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Gadolinium deposition

Julian A Rees, Gauthier J-P Deblonde, Dahlia D An, Camille Ansoborlo, Stacey S Gauny, Rebecca J Abergel
Several MRI contrast agent clinical formulations are now known to leave deposits of the heavy metal gadolinium in the brain, bones, and other organs of patients. This persistent biological accumulation of gadolinium has been recently recognized as a deleterious outcome in patients administered Gd-based contrast agents (GBCAs) for MRI, prompting the European Medicines Agency to recommend discontinuing the use of over half of the GBCAs currently approved for clinical applications. To address this problem, we find that the orally-available metal decorporation agent 3,4,3-LI(1,2-HOPO) demonstrates superior efficacy at chelating and removing Gd from the body compared to diethylenetriaminepentaacetic acid, a ligand commonly used in the United States in the GBCA Gadopentetate (Magnevist)...
March 13, 2018: Scientific Reports
Patrício Aguiar, Olga Azevedo, Rui Pinto, Jacira Marino, Carlos Cardoso, Nuno Sousa, Damião Cunha, Derralynn Hughes, José Luís Ducla Soares
BACKGROUND: Cardiomyopathy is a major determinant of overall Fabry disease (FD) prognosis, with the worst outcomes in patients with myocardial fibrosis. Late gadolinium enhancement is currently the gold standard for evaluation of replacement myocardial fibrosis; however, this event is irreversible, thus identification of biomarkers of earlier diffuse fibrosis is paramount. METHODS AND RESULTS: Type I collagen synthesis and degradation biomarkers (PICP [carboxyterminal propeptide of procollagen type I], ICTP [carboxyterminal telopeptide of type I collagen], and MMP1 [matrix metalloproteinase 1] and MMP2) and markers of bone synthesis and degradation were evaluated (to adjust type I collagen metabolism to bone turnover) in FD patients and controls...
March 13, 2018: Journal of the American Heart Association
Ryan T Fitzgerald, Vikas Agarwal, Jenny K Hoang, Frank Gaillard, Andrew Dixon, Emanuel Kanal
RATIONALE AND OBJECTIVES: Brain deposition of gadolinium following the administration of gadolinium-based contrast agents (GBCAs) was initially reported in 2014. Gadolinium deposition is now recognized as a dose-dependent consequence of exposure. The potential clinical implications are not yet understood. The purpose of this study was to determine radiologists' reporting practices in response to gadolinium deposition. MATERIALS AND METHODS: An electronic survey querying radiologists' practices regarding gadolinium deposition was distributed by Radiopaedia...
February 7, 2018: Current Problems in Diagnostic Radiology
Richard Pullicino, Mark Radon, Shubhabrata Biswas, Maneesh Bhojak, Kumar Das
Over the past 3 years, gadolinium-based contrast agents have been linked to MRI signal changes in the brain, which have been found to be secondary to gadolinium deposition in the brain, particularly in the dentate nuclei and globus pallidus even in patients having an intact blood-brain barrier and a normal renal function. This tends to occur more in linear agents than with macrocyclic agents. Nonetheless, there has been no significant evidence that this has any clinical consequence. We reviewed the current evidence related to this new phenomenon and the precautionary approach taken by regulatory agencies...
March 9, 2018: Clinical Neuroradiology
Luca Pasquini, Antonio Napolitano, Emiliano Visconti, Daniela Longo, Andrea Romano, Paolo Tomà, Maria Camilla Rossi Espagnet
In recent years, gadolinium-based contrast agents have been associated with different types of toxicity. In particular, nephrogenic systemic fibrosis, a progressive sclerotic-myxedematous systemic disease of unknown etiology, is related to gadolinium-based contrast agent administration in patients with kidney dysfunction. More recently, evidence of magnetic resonance signal intensity changes on pre-contrast T1-weighted images after multiple gadolinium-based contrast agent administrations resulted in the hypothesis of gadolinium brain accumulation in patients with normal renal function, subsequently confirmed in pathological samples...
March 5, 2018: CNS Drugs
Michael Hunter Lanier, Anup S Shetty, Amber Salter, Geetika Khanna
BACKGROUND: Gadolinium deposition in normal tissues is being increasingly recognized. Children with inflammatory bowel disease (IBD) undergo frequent imaging with contrast-enhanced MR enterography (MRE). PURPOSE: To determine the impact of intravenous (IV) gadolinium in assessment of pediatric IBD by MRE. STUDY TYPE: Retrospective, case series. POPULATION: Radiology information system was searched to identify all children who underwent MRE and endoscopy within 30 days in 2016...
March 5, 2018: Journal of Magnetic Resonance Imaging: JMRI
R Pullicino, K Das
Gadolinium-based contrast agents have greatly expanded the capability of magnetic resonance imaging and have been used extensively in neuroradiology over the past 30 years. When initially developed they were thought to be relatively harmless; it was later discovered they are associated with nephrogenic systemic fibrosis and should be used with caution in certain patient groups, especially those with renal failure. Lately it has been found that the use of these contrast agents may result in deposition of gadolinium in the brain even in patients with an intact blood-brain barrier...
September 2017: Journal of the Royal College of Physicians of Edinburgh
Val M Runge, Johannes T Heverhagen
The question of improved relaxivity, and potential efficacy therein, for a next-generation of magnetic resonance gadolinium chelates with extracellular distribution and renal excretion, which could also be viewed from the perspective of dose, is addressed on the basis of historical development, animal experimentation, and human trials. There was no systematic evaluation that preceded the choice of 0.1 mmol/kg as the standard dose for human imaging with the gadolinium chelates. In part, this dose was chosen owing to bloodwork abnormalities seen in phase I and phase II studies...
February 17, 2018: Investigative Radiology
Enhao Gong, John M Pauly, Max Wintermark, Greg Zaharchuk
BACKGROUND: There are concerns over gadolinium deposition from gadolinium-based contrast agents (GBCA) administration. PURPOSE: To reduce gadolinium dose in contrast-enhanced brain MRI using a deep learning method. STUDY TYPE: Retrospective, crossover. POPULATION: Sixty patients receiving clinically indicated contrast-enhanced brain MRI. SEQUENCE: 3D T 1 -weighted inversion-recovery prepped fast-spoiled-gradient-echo (IR-FSPGR) imaging was acquired at both 1...
February 13, 2018: Journal of Magnetic Resonance Imaging: JMRI
Eric M Gale, Peter Caravan
We discuss how the recent revelation that gadolinium (Gd) from commercially available MRI contrast agents is irreversibly and cumulatively deposited in the central nervous system is driving innovation toward Gd-free contrast agents for neuroradiology.
February 12, 2018: ACS Chemical Neuroscience
Carlo Salvarani, Robert D Brown, Teresa J H Christianson, John Huston, Stephen M Ansell, Caterina Giannini, Gene G Hunder
OBJECTIVES: To record the clinical findings, response to therapy, and course of patients with primary CNS vasculitis (PCNSV) associated with lymphoma. PATIENTS AND METHODS: We reviewed the histories of 936 patients with a diagnosis of any type of vasculitis and lymphoma who were seen at the Mayo Clinic over a 32-year period. Ten patients with both PCNSV and lymphoma were identified. We compared the findings in these 10 patients with those from 158 patients with PCNSV without lymphoma seen over 29 years...
February 2, 2018: Neurology
Richard C Semelka, Miguel Ramalho, Michael Jay, Lisa Hickey, Joseph Hickey
OBJECTIVES: The aim of this study was to report the use of intravenous calcium (Ca)-/zinc (Zn)-diethylene triamine penta-acetic acid (DTPA) for the treatment of 25 symptomatic patients diagnosed with gadolinium deposition disease (GDD). MATERIALS AND METHODS: Written informed consent was obtained. Twenty-five patients (18 women; mean age, 46.8 ± 15.3 years) with a diagnosis of GDD were included. All patients had received at least 1 administration of a gadolinium (Gd)-based contrast agent...
February 6, 2018: Investigative Radiology
F G Moser, C T Watterson, S Weiss, M Austin, J Mirocha, R Prasad, J Wang
BACKGROUND AND PURPOSE: In view of the recent observations that gadolinium deposits in brain tissue after intravenous injection, our aim of this study was to compare signal changes in the globus pallidus and dentate nucleus on unenhanced T1-weighted MR images in patients receiving serial doses of gadobutrol, a macrocyclic gadolinium-based contrast agent, with those seen in patients receiving linear gadolinium-based contrast agents. MATERIALS AND METHODS: This was a retrospective analysis of on-site patients with brain tumors...
February 1, 2018: AJNR. American Journal of Neuroradiology
Luca Pasquini, Maria Camilla Rossi Espagnet, Antonio Napolitano, Daniela Longo, Alice Bertaina, Emiliano Visconti, Paolo Tomà
In the last few years, several scientific papers and reports have demonstrated magnetic resonance (MR) signal intensity (SI) changes on pre-contrast T1-weighted images following multiple gadolinium-based contrast agents (GBCA) administrations, particularly following the exposure to linear GBCAs. Pathological animal and human post-mortem studies have confirmed the relationship between this radiological finding and the presence of gadolinium accumulation in vulnerable brain regions in patients with normal renal function...
January 27, 2018: La Radiologia Medica
Toshiaki Taoka, Shinji Naganawa
After Kanda's first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the 'glymphatic system', which is a coined word that combines 'gl' for glia cell and 'lymphatic' system...
January 25, 2018: Magnetic Resonance in Medical Sciences: MRMS
S Ghazala, J Bilal, E Ross, B Kalb, I B Riaz, K L Herbst
BACKGROUND/AIM: Dercum disease is a rare disorder of painful subcutaneous adipose tissue masses typically presenting as a constellation of signs and symptoms affecting most organs including slow lymphatic flow and fatty liver. METHOD: The University of Arizona Institutional Review Board considered this report exempt after patient consent. Multislice, multisequence magnetic resonance imaging (MRI) of the abdomen and pelvis was performed before and after d-amphetamine, with and without intravenous gadolinium...
January 17, 2018: American Journal of Medicine
Janina Boyken, Thomas Frenzel, Jessica Lohrke, Gregor Jost, Hubertus Pietsch
OBJECTIVE: The aim of this retrospective study was to determine the gadolinium (Gd) concentration in different brain areas in a pig cohort that received repeated administration of Gd-based contrast agents (GBCAs) at standard doses over several years, comparable with a clinical setting. MATERIAL AND METHODS: Brain tissue was collected from 13 Göttingen mini pigs that had received repeated intravenous injections of gadopentetate dimeglumine (Gd-DTPA; Magnevist) and/or gadobutrol (Gadovist)...
January 9, 2018: Investigative Radiology
Young Jin Ryu, Young Hun Choi, Jung-Eun Cheon, Woo-Jin Lee, Subin Park, Ji Eun Park, Woo Sun Kim, In-One Kim
PURPOSE: The aim of this study was to identify the signal intensity (SI) changes in the dentate nucleus (DN) and the globus pallidus (GP) on unenhanced T1-weighted magnetic resonance (MR) images after multiple administration of gadolinium-based contrast agents (GBCAs) in children and compare those changes between linear and macrocyclic GBCAs. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and the requirement for informed consent was waived...
April 2018: Investigative Radiology
Simona Bussi, Laure Penard, Roberta Bonafè, Catherine Botteron, Roberto Celeste, Alessandra Coppo, Roberta Queliti, Miles A Kirchin, Fabio Tedoldi, Federico Maisano
To determine the impact of single and cumulative doses of MultiHance on toxicity, pharmacokinetics, tissue gadolinium presence, behavior and neurological function in juvenile rats. Juvenile male and female rats received either physiological saline or MultiHance at 0.6, 1.25 or 2.5 mmol/kg bodyweight. Animals received either single or six consecutive MultiHance administrations and were sacrificed the day after the last administration or after a 60-day treatment-free period. Animals were assessed for behavior, cognitive function, grip strength, gait, pupillary reflex, and auditory reflex, as well as for physical development, sexual maturation and histopathology...
December 23, 2017: Regulatory Toxicology and Pharmacology: RTP
Francois Mathieu, Erin Morgan, Joyce So, David G Munoz, Warren Mason, Paul Kongkham
BACKGROUND: Oculoleptomeningeal amyloidosis (OLMA) represents a rare subtype of familial transthyretin (TTR) amyloidosis, characterized by deposition of amyloid in cranial and spinal leptomeninges along with ocular involvement. Of more than 100 TTR mutations identified, few have been associated with OLMA. Herein we describe the first report of leptomeningeal amyloidosis associated with the c.381T>G (p.Ile127Met) TTR mutation, linking this variant in the OLMA phenotype. CASE DESCRIPTION: A 53 year-old male presented with a 2-year history of progressive symptoms including upper and lower limb weakness, ataxia, peripheral and autonomic neuropathy...
December 22, 2017: World Neurosurgery
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