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    Exceedingly small iron oxide nanoparticles as positive MRI contrast agents.
    Proc Natl Acad Sci U S A 2017 Feb 13. Epub 2017 Feb 13.
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139;
    Medical imaging is routine in the diagnosis and staging of a wide range of medical conditions. In particular, magnetic resonance imaging (MRI) is critical for visualizing soft tissue and organs, with over 60 million MRI procedures performed each year worldwide. About one-third of these procedures are contrast-enhanced MRI, and gadolinium-based contrast agents (GBCAs) are the mainstream MRI contrast agents used in the clinic. Read More

    [Plasma exchange in nephrology: Indications and technique].
    Nephrol Ther 2017 Feb 16;13(1):43-55. Epub 2017 Jan 16.
    Service des urgences néphrologiques et transplantation rénale, hôpital Tenon, 4, rue de la Chine, 75020 Paris, France; Université Pierre-et-Marie-Curie, 4, place Jussieu, 75005 Paris, France.
    Plasma exchange is a non-selective apheresis technique that can be performed by filtration or centrifugation allowing rapid purification of high molecular weight pathogens. An immunosuppressive treatment is generally associated to reduce the rebound effect of the purified substance. Substitution solutes such as human albumin and macromolecules are needed to compensate for plasma extraction. Read More

    Gd-DTPA-induced dynamic metabonomic changes in rat biofluids.
    Magn Reson Imaging 2017 Jan 14. Epub 2017 Jan 14.
    Changchun Institute of Applied Chemistry Chinese Academy of Sciences, No. 5625, Renmin Street, Changchun 130022, China.
    Objectives: The purposes of this study were (1) to detect the dynamic metabonomic changes induced by gadopentetate dimeglumine (Gd-DTPA) and (2) to investigate the potential metabolic disturbances associated with the pathogenesis of nephrogenic systemic fibrosis (NSF) at the early stage.

    Methods: A nuclear magnetic resonance (NMR)-based metabolomics approach was used to investigate the urinary and serum metabolic changes induced by a single tail vein injection of Gd-DTPA (dosed at 2 and 5mmol/kg body weight) in rats. Urine and serum samples were collected on days 1, 2 and 7 after dosing. Read More

    Gadolinium-based contrast agents: A comprehensive risk assessment.
    J Magn Reson Imaging 2017 Jan 13. Epub 2017 Jan 13.
    Mallinckrodt Institute of Radiology, Washington University, Saint Louis, Missouri, USA.
    Gadolinium-based contrast agents (GBCAs) have been used in magnetic resonance imaging (MRI) since the 1980s and are now administered in up to 35% of all MRI examinations. While GBCAs were initially felt to carry minimal risk, the subsequent identification of GBCAs as the key etiologic factor in the development of nephrogenic systemic fibrosis (NSF) has raised concerns about the broader health impacts of gadolinium exposure. Clinicians, radiologists, and patients should be aware of the most up-to-date data pertaining to the risks of GBCA administration. Read More

    Differential Expression of Hedgehog and Snail in Cutaneous Fibrosing Disorders: Implications for Targeted Inhibition.
    Am J Clin Pathol 2016 Dec;146(6):709-717
    From the Dermatopathology Unit, Pathology Service, Massachusetts General Hospital and Harvard Medical School, Boston
    Objectives: To examine Hedgehog signaling in cutaneous fibrosing disorders for which effective approved therapies are lacking, expand our knowledge of pathophysiology, and explore the rationale for targeted inhibition.

    Methods: Stain intensity and percentage of cells staining for Sonic hedgehog (Shh), Indian hedgehog (Ihh), Patched (Ptch), glycogen synthase kinase 3 β (GSK3-β), β-catenin, and Snail were evaluated in human skin biopsy specimens of keloid, hypertrophic scar (Hscar), scleroderma, nephrogenic systemic fibrosis (NSF), scar, and normal skin using a tissue microarray.

    Results: Ihh, but not Shh, was detected in a significantly larger proportion of cells for all case types. Read More

    Severe thrombocytopenia induced by iodinated contrast after coronary angiography: The use of gadolinium contrast and intravascular ultrasound as an alternative to guide percutaneous coronary intervention.
    Rev Port Cardiol 2017 Jan 14;36(1):61.e1-61.e4. Epub 2016 Dec 14.
    Haemodynamic and Interventional Cardiology, University Hospital Virgen del Rocío, Seville, Spain.
    Acute contrast-induced thrombocytopenia is a rare event with the use of modern low osmolarity iodinated contrast media. The pathophysiological mechanism that causes platelet counts to drop has not been identified, but an immunological mechanism is suspected due to cytotoxicity after previous exposure to contrast. We report the case of a 47-year-old male patient with acute severe thrombocytopenia due to iodinated contrast media exposure. Read More

    [Cutaneous manifestations in renal diseases].
    Hautarzt 2016 Dec;67(12):960-969
    Dermatologische Abteilung, Donauspital, Langobardenstr. 122, 1220, Wien, Österreich.
    In addition to general skin changes like pallor or dryness and the frequent, often excruciating nephrogenic pruritus, specific diseases in patients with renal failure may occur. Acquired perforating dermatoses are usually also highly pruritic. Calciphylaxis is a severe disease with poor prognosis. Read More

    A novel blood-pooling MR contrast agent: Carboxymethyl-diethylaminoethyl dextran magnetite.
    Mol Med Rep 2016 Dec 21;14(6):5195-5198. Epub 2016 Oct 21.
    Department of Radiology, Shiga University of Medical Science, Otsu, Shiga 520‑2192, Japan.
    Gadofosveset trisodium is available as a prolonged pooling vascular contrast agent for magnetic resonance imaging. As gadolinium (Gd)-based agents may increase the risk for nephrogenic systemic fibrosis in patients with severe renal insufficiency, the present study synthesized carboxymethyl-diethylaminoethyl dextran magnetite (CMEADM) particles as a blood-pooling, non-Gd‑based contrast agent. CMEADM particles carry a negative or positive charge due to the binding of amino and carboxyl groups to the hydroxyl group of dextran. Read More

    The diagnostic value of non-contrast enhanced quiescent interval single shot (QISS) magnetic resonance angiography at 3T for lower extremity peripheral arterial disease, in comparison to CT angiography.
    J Cardiovasc Magn Reson 2016 Oct 20;18(1):71. Epub 2016 Oct 20.
    MR Scientific, SIEMENS Healthcare, Shanghai, China.
    Background: The high incidence of renal insufficiency in patients with Peripheral Arterial Disease raises the concern for nephrogenic systemic fibrosis (NSF) with respect to contrast enhanced MRA. The risk of NSF is eliminated with non-contrast enhanced magnetic resonance angiography. The purpose of the current study is to compare image quality and diagnostic performance of non-contrast enhanced Quiescent Interval Single Shot (QISS) magnetic resonance angiography at 3 T versus CT angiography for evaluation of lower extremity Peripheral Arterial Disease (PAD). Read More

    Revisiting the Pharmacokinetic Profiles of Gadolinium-Based Contrast Agents: Differences in Long-Term Biodistribution and Excretion.
    Invest Radiol 2016 Nov;51(11):691-700
    From Guerbet, Roissy CdG Cedex, France.
    Objectives: Gadolinium-based contrast agents (GBCAs) have been used for years for magnetic resonance imaging examinations. Because of their rapid blood clearance, they were considered as very safe products until some of them were shown to induce nephrogenic systemic fibrosis in patients with renal failure and hypersignals on T1-weighted unenhanced brain scans of patients with normal renal function. To date, these adverse effects have been related almost exclusively to the use of low-stability linear agents, which are more prone to release free gadolinium. Read More

    Incidence of Nephrogenic Systemic Fibrosis Using Gadobenate Dimeglumine in 1423 Patients With Renal Insufficiency Compared With Gadodiamide.
    Invest Radiol 2016 Nov;51(11):701-705
    From the Departments of *Radiology, and †Medical Physics, University of Wisconsin, Madison, WI; ‡Department of Dermatology, University of California San Francisco, San Francisco, CA; §Department of Radiology, Saint Louis University, Saint Louis, MO; ∥Division of Dermatology, John H. Stroger Jr Hospital of Cook County, Chicago, IL; Departments of ¶Medicine, and #Obstetrics and Gynecology, University of Wisconsin, Madison, WI.
    Objective: The purpose of this study was to assess the incidence of nephrogenic systemic fibrosis (NSF) before and after educational interventions, implementation of a clinical screening process, and change to gadobenate dimeglumine in patients who had an estimated glomerular filtration rate (eGFR) of 30 mL/min per 1.72 m or less.

    Methods: This is a Health Insurance Portability and Accountability Act compliant, institutional review board exempt study. Read More

    Incidence and Risk Factors for Gadolinium-Based Contrast Agent Immediate Reactions.
    Top Magn Reson Imaging 2016 Dec;25(6):257-263
    Department of Medical Imaging, University of Arizona, Tucson, AZ.
    Since their clinical introduction in 1988, gadolinium-based contrast agents (GBCAs) have demonstrated an excellent safety profile with a reported acute adverse reaction rate ranging from 0.01% to 2%. By comparison, the acute adverse reaction rate of low osmolar nonionic computed tomography contrast agents (CTCs) ranges from 0. Read More

    Observational study on the safety profile of gadoterate meglumine in 35,499 patients: The SECURE study.
    J Magn Reson Imaging 2016 Oct 11. Epub 2016 Oct 11.
    Central Institute for Radiology and Neuroradiology, Krankenhaus Nordwest, Frankfurt am Main, Germany.
    Purpose: To investigate the safety of gadoterate meglumine and identify the incidence of nephrogenic systemic fibrosis (NSF).

    Materials And Methods: An international prospective observational study was conducted from November 2008 to June 2013. A total of 35,499 adults and children who were scheduled to undergo contrast-enhanced MRI using gadoterate meglumine were analyzed (female, 53. Read More

    Gadolinium tissue deposition in brain and bone.
    Magn Reson Imaging 2016 Dec 5;34(10):1359-1365. Epub 2016 Oct 5.
    Until recognition of the association of nephrogenic systemic fibrosis (NSF) and gadolinium based contrast agents (GBCA) in 2006, these agents were considered extremely safe and without major adverse effects. Even after the recognition of NSF, most physicians considered all GBCAs to be safe when used in patients with normal renal function. This belief has been called into question with the discovery by Kanda in 2014 that gadolinium (Gd) is deposited in brain tissue in patients with normal kidney function. Read More

    Effects of Gadodiamide on cell proliferation and collagen production in cultured human dermal fibroblasts.
    Arch Dermatol Res 2016 Dec 28;308(10):695-701. Epub 2016 Sep 28.
    Department of Dermatology, Dokkyo Medical University, School of Medicine, Mibu, Tochigi, Japan.
    Nephrogenic systemic fibrosis (NSF) is a disease characterized by fibrosis of the systemic organs in patients with renal failure. Following the findings of recent epidemiological studies and the finding of gadolinium (Gd) in the skin tissue of NSF patients, it is now definitely known that the use of Gd contrast agents can trigger NSF. To date, however, the exact mechanism underlying the induction of fibrosis in various organs by Gd remains unexplained. Read More

    Exploring the elusive link between subclinical fibrosis and clinical events in end-stage renal disease: does cardiac magnetic resonance imaging hold the key?
    Kidney Int 2016 Oct;90(4):729-32
    Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada. Electronic address:
    Extensive myocardial fibrosis is known to occur in patients undergoing dialysis due to a variety of mechanisms not necessarily restricted to coronary artery disease. Fibrosis may predispose to reentry arrhythmias and long-term myocardial dysfunction, and sudden death and congestive heart failure are the most frequent causes of death in patients undergoing renal replacement therapy. Despite the high accuracy of magnetic resonance for imaging of myocardial fibrosis, its use has been restricted by the risk of inducing nephrogenic systemic sclerosis with the injection of gadolinium. Read More

    Association Between MRI Exposure During Pregnancy and Fetal and Childhood Outcomes.
    JAMA 2016 Sep;316(9):952-61
    Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada5Keenan Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.
    Importance: Fetal safety of magnetic resonance imaging (MRI) during the first trimester of pregnancy or with gadolinium enhancement at any time of pregnancy is unknown.

    Objective: To evaluate the long-term safety after exposure to MRI in the first trimester of pregnancy or to gadolinium at any time during pregnancy.

    Design, Setting, And Participants: Universal health care databases in the province of Ontario, Canada, were used to identify all births of more than 20 weeks, from 2003-2015. Read More

    Gadolinium toxicity: Iron and ferroportin as central targets.
    Magn Reson Imaging 2016 Dec 28;34(10):1373-1376. Epub 2016 Aug 28.
    Division of Nephrology & Center for Immunity, Inflammation and Regeneration, University of Virginia, Charlottesville, VA. Electronic address:
    Gadolinium-based magnetic resonance (MR) contrast agents (GBCM) causes a devastating systemic fibrosing illness, nephrogenic systemic fibrosis (NSF), in patients with reduced kidney function. GBCM targets iron-recycling CD163- and ferroportin-expressing macrophages to release labile iron that mediates gadolinium toxicity and NSF. GBCA might similarly target iron-rich, ferroportin-expressing structures such as globus pallidus and cerebellar dentate nucleus in the brain to result in metal accumulation and potential toxicity. Read More

    Unenhanced 3D turbo spin echo MR angiography of lower extremity arteries: comparison with 128-MDCT angiography.
    Radiol Med 2016 Dec 29;121(12):916-925. Epub 2016 Aug 29.
    Radiology Department, School of Medicine, Suleyman Demirel University, Isparta, 32260, Turkey.
    Purpose: This study aimed to investigate the feasibility and diagnostic power of unenhanced 3D turbo spin echo MR angiography sequence (a technique based on subtraction of corresponding images acquired in diastole and systole, Syngo Native Space-Siemens healthcare) to identify peripheral artery disease (PAD).

    Materials And Methods: Thirty patients (619 arterial segments in total) suspected with PAD and who were assessed with lower extremity MDCT angiography were examined starting from the level of aortic bifurcation for both lower extremities by 3D native space MR angiography. Two readers assessed the image quality of native space MR angiography and number of lesions, their degrees of stenosis and localizations. Read More

    Gadolinium deposition disease: Initial description of a disease that has been around for a while.
    Magn Reson Imaging 2016 Dec 13;34(10):1383-1390. Epub 2016 Aug 13.
    Department of Radiology, University of North Carolina, Chapel Hill, NC, USA; Department of Radiology, Hospital Garcia de Orta, Almada, Portugal.
    Purpose: To describe the clinical manifestations of presumed gadolinium toxicity in patients with normal renal function.

    Materials And Methods: Participants were recruited from two online gadolinium toxicity support groups. The survey was anonymous and individuals were instructed to respond to the survey only if they had evidence of normal renal function, evidence of gadolinium in their system beyond 30days of this MRI, and no pre-existent clinical symptoms and/or signs of this type. Read More

    Gadobutrol in Renally Impaired Patients: Results of the GRIP Study.
    Invest Radiol 2017 Jan;52(1):55-60
    From the *Institute of Clinical Radiology and Nuclear Medicine, University Hospital Mannheim, Mannheim, Germany; †Clinical Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology, Medical University Graz, Graz, Austria; ‡Department of Radiology and Nuclear Medicine, University of Basel Hospital, Basel, Switzerland; §Department of Diagnostic and Interventional Radiology, University Leipzig-Heart Center, Leipzig, Germany; ∥Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria; ¶Institute for Clinical Radiology, Ludwig-Maximilian University of Munich-Grosshadern Hospital, Munich, Germany; #Department of Medical Imaging, University Health Network and University of Toronto, Toronto, Ontario, Canada; **Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Frankfurt am Main, Germany; ††Department of Radiology Experimental Imaging Center, San Raffaele Hospital, Vita-Salute University, Milan, Italy; ‡‡Bayer Pharmaceuticals, Radiology, Whippany, NJ; §§Bayer Pharma AG, Radiology, Berlin, Germany; and ∥∥Department of Gynecology, Obstetrics, and Reproductive Medicine, University Medical School of Saarland, Homburg/Saar, Germany.
    Objective: The aim of this study was to assess the potential risk of gadobutrol-enhanced magnetic resonance imaging (MRI) in patients with moderate to severe renal impairment for the development of nephrogenic systemic fibrosis (NSF).

    Materials And Methods: We performed a prospective, international, multicenter, open-label study in 55 centers. Patients with moderate to severe renal impairment scheduled for any gadobutrol-enhanced MRI were included. Read More

    3 Tesla-Diffusion Tensor Imaging in Autosomal Dominant Polycystic Kidney Disease: The Nephrologist's Point of View.
    Nephron 2016 10;134(2):73-80. Epub 2016 Aug 10.
    Department of Clinical and Experimental Medicine, Nephrology and Dialysis Unit, University of Messina, Messina, Italy.
    Background/aims: CT, MRI and ultrasound are currently used for screening and follow-up of individuals affected by autosomal dominant polycystic kidney disease (ADPKD). Dynamic contrast-enhanced MRI studies renal perfusion after gadolinium administration, with possible side effects, such as nephrogenic systemic fibrosis. The aim of our study was to evaluate the clinical application of 3 Tesla (3T)-diffusion tensor image (DTI) in ADPKD patients, correlating its parameters, such as fractional anisotropy (FA), and apparent diffusion coefficient (ADC) with kidney function tests. Read More

    Adverse Reactions to Gadoterate Meglumine: Review of Over 25 Years of Clinical Use and More Than 50 Million Doses.
    Invest Radiol 2016 Sep;51(9):544-51
    From the *Department of Radiology, Saint Louis Hospital APHP and University Paris Diderot, Paris, France; †Department of Radiology, University of Washington School of Medicine, Seattle, WA; ‡Department of Neuroradiology, Université Paris Descartes; §INSERM UMR894, Hôpital Sainte-Anne, Paris; and ∥GUERBET, Roissy CdG, France.
    Objective: The aim of this study was to evaluate the safety profile of gadoterate meglumine from clinical trials, postmarketing observational studies, and pharmacovigilance reports of adverse drug reactions (ADRs) encompassing 25 years of clinical use and over 50 million administered doses.

    Materials And Methods: Assessment of the safety of gadoterate meglumine through processing and review of all safety data was collected after magnetic resonance imaging procedures. All ADRs originated from 3 major sources: (1) a clinical study database including 50 phase I to IV studies involving 2822 patients, (2) a safety database including 8 postmarketing safety studies (PMSs) involving 151,050 patients, and (3) a pharmacovigilance database compiling safety experience following over 50 million doses administered between March 1989 and September 2015. Read More

    Defining myocardial tissue abnormalities in end-stage renal failure with cardiac magnetic resonance imaging using native T1 mapping.
    Kidney Int 2016 Oct 5;90(4):845-52. Epub 2016 Aug 5.
    Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Scotland, UK.
    Noninvasive quantification of myocardial fibrosis in end-stage renal disease is challenging. Gadolinium contrast agents previously used for cardiac magnetic resonance imaging (MRI) are contraindicated because of an association with nephrogenic systemic fibrosis. In other populations, increased myocardial native T1 times on cardiac MRI have been shown to be a surrogate marker of myocardial fibrosis. Read More

    Unenhanced respiratory-navigated NATIVE(®) TrueFISP magnetic resonance angiography in the evaluation of renal arteries: Comparison with contrast-enhanced magnetic resonance angiography.
    Diagn Interv Imaging 2017 Feb 5;98(2):133-140. Epub 2016 Aug 5.
    Department of radiology, school of medicine, Süleyman Demirel university, 32260 Isparta, Turkey.
    Purpose: To compare unenhanced three-dimensional (3D) NATIVE(®) true fast imaging with steady-state precession (TrueFISP) magnetic resonance (MR) angiography with the more conventional MR angiography technique obtained after intravenous administration of a gadolinium chelate in the evaluation of renal arteries and their branches in patients with suspected renal artery stenosis.

    Materials And Methods: A total of 39 patients (25 men, 14 women) with a mean age of 51.4±17. Read More

    Adverse Effects of Gadolinium-Based Contrast Agents: Changes in Practice Patterns.
    Top Magn Reson Imaging 2016 Aug;25(4):163-9
    *Department of Radiology †Segal Cancer Centre ‡Lady Davis Institute for Medical Research, Jewish General Hospital & McGill University, Montreal, Quebec, Canada.
    Gadolinium-based contrast agents have been used for magnetic resonance imaging (MRI) examinations since the late 1980s with an excellent overall cumulative safety record. Initially favored for use in patients with renal impairment because of lack of significant nephrotoxic effect at clinical doses, in 2006, multiple reports convincingly linked the rare but serious disease nephrogenic systemic fibrosis to the administration of gadolinium-based contrast agents in patients with severe renal failure. This in turn led to new policies on administration of these agents, resulting in changes in practice patterns that have virtually resulted in the elimination of the disease after the year 2009. Read More

    Alternatives to GBCA: Are We There Yet?
    Top Magn Reson Imaging 2016 Aug;25(4):171-5
    University of Michigan Health System, Ann Arbor, MI.
    Gadolinium has been widely used as the contrast agent of choice for magnetic resonance imaging (MRI). However, gadolinium administration is not always desired due to its inherent enhancement properties and potential side effects (nephrogenic systemic fibrosis). This article reviews gadolinium alternatives, iron-, and manganese- based agents, and their current clinical usage for contrast-enhanced MRI examinations. Read More

    A Milestone: Approval of CEUS for Diagnostic Liver Imaging in Adults and Children in the USA.
    Ultraschall Med 2016 Jun 8;37(3):229-32. Epub 2016 Jun 8.
    The approval of microbubbles with the inert gas sulfur hexafluoride (SF6) and a palmitic acid shell (SonoVue(®), Bracco Geneva, CH) for the diagnostic imaging of liver tumors in adults and children by the FDA in the United States represents a milestone for contrast-enhanced ultrasound (CEUS).This warrants a look back at the history of the development of CEUS. The first publications based on echocardiographic observations of right ventricular contrast phenomena caused by tiny air bubbles following i. Read More

    Minor changes in the macrocyclic ligands but major consequences on the efficiency of gold nanoparticles designed for radiosensitization.
    Nanoscale 2016 Jun;8(23):12054-65
    Institut UTINAM, UMR 6213 CNRS-UBFC, Université de Bourgogne Franche-Comté, 25030 Besançon Cedex, France.
    Many studies have been devoted to adapting the design of gold nanoparticles to efficiently exploit their promising capability to enhance the effects of radiotherapy. In particular, the addition of magnetic resonance imaging modality constitutes an attractive strategy for enhancing the selectivity of radiotherapy since it allows the determination of the most suited delay between the injection of nanoparticles and irradiation. This requires the functionalization of the gold core by an organic shell composed of thiolated gadolinium chelates. Read More

    Altered Nitric Oxide System in Cardiovascular and Renal Diseases.
    Chonnam Med J 2016 May 20;52(2):81-90. Epub 2016 May 20.
    Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
    Nitric oxide (NO) is synthesized by a family of NO synthases (NOS), including neuronal, inducible, and endothelial NOS (n/i/eNOS). NO-mediated effects can be beneficial or harmful depending on the specific risk factors affecting the disease. In hypertension, the vascular relaxation response to acetylcholine is blunted, and that to direct NO donors is maintained. Read More

    Gadolinium in Humans: A Family of Disorders.
    AJR Am J Roentgenol 2016 Aug 25;207(2):229-33. Epub 2016 May 25.
    1 Department of Radiology, University of North Carolina at Chapel Hill, CB 7510 - 2001 Old Clinic Bldg, 101 Manning Dr, Chapel Hill, NC 27599-7510.
    Objective: The literature informs us that gadolinium can cause health issues. At least four major gadolinium disorders, including the two well-recognized nephrogenic systemic fibrosis and severe acute adverse event, have been identified.

    Conclusion: We propose naming the histopathologically proven presence of gadolinium in brain tissue "gadolinium storage condition," and we describe a new entity that represents symptomatic deposition of gadolinium in individuals with normal renal function, for which we propose the designation "gadolinium deposition disease. Read More

    Centrality of bone marrow in the severity of gadolinium-based contrast-induced systemic fibrosis.
    FASEB J 2016 Sep 24;30(9):3026-38. Epub 2016 May 24.
    University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA; South Texas Veterans Health Care System, San Antonio,Texas, USA
    Systemic fibrosis can be induced in humans with gadolinium-based contrast, and cumulative doses correlate with severity. Bone marrow-derived fibrocytes accumulate in the dermis. Whether target organs liberate chemokines to recruit these fibrocytes or whether fibrocytes are stimulated to home to the affected tissue is unknown. Read More

    Cardiovascular MRI with ferumoxytol.
    Clin Radiol 2016 Aug 21;71(8):796-806. Epub 2016 May 21.
    Diagnostic Cardiovascular Imaging Laboratory, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
    The practice of contrast-enhanced magnetic resonance angiography (CEMRA) has changed significantly in the span of a decade. Concerns regarding gadolinium (Gd)-associated nephrogenic systemic fibrosis in those with severely impaired renal function spurred developments in low-dose CEMRA and non-contrast MRA as well as efforts to seek alternative MR contrast agents. Originally developed for MR imaging use, ferumoxytol (an ultra-small superparamagnetic iron oxide nanoparticle), is currently approved by the US Food and Drug Administration for the treatment of iron deficiency anaemia in adults with renal disease. Read More

    Pathophysiology of gadolinium-associated systemic fibrosis.
    Am J Physiol Renal Physiol 2016 Jul 4;311(1):F1-F11. Epub 2016 May 4.
    University of Texas Health Science Center at San Antonio, San Antonio, Texas.
    Systemic fibrosis from gadolinium-based magnetic resonance imaging contrast is a scourge for the afflicted. Although gadolinium-associated systemic fibrosis is a rare condition, the threat of litigation has vastly altered clinical practice. Most theories concerning the etiology of the fibrosis are grounded in case reports rather than experiment. Read More

    Endothelial to Mesenchymal Transition (EndoMT) in the Pathogenesis of Human Fibrotic Diseases.
    J Clin Med 2016 Apr 11;5(4). Epub 2016 Apr 11.
    Jefferson Institute of Molecular Medicine, Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, 233 S. 10th Street, Suite 509 BLSB, Philadelphia, PA 19107, USA.
    Fibrotic diseases encompass a wide spectrum of clinical entities including systemic fibrotic diseases such as systemic sclerosis, sclerodermatous graft versus host disease, nephrogenic systemic fibrosis, and IgG₄-associated sclerosing disease, as well as numerous organ-specific disorders including radiation-induced fibrosis, and cardiac, pulmonary, liver, and kidney fibrosis. Although their causative mechanisms are quite diverse, these diseases share the common feature of an uncontrolled and progressive accumulation of fibrous tissue macromolecules in affected organs leading to their dysfunction and ultimate failure. The pathogenesis of fibrotic diseases is complex and despite extensive investigation has remained elusive. Read More

    Contrast-enhanced magnetic resonance venography in pediatric patients with chronic kidney disease: initial experience with ferumoxytol.
    Pediatr Radiol 2016 Aug 8;46(9):1332-40. Epub 2016 Apr 8.
    Department of Radiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
    Ferumoxytol is an ultra-small superparamagnetic iron oxide (USPIO) particle that is FDA-approved for parenteral treatment of iron deficiency anemia in adults with chronic kidney disease. Because of the association between gadolinium-based contrast agents and nephrogenic systemic fibrosis in patients with severe chronic kidney disease, we sought to evaluate the diagnostic role of ferumoxytol-enhanced MR venography in children with chronic kidney disease. Twenty children underwent 22 high-resolution ferumoxytol-enhanced MR venography examinations at 3. Read More

    Gadolinium-based contrast agent toxicity: a review of known and proposed mechanisms.
    Biometals 2016 Jun 6;29(3):365-76. Epub 2016 Apr 6.
    MedInsight Research Institute, Baltimore, MD, 21202, USA.
    Gadolinium chelates are widely used as contrast media for magnetic resonance imaging. The approved gadolinium-based contrast agents (GBCAs) have historically been considered safe and well tolerated when used at recommended dosing levels. However, for nearly a decade, an association between GBCA administration and the development of nephrogenic systemic fibrosis (NSF) has been recognized in patients with severe renal impairment. Read More

    Safety of gadobutrol in more than 1,000 pediatric patients: subanalysis of the GARDIAN study, a global multicenter prospective non-interventional study.
    Pediatr Radiol 2016 Aug 4;46(9):1317-23. Epub 2016 Apr 4.
    Medical & Clinical Affairs Radiology, Bayer Pharma, Berlin, Germany.
    Background: Gadobutrol is a gadolinium-based contrast agent, uniquely formulated at 1.0 mmol/ml. Although there is extensive safety evidence on the use of gadobutrol in adults, few studies have addressed the safety and tolerability of gadobutrol in pediatric patients. Read More

    Imaging patients with renal impairment.
    Abdom Radiol (NY) 2016 Jun;41(6):1108-21
    Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar Street, Room TE-2, PO Box 208042, New Haven, CT, 06520, USA.
    Imaging with intravascular contrast media is generally considered safe, particularly in patients without renal failure. However, as renal function deteriorates, the potential risk of nonallergic-type adverse events increases. This presents a unique challenge, particularly when the use of intravenous contrast media is deemed essential for diagnostic purposes. Read More

    Edema, Hyperpigmentation, Induration: 3 Skin Signs Heralding Danger in Patients on Maintenance Hemodialysis.
    Medicine (Baltimore) 2016 Mar;95(12):e3121
    From the Departments of Nephrology (SB, SW, AB, AK, AM), Infectiology (OW), and Dermatology (AK), University Duisburg-Essen, Essen, Germany; Medical Statistics Hamm (TK), Hamm, Germany; and Department of General, Visceral and Transplantation Surgery (GK), University Duisburg-Essen, Essen, Germany.
    Skin changes are common in patients on dialysis. This study focused on putative associations of specific skin findings with comorbidities and mortality.We performed a retrospective analysis of data from 508 patients on maintenance hemodialysis therapy in 7 centers in the German State of North Rhine Westphalia. Read More

    Safety of Gadobutrol: Results From 42 Clinical Phase II to IV Studies and Postmarketing Surveillance After 29 Million Applications.
    Invest Radiol 2016 Sep;51(9):537-43
    From the *Radiology, Bayer Pharma AG, Berlin; †Department of Gynecology, Obstetrics, and Reproductive Medicine, University Medical School of Saarland, Homburg, Saarland; ‡Global Integrated Analysis & Life Cycle Management Statistics, Bayer Pharma AG, Wuppertal, Germany; §Global Pharmacovigilance and Risk Management, and ∥Radiology, Bayer Pharma AG, Whippany, NJ.
    Objective: The aim of this study was to provide a systematic safety analysis of gadobutrol after more than 29 million applications in clinical routine.

    Materials And Methods: Forty-two clinical development phase II to IV studies on gadobutrol or comparator and the postmarketing safety surveillance database for gadobutrol (1998-2015) were analyzed. Adverse events (AEs) and drug-related AEs were evaluated in the clinical development database and spontaneous adverse drug reactions (ADRs) in the postmarketing database. Read More

    High Levels of Gadolinium Deposition in the Skin of a Patient With Normal Renal Function.
    Invest Radiol 2016 May;51(5):280-9
    From the Departments of *Radiology and Radiological Sciences; †Neurosurgery and Hematology/Oncology, and ‡Pathology, Medical University of South Carolina, Charleston, SC; §Departments of Radiology and Neurological Surgery, University of Washington, Seattle, WA; ∥Department of Physical Medicine & Rehabilitation and ¶Dermatology & Dermatologic Surgery, Medical University of South Carolina; and #National Institute of Standards and Technology, Chemical Sciences Division, Charleston, SC.
    Objective: The aim of this study was to assess gadolinium deposition in the skin of a patient with normal renal function, based on estimated glomerular filtration rate values greater than 59 mL/min/1.73 m(2) after exposure to large cumulative doses of gadolinium-based contrast agents (GBCAs).

    Materials And Methods: The patient underwent 61 contrasted brain MRI scans over the course of 11 years. Read More

    Safety of the Gadolinium-Based Contrast Agents for Magnetic Resonance Imaging, Focusing in Part on Their Accumulation in the Brain and Especially the Dentate Nucleus.
    Invest Radiol 2016 May;51(5):273-9
    From the Department of Diagnostic, Interventional, and Pediatric Radiology, University Hospital of Bern, Inselpital, Bern, Switzerland.
    The established class of intravenous contrast media for magnetic resonance imaging is the gadolinium chelates, more generally referred to as the gadolinium-based contrast agents (GBCAs). These can be differentiated on the basis of stability in vivo, with safety and tolerability of the GBCAs dependent upon chemical and biologic inertness. This review discusses first the background in terms of development of these agents and safety discussions therein, and second their relative stability based both on in vitro studies and clinical observations before and including the advent of nephrogenic systemic fibrosis. Read More

    High signal intensity in dentate nucleus and globus pallidus on unenhanced T1-weighted MR images in three patients with impaired renal function and vascular calcification.
    Contrast Media Mol Imaging 2016 May 11;11(3):245-50. Epub 2016 Jan 11.
    Institute of Diagnostic, Pediatric, and Interventional Radiology, University Hospital Bern (Inselspital), Bern, Switzerland.
    Gadolinium-based contrast agents (primarily those with linear chelates) are associated with a dose-dependent signal hyperintensity in the dentate nucleus and the globus pallidus on unenhanced T1-weighted MRI following administration to selected patients with normal renal function. The accumulation of gadolinium has also been reported in the skin, heart, liver, lung, and kidney of patients with impaired renal function suffering from nephrogenic systemic fibrosis (NSF). Here we report on three patients with impaired renal function and vascular calcification (two with confirmed NSF) whose unenhanced T1-weighted MRIs showed conspicuous high signal intensity in the dentate nucleus and the globus pallidus after they had been exposed to relatively low doses of linear gadolinium-based contrast agents (0. Read More

    Functional Magnetic Resonance Imaging in Acute Kidney Injury: Present Status.
    Biomed Res Int 2016 26;2016:2027370. Epub 2016 Jan 26.
    Sichuan Key Laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 63 Wenhua Road, Shunqing District, Nanchong, Sichuan 637000, China.
    Acute kidney injury (AKI) is a common complication of hospitalization that is characterized by a sudden loss of renal excretory function and associated with the subsequent development of chronic kidney disease, poor prognosis, and increased mortality. Although the pathophysiology of renal functional impairment in the setting of AKI remains poorly understood, previous studies have identified changes in renal hemodynamics, perfusion, and oxygenation as key factors in the development and progression of AKI. The early assessment of these changes remains a challenge. Read More

    Interaction of Gd-DTPA with phosphate and phosphite: toward the reaction intermediate in nephrogenic systemic fibrosis.
    Dalton Trans 2016 Mar;45(12):5388-94
    State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical engineering, Xiamen University, Xiamen, 361005, China.
    Direct reactions of the MRI contrast agent K2[Gd(DTPA)(H2O)]·5H2O (1) (H5DTPA = diethylenetriaminepentaacetic acid) with dipotassium hydrogen phosphate (K2HPO4) or phosphite (K2HPO3) result in the isolation of well-defined Gd-DTPA phosphite K6[Gd2(DTPA)2(HPO3)]·7H2O (2) or phosphate K6[Gd2(DTPA)2(HPO4)]·10H2O (3), respectively. Their lanthanum analogs K4[La2(DTPA)2(H2O)]·8H2O (4), K6[La2(DTPA)2(HPO3)]·7H2O (5) and K6[La2(DTPA)2(HPO4)]·10H2O (6) are used for comparison. The phosphate and phosphite groups are able to substitute the coordinated water molecules in 1 and 4 in a close physiological aqueous solution, and act as bridging ligands to link adjacent Ln(DTPA)(2-) (Ln = Gd and La) into dimeric structures. Read More

    Gadolinium deposition within the dentate nucleus and globus pallidus after repeated administrations of gadolinium-based contrast agents-current status.
    Neuroradiology 2016 May 12;58(5):433-41. Epub 2016 Feb 12.
    Faculty of Medicine, University of Nis, Bul. Dr. Zorana Djindjica 81, Nis, 18000, Serbia.
    Introduction: Gadolinium-based contrast agents (GBCAs) have been used clinically since 1988 for contrast-enhanced magnetic resonance imaging (CE-MRI). Generally, GBCAs are considered to have an excellent safety profile. However, GBCA administration has been associated with increased occurrence of nephrogenic systemic fibrosis (NSF) in patients with severely compromised renal function, and several studies have shown evidence of gadolinium deposition in specific brain structures, the globus pallidus and dentate nucleus, in patients with normal renal function. Read More

    Macrocyclic and Other Non-Group 1 Gadolinium Contrast Agents Deposit Low Levels of Gadolinium in Brain and Bone Tissue: Preliminary Results From 9 Patients With Normal Renal Function.
    Invest Radiol 2016 Jul;51(7):447-53
    From the *Department of Radiology, University of Washington, Seattle; †Department of Radiology, Toho University Ohashi Medical Center, Tokyo, Japan; ‡Department of Pathology, University of Washington, Seattle; §Department of Neurology, Toho University Omori Medical Center, Tokyo, Japan; and ∥Department of Environmental Health, University of Washington, Seattle.
    Objective: The purpose of this study was to determine whether gadolinium (Gd) is deposited in brain and bone tissues in patients receiving only non-Group 1 agents, either macrocyclic or linear protein interacting Gd-based contrast agents, with normal renal function. Group 1 agents are linear agents most associated with nephrogenic systemic fibrosis that the US Federal Drug Administration has defined as contraindicated in patients at risk for this disease.

    Materials And Methods: This study was institutional review board approved and Health Insurance Portability and Accountability Act compliant for retrospective review of records and also had signed autopsy consent authorizing use of decedent's tissue in research studies. Read More

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