Interferon-gamma release assay conversion after Mycobacterium tuberculosis exposure specifically associates with greater risk of progression to tuberculosis: A prospective cohort study in Leicester, UK.

OBJECTIVES: We investigated whether quantifying the serial QuantiFERON-TB Gold (QFT) response improves tuberculosis (TB) risk stratification in pulmonary TB (PTB) contacts. METHODS: A total of 297 untreated adult household PTB contacts, QFT tested at baseline and 3 months after index notification, were prospectively observed (median 1460 days). Normal variance of serial QFT responses was established in 46 extrapulmonary TB contacts. This informed categorisation of the response in QFT-positive PTB contacts as converters, persistently QFT-positive with significant increase (PPincrease), and without significant increase (PPno-increase). RESULTS: In total, eight co-prevalent TB (disease ≤3 months after index notification) and 12 incident TB (>3 months after index notification) cases were diagnosed. Genetic linkage to the index strain was confirmed in all culture-positive progressors. The cumulative 2-year incident TB risk in QFT-positive contacts was 8.4% (95% confidence interval, 3.0-13.6%); stratifying by serial QFT response, significantly higher risk was observed in QFT converters (28%), compared with PPno-increase (4.8%) and PPincrease (3.7%). Converters were characterised by exposure to index cases with a shorter interval from symptom onset to diagnosis (median reduction 50.0 days, P = 0.013). CONCLUSIONS: QFT conversion, rather than quantitative changes of a persistently positive serial QFT response, is associated with greater TB risk and exposure to rapidly progressive TB.

PET-CT-guided characterisation of progressive, preclinical tuberculosis infection and its association with low-level circulating Mycobacterium tuberculosis DNA in household contacts in Leicester, UK: a prospective cohort study.

BACKGROUND: Incipient tuberculosis, a progressive state of Mycobacterium tuberculosis infection with an increased risk of developing into tuberculosis disease, remains poorly characterised. Animal models suggest an association of progressive infection with bacteraemia. Circulating M tuberculosis DNA has previously been detected in pulmonary tuberculosis by use of Actiphage, a bacteriophage-based real-time PCR assay. We aimed to investigate whether serial [18F]fluorodeoxyglucose ([18F]FDG)-PET-CT could be used to characterise the state and progressive trajectory of incipient tuberculosis, and examine whether these PET-CT findings are associated with Actiphage-based detection of circulating M tuberculosis DNA. METHODS: We did a prospective 12-month cohort study in healthy, asymptomatic adults (aged ≥16 years) who were household contacts of patients with pulmonary tuberculosis, and who had a clinical phenotype of latent tuberculosis infection, in Leicester, UK. Actiphage testing of participants' blood samples was done at baseline, and [18F]FDG PET-CT at baseline and after 3 months. Baseline PET-CT features were classified as positive, indeterminate, or negative, on the basis of the quantitation (maximum standardised uptake value [SUVmax]) and distribution of [18F]FDG uptake. Microbiological sampling was done at amenable sites of [18F]FDG uptake. Changes in [18F]FDG uptake after 3 months were quantitatively categorised as progressive, stable, or resolving. Participants received treatment if features of incipient tuberculosis, defined as microbiological detection of M tuberculosis or progressive PET-CT change, were identified. FINDINGS: 20 contacts were recruited between Aug 5 and Nov 5, 2020; 16 of these participants had a positive result on IFNγ release assay (QuantiFERON-TB Gold Plus [QFT]) indicating tuberculosis infection. Baseline PET-CT scans were positive in ten contacts (all QFT positive), indeterminate in six contacts (three QFT positive), and negative in four contacts (three QFT positive). Four of eight PET-CT-positive contacts sampled had M tuberculosis identified (three through culture, one through Xpert MTB/RIF Ultra test) from intrathoracic lymph nodes or bronchial wash and received full antituberculosis treatment. Two further unsampled PET-CT-positive contacts were also treated: one with [18F]FDG uptake in the lung (SUVmax 9·4) received empirical antituberculosis treatment and one who showed progressive [18F]FDG uptake received preventive treatment. The ten untreated contacts with [18F]FDG uptake at baseline (seven QFT positive) had stable or resolving changes at follow-up and remained free of tuberculosis disease after 12 months. A positive baseline Actiphage test was associated with the presence of features of incipient tuberculosis requiring treatment (p=0·018). INTERPRETATION: Microbiological and inflammatory features of incipient tuberculosis can be visualised on PET-CT and are associated with M tuberculosis detection in the blood, supporting the development of pathogen-directed blood biomarkers of tuberculosis risk. FUNDING: MRC Confidence in Concept.

Understanding the Molecular Aspects of Vitamins in Parkinson's Disease: Present-day Concepts and Perspectives.

Parkinson's disease (PD) is designated as a convoluted nerve cell devastating disorder that encompasses the profound declination of dopaminergic (DArgic) nerve cells of the mesencephalon region. The condition is sketched by four eminent motor manifestations, namely, slow movement, muscle tension, shaking, and disrupted balance, but the pathology behind these manifestations is still vague. Modern-day medicinal treatment emphasizes curbing the manifestations via introducing a gold standard (levodopa) instead of forestalling the DArgic nerve cell destruction. Therefore, the invention and utilization of novel neuroprotective candidates are of paramount importance in overcoming PD. Vitamins are organic molecules engaged in the modulation of evolution, procreation, biotransformation, and other operations of the body. Numerous studies employing varying experimental models have promulgated a prominent linkage between vitamins and PD. Vitamins, owing to their antioxidant and gene expression modulation abilities, might be efficacious in PD therapy. Recent corroborations depict that adequate augmentation of vitamins might de-escalate the manifestations and emergence of PD; however, the safety of daily vitamin intake must be considered. By assembling the comprehensive information obtained from existing publications via searching various renowned medical portals, the investigators render in-depth insights into the physiological association amongst vitamins (D, E, B3, and C) and PD and concerned pathological processes and their safeguarding actions in varied PD models. Furthermore, the manuscript delineates the remedial aptitude of vitamins in PD therapy. Conclusively, augmentation of vitamins (owing to their antioxidant and gene expression regulation capabilities) might appear as a novel and terribly efficacious ancillary therapeutic approach for PD.

Exploring the multifocal role of phytoconstituents as antidepressants.

Depression is the most prevalent and devastating neuropsychiatric disorder. There are several conventional antidepressants used for the treatment of depression. But due to their undesired adverse effects, patient compliance is very poor. Thus, developing novel medications for the treatment of depression is a critical strategic priority for meeting therapeutic demands. Current research is looking for alternatives to traditional antidepressants to reduce undesired side effects and increase efficacy. Phytoconstituents provide a wide research range in antidepressant treatments. In the present article, we have conducted a comprehensive assessment of neurological evidence, which supports the usefulness of phytoconstituents in the treatment of the depressive disorder. Secondary plant metabolites including alkaloids, polyphenols, glycosides, saponins, and terpenoids were found to exhibit antidepressant action. Most of the phytoconstituents were found to mediate their antidepressant effect through the upregulation of brain-derived neurotrophic factor (BDNF), serotonin, noradrenaline, and dopamine. Some were also found to exert antidepressant effects by inhibiting the monoamine oxidase (MAO) activity and hypothalamic-pituitary-adrenal (HPA) axis overactivity.

Postulating the possible cellular signalling mechanisms of antibody drug conjugates in Alzheimer's disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders in the world. Although the basic pathology of the disease is elucidated, it is difficult to restore or prevent the worsening of neurodegeneration and its symptoms. Antibody and small molecule-based approaches have been studied and are in study individually, but a combined approach like conjugation has not been performed to date. The conjugation between antibodies and drugs which are already used for Alzheimer's treatment or developed specifically for this purpose may have better efficacy and dual action in mitigating Alzheimer's disease. A probable mechanism for antibody-drug conjugates in Alzheimer's disease is discussed in the present review.

A Persistent Tuberculosis Outbreak in the UK Is Characterized by Hydrophobic fadB4-Deficient Mycobacterium tuberculosis That Replicates Rapidly in Macrophages.

The genetic diversity of Mycobacterium tuberculosis can influence disease severity and transmissibility. To better understand how this diversity influences individuals and communities, we phenotyped M. tuberculosis that was causing a persistent outbreak in the East Midlands, United Kingdom. Compared to nonoutbreak isolates, bacilli had higher lipid contents and more hydrophobic cell surfaces. In macrophage infection models, the bacteria increased more rapidly, provoked the enhanced accumulation of macrophage lipid droplets and enhanced the secretion of IL-1ß. Natural deletions in fadB4, nrdB, and plcC distinguished the outbreak isolates from other lineage 3 isolates in the region. fadB4 is annotated with a putative role in cell envelope biosynthesis, so the loss of this gene has the potential to alter the interactions of bacteria with immune cells. Reintroduction of fadB4 to the outbreak strain led to a phenotype that more closely resembled those of nonoutbreak strains. The improved understanding of the microbiological characteristics and the corresponding genetic polymorphisms that associate with outbreaks have the potential to inform tuberculosis control. IMPORTANCE Tuberculosis (TB) killed 1.5 million people in 2020 and affects every country. The extent to which the natural genetic diversity of Mycobacterium tuberculosis influences disease manifestation at both the individual and epidemiological levels remains poorly understood. Insights into how pathogen polymorphisms affect patterns of TB have the potential to translate into clinical and public health practice. Two distinct lineage 3 strains isolated from local TB outbreaks, one of which (CH) was rapidly terminated and the other of which (Lro) persistently transmitted for over a decade, provided us with an opportunity to study these issues. We compared genome sequences, microbiological characteristics, and early immune responses that were evoked upon infection. Our results indicate that the natural lack of fadB4 in the Lro strain contributes to its unique features.

Blood transcriptomics reveal the evolution and resolution of the immune response in tuberculosis.

Blood transcriptomics have revealed major characteristics of the immune response in active TB, but the signature early after infection is unknown. In a unique clinically and temporally well-defined cohort of household contacts of active TB patients that progressed to TB, we define minimal changes in gene expression in incipient TB increasing in subclinical and clinical TB. While increasing with time, changes in gene expression were highest at 30 d before diagnosis, with heterogeneity in the response in household TB contacts and in a published cohort of TB progressors as they progressed to TB, at a bulk cohort level and in individual progressors. Blood signatures from patients before and during anti-TB treatment robustly monitored the treatment response distinguishing early and late responders. Blood transcriptomics thus reveal the evolution and resolution of the immune response in TB, which may help in clinical management of the disease.

Diagnostic Radiology Residency Assessment Tools: A Scoping Review.

PURPOSE: The multifaceted nature of learning in diagnostic radiology residency requires a variety of assessment methods. However, the scope and quality of assessment tools has not been formally examined. A scoping review was performed to identify assessment tools available for radiology resident training and to evaluate the validity of these tools. METHODS: A literature search was conducted through multiple databases and on-line resources. Inclusion criteria were defined as any tool used in assessment of radiology resident competence. Data regarding residents, evaluators and specifics of each tool was extracted. Each tool was subjected through a validation process with a customized rating scale using the 5 categories of validity: content, response process, internal structure, relations to other variables, and consequences. RESULTS: The initial search returned 447 articles; 35 were included. The most evaluated competency being overall knowledge (31%), most common published journal was Academic Radiology (24%); evaluations were most commonly set in the United States (57%). In terms of validation, we found low adherence to modern integrated validity, with 34% of studies including a definition of validity. When specifically examining the 5 domains of validation evidence presented, most were either absent or of low rigor (70%). Only one study presented a modern definition of validation (3%, 1/35). CONCLUSION: We identified 35 evaluation tools covering a variety of competency areas. However, few of these tools have been validated. Development of new validated assessment tools or validation of existing tools is essential for the ongoing transition to a competency-based curriculum.

Delivering CaRMS Transparency: Applicant Review and Selection Process of a Single-Center Diagnostic Radiology Residency Training Program.

PURPOSE: To report the current application review and selection process in our Canadian diagnostic radiology program at the University of Ottawa for both Canadian and international medical graduates. APPLICATION REVIEW AND SELECTION PROCESS: Submitted applications fulfilling institutional requirements were selected for a detailed file review after preliminary screening. A diverse group of file reviewers and interviewers was selected. Interviews were offered based on file review score sheet outcomes. Each interviewer generated a postinterview rank list. Applicants were reviewed and discussed from highest to lowest rank based on a preliminary compiled rank list generated from the average of the postinterview rank lists. Group discussion and a consensus model were used to create a final applicant rank list. CONCLUSIONS: We outlined our systematic, consistent selection process which aligns with current best practices. This description may inform other programs wishing to adopt or optimize strategies to improve candidate assessments and selection processes.

Diagnostic Radiology Residency Application Trends: Canadian Match Results From 2010-2020.

INTRODUCTION: Rapid advancements in artificial intelligence (AI) have generated uncertainty about the future of radiology among medical students. However, it is unclear whether this has affected radiology residency applications. The purpose of this study was to evaluate recent trends in the Canadian radiology residency match. METHODS: Canadian Resident Matching Service annual data reports from 2010-2020 were collected. Statistics were extracted for Canadian medical graduates applying to radiology in the R-1 main residency match and analyzed using linear regression. RESULTS: The number of available radiology residency positions decreased (P = .01); declining from 84 in 2010 to 81 in 2020 (mean = 83.1). The overall number of applicants did not change (P = .08, mean = 131.8). The proportion of applicants with radiology as their first choice decreased (P = .001); declining from 4.5% in 2010 to 3.1% in 2020 (mean = 3.4%). The number of applicants applying exclusively to radiology also decreased (P = .02); declining from 39 in 2010 to 16 in 2020 (mean = 23). Positions per applicant (P = 0.24, mean = 0.64), and positions per applicant with radiology as their first choice did not change (P = 0.07, mean = 0.91). CONCLUSION: While the overall number of students applying to radiology did not change, the number of applicants ranking radiology as their first or only choice decreased sharply. This analysis corroborates recent reports of increased workload, burnout, and declining reimbursement as well as uncertainty about the future of radiology due to advances in AI.

Socio-demographic heterogeneity in the prevalence of COVID-19 during lockdown is associated with ethnicity and household size: Results from an observational cohort study.

BACKGROUND: Accumulating evidence indicates that COVID-19 causes adverse outcomes in ethnic minority groups. However, little is known about the impact of ethnicity and household size on acquiring infection with SARS-CoV-2. METHODS: We undertook a retrospective cohort study, in Leicester (UK), of all individuals assessed for COVID-19 with polymerase chain reaction (PCR) testing at University Hospitals of Leicester NHS Trust between 1st March and 28th April 2020. We used logistic regression to identify sociodemographic, clinical and temporal factors associated with SARS-CoV-2 PCR positivity before/after lockdown. FINDINGS: 971/4051 (24.0%) patients with suspected COVID-19 were found to be PCR positive for SARS-CoV-2. PCR positivity was more common amongst individuals from ethnic minortiy backgrounds than their White counterparts (White 20.0%, South Asian 37.5%, Black 36.1%, Other 32.2%; p<0.001 for all ethnic minority groups vs White). After adjustment, compared to White ethnicity, South Asian (aOR 2.44 95%CI 2.01, 2.97), Black (aOR 2.56 95%CI 1.71, 3.84) and Other (aOR 2.53 95%CI 1.74, 3.70) ethnicities were more likely to test positive, as were those with a larger estimated household size (aOR 1.06 95%CI 1.02, 1.11). We saw increasing proportions of positive tests in the three weeks post-lockdown amongst the ethnic minority , but not the White, cohort. Estimated household size was associated with PCR positivity after, but not before, lockdown (aOR 1.10 95%CI 1.03, 1.16). INTERPRETATION: In individuals presenting with suspected COVID-19, those from ethnic minority communities and larger households had an increased likelihood of SARS-CoV-2 PCR positivity. Pandemic control measures may have more rapid impact on slowing viral transmission amongst those of White ethnicity compared to ethnic minority groups, Research is urgently required to understand the mechanisms underlying these disparities and whether public health interventions have differential effects on individuals from ethnic minority groups. FUNDING: 10.13039/100006662 NIHR.

Missed Breast Cancer: Effects of Subconscious Bias and Lesion Characteristics.

Medical errors are a substantial cause of morbidity and mortality and the third leading cause of death in the United States. Errors resulting in missed breast cancer are the most common reason for medical malpractice lawsuits against all physicians. Missed breast cancers are breast malignancies that are detectable at retrospective review of a previously obtained mammogram that was prospectively reported as showing negative, benign, or probably benign findings. Investigators in prior studies have found that up to 35% of both interval cancers and screen-detected cancers could be classified as missed. As such, in conjunction with having awareness of the most common misleading appearances of breast cancer, it is important to understand the cognitive processes and unconscious biases that can impact image interpretation, thereby helping to decrease the number of missed breast cancers. The various cognitive processes that lead to unconscious bias in breast imaging, such as satisfaction of search, inattention blindness, hindsight, anchoring, premature closing, and satisfaction of reporting, are outlined in this pictorial review of missed breast cancers. In addition, strategies for reducing the rates of these missed cancers are highlighted. The most commonly missed and misinterpreted lesions, including stable lesions, benign-appearing masses, one-view findings, developing asymmetries, subtle calcifications, and architectural distortion, also are reviewed. This information will help illustrate why and how breast cancers are missed and aid in the development of appropriate minimization strategies in breast imaging. ©RSNA, 2020.

Peritonitis from facultative anaerobic gram-negative bacilli likely due to translocation of bacteria from gut in a patient undergoing peritoneal dialysis.

The peritonitis caused by gram-negative organisms is a serious complication encountered in patients undergoing peritoneal dialysis, often causing high morbidity and mortality. There has been recognition of peritonitis caused by uncommon organisms because of improved microbiological detection techniques. The healthcare providers involved in the management of these patients should be very vigilant. We report a rare case of peritonitis caused by Citrobacter freundii. A 42-year-old male on peritoneal dialysis for five years presented with abdominal pain and cloudy effluent. The peritoneal fluid analysis was consistent with peritonitis, and peritoneal fluid culture grew Citrobacter freundii. The patient was treated with two courses of double antibiotic coverage with intraperitoneal ceftazidime and oral ciprofloxacin, which failed to resolve the infection and hence resulted in the removal the peritoneal dialysis catheter and dialysis modality change.

Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis.

Although mouse infection models have been extensively used to study the host response to Mycobacterium tuberculosis, their validity in revealing determinants of human tuberculosis (TB) resistance and disease progression has been heavily debated. Here, we show that the modular transcriptional signature in the blood of susceptible mice infected with a clinical isolate of M. tuberculosis resembles that of active human TB disease, with dominance of a type I interferon response and neutrophil activation and recruitment, together with a loss in B lymphocyte, natural killer and T cell effector responses. In addition, resistant but not susceptible strains of mice show increased lung B cell, natural killer and T cell effector responses in the lung upon infection. Notably, the blood signature of active disease shared by mice and humans is also evident in latent TB progressors before diagnosis, suggesting that these responses both predict and contribute to the pathogenesis of progressive M. tuberculosis infection.

A Novel, High-sensitivity, Bacteriophage-based Assay Identifies Low-level Mycobacterium tuberculosis Bacteremia in Immunocompetent Patients With Active and Incipient Tuberculosis.

The haematogenous dissemination of Mycobacterium tuberculosis (Mtb) is critical to the pathogenesis of progressive tuberculous infections in animal models. Using a novel, phage-based blood assay, we report the first concordant evidence in well-characterized, immunocompetent human cohorts, demonstrating associations of Mtb bacteremia with progressive phenotypes of latent infection and active pulmonary tuberculosis.

Breast pain and cancer: should we continue to work-up isolated breast pain?

PURPOSE: To assess the cancer detection rate (CDR) in patients presenting with isolated breast pain. METHODS: A retrospective review was performed of consecutive patients presenting to a large tertiary care academic center or an affiliated hospital with isolated breast pain from October 1, 2013 to September 30, 2015. Medical records were reviewed for patient demographics, pain characteristics, imaging findings, and outcome. RESULTS: The study cohort was comprised of 971 exams in 953 patients, with a median age of 50 years. A total of 62.5% (607/971) of the cases were assessed by mammography and ultrasound, 24.4% (237/971) by ultrasound only, and 13.1% (127/971) by mammography only. Including the abnormalities detected in the asymptomatic breast, 88.7% (861/971) of the cases were negative or had benign findings (BI-RADS 1 and 2), 6.8% (66/971) were probably benign (BI-RADS 3), 3.9% (38/971) were suspicious (BI-RADS 4), and 0.6% (6/971) were highly suggestive of malignancy (BI-RADS 5). CDR on initial work-up was 0.8% (8/953), of which 0.6% (4/690) was in average-risk patients while 1.5% (4/263) was in higher-than-average risk patients. CONCLUSIONS: CDR in patients presenting with isolated breast pain overall was low, comparable to the expected incidence of breast cancer in asymptomatic women. Work-up for isolated breast pain may therefore be unnecessary and lead to overutilization of healthcare resources. Routine screening mammography should be encouraged and higher-than-average risk patients may benefit from additional tests.

Outcomes after Surgery for Early Stage Breast Cancer in Women Staged With Preoperative Breast Magnetic Resonance Imaging According to Breast Tissue Density.

PURPOSE: To determine surgical outcomes and breast cancer disease-free survival outcomes of women with early stage breast cancer with and without use of preoperative breast MRI according to breast tissue density. METHODS: Women with early stage breast cancer diagnosed from 2004 to 2009 were classified into 2 groups: 1) those with dense and heterogeneously dense breasts (DB); 2) those with nondense breasts (NDB) (scattered fibroglandular and fatty replaced tissue). The 2 groups were reviewed to determine who underwent preoperative MRI. Breast tissue density was determined with mammography according to ACR BI-RADS. Patients were compared according to tumor size, grade, stage, and treatment. Survival analysis was performed using Kaplan-Meier estimates. RESULTS: In total, 261 patients with mean follow-up of 85 months (25-133) were included: 156 DB and 105 NDB. Disease-free survival outcomes were better in the DB group in patients with MRI than in those without MRI: patients with MRI had significantly fewer local recurrences (P < 0.016) and metachronous contralateral breast cancers (P < 0.001), but this was not the case in the NDB group. Mastectomies were higher in the DB group with preoperative MRI than in those without MRI (P < 0.01), as it was in the NDB group (P > 0.05). CONCLUSIONS: Preoperative breast MRI was associated with reduced local recurrence and metachronous contralateral cancers in the DB group, but not in the NDB group; however, the DB patients with MRI had higher mastectomy rates.

Can Adrenal Adenomas Be Differentiated From Adrenal Metastases at Single-Phase Contrast-Enhanced CT?

OBJECTIVE: The purpose of this study is to evaluate whether adrenal metastases can be reliably differentiated from adenomas at single-phase contrast-enhanced CT. MATERIALS AND METHODS: Sixty-one consecutive patients from a single-institution lung cancer registry (40 metastases and 36 adenomas) who underwent single-phase contrast-enhanced CT at baseline diagnosis were retrospectively studied by two radiologists (blinded to the diagnoses) who independently evaluated four features previously described in adenomas: smooth margin, rim enhancement, central vein sign (preserved adrenal vein), and homogeneity (using a 5-point Likert scale). A third radiologist measured size and attenuation and performed quantitative texture analysis. Comparisons were performed using chi-square, logistic regression, and ROC analysis. RESULTS: Metastases were larger than adenomas (mean [± SD] 24 ± 11 mm [range, 11-66 mm] vs 19 ± 5 mm [range, 11-34 mm]; p = 0.012), with overlap between groups. Attenuation of metastases and adenomas did not differ significantly (58.2 ± 21.0 HU [range, 21.0-108.0] vs 55.5 ± 21.5 HU [range, 14.0-105.0]; p = 0.582). Skewness and kurtosis did not differ between groups (p = 0.612 and 0.978, respectively), whereas entropy was higher in metastases (p = 0.013). The AUC for entropy to diagnose metastases was 0.65 (95% CI, 0.52-0.77). Tumor margin, rim enhancement, and the central vein sign did not differ between groups (p > 0.05). Metastases were considered more heterogeneous by both radiologists (p = 0.001 and 0.011, respectively), and agreement was satisfactory (κ = 0.51). Likert scores of 4 or 5 (mostly or completely heterogeneous) yielded sensitivity and specificity for diagnosis of metastases of 32.5% and 97.2%, respectively, for radiologist 1 and 22.5% and 97.2%, respectively, for radiologist 2. CONCLUSION: Adrenal metastases cannot be reliably differentiated from adenomas at single-phase contrast-enhanced CT. Increased tumor size and heterogeneity were specific findings but showed unacceptably low sensitivity.

Gadolinium Deposition in the Brain: A Systematic Review of Existing Guidelines and Policy Statement Issued by the Canadian Association of Radiologists.

Emerging evidence has confirmed that, following administration of a gadolinium-based contrast agent (GBCA), very small amounts of gadolinium will deposit in the brain of humans with intact blood-brain barriers. The literature is evolving rapidly and the degree to which gadolinium will deposit for a particular GBCA or class of GBCAs remains undetermined. Several studies suggest that linear GBCAs deposit more gadolinium in the brain compared with macrocyclic GBCAs; however, our understanding of the molecular composition of deposited gadolinium is preliminary, and the clinical significance of gadolinium deposition remains unknown. To date, there is no conclusive evidence linking gadolinium deposition in the brain with any adverse patient outcome. A panel of radiologists representing the Canadian Association of Radiologists was assembled to assist the Canadian medical imaging community in making informed decisions regarding the issue of gadolinium deposition in the brain. The objectives of the working group were: 1) to review the evidence from animal and human studies; 2) to systematically review existing guidelines and position statements issued by other organizations and health agencies; and 3) to formulate an evidence-based position statement on behalf of the Canadian Association of Radiologists. Based on our appraisal of the evidence and systematic review of 9 guidelines issued by other organizations, the working group established the following consensus statement. GBCA administration should be considered carefully with respect to potential risks and benefits, and only used when required. Standard dosing should be used and repeat administrations should be avoided unless necessary. Gadolinium deposition is one of several issues to consider when prescribing a particular GBCA. Currently there is insufficient evidence to recommend one class of GBCA over another. The panel considered it inappropriate to withhold a linear GBCA if a macrocyclic agent is unavailable, if hepatobiliary phase imaging is required, or if there is a history of severe allergic reaction to a macrocyclic GBCA. Further study in this area is required, and the evidence should be monitored regularly with policy statements updated accordingly.