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What is Gadolinium Contrast?
Gadolinium is a rare earth metal in the lanthanide family. It has 7 unpaired electrons, making it paramagnetic. When injected in our patient, it will shorten both the T1 and T2 of tissues it comes, within 3 ångström too. The effect of this, is more dramatic, on the T1 of tissues. Since the T1 of tissues get shortened due to gadolinium contrast, structures near the gadolinium ion will appear bright.
The amount of shortening is a result of the relaxivity of the agent. The higher the relaxivity of an agent, the more dramatic the T1 contrast would be.
Types of Agents
Extracellular Agents
These agents are primarily excreted by the kidneys. They are typically used in neurological imaging, but can be used for other areas of imaging. Different agents will have different labeling for body parts that can be imaged with it. Most of the gadolinium agents are extracellular.
Hepatobiliary Agents
These agents have shared liver and kidney excretion. They are used for liver imaging, because the liver excretion offers an additional hepatocyte phase that can be imaged after 20 minutes.
Blood Pool Agents
One blood-pooling agent that was, in existence, and sold is, now, not available. This agent had the unique ability to attach to albumin in the blood and stay intravascularly for longer periods of time. This aided in vascular imaging.
Kinetic vs Thermodynamic Stability
Ionic vs Non-ionic
Gadolinium based agents are different than iodinated agents. Ionic agents contain an ionic charge and non-ionic agents do not. In MRI, gadolinium based contrast agents which are ionic provide a significantly higher stability than non-ionic agents.
ICPMEducation
Linear vs Macrocyclic
There are two types of gadolinium bonds used in Gadolinium-based Contrast Agents or GBCAs – Linear and Macrocylic.
The goal is to take a gadolinium ion and attach it to a ligand or molecule which allows it to be excreted from our patient. The fear is that; this existing bond between the gadolinium ion and ligand will break, thereby causing the gadolinium to bond to a carbonate or phosphate and stay inside the patient.
A linear agent offers a sub-optimal bond between the gadolinium ion and the ligand. If this agents stays in our patient long enough, this bond has a high chance of breaking or disassociating.
Macrocyclic agents have a ligand that cages in the gadolinium ion offering a higher stability.
Gadolinium Agents
Unstable Agents (Associated with Many Cases of NSF)
Magnevist
(gadopentetate dimeglumine)
Structure: Linear Ionic
Manufacturer: Bayer
This agent is an extracellular agent that has been associated with nephrogenic system fibrosis case(s)
Optimark
(gadoversetamide)
Structure: Linear Nonionic
Manufacturer: Mallinckrodt
This agent is an extracellular agent which also contributed to a number of nephrogenic systemic fibrosis case(s)
Omniscan
(gadodiamide)
Structure: Linear Nonionic
Manufacturer: GE
This agent is an extracellular agent which was instrumental in some of the highest case(s) pertaining to nephrogenic systemic fibrosis
Agents Shown To Have Higher Stability
Dotarem
(gadoterate meglumine)
Structure: Macrocyclic Ionic
Manufacturer: Guerbet
This agent has a lower than average relaxivity, but is structured in a way that makes it very stable.
Prohance
(gadoteridol)
Structure: Macrocyclic Nonionic
Manufacturer: Bracco
This agent is an extracellular agent that is used as a more stable contrast alternative.
Gadavist
(gadobutrol)
Structure: Macrocyclic Nonionic
Manufacturer: Bayer
This is an extracellular agent used to image many body parts. It has a slightly higher than average relaxivity rate.
Multihance
(gadobenate dimeglumine)
Structure: Linear Ionic
Manufacturer: Bracco
This is considered to be an extracellular agent that also has 5% hepatobiliary excretion. It is considered to have the highest relaxivity among the extracelluar agents.
Clariscan
Clariscan
(gadoteric acid)
Structure: Macrocyclic Ionic
Manufacturer: GE
This agent is an extracellular agent that has a lower relaxivity.
Agents With Both Liver and Renal Excretion
Eovist
Eovist
(gadoxetate disodium)
Structure: Linear Ionic
Manufacturer: Bayer
This agent is a hepatobiliary agent. It is used for liver imaging. It is considered to have a high relaxivity.
GBCA - Affiliated Reactions
Non-Allergic/ Transient Reactions
These reactions are not a result of a histamine response in a patient. Common non-allergic reactions are:
- Nausea
- Headache
- Dizziness/Syncope
- Vomiting (Rare – Less than 1 in 100 injections)
Allergic Reactions
These reactions are a result of a build-up of histamines in our patient. They are a byproduct of certain physiological responses that can be life-threatening:
Mild
Itching, Rash, Hives (minimal)
Moderate
Swelling, increase itching, increased hives
Severe/Anaphylaxis
Throat/tongue swelling, trouble breathing, increased heart rate, death
GBCA-Associated Adverse Events
Nephrogenic Systemic Fibrosis (NSF)
NSF is a horrible disease that can be life-threatening. It results in fibrosis tissue growing around human tissues and organs, thereby contributing to severe pain.
It is a by-product of gadolinium dissociation and retention within a patient. This is considered a rare condition that requires adequate monitoring.
It is caused by transmetalation – a process in which gadolinium separates from its ligand. The ligand will bond to other metals such as carbon, iron, zinc, etc. and the gadolinium ion will bond with phosphates, carbonates, etc.
Patients with compromised renal function will hold on to the gadolinium contrast longer increasing the chance it will dissociate.
Better practices have been implemented to reduce this common occurrence. They involve:
- Limiting of dose
- Limiting gadolinium based contrast
- Monitoring kidney function
Gadolinium Retention
In recent years; it has been observed that, patients who have received prior doses of gadolinium demonstrate T1 shortening in certain areas of the brain. This prompted an ongoing medical/scientific research.
It turns out that all GBCAs demonstrated retention in different tissues. The level of retention differs from tissue to tissue – and is dependent on the GBCA itself.
Gadolinium retention is not related to the renal function of patients.It is; however, related to the amount of gadolinium administered over the course of an affected patient’s lifetime.
Gadolinium Associated Plaques
Some patients demonstrated superficial plaques on their skin due to gadolinium administration. A biopsy confirmed gadolinium retention for such cases.
Gadolinium is not a naturally occurring substance. Therefore; the only way the aforementioned patients retained gadolinium in their system, is through parenteral administration (injection) of gadolinium-based contrast media.
Resources
The Lighthouse Project
This website has individuals who recounted their issues pertaining to gadolinium toxicity.
Chuck Norris Lawsuit
https://www.cbsnews.com/news/chuck-norris-gena-norris-lawsuit-medical-companies-mri-contrast-agent/
Gena Norris claims that she was poisoned by gadolinium contrast.
Recent Literature
Dr. Robert McDonald
English (United States) 
English (UK)