Gadolinium Retention in Human Bone Tissue in Pediatric Patients

Study Overview
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Brief Summary
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The purpose of this study is to compare contrast agents, Dotarem or MultiHance. The study will test to see how much of these two contrast agents are deposited in the bones or tissues of pediatric patients. The patients receiving contrast will then be compared against pediatric patients who have not received any contrast prior to cardiac surgeries.

Detailed Description
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When injected into the body, gadolinium contrast medium makes certain tissues, abnormalities or disease processes more clearly visible on a magnetic resonance imaging (MRI) scans and therefore gadolinium based contrast agents (GBCAs) are widely used in medical imaging. Recently, new evidence suggests that following GBCA administration, gadolinium can be deposited in body tissues even in the presence of normal renal function. Therefore, it is essential to ensure that significant accumulation of free Gd3+ is not occurring in the bones of children undergoing clinical contrasted MRI scans. This is particularly important for those pediatric patients who will undergo multiple repeated MRI exams throughout their lifetime and thereby be exposed to a large cumulative dose of gadolinium contrast. As the differences in stability between the various GBCAs may be a factor in gadolinium exposure, the primary objective of this study is to assess gadolinium deposition in the bones of pediatric patients in two patient groups: 1. patients who received IV administration of gadolinium contrast agent (Dotarem) and 2. patients who received IV administration of gadolinium contrast agent (MultiHance). Once acquired the samples will be analyzed at an off-site facility, National Institute of Standards and Technology (NIST), using standardized equipment which has been certified for measuring gadolinium concentration in contrast agent samples. A signed agreement for the transfer of non-proprietary biological material between MUSC and NIST covers the transfer of the samples.

Official Title
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Gadolinium Retention in Human Bone Tissue in Pediatric Patients: A Comparison of Dotarem Versus MultiHance MRI Contrast Agents

Conditions
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Gadolinium, MultiHance, Dotarem, Magnetic Resonance Imaging, Gadolinium Retention

Intervention / Treatment
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* Drug: Pre-operative MRI with Dotarem
* Drug: Pre-operative MRI with MultiHance
* Procedure: Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male pediatric patient (patients aged newborn to 18 years old at the time of the MRI scan). Patients who require cardiac surgery for clinical purposes and meet one of the following three criteria: Patients who have undergone a routine contrast-enhanced MRI using MultiHance contrast agent only for clinical purposes. Patients who have undergone a routine contrast-enhanced MRI using Dotarem contrast agent only for clinical purposes. Patients who have not been exposed to gadolinium-based contrast agent administration Exclusion Criteria: Patient with abnormal renal function (defined as eGFR MDRD<30 ml/min/1.73m2). Patient previously exposed to any other type of MRI gadolinium based contrast agent either at MUSC or at an outside facility Pregnant or breast feeding female patient Patient with a contraindication to MRI (e.g., pacemaker, aneurysm clip, severe claustrophobia, infusion pumps, cochlear implants metallic or others according to standard practice at MUSC).

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control<br>Pediatric patients who have not been exposed to gadolinium-based contrast agent administration and who require cardiac surgery as part of their standard clinical treatment. | Procedure: Surgery<br>* Cardiac surgery<br>|
| Dotarem<br>Pediatric patients who have undergone routine contrast-enhanced MRI using only Dotarem contrast agent for clinical purposes and who require cardiac surgery as part of their standard clinical treatment. | Drug: Pre-operative MRI with Dotarem<br>* Dotarem® (gadoterate meglumine - Guerbet)<br>* Other names: gadoterate meglumine;Procedure: Surgery<br>* Cardiac surgery<br>|
| MultiHance<br>Pediatric patients who have undergone routine contrast-enhanced MRI using only MultiHance contrast agent for clinical purposes and who require cardiac surgery as part of their standard clinical treatment. | Drug: Pre-operative MRI with MultiHance<br>* MultiHance® (gadobenate dimeglumine - Bracco)<br>* Other names: gadobenate dimeglumine;Procedure: Surgery<br>* Cardiac surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the gadolinium concentration present in bone tissue in pediatric patients following a standard of care MRI with MultiHance, Dotarem, or without any exposure to contrast. | To determine the gadolinium concentration present in sternum and rib bone tissue in 2 groups of pediatric patients requiring cardiac surgery as part of their standard clinical treatment: (1) patients who had undergone the administration of a standard clinical dose of a linear GBCA (0.1 mmol/kg IV MultiHance), and (2) patients who had undergone the administration of a standard clinical dose of a macrocyclic GBCA (0.1 mmol/kg IV Dotarem). As a control, gadolinium concentration present in sternum bone tissue will also be determined in patients who had not been exposed to GBCA administration prior to surgery. | July 2017 to October 2022 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asses the number of exposures to contrast agent as a potential confounder. | Number of exposures to contrast agent is a potential confounder. Thus we will perform linear regression, with concentration as the outcome, and both type of contrast agent (i.e. group) and number of doses as independent variables. Although the sample size is small, we may consider evaluating an interaction between type of contrast and number of doses as an exploratory analysis. | July 2017 to October 2022 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gadolinium, MultiHance, Dotarem, Contrast agents, Magnetic Resonance Imaging, Gadolinium retention, Pediatric, Bone