Imaging for Early Detection of Pancreatic Ductal Adenocarcinoma: Updates and Challenges in the Implementation of Screening and Surveillance Programs.

Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive cancers. It has a poor 5-year survival rate of 12%, partly because most cases are diagnosed at advanced stages, precluding curative surgical resection. Early-stage PDA has significantly better prognoses due to increased potential for curative interventions, making early detection of PDA critically important to improved patient outcomes. We examine current and evolving early detection concepts, screening strategies, diagnostic yields among high-risk individuals, controversies, and limitations of standard-of-care imaging.

Tumor Growth Rate Informs Treatment Efficacy in Metastatic Pancreatic Adenocarcinoma: Application of a Growth and Regression Model to Pivotal Trial and Real-World Data.

BACKGROUND: Methods for screening agents earlier in development and strategies for conducting smaller randomized controlled trials (RCTs) are needed. METHODS: We retrospectively applied a tumor growth model to estimate the rates of growth of pancreatic cancer using radiographic tumor measurements or serum CA 19-9 values from 3033 patients with stages III-IV PDAC who were enrolled in 8 clinical trials or were included in 2 large real-world data sets. RESULTS: g correlated inversely with OS and was consistently lower in the experimental arms than in the control arms of RCTs. At the individual patient level, g was significantly faster for lesions metastatic to the liver relative to those localized to the pancreas. Regardless of regimen, g increased toward the end of therapy, often by over 3-fold. CONCLUSIONS: Growth rates of PDAC can be determined using radiographic tumor measurement and CA 19-9 values. g is inversely associated with OS and can differentiate therapies within the same trial and across trials. g can also be used to characterize changes in the behavior of an individual's PDAC, such as differences in the growth rate of lesions based on metastatic site, and the emergence of chemoresistance. We provide examples of how g can be used to benchmark phase II and III clinical data to a virtual reference arm to inform go/no go decisions and consider novel trial designs to optimize and accelerate drug development.

Separation of Plasmid DNA Topological Forms, Messenger RNA, and Lipid Nanoparticle Aggregates Using an Ultrawide Pore Size Exclusion Chromatography Column.

Health authorities have highlighted the need to determine oligonucleotide aggregates. However, existing technologies have limitations that have prevented the reliable analysis of size variants for large nucleic acids and lipid nanoparticles (LNPs). In this work, nucleic acid and LNP aggregation was examined using prototype, low adsorption ultrawide pore size exclusion chromatography (SEC) columns. A preliminary study was conducted to determine the column's physicochemical properties. A large difference in aggregate content (17.8 vs 59.7 %) was found for a model messenger RNA (mRNA) produced by different manufacturers. We further investigated the nature of the aggregates via a heat treatment. Interestingly, thermal stress irreversibly decreased the amount of aggregates from 59.7 to 4.1% and increased the main peak area 3.3-fold. To the best of our knowledge, for the first time, plasmid DNA topological forms and multimers were separated by analytical SEC. The degradation trends were compared to the data obtained with an anion exchange chromatography method. Finally, unconjugated and fragment antigen-binding (Fab)-guided LNPs were analyzed and their elution times were plotted against their sizes as measured by DLS. Multi-angle light scattering (MALS) was coupled to SEC in order to gain further insights on large species eluting before the LNPs, which were later identified as self-associating LNPs. This study demonstrated the utility of ultrawide pore SEC columns in characterizing the size variants of large nucleic acid therapeutics and LNPs.

A Multicenter Assessment of Interreader Reliability of LI-RADS Version 2018 for MRI and CT.

Background Various limitations have impacted research evaluating reader agreement for Liver Imaging Reporting and Data System (LI-RADS). Purpose To assess reader agreement of LI-RADS in an international multicenter multireader setting using scrollable images. Materials and Methods This retrospective study used deidentified clinical multiphase CT and MRI and reports with at least one untreated observation from six institutions and three countries; only qualifying examinations were submitted. Examination dates were October 2017 to August 2018 at the coordinating center. One untreated observation per examination was randomly selected using observation identifiers, and its clinically assigned features were extracted from the report. The corresponding LI-RADS version 2018 category was computed as a rescored clinical read. Each examination was randomly assigned to two of 43 research readers who independently scored the observation. Agreement for an ordinal modified four-category LI-RADS scale (LR-1, definitely benign; LR-2, probably benign; LR-3, intermediate probability of malignancy; LR-4, probably hepatocellular carcinoma [HCC]; LR-5, definitely HCC; LR-M, probably malignant but not HCC specific; and LR-TIV, tumor in vein) was computed using intraclass correlation coefficients (ICCs). Agreement was also computed for dichotomized malignancy (LR-4, LR-5, LR-M, and LR-TIV), LR-5, and LR-M. Agreement was compared between research-versus-research reads and research-versus-clinical reads. Results The study population consisted of 484 patients (mean age, 62 years ± 10 [SD]; 156 women; 93 CT examinations, 391 MRI examinations). ICCs for ordinal LI-RADS, dichotomized malignancy, LR-5, and LR-M were 0.68 (95% CI: 0.61, 0.73), 0.63 (95% CI: 0.55, 0.70), 0.58 (95% CI: 0.50, 0.66), and 0.46 (95% CI: 0.31, 0.61) respectively. Research-versus-research reader agreement was higher than research-versus-clinical agreement for modified four-category LI-RADS (ICC, 0.68 vs 0.62, respectively; P = .03) and for dichotomized malignancy (ICC, 0.63 vs 0.53, respectively; P = .005), but not for LR-5 (P = .14) or LR-M (P = .94). Conclusion There was moderate agreement for LI-RADS version 2018 overall. For some comparisons, research-versus-research reader agreement was higher than research-versus-clinical reader agreement, indicating differences between the clinical and research environments that warrant further study. © RSNA, 2023 Supplemental material is available for this article. See also the editorials by Johnson and Galgano and Smith in this issue.

The Organ Procurement and Transplantation Network hepatocellular carcinoma classification: Alignment with Liver Imaging Reporting and Data System, current gaps, and future direction.

The Organ Procurement and Transplantation Network (OPTN) updated its allocation policy for liver transplantation to align with the Liver Imaging Reporting and Data System (LI-RADS) for the diagnosis of hepatocellular carcinoma (HCC). LI-RADS computed tomography/magnetic resonance imaging algorithm had achieved congruency with the American Association for the Study of Liver Diseases (AASLD) HCC Practice Guidance in 2018, and therefore, alignment of OPTN, LI-RADS, and AASLD unifies HCC diagnostic approaches. The two changes to the OPTN HCC classification are adoption of LI-RADS terminology or lexicon for HCC major imaging features as well as the modification of OPTN Class-5A through the adoption of LI-RADS-5 criteria. However, despite this significant milestone, the OPTN allocation policy may benefit from further refinements such as adoption of treatment response assessment criteria after locoregional therapy and categorization criteria for lesions with atypical imaging appearances that are not specific for HCC. In this review, we detail the changes to the OPTN HCC classification to achieve alignment with LI-RADS, discuss current limitations of the OPTN classification, and explore future directions.

Percentage of Pancreatic Cysts on MRI With a Pancreatic Carcinoma: Systematic Review and Meta-Analysis.

BACKGROUND: Pancreatic cystic lesions (PCLs) are frequent on MRI and are thought to be associated with pancreatic adenocarcinoma (PDAC) necessitating long-term surveillance based on older studies suffering from selection bias. PURPOSE: To establish the percentage of patients with PCLs on MRI with a present or future PDAC. STUDY TYPE: Systematic review, meta-analysis. POPULATION: Adults with PCLs on MRI and a present or future diagnosis of PDAC were eligible. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus were searched to April 2022 (PROSPERO:CRD42022320502). Studies limited to PCLs not requiring surveillance, <100 patients, or those with a history/genetic risk of PDAC were excluded. FIELD STRENGTH/SEQUENCE: ≥1.5 T with ≥1 T2-weighted sequence. ASSESSMENT: Two investigators extracted data, with discrepancies resolved by a third. QUADAS-2 assessed bias. PDAC was diagnosed using a composite reference standard. STATISTICAL TESTS: A meta-analysis of proportions was performed at the patient-level with 95% confidence intervals (95% CI). RESULTS: Eight studies with 1289 patients contributed to the percentage of patients with a present diagnosis of PDAC, and 10 studies with 3422 patients to the percentage with a future diagnosis. Of patients with PCLs on MRI, 14.8% (95% CI 2.4-34.9) had a PDAC at initial MRI, which decreased to 6.0% (2.2-11.3) for studies at low risk of bias. For patients without PDAC on initial MRI, 2.0% (1.1-3.2) developed PDAC during surveillance, similar for low risk of bias studies at 1.9% (0.7-3.6), with no clear trend of increased PDAC for longer surveillance durations. For patients without worrisome features or high-risk stigmata, 0.9% (0.1-2.2) developed PDAC during surveillance. Of 10, eight studies had a median surveillance ≥3 years (range 3-157 months). Sources of bias included retrospectively limiting PCLs to those with histopathology and inconsistent surveillance protocols. DATA CONCLUSION: A low percentage of patients with PCLs on MRI develop PDAC while on surveillance. The first MRI revealing a PCL should be scrutinized for PDAC. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Comparing Survival Outcomes of Patients With LI-RADS-M Hepatocellular Carcinomas and Intrahepatic Cholangiocarcinomas.

BACKGROUND: There is a sparsity of data evaluating outcomes of patients with Liver Imaging Reporting and Data System (LI-RADS) (LR)-M lesions. PURPOSE: To compare overall survival (OS) and progression free survival (PFS) between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) meeting LR-M criteria and to evaluate factors associated with prognosis. STUDY TYPE: Retrospective. SUBJECTS: Patients at risk for HCC with at least one LR-M lesion with histologic diagnosis, from 8 academic centers, yielding 120 patients with 120 LR-M lesions (84 men [mean age 62 years] and 36 women [mean age 66 years]). FIELD STRENGTH/SEQUENCE: A 1.5 and 3.0 T/3D T1 -weighted gradient echo, T2 -weighted fast spin-echo. ASSESSMENT: The imaging categorization of each lesion as LR-M was made clinically by a single radiologist at each site and patient outcome measures were collected. STATISTICAL TESTS: OS, PFS, and potential independent predictors were evaluated by Kaplan-Meier method, log-rank test, and Cox proportional hazard model. A P value of <0.05 was considered significant. RESULTS: A total of 120 patients with 120 LR-M lesions were included; on histology 65 were HCC and 55 were iCCA. There was similar median OS for patients with LR-M HCC compared to patients with iCCA (738 days vs. 769 days, P = 0.576). There were no significant differences between patients with HCC and iCCA in terms of sex (47:18 vs. 37:18, P = 0.549), age (63.0 ± 8.4 vs. 63.4 ± 7.8, P = 0.847), etiology of liver disease (P = 0.202), presence of cirrhosis (100% vs. 100%, P = 1.000), tumor size (4.73 ± 3.28 vs. 4.75 ± 2.58, P = 0.980), method of lesion histologic diagnosis (P = 0.646), and proportion of patients who underwent locoregional therapy (60.0% vs. 38.2%, P = 0.100) or surgery (134.8 ± 165.5 vs. 142.5 ± 205.6, P = 0.913). Using multivariable analysis, nonsurgical compared to surgical management (HR, 4.58), larger tumor size (HR, 1.19), and higher MELD score (HR, 1.12) were independently associated with worse OS. DATA CONCLUSION: There was similar OS in patients with LR-M HCC and LR-M iCCA, suggesting that LR-M imaging features may more closely reflect patient outcomes than histology. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.

Liver Transplant for Nonhepatocellular Malignancies: A Review for Radiologists.

Although liver transplant is traditionally only performed for hepatocellular carcinoma (HCC), the last decade has seen a resurgence in its use for non-HCC malignancies, likely due to improvements in neoadjuvant treatment regimens and the establishment of well-defined eligibility criteria. Given promising survival results, patients with perihilar cholangiocarcinoma, neuroendocrine liver metastases, and hepatic hemangioendothelioma are eligible to receive Model for End-Stage Liver Disease (MELD) exception points for tumors that meet well-defined criteria. Patients with additional tumors such as colorectal cancer liver metastases, intrahepatic cholangiocarcinoma, and hepatocellular cholangiocarcinoma may undergo transplant at specialized centers with well-defined protocols, although these patients are not yet eligible for MELD exception. Transplant eligibility criteria commonly incorporate imaging findings; however, because of the relatively novel and evolving nature of liver transplant for non-HCC malignancies, radiologists may be unaware of relevant criteria or the implications of their imaging interpretations. Knowledge of the allocation process, previous studies, and liver transplant selection criteria facilitates radiologists' active participation in multidisciplinary discussion, leading to better and more equitable care for transplant candidates with non-HCC malignancy. This review provides an overview of transplant allocation and selection criteria in patients with non-HCC malignancy, with an emphasis on imaging features and the role of the radiologist.

Standardization of MRI Screening and Reporting in Individuals With Elevated Risk of Pancreatic Ductal Adenocarcinoma: Consensus Statement of the PRECEDE Consortium.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with a dismal survival rate. Screening the general population for early detection of PDAC is not recommended, but because early detection improves survival, high-risk individuals, defined as those meeting criteria based on a family history of PDAC and/or the presence of known pathogenic germline variant genes with PDAC risk, are recommended to undergo screening with MRI and/or endoscopic ultrasound at regular intervals. The Pancreatic Cancer Early Detection (PRECEDE) Consortium was formed in 2018 and is composed of gastroenterologists, geneticists, pancreatic surgeons, radiologists, statisticians, and researchers from 40 sites in North America, Europe, and Asia. The overarching goal of the PRECEDE Consortium is to facilitate earlier diagnosis of PDAC for high-risk individuals to increase survival of the disease. A standardized MRI protocol and reporting template are needed to enhance the quality of screening examinations, improve consistency of clinical management, and facilitate multiinstitutional research. We present a consensus statement to standardize MRI screening and reporting for individuals with elevated risk of pancreatic cancer.

MR Angiography Series: MR Angiography of the Extremities.

MR angiography (MRA) is a powerful tool for imaging of the extremities, allowing a thorough assessment of the arteries and veins in both the upper and lower limbs. Both contrast-enhanced and noncontrast MRA techniques are described in the online presentation, including practical tips and tricks to obtain all necessary information at every examination. This module is the sixth and final segment in a series created on behalf of the Society for Magnetic Resonance Angiography (SMRA), a group of researchers and clinicians who are passionate about the benefits of MRA but understand its challenges. The full digital presentation is available online. ©RSNA, 2022.

MR Angiography Series: Abdominal and Pelvic MR Angiography.

This review guides readers through the selection and setup of standardized MR angiography (MRA) protocols for the abdomen and pelvis for common clinical applications. Topics covered include renovascular MRA in potential kidney donors and in patients with hypertension; hepatic and mesenteric MRA in potential liver donors, patients with portal hypertension, and patients with chronic mesenteric ischemia; pelvic MRA for pretreatment planning before uterine fibroid embolization and in patients with pelvic congestion syndrome; and abdominal wall MRA for planning of breast reconstructive surgery. This module is the fifth in a series created on behalf of the Society for Magnetic Resonance Angiography (SMRA), a group of researchers and clinicians who are passionate about the benefits of MRA but understand its challenges. The full digital presentation is available online. ©RSNA, 2022.

MR Angiography Series: Noncardiac Chest MR Angiography.

This review guides readers through the selection and setup of standardized noncardiac chest MRA protocols, including contrast-enhanced MRA (CE-MRA) and noncontrast MRA (NC-MRA), sequences that can be used in a variety of clinical situations. After reviewing basic principles described in the first three tutorials in this series on CE-MRA and NC-MRA, this online presentation details the use of MRA in specific clinical scenarios: thoracic aortic aneurysm, aortic dissection, congenital heart disease, vasculitis, central veins, and pulmonary embolus. Tips and tricks for optimization of the sequences, image acquisition, and image interpretation are provided. This module is the fourth in a series created on behalf of the Society for Magnetic Resonance Angiography (SMRA), a group of researchers and clinicians who are passionate about the benefits of MRA but understand its challenges. The full digital presentation is available online. ©RSNA, 2022.

Imaging Features of Premalignant Biliary Lesions and Predisposing Conditions with Pathologic Correlation.

Biliary malignancies include those arising from the intrahepatic and extrahepatic bile ducts as well as the gallbladder and hepatopancreatic ampulla of Vater. The majority of intrahepatic and extrahepatic malignancies are cholangiocarcinomas (CCAs). They arise owing to a complex interplay between the patient-specific genetic background and multiple risk factors and may occur in the liver (intrahepatic CCA), hilum (perihilar CCA), or extrahepatic bile ducts (distal CCA). Biliary-type adenocarcinoma constitutes the most common histologic type of ampullary and gallbladder malignancies. Its prognosis is poor and surgical resection is considered curative, so early detection is key, with multimodality imaging playing a central role in making the diagnosis. There are several risk factors for biliary malignancy as well as predisposing conditions that increase the risk; this review highlights the pertinent imaging features of these entities with histopathologic correlation. The predisposing factors are broken down into three major categories: (a) congenital malformations such as choledochal cyst and pancreaticobiliary maljunction; (b) infectious or inflammatory conditions such as parasitic infections, hepatolithiasis, primary sclerosing cholangitis, and porcelain gallbladder; and (c) preinvasive epithelial neoplasms such as biliary intraepithelial neoplasm, intraductal papillary neoplasm of the bile duct, intra-ampullary papillary tubular neoplasm, and intracholecystic papillary neoplasm of the gallbladder. Recognizing the baseline features of these premalignant biliary entities and changes in their appearance over time that indicate the advent of malignancy in high-risk patients can lead to early diagnosis and potentially curative management. An invited commentary by Volpacchio is available online. Online supplemental material is available for this article. ©RSNA, 2022.

Machine learning in cardiovascular radiology: ESCR position statement on design requirements, quality assessment, current applications, opportunities, and challenges.

Machine learning offers great opportunities to streamline and improve clinical care from the perspective of cardiac imagers, patients, and the industry and is a very active scientific research field. In light of these advances, the European Society of Cardiovascular Radiology (ESCR), a non-profit medical society dedicated to advancing cardiovascular radiology, has assembled a position statement regarding the use of machine learning (ML) in cardiovascular imaging. The purpose of this statement is to provide guidance on requirements for successful development and implementation of ML applications in cardiovascular imaging. In particular, recommendations on how to adequately design ML studies and how to report and interpret their results are provided. Finally, we identify opportunities and challenges ahead. While the focus of this position statement is ML development in cardiovascular imaging, most considerations are relevant to ML in radiology in general. KEY POINTS: • Development and clinical implementation of machine learning in cardiovascular imaging is a multidisciplinary pursuit. • Based on existing study quality standard frameworks such as SPIRIT and STARD, we propose a list of quality criteria for ML studies in radiology. • The cardiovascular imaging research community should strive for the compilation of multicenter datasets for the development, evaluation, and benchmarking of ML algorithms.

MR Angiography Series: Fundamentals of Non-Contrast-enhanced MR Angiography.

Unlike CT angiography, which requires the use of contrast medium, MR angiography (MRA) can be performed without the use of contrast agents. This subfield of MRA is referred to as non-contrast-enhanced MRA (NC-MRA). While NC-MRA can be performed in many patients, it is especially useful in the imaging of pediatric and pregnant patients, as well as in patients with renal impairment. NC-MRA can also provide unique functional and hemodynamic information that is not obtainable with CT angiography or contrast-enhanced MRA. This module gives an overview of the predominant NC-MRA techniques that are currently available on modern clinical MRI systems, while also discussing some new and emerging topics in the field. This module is the second in a series created on behalf of the Society for Magnetic Resonance Angiography (SMRA), a group of researchers and clinicians who are passionate about the benefits of MRA but understand its challenges. The full digital presentation is available online. ©RSNA, 2021.

MR Angiography Series: Neurovascular MR Angiography.

Neurovascular MR angiography (MRA) is an evolving imaging technique and is crucial for the workup of numerous neurologic disorders. While CT angiography (CTA) provides a more rapid imaging assessment, in select patients it can impart a small risk of contrast material-induced nephrotoxicity or radiation-associated cancers. In addition, MRA offers some advantages over CTA for neurovascular evaluation, including higher temporal resolution and the capability for vessel wall imaging. This module is the third in a series created on behalf of the Society for Magnetic Resonance Angiography (SMRA), a group of researchers and clinicians who are passionate about the benefits of MRA but understand its challenges. The full digital presentation is available online. Work of the U.S. Government published under an exclusive license with the RSNA.

MR Angiography Series: Fundamentals of Contrast-enhanced MR Angiography.

The Society for Magnetic Resonance Angiography (SMRA) is a group of researchers and clinicians who are passionate about the benefits of MR angiography (MRA) but understand its challenges. Their mission is to study MRA, continually improve and innovate for the benefit of patients, and most important, educate the medical community so they can take full advantage of the benefits of MRA and overcome its challenges. In support of that mission, the authors have created a series of self-learning modules on behalf of the SMRA to demystify MRA protocols and help the reader perform patient-friendly high-quality MRA on a routine basis in clinical practice. The full digital presentation is available online. ©RSNA, 2021.

Athletic Injuries of the Thoracic Cage.

A variety of sports require exposure to high-impact trauma or characteristic repetitive movements that predispose to injuries around the thorax. Appropriate prognostication and timely management are vital, as untreated or undertreated injuries can lead to pain, disability, loss of playing time, or early termination of sports participation. The authors review common athletic injuries of the thoracic cage, encompassing muscular, osseous, and vascular conditions, with an emphasis on mechanism, imaging features, and management. The authors also review pertinent soft-tissue and bony anatomy, along with relevant sports biomechanics. Generalized muscle trauma and more specific injuries involving the pectoralis major, latissimus dorsi, teres major, pectoralis minor, lateral abdominal wall and intercostals, serratus anterior, and rectus abdominis muscles are discussed. Osseous injuries such as stress fractures, sternoclavicular dislocation, costochondral fractures, and scapular fractures are included. Finally, thoracic conditions such as snapping scapula, thoracic outlet syndrome, and Paget-Schroetter syndrome are also described. Specific MRI protocols are highlighted to address imaging challenges such as the variable anatomic orientation of thoracic structures and artifact from breathing motion. Athletes are susceptible to a wide range of musculoskeletal thoracic trauma. An accurate imaging diagnosis of thoracic cage injury and assessment of injury severity allow development of an adequate treatment plan. This can be facilitated by an understanding of functional anatomy, sports biomechanics, and the unique injuries for which athletes are at risk. ©RSNA, 2021.

Noncontrast Magnetic Resonance Angiography in the Era of Nephrogenic Systemic Fibrosis and Gadolinium Deposition.

ABSTRACT: Gadolinium-based contrast agents for clinical magnetic resonance imaging are overall safe. However, the discovery of nephrogenic systemic fibrosis in patients with severe renal impairment and gadolinium deposition in patients receiving contrast have generated developments in contrast-free imaging of the vasculature, that is, noncontrast magnetic resonance angiography. This article presents an update on noncontrast magnetic resonance angiography techniques, with comparison to other imaging alternatives. Potential benefits and challenges to implementation, and evidence to date for various clinical applications are discussed.