O-RADS MRI SCORE: An Essential First-Step Tool for the Characterization of Adnexal Masses.

The ovarian-adnexal reporting and data system on magnetic resonance imaging (O-RADS MRI) score is now a well-established tool to characterize pelvic gynecological masses based on their likelihood of malignancy. The main added value of O-RADS MRI over O-RADS US is to correctly reclassify lesions that were considered suspicious on US as benign on MRI. The crucial issue when characterizing an adnexal mass is to determine the presence/absence of solid tissue and thus need to perform gadolinium injection. O-RADS MR score was built on a multivariate analysis and must be applied as a step-by-step analysis: 1) Is the mass an adnexal mass? 2) Is there an associated peritoneal carcinomatosis? 3) Is there any significant amount of fatty content? 4) Is there any wall enhancement? 5) Is there any internal enhancement? 6) When an internal enhancement is detected, does the internal enhancement correspond to solid tissue or not? 7) Is the solid tissue malignant? With its high value to distinguish benign from malignant adnexal masses and its high reproducibility, the O-RADS MRI score could be a valuable tool for timely referral of a patient to an expert center for the treatment of ovarian cancers. Finally, to make a precise diagnosis allowing optimal personalized treatment, the radiologist in gynecological imaging will combine the O-RADS MRI score with many other clinical, biological, and other MR criteria to suggest a pathological hypothesis. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 3.

Consensus clustering methodology to improve molecular stratification of non-small cell lung cancer.

Recent advances in machine learning research, combined with the reduced sequencing costs enabled by modern next-generation sequencing, paved the way to the implementation of precision medicine through routine multi-omics molecular profiling of tumours. Thus, there is an emerging need of reliable models exploiting such data to retrieve clinically useful information. Here, we introduce an original consensus clustering approach, overcoming the intrinsic instability of common clustering methods based on molecular data. This approach is applied to the case of non-small cell lung cancer (NSCLC), integrating data of an ongoing clinical study (PROMOLE) with those made available by The Cancer Genome Atlas, to define a molecular-based stratification of the patients beyond, but still preserving, histological subtyping. The resulting subgroups are biologically characterized by well-defined mutational and gene-expression profiles and are significantly related to disease-free survival (DFS). Interestingly, it was observed that (1) cluster B, characterized by a short DFS, is enriched in KEAP1 and SKP2 mutations, that makes it an ideal candidate for further studies with inhibitors, and (2) over- and under-representation of inflammation and immune systems pathways in squamous-cell carcinomas subgroups could be potentially exploited to stratify patients treated with immunotherapy.

Post treatment imaging in patients with local advanced cervical carcinoma.

Cervical cancer (CC) is the fourth leading cause of death in women worldwide and despite the introduction of screening programs about 30% of patients presents advanced disease at diagnosis and 30-50% of them relapse in the first 5-years after treatment. According to FIGO staging system 2018, stage IB3-IVA are classified as locally advanced cervical cancer (LACC); its correct therapeutic choice remains still controversial and includes neoadjuvant chemo-radiotherapy, external beam radiotherapy, brachytherapy, hysterectomy or a combination of these modalities. In this review we focus on the most appropriated therapeutic options for LACC and imaging protocols used for its correct follow-up. We explore the imaging findings after radiotherapy and surgery and discuss the role of imaging in evaluating the response rate to treatment, selecting patients for salvage surgery and evaluating recurrence of disease. We also introduce and evaluate the advances of the emerging imaging techniques mainly represented by spectroscopy, PET-MRI, and radiomics which have improved diagnostic accuracy and are approaching to future direction.

Spatiotemporal optimisation of prostate intensity modulated proton therapy (IMPT) treatments.

Objective.In intensity modulated particle therapy (IMPT), the adoption of spatially and temporally heterogeneous dose distributions allows to decouple the fractionation scheme from the patient anatomy, so that an hypofractionated schedule can be selectively created inside the tumour, while simultaneously exploiting the fractionation effect in the healthy tissues. In this paper, the authors show the reproducibility of the method on a set of prostate patients, quantifying the dependencies of the achievable benefit with respect to conventional and hypofractionated schemes and the sensitivity of the method to setup errors and range uncertainty.Approach.On a cohort of 9 patients, non-uniform IMPT plans were optimised and compared to conventional and hypofractionated schedules. For each patient, the comparison of the three strategies has been based on the output of the cost function used to optimise the treatments. The analysis has been repeated considering differentα/ßratios for the tumour, namely 1.5, 3 and 4.5 Gy. For a single patient, setup errors and beam range uncertainty have been analysed: the plans, for each optimisation strategy, have been iteratively forward planned 500 times with randomly varying the patient position in each fraction, and 200 times for systematic range shift.Main results.An average 10% benefit has been shown for the lowestα/ßratio considered for the tumour, where the non-uniform schedule generally converges to hypofractionation; the benefit decreases to 5%-7% for higherα/ßratios, for which the non-uniform schedule always showed better outcomes with respect to the other fractionation schedules. An increased sensitivity to uncertainty, especially for setup errors, has been shown, which can be associated to the spatial non-uniformity of the dose distributions peculiar of the spatiotemporal plans.Significance.This work represents the first investigation of spatiotemporal fractionation for prostate cancer and the beginning of further investigations before clinical implementation can be considered.

Reference ranges for fetal brain structures using magnetic resonance imaging: systematic review.

OBJECTIVE: To evaluate the methodology of studies reporting reference ranges for fetal brain structures on magnetic resonance imaging (MRI). METHODS: MEDLINE, EMBASE, CINAHL and the Web of Science databases were searched electronically up to 31 December 2020 to identify studies investigating biometry and growth of the fetal brain and reporting reference ranges for brain structures using MRI. The primary aim was to evaluate the methodology of these studies. A list of 26 quality criteria divided into three domains, including 'study design', 'statistical and reporting methods' and 'specific aspects relevant to MRI', was developed and applied to evaluate the methodological appropriateness of each of the included studies. The overall quality score of a study, ranging between 0 and 26, was defined as the sum of scores awarded for each quality criterion and expressed as a percentage (the lower the percentage, the higher the risk of bias). RESULTS: Fifteen studies were included in this systematic review. The overall mean quality score of the studies evaluated was 48.7%. When focusing on each domain, the mean quality score was 42.0% for 'study design', 59.4% for 'statistical and reporting methods' and 33.3% for 'specific aspects relevant to MRI'. For the 'study design' domain, sample size calculation and consecutive enrolment of women were the items found to be at the highest risk of bias. For the 'statistical and reporting methods' domain, the presence of regression equations for mean and SD for each measurement, the number of measurements taken for each variable and the presence of postnatal assessment information were the items found to be at the highest risk of bias. For the 'specific aspects relevant to MRI' domain, whole fetal brain assessment was not performed in any of the included studies and was therefore considered to be the item at the highest risk of bias. CONCLUSIONS: Most of the previously published studies reporting fetal brain reference ranges on MRI are highly heterogeneous and have low-to-moderate quality in terms of methodology, which is similar to the findings reported for ultrasound studies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal MRI of CNS abnormalities.

Ultrasound (US) is currently the standard approach for the initial evaluation of fetal anatomy and maternal conditions during pregnancy; however, fetal magnetic resonance imaging (MRI) has now become a valuable adjunct to US in confirming/excluding suspected abnormalities and in the detection of additional abnormalities, thus changing the outcome of pregnancy and optimising perinatal management. MRI is a non-invasive diagnostic examination that does not involve ionising radiation and has no known associated negative side effects or reported delayed sequela according to the Safety Committee of the Society for MRI. The main drawback of MRI is fetal motion. The development of fast MRI sequences has significantly decreased fetal motion artefacts allowing the evaluation of the highly mobile fetus. Single-shot fast spin-echo (SSFSE) T2-weighted imaging is a standard sequence. T1-weighted sequences are primarily used to demonstrate haemorrhage, fat, and calcification. Balanced steady-state free-precession (SSFP) sequences are beneficial in demonstrating fetal structures as well as the heart and vessels. Diffusion-weighted imaging (DWI) and magnetic resonance spectroscopy (MRS) have important applications in fetal brain imaging. In this review, we illustrate a spectrum of structural abnormalities affecting the central nervous system and the spine. The aim of this article is to provide a practical approach for radiologists and clinicians to fetal MRI performance and interpretation.

Spontaneous hemoperitoneum in a pregnancy with endometriosis.

The protective effect of pregnancy on endometriosis is well known, but complications related to the pregnant state, such as hemoperitoneum, uroperitoneum and bowel perforation may occur.

RIDOS: A new system for online computation of the delivered dose distributions in scanning ion beam therapy.

PURPOSE: To describe a new system for scanned ion beam therapy, named RIDOS (Real-time Ion DOse planning and delivery System), which performs real time delivered dose verification integrating the information from a clinical beam monitoring system with a Graphic Processing Unit (GPU) based dose calculation in patient Computed Tomography. METHODS: A benchmarked dose computation algorithm for scanned ion beams has been parallelized and adapted to run on a GPU architecture. A workstation equipped with a NVIDIA GPU has been interfaced through a National Instruments PXI-crate with the dose delivery system of the Italian National Center of Oncological Hadrontherapy (CNAO) to receive in real-time the measured beam parameters. Data from a patient monitoring system are also collected to associate the respiratory phases with each spot during the delivery of the dose. Using both measured and planned spot properties, RIDOS evaluates during the few seconds of inter-spill time the cumulative delivered and prescribed dose distributions and compares them through a fast γ-index algorithm. RESULTS: The accuracy of the GPU-based algorithms was assessed against the CPU-based ones and the differences were found below 1‰. The cumulative planned and delivered doses are computed at the end of each spill in about 300 ms, while the dose comparison takes approximatively 400 ms. The whole operation provides the results before the next spill starts. CONCLUSIONS: RIDOS system is able to provide a fast computation of the delivered dose in the inter-spill time of the CNAO facility and allows to monitor online the dose deposition accuracy all along the treatment.

Radiobiological quantities in proton-therapy: Estimation and validation using Geant4-based Monte Carlo simulations.

PURPOSE: The Geant4 Monte Carlo simulation toolkit was used to reproduce radiobiological parameters measured by irradiating three different cancerous cell lines with monochromatic and clinical proton beams. METHODS: The experimental set-up adopted for irradiations was fully simulated with a dedicated open-source Geant4 application. Cells survival fractions was calculated coupling the Geant4 simulations with two analytical radiobiological models: one based on the LEM (Local Effect Model) approach and the other on a semi-empirical parameterisation. Results was evaluated and compared with experimental data. RESULTS AND CONCLUSIONS: The results demonstrated the Geant4 ability to reproduce radiobiological quantities for different cell lines.

'Survival': a simulation toolkit introducing a modular approach for radiobiological evaluations in ion beam therapy.

One major rationale for the application of heavy ion beams in tumour therapy is their increased relative biological effectiveness (RBE). The complex dependencies of the RBE on dose, biological endpoint, position in the field etc require the use of biophysical models in treatment planning and clinical analysis. This study aims to introduce a new software, named 'Survival', to facilitate the radiobiological computations needed in ion therapy. The simulation toolkit was written in C++ and it was developed with a modular architecture in order to easily incorporate different radiobiological models. The following models were successfully implemented: the local effect model (LEM, version I, II and III) and variants of the microdosimetric-kinetic model (MKM). Different numerical evaluation approaches were also implemented: Monte Carlo (MC) numerical methods and a set of faster analytical approximations. Among the possible applications, the toolkit was used to reproduce the RBE versus LET for different ions (proton, He, C, O, Ne) and different cell lines (CHO, HSG). Intercomparison between different models (LEM and MKM) and computational approaches (MC and fast approximations) were performed. The developed software could represent an important tool for the evaluation of the biological effectiveness of charged particles in ion beam therapy, in particular when coupled with treatment simulations. Its modular architecture facilitates benchmarking and inter-comparison between different models and evaluation approaches. The code is open source (GPL2 license) and available at https://github.com/batuff/Survival.

Tumour control in ion beam radiotherapy with different ions in the presence of hypoxia: an oxygen enhancement ratio model based on the microdosimetric kinetic model.

Few attempts have been made to include the oxygen enhancement ratio (OER) in treatment planning for ion beam therapy, and systematic studies to evaluate the impact of hypoxia in treatment with the beam of different ion species are sorely needed. The radiobiological models used to quantify the OER in such studies are mainly based on the dose-averaged LET estimates, and do not explicitly distinguish between the ion species and fractionation schemes. In this study, a new type of OER modelling, based on the microdosimetric kinetic model, taking into account the specificity of the different ions, LET spectra, tissues and fractionation schemes, has been developed. The model has been benchmarked with published in vitro data, HSG, V79 and CHO cells in aerobic and hypoxic conditions, for different ion irradiation. The model has been included in the simulation of treatments for a clinical case (brain tumour) using proton, lithium, helium, carbon and oxygen ion beams. A study of the tumour control probability (TCP) as a function of oxygen partial pressure, dose per fraction and primary ion type has been performed. The modelled OER depends on both the LET and ion type, also showing a decrease for an increased dose per fraction with a slope that depends on the LET and ion type, in good agreement with the experimental data. In the investigated clinical case, a significant increase in TCP has been found upon increasing the ion charge. Higher OER variations as a function of dose per fraction have also been found for low-LET ions (up to 15% varying from 2 to 8 Gy(RBE) for protons). This model could be exploited in the identification of treatment condition optimality in the presence of hypoxia, including fractionation and primary particle selection.

Review of technologies and procedures of clinical dosimetry for scanned ion beam radiotherapy.

In the last few years, the use of ions in radiation therapy is gaining interest and it is being considered medically necessary for a growing subset of tumours. Concurrently, the technologies involved in a particle therapy treatment are rapidly evolving, as well as the accuracy in the dose delivery in spite of the increased complexity. Since nowadays, the pencil beam scanning technique is showing very interesting features in terms of dose conformation and overall treatment outcome, the present review is intended to summarize the main procedures, detectors and tools adopted for the clinical dose verification. A list of dose measurements is provided, with the aim of being a valuable guidance for starting and future particle therapy facilities. Absorbed dose to water, relative dose, fluence and surrogates of the delivered dose are the main quantities measured by means of different detectors, specifically developed for point-like, 1D or 2D measurements. The dosimetric procedures are here categorized according to their purpose, distinguishing between system commissioning and clinical quality assurance. A separate discussion is dedicated to patient specific, in vivo and 4D dose verification, which aim at assessing the actual delivered dose. Together with the description of the currently used methods, challenges and perspectives toward an increasingly accurate and fast dose verification strategy are discussed.

MRI and US in the evaluation of fetal anomalies: The need to work together.

PURPOSE: Real-time virtual sonography (RVS) is a new technique that synchronizes real-time ultrasonography (US) and multiplanar reconstructed magnetic resonance imaging (MRI). The purpose of this study was to evaluate the feasibility and ability of RVS to assess the main pathologies in fetuses with suspected US anomalies. METHOD AND MATERIALS: Real-time virtual sonography (Hitachi, HI VISION Ascendus) was offered to 30 patients who had undergone fetal MRI. The acquired MRI image dataset was loaded into the fusion system and displayed together with the real-time US image. The ability of RVS to assess the main anatomical sites and fetal anomalies was evaluated. RESULTS: Real-time virtual sonography was technically possible in all cases. From a total of 30 patients, RVS helped the diagnosis in 10 cases. In 15 cases of encephalic pathology, fusion imaging improved the accuracy of the diagnosis; in the other 5 cases, MRI was superior to US even when using the RVS. CONCLUSION: This is a study on the feasibility and practical use of RVS. Thanks to information from both US and MRI, RVS allowed better identification of the fetal pathologies and improved the performance of the ultrasound examination. In our experience, it was really helpful in pathologies that would benefit from US follow-up.

Early and late onset complications of gynaecologic surgery: a multimodality imaging approach.

The role of imaging after surgery is pivotal to drive clinical management of early and/or late onset complications. Most frequently used imaging technique after pelvic surgery is Ultrasound (US), Magnetic Resonance Imaging (MRI) and Computed Tomography (CT). While Ultrasound is a standard procedure, using grey scale and/or colour Doppler evaluation, MRI and CT scan protocols should be derived on the basis of the specific indication of the exam. Correct evaluation of female pelvis after gynaecologic surgery, having in mind the most frequent complications, is based on the correct use of the instruments and on the experience of the examiner, who should be aware of the history of the patient, type of surgery and clinical symptoms for which the exam is required; the clinician should be aware of the possibilities and limits of the different techniques, in order to choose the most appropriate imaging modality and promptly make a correct diagnosis.

European society of urogenital radiology (ESUR) guidelines: MR imaging of pelvic endometriosis.

Endometriosis is a common gynaecological condition of unknown aetiology that primarily affects women of reproductive age. The accepted first-line imaging modality is pelvic ultrasound. However, magnetic resonance imaging (MRI) is increasingly performed as an additional investigation in complex cases and for surgical planning. There is currently no international consensus regarding patient preparation, MRI protocols or reporting criteria. Our aim was to develop clinical guidelines for MRI evaluation of pelvic endometriosis based on literature evidence and consensus expert opinion. This work was performed by a group of radiologists from the European Society of Urogenital Radiology (ESUR), experts in gynaecological imaging and a gynaecologist expert in methodology. The group discussed indications for MRI, technical requirements, patient preparation, MRI protocols and criteria for the diagnosis of pelvic endometriosis on MRI. The expert panel proposed a final recommendation for each criterion using Oxford Centre for Evidence Based Medicine (OCEBM) 2011 levels of evidence. KEY POINTS: • This report provides guidelines for MRI in endometriosis. • Minimal and optimal MRI acquisition protocols are provided. • Recommendations are proposed for patient preparation, best MRI sequences and reporting criteria.

Endometriosis and Glanzmann’s thrombasthenia.

Glanzmann’s thrombasthenia (GT) is a rare bleeding syndrome characterized by deficiency or defect of platelet aggregation complex. The pathogenesis of endometriosis is controversial but the strongest evidence leans towards retrograde menstruation. GT probably predisposes to endometriosis. The management of women affected by this disease can be difficult due to the risk of bleeding complications, especially during surgical treatment. We describe the cases of three sisters affected by endometriosis and GT, referred to our Department, who received different therapeutic management.

Assessing the association between 25-OH vitamin D levels and ROMA score in a population of obese women.

The “Risk of Malignancy Algorithm” (ROMA) combines the diagnostic power of the CA125 and HE4 markers with menopausal status to predict the risk for developing epithelial ovarian cancer (EOC). The aim of this study was to evaluate the association between 25-OH vitamin D levels and ROMA score in obese women. One hundred and eighteen patients with a Body Mass Index (BMI) > 30 kg/m2 (Group 1) and 80 women with a BMI less than 25 kg / m² (Group 2) were studied. The 25-OH vitamin D was quantified with LUMIPULSE® G 1200. As a threshold value, identified by ROC curve analysis, 20.2 ng/ mL (sensitivity 73.3%, specificity 84%) was chosen corresponding to the limit between sufficient and insufficient 25-OH vitamin D according to the World Health Organization (WHO). Low 25-OH vitamin D levels were observed in 64% of obese women and in 11% of normal-weight women (p less than 0.001). ROMA score above 13% was detected only in obese women (19%). An association between low levels of 25-OH vitamin D and ROMA score was observed. Indeed, 64% of obese women with ROMA score >13% had concomitant insufficient levels of 25-OH vitamin D, while only 36% of obese women with ROMA score >13% had sufficient 25-OH vitamin D levels (p less than 0.0001). This study suggests that the deficiency of 25- OH vitamin D in obese women has a possible correlation with high ROMA score.

Non mass-like enhancement categories detected by breast MRI and histological findings.

OBJECTIVE: To correlate the different non masslike enhancement categories detected by Magnetic Resonance Imaging (MRI) and the corresponding histological findings. PATIENTS AND METHODS: Two experienced radiologists reviewed the MRI examinations of 94 patients presenting non mass-like enhancements who had performed histological evaluation. According to the BI-RADS (Breast Imaging Reporting and Data System) lexicon, non masslike enhancements were classified as focal, linear, segmental, regional, ductal and diffuse enhancements. We focused on segmental, regional and ductal patterns. RESULTS: Among the 94 patients, 52.1% showed a regional pattern, 27.7% a segmental pattern and 20.2% a ductal pattern of enhancement. Of the 49 patients showing a regional pattern, the histological diagnosis was ductal invasive carcinoma (DIC) in 28 cases, ductal carcinoma in situ (DCIS) in 4 cases, lobular invasive carcinoma (LIC) in 3 cases and a benign disease in 9 cases. Of the 26 patients showing a segmental pattern, the histological outcome was DIC in 10 cases, DCIS in 7 cases and a benign disease in 5 cases. Among the 19 patients showing a ductal pattern, the result was DIC in 4 cases, DCIS in 4 cases and a benign disease in 7 cases. In most cases DIC presented as a regional pattern, while DCIS showed a segmental pattern in 26.9%, a ductal pattern in 21.1% and a regional pattern in 8.2% of cases. CONCLUSIONS: Our findings about ductal and segmental enhancements agree with the literature. We found a high rate of DIC presenting as a regional enhancement, instead; thus, we recommend a more detailed diagnosis, especially when an homogeneous/heterogeneous and clumped internal enhancement pattern is present.

Comparison of ultrasound and magnetic resonance imaging in the prenatal diagnosis of Apert syndrome: report of a case.

BACKGROUND: The birth prevalence of Apert syndrome is estimated at 1:64,500 and accounts for about 4.5 % of all craniosynostosis with a male/female ratio equal to 1:1. It is associated to allelic mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. Majority cases are sporadic. Prenatal ultrasound diagnosis is based on the detection of abnormal cranial shape, midfacial hypoplasia and bilateral syndactyly of hands and feet, hypertelorism, and exorbitism. Other abnormalities includes central nervous system anomalies, congenital heart diseases, cleft palate, and urogenital diseases. CASE REPORT: A 37-year-old Caucasian woman, gravida 2, para 1, was referred to our center of Prenatal Diagnosis for routine ultrasound at 21 weeks of gestation. We detected irregular head shape, dolicocephaly, prominent forehead, bilateral mild ventriculomegaly, suspicion of partial agenesis of the corpus callosum, hypertelorism, and midfacial hypoplasia, with a depressed nasal bridge and syndactyly, prompting a suspicion for Apert syndrome. Magnetic resonance excluded agenesis of corpus callosum and confirmed bilateral mild ventriculomegaly. A follow-up ultrasound, performed at 23 weeks, confirmed the anomalies showed in the previous scan. An amniocentesis was performed. The results showed a normal male karyotype, while the molecular genetic test confirmed a mutation in FGFR2 gene. Fetus macroscopic analysis showed compatible features. CONCLUSIONS: Our case underlines the complementary role of ultrasound and magnetic resonance imaging in the early prenatal diagnosis of Apert syndrome.

Magnetic resonance imaging of fetal heart: anatomical and pathological findings.

Congenital heart disease is one of the most frequent prenatal malformation representing an incidence of 5/1000 live births; moreover, it represents the first cause of death in the first year of life. There is a wide range of severity in congenital heart malformations from lesions which require no treatment such as small ventricular septal defects, to lesions which can only be treated with palliative surgery such as hypoplastic left heart syndrome. A good prenatal examination acquires great importance in order to formulate an early diagnosis and improve pregnancy management. Nowadays, echocardiography still represents the gold standard examination for fetal heart disease. However, especially when preliminary ultrasound is inconclusive, fetal MRI is considered as a third-level imaging modality. Preliminary experiences have demonstrated the validity of this reporting a diagnostic accuracy of 79%. Our article aims to outline feasibility of fetal MRI in the anatomic evaluation, the common indication to fetal MRI, its role in the characterization of congenital heart defects, and at last its main limitations.