Type of MRI contrast, tissue gadolinium, and fibrosis.

It has been presupposed that the thermodynamic stability constant (K(therm)) of gadolinium-based MRI chelates relate to the risk of precipitating nephrogenic systemic fibrosis. The present study compared low-K(therm) gadodiamide with high-K(therm) gadoteridol in cultured fibroblasts and rats with uninephrectomies. Gadolinium content was assessed using scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy in paraffin-embedded tissues. In vitro, fibroblasts demonstrated dose-dependent fibronectin generation, transforming growth factor-ß production, and expression of activated myofibroblast stress fiber protein α-smooth muscle actin. There were negligible differences with respect to toxicity or proliferation between the two contrast agents. In the rodent model, gadodiamide treatment led to greater skin fibrosis and dermal cellularity than gadoteridol. In the kidney, both contrast agents led to proximal tubule vacuolization and increased fibronectin accumulation. Despite large detectable gadolinium signals in the spleen, skin, muscle, and liver from the gadodiamide-treated group, contrast-induced fibrosis appeared to be limited to the skin and kidney. These findings support the hypothesis that low-K(therm) chelates have a greater propensity to elicit nephrogenic systemic fibrosis and demonstrate that certain tissues are resistant to these effects.

Gadolinium Retention after Contrast-Enhanced Magnetic Resonance Imaging: A Narratative Review.

Over the past five years, several studies have reported deposition and retention of gadolinium in the brain after administration of gadolinium-based contrast agents (GBCAs) during radiological procedures. Patients with renal insufficiency cannot filter gadolinium efficiently; however, gadolinium is also retained in the brain of some adults and pediatrics with no renal impairment. In the literature, data is mostly available from retrospective magnetic resonance imaging (MRI) studies, where gadolinium deposition may be indirectly measured by evaluating changes in T1 signal intensity in the brain tissues, particularly in the deep gray matter such as the dentate nucleus and/or globus pallidus. Many pathological studies have reported a direct correlation between T1 signal changes and gadolinium deposition in human and animal autopsy specimens, which raised concerns on the use of GBCAs, particularly with linear chelators. The association between gadolinium accumulation and occurrence of physical and neurological side effects or neurotoxic damage has not yet been conclusively demonstrated. Studies have also observed that gadolinium is deposited in the extracranial tissues, such as the liver, skin, and bone, of patients with normal kidney function. This narrative review describes the effects of different types of GBCAs in relation to gadolinium deposition, evaluates current evidence on gadolinium deposition in various tissues of the human body, and summarizes the current recommendations regarding the use of GBCAs.

Physicians with self-diagnosed gadolinium deposition disease: a case series.

OBJECTIVE: The objective of this study was to allow physicians with self-diagnosed gadolinium deposition disease symptoms to report their own experience. MATERIALS AND METHODS: Nine physicians (seven females), with a mean age of 50.5 ± 8.3 years, participated in this case series. Nationalities were American (n = 6), British, Portuguese, and Romanian. Medical practices included internal medicine (n = 2), trauma surgery, ophthalmology, gastroenterology, psychiatry, family medicine, obstetrics/gynecology, and general practice. RESULTS: Genetically, eight of the physicians were of central European origin. Underlying autoimmune conditions were present in four. Symptoms developed after a single injection in one physician and after multiple injections in eight. The precipitating agent was gadobenate dimeglumine in four physicians, gadobutrol in three, gadoterate meglumine in one, and gadopentetate dimeglumine in one. The most consistent symptoms were a burning sensation, brain fog, fatigue, distal paresthesia, fasciculations, headache, and insomnia. Eight of the physicians were compelled to change their practice of medicine. CONCLUSION: In the various physicians, gadolinium deposition disease showed common features and had a substantial impact on daily activity. Physicians are educated reporters on disease, so their personal descriptions should spark interest in further research.

OBJETIVO: O objetivo deste estudo foi possibilitar que médicos com sintomas de doença de deposição de gadolínio autodiagnosticada relatassem sua própria experiência. MATERIAIS E MÉTODOS: Nove médicos (sete mulheres), com média de idade de 50,5 ± 8,3 anos, participaram desta série de casos. As nacionalidades foram americana (n = 6), britânica, portuguesa e romena. As práticas médicas incluíram medicina interna (n = 2), traumatologia, oftalmologia, gastroenterologia, psiquiatria, medicina de família, ginecologia/obstetrícia e clínica geral. RESULTADOS: Geneticamente, oito dos médicos tinham origem europeia central. Condições autoimunes subjacentes estavam presentes em quatro médicos. Os sintomas se desenvolveram após uma única injeção em um médico e após várias injeções em oito. O agente precipitante foi gadobenato dimeglumina em quatro médicos, gadobutrol em três, gadoterato meglumina em um e gadopentetato dimeglumina em um. Os sintomas mais consistentes foram sensação de queimação, confusão mental, fadiga, parestesia distal, fasciculações, cefaleia e insônia. Oito dos médicos foram forçados a alterar a sua prática médica. CONCLUSÃO: Em vários médicos, a doença de deposição de gadolínio mostrou características comuns e teve um impacto substancial na atividade diária. Os médicos são repórteres treinados sobre doenças, assim, suas descrições pessoais devem despertar interesse em pesquisas futuras.

Physicians with self-diagnosed gadolinium deposition disease: a case series / Médicos com doença de deposição de gadolínio autodiagnosticada: relato de série

Abstract Objective: The objective of this study was to allow physicians with self-diagnosed gadolinium deposition disease symptoms to report their own experience. Materials and Methods: Nine physicians (seven females), with a mean age of 50.5 ± 8.3 years, participated in this case series. Nationalities were American (n = 6), British, Portuguese, and Romanian. Medical practices included internal medicine (n = 2), trauma surgery, ophthalmology, gastroenterology, psychiatry, family medicine, obstetrics/gynecology, and general practice. Results: Genetically, eight of the physicians were of central European origin. Underlying autoimmune conditions were present in four. Symptoms developed after a single injection in one physician and after multiple injections in eight. The precipitating agent was gadobenate dimeglumine in four physicians, gadobutrol in three, gadoterate meglumine in one, and gadopentetate dimeglumine in one. The most consistent symptoms were a burning sensation, brain fog, fatigue, distal paresthesia, fasciculations, headache, and insomnia. Eight of the physicians were compelled to change their practice of medicine. Conclusion: In the various physicians, gadolinium deposition disease showed common features and had a substantial impact on daily activity. Physicians are educated reporters on disease, so their personal descriptions should spark interest in further research.

Resumo Objetivo: O objetivo deste estudo foi possibilitar que médicos com sintomas de doença de deposição de gadolínio autodiagnosticada relatassem sua própria experiência. Materiais e Métodos: Nove médicos (sete mulheres), com média de idade de 50,5 ± 8,3 anos, participaram desta série de casos. As nacionalidades foram americana (n = 6), britânica, portuguesa e romena. As práticas médicas incluíram medicina interna (n = 2), traumatologia, oftalmologia, gastroenterologia, psiquiatria, medicina de família, ginecologia/obstetrícia e clínica geral. Resultados: Geneticamente, oito dos médicos tinham origem europeia central. Condições autoimunes subjacentes estavam presentes em quatro médicos. Os sintomas se desenvolveram após uma única injeção em um médico e após várias injeções em oito. O agente precipitante foi gadobenato dimeglumina em quatro médicos, gadobutrol em três, gadoterato meglumina em um e gadopentetato dimeglumina em um. Os sintomas mais consistentes foram sensação de queimação, confusão mental, fadiga, parestesia distal, fasciculações, cefaleia e insônia. Oito dos médicos foram forçados a alterar a sua prática médica. Conclusão: Em vários médicos, a doença de deposição de gadolínio mostrou características comuns e teve um impacto substancial na atividade diária. Os médicos são repórteres treinados sobre doenças, assim, suas descrições pessoais devem despertar interesse em pesquisas futuras.

Revisiting the risks of MRI with Gadolinium based contrast agents-review of literature and guidelines.

UNLABELLED: Gadolinium based contrast agents (GBCA) have been linked to the occurrence of nephrogenic systemic fibrosis (NSF) in renal impaired patients. The exact interaction between the various different available formulations and occurrence of NSF is not completely understood, but has been postulated. This association has triggered public health advisory bodies to issue guidelines and best practice recommendations on its use. As a result, the reported incidence of NSF, as well as the published use of GBCA-enhanced magnetic resonance imaging in renal impairment, has seen a decline. Understanding of the events that led to these recommendations can increase clinical awareness and the implications of their usage. We present a review of published literature and a brief overview of practice recommendations, guidelines and manuals on contrast safety to aide everyday imaging practice. TEACHING POINTS: • Low risk gadolinium based contrast agents should be the choice in renal insufficiency. • Higher doses have been linked to NSF development. Doses should be as low as possible. • Clear documentation of date, dose and type of formulation used should be noted. • Post-scan dialysis should be arranged as soon as possible and feasible. • Pre- existing inflammatory state is a risk factor; liver insufficiency is not a contraindication.