2. Application of Radiomics in the Female Pelvis: From Segmentation to Features Extraction
To obtain a quantitative reliable result in radiomics studies, it is fundamental to follow a precise radiomics pipeline, composed of five necessary steps: (1) image acquisition, (2) segmentation, (3) features extraction, (4) features selection, and (5) statistical analysis and modelling
[4][8]. All of them should be provided in the most robust way possible, especially to allow reproducibility between studies and centres.
Image acquisition is the first and one of the most important steps. When setting up a radiomics study, imaging protocol(s) must be well delineated (e.g., contrast media administration, timing of dynamic sequences, mandatory and optional MRI sequences). Data regarding CT and MRI protocols for the study of the female pelvis have been comprehensively detailed in the literature
[5][6][9,10].
Segmentation is a fundamental step in medical image analysis as it allows for the identification and isolation of specific anatomic structures or pathological regions within an image. For computing this aspect, region(s) of interest (ROIs) or volume(s) of interest (VOIs) should be drawn in the interested lesion, organ, or tissue. ROIs can be manually drawn by human readers, semi-automatically or automatically, each of them with advantages and disadvantages.
Manual segmentation has the main disadvantage of being time consuming: the reader should sketch the contours slice by slice using pointing devices. Moreover, this procedure can lead to a reduction in the robustness of radiomics features
[7][11].
On the other hand, semi-automatic and automatic approaches are based on available software or custom-made algorithms; in the case of the semi-automatic approach, the preliminary segmentation will be refined by a human reader
[7][8][11,12]. Semi-automatic segmentation strategies, providing putative contours that the expert operator is asked to refine or correct, represent a solution to reduce both times and inter-operator variability. Automatic segmentation techniques rely on deep or machine learning (DL and ML, respectively) strategies
[9][13]. These models learn step by step how to segment images if trained on a large amount of already labelled images.
Once the ROI or VOI is segmented, a wide range of quantitative features can be extracted. These features can be categorized into different groups such as shape-based features, intensity-based features, texture-based features, and spatial-relationship-based features. The process that leads to obtaining this quantitative data is named “feature extraction”. After that, feature selection is employed to identify the most relevant and discriminative features for a specific clinical task. This step helps reduce the computational burden and improve the robustness of subsequent analysis.
Finally, the extracted and selected radiomic features are subjected to statistical analysis and modelling. Various statistical methods, machine learning algorithms, or deep learning architectures can be applied to explore the relationships between these features and clinical outcomes or other relevant parameters
[10][14].
One of the most important limitations to be underlined regards radiomics features obtained by different scanners and institutions. In fact, radiomic features are usually strictly dependent on different factors, such as acquisition data, MR technical features, and contrast media, being employed. For these reasons, whether it is necessary to compare radiomics data deriving from different scanners or from multiple institutions, it is of utmost importance to provide a post-processing step, in order to reduce potential bias. Different methods were proposed, including denoising
[11][15], N4 bias field correction
[12][16], voxel size resampling and interpolation, discretization
[13][17], and ComBat harmonization
[14][18].
3. Endometrial Cancer
Endometrial cancer (EC) is the most common gynaecological malignancy in industrialized countries, with an expected increasing incidence worldwide
[15][16][17][19,20,21]. EC usually affects postmenopausal patients (75–80% of cases), with a peak between 55 and 65 years, and its most frequent clinical manifestation is abnormal postmenopausal bleeding
[15][18][19,22].
Diagnosis is based on minimally invasive procedures (hysteroscopy, endometrial biopsy, dilatation, and curettage) and transvaginal ultrasound (TVUS)
[18][19][22,23]. However, MRI is considered the best technique for pre-operative staging
[20][21][24,25].
EC is classified according to the recently updated International Federation of Gynaecology and Obstetrics (FIGO) staging system
[22][26] and is traditionally grouped into two major prognostic groups (type I and type II), based on the histological type and FIGO histological grading system
[23][24][25][27,28,29]. Type I tumours account for approximately 80% of endometrial neoplasms and include endometrioid histotypes with pathological grading G1 and G2. This category of EC is characterized by a good prognosis and is typically estrogen responsive. Type II represents approximately 20% of overall endometrial tumours and includes high-grade (G3) endometrioid and non-endometrioid forms (clear-cell, mucinous, carcinosarcomas, undifferentiated forms). This group usually shows a more aggressive course and does not correlate with estrogenic exposure.
In order to provide therapeutic management guidelines, the European Society of Gynaecological Oncology (ESMO), European Society for Radiotherapy and Oncology (ESTRO), and European Society of Gynaecological Oncology (ESGO) guidelines stratify EC into four risk categories (low, intermediate, high intermediate, and high risk) according to histology, grade, stage, and the presence of lymph vascular space invasion (LVSI), which describe tumour behaviour and the likelihood of recurrences, directing toward possible adjuvant therapy
[18][22]. EC clinical behaviour is also influenced by its genomic features; therefore, a reclassification of EC based on genomics has been recently proposed considering four categories (POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high)
[26][30].
Deep myometrial invasion (DMI) allows for the differentiation between the FIGO stages IA and IB, the most important morphological prognostic factor
[27][28][31,32]. Even if MRI is the most accurate technique for the evaluation of DMI, its detection is not always straightforward and has shown relatively high inter-observer variability, particularly when the endometrium is thinned (i.e., older patients, endometrial cavity distension), when the endometrial–myometrial interface is obscured by fibroids or adenomyosis, and when the lesion is located in uterine cornual regions
[27][28][29][30][31,32,33,34].
Another key prognostic factor is the presence of pelvic or para-aortic nodes metastases (LNM), which is also essential in guiding the therapeutic approach. The principal criterion for suspecting nodes metastases is based on nodal size (short axis > 1 cm). However, this criterion has a low specificity because hyperplastic nodes can also be enlarged, which may lead to a high percentage of false-positive results. At the same time, it has been demonstrated that nodes with a short axis lower than 1 cm are sometimes proved as metastatic at pathology
[20][31][24,35].
Many studies investigated the possible role of radiomics in improving the assessment of EC
[32][33][36,37]. The most common imaging modality employed in radiomics investigation studies for EC diagnosis and staging was MRI, using standard diagnostic MRI protocols. According to the latest guidelines of the European Society of Urogenital Radiology (ESUR), pelvic MRI protocol for EC assessment includes T2WI, diffusion-weighted (DWI), and dynamic contrast-enhanced (DCE) imaging
[20][24].
4. Cervical Cancer
Cervical cancer (CC) is ranked fourth among malignancies in terms of incidence, prevalence, and mortality in women worldwide; however, when early diagnosis is made, CC is one of the most successfully treatable forms of cancer
[34][60]. Patients with CC are staged according to the TNM classification, and the clinical staging is based on the FIGO staging system
[35][61]. The initial workup for assessment of pelvic tumour extent and to guide treatment options is based on pelvic MRI according to consensus recommendations by the ESMO, ESTRO, and European Society of Pathology (ESP) guidelines
[36][62].
Radiological assessment of cervical malignancy for the initial staging, response monitoring, and evaluation of disease recurrence is performed on pelvic MRI according to the ESUR guidelines
[37][63]. The standard pelvic MRI protocol includes T1WI without and with saturation, T2WI with a slice thickness of 4 mm or less, and DWI sequences while contrast-enhanced MRI remains optional. However, pelvic MRI has some limitations in the assessment of CC, mainly related to the limited accuracy for nodes status, largely based on the size criteria (i.e., ≥1.0 cm in short axis) which yields a low pooled sensitivity of 56–61%
[38][64], in the assessment of parametrial invasion with a pooled sensitivity of 76% and specificity of 94%
[39][65], as well as in the evaluation of residual disease after chemoradiation therapy with sensitivity and specificity of 80% and 55%, respectively
[40][66]. Given the current limitations of standard imaging techniques, over the last decade, there has been an increasing number of studies investigating if radiomics applied to CT or MRI may fill the current gaps in patients with CC.
Most of these radiomics studies proved a moderate to high performance of radiomics or combined clinical–radiomics models suggesting that radiomics might be used as a prognostic biomarker and helpful in tailoring therapeutic management. In addition, some papers addressed technical issues about radiomics, including the development of a fully automatic whole-volume tumour segmentation tool
[41][67], evaluation of robustness, stability, and reproducibility of radiomic features in pelvic MRI, suggesting the application of normalization prior to features extraction
[42][43][44][45][68,69,70,71] and the definition of the best volume of interest to achieve a specific outcome
[46][72].
5. Mesenchymal Tumours
Uterine mesenchymal tumours arise from uterine smooth muscle, endometrial stroma, or a combination of both
[47][132]. Benign leiomyomas (LM) are the most common mesenchymal uterine tumours, affecting up to 80% of women of reproductive age
[48][133]. Conversely, uterine sarcomas (US) are a rare form of mesenchymal tumours, accounting for approximately 1% of gynaecological neoplasms and 3–7% of all uterine malignancies, and have a poor prognosis
[49][134]. Currently, there are no reliable imaging criteria for distinguishing US, especially leiomyosarcomas, from LM with atypical features, including degeneration or unusual pattern of growth
[50][135]. The final diagnosis is usually made only after the surgery, based on postoperative histopathological assessment.
Considering the overlap imaging features in atypical LM and US, several authors investigated the possible role of MRI texture analysis in aiding radiologists in the differential diagnosis between these two entities
[51][136]. However, the majority of these publications are retrospective and monocentric, beyond being limited by small sample cohorts of patients, particularly those with malignant lesions.
Malek et al. developed a radiomic model based on MR perfusion, which showed good diagnostic values (accuracy, sensitivity, and specificity of 91%, 100%, and 90%, respectively)
[52][137]. The same authors aimed to develop a decision tree and a complex algorithm to differentiate US and LM, with accuracies of 96% and 100%, respectively. However, the algorithm was reported to be time consuming, with a special limit for everyday clinical practice
[53][138].
Finally, Xie et al. reported that a radiomic model based on ADC map can predict pathological results of patients with sarcomas and atypical leiomyomas with an AUC of 0.83
[54][139].
Nakagawa and colleagues compared the performance of ML using multiparametric MRI and positron-emission tomography (PET), concluding that the MRI-based model was superior to the PET one and comparable with that of experienced radiologists
[55][140]. Another investigation compared the diagnostic performance of three different volumes of interests (VOIs)—lesion, lesion and surrounding tissue, and whole uterus—in ADC map-based radiomic analysis for distinguishing US and LM. The results showed that the model based on features extracted from VOIs covering the whole uterus had the best diagnostic performance (AUC: 0.876, sensitivity: 76.3%, and specificity: 84.5%)
[56][141]. Yang and Stamp focused their research on distinguishing low-grade US and LM, testing different ML models and various cutting-edge deep learning techniques. For the classic techniques considered, the highest classification accuracy was 0.85, while the most accurate learning model achieved an accuracy of approximately 0.87
[57][142].
6. Ovarian Pathologies
Ovarian lesions are a frequent cause of gynaecological pathologies with both benign and malignant conditions frequently encountered in clinical practice. Ovarian cancer is in the seventh place for cancer incidence in females and it is associated with high mortality
[58][143]. Epithelial tumours are the most common cause of ovarian cancer, and they include a wide spectrum of lesions with different histopathological features, risk factors, treatment options, and prognosis
[58][143]. Particularly, the most common ovarian lesions are serous and mucinous tumours. In this complex clinical context, radiomics can serve as a relevant tool to improve the diagnosis, management, and prediction of prognosis in patients with ovarian pathologies
[59][144]. Several studies explored the performance of radiomics with a plethora of different aims and outcomes in ovarian pathologies.
Ultrasound, CT, and MRI are the most used imaging techniques in patients with ovarian pathologies. Ultrasound is the first imaging modality for the assessment of ovarian pathologies but the differential diagnosis between different entities may be challenging based only on the qualitative assessment. Initial single-centre studies applied the radiomics analysis on ultrasound images to predict the histopathological types and grades of epithelial ovarian cancers
[60][61][145,146] and prognosis
[62][147] with reported good performances but validation can be problematic as the ultrasound images’ acquisitions depend on operator experience.
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