A Practical Guide for Paid Family and Medical Leave in Radiology, From the AJR Special Series on DEI.

Paid family and medical leave (FML) has significant benefits to organizations, including improvements in employee recruitment and retention, workplace culture, and employee morale and productivity, and is supported by evidence for overall cost savings. Furthermore, paid FML related to childbirth has significant benefits to individuals and families, including but not limited to improved maternal and infant health outcomes and improved breastfeeding initiation and duration. In the case of nonchildbearing parental leave, paid FML is associated with more equitable long-term division of household labor and childcare. Paid FML is increasingly being recognized as an important issue in medicine, as evidenced by the recent passage of policies by national societies and governing bodies, including the American Board of Medical Specialties, American Board of Radiology, Accreditation Council for Graduate Medical Education (ACGME), American College of Radiology, and American Medical Association. Implementation of paid FML requires adherence to federal, state, and local laws as well as institutional requirements. Specific requirements pertain to trainees from national governing bodies, such as the ACGME and medical specialty boards. Flexibility, work coverage, culture, and finances are additional considerations for ensuring an optimal paid FML policy that accounts for concerns of all impacted individuals.

Standard Adult Gastric Emptying Scintigraphy Criteria Is Applicable for Partial Meal Ingestion.

BACKGROUND/AIMS: Gastric emptying scintigraphy is commonly performed to assess for dysmotility. A standardized meal with associated threshold criteria was established in 2000 to enable robust interpretation. However, no guidance is available to interpret results when patients do not ingest the entire meal. The purpose of this study is to determine the continued appropriateness of the threshold criteria in contemporary clinical practice and its relevance for partially ingested meals. METHODS: This retrospective study analyzed patients (n = 1365 total) who underwent solid-phase gastric emptying scintigraphy at an academic medical center. Patients were stratified based on their completion of the standard meal. Patients were further stratified into normal and delayed gastric emptying cohorts based on the current criteria. Percent gastric retention values at 1, 2, 3, and 4 h were compared. RESULTS: Median (95% upper reference) normal gastric retention values for the complete standard meal were 64% (87%) at 1 h, 25% (60%) at 2 h, 13% (54%) at 3 h and 4% (9%) at 4 h. Consumption of at least 50% of the standard meal yielded similar retention; 53% (86%) at 1 h, 19% (58%) at 2 h, 6% (29%) at 3 h and 3% (10%) at 4 h. There was no significant age- or gender-specific differences using the current criteria, and no differences were observed based on diabetic status. Retention values matched well with the current criteria and validated with data-driven clustering. CONCLUSION: Adult normative standards for gastric emptying scintigraphy are appropriate for differentiating normal and delayed populations and can be applied to partial meals with at least 50% completion.

Detecting Immune Response to Therapies Targeting PDL1 and BRAF by Using Ferumoxytol MRI and Macrin in Anaplastic Thyroid Cancer.

Background Anaplastic thyroid cancer (ATC) is aggressive with a poor prognosis, partly because of the immunosuppressive microenvironment created by tumor-associated macrophages (TAMs). Purpose To understand the relationship between TAM infiltration, tumor vascularization, and corresponding drug delivery by using ferumoxytol-enhanced MRI and macrin in an ATC mouse model. Materials and Methods ATC tumors were generated in 6-8-week-old female B6129SF1/J mice through intrathyroid injection to model orthotopic tumors, or intravenously to model hematogenous metastasis, and prospectively enrolled randomly into treatment cohorts (n = 94 total; August 1, 2018, to January 15, 2020). Mice were treated with vehicle or combined serine/threonine-protein kinase B-Raf (BRAF) kinase inhibitor (BRAFi) and anti-PDL1 antibody (aPDL1). A subset was cotreated with therapies, including an approximately 70-nm model drug delivery nanoparticle (DDNP) to target TAM, and an antibody-neutralizing colony stimulating factor 1 receptor (CSF1R). Imaging was performed at the macroscopic level with ferumoxytol-MRI and microscopically with macrin. Genetically engineered BrafV600E/WT p53-null allografts were used and complemented by a GFP-transgenic derivative and human xenografts. Tumor-bearing organs were processed by using tissue clearing and imaged with confocal microscopy and MRI. Two-tailed Wilcoxon tests were used for comparison (≥five per group). Results TAM levels were higher in orthotopic thyroid tumors compared with pulmonary metastatic lesions by 79% ± 23 (standard deviation; P < .001). These findings were concordant with ferumoxytol MRI, which showed 136% ± 88 higher uptake in thyroid lesions (P = .02) compared with lung lesions. BRAFi and aPDL1 combination therapy resulted in higher tumor DDNP delivery by 39% ± 14 in pulmonary lesions (P = .004). Compared with the untreated group, tumors following BRAFi, aPDL1, and CSF1R-blocking antibody combination therapy did not show greater levels of TAM or DDNP (P = .82). Conclusion In a mouse model of anaplastic thyroid cancer, ferumoxytol MRI showed 136% ± 88 greater uptake in orthotopic thyroid tumors compared with pulmonary lesions, which reflected high vascularization and greater tumor-associated macrophage (TAM) levels. Serine/threonine-protein kinase B-Raf inhibitor and anti-programmed death ligand 1 antibody elicited higher local TAM levels and 43% ± 20 greater therapeutic nanoparticle delivery but not higher vascularization in pulmonary tumors. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Luker in this issue.

Pediatric Solid Gastric Emptying Scintigraphy: Normative Value Guidelines and Nonstandard Meal Alternatives.

INTRODUCTION: Adult standards for gastric emptying scintigraphy, including the type of meal and range of normative values for percent gastric emptying, are routinely used in pediatric practice, but to date have not been validated. The purpose of this study is to determine whether the use of adult criteria for gastric emptying scintigraphy is valid for children and whether alternative nonstandard meals can also be offered based on these criteria. METHODS: This retrospective study analyzed patients (n = 1,151 total) who underwent solid-phase gastric emptying scintigraphy. Patients were stratified into normal and delayed gastric emptying cohorts based on adult criteria, i.e., with normal gastric emptying defined as ≤10% gastric retention at 4 hours. Patients were further stratified based on the type of meal, namely complete or partial adult standard meals or alternative cheese-based meals. Percent gastric retention values at 1, 2, 3, and 4 hours were compared. RESULTS: The median (95% upper reference limit) percentage gastric retention values for the complete standard meal were 72% (93%) at 1 hour, 39% (65%) at 2 hours, 15% (33%) at 3 hours, and 6% (10 %) at 4 hours. By comparison, the values for cheese-based meals were 60% (87%) at 1 hour, 29% (61%) at 2 hours, 10% (30%) at 3 hours, and 5% (10%) at 4 hours. Consumption of at least 50% of the standard meal yielded similar retention percentages; 68% (89%) at 1 hour, 32% (57%) at 2 hours, 10% (29%) at 3 hours, and 5% (10%) at 4 hours. There were no significant age- or sex-specific differences using the adult criteria. DISCUSSION: The adult normative standards for gastric emptying scintigraphy are applicable for use in the pediatric population. These same standards can be also be applied to nonstandard meal options, including cheese-based alternative meals and partial standard meals.

Understanding the in vivo Fate of Advanced Materials by Imaging.

Engineered materials are ubiquitous in biomedical applications ranging from systemic drug delivery systems to orthopedic implants, and their actions unfold across multiple time- and length-scales. The efficacy and safety of biologics, nanomaterials, and macroscopic implants are all dictated by the same general principles of pharmacology as apply to small molecule drugs, comprising how the body affects materials (pharmacokinetics, PK) and conversely how materials affect the body (pharmacodynamics, PD). Imaging technologies play an increasingly insightful role in monitoring both of these processes, often simultaneously: translational macroscopic imaging modalities such as MRI and PET/CT offer whole-body quantitation of biodistribution and structural or molecular response, while ex vivo approaches and optical imaging via in vivo (intravital) microscopy reveal behaviors at subcellular resolution. In this review, the authors survey developments in imaging the in situ behavior of systemically and locally administered materials, with a particular focus on using microscopy to understand transport, target engagement, and downstream host responses at a single-cell level. The themes of microenvironmental influence, controlled drug release, on-target molecular action, and immune response, especially as mediated by macrophages and other myeloid cells are examined. Finally, the future directions of how new imaging technologies may propel efficient clinical translation of next-generation therapeutics and medical devices are proposed.

Clinical Implementation of a Free-Breathing, Motion-Robust Dynamic Contrast-Enhanced MRI Protocol to Evaluate Pleural Tumors.

OBJECTIVE. The purpose of this study was to develop a motion insensitive clinical dynamic contrast-enhanced MRI (DCE-MRI) protocol to assess the response of pleural tumors in clinical trials. MATERIALS AND METHODS. Thirty-two patients with pleura-based lesions were administered contrast material and imaged with gradient-recalled echo DCE-MRI sequence variants: either a traditional cartesian k-space acquisition (FLASH), a time-resolved imaging with stochastic trajectories acquisition (TWIST), or a radial stack-of-stars acquisition (radial) sequence in addition to other standard-of-care imaging sequences. Each image acquisition's sensitivity to motion was evaluated by comparing the motion of the thoracic border in 3D throughout the acquisition. One-way ANOVA was used to compare the image quality between different acquisitions. The 95% CIs were calculated for mean thoracic border displacement. The effects of motion on kinetic parameter estimation were explored with simulations according to clinically acquired data. RESULTS. Radial was the most motion-robust sequence with subvoxel mean displacement in the superior-inferior direction (0.4 ± 1.2 [SD] mm). FLASH showed intermediate displacement (4.6 ± 2.0 mm), whereas TWIST was most sensitive to motion (6.4 ± 3.4 mm). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the images acquired with the radial sequence were on par or better than the FLASH and TWIST sequences when reconstructed with an improved density compensation algorithm. Simulations showed that motion on scans showing pleural-based lesions can lead to markedly inaccurate kinetic parameter estimation and inappropriate kinetic model convergence within a nested model analysis. CONCLUSION. A practical radial k-space trajectory sequence that provides motion-insensitive pharmacokinetic parameters was incorporated as part of the DCE-MRI protocol of pleural tumors. Validation and usefulness in clinical trials assessing response to therapy is needed.

Optimal acquisition and modeling parameters for accurate assessment of low Ktrans blood-brain barrier permeability using dynamic contrast-enhanced MRI.

PURPOSE: To determine optimal parameters for acquisition and processing of dynamic contrast-enhanced MRI (DCE-MRI) to detect small changes in near normal low blood-brain barrier (BBB) permeability. METHODS: Using a contrast-to-noise ratio metric (K-CNR) for Ktrans precision and accuracy, the effects of kinetic model selection, scan duration, temporal resolution, signal drift, and length of baseline on the estimation of low permeability values was evaluated with simulations. RESULTS: The Patlak model was shown to give the highest K-CNR at low Ktrans . The Ktrans transition point, above which other models yielded superior results, was highly dependent on scan duration and tissue extravascular extracellular volume fraction (ve ). The highest K-CNR for low Ktrans was obtained when Patlak model analysis was combined with long scan times (10-30 min), modest temporal resolution (<60 s/image), and long baseline scans (1-4 min). Signal drift as low as 3% was shown to affect the accuracy of Ktrans estimation with Patlak analysis. CONCLUSION: DCE acquisition and modeling parameters are interdependent and should be optimized together for the tissue being imaged. Appropriately optimized protocols can detect even the subtlest changes in BBB integrity and may be used to probe the earliest changes in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis.

Massive pancreatic pseudocyst with portal vein fistula: case report and proposed treatment algorithm.

Pancreatic pseudocyst is a relatively common occurrence resulting from acute or chronic pancreatitis. However, a rare subset of these patients present with a pseudocyst fistulizing into the portal vein. We present the case of a 58 year-old woman with a rapidly expanding pancreatic pseudocyst with portal venous fistulization causing portal vein thrombosis, in addition to biliary and duodenal obstruction. The patient underwent surgical decompression with a cyst-gastrostomy and was well until one week post-operatively when she experienced massive gastrointestinal hemorrhage leading to her death. A review of the literature is presented and a treatment algorithm to manage patients with pancreatic pseudocyst to portal vein fistula is proposed.

ROCKETSHIP: a flexible and modular software tool for the planning, processing and analysis of dynamic MRI studies.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a promising technique to characterize pathology and evaluate treatment response. However, analysis of DCE-MRI data is complex and benefits from concurrent analysis of multiple kinetic models and parameters. Few software tools are currently available that specifically focuses on DCE-MRI analysis with multiple kinetic models. Here, we developed ROCKETSHIP, an open-source, flexible and modular software for DCE-MRI analysis. ROCKETSHIP incorporates analyses with multiple kinetic models, including data-driven nested model analysis. RESULTS: ROCKETSHIP was implemented using the MATLAB programming language. Robustness of the software to provide reliable fits using multiple kinetic models is demonstrated using simulated data. Simulations also demonstrate the utility of the data-driven nested model analysis. Applicability of ROCKETSHIP for both preclinical and clinical studies is shown using DCE-MRI studies of the human brain and a murine tumor model. CONCLUSION: A DCE-MRI software suite was implemented and tested using simulations. Its applicability to both preclinical and clinical datasets is shown. ROCKETSHIP was designed to be easily accessible for the beginner, but flexible enough for changes or additions to be made by the advanced user as well. The availability of a flexible analysis tool will aid future studies using DCE-MRI. A public release of ROCKETSHIP is available at https://github.com/petmri/ROCKETSHIP .

Multimodality PET/MRI agents targeted to activated macrophages.

The recent emergence of multimodality imaging, particularly the combination of PET and MRI, has led to excitement over the prospect of improving detection of disease. Iron oxide nanoparticles have become a popular platform for the fabrication of PET/MRI probes owing to their advantages of high MRI detection sensitivity, biocompatibility, and biodegradability. In this article, we report the synthesis of dextran-coated iron oxide nanoparticles (DIO) labeled with the positron emitter (64)Cu to generate a PET/MRI probe, and modified with maleic anhydride to increase the negative surface charge. The modified nanoparticulate PET/MRI probe (MDIO-(64)Cu-DOTA) bears repetitive anionic charges on the surface that facilitate recognition by scavenger receptor type A (SR-A), a ligand receptor found on activated macrophages but not on normal vessel walls. MDIO-(64)Cu-DOTA has an average iron oxide core size of 7-8 nm, an average hydrodynamic diameter of 62.7 nm, an r1 relaxivity of 16.8 mM(-1) s(-1), and an r 2 relaxivity of 83.9 mM(-1) s(-1) (37 °C, 1.4 T). Cell studies confirmed that the probe was nontoxic and was specifically taken up by macrophages via SR-A. In comparison with the nonmodified analog, the accumulation of MDIO in macrophages was substantially improved. These characteristics demonstrate the promise of MDIO-(64)Cu-DOTA for identification of vulnerable atherosclerotic plaques via the targeting of macrophages.

Creating the freedom to thrive: Honoring the legacy of RSNA gold medalist, Deborah Levine, MD.

Awarded the Radiological Society of North America (RSNA) Gold Medal in 2018, Dr. Deborah Levine's research, journalism, and mentorship have left an indelible mark on the radiology field. Her work in ultrasound led to its use as the standard for monitoring benign adnexal cysts. She helped popularize obstetric magnetic resonance imaging (MRI) through her research on its use in placental accreta and fetal abnormalities, which led to the development of the 'Compendium of Fetal MRI' website. This work in research led naturally to a career in journalism, where she eventually became Senior Deputy Editor of Radiology and founded Radiology Select. Concurrently with her personal achievements, Dr. Levine has dedicated herself to the mentorship of her female trainees. She sought various leadership positions to learn more about and advocate for the promotion and support of female leadership in radiology departments. In many ways, Dr. Levine's career and work have transformed radiology as we know it today for both patients and physicians.

Tau propagation in the brain olfactory circuits is associated with smell perception changes in aging.

The direct access of olfactory afferents to memory-related cortical systems has inspired theories about the role of the olfactory pathways in the development of cortical neurodegeneration in Alzheimer's disease (AD). In this study, we used baseline olfactory identification measures with longitudinal flortaucipir and PiB PET, diffusion MRI of 89 cognitively normal older adults (73.82 ± 8.44 years; 56% females), and a transcriptomic data atlas to investigate the spatiotemporal spreading and genetic vulnerabilities of AD-related pathology aggregates in the olfactory system. We find that odor identification deficits are predominantly associated with tau accumulation in key areas of the olfactory pathway, with a particularly strong predictive power for longitudinal tau progression. We observe that tau spreads from the medial temporal lobe structures toward the olfactory system, not the reverse. Moreover, we observed a genetic background of odor perception-related genes that might confer vulnerability to tau accumulation along the olfactory system.

Neurolymphomatosis in Recrudescent Diffuse Large B-cell Lymphoma.

Neurolymphomatosis is an uncommon manifestation of lymphoma, often presenting with painful polyneuropathy or polyradiculopathy and concomitant distal extremity weakness. Differentiation from other etiologies resulting in similar neuropathic symptoms such as compressive or inflammatory pathologies can be difficult and often results in delayed diagnosis. Here we describe a case of neurolymphomatosis affecting a 64-year-old man with a history of diffuse large B-cell lymphoma (DLBCL) in remission presenting with a right-sided foot drop following a gunshot wound. MRI at that time demonstrated thickening and enhancement of the cauda equina nerve roots. Over the course of the subsequent eight months, he developed left lower extremity sensory symptoms, left-sided foot drop and signs of upper motor neuron involvement, including left facial weakness, dysphonia, and dysphagia. 18F-FDG PET/CT revealed intensely avid left lumbosacral nerve roots, bilateral lower extremity and left upper extremity neurovascular bundles. Left sural nerve biopsies showed infiltration of DLBCL and confirmed neurolymphomatosis. We highlight the role of 18F-FDG PET/CT, with histological verification, for the diagnosis of an extended course of neurolymphomatosis occurring in the absence of typical painful neuropathy but with cranial and peripheral neuropathies.

COVID-19: Findings in nuclear medicine from head to toe.

COVID-19 is a multisystemic disease, and hence its potential manifestations on nuclear medicine imaging can extend beyond the lung. Therefore, it is important for the nuclear medicine physician to recognize these manifestations in the clinic. While FDG-PET/CT is not indicated routinely in COVID-19 evaluation, its unique capability to provide a functional and anatomical assessment of the entire body means that it can be a powerful tool to monitor acute, subacute, and long-term effects of COVID-19. Single-photon scintigraphy is routinely used to assess conditions such as pulmonary embolism, cardiac ischemia, and thyroiditis, and COVID-19 may present in these studies. The most common nuclear imaging finding of COVID-19 vaccination to date is hypermetabolic axillary lymphadenopathy. This may pose important diagnostic and management dilemmas in oncologic patients, particularly those with malignancies where the axilla constitutes a lymphatic drainage area. This article aims to summarize the relevant literature published since the beginning of the pandemic on the intersection between COVID-19 and nuclear medicine.

Key Factors to Attract More U.S. Diagnostic Radiology Residents into the Field of Nuclear Medicine and Molecular Imaging: A National Survey.

RATIONALE AND OBJECTIVES: To understand the current state of radiology residents' exposure to nuclear medicine and molecular imaging (NM/MI), determine key factors that may attract more trainees into the field, and identify differentiating aspects between those specializing in NM/MI and those who are not. MATERIALS AND METHODS: An anonymous web-based survey was sent to contacts at all diagnostic radiology residency programs in the United States for dissemination to their residents, collecting information about trainees' NM/MI exposure during residency and factors that may attract them to NM/MI. RESULTS: A total of 198 trainees responded to the survey, 34 of whom plan on pursuing a career in NM/MI. Most trainees reported early exposure to NM/MI during residency; most (97.4%) reported ample exposure to general NM/MI and oncologic studies. Less than 3% of trainees reported adequate exposure to therapies, neurological applications, molecular imaging/research advances, and physics. Respondents reported a need for better quality education (38.9%) and exposure to mentors (28.8%) as ways to attract trainees to NM/MI. Routinely encountered clinical pathology was the most interesting for those specializing in NM/MI (29.4%), whereas lifestyle was the most attractive aspect of NM/MI for those not pursuing a career in the field (27.4%). NM/MI-associated research was the least attractive for those specializing in NM/MI (35.3%), while job market concerns was the least attractive aspect for those not specializing in NM/MI (37.2%). Trainees planning to specialize in NM/MI reported higher satisfaction with their orientation to NM/MI during their first clinical rotation compared to those who do not plan to specialize in the field (3.03/5.00 and 2.67/5.00, respectively, p = 0.04). CONCLUSION: This survey highlights several factors that training programs and national societies can target to improve interest in NM/MI among radiology residents. We found that optimized education initiatives, including improved orientation to the field, increased mentoring, and career opportunities are essential levers for recruiting radiology trainees into the NM/MI workforce.

Thyroid Cancers Exhibit Oncogene-Enhanced Macropinocytosis that Is Restrained by IGF1R and Promote Albumin-Drug Conjugate Response.

PURPOSE: Oncogene-driven macropinocytosis fuels nutrient scavenging in some cancer types, yet whether this occurs in thyroid cancers with prominent MAPK-ERK and PI3K pathway mutations remains unclear. We hypothesized that understanding links between thyroid cancer signaling and macropinocytosis might uncover new therapeutic strategies. EXPERIMENTAL DESIGN: Macropinocytosis was assessed across cells derived from papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), non-malignant follicular thyroid, and aggressive anaplastic thyroid cancer (ATC), by imaging fluorescent dextran and serum albumin. The impacts of ectopic BRAFV600E and mutant RAS, genetic PTEN silencing, and inhibitors targeting RET, BRAF, and MEK kinases were quantified. BrafV600E p53-/- ATC tumors in immunocompetent mice were used to measure efficacy of an albumin-drug conjugate comprising microtubule-destabilizing monomethyl auristatin E (MMAE) linked to serum albumin via a cathepsin-cleavable peptide (Alb-vc-MMAE). RESULTS: FTC and ATC cells showed greater macropinocytosis than non-malignant and PTC cells. ATC tumors accumulated albumin at 8.8% injected dose per gram tissue. Alb-vc-MMAE, but not MMAE alone, reduced tumor size by >90% (P < 0.01). ATC macropinocytosis depended on MAPK/ERK activity and nutrient signaling, and increased by up to 230% with metformin, phenformin, or inhibition of IGF1Ri in monoculture but not in vivo. Macrophages also accumulated albumin and express the cognate IGF1R ligand, IGF1, which reduced ATC responsiveness to IGF1Ri. CONCLUSIONS: These findings identify regulated oncogene-driven macropinocytosis in thyroid cancers and demonstrate the potential of designing albumin-bound drugs to efficiently treat them.