{"paper_id":"f26d41e6-7ec4-4b43-9351-675f4b707a90","body_text":"In ovarian disorders, conventional morphological evaluation in T1-weighted (T1W) and\nT2-weighted (T2W) magnetic resonance imaging (MRI) sequences is essential. However,\ndiffusion-weighted imaging (DWI) has undeniable diagnostic value, providing\nexcellent tissue contrast based on the molecular diffusion of\nwater ( 1 ) . This fact is particularly relevant in\ndifferentiating between benign and malignant ovarian tumors ( 2 ) . In general, the latter\nshow restricted diffusion, whereas the former do not. Nevertheless, there are some\nexceptions. The restricted diffusion of water molecules is proportional to the\nfollowing: expansion of the intracellular compartment, as in cytotoxic edema;\nincreased cell membrane density due to hypercellularity; increased fluid viscosity;\nand increased tortuosity of the extracellular space ( 3 ) . In fact, restricted\ndiffusion may be observed in normal tissue, in solid non-malignant lesions with high\ncellular density, or in cystic non-malignant lesions with high\nviscosity ( 3 ) . To avoid diagnostic pitfalls, DWI should always be\nevaluated in conjunction with the apparent diffusion coefficient (ADC) maps and\ncorrelated with conventional anatomic MRI scans (T1W and T2W sequences).\n\nDWI is a functional MRI technique, performed without contrast administration,\nthat provides information about the intracellular, transcellular, and\nextracellular Brownian motion of water molecules in a tissue (true diffusion),\nas well as the microcirculation (perfusion), which can be evaluated\nseparately ( 1 ) . In tissues with increased cellularity and a\nresultant increase in cell membrane surface area, there is a decrease in\nBrownian motion (i.e., restricted diffusion), whereas there is an increase in\nBrownian motion (i.e., free diffusion) in tissues with decreased cellularity.\nThe ADC, which represents a combination of true diffusion and perfusion, is a\nnumerical value assigned to the degree of such motion in a tissue and has been\nused as a marker of cellularity.\nFree diffusion, qualitatively visible as progressive signal loss on DWI obtained\nwith increasing b values and quantitatively measured as a region with a high\nADC, can be seen in tissues with low cellularity ( 4 ) . In contrast,\nrestricted diffusion, qualitatively visible as high signal intensity on DWI\nobtained with increasing b values and quantitatively measured as a region with a\nlow ADC, is associated with hypercellularity and has been used as an indicator\nof potential malignancy ( 4 ) .\nIn DWI, the b values represent different diffusion-sensitizing gradient strengths\nand are expressed as s/mm 2  (time/area). Because the ADC is the slope\nof exponential decrease in signal intensities between DWI sequences with\ndifferent b values, DWI with ADC mapping is performed with at least two\ndifferent b values. At lower b values, the perfusion-related contribution is\nhigher, which can affect the ADC, and the image mirrors a heavily T2W\nfat-suppressed sequence. The predominant contributor changes from perfusion to\ndiffusion at b values in the 100-300 s/mm 2 \nrange ( 1 ) . At higher b values (> 1000\ns/mm 2 ), there can be a progressive decrease in the signal-to-noise\nratio ( 5 ) .\nThe ADC is expressed as a numerical value × 10 −3 \nmm 2 /s and represents a quantitative metric. It quantifies the\nprogressive loss of signal in a tissue of interest visible on DWI performed with\nsuccessively increasing b values. A region of interest can be drawn by the\nradiologist in the tissue of interest to obtain a numeric\nvalue ( 4 ) . The region of interest results in automatically\ngenerated ADCs, presented as minimum, mean, and maximum values or as a mean\nvalue.\nIn pelvic examinations, DWI is most commonly acquired in the axial plane.\nHowever, obtaining sequences with the same orientation as that of T2W images\nallows fusion imaging and optimizes anatomic correlation ( 6 ) .\nOne should bear in mind some pitfalls when interpreting DWI sequences. In\ngeneral, high-cellularity tumors demonstrate restricted diffusion, whereas\nnormal tissue does not. However, benign tissue components, such as blood, fat,\nnecrosis and pus, may also show restricted diffusion ( 6 ) . As a result, DWI\ncharacteristics of benign and malignant tumors, including those of the ovary,\nmay overlap ( 7 ) . It is crucial to correlate DWI and ADC data\nwith morphological characteristics to minimize the probability of\nmisinterpretation.\nIt is also important to keep in mind the fact that DWI is based on T2W images,\ncausing tissues with long T2 relaxation time, such as simple cysts, to show high\nsignal intensity-the so-called T2-shine-through effect. However, an ovarian mass\nwith a hypointense signal on DWI, the ADC map, and T2W images-the so-called\nT2-blackout effect-is most likely a benign mass ( 2 ) , making DWI\nparticularly suited to excluding the possibility of malignancy.\n\nThe ovaries are usually ovoid in shape and average 10 cm 3  in\nvolume ( 8 ) . The zonal anatomy is best appreciated on T2W\nimages, the normal medulla showing increased signal intensity relative to the\ncortex, reflecting the greater amount of loosely packed stroma and blood\nvessels, and diminished cellularity of the medulla ( 8 ) . In women of\nreproductive age, there are multiple follicles in the cortex, appearing as\nthin-walled cystic structures, the fluid content of which results in high signal\nintensity on T2W images and low signal intensity on T1W\nimages ( 8 ) . On T2W images, the corpus luteum demonstrates\nwall thickening, with low to intermediate signal intensity, that corresponds to\na layer of luteinized theca cells ( 8 ) .\nIn women of reproductive age, the normal ovary may have high enough signal\nintensity to be identified on DWI sequences from zero to high b values,\nespecially during the luteal phase. Ovarian follicles may show high signal\nintensity on all DWI sequences (even at high b values), with concomitant high\nADCs ( 9 ) .\nMature cystic teratomas are the most common ovarian tumors in women under 45\nyears of age ( 10 ) . They are composed of mature tissue from at\nleast two of the three germ cell layers (endoderm, mesoderm, and ectoderm);\nin 88% of cases, they are filled with sebaceous material, which is liquid at\nbody temperature, and are lined with keratinized squamous\nepithelium ( 11 ) . They grow slowly, at an average rate of\n1.8 mm each year, prompting some researchers to advocate nonsurgical\nmanagement of smaller (< 6 cm) tumors ( 12 ) . In 10% of\ncases, the tumors are bilateral ( 13 ) . Mature cystic teratomas\ncontain hair follicles, skin glands, muscle, and other tissues. There is\nusually a raised protuberance projecting into the cyst cavity, known as a\nRokitansky nodule ( 13 ) . Ectodermal tissue (skin and neural\nderivatives) is invariably present, as are mesodermal tissue (fat, bone,\ncartilage, and muscle) in over 90% of cases and endodermal tissue (e.g.,\ngastrointestinal epithelium, bronchial epithelium, and thyroid tissue) in\nmost cases ( 13 ) . Although it is one of the most relevant\nfeatures, adipose tissue is present in only 67-75% of\ncases ( 13 ) .\nMature cystic teratomas have typical imaging features on MRI ( Table 1 ). Their adipose content\ndisplays a signal that is hyperintense on T1W images and becomes hypointense\nafter selective fat saturation. This characteristic is sufficient to\nestablish the diagnosis of a ovarian teratoma ( 13 ) .\nFindings in benign ovarian lesions with restricted diffusion.\nWith hemorrhagic infarction. FS, fat saturation.\nIt has been suggested that the abnormal signal intensity displayed on DWI by\nmost mature cystic teratomas is caused by the presence of keratin, a protein\noriginating from the cytoskeletal structure of the\nepidermis ( 7 ) . Other sites showing abnormal signal\nintensity include Rokitansky nodules and fat globules ( 7 ) . The restricted\nBrownian movement of water molecules within the keratinous substance results\nin a high signal intensity on DWI and low ADCs ( Figure 1 ). In fact, DWI can facilitate the diagnosis of\nmature cystic teratomas, especially those containing a small amount of fat\nthat is not detectable by conventional MRI ( 14 , 15 ) .\nFigure 1 MRI of a 32-year-old female patient with a left mature cystic\nteratoma.  A:  Axial T1W image showing a cystic\nlesion with areas of high signal intensity in which the signal\nbecame hypointense after fat saturation (not represented).\n B:  Axial DWI at b = 1000 s/mm 2 ,\nshowing areas of high signal intensity within the lesion.\n C:  ADC map showing low ADCs within the\nlesion.\nMRI of a 32-year-old female patient with a left mature cystic\nteratoma.  A:  Axial T1W image showing a cystic\nlesion with areas of high signal intensity in which the signal\nbecame hypointense after fat saturation (not represented).\n B:  Axial DWI at b = 1000 s/mm 2 ,\nshowing areas of high signal intensity within the lesion.\n C:  ADC map showing low ADCs within the\nlesion.\nMature cystic teratomas undergo malignant transformation in 1-2% of the\ncases ( 13 ) . Malignant transformation tends to occur in\nolder women (between 60 and 70 years of age), squamous cell carcinoma being\nthe most common histological type. In such cases, they can show restricted\ndiffusion in their solid component, due to\nhypercellularity ( 10 ) . The morphological correlation is\nmandatory, because malignant mural nodules tend to show intermediate signal\nintensity on T2W images and enhancement after gadolinium\nadministration ( 15 ) .\nWhen an ovarian follicle enlarges during the menstrual cycle but does not\nrupture for ovulation, a follicular cyst, typically measuring between 3 cm\nand 6 cm, may develop. In some cases, these cysts undergo hemorrhage,\nbecoming hemorrhagic cysts. On MRI, a hemorrhagic cyst usually has high\nsignal intensity on T1W images and intermediate to high signal intensity on\nT2W images ( Table 1 ). There is smooth\nenhancement on the cyst wall, without vegetations or\nnodularity ( 6 ) . Because of their blood content, hemorrhagic\ncysts may display restricted diffusion ( 6 ) .\nEndometriomas, also known as endometriotic cysts, are benign cysts that\nconstitute an ovarian manifestation of endometriosis. On MRI, endometriomas\ntypically appear as cystic lesions, typically multiple or bilateral, with\nthick walls ( 16 ) . They show high signal intensity on T1W\nimages, with or without selective fat suppression, and relatively low signal\nintensity on T2W images-the shading sign ( 17 ) . However, this\nsign is not exclusive to endometriomas, given the fact that T2 shading can\nalso be observed in hemorrhagic cysts and other benign or malignant\nnon-endometrioid adnexal tumors ( 18 ) , leading to diagnostic\ndifficulties.\nBecause endometriomas contain blood and some hemosiderin, they show T1\nshortening, high signal intensity on DWI, and lower\nADCs ( 7 ) , as depicted in  Figure 2 . The presence of restricted diffusion in\nendometriomas may hamper the detection of malignant transformation, making\nthe correlation with other sequences mandatory. Solid nodules showing\nintermediate signal intensity on T2W images, peritoneal metastases,\nthickened septa (> 3 mm), or contrast enhancement are likely to be\nmalignant ( 19 ) . Clear cell and endometrioid carcinomas are\nthe most common malignant tumors associated with endometriomas.\nFigure 2 MRI of a 41-year-old female patient with endometriomas.\n A:  Axial T1W image with fat suppression,\nshowing bilateral cystic lesions with high signal intensity.\n B:  Axial DWI at b = 1000 s/mm 2 ,\nshowing areas of high signal intensity within the lesions.\n C:  ADC map showing low ADCs within the\nlesions.\nMRI of a 41-year-old female patient with endometriomas.\n A:  Axial T1W image with fat suppression,\nshowing bilateral cystic lesions with high signal intensity.\n B:  Axial DWI at b = 1000 s/mm 2 ,\nshowing areas of high signal intensity within the lesions.\n C:  ADC map showing low ADCs within the\nlesions.\nDWI and ADC mapping may play roles in differentiating between hemorrhagic\ncysts and endometrioma. In a recent study, including 24 benign cystic\nhemorrhagic adnexal lesions, Balaban et al. ( 20 )  reported that\nADCs were significantly lower in endometriomas than in hemorrhagic cysts, a\nfact that can be used to differentiate between the two conditions. There\nare, however, more reliable ways of making this distinction, in particular\nthe presence of the T2 dark spot sign, which has high specificity for\nchronic hemorrhage ( 16 ) .\nOvarian torsion usually presents as acute severe pelvic pain and is caused by\npartial or complete rotation of the ovarian vascular pedicle. Predisposing\nfactors include an underlying ovarian tumor (especially one > 6 cm),\nhypermobile adnexa, and elongated fallopian tubes ( 21 ) . Ovarian\ntorsion most commonly affects women under 30 years of\nage ( 21 ) .\nIn cases of ovarian torsion, venous blood flow is initially compromised,\ncausing edema and swelling. Later, the dual arterial blood supply is also\ncompromised, leading to hemorrhagic infarction ( 22 ) , which in turn\nresults in irreversible loss of the ovary.\nThe most common characteristics of the lesion in adults are an enlarged ovary\nwith areas of signal hyperintensity on T1W and T2W images ( Table 1 ), due to hemorrhage and edema,\nrespectively. Peripheral follicles can also be\nobserved ( 23 ) . In the late phases, gangrenous necrosis\ndevelops.\nTo date, there have been no studies demonstrating that the use of DWI adds\nvalue in the diagnosis of ovarian torsion. However, DWI has been shown to be\nbeneficial in identifying hemorrhagic infarction ( 24 ) : low ADCs are\nmore common in torsed ovaries with hemorrhagic infarction than in those\nwithout.\nIn the majority of cases, tubo-ovarian abscesses result from pelvic\ninflammatory disease, being more common in women of reproductive\nage ( 25 ) . Tubo-ovarian abscesses are thick-walled,\nmultilocular adnexal masses. They may contain septa, pus, gas, or fluid,\nwith or without fluid-debris levels ( 25 ) . The content usually displays\na heterogeneously intermediate signal on T2W images ( Table 1 ). Areas of necrosis or loculated fluid\ncollections may resemble serous fluid but can also be proteinaceous or\nhemorrhagic with T1 shortening ( 26 ) . Tubo-ovarian abscesses are\nsurrounded by thick, markedly enhancing outer borders.\nTubo-ovarian abscesses comprise viscous proteinaceous fluid containing\nbacteria, inflammatory cells, cellular debris, and necrotic tissue. When the\ncontent is more viscous, the signal intensity is higher on DWI and lower on\nthe ADC map ( 27 ) , as shown in  Figure 3 . Depending on the viscosity of the pus, the abscess\ncontents may show heterogeneous restricted diffusion. Chronic abscesses,\nabscesses smaller than 1 cm in diameter, and abscesses in patients on\nantibiotic therapy may not show restricted diffusion ( 28 ) .\nFigure 3 MRI of a 39-year-old female patient with a left tubo-ovarian\nabscess.  A:  Axial T2W image showing a cystic lesion\nwith heterogeneous high-signalintensity content.  B: \nAxial DWI at b = 1000 s/mm 2 , showing areas of high\nsignal intensity within the lesion.  C:  ADC map\nshowing low ADCs within the lesion.\nMRI of a 39-year-old female patient with a left tubo-ovarian\nabscess.  A:  Axial T2W image showing a cystic lesion\nwith heterogeneous high-signalintensity content.  B: \nAxial DWI at b = 1000 s/mm 2 , showing areas of high\nsignal intensity within the lesion.  C:  ADC map\nshowing low ADCs within the lesion.\nDWI also plays a role in making a distinction between tubo-ovarian abscesses\nand cystic or necrotic neoplasms. Neoplasms typically show restricted\ndiffusion at the periphery, where the cell density is higher, whereas\nabscesses show central restricted diffusion ( 24 ) .\nFibromas are the most common solid ovarian tumors and account for 4% of all\novarian neoplasms ( 29 ) . Fibromas are benign tumors that can\npresent at any age, although the mean age of occurrence is in the late\nforties. Fibromas that are highly cellular are classified as either cellular\nfibromas or fibrosarcomas. Cellular fibromas constitute 10% of all ovarian\nfibromas and have low malignant potential, whereas fibrosarcomas are\nmalignant tumors ( 29 , 30 ) .\nOn MRI, fibromas usually present low signal intensity on T1W images, low\nsignal intensity on T2W images, and weak, delayed enhancement after contrast\nadministration. In the majority of these tumors, T2-shortening effects,\ncaused by the abundant collagen contents and the decreased extracellular\nfluid, result in a signal decrease on T2W images ( 31 ) . The pathology\nexamination can reveal edema and cystic degeneration, which explain the\nvarying degree of intermediate to high signal intensity portions on T2W\nimages, which may mimic malignancy, in some cases ( 32 ) .\nThecomas account for 0.5-1.0% of all primary ovarian tumors and are most\nlikely to occur in postmenopausal women ( 29 ) . In most\ncases, they exhibit estrogenic activity ( 33 ) . With rare\nexceptions, they are considered benign neoplasms ( 29 ) .\nOn MRI, when compared with predominantly fibrous tumors, pure thecomas tend\nto exhibit higher signal intensity on T2W images and more avid contrast\nenhancement, a major pitfall in the diagnosis of malignant ovarian tumors of\nthe ovary ( 30 ) . The accurate diagnosis of these tumors and\ntheir differentiation from malignant tumors is critical for correct patient\nmanagement. DWI, in combination with ADC mapping, may play a role in making\nthat distinction. According to the most recent European Society of\nUrogenital Radiology guidelines for indeterminate adnexal masses, a solid\nlesion that exhibits low signal intensity on T2W images and on DWI with high\nb values is highly likely to be benign ( 2 , 34 ) . However, isolated ADC\nmeasurements in the solid component have not been found to contribute to\ndifferentiating between benign and malignant adnexal masses, possibly due to\nthe lower mean ADCs in benign fibrous tumors associated with dense fibrous\nstromal proliferation. In such tumors, no signal increase is observed on\nDWI, despite their low ADCs, probably as a consequence of the T2 blackout\neffect ( 2 ) . Nevertheless, some fibromas and thecomas in\nthis group may show restricted diffusion. For instance, functioning thecomas\nand cellular fibromas may show high signal intensity on DWI and relatively\nlow ADCs ( Figure 4 ), due to their\nrelatively high cellularity ( 35 - 37 ) .\nFigure 4 MRI of a 67-year-old female patient with thecoma.  A: \nAxial T2W image showing a solid lesion with intermediate signal\nintensity.  B:  Axial DWI at b = 1000\ns/mm 2 , showing high signal intensity within the\nlesion.  C:  ADC map showing low ADCs within the\nlesion.\nMRI of a 67-year-old female patient with thecoma.  A: \nAxial T2W image showing a solid lesion with intermediate signal\nintensity.  B:  Axial DWI at b = 1000\ns/mm 2 , showing high signal intensity within the\nlesion.  C:  ADC map showing low ADCs within the\nlesion.\n\nIn ovarian disorders, conventional morphological evaluation with T1W and T2W images\nis essential. However, DWI has experienced a rise in popularity, due to its\nundeniable diagnostic value, particularly in differentiating between benign and\nmalignant tumors. It is advisable to use DWI as a complementary sequence, whenever\npossible, because it can provide excellent tissue contrast based on the molecular\ndiffusion of water within tumors. As a general rule, malignant tumors present\nrestricted diffusion, whereas benign tumors do not. Nevertheless, radiologists\nshould be aware of some lesions that constitute exceptions to that rule: teratomas,\nendometriomas, hemorrhagic cysts, ovarian abscesses, ovarian infarction, and some\nbenign sex cord-stromal tumors.","source_license":"CC-BY-4.0","license_restricted":false}