic spread. DWI has been shown to be superior in identifying small peritoneal lesions when compared to CT.32,63 Small volume peritoneal implants at the dome of the diaphragm, lesser sac, or sub-capsular liver and spleen deposits can be difficult to identify on CT and conventional MRI64 (Fig 9). The intrinsic contrast resolution of restricted diffusion on DWI can highlight metastases in these difficult locations and thereby improve staging accuracy.
Treatment planning Following comprehensive staging with CT, the standard of care for newly diagnosed advanced ovarian cancer is
cytoreductive surgery with neoadjuvant or adjuvant chemotherapy. Cytoreductive surgery has been shown to increase overall survival if there is no residual visible tumour at the completion of surgery.65 Therefore, the preoperative assessment of tumour burden and potential resectability has an essential role in guiding management. Areas that radiologists should specifically review that can affect resectability are: suprarenal retroperitoneal lymph nodes >1 cm; diffuse small bowel adhesions/thickening; lesions >1 cm in the small bowel mesentery; the root of the superior mesenteric artery; the perisplenic area, and lesser sac.66 Michielsen et al. demonstrated whole-body DWI showed better sensitivity than CT for detecting involvement of surgically critical tumour sites, including the mesenteric root (92% versus 31%), small bowel (93% versus 21%), colon (91 % versus 27%), and unresectable distant metastases (90% versus 20%).67 Whole-body MRI compares equally with FDG-PET/CT for identifying primary tumours and retroperitoneal lymph nodes, but has a higher accuracy for peritoneal staging compared with FDG-PET/CT63; however PET/CT has been shown to be more accurate in the diagnosis of supradiaphragmatic metastases.68 Kyriazi et al. investigated the ADC maps in eight patients with metastatic primary ovarian carcinoma during the first and third cycles of neoadjuvant chemotherapy.69 Mean ADC increased significantly from baseline after both first
Figure 9 A 58-year-old woman with stage IIIC high-grade serous carcinoma of the ovary. (a) T2W axial imaging demonstrates peritoneal disease in the upper abdomen. The high signal intensity on DWI (b) and low signal intensity on ADC map (c) shows restricted diffusion within the peritoneal disease. This improves the conspicuity of peritoneal deposits in difficult to review regions including: subdiaphragmatic (white arrow), falciform ligament/porta hepatis (dashed arrow), subcapsular splenic (arrowhead), and left upper quadrant (asterisk) tumour deposits. Please cite this article in press as: Addley H, et al., Diffusion-weighted imaging in gynaecological malignancy, Clinical Radiology (2017), http:// dx.doi.org/10.1016/j.crad.2017.07.014
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and third cycles in both ovarian and omental disease. This may represent a functional marker of early response to treatment and affect treatment planning, although more work is needed before this is implemented as a biomarker in clinical practice.
Recurrence Approximately 75% of women with ovarian cancer present with advanced (stage III or IV) disease, which is associated with an increased risk of post-treatment recurrence. Following optimal surgical debulking, patients with lowvolume residual disease (lesions <1 cm in size) have a 60e70% risk of recurrence, whereas patients with highvolume residual disease (lesions >1 cm) have an 80e85% risk of recurrence.70 Therefore, identifying residual and recurrent disease and classifying its location (local pelvic, peritoneal lesion, lymph node, and distant metastasis) is important to guide further management. Michielsen et al. demonstrated that whole-body DWI improved the sensitivity of detecting recurrent ovarian cancer compared to CT, especially in the assessment of the root of the mesentery and serosal disease of the small and large bowel.67 Ovarian cancer demonstrates marked tumour heterogeneity between the primary tumour and peritoneal deposits presumably secondary to the variability of ovarian tumour genetics. This heterogeneity can affect treatment response and recurrence. Sala et al. identified differences in ADC between the primary ovarian tumour, omental deposits, and peritoneal deposits.71 Peritoneal deposits have a significantly lower mean ADC than the primary ovarian lesion or omental deposits. DWI and ADC may therefore have a vital role in improving our knowledge of tumour dedifferentiation, resistance to second-line cytotoxic treatments and aiding future management of these patients.
Conclusion DWI has numerous specific roles in the imaging of gynaecological malignancy. Interpretation of DWI is dependent upon a clear understanding of its role in different diseases and its place in primary and posttreatment investigation in addition to typical pitfalls, to avoid misinterpretation of findings. Multiple studies have assessed the role of DWI in staging cervical and endometrial cancers and demonstrated the improvement in staging accuracy. In ovarian and endometrial cancer, the restricted diffusion within peritoneal disease aids detection of disease dissemination, which enables accurate treatment decisions and surgical planning. DWI allows differentiation of malignant ovarian lesions from benign mimics, in conjunction with standard MRI sequences.
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3. Koh D-M, Collins DJ. Diffusion-weighted MRI in the body: applications and challenges in oncology. AJR Am J Roentgenol 2007;188:1622e35. 4. Namimoto T, Awai K, Nakaura T, et al. Role of diffusion-weighted imaging in the diagnosis of gynecological diseases. Eur Radiol 2008;19:745e60. 5. Provenzale JM, Engelter ST, Petrella JR, et al. Use of MR exponential diffusion-weighted images to eradicate T2 “shine-through” effect. AJR Am J Roentgenol 1999;172:537e9. 6. Perrone A, Guerrisi Pietro, Izzo L, et al. Diffusion-weighted MRI in cervical lymph nodes: Differentiation between benign and malignant lesions. Eur J Radiol 2011;77:281e6. 7. Nakai G, Matsuki M, Inada Y, et al. Detection and evaluation of pelvic lymph nodes in patients with gynecologic malignancies using body diffusion-weighted magnetic resonance imaging. J Comput Assist Tomogr 2008;32:764e8. 8. Kim JK, Kim KA, Park B-W, et al. Feasibility of diffusion-weighted imaging in the differentiation of metastatic from nonmetastatic lymph nodes: early experience. J Magn Reson Imaging 2008;28:714e9. 9. Lin G, Ho K-C, Wang J-J, et al. Detection of lymph node metastasis in cervical and uterine cancers by diffusion-weighted magnetic resonance imaging at 3T. J Magn Reson Imaging 2008;28:128e35. 10. Fujii S, Kakite S, Nishihara K, et al. Diagnostic accuracy of diffusionweighted imaging in differentiating benign from malignant ovarian lesions. J Magn Reson Imaging 2008;28:1149e56. 11. Forstner R, Thomassin-Naggara I, Cunha TM, et al. ESUR recommendations for MRI of the sonographically indeterminate adnexal mass: an update. Eur Radiol 2016:1e10. 12. Takeuchi M, Matsuzaki K, Nishitani H. Diffusion-weighted magnetic resonance imaging of ovarian tumors: differentiation of benign and malignant solid components of ovarian masses. J Comput Assist Tomogr 2010;34:173e6. 13. Tamai K, Koyama T, Saga T, et al. The utility of diffusion-weighted MRI for differentiating uterine sarcomas from benign leiomyomas. Eur Radiol 2008;18:723e30. 14. Oto A, Schmid-Tannwald C, Agrawal G, et al. Diffusion-weighted MRI of abdominopelvic abscesses. Emerg Radiol 2011;18:515e24. 15. Cancer Research UK. Cancer Statistics for the UK. Available at: http:// www.cancerresearchuk.org/health-professional/cancer-statistics. Accessed November 2016. 16. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013;49:1374e403. 17. Breijer MC, Timmermans A, van Doorn HC, et al. Diagnostic Strategies for Postmenopausal Bleeding. Obstet Gynecol Int 2010;2010:1e5. 18. Colombo N, Preti E, Landoni F, et al. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2011;22:vi35e9. 19. Bharwani N, Miquel ME, Sahdev A, et al. Diffusion-weighted imaging in the assessment of tumour grade in endometrial cancer. Br J Radiol 2011;84:997e1004. 20. Fujii S, Matsusue E, Kigawa J, et al. Diagnostic accuracy of the apparent diffusion coefficient in differentiating benign from malignant uterine endometrial cavity lesions: initial results. Eur Radiol 2008;18:384e9. 21. Takeuchi M, Matsuzaki K, Nishitani H. Diffusion-weighted magnetic resonance imaging of endometrial cancer: differentiation from benign endometrial lesions and preoperative assessment of myometrial invasion. Acta Radiol 2009;50:947e53. 22. Inada Y, Matsuki M, Nakai G, et al. Body diffusion-weighted MRI of uterine endometrial cancer: Is it helpful in the detection of cancer in nonenhanced MRI? Eur J Radiol 2009;70:122e7. 23. Rechichi G, Galimberti S, Signorelli M, et al. Endometrial cancer: correlation of apparent diffusion coefficient with tumor grade, depth of myometrial invasion, and presence of lymph node metastases. AJR Am J Roentgenol 2011;197:256e62. 24. Woo S, Cho JY, Kim SY, et al. Histogram analysis of apparent diffusion coefficient map of diffusion-weighted MRI in endometrial cancer: a preliminary correlation study with histological grade. Acta Radiol 2014;55:1270e7. 25. Pecorelli S, Benedet JL, Creasman WT, et al. FIGO staging of gynecologic cancer. Int J Gynecol Obstet 1999;64:5e10.
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26. Kinkel K, Forstner R, Danza FM, et al. Staging of endometrial cancer with MRI: guidelines of the European Society of Urogenital Imaging. Eur Radiol 2009;19:1565e74. 27. Sala E, Rockall AG, Freeman SJ, et al. The added Role of MR imaging in treatment stratification of patients with gynecologic malignancies: what the radiologist needs to know. Radiology 2013;266:717e40. 28. Todo Y, Kato H, Kaneuchi M, et al. Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis. Lancet 2010;375:1165e72. 29. Beddy P, Moyle P, Kataoka M, et al. Evaluation of depth of myometrial invasion and overall staging in endometrial cancer: comparison of diffusion-weighted and dynamic contrast-enhanced MR imaging. Radiology 2012;262:530e7. 30. Rechichi G, Galimberti S, Signorelli M, et al. Myometrial invasion in endometrial cancer: diagnostic performance of diffusion-weighted MRI at 1.5-T. Eur Radiol 2009;20:754e62. 31. Sala E, Rockall A, Rangarajan D, et al. The role of dynamic contrastenhanced and diffusion weighted magnetic resonance imaging in the female pelvis. Eur J Radiol 2010;76:367e85. 32. Fujii S, Matsusue E, Kanasaki Y, et al. Detection of peritoneal dissemination in gynecological malignancy: evaluation by diffusion-weighted MRI. Eur Radiol 2007;18:18e23. 33. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study373; 2009. p. 125e36. 34. Nakamura K, Imafuku N, Nishida T, et al. Measurement of the minimum apparent diffusion coefficient (ADCmin) of the primary tumor and CA125 are predictive of disease recurrence for patients with endometrial cancer. Gynecol Oncol 2012;124:335e9. 35. Sohaib SA, Houghton SL, Meroni R, et al. Recurrent endometrial cancer: patterns of recurrent disease and assessment of prognosis. Clin Radiol 2007;62:28e34. discussion 35e6. 36. Kuang F, Yan Z, Li H, et al. Diagnostic accuracy of diffusion-weighted MRI for differentiation of cervical cancer and benign cervical lesions at 3.0T: comparison with routine MRI and dynamic contrast-enhanced MRI. J Magn Reson Imaging 2015;42:1094e9. 37. Charles-Edwards EM, Messiou C, Morgan VA, et al. Diffusion-weighted imaging in cervical cancer with an endovaginal technique: potential value for improving tumor detection in stage Ia and Ib1 disease. Radiology 2008;249:541e50. 38. Hou B, Xiang S-F, Yao G-D, et al. Diagnostic significance of diffusionweighted MRI in patients with cervical cancer: a meta-analysis. Tumour Biol 2014;35:11761e9. 39. Xue H, Ren C, Yang J, et al. Histogram analysis of apparent diffusion coefficient for the assessment of local aggressiveness of cervical cancer. Arch Gynecol Obstet 2014;290:341e8. 40. Pecorelli S, Zigliani L, Odicino F. Revised FIGO staging for carcinoma of the cervix. Int J Gynecol Obstet 2009;105:107e8. 41. Colombo N, Carinelli S, Colombo A, et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012;23(Suppl 7):vii27e32. 42. Lin Y, Chen Z, Kuang F, et al. Evaluation of International Federation of Gynecology and Obstetrics Stage IB Cervical Cancer: comparison of diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging at 3.0 T. J Comput Assist Tomogr 2013;37:989e94. 43. Zand KR. Magnetic resonance imaging of the cervix. Cancer Imaging 2007;7:69e76. 44. Park JJ, Kim CK, Park SY, et al. Parametrial invasion in cervical cancer: fused T2-weighted imaging and high- b-value diffusion-weighted imaging with background body signal suppression at 3 T. Radiology 2015;274:734e41. 45. Park JJ, Kim CK, Park SY, et al. Value of diffusion-weighted imaging in predicting parametrial invasion in stage IA2eIIA cervical cancer. Eur Radiol 2014;24:1081e8. 46. Nougaret S, Tirumani SH, Addley H, et al. Pearls and pitfalls in MRI of gynecologic malignancy with diffusion-weighted technique. AJR Am J Roentgenol 2013;200:261e76. 47. Harry VN, Semple SI, Gilbert FJ, et al. Diffusion-weighted magnetic resonance imaging in the early detection of response to chemoradiation in cervical cancer. Gynecol Oncol 2008;111:213e20. 48. Harry VN. Novel imaging techniques as response biomarkers in cervical cancer. Gynecol Oncol 2010;116:253e61.
49. Liu Y, Bai R, Sun H, et al. Diffusion-weighted imaging in predicting and monitoring the response of uterine cervical cancer to combined chemoradiation. Clin Radiol 2009;64:1067e74. 50. Babar S, Rockall A, Goode A, et al. Magnetic resonance imaging appearances of recurrent cervical carcinoma. Int J Gynecol Cancer 2007;17:637e45. 51. Mittra E, El-Maghraby T, Rodriguez CA, et al. Efficacy of 18F-FDG PET/CT in the evaluation of patients with recurrent cervical carcinoma. Eur J Nucl Med Mol Imaging 2009;36:1952e9. 52. Addley HC, Vargas HA, Moyle PL, et al. Pelvic imaging following chemotherapy and radiation therapy for gynecologic malignancies. RadioGraphics 2010;30:1843e56. 53. Nunes N, Ambler G, Foo X, et al. Use of IOTA simple rules for diagnosis of ovarian cancer: meta-analysis. Ultrasound Obstet Gynecol 2014;44:503e14. 54. Thomassin-Naggara I, Toussaint I, Perrot N, et al. Characterization of complex adnexal masses: value of adding perfusion- and diffusionweighted MRI to conventional MRI. Radiology 2011;258:793e803. 55. Rockall AG. Diffusion weighted MRI in ovarian cancer. Curr Opin Oncol 2014;26:529e35. 56. Thomassin-Naggara I, Balvay D, Aubert E, et al. Quantitative dynamic contrast-enhanced MRI analysis of complex adnexal masses: a preliminary study. Eur Radiol 2011;22:738e45. 57. Thomassin-Naggara I, Aubert E, Rockall A, et al. Adnexal masses: development and preliminary validation of an MRI scoring system. Radiology 2013;267:432e43. 58. Thomassin-Naggara I, Daraï E, Cuenod CA, et al. Contribution of diffusion-weighted MRI for predicting benignity of complex adnexal masses. Eur Radiol 2009;19:1544e52. 59. Prat J, FIGO Committee on Gynecologic Oncology. FIGO’s staging classification for cancer of the ovary, fallopian tube, and peritoneum: abridged republication. J Gynecol Oncol 2015;26:87e9. 60. Motoshima S, Irie H, Nakazono T, et al. Diffusion-weighted MRI in gynecologic cancers. J Gynecol Oncol 2011;22:275. 61. Suh DH, Kim TH, Kim J-W, et al. Improvements to the FIGO staging for ovarian cancer: reconsideration of lymphatic spread and intraoperative tumor rupture. J Gynecol Oncol 2013;24:352. 62. Roy C, Bierry G, Matau A, et al. Value of diffusion-weighted imaging to detect small malignant pelvic lymph nodes at 3 T. Eur Radiol 2010;20:1803e11. 63. Michielsen K, Vergote I, Op de beeck K, et al. Whole-body MRI with diffusion-weighted sequence for staging of patients with suspected ovarian cancer: a clinical feasibility study in comparison to CT and FDGPET/CT. Eur Radiol 2013;24:889e901. 64. Low RN, Sebrechts CP, Barone RM, et al. Diffusion-weighted MRI of peritoneal tumors: comparison with conventional MRI and surgical and histopathologic findingsda feasibility study. AJR Am J Roentgenol 2009;193:461e70. 65. Chang S-J, Hodeib M, Chang J, et al. Survival impact of complete cytoreduction to no gross residual disease for advanced-stage ovarian cancer: a meta-analysis. Gynecol Oncol 2013;130:493e8. 66. Suidan RS, Ramirez PT, Sarasohn DM, et al. A multicenter prospective trial evaluating the ability of preoperative computed tomography scan and serum CA-125 to predict suboptimal cytoreduction at primary debulking surgery for advanced ovarian, fallopian tube, and peritoneal cancer. Gynecol Oncol 2014;134:455e61. 67. Michielsen KLM, Vergote I, Dresen R, et al. Whole-body diffusionweighted magnetic resonance imaging in the diagnosis of recurrent ovarian cancer: a clinical feasibility study. Br J Radiol 2016;89:20160468. 68. Schmidt S, Meuli RA, Achtari C, et al. Peritoneal carcinomatosis in primary ovarian cancer staging: comparison between MDCT, MRI, and 18FFDG PET/CT. Clin Nucl Med 2015;40:371e7. 69. Kyriazi S, Nye E, Stamp G, et al. Value of diffusion-weighted imaging for assessing site-specific response of advanced ovarian cancer to neoadjuvant chemotherapy: correlation of apparent diffusion coefficients with epithelial and stromal densities on histology. Cancer Biomark 2010;7:201e10. 70. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10e29. 71. Sala E, Priest AN, Kataoka M, et al. Apparent diffusion coefficient and vascular signal fraction measurements with magnetic resonance imaging: feasibility in metastatic ovarian cancer at 3 Tesla. Eur Radiol 2009;20:491e6.
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Review
Diffusion-weighted imaging in gynaecological malignancy H. Addley, P. Moyle, S. Freeman* Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK
art icl e i nformat ion Article history: Received 5 December 2016 Received in revised form 10 July 2017 Accepted 17 July 2017
Diffusion weighted imaging (DWI) has become an essential part of the gynaecological magnetic resonance imaging (MRI) protocol. DWI is used as an adjunct to conventional MRI sequences and has been shown to improve reporting accuracy in the imaging of gynaecological malignancy. In this review, we discuss the role of DWI in the diagnosis, staging, and assessment of treatment response of endometrial, cervical, and ovarian cancer. We also review the role of DWI in the assessment of the sonographically indeterminate ovarian lesion. Further, we highlight potential pitfalls that can beset the accurate interpretation of DWI in patients with gynaecological malignancy. Crown Copyright Ó 2017 Published by Elsevier Ltd on behalf of The Royal College of Radiologists. All rights reserved.
Introduction Diffusion weighted imaging (DWI) has become an essential part of the gynaecological magnetic resonance imaging (MRI) protocol. Amongst several advantages, DWI has been shown to improve reporting accuracy in the staging of uterine and ovarian cancers; however, there are pitfalls associated with DWI, which must be understood to avoid image misinterpretation. This review article aims to outline the role of DWI in the investigation and staging of gynaecological malignancy and aims to highlight the potential pitfalls. DWI is a method to visualise the three-dimensional microscopic movement of water molecules within the intra- and extracellular compartments. DWI visualises the variability in water mobility due to changes in tissue cellularity, cell membrane integrity, and fluid viscosity.1,2 * Guarantor and correspondent: S. Freeman, Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK. Tel.: þ1223 216203; fax: þ1223 217847. E-mail address: [email protected] (S. Freeman).
The more restricted the movement of water, the higher the signal intensity generated on DWI. The apparent diffusion coefficient (ADC) can provide quantitative assessment by using different b-values to calculate the degree of diffusion; restricted diffusion is displayed as low signal intensity on an ADC map. The movement of water molecules is typically restricted within the tumour microenvironment due to the increased cellularity.3 Due to this restriction in movement of water molecules, the majority of tumours demonstrate higher DWI signal intensity and lower ADC values when compared with adjacent normal tissue. As a consequence of increased conspicuity, DWI can be utilised to improve tumour detection, staging, and response assessment.
Image acquisition technique Diffusion-weighted (DW) images are acquired at a low bvalue (typically b¼0 or b¼50 s/mm2) and at high b-values (typical high b-values include 500, 800, or 1000 s/mm2). The acquisition of a minimum of two b-values allows assessment of restricted diffusion as the b-value increases
http://dx.doi.org/10.1016/j.crad.2017.07.014 0009-9260/Crown Copyright Ó 2017 Published by Elsevier Ltd on behalf of The Royal College of Radiologists. All rights reserved.
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and improves the accuracy of the ADC value. There is variability between different institutions regarding optimal bvalues, but it is well recognised that b-values >1000 s/mm2 reduce the signal-to-noise ratio (SNR) giving no further benefit in the assessment of ADC value. Methods to reduce artefacts seen at the higher b-value acquisition include parallel imaging or multiple averaging. The plane of DWI acquisition depends upon the disease entity being investigated. Typically, in the assessment of endometrial cancer, DWI is acquired in the sagittal and axial oblique plane (perpendicular to the endometrial cavity), to help assess myometrial invasion. In cervical cancer, sagittal, and axial oblique DWI perpendicular to the endocervical canal is obtained to help assess the parametrium. Obtaining the DWI sequences in the same plane as the T2-weighted (T2W) images allows for direct correlation, which is vital for correct assessment of restricted diffusion. The field of view used for the axial oblique in DWI should remain the same as for the T2W sequence (typically 20e24 cm). The quality of the high b-value DWI should be assessed to ensure that the high signal intensity of fluid within the bladder has been successfully suppressed: urine in the bladder should be seen as low signal intensity. Once this has been ascertained, the lesion should be interrogated for the presence of increased signal intensity, and subsequently, comparison made with the ADC map. Only once the lesion has been shown to be of high signal intensity on DWI and low signal intensity on ADC maps can the lesion be interpreted as having restricted diffusion.
Artefacts There are unique challenges to the acquisition and interpretation of DWI in gynaecological imaging. These include the movement of the pelvic organs within the pelvis secondary to bladder filling and bowel peristalsis. This causes misregistration between T2W and DWI as the uterine body and cervix can become displaced between the acquisitions of the different sequences. Acquiring T2W and DWI contemporaneously in the same plane can reduce this difficulty. In addition, the use of intramuscular or intravenous hyoscine butylbromide is strongly recommended to reduce bowel peristalsis. DWI is highly susceptible to metal artefact. The presence of orthopaedic implants such as a hip replacement can distort DWI images rendering them non-diagnostic. In this scenario, dynamic contrast-enhanced imaging postgadolinium administration may be warranted as an alternative to DWI to improve tumour delineation. In addition, pelvic DWI is also susceptible to distortion arising from rectal gas within the spatial field. This susceptibility artefact can be reduced by parallel imaging techniques, utilising multiphase array coils, which allows the echo time and echo train length to be shortened.4
Pitfalls T2 shine-through is a potential pitfall, where the presence of high signal intensity on T2W imaging remains
visible on high b-value DWI.5 This pitfall can be avoided by scrupulously correlating the DWI findings with the ADC map (Fig 1). In T2 shine-through, the lesion will be of high signal intensity on T2W imaging and high signal intensity on DWI, but importantly will also retain high signal intensity on ADC maps. Not all areas of restricted diffusion on DWI are malignant tumours, and there are several normal tissues and benign processes that can cause restricted diffusion. Notably, all lymph nodes demonstrate restricted diffusion on DWI and research remains inconclusive whether ADC values can be used to differentiate normal from infiltrated nodes.6e8 The diagnosis of lymph node tumour invasion remains dependent upon the node size and signal intensity on T2W imaging (replacement of the fatty hilum and similar signal intensity to the primary tumour); however, the degree of restriction on DWI improves the conspicuity of lymph nodes, which in turn improves staging accuracy.9 Similarly, the ovaries commonly demonstrate restricted diffusion on DWI and ADC maps. Therefore, correlation with the appearance on T2W imaging is essential to identify whether pathology is present. The presence of high signal intensity on DWI can enable the identification of the ovaries, which can be difficult with multiple abutting bowel loops. In particular, DWI can be useful in the evaluation of € llerian duct anomalies when the ovaries may have an Mu ectopic position. Benign pelvic disease, including endometriomas, dermoid cysts, fibroids, fibromas, and tubo-ovarian abscesses, can also result in restricted diffusion on DWI. Nearly 50% of endometriomas demonstrate restricted diffusion on DWI, usually within intra-cystic blood clots and should not be over-interpreted as the presence of tumour10,11(Fig 2). Endometriomas can be fully characterised with conventional sequences including T1W and T1W imaging with fat saturation; however, given the risk of malignancy within endometriomas, the T2W imaging should be carefully assessed for the presence of corresponding internal solid mural nodules. If soft-tissue mural nodules are identified, further evaluation following administration of intravenous gadolinium is recommended.11 Mature teratomas commonly demonstrate restricted diffusion on DWI. The restricted diffusion is seen within keratinoid substances and Rokitansky nodules; however, mature teratomas can be fully characterised on T1W and T1W fat-saturated imaging, by the presence of fat within an ovarian mass. This scenario exemplifies the importance of the use of DWI as an adjunct rather than a replacement for conventional imaging sequences in lesion characterisation.10 The presence of restricted diffusion within cellular leiomyomas and ovarian fibromas occurs due to their inherent dense cellularity.12,13 Image interpretation should always be made in context with the appearances on T1W and T2W imaging. DWI cannot reliably distinguish between cellular leiomyomas and leiomyosarcomas, as both may show restricted diffusion. ADC is also unable to differentiate between these two entities as both demonstrate low signal intensity on ADC maps, with overlap of ADC values of leiomyosarcoma with typical fibroids.13
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Figure 1 A 72-year-old woman had an incidental left ovarian mass identified at CT. MRI was performed for further characterisation and identified a cystic mass with fibrous low signal intensity elements, consistent with a cystadenofibroma. The fluid within the lesion demonstrates high signal intensity on T2W imaging (a) which remained high signal intensity on DWI (b) and ADC map (c) (arrows) representing T2 shinethrough.
Figure 2 A 33-year-old woman presented with pelvic pain. An ultrasound revealed a complex right ovarian cyst. On MRI, the lesion was characterised as an endometrioma on T1WI with fat saturation (a). The high signal intensity on DWI (b) and low signal intensity on ADC map (c) represents restricted diffusion within blood products and should not be misinterpreted as malignancy.
Tubo-ovarian abscesses also represent a pitfall on DWI as the abscess contents demonstrate restricted diffusion due to highly concentrated molecular components14 (Fig 3). Confusion can be avoided by interpreting the conventional MRI images in the appropriate clinical context.
Endometrial cancer Diagnosis In Europe, endometrial cancer represents the commonest gynaecological cancer, with an increase in incidence of 25% seen in the UK over the last decade.15,16 Endometrial cancer commonly presents with postmenopausal bleeding where ultrasound remains the primary investigation of choice. An endometrial thickness of >4e5 mm should be further investigated with endometrial biopsy.17,18 When endometrial sampling is not possible (usually due to cervical stenosis) or if histopathology results are inconclusive or inconsistent with the clinical suspicion,
DWI can be helpful to differentiate the presence of endometrial cancer over benign disease. The presence of restricted diffusion within an endometrial mass will raise suspicion for the presence of tumour regardless of biopsy findings, which can be subject to sampling error. Studies have shown that the ADC values of endometrial cancer are significantly lower than in benign endometrial polyps and normal endometrium, with a sensitivity of approximately 96%.19e21 Endometrial cancer is usually well delineated on T2W imaging as an intermediate signal intensity soft-tissue mass within the endometrial cavity; however, in cases where the endometrium is distorted by the presence of leiomyomas or adenomyosis, the restricted diffusion in endometrial cancer aids tumour detection on DWI. Inada et al., found that 96% of tumours could be identified on fused DWI or T2W imaging.22 The ADC values of endometrial cancer have been evaluated and no correlation was found with tumour grade, depth of myometrial invasion, or the presence of nodal metastases.23 More recent studies, however, have shown
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Figure 3 An 81-year-old woman presented with weight loss, lower abdominal pain and raised inflammatory markers. CT identified a right adnexal mass. MRI identified a thick-walled cystic collection in the right ovary on T2W imaging (a) with high signal intensity on DWI (b) and low signal intensity on ADC (c) (arrows). The restricted diffusion is due to the thick pus impeding the diffusion of water.
that there is a significant difference in ADC histograms between high- and low-grade tumours.24
Staging The staging of endometrial cancers is based upon both surgical and histological findings, using the FIGO (Federation Internationale Gynecologie Obstetrique) staging classification.25 The European Society of Urogenital Radiology (ESUR) recommends the use of MRI to stage patients preoperatively.26 The MRI stage, in conjunction with histological type and grade of tumour, enables risk stratification and treatment planning for the individual patient.27 Stage I disease represents endometrial cancer confined to the myometrium and is subdivided into Stage IA (<50% myometrial invasion) or stage IB (50% myometrial invasion). DWI is acquired in the sagittal and axial oblique plane (perpendicular to the endometrial cavity) to enable accurate assessment of the depth of myometrial invasion, as this correlates with the risk of lymph node metastases.28 Multiple studies have reviewed DWI and dynamic contrastenhanced (DCE) imaging for their role of improving assessment of the depth of myometrial invasion. Studies have shown that the addition of DWI to T2W imaging improves staging accuracy of myometrial invasion, with a sensitivity of up to 92%29,30 (Fig 4). DWI has many
advantages over DCE imaging as it does not require estimated glomerular filtration rate (eGFR) measurement and can be utilised when gadolinium is contraindicated (allergy, poor renal function). In addition, peri-tumoural inflammation may overestimate the extent of tumour invasion on DCE. This pitfall is avoided in DWI as inflammation does not cause restricted diffusion.31 DWI can also aid the detection of unexpected extrauterine tumour deposits. For example, drop metastases within the endocervical canal and vagina (Fig 5) as well as spread to the adnexa and peritoneum can be more clearly identified using DWI.29 Fuji et al. have also shown that DWI enables the detection of peritoneal spread of disease, with a sensitivity and specificity of 90% and 95.5%, respectively.32
Treatment planning Despite the current FIGO staging guidelines, full pelvic and abdominal lymph node dissection is controversial due to the associated morbidity, with limited improvement in prognosis.33 It is therefore essential to identify potentially infiltrated lymph nodes prior to surgery to aid surgical planning. Although DWI cannot be utilised to distinguish benign from malignant nodes, its usage improves nodal detection due to the improved conspicuity of high signal intensity on DWI.6e8
Figure 4 A 73-year-old woman with post-menopausal bleeding was shown to have endometrial thickening on ultrasound. Subsequent histology from Pipelle sampling revealed an endometrial carcinoma. (a) MRI staging showed a markedly thickened endometrium on sagittal T2W imaging (arrow); however, the assessment of the depth of myometrial invasion was difficult in the presence of multiple fibroids. The DWI (b) and ADC map (c) reveal >50% myometrial invasion posteriorly (arrow). Please cite this article in press as: Addley H, et al., Diffusion-weighted imaging in gynaecological malignancy, Clinical Radiology (2017), http:// dx.doi.org/10.1016/j.crad.2017.07.014
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Figure 5 A 67-year-old woman presented with post-menopausal bleeding. A polyp containing grade 2 endometrioid carcinoma was removed at hysteroscopy; however, at staging MRI, the sagittal T2W imaging (a) revealed subtle intermediate signal intensity in the lower third of the vagina. (b) On sagittal DWI, the drop metastasis is clearly visible as a high signal intensity lesion (white arrows). The soft-tissue lesion invading the distal sigmoid serosa seen on T2W imaging does not demonstrate restricted diffusion on DWI and represents an endometriotic deposit (arrowhead).
Recurrence Surgery is curative in the majority of patients with endometrial cancer; however, patients with high-grade histology, type II endometrial cancers (clear cell and serous papillary tumours) or an advanced stage at diagnosis are at a higher risk of recurrence. The minimum ADC value of endometrial cancer correlates with the risk of recurrence; a low minimum ADC value within the primary endometrial cancer correlates with lower disease-free survival.34 Tumour recurrence typically occurs in the first 3 years after surgery (87%) with the commonest sites of recurrence being the vaginal vault (42%) and regional lymph nodes (46%).35 Computed tomography (CT) is routinely used in the follow-up of high-risk patients to identify recurrent disease within the lungs or lymph nodes; however, the vaginal vault can be difficult to assess with CT and MRI provides improved soft-tissue resolution, if recurrence is suspected. DWI is particularly useful to distinguish between postradiotherapy soft-tissue thickening or inflammation and recurrent disease.
Cervical cancer Diagnosis Cervical cancer is the third most common gynaecological cancer, but the commonest cancer in females under 35years old.15 Cervical cancer is diagnosed clinically in the majority of cases, with a limited role for imaging in the initial diagnosis.
DWI is as accurate as DCE in the detection of cervical tumours, but can have a role in the diagnosis of tumours situated high within the endocervical canal, not immediately amenable to biopsy.36 In small tumours, DWI improves tumour detection following biopsy or excision (LLETZ or cone biopsy) as post-procedure inflammatory changes can distort the normal anatomy on T2W imaging. The presence of restricted diffusion can differentiate inflammation from malignancy. Some authors propose the use of an endovaginal coil to improve signal return.37 The ADC value has been shown to be significantly lower in malignant tumours when compared with the normal background parenchyma.38 In addition, Xue et al. have shown that there is correlation between histological grade of tumours and the ADC value, with higher-grade tumours having lower-grade ADC values.39
Staging Cervical cancer staging is performed clinically using the revised 2009 FIGO staging classification40; however, MRI now has an established role in cervical cancer staging and has been adopted in the main radiological and oncological guidelines.41 High resolution T2W imaging is required to accurately depict tumour size. DWI, in combination with T2W imaging, has been shown to be equivalent to DCE-MRI in distinguishing between Ib1 and Ib2 tumours (lesions confined to the cervix 4 cm and >4 cm, respectively); however, DWI has the advantage of alleviating the cost and additional factors associated with the administration of intravenous contrast medium.42 Axial oblique imaging (perpendicular to the endocervical canal), with T2W imaging and DWI, allows assessment of
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parametrial invasion (stage IIB), which determines whether surgery or chemoradiotherapy is the appropriate treatment strategy.27 On T2W imaging, the presence of an intact low signal intensity cervical stromal ring excludes parametrial invasion.43 One study demonstrated that the use of wholebody DWI fused with T2W imaging improved detection of parametrial invasion with a significantly higher specificity (up to 99%), when compared with T2W imaging alone (up to 88.7%).44 Utilising multivariate analysis to define independent imaging predictors for pathologically-proven parametrial invasion, Park et al. identified low tumour ADC value and the presence of parametrial extension on T2W imaging.45 DWI is also very helpful in patients with infiltrative tumours, when the tumour boundaries are difficult to depict on T2W imaging.31 By comparing the area of restricted diffusion on DWI with the T2W imaging findings, the delineation of tumour infiltration is improved. Sagittal DWI aids the detection of direct tumour spread to the vagina and the presence of drop metastases.
Treatment planning Accurate local staging of the tumour enables optimal treatment planning for patients, either for chemoradiation or surgery. In clinical practice, restricted diffusion within the cervical tumour can provide more accurate delineation of small tumours, particularly if fertility-sparing surgery is being planned37,46(Fig 6). In the group of patients requiring chemoradiation, further MRI examinations are crucial both to aid treatment planning and to assess treatment response. The role of DWI in treatment response during radiation treatment is vital. Following chemoradiation, the margin between tumour and normal tissues becomes less well-defined on T2W imaging. DWI has a major role in differentiating between post-treatment changes, such as oedema, inflammation, and fibrosis, from residual tumour in these patients. DWI findings have been evaluated as a biomarker of cervical tumour treatment response47e49 (Fig 3). The ADC values have been demonstrated to increase as early as 2 weeks post-treatment before detectable involution of tumour. The tumour ADC value and the change in ADC value predicts
successful clinical response.47 Identification of residual disease following chemoradiation is essential to patient management, as there is a window of opportunity for these patients to undergo exenterative surgery following their chemoradiation.
Recurrence In cervical cancer, 60e70% of cases of post-treatment recurrence occur within 2 years of treatment.50 MRI is the best technique for assessment of local recurrence in the pelvis and is combined with 2-[18F]-fluoro-2-deoxy-Dglucose positron-emission tomography (PET)/CT for the assessment of distant metastases.51 Recurrent disease on T2W imaging is demonstrated as an area of intermediate signal intensity which, given the changes within the pelvis following either surgery or chemoradiation, can be challenging to diagnose in small volume disease.52 Abnormal signal intensity within the cervix on T2W imaging is further assessed with DWI. Both tumour recurrence and posttreatment inflammation may reveal high signal intensity on DWI, but only recurrent tumour will demonstrate restriction on ADC maps (Fig 7). Although post-radiation fibrosis can give low ADC values, the appearance on T2W imaging is frequently also low signal intensity and will not demonstrate high signal intensity compared to tumour on the high b-value images.46
Ovarian cancer Diagnosis Ovarian cancer is the sixth most common cancer in women in the UK. The clinical presentation is relatively non-specific, resulting in almost 60% of patients being diagnosed at a late stage (stage III of IV). Survival is strongly linked to the stage at diagnosis with 1-year survival of 99% for stage I disease declining to 51% for stage IV disease.15 Therefore, It is imperative that patients undergo accurate ultrasound assessment once a pelvic mass is suspected. Ultrasound remains the predominant imaging method in the initial detection and diagnosis of an adnexal mass.
Figure 6 A 36-year-old woman with post-coital bleeding underwent staging MRI following histological confirmation of cervical malignancy. (a) Axial T2W imaging demonstrates intermediate signal intensity area within the cervix. On axial oblique imaging, the tumour demonstrates high signal intensity on DWI (b) and low signal intensity on the ADC map (c) in keeping with restricted diffusion. The boundaries of the tumour are clearly defined on the DWI with no evidence of parametrial invasion. Please cite this article in press as: Addley H, et al., Diffusion-weighted imaging in gynaecological malignancy, Clinical Radiology (2017), http:// dx.doi.org/10.1016/j.crad.2017.07.014
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Figure 7 A 46-year-old woman with a FIGO stage IIIb carcinoma of the cervix was treated with chemoradiation. The end of treatment MRI identified residual intermediate signal intensity in the lower uterine segment/cervix (a) with high signal intensity on DWI (b) and low signal intensity on ADC map (c) (arrows). This was confirmed as residual tumour on histology.
Nevertheless, even using the International Ovarian Tumour Analysis group (IOTA) simple rules, 22% of ovarian lesions remained indeterminate on ultrasound.53 MRI now plays a pivotal role in the investigation of sonographicallyindeterminate adnexal masses. Ovarian cancer often presents at a late stage with peritoneal disease and ascites already present; however, in patients presenting with early-stage disease, without clear extra-ovarian spread of disease, MRI is invaluable in differentiating the adnexal masses with high risk of malignancy from those of potentially benign origin. Using standard MRI sequences including T2W imaging, T1W imaging with and without fat saturation, the majority of adnexal lesions can be accurately diagnosed. The ESUR has recently updated the recommendations for MRI of the sonographically-indeterminate adnexal mass, by defining the role and diagnostic value of DWI.11 Diagnostic confidence is increased by approximately 15% when DWI is added to conventional MRI and is particularly helpful in characterising benign lesions with no restricted diffusion.54 The Adnex MRI scoring system is a standardised method of MRI and reporting to categorise complex adnexal masses, which includes DWI as one of its criteria.55 The Adnex MRI score system divides masses into five categories from score 1 corresponding to no mass through to score 5 that describes a probably malignant mass and has shown excellent validation in feasibility studies.56 Specifically these studies show the value of DWI in assessing non-fatty, non-haemorrhagic pelvic masses that are entirely solid, or complex masses that are either septate cysts or complex solid and cystic masses.57 The adnexal masses seen in ovarian cancer of both highgrade and low-grade tumours both demonstrate restricted diffusion on DWI and ADC.55 Takeuchi et al. demonstrated there was a difference in the mean ADC values between benign and malignant ovarian tumors.12 With a cut-off ADC value of 1.15103 mm2/s, there was a sensitivity of 74% and a specificity of 80% for differentiating benign from malignant or borderline ovarian lesions. By reducing the ADC cutoff further to 1103 mm2/s, the sensitivity drops to 46% but specificity increases to 100%.
Care must be taken in interpreting tumours with low cellular density and high fluid content such as mucinous tumours, serous papillary tumours or tumours with necrosis or cystic areas. These can have high signal intensity on DWI due to T2 shine-through of the fluid component and therefore careful reference to the ADC map and T2W imaging is mandatory. If an indeterminate adnexal mass is of low signal intensity on T2W imaging, and the entire mass displays low signal on DWI obtained with a b-value of 800e1000 s/mm2, there is a very high likelihood of benign disease, for example, cystadenofibromas, ovarian fibromas, and pedunculated leiomyomas.58 In this scenario, DWI can replace DCE T1W imaging, which can be particularly useful in women when gadolinium should be avoided. It should be remembered that some fibromas are densely cellular and therefore demonstrate restricted diffusion on DWI; however, these lesions are often fully characterised on conventional MRI sequences. When there is an indeterminate adnexal mass, which has a solid component revealing high signal on the high-bvalue DWI, it may be benign or malignant. In these cases DCE MRI is recommended as per the ESUR 2016 update.11
Staging Ovarian cancer is usually staged according to the FIGO surgicalepathological staging system.59 CT is the standard technique to stage ovarian cancer given its fast image acquisition and wide availability; however, there are limitations of soft-tissue contrast resolution between normal and malignant tissue on CT; in particular, there remains difficulty in distinguishing between bowel wall and serosal deposits, as well as between unopacified small bowel loops and peritoneal deposits, even with the use of oral and intravenous contrast medium. Advanced MRI techniques, such as DWI, can overcome many of these staging issues.60 The combined interpretation of DWI with conventional MRI sequences has been shown to increase reporting accuracy in lesion detection beyond the adnexa and therefore confirm the presence of disseminated malignant disease32 (Fig 8).
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Figure 8 A 58-year-old woman with stage IIIC high-grade serous carcinoma of the ovary. (a) T2W axial imaging demonstrates bilateral solid adnexal masses (arrows). (b) The ovarian tumours reveal high signal intensity on DWI and (c) low signal intensity on ADC map. Although peritoneal disease can be seen on the T2W imaging, the restricted diffusion on DWI significantly improves disease identification (b). The arrowheads identify the peritoneal disease outlining the pouch of Douglas and peritoneal reflection.
Patients with isolated retroperitoneal lymph node metastases (FIGO stage IIIA1) have been shown to have a better prognosis than those patients with peritoneal metastases >2 cm (stage IIIC) with a 5-year survival of 57.5% versus 35.8%.61 As previously discussed, DWI cannot accurately differentiate normal from infiltrated lymph nodes; however, their increased conspicuity on DWI aids detection, which in turn can be cross-correlated with size and morphology on conventional MRI sequences.62 The same principle exists with extra-abdominal nodes and therefore potentially highlights changes in staging, for example, inguinal lymph nodes represent stage IVB disease. Ovarian carcinoma commonly metastases to the peritoneum through transcoelomic spread. DWI has been shown to be superior in identifying small peritoneal lesions when compared to CT.32,63 Small volume peritoneal implants at the dome of the diaphragm, lesser sac, or sub-capsular liver and spleen deposits can be difficult to identify on CT and conventional MRI64 (Fig 9). The intrinsic contrast resolution of restricted diffusion on DWI can highlight metastases in these difficult locations and thereby improve staging accuracy.
Treatment planning Following comprehensive staging with CT, the standard of care for newly diagnosed advanced ovarian cancer is
cytoreductive surgery with neoadjuvant or adjuvant chemotherapy. Cytoreductive surgery has been shown to increase overall survival if there is no residual visible tumour at the completion of surgery.65 Therefore, the preoperative assessment of tumour burden and potential resectability has an essential role in guiding management. Areas that radiologists should specifically review that can affect resectability are: suprarenal retroperitoneal lymph nodes >1 cm; diffuse small bowel adhesions/thickening; lesions >1 cm in the small bowel mesentery; the root of the superior mesenteric artery; the perisplenic area, and lesser sac.66 Michielsen et al. demonstrated whole-body DWI showed better sensitivity than CT for detecting involvement of surgically critical tumour sites, including the mesenteric root (92% versus 31%), small bowel (93% versus 21%), colon (91 % versus 27%), and unresectable distant metastases (90% versus 20%).67 Whole-body MRI compares equally with FDG-PET/CT for identifying primary tumours and retroperitoneal lymph nodes, but has a higher accuracy for peritoneal staging compared with FDG-PET/CT63; however PET/CT has been shown to be more accurate in the diagnosis of supradiaphragmatic metastases.68 Kyriazi et al. investigated the ADC maps in eight patients with metastatic primary ovarian carcinoma during the first and third cycles of neoadjuvant chemotherapy.69 Mean ADC increased significantly from baseline after both first
Figure 9 A 58-year-old woman with stage IIIC high-grade serous carcinoma of the ovary. (a) T2W axial imaging demonstrates peritoneal disease in the upper abdomen. The high signal intensity on DWI (b) and low signal intensity on ADC map (c) shows restricted diffusion within the peritoneal disease. This improves the conspicuity of peritoneal deposits in difficult to review regions including: subdiaphragmatic (white arrow), falciform ligament/porta hepatis (dashed arrow), subcapsular splenic (arrowhead), and left upper quadrant (asterisk) tumour deposits. Please cite this article in press as: Addley H, et al., Diffusion-weighted imaging in gynaecological malignancy, Clinical Radiology (2017), http:// dx.doi.org/10.1016/j.crad.2017.07.014
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and third cycles in both ovarian and omental disease. This may represent a functional marker of early response to treatment and affect treatment planning, although more work is needed before this is implemented as a biomarker in clinical practice.
Recurrence Approximately 75% of women with ovarian cancer present with advanced (stage III or IV) disease, which is associated with an increased risk of post-treatment recurrence. Following optimal surgical debulking, patients with lowvolume residual disease (lesions <1 cm in size) have a 60e70% risk of recurrence, whereas patients with highvolume residual disease (lesions >1 cm) have an 80e85% risk of recurrence.70 Therefore, identifying residual and recurrent disease and classifying its location (local pelvic, peritoneal lesion, lymph node, and distant metastasis) is important to guide further management. Michielsen et al. demonstrated that whole-body DWI improved the sensitivity of detecting recurrent ovarian cancer compared to CT, especially in the assessment of the root of the mesentery and serosal disease of the small and large bowel.67 Ovarian cancer demonstrates marked tumour heterogeneity between the primary tumour and peritoneal deposits presumably secondary to the variability of ovarian tumour genetics. This heterogeneity can affect treatment response and recurrence. Sala et al. identified differences in ADC between the primary ovarian tumour, omental deposits, and peritoneal deposits.71 Peritoneal deposits have a significantly lower mean ADC than the primary ovarian lesion or omental deposits. DWI and ADC may therefore have a vital role in improving our knowledge of tumour dedifferentiation, resistance to second-line cytotoxic treatments and aiding future management of these patients.
Conclusion DWI has numerous specific roles in the imaging of gynaecological malignancy. Interpretation of DWI is dependent upon a clear understanding of its role in different diseases and its place in primary and posttreatment investigation in addition to typical pitfalls, to avoid misinterpretation of findings. Multiple studies have assessed the role of DWI in staging cervical and endometrial cancers and demonstrated the improvement in staging accuracy. In ovarian and endometrial cancer, the restricted diffusion within peritoneal disease aids detection of disease dissemination, which enables accurate treatment decisions and surgical planning. DWI allows differentiation of malignant ovarian lesions from benign mimics, in conjunction with standard MRI sequences.
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Please cite this article in press as: Addley H, et al., Diffusion-weighted imaging in gynaecological malignancy, Clinical Radiology (2017), http:// dx.doi.org/10.1016/j.crad.2017.07.014