Urinary Bladder Masses, Rare Subtypes, and Masslike Lesions: Radiologic-Pathologic Correlation.

Urinary bladder masses are commonly encountered in clinical practice, with 95% arising from the epithelial layer and rarer tumors arising from the lamina propria, muscularis propria, serosa, and adventitia. The extent of neoplastic invasion into these bladder layers is assessed with multimodality imaging, and the MRI-based Vesical Imaging Reporting and Data System is increasingly used to aid tumor staging. Given the multiple layers and cell lineages, a diverse array of pathologic entities can arise from the urinary bladder, and distinguishing among benign, malignant, and nonneoplastic entities is not reliably feasible in most cases. Pathologic assessment remains the standard of care for classification of bladder masses. Although urothelial carcinoma accounts for most urinary bladder malignancies in the United States, several histopathologic entities exist, including squamous cell carcinoma, adenocarcinoma, melanoma, and neuroendocrine tumors. Furthermore, there are variant histopathologic subtypes of urothelial carcinoma (eg, the plasmacytoid variant), which are often aggressive. Atypical benign bladder masses are diverse and can have inflammatory or iatrogenic causes and mimic malignancy. © RSNA, 2022 Online supplemental material is available for this article.

Renal Mass Imaging with MRI Clear Cell Likelihood Score: A User's Guide.

Small solid renal masses (SRMs) are frequently detected at imaging. Nearly 20% are benign, making careful evaluation with MRI an important consideration before deciding on management. Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma subtype with potentially aggressive behavior. Thus, confident identification of ccRCC imaging features is a critical task for the radiologist. Imaging features distinguishing ccRCC from other benign and malignant renal masses are based on major features (T2 signal intensity, corticomedullary phase enhancement, and the presence of microscopic fat) and ancillary features (segmental enhancement inversion, arterial-to-delayed enhancement ratio, and diffusion restriction). The clear cell likelihood score (ccLS) system was recently devised to provide a standardized framework for categorizing SRMs, offering a Likert score of the likelihood of ccRCC ranging from 1 (very unlikely) to 5 (very likely). Alternative diagnoses based on imaging appearance are also suggested by the algorithm. Furthermore, the ccLS system aims to stratify which patients may or may not benefit from biopsy. The authors use case examples to guide the reader through the evaluation of major and ancillary MRI features of the ccLS algorithm for assigning a likelihood score to an SRM. The authors also discuss patient selection, imaging parameters, pitfalls, and areas for future development. The goal is for radiologists to be better equipped to guide management and improve shared decision making between the patient and treating physician. © RSNA, 2023 Quiz questions for this article are available in the supplemental material. See the invited commentary by Pedrosa in this issue.

Guide for starting or optimizing a 3D printing clinical service.

Three-dimensional (3D) printing has applications in many fields and has gained substantial traction in medicine as a modality to transform two-dimensional scans into three-dimensional renderings. Patient-specific 3D printed models have direct patient care uses in surgical and procedural specialties, allowing for increased precision and accuracy in developing treatment plans and guiding surgeries. Medical applications include surgical planning, surgical guides, patient and trainee education, and implant fabrication. 3D printing workflow for a laboratory or clinical service that produces anatomic models and guides includes optimizing imaging acquisition and post-processing, segmenting the imaging, and printing the model. Quality assurance considerations include supervising medical imaging expert radiologists' guidance and self-implementing in-house quality control programs. The purpose of this review is to provide a workflow and guide for starting or optimizing laboratories and clinical services that 3D-print anatomic models or guides for clinical use.

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.

Body MRI: Imaging Protocols, Techniques, and Lessons Learned.

Body MRI has evolved from a niche subspecialty to a standard modality in the practice of abdominal radiology. However, the practicing radiologist may feel uncomfortable interpreting body MRI studies owing to a lack of case volume and inconsistent exposure. The authors highlight teaching points and subtleties central to better acquisition and interpretation of body MRI studies. Appropriate contrast agent selection and arterial phase acquisition timing provide greater diagnostic certainty in answering common clinical questions at liver MRI, such as assessing cirrhosis and evaluating focal liver lesions. Clinically relevant artifacts and physiologic phenomena, such as magnetic susceptibility and transient hepatic intensity difference, must be recognized and appropriately used when reading a study. Fat within organs and lesions is commonly encountered at body MRI. The authors discuss the nuances of common and uncommon entities, how to address fat suppression failure, assessment of bone marrow at body MRI, and an organized approach to fat-containing renal and adrenal masses. Motion artifacts are more commonly encountered at body MRI than at MRI of other anatomic regions, and understanding the various techniques, their benefits, and trade-offs will aid the body imager in protocol design and moving beyond "nondiagnostic" examinations. Challenging anatomic sites to evaluate at body MRI are reviewed. Finally, the authors offer tips for accurate interpretation of diffusion-weighted imaging, hepatobiliary phase imaging, and posttreatment imaging studies. By reviewing this article, the abdominal imager will be better prepared to perform and interpret body MRI studies confidently and accurately. An invited commentary by Kalb is available online. Online supplemental material is available for this article. ©RSNA, 2022.

Ultrasound-Guided Thrombin Injection for the Treatment of Bleeding Following Kidney and Liver Biopsies.

The purpose of this study was to describe the technique and outcomes of percutaneous thrombin injection into the superficial aspect of actively bleeding liver and kidney biopsy tracks identified with color Doppler ultrasound with the aim of hemorrhage termination. After percutaneous thrombin injection, 15/16 (94%) patients did not require further intervention. Ultrasound-guided thrombin injection into the superficial site of active bleeding is an effective technique for terminating bleeding in the immediate post-procedure period following kidney and liver biopsies and should be considered if active bleeding persists on color Doppler after ≥30 minutes of compression and observation.

CT of Penetrating Abdominopelvic Trauma.

Penetrating abdominopelvic trauma usually results from abdominal cavity violation from a firearm injury or a stab wound and is a leading cause of morbidity and mortality from traumatic injuries. Penetrating trauma can have subtle or complex imaging findings, posing a diagnostic challenge for radiologists. Contrast-enhanced CT is the modality of choice for evaluating penetrating injuries, with good sensitivity and specificity for solid-organ and hollow viscus injuries. Familiarity with the projectile kinetics of penetrating injuries is an important skill set for radiologists and aids in the diagnosis of both overt and subtle injuries. CT trajectography is a useful tool in CT interpretation that allows the identification of subtle injuries from the transfer of kinetic injury from the projectile to surrounding tissue. In CT trajectography, after the entry and exit wounds are delineated, the two points can be connected by placing cross-cursors and swiveling the cut planes obliquely in orthogonal planes to obtain a double-oblique orientation to visualize the wound track in profile. The path of the projectile and its ensuing damage is not always straight, and the imaging characteristics of free fluid of different attenuation in the abdomen (including hemoperitoneum) can support the diagnosis of visceral and vascular injuries. In addition, CT is increasingly used for evaluation of patients after damage control surgery and helps guide the management of injuries that were overlooked at surgery. An invited commentary by Paes and Munera is available online. Online supplemental material is available for this article. ©RSNA, 2021.

Airway cholinergic history modifies mucus secretion properties to subsequent cholinergic challenge in diminished chloride and bicarbonate conditions.

NEW FINDINGS: What is the central question of this study? What is the impact of airway cholinergic history on the properties of airway mucus secretion in a cystic fibrosis-like environment? What is the main finding and its importance? Prior cholinergic challenge slightly modifies the characteristics of mucus secretion in response to a second cholinergic challenge in a diminished bicarbonate and chloride transport environment. Such modifications might lead to retention of mucus on the airway surface, thereby potentiating exacerbations of airway disease. ABSTRACT: Viral infections precipitate exacerbations in many airway diseases, including asthma and cystic fibrosis. Although viral infections increase cholinergic transmission, few studies have examined how cholinergic history modifies subsequent cholinergic responses in the airway. In our previous work, we found that airway resistance in response to a second cholinergic challenge was increased in young pigs with a history of airway cholinergic stimulation. Given that mucus secretion is regulated by the cholinergic nervous system and that abnormal airway mucus contributes to exacerbations of airway disease, we hypothesized that prior cholinergic challenge would also modify subsequent mucus responses to a secondary cholinergic challenge. Using our established cholinergic challenge-rechallenge model in pigs, we atomized the cholinergic agonist bethanechol or saline control to pig airways. Forty-eight hours later, we removed tracheas and measured mucus secretion properties in response to a second cholinergic stimulation. The second cholinergic stimulation was conducted in conditions of diminished chloride and bicarbonate transport to mimic a cystic fibrosis-like environment. In pigs previously challenged with bethanechol, a second cholinergic stimulation produced a mild increase in sheet-like mucus films; these films were scarcely observed in animals originally challenged with saline control. The subtle increase in mucus films was not associated with changes in mucociliary transport. These data suggest that prior cholinergic history might modify mucus secretion characteristics with subsequent stimulation in certain environmental conditions or disease states. Such modifications and/or more repetitive stimulation might lead to retention of mucus on the airway surface, thereby potentiating exacerbations of airway disease.

A Radiology Trainee's Guide to Unique Opportunities Offered by the Radiological Society of North America.

The Radiological Society of North America (RSNA) offers educational resources and career development opportunities through many opportunities for trainees. However, trainees frequently lack access to or awareness of these opportunities and requirements. The purpose of this article is to promote access to RSNA trainee opportunities by illustrating their qualifications, advantages, and characteristics. Access to opportunities starts with RSNA membership, which grants access to several educational, research, and career development offerings. One focal point of RSNA opportunities is the RSNA Annual Meeting in Chicago, Ill, which provides several trainee-specific events. RSNA educational opportunities include access to board preparation content and information about emerging radiologic technologies. Research opportunities include mentor pairing, project development workshops, venues for presentation and publication, and the William W. Olmsted Editorial Fellowship for Trainees. Career development opportunities include positions for society involvement, leadership, and job searching. Collectively, the information presented in this article can guide the approach to early radiology career development for interested medical students, residents, fellows, and faculty advisers. ©RSNA, 2020.

Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung.

Cystic fibrosis (CF) is a life-shortening disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although bacterial lung infection and the resulting inflammation cause most of the morbidity and mortality, how the loss of CFTR function first disrupts airway host defence has remained uncertain. To investigate the abnormalities that impair elimination when a bacterium lands on the pristine surface of a newborn CF airway, we interrogated the viability of individual bacteria immobilized on solid grids and placed onto the airway surface. As a model, we studied CF pigs, which spontaneously develop hallmark features of CF lung disease. At birth, their lungs lack infection and inflammation, but have a reduced ability to eradicate bacteria. Here we show that in newborn wild-type pigs, the thin layer of airway surface liquid (ASL) rapidly kills bacteria in vivo, when removed from the lung and in primary epithelial cultures. Lack of CFTR reduces bacterial killing. We found that the ASL pH was more acidic in CF pigs, and reducing pH inhibited the antimicrobial activity of ASL. Reducing ASL pH diminished bacterial killing in wild-type pigs, and, conversely, increasing ASL pH rescued killing in CF pigs. These results directly link the initial host defence defect to the loss of CFTR, an anion channel that facilitates HCO(3)(-) transport. Without CFTR, airway epithelial HCO(3)(-) secretion is defective, the ASL pH falls and inhibits antimicrobial function, and thereby impairs the killing of bacteria that enter the newborn lung. These findings suggest that increasing ASL pH might prevent the initial infection in patients with CF, and that assaying bacterial killing could report on the benefit of therapeutic interventions.

Assessing mucociliary transport of single particles in vivo shows variable speed and preference for the ventral trachea in newborn pigs.

Mucociliary transport (MCT) is an innate defense mechanism that removes particulates, noxious material, and microorganisms from the lung. Several airway diseases exhibit abnormal MCT, including asthma, chronic bronchitis, and cystic fibrosis. However, it remains uncertain whether MCT abnormalities contribute to the genesis of disease or whether they are secondary manifestations that may fuel disease progression. Limitations of current MCT assays and of current animal models of human disease have hindered progress in addressing these questions. Therefore, we developed an in vivo assay of MCT, and here we describe its use in newborn wild-type pigs. We studied pigs because they share many physiological, biochemical, and anatomical features with humans and can model several human diseases. We used X-ray multidetector-row-computed tomography to track movement of individual particles in the large airways of newborn pigs. Multidetector-row-computed tomography imaging provided high spatial and temporal resolution and registration of particle position to airway anatomy. We discovered that cilia orientation directs particles to the ventral tracheal surface. We also observed substantial heterogeneity in the rate of individual particle movement, and we speculate that variations in mucus properties may be responsible. The increased granularity of MCT data provided by this assay may provide an opportunity to better understand host defense mechanisms and the pathogenesis of airway disease.

Glycaemic regulation and insulin secretion are abnormal in cystic fibrosis pigs despite sparing of islet cell mass.

Diabetes is a common and significant co-morbidity in cystic fibrosis (CF). The pathogenesis of cystic fibrosis related diabetes (CFRD) is incompletely understood. Because exocrine pancreatic disease is similar between humans and pigs with CF, the CF pig model has the potential to contribute significantly to the understanding of CFRD pathogenesis. We determined the structure of the endocrine pancreas in fetal, newborn and older CF and non-CF pigs and assessed endocrine pancreas function by intravenous glucose tolerance test (IV-GTT). In fetal pigs, pancreatic insulin and glucagon density was similar between CF and non-CF. In newborn and older pigs, the insulin and glucagon density was unchanged between CF and non-CF per total pancreatic area, but increased per remnant lobular tissue in CF reflecting exocrine pancreatic loss. Although fasting glucose levels were not different between CF and non-CF newborns, CF newborns demonstrated impaired glucose tolerance and increased glucose area under the curve during IV-GTT. Second phase insulin secretion responsiveness was impaired in CF newborn pigs and significantly lower than that observed in non-CF newborns. Older CF pigs had elevated random blood glucose levels compared with non-CF. In summary, glycaemic abnormalities and insulin secretion defects were present in newborn CF pigs and spontaneous hyperglycaemia developed over time. Functional changes in CF pig pancreas were not associated with a decline in islet cell mass. Our results suggest that functional islet abnormalities, independent of structural islet loss, contribute to the early pathogenesis of CFRD.

Air trapping and airflow obstruction in newborn cystic fibrosis piglets.

RATIONALE: Air trapping and airflow obstruction are being increasingly identified in infants with cystic fibrosis. These findings are commonly attributed to airway infection, inflammation, and mucus buildup. OBJECTIVES: To learn if air trapping and airflow obstruction are present before the onset of airway infection and inflammation in cystic fibrosis. METHODS: On the day they are born, piglets with cystic fibrosis lack airway infection and inflammation. Therefore, we used newborn wild-type piglets and piglets with cystic fibrosis to assess air trapping, airway size, and lung volume with inspiratory and expiratory X-ray computed tomography scans. Micro-computed tomography scanning was used to assess more distal airway sizes. Airway resistance was determined with a mechanical ventilator. Mean linear intercept and alveolar surface area were determined using stereologic methods. MEASUREMENTS AND MAIN RESULTS: On the day they were born, piglets with cystic fibrosis exhibited air trapping more frequently than wild-type piglets (75% vs. 12.5%, respectively). Moreover, newborn piglets with cystic fibrosis had increased airway resistance that was accompanied by luminal size reduction in the trachea, mainstem bronchi, and proximal airways. In contrast, mean linear intercept length, alveolar surface area, and lung volume were similar between both genotypes. CONCLUSIONS: The presence of air trapping, airflow obstruction, and airway size reduction in newborn piglets with cystic fibrosis before the onset of airway infection, inflammation, and mucus accumulation indicates that cystic fibrosis impacts airway development. Our findings suggest that early airflow obstruction and air trapping in infants with cystic fibrosis might, in part, be caused by congenital airway abnormalities.

Post-contrast abdominal magnetic resonance imaging of critically ill patients using compressed sensing free-breathing golden radial angle imaging.

Obtaining diagnostic-quality magnetic resonance imaging (MRI) of the abdomen in critically ill patients can be difficult due to challenges with breath-holding and the inability to follow technologist instructions. Protocols that harness advances in commercially available MRI techniques provide a potential solution, particularly using the golden radial angle sparse parallel (GRASP) technique for dynamic post-contrast T1-weighted imaging. The GRASP technique uses a combination of free-breathing, a stack-of-stars radial acquisition, and compressed sensing reconstruction acquired over several minutes to produce motion-free images at time points defined by the user; these include the non-contrast, arterial, venous, and delayed images, which are typical of abdominal MRI protocols. The three cases discussed herein illustrate the use of this technique in providing both exquisite image quality and diagnostic value in the care of critically ill patients with hepatopancreaticobiliary diseases. Our work aims to raise awareness of this technique and its utility in imaging patients who cannot hold their breath for dynamic T1-weighted post-contrast imaging.

Cure of Disseminated Human Lymphoma with [177Lu]Lu-Ofatumumab in a Preclinical Model.

Although immunotherapies that target CD20 on most non-Hodgkin lymphoma (NHL) cells have improved patient outcomes, current therapies are inadequate because many cases are, or become, refractory or undergo relapse. Here, we labelled the third-generation human anti-CD20 antibody ofatumumab with 177Lu, determined the in vitro characteristics of [177Lu]Lu-ofatumumab, estimated human dosimetry, and assayed tumor targeting and therapeutic efficacy in a murine model of disseminated NHL. Methods: CHX-A″-diethylenetriaminepentaacetic acid-[177Lu]Lu-ofatumumab was prepared. We evaluated radiochemical yield, purity, in vitro immunoreactivity, stability, (n = 7), affinity, and killing of CD20-expressing Raji cells (n = 3). Human dosimetry was estimated from biodistribution studies as percentage injected activity per gram using C57BL/6N mice. Tissue and organ biodistribution was determined in R2G2 immunodeficient mice with subcutaneous Raji-cell tumors. Therapy studies used R2G2 mice with disseminated human Raji-luc tumor cells (n = 10 mice/group). Four days after cell injection, the mice were left untreated or were treated with ofatumumab, 8.51 MBq of [177Lu]Lu-IgG, or 0.74 or 8.51 MBq of [177Lu]Lu-ofatumumab. Survival, weight, and bioluminescence were tracked. Results: Radiochemical yield was 93% ± 2%, radiochemical purity was 99% ± 1%, and specific activity was 401 ± 17 MBq/mg. Immunoreactivity was substantially preserved, and more than 75% of 177Lu remained chelated after 7 d in serum. [177Lu]Lu-ofatumumab specifically killed Raji-luc cells in vitro (P < 0.05). Dosimetry estimated that an effective dose for human administration is 0.36 mSv/MBq and that marrow may be the dose-limiting organ. Biodistribution in subcutaneous tumors 1, 3, and 7 d after [177Lu]Lu-ofatumumab injection was 11, 15, and 14 percentage injected activity per gram, respectively. In the therapy study, median survival of untreated mice was 19 d, not statistically different from mice treated with 8.51 MBq of [177Lu]Lu-IgG (25 d). Unlabeled ofatumumab increased survival to 46 d, similar to 0.74 MBq of [177Lu]Lu-ofatumumab (59 d), with both being superior to no treatment (P < 0.0003). Weight loss and increased tumor burden preceded death or killing of the animal for cause. In contrast, treatment with 8.51 MBq of [177Lu]Lu-ofatumumab dramatically increased median survival (>221 d), permitted weight gain, eliminated detectable tumors, and was curative in 9 of 10 mice. Conclusion: [177Lu]Lu-ofatumumab shows favorable in vitro characteristics, localizes to tumor, and demonstrates curative therapeutic efficacy in a disseminated lymphoma model, showing potential for clinical translation to treat NHL.

Pilot Study on the Influence of Incentive Spirometry on Percutaneous Image-Guided Intra-Abdominal Drainage Catheter Pressure: A Potential Method to Enhance Drainage.

Background: To report the evaluation of incentive spirometry (IS)-induced pressure changes in intra-abdominal drainage catheters and consider its use for maintaining catheter patency and enhancing drainage. Methods: Prospective study of patients with indwelling intra-abdominal drainage catheters for abdominal fluid collections who had their intra-abdominal pressures measured while performing incentive spirometry. Patients were instructed in the use of an incentive spirometer. Within a week after initial drainage, pressure changes with IS were evaluated three times at 1500 cc and three times at maximum inspiratory effort. Intra-abdominal pressure (IAP) was measured using a pressure monitor connected to the drainage catheter. Results: Twenty patients (men, 12; women, 8). Fluid collection locations were pelvis, Right-upper quadrant (RUQ), Left-upper quadrant (LUQ), Left-lower quadrant (LLQ), and Right-lower quadrant (RLQ). A total of 16 of 20 patients showed an elevation of IAP with IS. At 1500 cc, the pressure increased by an average of 41.24 mmH2O. At maximal inspiratory effort, the pressure increased by an average of 48.26 mmH2O. Pressure increase was greater in upper abdomen catheters. Four patients with lower abdominal and pelvic collections showed minimal pressure changes with IS. Conclusion: IS increases IAP and fluid flow through abdominal drainage catheters. Future studies are warranted to determine whether the use of IS enhances catheter performance and facilitates drainage via its effect on IAP.

Frequency of Hepatic Metastatic Disease in Patients with Stage IV Breast Cancer Is Similar for Steatotic and Non-Steatotic Livers.

Background: Breast cancer is the most common non-cutaneous malignancy and the second leading cause of cancer mortality in the United States. Breast cancer is a heterogeneous disease; diagnosis at an early stage renders it potentially curable, whereas advanced metastatic disease carries a worse prognosis. Objectives: To investigate whether hepatic steatosis (HS) is associated with liver metastases in patients with newly diagnosed stage IV female breast cancer patients (either de novo metastatic breast cancer or recurrent metastatic breast cancer) using non-contrast computed tomography (CT) as a marker of HS. Design: Retrospective analysis. Methods: We retrospectively identified 168 patients with stage IV breast cancer with suitable imaging from a prospectively maintained oncologic database. Three radiologists manually defined hepatic regions of interest on non-contrast CT images, and attenuation data were extracted. HS was defined as a mean attenuation <48 Hounsfield units. The frequency of hepatic metastatic disease was calculated for patient with and without HS. Relationships between HS and various patient (age, body mass index, race) and tumor (hormone receptor status, HER2 status, tumor grade) characteristics were also analyzed. Results: There were 4 patients with liver metastasis in the HS group (41 patients) versus 20 patients with liver metastases in the non-HS group (127 patients). The difference in frequencies of liver metastases among patients with (9.8%) versus without (15.7%) hepatic steatosis (odds ratio = 1.72 [0.53-7.39]) was not statistically significant (P = .45). Body mass index was significantly higher (P = .01) among patients with hepatic steatosis (32.2 ± 7.3 vs 28.8 ± 7.1 kg/m2). Otherwise, there were no significant differences between patients with versus without HS with respect to regarding age, race, hormone receptor status, HER2 status, or tumor grade. Conclusion: The frequency of hepatic metastatic disease in patients with stage IV breast cancer is similar for steatotic and non-steatotic livers.