- Contrast agents are substances used in MRI to increase contrast between tissues. Gadolinium is commonly used as it has 7 unpaired electrons giving it a strong magnetic moment. However, gadolinium is toxic so it must be bound to chelate molecules. - Some gadolinium-based contrast agents have been linked to Nephrogenic Systemic Fibrosis (NSF), a rare condition causing fibrosis of skin and tissues. NSF seems to occur when free gadolinium ions are released from the chelate in patients with kidney problems who cannot eliminate the agent quickly. - To reduce risks, health regulators now classify agents as high, medium, or low risk for NSF. Strict guidelines around

1. How safe are
Gd-based MR
contrast agents
Introduced by
Abdulrahman Alquait
Medical imaging MSc student

2. -What is a contrast agent?
It is a substance which is put
into the body with the intention
of increasing the image contrast
between two tissues, or
between a tissue and an
abnormal region within it.

3. How can we enhance image
contrast in MRI?
 The parameters most commonly used to
provide image contrast are:
• Proton density.
• T1 relaxation time.
• T2 relaxation time.
 Most contrast agents achieve their effect
by changing the relaxation times of water
protons in tissue.

4. How?
 Dipole-dipole interaction between the water
protons and those of the “relaxing agent”
results in an increased relaxation rate given
by:
𝟏
∆𝑻 𝟏,𝟐
∝
𝜸 𝑨
𝟐
𝜸 𝑩
𝟐
𝒓 𝟔
 𝛾 𝐴 = gyromagnetic ratio of water protons.
 𝛾 𝐵= gyromagnetic ratio of relaxing agent.
 r = separation between water protons and relaxing agent protons.

5. What is an ideal contrast gent?
 A good relaxing agent should have a large
value for (𝜸 𝑩).
 The electron is highly effective since its
gyromagnetic ratio is 600 times that of the
proton.
 In general, electrons occur in pairs round their
nuclei and give no net magnetic moment.
 Substances with unpaired electrons are ideal
for our purpose.

6. Why Gadolinium?
- What is Gadolinium A sample of gadolinium
- A paramagnetic
substance.
- atomic number of 64.
- 7 unpaired electrons
(large magnetic
moment).
- TOXIC.

7. Gd- based contrast agent
chelates.
 To reduce their toxicity they have to be
bound in chelates.
 chelates are complexes with at least two
bonds (e.g. DTPA, DOTA).
 Chelates has to be very stable so virtually
no free ion is released inside the body.
 Chelates must have short half-life (2
hours) to be excreted from the body.

8. Gd- based contrast agents
 contra indications
 Allergy .
 Pregnancy (assessed according to the risk/benefit ratio).
 Adverse effects
 Nausea, headache, taste alteration.
 Nephrogenic Systemic Fibrosis (NSF).

9. NSF
 also known as nephrogenic fibrosing dermopathy
(NFD), is a rare condition that involves fibrosis of the
skin and connective tissues, which can lead to
contractures and joint immobility.
 NSF usually starts in the extremities, sometimes
involving the trunk, and other organs can become
affected later including the lungs, liver, muscles, and
heart, in some cases leading to a fatal outcome.
 Only occurred in patients with renal dysfunction.

10. NSF

11. NSF MECHANISM
 The mechanism by which some gadolinium-containing
contrast agents might trigger NSF is under
investigation.
 Patients with severe renal impairment have an
increased risk of NSF because they take longer to
eliminate the contrast agent from the body compared
with those without renal impairment.
 Gadolinium ions (Gd3+) may be released into the body
from a chelate complex of the gadolinium-containing
contrast agent by transmetallation with ions from the
body (e.g. zinc, iron, calcium, magnesium).
 Free Gd3+ can accumulate in tissues and organs and
trigger fibrosis, leading to NSF.

12. Brand name Generic name
Chemical
structure
Charge
Elimination
pathway
Protein
binding
Cases of NSF
Omniscan gadodiamide Linear Non-ionic Kidney None Yes
OptiMARK
gadoversetami
de
Linear Non-ionic Kidney None Yes
Magnevist
gadopentetic
acid
Linear Ionic Kidney None Yes
MultiHance Gadobenic acid Linear Ionic
97% Kidney,
3% Bile
<5% Yes
Primovist gadoxetic acid Linear Ionic
50% Kidney,
50% Bile
<15% No
Vasovist gadofosveset Linear Ionic
91% Kidney,
9% Bile
>85% No
ProHance gadoteridol Cyclic Non-ionic Kidney None No
Gadovist gadobutrol Cyclic Non-ionic Kidney None No
Dotarem Gadoteric acid Cyclic Ionic Kidney None No
Eight gadolinium-containing contrast agents are currently authorized in the UK:

13. New advice to minimise the
risk of NSF by MHRA*
 On the basis of current evidence, the risk
classification is as follows:
• High risk,
-Omniscan, OptiMARK and Magnevist.
• Medium risk,
-MultiHance, Primovist and Vasovist.
• Low risk,
-Gadovist, ProHance and Dotarem.
* Medicines and Healthcare products Regulatory Agency (Jan 2010) .

14. Risk-minimization measures considered by
MHRA for Gd-based contrast agents:
 Renal-function monitoring.
 Renal impairment.
 Perioperative liver-transplantation period.
 Neonates.
 Infants.
 Breastfeeding.
 Pregnancy.
 Haemodialysis.
 Recording of the agent used.
 Reporting of suspected adverse reactions.

15. Conclusion
 Millions of Gd- based contrast agents are performed world
wide.
 As of March 2010, more than 335 cases of NSF have been
identified according to the Yale NSF Registry.
 NSF has occurred only in people with kidney disease.
 NSF affects males and females and has been confirmed in
children and the elderly.
 It has been identified in patients from a variety of ethnic
backgrounds from North and South America, Europe, Asia
and Australia.
 Two U.S. universities were able to eliminate cases of NSF
among their patients receiving MRI scans by switching to a
different gadolinium-based contrast agent and by adopting
stricter guidelines for contrast use.

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