Gadolinium Deposition In Tissue Research Articles

Accuracy of Noncontrast T2 SPACE in Active MS Cord Lesion Detection.

The diagnosis of active MS lesions is often based on postgadolinium T1-weighted MR imaging. Recent studies suggest a risk of IV gadolinium to patients, predominantly based on gadolinium deposition in tissue. Noncontrast sequences have shown promise in MS diagnosis, but none differentiate acute from chronic MS lesions. We hypothesized that 3D T2 sampling perfection with application-optimized contrasts by using different flip angle evolution (SPACE) MR imaging can help detect and differentiate active-versus-chronic MS lesions without the need for IV contrast. In this single-center retrospective study, 340 spinal MR imaging cases of MS were collected in a 24-month period. Two senior neuroradiologists blindly and independently reviewed postcontrast T1-weighted sagittal and T2-SPACE sagittal images for the presence of MS lesions, associated cord expansion/atrophy on T2-SPACE, and enhancement on postcontrast T1WI. Discrepancies were resolved by consensus between the readers. Sensitivity, specificity, and accuracy of T2-SPACE compared with postcontrast T1WI were computed, and interobserver agreement was calculated. The sensitivity of lesion detection on T2-SPACE was 85.71%, 95% CI, 63.66%-96.95%; with a specificity of 93.52%, 95% CI, 90.06%-96.05%; and an accuracy of 92.99%, 95% CI, 89.58%-95.56. Additionally, 16/21 (84.2%) acute enhancing cord lesions showed cord expansion on T2-SPACE. The interobserver agreement was 92%. Our study shows that T2-SPACE facilitates noncontrast detection of acute MS lesions with high accuracy compared with postcontrast T1WI and with high interobserver agreement. The lack of gadolinium use provides an advantage, bypassing any potential adverse effects of repetitive contrast administration.

Safety considerations related to intravenous contrast agents in pediatric imaging.

Intravenous contrast media are used in MRI, CT and US studies for anatomical evaluation and lesion characterization. Safety is always of paramount importance when administering any contrast media to children, and it is important for radiologists and ordering providers to be knowledgeable of the safety profiles and potential adverse events that can occur. This manuscript reviews the frequency and types of adverse events associated with intravenous contrast agents reported in the pediatric literature. Overall, intravenous contrast agents are very safe to use in children. However, familiarity with how to treat and prevent these uncommon events is crucial in preventing poor outcomes. In addition, an understanding of gadolinium deposition in tissues can help facilitate conversations with concerned physicians and parents. This review provides a concise yet comprehensive reference for radiologists and ordering providers on intravenous contrast safety considerations in the pediatric patient.

Gadolinium deposition in tissue following multiple contrast-enhanced MRI examinations

تعتبر عوامل التباين المعتمدة على الجادولينيوم (GBCAs) آمنة للغاية منذ إدخالها للاستخدام السريري في عام 1988. ومع ذلك ، في عام 2006 ، تم الإبلاغ عن التليف الجهازي الكلوي (NSF) في المرضى الذين يعانون من الفشل الكلوي في المرحلة النهائية والذين تعرضوا لبعض GBCAs. في عام 2014 ، وجد أن ترسب الجادولينيوم يحدث في أنسجة المخ لدى المرضى المعرضين لدراسات GBCA المتعددة. يهدف هذا المشروع إلى مراجعة الدراسات المنشورة حاليًا بشأن تراكم الجادولينيوم في الأنسجة بعد إدارات GBCA المتكررة لتحديد وتلخيص النتائج الأخيرة لهذه المشكلة. تم البحث إلكترونيًا عن ست قواعد بيانات علمية للدراسات ذات الصلة بين عامي 2009 ويوليو 2016. كما تم فحص قوائم المراجع وتعقبها للعثور على المقالات ذات الصلة. تم تقييم الدراسات من حيث صلتها بالموضوع إما عن طريق مسح عناوينها وملخصاتها أو قراءة النص الكامل. أسفر البحث الأولي عن 1765 ورقة ، والتي تم تضييقها بعد ذلك إلى 14 دراسة استوفت معايير الاشتمال. تم العثور على دراستين أخريين من خلال البحث يدويًا في قوائم المراجع. من بين هذه الدراسات ، قيمت ثلاث دراسات احتباس الجادولينيوم في أنسجة المخ على نماذج حيوانية ، بينما كانت الدراسات الـ 13 المتبقية دراسات بحثية بشرية.

Use and Safety of Gadolinium Based Contrast Agents in Pediatric MR Imaging.

Gadolinium-based contrast agents (GBCA) used for MR imaging are a valuable imaging resource that has benefited patient management over last three decades and largely have a high safety profile. However, recently, adverse effects related to GBCA like nephrogenic systemic fibrosis (NSF) and asymptomatic gadolinium deposition in tissues including brain are concerning. While NSF has largely stopped occurring due to precautions and guidelines to not use GBCA in patients with poor renal function, the long term effects of gadolinium deposition, especially in brain, are not known at this stage. Cautious approach needs to be taken with risk-benefit analysis in each patient to avoid its administration when not necessary. In this review, authors discuss basics of gadolinium, mechanism of enhancement, agents in clinical use and safety issues, and in the end, offer some solutions for safety concerns.

Pharmacokinetics of gadolinium-based contrast agents

Gadolinium-based contrast agents are used routinely in magnetic resonance imaging (MRI). They can be detected over along period of time in some tissues (skin, brain, bone). What is known on the pharmacokinetics of gadolinium-based contrast agents and on gadolinium deposition in various tissues? Fundamental research and expert recommendations are discussed. Gadolinium-based contrast agents are distributed rapidly within the body and are eliminated by the kidneys. Afast initial elimination (half-life approximately 2 h) is followed by aslow elimination phase (half-life approximately 6days), reflecting slow release from tissues. Deposition in the brain was observed mainly after administration of linear, non-ionic contrast agents. Whether gadolinium deposition in tissues consists of chelated or free gadolinium and whether otherwise healthy subjects are affected to asimilar extent, is unclear. Currently, there are no proven risks associated with gadolinium deposition in the brain. Risks and benefits should be considered on an individual basis before MRI with gadolinium-based contrast agents (expected benefit, potentially undetected risks, available alternatives and their risks). Quantification of gadolinium in urine or blood from patients is not meaningful and should not be done outside clinical studies.

Gadolinium tissue deposition in the periodontal ligament of mice with reduced renal function exposed to Gd-based contrast agents

Gadolinium deposition in tissue is linked to nephrogenic systemic fibrosis (NSF): a rare disorder occurring in patients with severe chronic kidney disease and associated with administration of Gd-based contrast agents (GBCAs) for Magnetic Resonance Imaging (MRI). It is suggested that the GBCAs prolonged permanence in blood in these patients may result in a Gd precipitation in peripheral or central organs, where it initiates a fibrotic process. In this study we investigated new sites of retention/precipitation of Gd in a mouse model of renal disease (5/6 nephrectomy) receiving two doses (closely after each other) of a linear GBCA. Two commercial GBCAs (Omniscan® and Magnevist®) were administered at doses slightly higher than those used in clinical practice (0.7 mmol/kg body weight, each). The animals were sacrificed one month after the last administration and the explanted organs (kidney, liver, femur, dorsal skin, teeth) were analysed by X-ray fluorescence (XRF) at two synchrotron facilities. The XRF analysis with a millimetre-sized beam at the SYRMEP beamline (Elettra, Italy) produced no detectable levels of Gd in the examined tissues, with the notable exception of the incisors of the nephrectomised mice. The XRF analyses at sub-micron resolution performed at ID21 (ESRF, France) allowed to clearly localize Gd in the periodontal ligaments of teeth both from Omniscan® and Magnevist® treated nephrectomised mice. The latter results were further confirmed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The study prompts that prolonged permanence of GBCAs in blood may result in Gd retention in this particular muscular tissue, opening possibilities for diagnostic applications at this level when investigating Gd-related toxicities.

Gadolinium (III)-Based Contrast Agents, Gadolinium Deposition in Tissues and the Clinical Significance: A Review

Gadolinium (III)-Based Contrast Agents, Gadolinium Deposition in Tissues and the Clinical Significance: A Review

Response to the Comments by Dr. Endrikat et al. on the article "Tissue gadolinium deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA: evaluation with inductively coupled plasma mass spectrometry (ICP-MS)" by Tomohiro Sato, Tsutomu Tamada, Shigeru Watanabe et al. DOI 10.1007/s11547-014-0492-y.

Response to the Comments by Dr. Endrikat et al. on the article "Tissue gadolinium deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA: evaluation with inductively coupled plasma mass spectrometry (ICP-MS)" by Tomohiro Sato, Tsutomu Tamada, Shigeru Watanabe et al. DOI 10.1007/s11547-014-0492-y.

Comments on the article "Tissue gadolinium deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA: evaluation with inductively coupled plasma mass spectrometry (ICP-MS)" by Tomohiro Sato, Tsutomu Tamada, Shigeru Watanabe et al. DOI 10.1007/s11547-014-0492-y.

To the editor, We read with great interest the study by Tomohiro Sato et al. published online, January 9, 2015. The authors demonstrated, in an experiment on 2 × 5 rats, that application of 0.625 mmol/kg Gd-EOB-DTPA resulted in significantly higher gadolinium tissue deposition in hepatorenally impaired rats compared to renally impaired rats. The effect was statistically significant in kidneys, spleen and liver but not in other organs. Based on the methodology used to detect the tissue gadolinium (Gd), the time point of the analysis and the missing validation of the animal model, we think that this experimental setting does not allow any conclusions on gadolinium tissue deposits. The authors state that “ICP-MS cannot distinguish between chelated and unchelated Gd”. Thus, the time point to analyze Gd tissue deposition is crucial. The authors do not provide a rationale for analyzing tissue 7 days after last GBCA application. At this early time point, it is reasonable to assume that the measurements not only assessed Gd deposits but also chelated soluble Gd. We suggest that the analysis should be done after the majority of this soluble chelated Gd is most likely excreted. Pietsch et al. demonstrated that a steady-state level of skin Gd was reached only after 53 days p.i. of high doses of linear GBCAs. The time to reach steady state depended on the stability level of the linear GBCA [1]. Consequently, we think that 53 days p.i. would be the earliest reasonable time point for determination of Gd tissues deposits. The excretion kinetics of Gd-EOB-DTPA of the animal model was not thoroughly described prior to start of the experiments. The authors induced hepatic impairment by application of carbon tetrachloride (CCl4) without knowing the effect of CCl4 on the 1/6 remnant kidney tissue. A reasonable first step should have been to describe Gd-EOB-DTPA kinetics in renally vs hepatorenally impaired animals. If this induction of renal and hepatic impairment results in extremely prolonged excretion kinetics, GBCA would be still circulating 7 day p.i. and would compromise the conclusions on Gd tissue deposits. In addition, the hepatocyte-specific uptake and hepatobiliary excretion of Gd-EOB-DTPA are based on the saturable uptake by anion-transporting polypeptide 1 transporters (Oatp1) [2]. Liver fibrosis strongly influences the hepatocyte-specific uptake of Gd-EOB-DTPA [3]. Therefore, evaluation of the pharmacokinetics is a pre-requisite to validate this animal model. Finally, some clinical considerations. Gd-EOB-DTPA was administered 12 times over a period of 6 weeks at a dose of 0.625 mmol/kg. The approved dose of Gd-EOB-DTPA is 0.025 mmol/kg for one single liver MRI, which is usually sufficient for diagnosis. Thus, this 300 times overdosing does not reflect any clinically relevant situation. In the rare case that patients have both severe renal and severe liver impairments, even more caution would be exercised. In conclusion, based on the methodology used to detect the tissue Gd, the time point of the analysis and the missing validation of the animal model, we think that this experimental setting does not allow any conclusions on gadolinium tissue deposits. The authors only support the broadly accepted hypothesis that reduced elimination kinetics leads to a higher gadolinium exposure.

Tissue gadolinium deposition in renally impaired rats exposed to different gadolinium-based MRI contrast agents: Evaluation with inductively coupled plasma mass spectrometry (ICP-MS)

ObjectivesTo quantify tissue gadolinium (Gd) deposition in renally impaired rats exposed to Gd-EOB-DTPA and other Gd-based MRI contrast agents by means of inductively coupled plasma mass spectrometry (ICP-MS), and to compare the differences in distribution among major organs as possible triggers for nephrogenic systemic fibrosis (NSF). MethodsA total of 15 renally impaired rats were injected with Gd-EOB-DTPA, Gd-DTPA-BMA and Gd-HP-DO3A. Gd contents of skin, liver, kidney, lung, heart, spleen, diaphragm and femoral muscle were measured by inductively coupled plasma mass spectrometry (ICP-MS). Histological assessment was also conducted. ResultsTissue Gd deposition in all organs was significantly higher (P=0.005~0.009) in the Gd-DTPA-BMA group than in the Gd-HP-DO3A and Gd-EOB-DTPA groups. In the Gd-DTPA-BMA group, Gd was predominantly deposited in kidney (1306±605.7μg/g), followed by skin, liver, lung, spleen, femoral muscle, diaphragm and heart. Comparing Gd-HP-DO3A and Gd-EOB-DTPA groups, Gd depositions in the kidney, liver and lung were significantly lower (P=0.009~0.011) in the Gd-EOB-DTPA group than in the Gd-HP-DO3A group although no significant differences were seen for any other organs. ConclusionsGd-EOB-DTPA is a stable and safe Gd-based contrast agent (GBCA) showing lower Gd deposition in major organs in renally impaired rats, compared with other GBCAs. This fact suggests that the risk of NSF onset would be low in the use of Gd-EOB-DTPA.

Tissue gadolinium deposition and fibrosis mimicking nephrogenic systemic fibrosis (NSF)–subclinical nephrogenic systemic fibrosis?

Nephrogenic systemic fibrosis is a condition with significant and often debilitating cutaneous manifestations. Recent research on this disease has delineated an association between nephrogenic systemic fibrosis and exposure to magnetic resonance imaging studies using gadolinium-based contrast agents in patients with ongoing renal failure. This metal has been detected in cutaneous biopsy specimens taken from lesional skin suggesting that gadolinium provides an impetus for the deposition of circulating fibrocytes in the skin and subsequent fibrosis. We describe a hemodialysis-dependent liver transplant recipient who received a gadolinium-based contrast agent and demonstrated insoluble gadolinium deposition in a fibrotic dermis and subcutaneous septum using scanning electron microscopy/energy dispersive x-ray spectroscopy. He has yet to manifest symptoms and signs of nephrogenic systemic fibrosis 3 years after his magnetic resonance imaging study.