Biliary Disorders, Anomalies, and Malignancies in Children.

Biliary abnormalities in children are uncommon, and the spectrum of biliary disorders is broader than in adult patients. Unlike in adults, biliary disorders in children are rarely neoplastic and are more commonly rhabdomyosarcoma rather than cholangiocarcinoma. Pediatric biliary disorders may be embryologic or congenital, such as anatomic gallbladder anomalies, anomalous pancreaticobiliary tracts, various cholestatic processes, congenital cystic lesions, or genetic conditions. They may also be benign, such as biliary filling anomalies, biliary motility disorders, and biliary inflammatory and infectious disorders. Distinguishing these entities with a single imaging modality is challenging. US is the primary imaging modality for initial evaluation of biliary abnormalities in children, due to its wide availability, lack of ionizing radiation, and low cost and because it requires no sedation. Other examinations such as MRI, CT, and nuclear medicine examinations may provide anatomic and functional information to narrow the diagnosis further. Hepatobiliary-specific contrast material with MRI can provide better assessment of biliary anatomy on delayed images than can traditional MRI contrast material. MR cholangiopancreatography (MRCP) allows visualization of the intra- and extrahepatic biliary ducts, which may not be possible with endoscopic retrograde cholangiopancreatography (ERCP). Suspected biliary atresia requires multiple modalities for diagnosis and timely treatment. Determining the type of choledochal cyst calls for a combination of initial US and MRCP. Many benign and malignant biliary masses require biopsy for definitive diagnosis. Knowledge of the imaging appearances of different pediatric biliary abnormalities is necessary for appropriate imaging workup, providing a diagnosis or differential diagnosis, and guiding appropriate management. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Pictorial Review of Common and Uncommon Pediatric Breast Lesions.

Breast masses in children and adolescents are uncommon, and the spectrum of pediatric breast masses is predominantly benign and different from that in adults. Knowledge of the clinical presentation and imaging features of the various stages of normal development and mass-forming lesions in the pediatric breast can guide a tailored imaging approach and help the radiologist make a definitive diagnosis. Breast development begins during fetal gestation along the embryologic milk lines and continues through puberty as the breast matures through the Tanner stages of development. Normal and developmental variants and benign neoplastic and nonneoplastic lesions in the pediatric breast are common causes of concern. Malignant breast masses in children are rare and are more often due to metastasis than primary breast cancer. When clinically warranted, US is the mainstay for imaging the pediatric breast and requires careful correlation of sonographic findings with patient age and history. Breast MRI can be used to further characterize lesions and evaluate the extent of disease. Biopsy should be considered only for suspicious findings and must be weighed against the risk of iatrogenic injury to the developing breast. Given that the majority of mass-forming lesions in the pediatric breast are benign, the diagnostic and management approach should emphasize "first do no harm." Knowledge of the imaging appearance of normal breast development and the spectrum of benign and malignant pediatric breast masses is necessary to make the correct diagnosis. © RSNA, 2022.

False-Positive and False-Negative Contrast-enhanced Mammograms: Pitfalls and Strategies to Improve Cancer Detection.

Contrast-enhanced mammography (CEM) is a relatively new breast imaging modality that uses intravenous contrast material to increase detection of breast cancer. CEM combines the structural information of conventional mammography with the functional information of tumor neovascularity. Initial studies have demonstrated that CEM and MRI perform with similar accuracies, with CEM having a slightly higher specificity (fewer false positives), although larger studies are needed. There are various reasons for false positives and false negatives at CEM. False positives at CEM can be caused by benign lesions with vascularity, including benign tumors, infection or inflammation, benign lesions in the skin, and imaging artifacts. False negatives at CEM can be attributed to incomplete or inadequate visualization of lesions, marked background parenchymal enhancement (BPE) obscuring cancer, lack of lesion contrast enhancement due to technical issues or less-vascular cancers, artifacts, and errors of lesion perception or characterization. When possible, real-time interpretation of CEM studies is ideal. If additional views are necessary, they may be obtained while contrast material is still in the breast parenchyma. Until recently, a limitation of CEM was the lack of CEM-guided biopsy capability. However, in 2020, the U.S. Food and Drug Administration cleared two devices to support CEM-guided biopsy using a stereotactic biopsy technique. The authors review various causes of false-positive and false-negative contrast-enhanced mammograms and discuss strategies to reduce these diagnostic errors to improve cancer detection while mitigating unnecessary additional imaging and procedures. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Imaging Characteristics of and Multidisciplinary Management Considerations for Atypical Ductal Hyperplasia and Flat Epithelial Atypia: Review of Current Literature.

High-risk lesions of the breast are frequently encountered in percutaneous biopsy specimens. While benign, these lesions have historically undergone surgical excision due to their potential to be upgraded to malignancy. However, there is emerging evidence that a tailored management approach should be considered to reduce overtreatment of these lesions. Flat epithelial atypia (FEA) and atypical ductal hyperplasia (ADH) are two of the most commonly encountered high-risk lesions. FEA has been shown to have a relatively low rate of progression to malignancy, and some guidelines are now recommending observation over routine excision in select cases. Selective observation may be reasonable in cases where the target lesion is small and completely removed at biopsy and when there are no underlying risk factors, such as a history of breast cancer or genetic mutation or concurrent ADH. ADH has the highest potential upgrade rate to malignancy of all the high-risk lesions. Most society guidelines continue to recommend surgical excision of this lesion. More recently, some literature suggests that ADH lesions that appear completely removed at biopsy, involve limited foci (less than two or three) with no necrosis or significant atypia, manifest as a small group of mammographic calcifications, or demonstrate no enhancement at MRI may be reasonable for observation. Ultimately, management of all high-risk lesions must be based on a multidisciplinary approach that considers all patient, radiologic, clinical, and histopathologic factors. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Digital Phenotyping for Mood Disorders: Methodology-Oriented Pilot Feasibility Study.

BACKGROUND: In the burgeoning area of clinical digital phenotyping research, there is a dearth of literature that details methodology, including the key challenges and dilemmas in developing and implementing a successful architecture for technological infrastructure, patient engagement, longitudinal study participation, and successful reporting and analysis of diverse passive and active digital data streams. OBJECTIVE: This article provides a narrative rationale for our study design in the context of the current evidence base and best practices, with an emphasis on our initial lessons learned from the implementation challenges and successes of this digital phenotyping study. METHODS: We describe the design and implementation approach for a digital phenotyping pilot feasibility study with attention to synthesizing key literature and the reasoning for pragmatic adaptations in implementing a multisite study encompassing distinct geographic and population settings. This methodology was used to recruit patients as study participants with a clinician-validated diagnostic history of unipolar depression, bipolar I disorder, or bipolar II disorder, or healthy controls in 2 geographically distinct health care systems for a longitudinal digital phenotyping study of mood disorders. RESULTS: We describe the feasibility of a multisite digital phenotyping pilot study for patients with mood disorders in terms of passively and actively collected phenotyping data quality and enrollment of patients. Overall data quality (assessed as the amount of sensor data obtained vs expected) was high compared to that in related studies. Results were reported on the relevant demographic features of study participants, revealing recruitment properties of age (mean subgroup age ranged from 31 years in the healthy control subgroup to 38 years in the bipolar I disorder subgroup), sex (predominance of female participants, with 7/11, 64% females in the bipolar II disorder subgroup), and smartphone operating system (iOS vs Android; iOS ranged from 7/11, 64% in the bipolar II disorder subgroup to 29/32, 91% in the healthy control subgroup). We also described implementation considerations around digital phenotyping research for mood disorders and other psychiatric conditions. CONCLUSIONS: Digital phenotyping in affective disorders is feasible on both Android and iOS smartphones, and the resulting data quality using an open-source platform is higher than that in comparable studies. While the digital phenotyping data quality was independent of gender and race, the reported demographic features of study participants revealed important information on possible selection biases that may result from naturalistic research in this domain. We believe that the methodology described will be readily reproducible and generalizable to other study settings and patient populations given our data on deployment at 2 unique sites.

Establishing Normal Testicular 18F-FDG PET/CT SUVs.

OBJECTIVE. Knowledge of normal testicular 18F-FDG PET/CT (FDG PET/CT) SUVs is crucial for accurate examination interpretation. The objective of this study was to establish normal testicular SUV ranges among adult men receiving health care in North America. MATERIALS AND METHODS. A retrospective review of an institutional electronic database identified adult men undergoing pretreatment clinical FDG PET/CT examinations from March 15, 2013, through March 15, 2018. An FDG PET/CT image review of 700 testicles in 350 male patients was performed. Data collected included testicular SUVmax, SUVmean, and visual PET pattern of uptake. RESULTS. Testicular SUVmean and SUVmax values (mean ± SD) by age group were as follows: 3.1 ± 0.7 and 3.8 ± 0.9 for the age group of 18-30 years; 3.2 ± 0.6 and 4.0 ± 0.8, 31-40 years; 3.1 ± 0.4 and 3.8 ± 0.5, 41-50 years; 3.0 ± 0.5 and 3.7 ± 0.7, 51-60 years; 2.9 ± 0.5 and 3.5 ± 0.7, 61-70 years; 2.8 ± 0.5 and 3.5 ± 0.7, 71-80 years; and 2.6 ± 0.5 and 3.3 ± 0.6, more than 80 years. A statistically significant difference exists between age groups for testicular SUVmean (p ≤ .001) and SUVmax (p < .001), with SUVs peaking in the 4th decade of life and subsequently declining with age. A small but significant negative correlation exists between blood glucose level and testicular SUVmean (r = -0.12). CONCLUSION. This study reports the largest currently known cohort of SUVs in normal testicles and may guide clinical interpretation of testicular FDG activity. Discrepancies in normal SUVs may exist because of differences in patient demographics and PET technology.

Perceptions and Experiences of Medical Assistance in Dying Among Illicit Substance Users and People Living in Poverty.

Since medical assistance in dying (MAiD) became legal in Canada in 2016, there have been concerns about vulnerable people feeling pressured to end their lives. It is important to understand what people in marginalized communities know and feel about MAiD in order to help prevent any pressure to hasten death and to prevent any barriers to accessing assisted death. This qualitative study explored the perceptions and experiences of MAiD and other end-of-life care options with 46 people who were illicit substance users, living in poverty, or who worked with marginalized people in these communities. Six broad themes were identified: the importance of family, friends, and community; the effects of the opioid crisis; barriers to accessing end-of-life care services; support for MAiD; the difference between suicide and MAiD; and what constitutes a good death. Findings from this research may be used to help inform future legislation, professional guidelines, and standards of best practice.

Tomosynthesis-Guided Needle Localization of Breast and Axillary Lesions: Our Initial Experience.

OBJECTIVE: The purpose of this study is to review tomosynthesis-guided wire and seed needle localizations of the breast and axilla performed at our institution. CONCLUSION: Tomosynthesis-guided needle localizations were performed for 38 lesions, including 14 architectural distortions, five groups of calcifications, two focal asymmetries, three masses, four breast clips, and 10 axillary clips. All lesions were successfully removed at surgery, indicating that breast and axillary lesions can be precisely localized under tomosynthesis.

How to Recognize and Correct Artifacts on Contrast-Enhanced Mammography.

Contrast-enhanced mammography (CEM) has emerged as an important new technology in breast imaging. It can demonstrate a number of imaging artifacts that have the potential to limit interpretation by either obscuring or potentially mimicking disease. Commonly encountered artifacts on CEM include patient motion artifacts (ripple and misregistration), pectoral highlighting artifact, breast implant artifact, halo artifact, corrugation artifact, cloudy fat artifact, contrast artifacts (retention and contamination), skin artifacts (skin line enhancement and skin overexposure), and skin lesions. Skin lesions may demonstrate a variety of imaging appearances and have both benign and malignant etiologies. It is important that the technologist, radiologist, and physicist be aware of potential artifacts and skin enhancement on CEM that may affect interpretation and understand their causes and potential solutions.

MRI phenotypes associated with breast cancer predisposing genetic variants, a multisite review.

PURPOSE: Examine MRI phenotypes of breast cancers arising in patients with various pathogenic variants, to assess for imaging trends and associations. METHOD: Multisite retrospective review evaluated 410 patients from 2001 to 2020 with breast cancer and a predisposing pathogenic variant who underwent breast MRI at time of cancer diagnosis. Dominant malignant lesion features were reported, including lesion type (mass versus non-mass enhancement), size, shape, margin, internal enhancement pattern, plus other features. Kruskal-Wallis test, Fisher's exact test, and pairwise comparisons performed comparing imaging manifestations for the most frequent genetic results. RESULTS: BRCA1 (29.5 %) and BRCA2 (25.9 %) variants were most common, followed by CHEK2 (16.6 %), ATM (8.0 %), and PALB2 (6.3 %), with significant associated differences in race/ethnicity (p = 0.040), age at cancer diagnosis (p = 0.005), tumor shapes (p = 0.001), margins (p < 0.001), grade (p < 0.001), internal enhancement pattern (rim enhancement) (p < 0.001), kinetics (washout) (p < 0.001), and presence of necrosis (p < 0.001). CHEK2 and ATM tumors were often lower grade with spiculated margins (CHEK2: 47.1 %, ATM: 45.5 %), rarely exhibiting washout or tumor necrosis (p < 0.001), and were mostly comprised of luminal molecular subtypes (CHEK2: 88.2 %, ATM: 90.9 %). BRCA1 tumors had the highest proportions with round shape (31.4 %), circumscribed margins (24.0 %), rim enhancement (24.0 %), washout (58.7 %), and necrosis (19.8 %), with 47.9 % comprised of triple negative subtype. Bilateral mastectomy was performed in higher proportions of patients with BRCA1 (84.3 %) and BRCA2 (75.5 %) variants compared to others. CONCLUSIONS: Genetic and molecular profiles of breast cancers demonstrate reproducible MRI phenotypes.

Bargain Hunting for Buffered Lidocaine: A Collaborative Discovery of Cost-saving Strategies That Can Improve Patient Care.

Buffered lidocaine is a local anesthetic option during percutaneous needle-directed procedures in the breast. At our institution, sodium bicarbonate (the buffer) is dispensed in volumes that frequently lead to medical waste and shortages. In this study, we describe how moving the buffering of lidocaine from the procedure room to our clinical hospital pharmacy results in a reduction in costs and improves satisfaction across the breast radiology department. While cost savings are difficult to tease out in practices that opt for bundled payments, we were able to access pricing and supply data and coordinate with our pharmacy to change our practice. Making these changes saves our practice $26 000 a year and allows us to continue to offer buffered lidocaine even during sodium bicarbonate shortages. This manuscript describes how these changes came about and their economic impact.

A big white dot after CPR.

INTRODUCTION: Patients may remain comatose after the resumption of spontaneous circulation with cardiopulmonary resuscitation. A primary neurologic event may precede a cardiac standstill. CASE REPORT: We present a 33-year-old patient with successful resuscitation for pulseless electrical activity and a "normal computed tomography (CT) scan." Further scrutiny showed a hyperdense basilar artery sign ('big white dot') that led to a CT angiogram confirming an embolus to the proximal basilar artery. His examination showed fixed and dilated midsize (mesencephalic) pupils and extensor posturing. Endovascular retrieval of the clot was successful, but there was a devastating ischemic injury to the brainstem. CONCLUSION: This case reminds us to consider neurologic causes of cardiac arrest.

Immune defenses against Batrachochytrium dendrobatidis, a fungus linked to global amphibian declines, in the South African clawed frog, Xenopus laevis.

Batrachochytrium dendrobatidis is a chytrid fungus that causes the lethal skin disease chytridiomycosis in amphibians. It is regarded as an emerging infectious disease affecting diverse amphibian populations in many parts of the world. Because there are few model amphibian species for immunological studies, little is known about immune defenses against B. dendrobatidis. We show here that the South African clawed frog, Xenopus laevis, is a suitable model for investigating immunity to this pathogen. After an experimental exposure, a mild infection developed over 20 to 30 days and declined by 45 days postexposure. Either purified antimicrobial peptides or mixtures of peptides in the skin mucus inhibited B. dendrobatidis growth in vitro. Skin peptide secretion was maximally induced by injection of norepinephrine, and this treatment resulted in sustained skin peptide depletion and increased susceptibility to infection. Sublethal X-irradiation of frogs decreased leukocyte numbers in the spleen and resulted in greater susceptibility to infection. Immunization against B. dendrobatidis induced elevated pathogen-specific IgM and IgY serum antibodies. Mucus secretions from X. laevis previously exposed to B. dendrobatidis contained significant amounts of IgM, IgY, and IgX antibodies that bind to B. dendrobatidis. These data strongly suggest that both innate and adaptive immune defenses are involved in the resistance of X. laevis to lethal B. dendrobatidis infections.

Stereotypic behaviour in standard non-enriched cages is an alternative to depression-like responses in C57BL/6 mice.

Depressive-like forms of waking inactivity have been recently observed in laboratory primates and horses. We tested the hypotheses that being awake but motionless within the home-cage is a depression-like symptom in mice, and that in impoverished housing, it represents an alternative response to stereotypic behaviour. We raised C57BL/6 ('C57') and DBA/2 ('DBA') females to adulthood in non-enriched (n=62 mice) or enriched (n=60 mice) cages, observing home-cage behaviour during the active (dark) phases. We predicted that being still but awake would be reduced by environmental enrichment; more pronounced in C57s, as the strain most prone to learned helplessness; negatively related to stereotypic behaviour; and positively related to immobility in Forced Swim Tests (FST). Compared to enriched mice, non-enriched subjects did spend more time spent being inactive but awake, especially if they displayed relatively little stereotypic behaviour. C57 mice also spent more time awake but motionless than DBAs. Furthermore, even after statistically controlling for housing type and strain, this behaviour very strongly tended to predict increased immobility in the FST, while high levels of stereotypic behaviours in contrast predicted low immobility in the FST. Being awake but motionless is thus a reaction to non-enriched housing that seems to be an alternative to stereotypic behaviour, and could reflect depression-like states.

Cage-induced stereotypic behaviour in laboratory mice covaries with nucleus accumbens FosB/ΔFosB expression.

Stereotypic behaviour (SB) occurs in certain human disorders (e.g. autism), and animals treated with stimulants or raised in impoverished conditions, including laboratory mice in standard cages. Dysfunctional cortico-basal ganglia pathways have been implicated in these examples, but for cage-induced forms of SB, the relative roles of ventral versus dorsal striatum had not been fully ascertained. Here, we used immunohistochemical staining of FosB and ΔFosB to assess long-term activation within the nucleus accumbens and caudate-putamen of C57BL/6 mice. Housed in typical laboratory cages, these mice spontaneously developed different degrees of route-tracing, bar-mouthing and other forms of SB (spending 0% to over 50% of their active time budgets in this behaviour). The most highly stereotypic mice showed the most elevated FosB/ΔFosB activity in the nucleus accumbens. No such patterns occurred in the caudate-putamen. The cage-induced SB common in standard-housed mice thus involves elevated activity within the ventral striatum, suggesting an aetiology closer to compulsive gambling, eating and drug-seeking than to classic amphetamine stereotypies and other behaviours induced by motor loop over-activation.

Mirtazapine treatment after conditioning with methamphetamine alters subsequent expression of place preference.

Methamphetamine (MP) is a widely abused psychostimulant. There are currently no FDA approved pharmacotherapies for the MP addict. The antidepressant, mirtazapine (Mirt) is a high affinity antagonist at several monoaminergic receptors that are affected by MP. This study evaluated the potential of Mirt as a therapeutic agent for MP addiction and described associated changes in neuronal signaling. A single pairing conditioned place preference (CPP) paradigm was utilized as a behavioral measure of MP-induced effects. Rats learned to associate unique environmental cues with the effects of 1.0 mg/kg (i.p.) MP (day 1) or saline (day 2). Mirt (5.0 mg/kg i.p.) was given in the home cage on day 3 and CPP was assessed on day 4. To evaluate signaling events that correlate with this behavior, brain tissue of these rats were dissected for immunoblot assays of extracellular signal-regulated kinase (ERK) and a transcriptional regulator, cAMP response element-binding protein (CREB) after the CPP test. During the CPP test, rats conditioned with MP spent more time in the environment associated with MP. Importantly, rats given Mirt did not express CPP. MP-induced CPP was associated with a decrease in phosphorylated CREB (pCREB) in the ventral tegmental area, and decreased phosphorylated ERK and pCREB in the nucleus accumbens and treatment with Mirt did not reverse these changes. No changes in signaling proteins were obtained from rats similarly treated with MP and Mirt, without exposure to cues of the conditioning paradigm. Overall, a post-conditioning treatment with Mirt can nullify MP-induced associative learning. However, additional studies are needed to ascertain the molecular events underlying this effect of Mirt.

Validación de un programa de enzeñanza de nutrición en agronomía / Evaluation of a teaching program of nutrition in agronomy

El objetivo de este estudio fue evaluar el conjunto de materiales didácticos sobre alimentación, nutrición y agricultura, adaptados en el Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, en el ámbito de un proyecto conjunto con la AID y la Faculdad de Agronomía de la Universidad Católica de Chile (U.C.), cuyo propósito es incorporar la enseñanza de nutrición humana en la formación curricular del Ingeniero Agrónomo de América Latina. Se dictó un curso de un semestre (54 horas) a 22 alumnos del 7§ semestre de Agronomía y dos Ingenieros Agrónomos de Ecuador (becados por la AID). Se aplicó un conjunto de instrumento de evaluación del conocimiento inicial y final. El 83.3% de los alumnos aprobó el examen final (>75% de respuestas correctas). La diferencia entre los conocimientos iniciales y finales fue altamente significativa (P <0.001). En opinión de alumnos y docentes, el Libro del Profesor y el Texto General contribuyeron efectivamente al logro de los objetivos de aprendizaje, necesitando algunas modificaciones el Manual para el Alumno