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.

Atomically Precise Defective Copper Nanocluster Catalysts for Highly Selective C-C Cross-Coupling Reactions.

Point defects in nanoparticles have long been hypothesized to play an important role in governing the particle's electronic structure and physicochemical properties. However, single point defects in material systems usually exist with other heterogeneities, obscuring the chemical role of the effects. Herein, we report the synthesis of novel atomically precise, copper hydride nanoclusters (NCs), [Cu28 H10 (C7 H7 S)18 (TPP)3 ] (Cu28 ; TPP: triphenylphosphine; C7 H7 S: o-thiocresol) with a defined defect in the gram scale via a one-pot reduction method. The Cu28 acts as a highly selective catalyst for C-C cross-couplings. The work highlights the potential of defective NCs as model systems for investigating individual defects, correlating defects with physiochemical properties, and rationally designing new nanoparticle catalysts.

Investigations of the Interaction Mechanism Between Orphenadrine Hydrochloride and Bovine Serum Albumin by Spectroscopic and Voltammetric Techniques.

The interaction of orphenadrine hydrochloride (ORD) with the model protein, bovine serum albumin (BSA), was investigated using a variety of spectroscopic techniques such as steady-state fluorescence, ultraviolet-visible, Fourier transform infrared, 3-D spectroscopy, and electrochemical methods under physiological conditions. Stern-Volmer plots were used to calculate fluorescence quenching at various temperatures. The findings point to a static quenching mechanism between ORD and BSA. At various reaction times, the binding sites (n) and binding constants (K) of ORD to BSA were recorded. Thermodynamic parameters ∆H0, ∆S0 and ∆G0 between ORD and BSA were calculated and reported. The average binding distance (r) between the donor (BSA) and acceptor (ORD) molecules was predicted using Förster's theory. Three-dimensional fluorescence spectra, Fourier transform infrared spectra, and synchronous fluorescence studies all supported the alternations in protein structure following the interaction with ORD. A displacement study using site probes such as warfarin, ibuprofen, and digitoxin confirmed ORD binding at Sudlow's site I of BSA. The effect of common metal ions such as Cu2+, Ni2+, Ca2+, Co2+, and Zn2+ on binding constant values was investigated and reported.

Alleviation of arthritis through prevention of neutrophil extracellular traps by an orally available inhibitor of protein arginine deiminase 4.

Protein arginine deiminases (PAD) 4 is an enzyme that catalyzes citrullination of protein and its role in autoimmune diseases has been established through clinical genetics and gene knock out studies in mice. Further, studies with PAD4 - deficient mice have shown that PAD4 deficiency does not lead to increased infection or immune suppression, which makes PAD4 an attractive therapeutic target for auto-immune and inflammatory diseases. PAD4 has critical enzymatic role of promoting chromatin decondensation and neutrophil extracellular traps (NETs) formation that is associated with a number of immune-mediated pathological conditions. Here, we present a non-covalent PAD4 inhibitor JBI-589 with high PAD4 isoform selectivity and delineated its binding mode at 2.88 Å resolution by X-ray crystallography. We confirmed its effectiveness in inhibiting NET formation in vitro. Additionally, by using two mouse arthritis models for human rheumatoid arthritis (RA), the well-known disease associated with PAD4 clinically, we established its efficacy in vivo. These results suggest that JBI-589 would be beneficial for both PAD4 and NET-associated pathological conditions.

Comparison of postoperative analgesia with two different doses of dexmedetomidine as an adjuvant to ropivacaine in adductor canal block for unilateral total knee replacement surgery: A randomized double-blinded study.

Background and Aims: Multimodal analgesia is used to treat severe postoperative pain (POP) in total knee replacement (TKR) surgery. Adjuvants are used with local anesthetics to improve the quality and duration of pain relief. Studies comparing different doses of dexmedetomidine in adductor canal block (ACB) are sparse to date. This study compares postoperative analgesia with two different doses of dexmedetomidine as an adjuvant to 0.2% ropivacaine in ACB for unilateral TKR. Material and Methods: In this prospective, randomized, double-blinded comparative study, sixty patients were divided into two groups: A and B. Postoperatively perineural catheter was inserted and all patients received 0.2% ropivacaine 20 mL bolus followed by an infusion of 0.2% ropivacaine with dexmedetomidine (0.5 µg/Kg in Group A and 1 µg/Kg in Group B) at 8 mL/h. Postoperative pain, motor blockade, rescue analgesia, hemodynamic parameters, sedation, and adverse effects were recorded. Student t, Chi-square, and Mann-Whitney tests were used. Results: Most patients were elderly females (M:15, F:45). Postoperatively, from 2nd to 24th hour, pain score was less in Group B (P < 0.05). The requirement of rescue analgesic was also less in Group B (A:B 330 µg:60 µg; 23%:6%). Motor blockade assessed using modified Bromage scale and sedation using Richmond agitation sedation scale did not show any statistical difference. Conclusion: Dexmedetomidine infusion at 1 µg/Kg is a better adjuvant to 0.2% ropivacaine than 0.5 µg/Kg in ACB. It provides better analgesia without producing sedation, motor blockade, hemodynamic changes, or any adverse effects.

Exposure to Neighborhood-Level Racial Residential Segregation in Young Adulthood to Midlife and Incident Subclinical Atherosclerosis in Black Adults: The Coronary Artery Risk Development in Young Adults Study.

BACKGROUND: Neighborhood-level racial residential segregation has been linked to several cardiovascular disease risk factors and outcomes in Black adults, but its impact on subclinical atherosclerosis remains unknown. In addition, although the impact of segregation on health may vary over the life course, most studies have examined segregation exposure at a single point in time. This article takes a life course approach by examining associations of exposure to neighborhood-level racial residential segregation in young adulthood and patterns of exposure from young adulthood to midlife with coronary artery calcification (CAC) incidence. METHODS: We used data on 1125 Black CARDIA study (Coronary Artery Risk Development in Young Adults) participants free of CAC. Residential segregation was assessed using the Gi* statistic and measured when participants were young adults (18-30 years old, in 1985-1986) and as the pattern from young adulthood to midlife (15 years later). Poisson regression with generalized estimating equations models was used to measure CAC incidence. RESULTS: We found participants living in low segregation neighborhoods in young adulthood had 0.52 (rate ratio [95% CI: 0.28-0.98]) times lower risk of developing CAC compared with high segregation after adjusting for young adulthood sociodemographic characteristics and neighborhood poverty. Associations were attenuated and no longer statistically significant with adjustment for midlife CAC risk factors hypothesized to be on the causal pathway (rate ratio: 0.56 [95% CI: 0.29-1.09]). Findings for patterns of segregation over time suggest participants living in low segregation neighborhoods in young adulthood were less likely to develop CAC than those who started out in medium/high segregation neighborhoods, regardless of where they lived in midlife (rate ratio for increase from low to medium/high: 0.42 [95% CI: 0.19-0.95]; rate ratio for continuously low versus continuously medium/high segregation neighborhoods: 0.75 [95% CI: 0.31-1.83]). CONCLUSIONS: We found that participants living in more segregated neighborhoods in young adulthood were more likely to develop CAC due at least in part to differences in CAC risk factor burden accumulated over follow-up.

Population pharmacokinetic/pharmacodynamic assessment of imipenem/cilastatin/relebactam in patients with hospital-acquired/ventilator-associated bacterial pneumonia.

In the phase III RESTORE-IMI 2 study (ClinicalTrials.gov: NCT02493764), the combination antibacterial agent imipenem/cilastatin/relebactam (IMI/REL) demonstrated noninferiority to piperacillin/tazobactam for the end points of all-cause mortality at day 28 and favorable clinical response at the early follow-up visit in adult participants with gram-negative hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP). Existing population pharmacokinetic models for imipenem (IPM) and REL were updated using data from patients with HABP/VABP from RESTORE-IMI 2. Creatinine clearance (CrCl), body weight, infection type, and ventilation status were significant covariates in the updated model. The following simulations were performed to calculate the pharmacokinetic/pharmacodynamic joint probability of target attainment among patients with HABP/VABP and varying degrees of renal function: augmented renal clearance (CrCl ≥150 ml/min), normal renal function (CrCl ≥90 to <150 ml/min), renal impairment (mild, CrCl ≥60 to <90 ml/min; moderate, CrCl ≥30 to <60 ml/min; or severe, CrCl ≥15 to <30 ml/min), and end-stage renal disease (CrCl <15 ml/min). At the recommended IMI/REL dosing regimens across renal categories, greater than 90% of patients in all renal function groups were predicted to achieve joint pharmacokinetic/pharmacodynamic targets at a minimum inhibitory concentration breakpoint of ≤2 µg/ml, regardless of ventilation status. This modeling and simulation analysis supports use of the recommended IMI/REL dosing regimens, adjusted based on renal function, in patients with HABP/VABP.

Computed Tomography Techniques, Protocols, Advancements, and Future Directions in Liver Diseases.

Computed tomography (CT) is often performed as the initial imaging study for the workup of patients with known or suspected liver disease. Our article reviews liver CT techniques and protocols in clinical practice along with updates on relevant CT advances, including wide-detector CT, radiation dose optimization, and multienergy scanning, that have already shown clinical impact. Particular emphasis is placed on optimizing the late arterial phase of enhancement, which is critical to evaluation of hepatocellular carcinoma. We also discuss emerging techniques that may soon influence clinical care.

CT Esophagography for Evaluation of Esophageal Perforation.

Esophageal emergencies such as rupture or postoperative leak are uncommon but may be life threatening when they occur. Delay in their diagnosis and treatment may significantly increase morbidity and mortality. Causes of esophageal injury include iatrogenic (including esophagogastroduodenoscopy and stent placement), foreign body ingestion, blunt or penetrating trauma to the chest or abdomen, and forceful retching, also called Boerhaave syndrome. Although fluoroscopic esophagography remains the imaging study of choice according the American College of Radiology appropriateness criteria, CT esophagography has been shown to be at least equal to if not superior to fluoroscopic evaluation for esophageal injury. In addition, CT esophagography allows diagnosis of extraesophageal abnormalities, both as the cause of the patient's symptoms as well as incidental findings. CT esophagography also allows rapid diagnosis since the examination can be readily performed in most clinical settings and requires no direct radiologist supervision, requiring only properly trained technologists and a CT scanner. Multiple prior studies have shown the limited utility of fluoroscopic esophagography after a negative chest CT scan and the increase in accuracy after adding oral contrast agent to CT examinations, although there is considerable variability of CT esophagography protocols among institutions. Development of a CT esophagography program, utilizing a well-defined protocol with input from staff from the radiology, gastroenterology, emergency, and general surgery departments, can facilitate more rapid diagnosis and patient care, especially in overnight and emergency settings. The purpose of this article is to familiarize radiologists with CT esophagography techniques and imaging findings of emergent esophageal conditions. Online supplemental material is available for this article. ©RSNA, 2021.

Structured Reporting in Ultrasound.

Structured reporting of ultrasound examinations can add value throughout the imaging chain. Reports may be created in a more efficient manner, with increased accuracy and clarity. Communication with referring providers and patients may be improved. Patient care can be enhanced through improved adherence with guidelines and local best practices. Radiology departments may benefit from improved billing and quality reporting. Consistent discrete data can enable research and collaborations between institutions. This article will review the multifaceted impact of structuring ultrasound reports.

White paper on pancreatic ductal adenocarcinoma from society of abdominal radiology's disease-focused panel for pancreatic ductal adenocarcinoma: Part I, AJCC staging system, NCCN guidelines, and borderline resectable disease.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive gastrointestinal malignancy with a poor 5-year survival rate. Accurate staging of PDAC is an important initial step in the development of a stage-specific treatment plan. Different staging systems/consensus statements convened by different societies and academic practices are currently used. The most recent version of the American Joint Committee on Cancer (AJCC) tumor/node/metastases (TNM) staging system for PDAC has shifted its focus from guiding management to assessing prognosis. In order to preoperatively define the resectability of PDAC and to guide management, additional classification systems have been developed. The National Comprehensive Cancer Network (NCCN) guidelines, one of the most commonly used systems, provide recommendations on the management and the determination of resectability for PDAC. The NCCN divides PDAC into three categories of resectability based on tumor-vessel relationship: 'resectable,' 'borderline resectable,' and 'unresectable'. Among these, the borderline disease category is of special interest given its evolution over time and the resulting variations in the definition and the associated recommendations for management between different societies. It is important to be familiar with the evolving criteria, and treatment and follow-up recommendations for PDAC. In this article, the most current AJCC staging (8th edition), NCCN guidelines (version 2.2019-April 9, 2019), and challenges and controversies in borderline resectable PDAC are reviewed.

White paper on pancreatic ductal adenocarcinoma from society of abdominal radiology's disease-focused panel for pancreatic ductal adenocarcinoma: Part II, update on imaging techniques and screening of pancreatic cancer in high-risk individuals.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive gastrointestinal malignancy with a poor 5-year survival rate. Its high mortality rate is attributed to its aggressive biology and frequently late presentation. While surgical resection remains the only potentially curative treatment, only 10-20% of patients will present with surgically resectable disease. Over the past several years, development of vascular bypass graft techniques and introduction of neoadjuvant treatment regimens have increased the number of patients who can undergo resection with a curative intent. While the role of conventional imaging in the detection, characterization, and staging of patients with PDAC is well established, its role in monitoring treatment response, particularly following neoadjuvant therapy remains challenging because of the complex anatomic and histological nature of PDAC. Novel morphologic and functional imaging techniques (such as DECT, DW-MRI, and PET/MRI) are being investigated to improve the diagnostic accuracy and the ability to measure response to therapy. There is also a growing interest to detect PDAC and its precursor lesions at an early stage in asymptomatic patients to increase the likelihood of achieving cure. This has led to the development of pancreatic cancer screening programs. This article will review recent updates in imaging techniques and the current status of screening and surveillance of individuals at a high risk of developing PDAC.

Sonographic Appearances of Portal Vein Abnormalities.

Portal venous system evaluation is required in many clinical circumstances, as substantial morbidity and mortality can be associated with a spectrum of portal vein abnormalities. Portal venous system pathologies can be congenital or acquired, and the knowledge of their imaging appearances will allow for a confident diagnosis and appropriate treatment options. In addition, a firm understanding of anatomical variants is important for planning surgical procedures and percutaneous interventions of the liver. This article will review various imaging appearances of portal venous systems abnormalities.

Magnetic Resonance-Guided Focused Ultrasound: A Brief Review With Emphasis on the Treatment of Extra-abdominal Desmoid Tumors.

Magnetic resonance-guided focused ultrasound (MRgFUS) utilizes high-intensity focused ultrasound to noninvasively, thermally ablate lesions within the body while sparing the intervening tissues. Magnetic resonance imaging provides treatment planning and guidance, and real-time magnetic resonance thermometry provides continuous monitoring during therapy. Magnetic resonance-guided focused ultrasound is ideally suited for the treatment of extra-abdominal desmoid fibromatosis due to its noninvasiveness, lack of ionizing radiation, low morbidity, and good safety profile. Conventional treatments for these benign tumors, including surgery, radiation, and chemotherapy, can carry significant morbidity. Magnetic resonance-guided focused ultrasound provides a safe and effective alternative treatment in this often-young and otherwise healthy patient population. While there is considerable experience with MRgFUS for treatment of uterine fibroids, painful bone lesions, and essential tremor, there are few reports in the literature of its use for treatment of benign or malignant soft tissue tumors. This article reviews the principles and biologic effects of high-intensity focused ultrasound, provides an overview of the MRgFUS treatment system and use of magnetic resonance thermometry, discusses the use of MRgFUS for the treatment of extra-abdominal desmoid tumors, and provides several case examples.

CT automated exposure control using a generalized detectability index.

PURPOSE: Identifying an appropriate tube current setting can be challenging when using iterative reconstruction due to the varying relationship between spatial resolution, contrast, noise, and dose across different algorithms. This study developed and investigated the application of a generalized detectability index ( d gen ' ) to determine the noise parameter to input to existing automated exposure control (AEC) systems to provide consistent image quality (IQ) across different reconstruction approaches. METHODS: This study proposes a task-based automated exposure control (AEC) method using a generalized detectability index ( d gen ' ). The proposed method leverages existing AEC methods that are based on a prescribed noise level. The generalized d gen ' metric is calculated using lookup tables of task-based modulation transfer function (MTF) and noise power spectrum (NPS). To generate the lookup tables, the American College of Radiology CT accreditation phantom was scanned on a multidetector CT scanner (Revolution CT, GE Healthcare) at 120 kV and tube current varied manually from 20 to 240 mAs. Images were reconstructed using a reference reconstruction algorithm and four levels of an in-house iterative reconstruction algorithm with different regularization strengths (IR1-IR4). The task-based MTF and NPS were estimated from the measured images to create lookup tables of scaling factors that convert between d gen ' and noise standard deviation. The performance of the proposed d gen ' -AEC method in providing a desired IQ level over a range of iterative reconstruction algorithms was evaluated using the American College of Radiology (ACR) phantom with elliptical shell and using a human reader evaluation on anthropomorphic phantom images. RESULTS: The study of the ACR phantom with elliptical shell demonstrated reasonable agreement between the d gen ' predicted by the lookup table and d ' measured in the images, with a mean absolute error of 15% across all dose levels and maximum error of 45% at the lowest dose level with the elliptical shell. For the anthropomorphic phantom study, the mean reader scores for images resulting from the d gen ' -AEC method were 3.3 (reference image), 3.5 (IR1), 3.6 (IR2), 3.5 (IR3), and 2.2 (IR4). When using the d gen ' -AEC method, the observers' IQ scores for the reference reconstruction were statistical equivalent to the scores for IR1, IR2, and IR3 iterative reconstructions (P > 0.35). The d gen ' -AEC method achieved this equivalent IQ at lower dose for the IR scans compared to the reference scans. CONCLUSIONS: A novel AEC method, based on a generalized detectability index, was investigated. The proposed method can be used with some existing AEC systems to derive the tube current profile for iterative reconstruction algorithms. The results provide preliminary evidence that the proposed d gen ' -AEC can produce similar IQ across different iterative reconstruction approaches at different dose levels.

Automated quantification and evaluation of motion artifact on coronary CT angiography images.

PURPOSE: This study developed and validated a Motion Artifact Quantification algorithm to automatically quantify the severity of motion artifacts on coronary computed tomography angiography (CCTA) images. The algorithm was then used to develop a Motion IQ Decision method to automatically identify whether a CCTA dataset is of sufficient diagnostic image quality or requires further correction. METHOD: The developed Motion Artifact Quantification algorithm includes steps to identify the right coronary artery (RCA) regions of interest (ROIs), segment vessel and shading artifacts, and to calculate the motion artifact score (MAS) metric. The segmentation algorithms were verified against ground-truth manual segmentations. The segmentation algorithms were also verified by comparing and analyzing the MAS calculated from ground-truth segmentations and the algorithm-generated segmentations. The Motion IQ Decision algorithm first identifies slices with unsatisfactory image quality using a MAS threshold. The algorithm then uses an artifact-length threshold to determine whether the degraded vessel segment is large enough to cause the dataset to be nondiagnostic. An observer study on 30 clinical CCTA datasets was performed to obtain the ground-truth decisions of whether the datasets were of sufficient image quality. A five-fold cross-validation was used to identify the thresholds and to evaluate the Motion IQ Decision algorithm. RESULTS: The automated segmentation algorithms in the Motion Artifact Quantification algorithm resulted in Dice coefficients of 0.84 for the segmented vessel regions and 0.75 for the segmented shading artifact regions. The MAS calculated using the automated algorithm was within 10% of the values obtained using ground-truth segmentations. The MAS threshold and artifact-length thresholds were determined by the ROC analysis to be 0.6 and 6.25 mm by all folds. The Motion IQ Decision algorithm demonstrated 100% sensitivity, 66.7% ± 27.9% specificity, and a total accuracy of 86.7% ± 12.5% for identifying datasets in which the RCA required correction. The Motion IQ Decision algorithm demonstrated 91.3% sensitivity, 71.4% specificity, and a total accuracy of 86.7% for identifying CCTA datasets that need correction for any of the three main vessels. CONCLUSION: The Motion Artifact Quantification algorithm calculated accurate (<10% error) motion artifact scores using the automated segmentation methods. The developed algorithms demonstrated high sensitivity (91.3%) and specificity (71.4%) in identifying datasets of insufficient image quality. The developed algorithms for automatically quantifying motion artifact severity may be useful for comparing acquisition techniques, improving best-phase selection algorithms, and evaluating motion compensation techniques.

Characterizing indeterminate liver lesions in patients with localized pancreatic cancer at the time of diagnosis.

BACKGROUND: In patients with newly diagnosed pancreatic cancer, the classification of indeterminate liver lesions is an unanswered clinical dilemma as misclassification of these lesions can impact the assignment of clinical stage and subsequent treatment planning. Our objective was to design a standardized classification system to more accurately define the risk of malignancy in indeterminate liver lesions. METHODS: In this retrospective study, patients with localized, non-metastatic pancreatic cancer were identified and pre-treatment computed tomography (CT) scans were evaluated for the presence or absence of liver lesions. Liver lesions were defined as definitely benign (1) or indeterminate (2). Indeterminate lesions were further sub-classified as either indeterminate probably benign (2B) or indeterminate possibly malignant (2M). The index liver lesion was evaluated on follow-up imaging for stability or unequivocal disease progression. RESULTS: From 2008 to 2015, 304 patients with localized, non-metastatic pancreatic cancer were identified and 125 (41%) patients had liver lesions. Of the 125 patients, the liver lesions in 35 (28%) were classified as definitely benign and in 90 (72%) patients they were classified as indeterminate. The 90 patients with indeterminate lesions included 80 (89%) classified as indeterminate probably benign (2B) and 10 (11%) classified as indeterminate possibly malignant (2M). After a median follow-up of 56 weeks, no patient with a definitely benign lesion had metastatic disease progression of the index lesion. Of the 90 patients with indeterminate liver lesions, the index lesion progressed to unequivocal liver metastasis in 8 (9%) patients; 5 (6%) of the 80 lesions classified as indeterminate probably benign (2B), and 3 (30%) of the ten lesions classified as indeterminate possibly malignant (2M). The sensitivity of the classification system was 38% and the specificity was 91%. The positive predictive value was 30% and the negative predictive value was 94%. CONCLUSIONS: A significant proportion of patients with localized pancreatic cancer will have liver lesions identified at the time of diagnosis and most of these lesions will have indeterminate characteristics. A classification system which further stratifies indeterminate liver lesions by malignant potential can assist clinicians in determining optimal treatment plan and is associated with a high negative predictive value.

Pancreatic adenocarcinoma: cross-sectional imaging techniques.

Pancreatic adenocarcinoma is a common malignancy that has a poor prognosis. Imaging is vital in its detection, staging, and management. Although a variety of imaging techniques are available, MDCT is the preferred imaging modality for staging and assessing the resectability of pancreatic adenocarcinoma. MR also has an important adjunct role, and may be used in addition to CT or as a problem-solving tool. A dedicated pancreatic protocol should be acquired as a biphasic technique optimized for the detection of pancreatic adenocarcinoma and to allow accurate local and distant disease staging. Emerging techniques like dual-energy CT and texture analysis of CT and MR images have a great potential in improving lesion detection, characterization, and treatment monitoring.