Nuclear Medicine and Molecular Imaging Applications in Gynecologic Malignancies: A Comprehensive Review.

Gynecologic malignancies, consisting of endometrial, cervical, ovarian, vulvar, and vaginal cancers, pose significant diagnostic and management challenges due to their complex anatomic location and potential for rapid progression. These tumors cause substantial morbidity and mortality, often because of their delayed diagnosis and treatment. An estimated 19% of newly diagnosed cancers among women are gynecologic in origin. In recent years, there has been growing evidence supporting the integration of nuclear medicine imaging modalities in the diagnostic work-up and management of gynecologic cancers. The sensitivity of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) combined with the anatomical specificity of computed tomography (CT) and magnetic resonance imaging (MRI) allows for the hybrid evaluation of metabolic activity and structural abnormalities that has become an indispensable tool in oncologic imaging. Lymphoscintigraphy, using technetium 99m (99mTc) based radiotracers along with single photon emission computed tomography/ computed tomography (SPECT/CT), holds a vital role in the identification of sentinel lymph nodes to minimize the surgical morbidity from extensive lymph node dissections. While not yet standard for gynecologic malignancies, promising therapeutic nuclear medicine agents serve as specialized treatment options for patients with advanced or recurrent disease. This article aims to provide a comprehensive review on the nuclear medicine applications in gynecologic malignancies through the following objectives: 1) To describe the role of nuclear medicine in the initial staging, lymph node mapping, response assessment, and recurrence/surveillance imaging of common gynecologic cancers, 2) To review the limitations of 18F-FDG PET/CT and promising applications of 18F-FDG PET/MRI in gynecologic malignancy, 3) To underscore the promising theragnostic applications of nuclear medicine, 4) To highlight the current role of nuclear medicine imaging in gynecologic cancers as per the National Comprehensive Cancer Network (NCCN), European Society of Surgical Oncology (ESGO), and European Society of Medical Oncology (ESMO) guidelines.

O-RADS US v2022: An Update from the American College of Radiology's Ovarian-Adnexal Reporting and Data System US Committee.

First published in 2019, the Ovarian-Adnexal Reporting and Data System (O-RADS) US provides a standardized lexicon for ovarian and adnexal lesions, enables stratification of these lesions with use of a numeric score based on morphologic features to indicate the risk of malignancy, and offers management guidance. This risk stratification system has subsequently been validated in retrospective studies and has yielded good interreader concordance, even with users of different levels of expertise. As use of the system increased, it was recognized that an update was needed to address certain clinical challenges, clarify recommendations, and incorporate emerging data from validation studies. Additional morphologic features that favor benignity, such as the bilocular feature for cysts without solid components and shadowing for solid lesions with smooth contours, were added to O-RADS US for optimal risk-appropriate scoring. As O-RADS US 4 has been shown to be an appropriate cutoff for malignancy, it is now recommended that lower-risk O-RADS US 3 lesions be followed with US if not excised. For solid lesions and cystic lesions with solid components, further characterization with MRI is now emphasized as a supplemental evaluation method, as MRI may provide higher specificity. This statement summarizes the updates to the governing concepts, lexicon terminology and assessment categories, and management recommendations found in the 2022 version of O-RADS US.

Gynecologic oncology tumor board: the central role of the radiologist.

This manuscript is a collaborative, multi-institutional effort by members of the Society of Abdominal Radiology Uterine and Ovarian Cancer Disease Focus Panel and the European Society of Urogenital Radiology Women Pelvic Imaging working group. The manuscript reviews the key role radiologists play at tumor board and highlights key imaging findings that guide management decisions in patients with the most common gynecologic malignancies including ovarian cancer, cervical cancer, and endometrial cancer.

Assessment of Amniotic Fluid Volume in Pregnancy.

Amniotic fluid (AF) is an integral part of the fetal environment and is essential for fetal growth and development. Pathways of AF recirculation include the fetal lungs, swallowing, absorption through the fetal gastrointestinal tract, excretion through fetal urine production, and movement. In addition to being a marker for fetal health, adequate AF is necessary for fetal lung development, growth, and movement. The role of diagnostic imaging is to provide a detailed fetal survey, placental evaluation, and clinical correlation with maternal conditions to help identify causes of AF abnormalities and thereby enable specific therapy. Oligohydramnios prompts evaluation for fetal growth restriction as well as genitourinary issues, including renal agenesis, multicystic dysplastic kidneys, ureteropelvic junction obstruction, and bladder outlet obstruction. Premature preterm rupture of membranes should also be clinically excluded as a cause of oligohydramnios. Clinical trials evaluating amnioinfusion are underway as a potential intervention for renal causes of oligohydramnios. Most cases of polyhydramnios are idiopathic, with maternal diabetes being a common cause. Polyhydramnios prompts evaluation for fetal gastrointestinal obstruction and oropharyngeal or thoracic masses, as well as neurologic or musculoskeletal anomalies. Amnioreduction is performed only for maternal indications such as symptomatic polyhydramnios causing maternal respiratory distress. Polyhydramnios with fetal growth restriction is paradoxical and can occur with maternal diabetes and hypertension. When these maternal conditions are absent, this raises concern for aneuploidy. The authors describe the pathways of AF production and circulation, US and MRI assessment of AF, disease-specific disruption of AF pathways, and an algorithmic approach to AF abnormalities. ©RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Adnexal Lesion Imaging: Past, Present, and Future.

Currently, imaging is part of the standard of care for patients with adnexal lesions prior to definitive management. Imaging can identify a physiologic finding or classic benign lesion that can be followed up conservatively. When one of these entities is not present, imaging is used to determine the probability of ovarian cancer prior to surgical consultation. Since the inclusion of imaging in the evaluation of adnexal lesions in the 1970s, the rate of surgery for benign lesions has decreased. More recently, data-driven Ovarian-Adnexal Reporting and Data System (O-RADS) scoring systems for US and MRI with standardized lexicons have been developed to allow for assignment of a cancer risk score, with the goal of further decreasing unnecessary interventions while expediting the care of patients with ovarian cancer. US is used as the initial modality for the assessment of adnexal lesions, while MRI is used when there is a clinical need for increased specificity and positive predictive value for the diagnosis of cancer. This article will review how the treatment of adnexal lesions has changed due to imaging over the decades; the current data supporting the use of US, CT, and MRI to determine the likelihood of cancer; and future directions of adnexal imaging for the early detection of ovarian cancer.

Noninvasive prenatal screening and maternal malignancy: role of imaging.

Noninvasive prenatal screening (NIPS) tests for fetal chromosomal anomalies through maternal blood sampling. It is becoming widely available and standard of care for pregnant women in many countries. It is performed in the first trimester of pregnancy, usually between 9 and 12 weeks. Fragments of fetal cell-free deoxyribonucleic acid (DNA) floating in maternal plasma are detected and analyzed by this test to assess for chromosomal aberrations. Similarly, maternal tumor-derived cell-free DNA (ctDNA) released from the tumor cells also circulates in the plasma. Hence, the presence of genomic anomalies originating from maternal tumor-derived DNA may be detected on the NIPS-based fetal risk assessment in pregnant patients. Presence of multiple aneuploidies or autosomal monosomies are the most commonly reported NIPS abnormalities detected with occult maternal malignancies. When such results are received, the search for an occult maternal malignancy begins, in which imaging plays a crucial role. The most commonly detected malignancies via NIPS are leukemia, lymphoma, breast and colon cancers. Ultrasound is a reasonable radiation-free modality for imaging during pregnancy, specially when there are localizing symptoms or findings, such as palpable lumps. While there are no consensus guidelines on the imaging evaluation for these patients, when there are no localizing symptoms or clinically palpable findings, whole body MRI is recommended as the radiation-free modality of choice to search for an occult malignancy. Based on clinical symptoms, practice patterns, and available resources, breast ultrasound, chest radiographs, and targeted ultrasound evaluations can also be performed initially or as a follow-up for MRI findings. CT is reserved for exceptional circumstances due to its higher radiation dose. This article intends to increase awareness of this rare but stressful clinical scenario and guide imaging evaluation for occult malignancy detected via NIPS during pregnancy.

The radiologist's role in a multidisciplinary approach to cancer in pregnancy.

Pregnancy-associated cancer (PAC) occurs in approximately 1 in 1000 pregnancies, and the incidence is expected to rise due to delayed childbearing (Silverstein et al. in JCO Oncol Pract 16:545-557, 2020; Woitek et al. in ESMO Open 1:e000017, 2016). Diagnosis and management of PACs are challenging and diagnosis is often delayed as symptoms may overlap with physiologic changes of pregnancy (Jha et al. in RadioGraphics 42:220005, 2022). These patients are best cared for by a multidisciplinary healthcare team composed of experts (Silverstein et al. in JCO Oncol Pract 16:545-557, 2020). Management of these patients must balance optimal maternal care with potentially harmful fetal effects. This involves honest, forthright, and sometimes difficult discussions between the care team and the patient throughout the entirety of care. Radiologists play a significant role in timely cancer diagnosis, staging and follow-up during and after pregnancy, accurate determination of gestational age, and in assessing fetal growth and well-being throughout pregnancy.

The Ovarian/Adnexal Reporting and Data System for Ultrasound: From Standardized Terminology to Optimal Risk Assessment and Management.

The American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System (O-RADS) lexicon and risk assessment tool for ultrasound (US) provides a framework for characterization of ovarian and adnexal pathology with the ultimate goal of harmonizing reporting and patient management strategies. Since the first O-RADS US publication in 2018, multiple validation studies have shown O-RADS US to have excellent diagnostic accuracy, with the majority of these studies using O-RADS 4 as the optimal cut-off for detecting ovarian cancer. Most of the existing validation studies include a dedicated training phase and confirm that ORADS US categories and lexicon descriptors are associated with high level inter-read agreement, regardless of radiologist training level or practice experience. O-RADS US has a similar inter-reader agreement when compared to Gynecologic Imaging Reporting and Data System (GIRADS), Assessment of Different Neoplasias in the adnexa (ADNEX), and International Tumor Analysis Group (IOTA) simple rules. System descriptors have been shown to correlate with expected malignancy rates and the O-RADS US risk stratification system has been shown to perform in the expected range of malignancy risk per category. Further directions will focus on clarifying governing concepts and lexicon terminology as well as further refining risk stratification categories based on data from published validation studies.

MR Imaging of Endometriosis of the Adnexa.

Endometriosis is the presence of ectopic endometrial glands outside of the uterus. MR imaging is particularly useful for characterizing deep infiltrating endometriosis but can also be useful in characterizing endometriomas and hematosalpinges, characterizing broad ligament deposits, assessing for endometriosis-associated malignancy, and differentiating malignancy from decidualized endometriomas. Masses and cysts with hemorrhagic or proteinaceous contents can sometimes be difficult to distinguish from endometriomas. Imaging protocols should include pre-contrast T1-weighted imaging with fat saturation, T2-weighted imaging without fat saturation, opposed- and in-phase or Dixon imaging, administration of contrast media, and subtraction imaging.

MR of Fallopian Tubes: MR Imaging Clinics.

MR imaging has an important role in imaging evaluation of fallopian tube (FT) pathology, ranging from benign to malignant conditions. Congenital Mullerian anomalies of FTs such as accessory tubal ostia and unicornuate uterus and associated pathology are well assessed by MR imaging. Benign diseases include hydrosalpinx, pelvic inflammatory disease, and its manifestations including salpingitis, pyosalpinx, tubo-ovarian abscess, and tubal endometriosis manifesting as hematosalpinx. Acute benign conditions include isolated FT torsion and ectopic pregnancy. Neoplastic conditions include benign paratubal cysts to malignant primary FT carcinomas.

Sequelae of Eating Disorders at Imaging.

Although eating disorders are common, they tend to be underdiagnosed and undertreated because social stigma tends to make patients less likely to seek medical attention and less compliant with medical treatment. Diagnosis is crucial because these disorders can affect any organ system and are associated with the highest mortality rate of any psychiatric disorder. Because of this, imaging findings, when recognized, can be vital to the diagnosis and management of eating disorders and their related complications. The authors familiarize the radiologist with the pathophysiology and sequelae of eating disorders and provide an overview of the related imaging findings. Some imaging findings associated with eating disorders are nonspecific, and others are subtle. The presence of these findings should alert the radiologist to correlate them with the patient's medical history and laboratory results and the clinical team's findings at the physical examination. The combination of these findings may suggest a diagnosis that might otherwise be missed. Topics addressed include (a) the pathophysiology of eating disorders, (b) the clinical presentation of patients with eating disorders and their medical complications and sequelae, (c) the imaging features associated with common and uncommon sequelae of eating disorders, (d) an overview of management and treatment of eating disorders, and (e) conditions that can mimic eating disorders (eg, substance abuse, medically induced eating disorders, and malnourishment in patients with cancer). Online supplemental material is available for this article. ©RSNA, 2022.

Imaging Cancer in Pregnancy.

Pregnancy-associated cancer (PAC) is defined as cancer that is detected during pregnancy and up to 1 year postpartum. Although rare (~1:1000 pregnancies), PAC is increasing owing to postponed childbearing and advanced maternal age at conception. Cancer-related symptoms masked by physiologic gestational changes may delay diagnosis. Imaging, clinical management, and treatment require a carefully choreographed multidisciplinary team approach. The risk-benefit of every imaging modality, the strategies to balance the safety of mother and fetus, and the support of the patient and family at every step are crucial. US and MRI are preferred imaging modalities that lack ionizing radiation. Radiation dose concerns should be addressed, noting that most imaging examinations (including mammography, radiography, CT, and technetium 99m-labeled sulfur colloid sentinel lymph node staging) are performed at radiation levels below thresholds at which deterministic side effects are seen. Dose estimates should be provided after each examination. The use of iodinated intravenous contrast material is safe during pregnancy, but gadolinium-based contrast material should be avoided. Accurate diagnosis and staging combined with gestational age affect decisions about surgery and chemotherapy. Whole-body MRI with diffusion-weighted sequences is ideal to screen for primary and metastatic sites, determine disease stage, identify biopsy targets, and guide further cancer site-specific imaging. The authors provide an update of the imaging triage, safety considerations, cancer-specific imaging, and treatment options for cancer in pregnancy. An invited commentary by Silverstein and Van Loon is available online. Online supplemental material is available for this article. ©RSNA, 2022.

Diagnostic Performance of the Ovarian-Adnexal Reporting and Data System (O-RADS) Ultrasound Risk Score in Women in the United States.

Importance: The American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System (O-RADS) ultrasound (US) risk scoring system has been studied in a selected population of women referred for suspected or known adnexal lesions. This population has a higher frequency of malignant neoplasms than women presenting to radiology departments for pelvic ultrasonography for a variety of indications, potentially impacting the diagnostic performance of the risk scoring system. Objective: To evaluate the risk of malignant neoplasm and diagnostic performance of O-RADS US risk scoring system in a multi-institutional, nonselected cohort. Design, Setting, and Participants: This multi-institutional cohort study included a population of nonselected women in the United States who presented to radiology departments for routine pelvic ultrasonography between 2011 and 2014, with pathology confirmation imaging follow up or 2 years of clinical follow up. Exposure: Analysis of 1014 adnexal lesions using the O-RADS US risk stratification system. Main Outcomes and Measures: Frequency of ovarian cancer and diagnostic performance of the O-RADS US risk stratification system. Results: This study included 913 women with 1014 adnexal lesions. The mean (SD) age of the patients was 42.4 (13.9 years), and 674 of 913 (73.8%) were premenopausal. The overall frequency of malignant neoplasm was 8.4% (85 of 1014 adnexal lesions). The frequency of malignant neoplasm for O-RADS US 2 was 0.5% (3 of 657 lesions; <1% expected); O-RADS US 3, 4.5% (5 of 112 lesions; <10% expected); O-RADS US 4, 11.6% (18 of 155; 10%-50% expected); and O-RADS 5, 65.6% (59 of 90 lesions; >50% expected). O-RADS US 4 was the optimum cutoff for diagnosing cancer with sensitivity of 90.6% (95% CI, 82.3%-95.9%), specificity of 81.9% (95% CI, 79.3%-84.3%), positive predictive value of 31.4% (95% CI, 25.7%-37.7%) and negative predictive value of 99.0% (95% CI, 98.0%-99.6%). Conclusions and Relevance: In this cohort study of a nonselected patient population, the O-RADS US risk stratification system performed within the expected range as published by the ACR O-RADS US committee. The frequency of malignant neoplasm was at the lower end of the published range, partially because of the lower prevalence of cancer in a nonselected population. However, a high negative predictive value was maintained, and when a lesion can be classified as an O-RADS US 2, the risk of cancer is low, which is reassuring for both clinician and patient.

Ovarian Cancer Detection in Average-Risk Women: Classic- versus Nonclassic-appearing Adnexal Lesions at US.

Background Several US risk stratification schemas for assessing adnexal lesions exist. These multiple-subcategory systems may be more multifaceted than necessary for isolated adnexal lesions in average-risk women. Purpose To explore whether a US-based classification scheme of classic versus nonclassic appearance can be used to help appropriately triage women at average risk of ovarian cancer without compromising diagnostic performance. Materials and Methods This retrospective multicenter study included isolated ovarian lesions identified at pelvic US performed between January 2011 and June 2014, reviewed between September 2019 and September 2020. Lesions were considered isolated in the absence of ascites or peritoneal implants. Lesions were classified as classic or nonclassic based on sonographic appearance. Classic lesions included simple cysts, hemorrhagic cysts, endometriomas, and dermoids. Otherwise, lesions were considered nonclassic. Outcomes based on histopathologic results or clinical or imaging follow-up were recorded. Diagnostic performance and frequency of malignancy were calculated. Frequency of malignancy between age groups was compared using the χ2 test, and Poisson regression was used to explore relationships between imaging features and malignancy. Results A total of 970 isolated lesions in 878 women (mean age, 42 years ± 14 [SD]) were included. The malignancy rate for classic lesions was less than 1%. Of 970 lesions, 53 (6%) were malignant. The malignancy rate for nonclassic lesions was 32% (33 of 103) when blood flow was present and 8% (16 of 194) without blood flow (P < .001). For women older than 60 years, the malignancy rate was 50% (10 of 20 lesions) when blood flow was present and 13% (five of 38) without blood flow (P = .004). The sensitivity, specificity, positive predictive value, and negative predictive value of the classic-versus-nonclassic schema was 93% (49 of 53 lesions), 73% (669 of 917 lesions), 17% (49 of 297 lesions), and 99% (669 of 673 lesions), respectively, for detection of malignancy. Conclusion Using a US classification schema of classic- or nonclassic-appearing adnexal lesions resulted in high sensitivity and specificity in the diagnosis of malignancy in ovarian cancer. The highest risk of cancer was in isolated nonclassic lesions with blood flow in women older than 60 years. © RSNA, 2022 See also the editorial by Baumgarten in this issue.

O-RADS MRI Risk Stratification System: Guide for Assessing Adnexal Lesions from the ACR O-RADS Committee.

MRI plays an important role as a secondary test or problem-solving modality in the evaluation of adnexal lesions depicted at US. MRI has increased specificity compared with US, decreasing the number of false-positive diagnoses for malignancy and thereby avoiding unnecessary or over-extensive surgery in patients with benign lesions or borderline tumors, while women with possible malignancies can be expeditiously referred for oncologic surgical evaluation. The Ovarian-Adnexal Reporting and Data System (O-RADS) MRI Committee is an international collaborative effort formed under the direction of the American College of Radiology and includes a diverse group of experts on adnexal imaging and management who developed the O-RADS MRI risk stratification system. This scoring system assigns a probability of malignancy based on the MRI features of an adnexal lesion and provides information to facilitate optimal patient management. The widespread implementation of a codified reporting system will lead to improved interpretation agreement and standardized communication between radiologists and referring physicians. In addition, it will allow for high-quality multi-institutional collaborations-an important unmet need that has hampered the performance of high-quality research in this area in the past. This article provides guidelines on using the O-RADS MRI risk stratification system in clinical practice, as well as in the educational and research settings.

Neuroradiology in Transgender Care: Facial Feminization, Laryngeal Surgery, and Beyond.

Transgender individuals experience incongruence between their gender identity and the sex assigned to them at birth. This incongruence can cause many transgender individuals to experience distressing physical and mental discord, a diagnosis known as gender dysphoria. Craniofacial structures have distinct anthropometric characteristics that affect perceived masculinity and femininity. The face, neck, and voice are highly exposed anatomic areas that have recognizable gender-specific characteristics that may hinder a transgender individual's successful social integration and public acceptance. Reconstructive facial and laryngeal procedures are among the surgical options transgender persons may elect to undergo to better align their physical appearance with their gender identity. These include feminization surgeries such as facial feminization and reduction chondrolaryngoplasty, as well as masculinizing facial and laryngeal surgeries. Maxillofacial CT is frequently used in the preoperative evaluation of patients before facial feminization surgery (FFS). Several CT measurements guide surgeons to the optimal correction required in FFS to achieve appropriate aesthetic planes. Mapping important craniofacial landmarks to avoid untoward surgical complications is crucial. Transgender patients may encounter other neurologic complications that require neuroimaging evaluation. For example, gender-affirming hormone therapy (eg, estrogen and testosterone) may increase the risk of stroke or may influence growth of various hormone-sensitive tumors such as pituitary adenomas. Radiologists may interpret imaging examinations in transgender patients for routine care or for evaluation before and after facial and laryngeal surgeries and must be aware of the role of neuroimaging in the care of this population. An invited commentary by Callen is available online. The online slide presentation from the RSNA Annual Meeting is available for this article. ©RSNA, 2022.

Ovarian cancer reporting lexicon for computed tomography (CT) and magnetic resonance (MR) imaging developed by the SAR Uterine and Ovarian Cancer Disease-Focused Panel and the ESUR Female Pelvic Imaging Working Group.

OBJECTIVES: Imaging evaluation is an essential part of treatment planning for patients with ovarian cancer. Variation in the terminology used for describing ovarian cancer on computed tomography (CT) and magnetic resonance (MR) imaging can lead to ambiguity and inconsistency in clinical radiology reports. The aim of this collaborative project between Society of Abdominal Radiology (SAR) Uterine and Ovarian Cancer (UOC) Disease-focused Panel (DFP) and the European Society of Uroradiology (ESUR) Female Pelvic Imaging (FPI) Working Group was to develop an ovarian cancer reporting lexicon for CT and MR imaging. METHODS: Twenty-one members of the SAR UOC DFP and ESUR FPI working group, one radiology clinical fellow, and two gynecologic oncology surgeons formed the Ovarian Cancer Reporting Lexicon Committee. Two attending radiologist members of the committee prepared a preliminary list of imaging terms that was sent as an online survey to 173 radiologists and gynecologic oncologic physicians, of whom 67 responded to the survey. The committee reviewed these responses to create a final consensus list of lexicon terms. RESULTS: An ovarian cancer reporting lexicon was created for CT and MR Imaging. This consensus-based lexicon has 6 major categories of terms: general, adnexal lesion-specific, peritoneal carcinomatosis-specific, lymph node-specific, metastatic disease -specific, and fluid-specific. CONCLUSIONS: This lexicon for CT and MR imaging evaluation of ovarian cancer patients has the capacity to improve the clarity and consistency of reporting disease sites seen on imaging. KEY POINTS: • This reporting lexicon for CT and MR imaging provides a list of consensus-based, standardized terms and definitions for reporting sites of ovarian cancer on imaging at initial diagnosis or follow-up. • Use of standardized terms and morphologic imaging descriptors can help improve interdisciplinary communication of disease extent and facilitate optimal patient management. • The radiologists should identify and communicate areas of disease, including difficult to resect or potentially unresectable disease that may limit the ability to achieve optimal resection.