Development and validation of an image biomarker to identify metabolic dysfunction associated steatohepatitis: MR-MASH score.

BACKGROUND AND AIMS: Diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) requires histology. In this study, a magnetic resonance imaging (MRI) score was developed and validated to identify MASH in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Secondarily, a screening strategy for MASH diagnosis was investigated. METHODS: This prospective multicentre study included 317 patients with biopsy-proven MASLD and contemporaneous MRI. The discovery cohort (Spain, Portugal) included 194 patients. NAFLD activity score (NAS) and fibrosis were assessed with the NASH-CRN histologic system. MASH was defined by the presence of steatosis, lobular inflammation, and ballooning, with NAS ≥4 with or without fibrosis. An MRI-based composite biomarker of Proton Density Fat Fraction and waist circumference (MR-MASH score) was developed. Findings were afterwards validated in an independent cohort (United States, Spain) with different MRI protocols. RESULTS: In the derivation cohort, 51% (n = 99) had MASH. The MR-MASH score identified MASH with an AUC = .88 (95% CI .83-.93) and strongly correlated with NAS (r = .69). The MRI score lower cut-off corresponded to 88% sensitivity with 86% NPV, while the upper cut-off corresponded to 92% specificity with 87% PPV. MR-MASH was validated with an AUC = .86 (95% CI .77-.92), 91% sensitivity (lower cut-off) and 87% specificity (upper cut-off). A two-step screening strategy with sequential MR-MASH examination performed in patients with indeterminate-high FIB-4 or transient elastography showed an 83-84% PPV to identify MASH. The AUC of MR-MASH was significantly higher than that of the FAST score (p < .001). CONCLUSIONS: The MR-MASH score has clinical utility in the identification and management of patients with MASH at risk of progression.

Pancreatic steatosis and iron overload increases cardiovascular risk in non-alcoholic fatty liver disease.

Objective: To assess the prevalence of pancreatic steatosis and iron overload in non-alcoholic fatty liver disease (NAFLD) and their correlation with liver histology severity and the risk of cardiometabolic diseases. Method: A prospective, multicenter study including NAFLD patients with biopsy and paired Magnetic Resonance Imaging (MRI) was performed. Liver biopsies were evaluated according to NASH Clinical Research Network, hepatic iron storages were scored, and digital pathology quantified the tissue proportionate areas of fat and iron. MRI-biomarkers of fat fraction (PDFF) and iron accumulation (R2*) were obtained from the liver and pancreas. Different metabolic traits were evaluated, cardiovascular disease (CVD) risk was estimated with the atherosclerotic CVD score, and the severity of iron metabolism alteration was determined by grading metabolic hiperferritinemia (MHF). Associations between CVD, histology and MRI were investigated. Results: In total, 324 patients were included. MRI-determined pancreatic iron overload and moderate-to severe steatosis were present in 45% and 25%, respectively. Liver and pancreatic MRI-biomarkers showed a weak correlation (r=0.32 for PDFF, r=0.17 for R2*). Pancreatic PDFF increased with hepatic histologic steatosis grades and NASH diagnosis (p<0.001). Prevalence of pancreatic steatosis and iron overload increased with the number of metabolic traits (p<0.001). Liver R2* significantly correlated with MHF (AUC=0.77 [0.72-0.82]). MRI-determined pancreatic steatosis (OR=3.15 [1.63-6.09]), and iron overload (OR=2.39 [1.32-4.37]) were independently associated with high-risk CVD. Histologic diagnosis of NASH and advanced fibrosis were also associated with high-risk CVD. Conclusion: Pancreatic steatosis and iron overload could be of utility in clinical decision-making and prognostication of NAFLD.

Pancreatic cancer, radiomics and artificial intelligence.

Patients with pancreatic ductal adenocarcinoma (PDAC) are generally classified into four categories based on contrast-enhanced CT at diagnosis: resectable, borderline resectable, unresectable, and metastatic disease. In the initial grading and staging of PDAC, structured radiological templates are useful but limited, as there is a need to define the aggressiveness and microscopic disease stage of these tumours to ensure adequate treatment allocation. Quantitative imaging analysis allows radiomics and dynamic imaging features to provide information of clinical outcomes, and to construct clinical models based on radiomics signatures or imaging phenotypes. These quantitative features may be used as prognostic and predictive biomarkers in clinical decision-making, enabling personalised management of advanced PDAC. Deep learning and convolutional neural networks also provide high level bioinformatics tools that can help define features associated with a given aspect of PDAC biology and aggressiveness, paving the way to define outcomes based on these features. Thus, the prediction of tumour phenotype, treatment response and patient prognosis may be feasible by using such comprehensive and integrated radiomics models. Despite these promising results, quantitative imaging is not ready for clinical implementation in PDAC. Limitations include the instability of metrics and lack of external validation. Large properly annotated datasets, including relevant semantic features (demographics, blood markers, genomics), image harmonisation, robust radiomics analysis, clinically significant tasks as outputs, comparisons with gold-standards (such as TNM or pretreatment classifications) and fully independent validation cohorts, will be required for the development of trustworthy radiomics and artificial intelligence solutions to predict PDAC aggressiveness in a clinical setting.

Glioblastoma versus solitary brain metastasis: MRI differentiation using the edema perfusion gradient.

BACKGROUND AND PURPOSE: Differentiation between glioblastoma multiforme (GBM) and solitary brain metastasis (SBM) remains a challenge in neuroradiology with up to 40% of the cases to be incorrectly classified using only conventional MRI. The inclusion of perfusion MRI parameters provides characteristic features that could support the distinction of these pathological entities. On these grounds, we aim to use a perfusion gradient in the peritumoral edema. METHODS: Twenty-four patients with GBM or an SBM underwent conventional and perfusion MR imaging sequences before tumors' surgical resection. After postprocessing of the images, quantification of dynamic susceptibility contrast (DSC) perfusion parameters was made. Three concentric areas around the tumor were defined in each case. The monocompartimental and pharmacokinetics parameters of perfusion MRI were analyzed in both series. RESULTS: DSC perfusion MRI models can provide useful information for the differentiation between GBM and SBM. It can be observed that most of the perfusion MR parameters (relative cerebral blood volume, relative cerebral blood flow, relative Ktrans, and relative volume fraction of the interstitial space) clearly show higher gradient for GBM than SBM. GBM also demonstrates higher heterogeneity in the peritumoral edema and most of the perfusion parameters demonstrate higher gradients in the area closest to the enhancing tumor. CONCLUSION: Our results show that there is a difference in the perfusion parameters of the edema between GBM and SBM demonstrating a vascularization gradient. This could help not only for the diagnosis, but also for planning surgical or radiotherapy treatments delineating the real extension of the tumor.

Automated Whole-Liver MRI Segmentation to Assess Steatosis and Iron Quantification in Chronic Liver Disease.

Background Standardized manual region of interest (ROI) sampling strategies for hepatic MRI steatosis and iron quantification are time consuming, with variable results. Purpose To evaluate the performance of automatic MRI whole-liver segmentation (WLS) for proton density fat fraction (PDFF) and iron estimation (transverse relaxometry [R2*]) versus manual ROI, with liver biopsy as the reference standard. Materials and Methods This prospective, cross-sectional, multicenter study recruited participants with chronic liver disease who underwent liver biopsy and chemical shift-encoded 3.0-T MRI between January 2017 and January 2021. Biopsy evaluation included histologic grading and digital pathology. MRI liver sampling strategies included manual ROI (two observers) and automatic whole-liver (deep learning algorithm) segmentation for PDFF- and R2*-derived measurements. Agreements between segmentation methods were measured using intraclass correlation coefficients (ICCs), and biases were evaluated using Bland-Altman analyses. Linear regression analyses were performed to determine the correlation between measurements and digital pathology. Results A total of 165 participants were included (mean age ± standard deviation, 55 years ± 12; 96 women; 101 of 165 participants [61%] with nonalcoholic fatty liver disease). Agreements between mean measurements were excellent, with ICCs of 0.98 for both PDFF and R2*. The median bias was 0.5% (interquartile range, -0.4% to 1.2%) for PDFF and 2.7 sec-1 (interquartile range, 0.2-5.3 sec-1) for R2* (P < .001 for both). Margins of error were lower for WLS than ROI-derived parameters (-0.03% for PDFF and -0.3 sec-1 for R2*). ROI and WLS showed similar performance for steatosis (ROI AUC, 0.96; WLS AUC, 0.97; P = .53) and iron overload (ROI AUC, 0.85; WLS AUC, 0.83; P = .09). Correlations with digital pathology were high (P < .001) between the fat ratio and PDFF (ROI r = 0.89; WLS r = 0.90) and moderate (P < .001) between the iron ratio and R2* (ROI r = 0.65; WLS r = 0.64). Conclusion Proton density fat fraction and transverse relaxometry measurements derived from MRI automatic whole-liver segmentation (WLS) were accurate for steatosis and iron grading in chronic liver disease and correlated with digital pathology. Automated WLS estimations were higher, with a lower margin of error than manual region of interest estimations. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Moura Cunha and Fowler in this issue.

Mapping the scientific research on radiology departments: Global trends in publication, collaboration and trending topics.

PURPOSE: To characterize the global research trend in radiology departments based on bibliometric indicators. MATERIAL AND METHOD: As a source of information, Science Citation Index Expanded and Journal Citation Reports from Web of Science Core Collection (WoSCC) were used. Annual trends, journals of publication, subject categories of journals, collaboration indexes between authors and institutions, network of cowords and most cited papers were identified and analysed. The period of study was 2009-2018. RESULTS: 283,587 downloaded papers were analysed. The number of articles was increasing, as well as the percentage of funded works. Papers were published in 7314 different journals, being the most productive Plos One (5077), followed by American Journal of Roentgenology (4602) and European Radiology (3644). Most productive subject categories of journals were Radiology, Nuclear Medicine & Medical Imaging (86,568 papers), Clinical Neurology (29,722) and Surgery (23,564). International collaboration has increased more than 5 points, from 15.2% in 2009 to 20.7% in 2018. CONCLUSIONS: Most cited articles were published in high impact journals outside the scope of diagnostic imaging. Most influential topics included technical innovations within imaging modalities. MRI replaced conventional radiography and CT as the imaging technique of choice in imaging research.

Early treatment with anti-tumor necrosis factor agents improves long-term effectiveness in symptomatic stricturing Crohn's disease.

BACKGROUND: There is limited evidence on the effectiveness of biological therapy in stricturing complications in patients with Crohn's disease. AIM: The study aims to determine the effectiveness of anti-tumor necrosis factor (TNF) agents in Crohn's disease complicated with symptomatic strictures. METHODS: In this multicentric and retrospective study, we included adult patients with symptomatic stricturing Crohn's disease receiving their first anti-TNF therapy, with no previous history of biological, endoscopic or surgical therapy. The effectiveness of the anti-TNF agent was defined as a composite outcome combining steroid-free drug persistence with no use of new biologics or immunomodulators, hospital admission, surgery or endoscopic therapy during follow-up. RESULTS: Overall, 262 patients with Crohn's disease were included (53% male; median disease duration, 35 months, 15% active smokers), who received either infliximab (N = 141, 54%) or adalimumab (N = 121, 46%). The treatment was effective in 87% and 73% of patients after 6 and 12 months, respectively, and continued to be effective in 26% after a median follow-up of 40 months (IQR, 19-85). Nonetheless, 15% and 21% of individuals required surgery after 1 and 2 years, respectively, with an overall surgery rate of 32%. Postoperative complications were identified in 15% of patients, with surgical site infection as the most common. Starting anti-TNF therapy in the first 18 months after the diagnosis of Crohn's disease or the identification of stricturing complications was associated with a higher effectiveness (HR 1.62, 95% CI 1.18-2.22; and HR 1.55, 95% CI 1.1-2.23; respectively). Younger age, lower albumin levels, strictures located in the descending colon, concomitant aminosalicylates use or presence of lymphadenopathy were associated with lower effectiveness. CONCLUSIONS: Anti-TNF agents are effective in approximately a quarter of patients with Crohn's disease and symptomatic intestinal strictures, and 68% of patients are free of surgery after a median of 40 months of follow-up. Early treatment and some potential predictors of response were associated with treatment success in this setting.

Talipes Equinovarus Treatment in Infants Treated by the Ponseti Method Compared With Posterior-Only Release: A Mid-Childhood Comparison of Results.

The aim of this study is to evaluate children in middle childhood with clubfoot treated with Ponseti method vs posterior-only release and to compare their results to a control group with 4 modules (physical examination, gait study, radiographic measurements, and questionnaires). From 01/01/2004 until 01/01/2009, 31 children (45 feet) were treated with the posterior-only release protocol and 22 patients (34 feet) were treated with the Ponseti method. In 2016, patients were evaluated and compared with 25 children without neuromuscular disorders. Parents completed 3 outcome questionnaires. Radiographs evaluated residual deformity and osteoarthritis. A physical examination and a 3-dimensional gait analysis were performed to evaluate range of motion, kinematic, and kinetic data. Recurrence rate was similar between treatment groups; however, type of surgery to treat residual deformity was more aggressive in the posterior-only release (91% required major surgery), p = .024. Radiographic examination showed similar residual deformity with greater hindfoot varus in posterior-only release (68%), p = .02. Reduced cadence, increased stance dorsiflexion, calcaneus gait and forced eversion prior to swing were the main characteristics of gait in posterior-only release. Four (11%) feet treated with posterior-only release vs 11 (33%) feet treated with Ponseti method had a normal gait, p = .016. Our study showed that biomechanical function and long-term outcomes of children in middle childhood treated with the Ponseti method more closely compare with healthy individuals than those treated using posterior-only surgical technique.

Core curriculum illustration: epiploic appendagitis.

This is the 45th installment of a series that will highlight one case per publication issue from the bank of cases available online as part of the American Society of Emergency Radiology (ASER) educational resources. Our goal is to generate more interest in and use of our online materials. To view more cases online, please visit the ASER Core Curriculum and Recommendations for Study online at: http://www.erad.org/page/CCIP_TOC.

Multi-parametric MR Imaging Biomarkers Associated to Clinical Outcomes in Gliomas: A Systematic Review.

PURPOSE: To systematically review evidence regarding the association of multiparametric biomarkers with clinical outcomes and their capacity to explain relevant subcompartments of gliomas. MATERIALS AND METHODS: Scopus database was searched for original journal papers from January 1st, 2007 to February 20th, 2017 according to PRISMA. Four hundred forty-nine abstracts of papers were reviewed and scored independently by two out of six authors. Based on those papers we analyzed associations between biomarkers, subcompartments within the tumor lesion, and clinical outcomes. From all the articles analyzed, the twenty-seven papers with the highest scores were highlighted to represent the evidence about MR imaging biomarkers associated with clinical outcomes. Similarly, eighteen studies defining subcompartments within the tumor region were also highlighted to represent the evidence of MR imaging biomarkers. Their reports were critically appraised according to the QUADAS-2 criteria. RESULTS: It has been demonstrated that multi-parametric biomarkers are prepared for surrogating diagnosis, grading, segmentation, overall survival, progression-free survival, recurrence, molecular profiling and response to treatment in gliomas. Quantifications and radiomics features obtained from morphological exams (T1, T2, FLAIR, T1c), PWI (including DSC and DCE), diffusion (DWI, DTI) and chemical shift imaging (CSI) are the preferred MR biomarkers associated to clinical outcomes. Subcompartments relative to the peritumoral region, invasion, infiltration, proliferation, mass effect and pseudo flush, relapse compartments, gross tumor volumes, and highrisk regions have been defined to characterize the heterogeneity. For the majority of pairwise cooccurrences, we found no evidence to assert that observed co-occurrences were significantly different from their expected co-occurrences (Binomial test with False Discovery Rate correction, α=0.05). The co-occurrence among terms in the studied papers was found to be driven by their individual prevalence and trends in the literature. CONCLUSION: Combinations of MR imaging biomarkers from morphological, PWI, DWI and CSI exams have demonstrated their capability to predict clinical outcomes in different management moments of gliomas. Whereas morphologic-derived compartments have been mostly studied during the last ten years, new multi-parametric MRI approaches have also been proposed to discover specific subcompartments of the tumors. MR biomarkers from those subcompartments show the local behavior within the heterogeneous tumor and may quantify the prognosis and response to treatment of gliomas.

Glioblastoma: Vascular Habitats Detected at Preoperative Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging Predict Survival.

Purpose To determine if preoperative vascular heterogeneity of glioblastoma is predictive of overall survival of patients undergoing standard-of-care treatment by using an unsupervised multiparametric perfusion-based habitat-discovery algorithm. Materials and Methods Preoperative magnetic resonance (MR) imaging including dynamic susceptibility-weighted contrast material-enhanced perfusion studies in 50 consecutive patients with glioblastoma were retrieved. Perfusion parameters of glioblastoma were analyzed and used to automatically draw four reproducible habitats that describe the tumor vascular heterogeneity: high-angiogenic and low-angiogenic regions of the enhancing tumor, potentially tumor-infiltrated peripheral edema, and vasogenic edema. Kaplan-Meier and Cox proportional hazard analyses were conducted to assess the prognostic potential of the hemodynamic tissue signature to predict patient survival. Results Cox regression analysis yielded a significant correlation between patients' survival and maximum relative cerebral blood volume (rCBVmax) and maximum relative cerebral blood flow (rCBFmax) in high-angiogenic and low-angiogenic habitats (P < .01, false discovery rate-corrected P < .05). Moreover, rCBFmax in the potentially tumor-infiltrated peripheral edema habitat was also significantly correlated (P < .05, false discovery rate-corrected P < .05). Kaplan-Meier analysis demonstrated significant differences between the observed survival of populations divided according to the median of the rCBVmax or rCBFmax at the high-angiogenic and low-angiogenic habitats (log-rank test P < .05, false discovery rate-corrected P < .05), with an average survival increase of 230 days. Conclusion Preoperative perfusion heterogeneity contains relevant information about overall survival in patients who undergo standard-of-care treatment. The hemodynamic tissue signature method automatically describes this heterogeneity, providing a set of vascular habitats with high prognostic capabilities. © RSNA, 2018.

Use of whole body CT to detect patterns of CPR-related injuries after sudden cardiac arrest.

AIMS AND OBJECTIVES: We have recently implemented a dedicated sudden cardiac arrest (SCA) - whole-body computed tomography (WBCT) protocol to evaluate SCA patients with return of spontaneous circulation (ROSC) following cardiopulmonary resuscitation (CPR). The aim of this study is to evaluate the number and pattern of CPR-related injuries in ROSC patients with SCA-WBCT. METHODS AND MATERIALS: Single-centre retrospective review of 39 patients (13 female; 20 male, mean age 51.8 years) with non-traumatic, out-of-hospital SCA and ROSC and evaluation with dedicated SCA-WBCT over a 10-month period. RESULTS: In-hospital mortality was 54%. CPR-related injuries were detected in 85% (33/39). Chest injuries were most common on WBCT: 85% (33) subjects had rib fractures (mean of 8.5 fractures/subject); 31% (12) sternal fractures; 13% (5) mediastinal haematoma; 10% (4) pneumothorax; 8% (3) pneumomediastinum and 3% (1) haemothorax. Three subjects (8%) had abdominal injuries on WBCT, including one hepatic haematoma with active haemorrhage. CONCLUSION: CPR-related injuries on WBCT after ROSC are common, with serial rib fractures detected most commonly. An unexpectedly high rate of abdominal injuries was detected on SCA-WBCT. Radiologists need to be attuned to the spectrum of CPR-related injuries in WBCT, including abdominal injuries and subtle rib fractures. KEY POINTS: • CPR frequently causes injuries. • Radiologists should be aware of the spectrum of CPR related injuries. • Rib fractures are frequent and radiologic findings often subtle. • Clinically unexpected abdominal injuries may be present.

Post-treatment changes of tumour perfusion parameters can help to predict survival in patients with high-grade astrocytoma.

OBJECTIVES: Vascular characteristics of tumour and peritumoral volumes of high-grade gliomas change with treatment. This work evaluates the variations of T2*-weighted perfusion parameters as overall survival (OS) predictors. METHODS: Forty-five patients with histologically confirmed high-grade astrocytoma (8 grade III and 37 grade IV) were included. All patients underwent pre- and post-treatment T2*-weighted contrast-enhanced magnetic resonance (MR) imaging. Tumour, peritumoral and control volumes were segmented. Relative variations of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), Ktrans-T2*, kep-T2*, ve-T2* and vp-T2* were calculated. Differences regarding tumour grade and surgical resection extension were evaluated with ANOVA tests. For each parameter, two groups were defined by non-supervised clusterisation. Survival analysis were performed on these groups. RESULTS: For the tumour region, the 90th percentile increase or stagnation of CBV was associated with shorter survival, while a decrease related to longer survival (393 ± 189 vs 594 ± 294 days; log-rank p = 0.019; Cox hazard-ratio, 2.31; 95% confidence interval [CI], 1.12-4.74). Ktrans-T2* showed similar results (414 ± 177 vs 553 ± 312 days; log-rank p = 0.037; hazard-ratio, 2.19; 95% CI, 1.03-4.65). The peritumoral area values showed no relationship with OS. CONCLUSIONS: Post-treatment variations of the highest CBV and Ktrans-T2* values in the tumour volume are predictive factors of OS in patients with high-grade gliomas. KEY POINTS: • Vascular characteristics of high-grade glioma tumour and peritumoral regions change with treatment. • Quantitative assessment of MRI perfusion provides valuable information regarding tumour aggressiveness. • Quantitative T2*-weighted perfusion parameters can help to predict overall survival. • Post-treatment variations of CBV and K trans-T2 values are predictive factors of OS. • Increased values may justify treatment intensification in these patients.

ASER core curriculum illustration project: aortic intramural hematoma (IMH).

This is the 23rd installment of a series that will highlight one case per publication issue from the bank of cases available online as part of the American Society of Emergency Radiology (ASER) educational resources. Our goal is to generate more interest in and use of our online materials. To view more cases online, please visit the ASER Core Curriculum and Recommendations for Study online at http://www.aseronline.org/curriculum/toc.htm .

Core curriculum illustration: rib fractures.

This is the 24th installment of a series that will highlight one case per publication issue from the bank of cases available online as part of the American Society of Emergency Radiology (ASER) educational resources. Our goal is to generate more interest in and use of our online materials. To view more cases online, please visit the ASER Core Curriculum and Recommendations for Study online at http://www.aseronline.org/curriculum/toc.htm .