Can Diffusion weighted MR imaging add diagnostic information in the evaluation of uterine tumor?

Introduction Diffusion-weighted imaging (DWI) is a functional imaging technique , applied in Magnetic Resonance imaging, whose contrast derives from the random motion of water molecules within explored tissues. Since image contrast is derived from inherent differences in the restriction of the movement of water molecules, no exogenous contrast medium administration is required, so that DWI sequences can now be included in routine patient assessment. DWI uses t he measurement of Brownian movements of water molecules by applying symmetric pairs of equally weighted diffusion sensitizing gradients about the 180°refocusing pulse of a spin - echo T2-weighted sequence. Static water molecules develop additional phase inco herencies from the application of the first diffusion gradient, but these incoherencies are eliminated by the application of the second gradient, resulting in no additional net loss of signal (aside from normal T2 decay) [1]. However, mobile water is not c ompletely rephased by the second gradient owing to movement to a different microenvironment during the application of the first gradient, so that a subsequent reduction in signal intensity is observed. DWI sensitivity to water motion is dependent on three main parameters: the gradient amplitude, the duration, and the time interval (b-value) between paired diffusion gradients [2]. Tissues containing water that is moving the most freely (eg, within blood vessels, ducts, or the bladder) will demonstrate greate r signal losses after the application of the smallest diffusion gradients (<100 sec/mm2). Signal losses caused by water motion in the extracellular space of tumors occur at higher b values because water motion is modified by interactions with hydrophobic c ell membranes and macromolecules (increased extracellular space tortuosity) [3]. In solid tumors of high cellularity, there are additional significant reductions in extracellular space, resulting in further restrictions to free water movement. When DWI is used in gynecologic applications, cervical cancers have been shown to have significantly lower apparent diffusion coefficient (ADC) values than normal cervical tissue [4]. Similar findings have been noted in endometrial cancers, with a tendency toward lowe r ADC values in higher-grade lesions. ADC value The ADC value (measured in mm2/sec) is usually calculated by the slope of the line of the natural logarithm of signal intensity (y axis) versus b values (x axis) [5]. DWI imaging: applications in female pelvic neoplasms Cervical cancer Cervical cancer is the second most common female cancer in the world and it occurs predominantly in women between the age of 30 and 44 years [6]. The American Cancer Society provides the following list of risk factors for cervical cancer: Human Papillomavirus (HPV) infection, smoking, HIV infection, chlamydia infection, dietary factors, hormonal contraception, multiple pregnancies, exposure to the hormonal drug diethylstilbestrol (DES) and a family history of cervical cancer [7]. Cervical cancer: Histopathology The World Health Organization (WHO) recognizes two main histological types of invasive cervical cancer.  Squamous carcinoma (which constitute about 85% of all cases)  Adenocarcinoma (which constitute about 10-12% of all cases) Several other types of carcinoma (eg adenosquamous carcinoma, adenoid cystic carcinoma, metastatic carcinoma) make up the remaining 3-5% of all cases. Squamous carcinomas are further typed according to whether they are keratinizing or not keratinizing carcinomas. Keratinizing carcinomas may be well differentiated or moderately differentiated and are composed of large tumour cells. Non-keratinizing carcinomas (poorly differentiated carcinomas) may be of large cell or small cell type [8]. Most cervical squamous cell carcinomas grow at the squamocolumnar junction (SCJ). In young women, the SCJ is located outside the external uterine os, and the tumor tends to grow outward (exophytic growth pattern). In contrast, in elderly patients, the SCJ is located within the cervical canal. In these patients, cervical cancer tends to grow inward along the cervical canal (endophytic growth pattern) [9]. Adenocarcinomas are less commonly found and although each type is histologically distinct, it is not uncommon to find two or more histological forms of adenocarcinoma in a single tumour .The frequent coexistence of glandular and squamous carcinoma suggest that they may have a common origin in the reserve cells of the cervix as well as a common etiology. The most frequent type of adenocarcinoma to be found in the cervix is the endocervical type of mucinous adenocarcinoma. Three grades of endocervical carcinoma are recognized -well differentiated, moderately differentiated and poorly differentiated - depending on the similarity of the tumour cell to the glandular epithelial lining the endocervix. In fact, in endocervical adenocarcinoma, endocervical type, different subtypes can be found (endometrioid type, clear cell type, papillary serous type, intestinal type, mixed type) [10]. Cervical cancer: MR features At baselineT2 w.i MR examination, cervical cancers appear as slightly hyperintense masses, while their predominantly signal intensity on baseline T1 w.i is hypointensity. On vascular dynamic study, cervical cancers can show no enhancement or slighly marginal enhancement on arterial phase. Endometrial cancer Endometrial cancer is the most common malignancy of the genital tract and overall the endometrium is the fourth most frequent cancer site. Risk factor for endometrial cancer include obesity, diabetes, oestrogen therapy, polycystic ovarian syndrome and westernization of lifestyle.[11]. Approximately 75% of cases occur in postmenopausal women, with the median age at diagnosis being 70 years. Endometrial cancer: Histopathology Endometrial tumors can be have different histology: endometrial carcinoma (with its histopathologic subtypes: villoglandular or papillary, secretory, ciliated cell, adenocarcinoma with squamous differentiation), adenocarcinoma (serous, mucinous, clear cell), squamous cell carcinoma; undifferentiated carcinoma; mixed carcinoma, metastatic carcinoma and carcinosarcoma. Adenocarcinomas account for 90% of endometrial neoplasms, whereas uterine sarcomas are relatively rare and account for only 2%–6%; the remaining histologic types include adenocarcinoma, with squamous cell differentiation and adenosquamous carcinoma [12]. Endometrial cancer: MR features At MR examination, endometrial cancer is iso-hypointense in respect to the surrounding normal endometrium on baseline T1w.i -weighted images, while it does most commonly show heterogeneous, iso up to hyperintensity on baseline T2wi. Neoplasms are usually mildly hyperintense on baseline T2w.i. in respect to myometrium. Endometrial cancer can have different pattern of appearances on baseline T2 w.i.: hypointense pseudonodular lesions, diffuse endometrial thickening, hypointense vegetations, or infiltrative endometrial plaques with heterogeneous signal intensity. Endometrial carcinomas are divided into two types: one shows as a well-demarcated exophytic mass (Type I), while the other shows as an invasive, endophytic growth toward the myometrium (Type II). The former subtype is considered to be malignant with favorable prognosis [13].